PMC:7601109 / 9375-14492 JSONTXT

Annnotations TAB JSON ListView MergeView

    LitCovid-PD-UBERON

    {"project":"LitCovid-PD-UBERON","denotations":[{"id":"T8","span":{"begin":4711,"end":4715},"obj":"Body_part"}],"attributes":[{"id":"A8","pred":"uberon_id","subj":"T8","obj":"http://purl.obolibrary.org/obo/UBERON_0000014"}],"text":"2.1. Royal Jelly: Its Constituents, Biological, and Pharmacological Activities\nRoyal jelly is a thick, milky, white-yellowish, acidic colloid substance secreted from the hypopharyngeal and mandibular salivary glands of young nurse honey bees (5–15 days old) [32,43]. In general, fresh royal jelly mostly consists of water (67% w/w) in addition to carbohydrates (16%), proteins and amino acids (12.5%), fat (5%), and many other elements [32]. However, royal jelly content of these substances noticeably varies depending on numerous factors like botanical source, bee species, bee artificial feeding, weather, season, location, method of processing, and the like [2,44].\nProtein is the most copious active element in royal jelly, representing half the weight of its dry matter [2]. It vastly comprises nine 49–87 kDa water-insoluble proteins, known as major royal jelly proteins 1–9 (MRJPs1-9) [2,45]. MRJPs constitute more than 80% of royal jelly protein content, and MRJPs1–5 constitute 82–90% of all MRJPs. MRJPs contain 400–578 amino acids that contribute to the antioxidant effect of royal jelly as well as its role in cell proliferation, cell adhesion, cell growth, and immunity [46,47]. Novel non-MRJPs proteins have been newly discovered [48]. Royalisin, jelleines, and aspimin are examples of other proteins that exist in royal jelly, albeit in small amounts. These proteins as well as MRJPs demonstrate strong antimicrobial and bactericidal activities even against the most drug-resistant bacterial strains such as methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, vancomycin-resistant Enterococci, as well as extended-spectrum β-lactamase-producing Proteus mirabilis and Escherichia coli [28,29].\nCarbohydrates (e.g., fructose, glucose maltose, trehalose, melibiose, ribose, and erlose) constitute 7.5–16% or royal jelly content [49]. Reducing sugars in royal jelly are thought to contribute to its epigenetic effect through the activation of insulin-like growth factor 1 (IGF-1) and mammalian target of rapamycin (mTOR) signaling cascades. Thus, they stimulate caste differentiation of Apis mellifera larvae into queens by increasing intake of food and key nutrients [50].\nLipids make up 7–18% of the dry weight of royal jelly. This fraction largely comprises a group of unique and rare saturated or monounsaturated short and medium chain fatty acids that are terminally or internally hydroxylated with terminal mono- or dicarboxylic acid functions [2,28]. The vast majority of royal jelly fat content (80–85%) consists of short hydroxyl fatty acids such as trans-10-hydroxy-2-decenoic acid (10-HDA), which exists only in royal jelly; and therefore, it is known as royal jelly acid or queen bee acid [28,49,51]. 10-HDA is one of the most potent bioactive elements in royal jelly expressing strong anti-aging, neuroprotective, antiproliferative, antimicrobial, antioxidant, anti-inflammatory, and epigenetic effects [52,53,54,55,56,57,58]. In addition, the lipid fraction of royal jelly contains phenolic acids (4–10%), wax (5–6%), steroids (3–4%), and phospholipids (0.4–0.8%) [49].\nA wide range of minor constituents and bioactive compounds exist profusely in royal jelly such as acetylcholine, nucleotides (adenosine, guanosine, adenosine tri-phosphate (ATP), adenosine monophosphate (AMP)), minerals (iron, sodium, calcium, potassium, zinc, magnesium, manganese, and copper), amino acids (8 out of 9 essential amino acids Val, Leu, Ile, Thr, Met, Phe, Lys, and Trp), vitamins (retinol (A), ascorbic acid (C), tocopherol (E), riboflavin (B2), niacin (B3), and other B vitamins), esters, aldehydes, ketones, alcohol, and minor heterocyclic compounds [2,28,49,59,60,61]. It is worth noting that royal jelly loses most of its bioactive ingredients and biological properties when stored at a temperature of 5 °C or higher. Therefore, freezing is the best method to store royal jelly [62]. Enzymatic treatment of royal jelly removes allergen proteins and enhances its nutrient content in addition to improving its digestibility and absorption in the gut without altering its freshness [2,59].\nRoyal jelly has been historically used as a beautifying agent by famous queens such as Cleopatra, and it is still involved in the cosmetic industry [29,56]. Its rich content of bioactive compounds grants it a plethora of diverse health benefits such as antioxidant, anti-inflammatory, neurotrophic, hypotensive, antidiabetic, antilipidemic, antirheumatic, anticarcinogenic, anti-fatigue, antiadipogenic, and antimicrobial activities [43,45,63]. Therefore, it is widely used to treat multiple serious conditions including diabetes, hypertension, hyperlipidemia, cancer, skin diseases, and neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease [2,43,46,59,64]. In addition, bee queens (which enjoy long lifespan as well as super fertility and physical qualities) consume royal jelly throughout their entire lives, and royal jelly is considered a promising anti-aging nutraceutical that can positively enhance fertility and improve body composition [2]."}

    LitCovid-PD-FMA-UBERON

    {"project":"LitCovid-PD-FMA-UBERON","denotations":[{"id":"T90697","span":{"begin":200,"end":215},"obj":"Body_part"},{"id":"T50189","span":{"begin":347,"end":360},"obj":"Body_part"},{"id":"T52154","span":{"begin":368,"end":376},"obj":"Body_part"},{"id":"T12159","span":{"begin":381,"end":392},"obj":"Body_part"},{"id":"T36157","span":{"begin":669,"end":676},"obj":"Body_part"},{"id":"T12076","span":{"begin":831,"end":839},"obj":"Body_part"},{"id":"T19811","span":{"begin":868,"end":876},"obj":"Body_part"},{"id":"T75404","span":{"begin":946,"end":953},"obj":"Body_part"},{"id":"T58144","span":{"begin":1030,"end":1041},"obj":"Body_part"},{"id":"T63883","span":{"begin":1122,"end":1126},"obj":"Body_part"},{"id":"T64052","span":{"begin":1142,"end":1146},"obj":"Body_part"},{"id":"T76306","span":{"begin":1157,"end":1161},"obj":"Body_part"},{"id":"T99095","span":{"begin":1208,"end":1216},"obj":"Body_part"},{"id":"T88467","span":{"begin":1306,"end":1314},"obj":"Body_part"},{"id":"T44328","span":{"begin":1373,"end":1381},"obj":"Body_part"},{"id":"T82461","span":{"begin":1748,"end":1761},"obj":"Body_part"},{"id":"T51125","span":{"begin":1779,"end":1786},"obj":"Body_part"},{"id":"T48456","span":{"begin":1895,"end":1901},"obj":"Body_part"},{"id":"T22505","span":{"begin":1994,"end":2001},"obj":"Body_part"},{"id":"T26826","span":{"begin":2225,"end":2231},"obj":"Body_part"},{"id":"T63696","span":{"begin":2391,"end":2402},"obj":"Body_part"},{"id":"T37417","span":{"begin":2590,"end":2601},"obj":"Body_part"},{"id":"T88314","span":{"begin":3008,"end":3013},"obj":"Body_part"},{"id":"T22909","span":{"begin":3104,"end":3117},"obj":"Body_part"},{"id":"T52605","span":{"begin":3233,"end":3246},"obj":"Body_part"},{"id":"T89917","span":{"begin":3248,"end":3259},"obj":"Body_part"},{"id":"T90138","span":{"begin":3431,"end":3442},"obj":"Body_part"},{"id":"T11204","span":{"begin":3465,"end":3476},"obj":"Body_part"},{"id":"T52172","span":{"begin":3991,"end":3999},"obj":"Body_part"},{"id":"T50423","span":{"begin":4099,"end":4102},"obj":"Body_part"},{"id":"T96868","span":{"begin":4711,"end":4715},"obj":"Body_part"},{"id":"T46808","span":{"begin":5096,"end":5100},"obj":"Body_part"}],"attributes":[{"id":"A16854","pred":"fma_id","subj":"T90697","obj":"http://purl.org/sig/ont/fma/fma9597"},{"id":"A1834","pred":"fma_id","subj":"T50189","obj":"http://purl.org/sig/ont/fma/fma82737"},{"id":"A1515","pred":"fma_id","subj":"T52154","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A46851","pred":"fma_id","subj":"T12159","obj":"http://purl.org/sig/ont/fma/fma82739"},{"id":"A11434","pred":"fma_id","subj":"T36157","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A27772","pred":"fma_id","subj":"T12076","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A89175","pred":"fma_id","subj":"T19811","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A37965","pred":"fma_id","subj":"T75404","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A14739","pred":"fma_id","subj":"T58144","obj":"http://purl.org/sig/ont/fma/fma82739"},{"id":"A61248","pred":"fma_id","subj":"T63883","obj":"http://purl.org/sig/ont/fma/fma68646"},{"id":"A1231","pred":"fma_id","subj":"T64052","obj":"http://purl.org/sig/ont/fma/fma68646"},{"id":"A95320","pred":"fma_id","subj":"T76306","obj":"http://purl.org/sig/ont/fma/fma68646"},{"id":"A85537","pred":"fma_id","subj":"T99095","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A12155","pred":"fma_id","subj":"T88467","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A14837","pred":"fma_id","subj":"T44328","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A92844","pred":"fma_id","subj":"T82461","obj":"http://purl.org/sig/ont/fma/fma82737"},{"id":"A42306","pred":"fma_id","subj":"T51125","obj":"http://purl.org/sig/ont/fma/fma82743"},{"id":"A75530","pred":"fma_id","subj":"T48456","obj":"http://purl.org/sig/ont/fma/fma82737"},{"id":"A99789","pred":"fma_id","subj":"T22505","obj":"http://purl.org/sig/ont/fma/fma83365"},{"id":"A80892","pred":"fma_id","subj":"T26826","obj":"http://purl.org/sig/ont/fma/fma67264"},{"id":"A3491","pred":"fma_id","subj":"T63696","obj":"http://purl.org/sig/ont/fma/fma82738"},{"id":"A46790","pred":"fma_id","subj":"T37417","obj":"http://purl.org/sig/ont/fma/fma82738"},{"id":"A98021","pred":"fma_id","subj":"T88314","obj":"http://purl.org/sig/ont/fma/fma67264"},{"id":"A58874","pred":"fma_id","subj":"T22909","obj":"http://purl.org/sig/ont/fma/fma82779"},{"id":"A86221","pred":"fma_id","subj":"T52605","obj":"http://purl.org/sig/ont/fma/fma61789"},{"id":"A90655","pred":"fma_id","subj":"T89917","obj":"http://purl.org/sig/ont/fma/fma82740"},{"id":"A46711","pred":"fma_id","subj":"T90138","obj":"http://purl.org/sig/ont/fma/fma82739"},{"id":"A61173","pred":"fma_id","subj":"T11204","obj":"http://purl.org/sig/ont/fma/fma82739"},{"id":"A81722","pred":"fma_id","subj":"T52172","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A72166","pred":"fma_id","subj":"T50423","obj":"http://purl.org/sig/ont/fma/fma7199"},{"id":"A51356","pred":"fma_id","subj":"T96868","obj":"http://purl.org/sig/ont/fma/fma7163"},{"id":"A77615","pred":"fma_id","subj":"T46808","obj":"http://purl.org/sig/ont/fma/fma256135"}],"text":"2.1. Royal Jelly: Its Constituents, Biological, and Pharmacological Activities\nRoyal jelly is a thick, milky, white-yellowish, acidic colloid substance secreted from the hypopharyngeal and mandibular salivary glands of young nurse honey bees (5–15 days old) [32,43]. In general, fresh royal jelly mostly consists of water (67% w/w) in addition to carbohydrates (16%), proteins and amino acids (12.5%), fat (5%), and many other elements [32]. However, royal jelly content of these substances noticeably varies depending on numerous factors like botanical source, bee species, bee artificial feeding, weather, season, location, method of processing, and the like [2,44].\nProtein is the most copious active element in royal jelly, representing half the weight of its dry matter [2]. It vastly comprises nine 49–87 kDa water-insoluble proteins, known as major royal jelly proteins 1–9 (MRJPs1-9) [2,45]. MRJPs constitute more than 80% of royal jelly protein content, and MRJPs1–5 constitute 82–90% of all MRJPs. MRJPs contain 400–578 amino acids that contribute to the antioxidant effect of royal jelly as well as its role in cell proliferation, cell adhesion, cell growth, and immunity [46,47]. Novel non-MRJPs proteins have been newly discovered [48]. Royalisin, jelleines, and aspimin are examples of other proteins that exist in royal jelly, albeit in small amounts. These proteins as well as MRJPs demonstrate strong antimicrobial and bactericidal activities even against the most drug-resistant bacterial strains such as methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, vancomycin-resistant Enterococci, as well as extended-spectrum β-lactamase-producing Proteus mirabilis and Escherichia coli [28,29].\nCarbohydrates (e.g., fructose, glucose maltose, trehalose, melibiose, ribose, and erlose) constitute 7.5–16% or royal jelly content [49]. Reducing sugars in royal jelly are thought to contribute to its epigenetic effect through the activation of insulin-like growth factor 1 (IGF-1) and mammalian target of rapamycin (mTOR) signaling cascades. Thus, they stimulate caste differentiation of Apis mellifera larvae into queens by increasing intake of food and key nutrients [50].\nLipids make up 7–18% of the dry weight of royal jelly. This fraction largely comprises a group of unique and rare saturated or monounsaturated short and medium chain fatty acids that are terminally or internally hydroxylated with terminal mono- or dicarboxylic acid functions [2,28]. The vast majority of royal jelly fat content (80–85%) consists of short hydroxyl fatty acids such as trans-10-hydroxy-2-decenoic acid (10-HDA), which exists only in royal jelly; and therefore, it is known as royal jelly acid or queen bee acid [28,49,51]. 10-HDA is one of the most potent bioactive elements in royal jelly expressing strong anti-aging, neuroprotective, antiproliferative, antimicrobial, antioxidant, anti-inflammatory, and epigenetic effects [52,53,54,55,56,57,58]. In addition, the lipid fraction of royal jelly contains phenolic acids (4–10%), wax (5–6%), steroids (3–4%), and phospholipids (0.4–0.8%) [49].\nA wide range of minor constituents and bioactive compounds exist profusely in royal jelly such as acetylcholine, nucleotides (adenosine, guanosine, adenosine tri-phosphate (ATP), adenosine monophosphate (AMP)), minerals (iron, sodium, calcium, potassium, zinc, magnesium, manganese, and copper), amino acids (8 out of 9 essential amino acids Val, Leu, Ile, Thr, Met, Phe, Lys, and Trp), vitamins (retinol (A), ascorbic acid (C), tocopherol (E), riboflavin (B2), niacin (B3), and other B vitamins), esters, aldehydes, ketones, alcohol, and minor heterocyclic compounds [2,28,49,59,60,61]. It is worth noting that royal jelly loses most of its bioactive ingredients and biological properties when stored at a temperature of 5 °C or higher. Therefore, freezing is the best method to store royal jelly [62]. Enzymatic treatment of royal jelly removes allergen proteins and enhances its nutrient content in addition to improving its digestibility and absorption in the gut without altering its freshness [2,59].\nRoyal jelly has been historically used as a beautifying agent by famous queens such as Cleopatra, and it is still involved in the cosmetic industry [29,56]. Its rich content of bioactive compounds grants it a plethora of diverse health benefits such as antioxidant, anti-inflammatory, neurotrophic, hypotensive, antidiabetic, antilipidemic, antirheumatic, anticarcinogenic, anti-fatigue, antiadipogenic, and antimicrobial activities [43,45,63]. Therefore, it is widely used to treat multiple serious conditions including diabetes, hypertension, hyperlipidemia, cancer, skin diseases, and neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease [2,43,46,59,64]. In addition, bee queens (which enjoy long lifespan as well as super fertility and physical qualities) consume royal jelly throughout their entire lives, and royal jelly is considered a promising anti-aging nutraceutical that can positively enhance fertility and improve body composition [2]."}

    LitCovid-PD-MONDO

    {"project":"LitCovid-PD-MONDO","denotations":[{"id":"T36","span":{"begin":1592,"end":1613},"obj":"Disease"},{"id":"T37","span":{"begin":4663,"end":4671},"obj":"Disease"},{"id":"T38","span":{"begin":4673,"end":4685},"obj":"Disease"},{"id":"T39","span":{"begin":4687,"end":4701},"obj":"Disease"},{"id":"T40","span":{"begin":4703,"end":4709},"obj":"Disease"},{"id":"T41","span":{"begin":4711,"end":4724},"obj":"Disease"},{"id":"T42","span":{"begin":4730,"end":4756},"obj":"Disease"},{"id":"T43","span":{"begin":4765,"end":4784},"obj":"Disease"},{"id":"T44","span":{"begin":4789,"end":4808},"obj":"Disease"}],"attributes":[{"id":"A36","pred":"mondo_id","subj":"T36","obj":"http://purl.obolibrary.org/obo/MONDO_0030602"},{"id":"A37","pred":"mondo_id","subj":"T37","obj":"http://purl.obolibrary.org/obo/MONDO_0005015"},{"id":"A38","pred":"mondo_id","subj":"T38","obj":"http://purl.obolibrary.org/obo/MONDO_0005044"},{"id":"A39","pred":"mondo_id","subj":"T39","obj":"http://purl.obolibrary.org/obo/MONDO_0021187"},{"id":"A40","pred":"mondo_id","subj":"T40","obj":"http://purl.obolibrary.org/obo/MONDO_0004992"},{"id":"A41","pred":"mondo_id","subj":"T41","obj":"http://purl.obolibrary.org/obo/MONDO_0005093"},{"id":"A42","pred":"mondo_id","subj":"T42","obj":"http://purl.obolibrary.org/obo/MONDO_0005559"},{"id":"A43","pred":"mondo_id","subj":"T43","obj":"http://purl.obolibrary.org/obo/MONDO_0004975"},{"id":"A44","pred":"mondo_id","subj":"T44","obj":"http://purl.obolibrary.org/obo/MONDO_0005180"}],"text":"2.1. Royal Jelly: Its Constituents, Biological, and Pharmacological Activities\nRoyal jelly is a thick, milky, white-yellowish, acidic colloid substance secreted from the hypopharyngeal and mandibular salivary glands of young nurse honey bees (5–15 days old) [32,43]. In general, fresh royal jelly mostly consists of water (67% w/w) in addition to carbohydrates (16%), proteins and amino acids (12.5%), fat (5%), and many other elements [32]. However, royal jelly content of these substances noticeably varies depending on numerous factors like botanical source, bee species, bee artificial feeding, weather, season, location, method of processing, and the like [2,44].\nProtein is the most copious active element in royal jelly, representing half the weight of its dry matter [2]. It vastly comprises nine 49–87 kDa water-insoluble proteins, known as major royal jelly proteins 1–9 (MRJPs1-9) [2,45]. MRJPs constitute more than 80% of royal jelly protein content, and MRJPs1–5 constitute 82–90% of all MRJPs. MRJPs contain 400–578 amino acids that contribute to the antioxidant effect of royal jelly as well as its role in cell proliferation, cell adhesion, cell growth, and immunity [46,47]. Novel non-MRJPs proteins have been newly discovered [48]. Royalisin, jelleines, and aspimin are examples of other proteins that exist in royal jelly, albeit in small amounts. These proteins as well as MRJPs demonstrate strong antimicrobial and bactericidal activities even against the most drug-resistant bacterial strains such as methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, vancomycin-resistant Enterococci, as well as extended-spectrum β-lactamase-producing Proteus mirabilis and Escherichia coli [28,29].\nCarbohydrates (e.g., fructose, glucose maltose, trehalose, melibiose, ribose, and erlose) constitute 7.5–16% or royal jelly content [49]. Reducing sugars in royal jelly are thought to contribute to its epigenetic effect through the activation of insulin-like growth factor 1 (IGF-1) and mammalian target of rapamycin (mTOR) signaling cascades. Thus, they stimulate caste differentiation of Apis mellifera larvae into queens by increasing intake of food and key nutrients [50].\nLipids make up 7–18% of the dry weight of royal jelly. This fraction largely comprises a group of unique and rare saturated or monounsaturated short and medium chain fatty acids that are terminally or internally hydroxylated with terminal mono- or dicarboxylic acid functions [2,28]. The vast majority of royal jelly fat content (80–85%) consists of short hydroxyl fatty acids such as trans-10-hydroxy-2-decenoic acid (10-HDA), which exists only in royal jelly; and therefore, it is known as royal jelly acid or queen bee acid [28,49,51]. 10-HDA is one of the most potent bioactive elements in royal jelly expressing strong anti-aging, neuroprotective, antiproliferative, antimicrobial, antioxidant, anti-inflammatory, and epigenetic effects [52,53,54,55,56,57,58]. In addition, the lipid fraction of royal jelly contains phenolic acids (4–10%), wax (5–6%), steroids (3–4%), and phospholipids (0.4–0.8%) [49].\nA wide range of minor constituents and bioactive compounds exist profusely in royal jelly such as acetylcholine, nucleotides (adenosine, guanosine, adenosine tri-phosphate (ATP), adenosine monophosphate (AMP)), minerals (iron, sodium, calcium, potassium, zinc, magnesium, manganese, and copper), amino acids (8 out of 9 essential amino acids Val, Leu, Ile, Thr, Met, Phe, Lys, and Trp), vitamins (retinol (A), ascorbic acid (C), tocopherol (E), riboflavin (B2), niacin (B3), and other B vitamins), esters, aldehydes, ketones, alcohol, and minor heterocyclic compounds [2,28,49,59,60,61]. It is worth noting that royal jelly loses most of its bioactive ingredients and biological properties when stored at a temperature of 5 °C or higher. Therefore, freezing is the best method to store royal jelly [62]. Enzymatic treatment of royal jelly removes allergen proteins and enhances its nutrient content in addition to improving its digestibility and absorption in the gut without altering its freshness [2,59].\nRoyal jelly has been historically used as a beautifying agent by famous queens such as Cleopatra, and it is still involved in the cosmetic industry [29,56]. Its rich content of bioactive compounds grants it a plethora of diverse health benefits such as antioxidant, anti-inflammatory, neurotrophic, hypotensive, antidiabetic, antilipidemic, antirheumatic, anticarcinogenic, anti-fatigue, antiadipogenic, and antimicrobial activities [43,45,63]. Therefore, it is widely used to treat multiple serious conditions including diabetes, hypertension, hyperlipidemia, cancer, skin diseases, and neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease [2,43,46,59,64]. In addition, bee queens (which enjoy long lifespan as well as super fertility and physical qualities) consume royal jelly throughout their entire lives, and royal jelly is considered a promising anti-aging nutraceutical that can positively enhance fertility and improve body composition [2]."}

    LitCovid-PD-CLO

    {"project":"LitCovid-PD-CLO","denotations":[{"id":"T55123","span":{"begin":68,"end":78},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T46616","span":{"begin":94,"end":95},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T21286","span":{"begin":209,"end":215},"obj":"http://purl.obolibrary.org/obo/UBERON_0002530"},{"id":"T57925","span":{"begin":209,"end":215},"obj":"http://www.ebi.ac.uk/efo/EFO_0000797"},{"id":"T33054","span":{"begin":402,"end":405},"obj":"http://purl.obolibrary.org/obo/UBERON_0001013"},{"id":"T60055","span":{"begin":697,"end":703},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T90473","span":{"begin":1122,"end":1126},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T81345","span":{"begin":1142,"end":1146},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T12312","span":{"begin":1157,"end":1161},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T89853","span":{"begin":1245,"end":1247},"obj":"http://purl.obolibrary.org/obo/CLO_0001382"},{"id":"T90880","span":{"begin":1449,"end":1459},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T31110","span":{"begin":1980,"end":1990},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T96389","span":{"begin":1994,"end":2001},"obj":"http://purl.obolibrary.org/obo/PR_000009054"},{"id":"T79073","span":{"begin":2072,"end":2081},"obj":"http://purl.obolibrary.org/obo/SO_0000418"},{"id":"T29935","span":{"begin":2153,"end":2159},"obj":"http://purl.obolibrary.org/obo/UBERON_0002548"},{"id":"T56321","span":{"begin":2242,"end":2244},"obj":"http://purl.obolibrary.org/obo/CLO_0050510"},{"id":"T13303","span":{"begin":2312,"end":2313},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T72270","span":{"begin":2542,"end":2545},"obj":"http://purl.obolibrary.org/obo/UBERON_0001013"},{"id":"T57805","span":{"begin":3093,"end":3096},"obj":"http://purl.obolibrary.org/obo/CLO_0001302"},{"id":"T13581","span":{"begin":3135,"end":3136},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T34339","span":{"begin":3477,"end":3480},"obj":"http://purl.obolibrary.org/obo/CLO_0037067"},{"id":"T88854","span":{"begin":3541,"end":3542},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T62028","span":{"begin":3605,"end":3607},"obj":"http://purl.obolibrary.org/obo/CLO_0001812"},{"id":"T22363","span":{"begin":3620,"end":3621},"obj":"http://purl.obolibrary.org/obo/CLO_0001021"},{"id":"T29760","span":{"begin":3840,"end":3841},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T47067","span":{"begin":4099,"end":4102},"obj":"http://purl.obolibrary.org/obo/UBERON_0001007"},{"id":"T11775","span":{"begin":4099,"end":4102},"obj":"http://purl.obolibrary.org/obo/UBERON_0001555"},{"id":"T63787","span":{"begin":4099,"end":4102},"obj":"http://www.ebi.ac.uk/efo/EFO_0000834"},{"id":"T18495","span":{"begin":4154,"end":4157},"obj":"http://purl.obolibrary.org/obo/CLO_0051582"},{"id":"T1374","span":{"begin":4184,"end":4185},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T8507","span":{"begin":4349,"end":4350},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T38314","span":{"begin":4564,"end":4574},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T51767","span":{"begin":4711,"end":4715},"obj":"http://purl.obolibrary.org/obo/UBERON_0000014"},{"id":"T93540","span":{"begin":4711,"end":4715},"obj":"http://purl.obolibrary.org/obo/UBERON_0001003"},{"id":"T40396","span":{"begin":4711,"end":4715},"obj":"http://purl.obolibrary.org/obo/UBERON_0002097"},{"id":"T92016","span":{"begin":4711,"end":4715},"obj":"http://purl.obolibrary.org/obo/UBERON_0002199"},{"id":"T67474","span":{"begin":4711,"end":4715},"obj":"http://www.ebi.ac.uk/efo/EFO_0000962"},{"id":"T22291","span":{"begin":5009,"end":5010},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"}],"text":"2.1. Royal Jelly: Its Constituents, Biological, and Pharmacological Activities\nRoyal jelly is a thick, milky, white-yellowish, acidic colloid substance secreted from the hypopharyngeal and mandibular salivary glands of young nurse honey bees (5–15 days old) [32,43]. In general, fresh royal jelly mostly consists of water (67% w/w) in addition to carbohydrates (16%), proteins and amino acids (12.5%), fat (5%), and many other elements [32]. However, royal jelly content of these substances noticeably varies depending on numerous factors like botanical source, bee species, bee artificial feeding, weather, season, location, method of processing, and the like [2,44].\nProtein is the most copious active element in royal jelly, representing half the weight of its dry matter [2]. It vastly comprises nine 49–87 kDa water-insoluble proteins, known as major royal jelly proteins 1–9 (MRJPs1-9) [2,45]. MRJPs constitute more than 80% of royal jelly protein content, and MRJPs1–5 constitute 82–90% of all MRJPs. MRJPs contain 400–578 amino acids that contribute to the antioxidant effect of royal jelly as well as its role in cell proliferation, cell adhesion, cell growth, and immunity [46,47]. Novel non-MRJPs proteins have been newly discovered [48]. Royalisin, jelleines, and aspimin are examples of other proteins that exist in royal jelly, albeit in small amounts. These proteins as well as MRJPs demonstrate strong antimicrobial and bactericidal activities even against the most drug-resistant bacterial strains such as methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, vancomycin-resistant Enterococci, as well as extended-spectrum β-lactamase-producing Proteus mirabilis and Escherichia coli [28,29].\nCarbohydrates (e.g., fructose, glucose maltose, trehalose, melibiose, ribose, and erlose) constitute 7.5–16% or royal jelly content [49]. Reducing sugars in royal jelly are thought to contribute to its epigenetic effect through the activation of insulin-like growth factor 1 (IGF-1) and mammalian target of rapamycin (mTOR) signaling cascades. Thus, they stimulate caste differentiation of Apis mellifera larvae into queens by increasing intake of food and key nutrients [50].\nLipids make up 7–18% of the dry weight of royal jelly. This fraction largely comprises a group of unique and rare saturated or monounsaturated short and medium chain fatty acids that are terminally or internally hydroxylated with terminal mono- or dicarboxylic acid functions [2,28]. The vast majority of royal jelly fat content (80–85%) consists of short hydroxyl fatty acids such as trans-10-hydroxy-2-decenoic acid (10-HDA), which exists only in royal jelly; and therefore, it is known as royal jelly acid or queen bee acid [28,49,51]. 10-HDA is one of the most potent bioactive elements in royal jelly expressing strong anti-aging, neuroprotective, antiproliferative, antimicrobial, antioxidant, anti-inflammatory, and epigenetic effects [52,53,54,55,56,57,58]. In addition, the lipid fraction of royal jelly contains phenolic acids (4–10%), wax (5–6%), steroids (3–4%), and phospholipids (0.4–0.8%) [49].\nA wide range of minor constituents and bioactive compounds exist profusely in royal jelly such as acetylcholine, nucleotides (adenosine, guanosine, adenosine tri-phosphate (ATP), adenosine monophosphate (AMP)), minerals (iron, sodium, calcium, potassium, zinc, magnesium, manganese, and copper), amino acids (8 out of 9 essential amino acids Val, Leu, Ile, Thr, Met, Phe, Lys, and Trp), vitamins (retinol (A), ascorbic acid (C), tocopherol (E), riboflavin (B2), niacin (B3), and other B vitamins), esters, aldehydes, ketones, alcohol, and minor heterocyclic compounds [2,28,49,59,60,61]. It is worth noting that royal jelly loses most of its bioactive ingredients and biological properties when stored at a temperature of 5 °C or higher. Therefore, freezing is the best method to store royal jelly [62]. Enzymatic treatment of royal jelly removes allergen proteins and enhances its nutrient content in addition to improving its digestibility and absorption in the gut without altering its freshness [2,59].\nRoyal jelly has been historically used as a beautifying agent by famous queens such as Cleopatra, and it is still involved in the cosmetic industry [29,56]. Its rich content of bioactive compounds grants it a plethora of diverse health benefits such as antioxidant, anti-inflammatory, neurotrophic, hypotensive, antidiabetic, antilipidemic, antirheumatic, anticarcinogenic, anti-fatigue, antiadipogenic, and antimicrobial activities [43,45,63]. Therefore, it is widely used to treat multiple serious conditions including diabetes, hypertension, hyperlipidemia, cancer, skin diseases, and neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease [2,43,46,59,64]. In addition, bee queens (which enjoy long lifespan as well as super fertility and physical qualities) consume royal jelly throughout their entire lives, and royal jelly is considered a promising anti-aging nutraceutical that can positively enhance fertility and improve body composition [2]."}

    LitCovid-PD-CHEBI

    {"project":"LitCovid-PD-CHEBI","denotations":[{"id":"T43","span":{"begin":285,"end":296},"obj":"Chemical"},{"id":"T44","span":{"begin":316,"end":321},"obj":"Chemical"},{"id":"T45","span":{"begin":347,"end":360},"obj":"Chemical"},{"id":"T46","span":{"begin":368,"end":376},"obj":"Chemical"},{"id":"T47","span":{"begin":381,"end":392},"obj":"Chemical"},{"id":"T48","span":{"begin":381,"end":386},"obj":"Chemical"},{"id":"T49","span":{"begin":387,"end":392},"obj":"Chemical"},{"id":"T50","span":{"begin":451,"end":462},"obj":"Chemical"},{"id":"T51","span":{"begin":669,"end":676},"obj":"Chemical"},{"id":"T52","span":{"begin":715,"end":726},"obj":"Chemical"},{"id":"T53","span":{"begin":815,"end":820},"obj":"Chemical"},{"id":"T54","span":{"begin":831,"end":839},"obj":"Chemical"},{"id":"T55","span":{"begin":856,"end":867},"obj":"Chemical"},{"id":"T56","span":{"begin":868,"end":876},"obj":"Chemical"},{"id":"T57","span":{"begin":934,"end":945},"obj":"Chemical"},{"id":"T58","span":{"begin":946,"end":953},"obj":"Chemical"},{"id":"T59","span":{"begin":1030,"end":1041},"obj":"Chemical"},{"id":"T60","span":{"begin":1030,"end":1035},"obj":"Chemical"},{"id":"T61","span":{"begin":1036,"end":1041},"obj":"Chemical"},{"id":"T62","span":{"begin":1065,"end":1076},"obj":"Chemical"},{"id":"T63","span":{"begin":1087,"end":1098},"obj":"Chemical"},{"id":"T64","span":{"begin":1208,"end":1216},"obj":"Chemical"},{"id":"T65","span":{"begin":1306,"end":1314},"obj":"Chemical"},{"id":"T66","span":{"begin":1329,"end":1340},"obj":"Chemical"},{"id":"T67","span":{"begin":1373,"end":1381},"obj":"Chemical"},{"id":"T68","span":{"begin":1418,"end":1431},"obj":"Chemical"},{"id":"T69","span":{"begin":1482,"end":1486},"obj":"Chemical"},{"id":"T70","span":{"begin":1523,"end":1534},"obj":"Chemical"},{"id":"T71","span":{"begin":1615,"end":1625},"obj":"Chemical"},{"id":"T73","span":{"begin":1769,"end":1777},"obj":"Chemical"},{"id":"T74","span":{"begin":1779,"end":1786},"obj":"Chemical"},{"id":"T76","span":{"begin":1787,"end":1794},"obj":"Chemical"},{"id":"T77","span":{"begin":1796,"end":1805},"obj":"Chemical"},{"id":"T78","span":{"begin":1807,"end":1816},"obj":"Chemical"},{"id":"T79","span":{"begin":1818,"end":1824},"obj":"Chemical"},{"id":"T81","span":{"begin":1830,"end":1836},"obj":"Chemical"},{"id":"T82","span":{"begin":1860,"end":1871},"obj":"Chemical"},{"id":"T83","span":{"begin":1905,"end":1916},"obj":"Chemical"},{"id":"T84","span":{"begin":1994,"end":2001},"obj":"Chemical"},{"id":"T85","span":{"begin":2055,"end":2064},"obj":"Chemical"},{"id":"T86","span":{"begin":2209,"end":2218},"obj":"Chemical"},{"id":"T87","span":{"begin":2267,"end":2278},"obj":"Chemical"},{"id":"T88","span":{"begin":2314,"end":2319},"obj":"Chemical"},{"id":"T89","span":{"begin":2378,"end":2402},"obj":"Chemical"},{"id":"T90","span":{"begin":2391,"end":2402},"obj":"Chemical"},{"id":"T91","span":{"begin":2397,"end":2402},"obj":"Chemical"},{"id":"T92","span":{"begin":2473,"end":2490},"obj":"Chemical"},{"id":"T93","span":{"begin":2486,"end":2490},"obj":"Chemical"},{"id":"T94","span":{"begin":2530,"end":2541},"obj":"Chemical"},{"id":"T95","span":{"begin":2581,"end":2589},"obj":"Chemical"},{"id":"T97","span":{"begin":2590,"end":2601},"obj":"Chemical"},{"id":"T98","span":{"begin":2596,"end":2601},"obj":"Chemical"},{"id":"T99","span":{"begin":2619,"end":2626},"obj":"Chemical"},{"id":"T100","span":{"begin":2627,"end":2642},"obj":"Chemical"},{"id":"T101","span":{"begin":2629,"end":2642},"obj":"Chemical"},{"id":"T102","span":{"begin":2638,"end":2642},"obj":"Chemical"},{"id":"T103","span":{"begin":2647,"end":2650},"obj":"Chemical"},{"id":"T104","span":{"begin":2674,"end":2685},"obj":"Chemical"},{"id":"T105","span":{"begin":2717,"end":2728},"obj":"Chemical"},{"id":"T106","span":{"begin":2729,"end":2733},"obj":"Chemical"},{"id":"T107","span":{"begin":2747,"end":2751},"obj":"Chemical"},{"id":"T108","span":{"begin":2767,"end":2770},"obj":"Chemical"},{"id":"T109","span":{"begin":2819,"end":2830},"obj":"Chemical"},{"id":"T110","span":{"begin":2897,"end":2910},"obj":"Chemical"},{"id":"T111","span":{"begin":2912,"end":2923},"obj":"Chemical"},{"id":"T112","span":{"begin":3008,"end":3013},"obj":"Chemical"},{"id":"T113","span":{"begin":3026,"end":3037},"obj":"Chemical"},{"id":"T114","span":{"begin":3056,"end":3061},"obj":"Chemical"},{"id":"T115","span":{"begin":3071,"end":3074},"obj":"Chemical"},{"id":"T116","span":{"begin":3083,"end":3091},"obj":"Chemical"},{"id":"T117","span":{"begin":3104,"end":3117},"obj":"Chemical"},{"id":"T118","span":{"begin":3213,"end":3224},"obj":"Chemical"},{"id":"T119","span":{"begin":3233,"end":3246},"obj":"Chemical"},{"id":"T120","span":{"begin":3248,"end":3259},"obj":"Chemical"},{"id":"T121","span":{"begin":3261,"end":3270},"obj":"Chemical"},{"id":"T122","span":{"begin":3272,"end":3281},"obj":"Chemical"},{"id":"T123","span":{"begin":3283,"end":3292},"obj":"Chemical"},{"id":"T124","span":{"begin":3297,"end":3306},"obj":"Chemical"},{"id":"T128","span":{"begin":3308,"end":3311},"obj":"Chemical"},{"id":"T130","span":{"begin":3314,"end":3323},"obj":"Chemical"},{"id":"T131","span":{"begin":3339,"end":3342},"obj":"Chemical"},{"id":"T134","span":{"begin":3346,"end":3354},"obj":"Chemical"},{"id":"T135","span":{"begin":3356,"end":3360},"obj":"Chemical"},{"id":"T136","span":{"begin":3362,"end":3368},"obj":"Chemical"},{"id":"T137","span":{"begin":3370,"end":3377},"obj":"Chemical"},{"id":"T139","span":{"begin":3379,"end":3388},"obj":"Chemical"},{"id":"T140","span":{"begin":3390,"end":3394},"obj":"Chemical"},{"id":"T142","span":{"begin":3396,"end":3405},"obj":"Chemical"},{"id":"T143","span":{"begin":3407,"end":3416},"obj":"Chemical"},{"id":"T145","span":{"begin":3422,"end":3428},"obj":"Chemical"},{"id":"T147","span":{"begin":3431,"end":3442},"obj":"Chemical"},{"id":"T148","span":{"begin":3431,"end":3436},"obj":"Chemical"},{"id":"T149","span":{"begin":3437,"end":3442},"obj":"Chemical"},{"id":"T150","span":{"begin":3465,"end":3476},"obj":"Chemical"},{"id":"T151","span":{"begin":3465,"end":3470},"obj":"Chemical"},{"id":"T152","span":{"begin":3471,"end":3476},"obj":"Chemical"},{"id":"T153","span":{"begin":3477,"end":3480},"obj":"Chemical"},{"id":"T155","span":{"begin":3482,"end":3485},"obj":"Chemical"},{"id":"T158","span":{"begin":3487,"end":3490},"obj":"Chemical"},{"id":"T160","span":{"begin":3492,"end":3495},"obj":"Chemical"},{"id":"T162","span":{"begin":3497,"end":3500},"obj":"Chemical"},{"id":"T165","span":{"begin":3502,"end":3505},"obj":"Chemical"},{"id":"T167","span":{"begin":3507,"end":3510},"obj":"Chemical"},{"id":"T170","span":{"begin":3516,"end":3519},"obj":"Chemical"},{"id":"T173","span":{"begin":3522,"end":3530},"obj":"Chemical"},{"id":"T174","span":{"begin":3532,"end":3539},"obj":"Chemical"},{"id":"T175","span":{"begin":3545,"end":3558},"obj":"Chemical"},{"id":"T177","span":{"begin":3554,"end":3558},"obj":"Chemical"},{"id":"T178","span":{"begin":3564,"end":3574},"obj":"Chemical"},{"id":"T179","span":{"begin":3580,"end":3590},"obj":"Chemical"},{"id":"T181","span":{"begin":3592,"end":3594},"obj":"Chemical"},{"id":"T182","span":{"begin":3597,"end":3603},"obj":"Chemical"},{"id":"T183","span":{"begin":3620,"end":3630},"obj":"Chemical"},{"id":"T184","span":{"begin":3622,"end":3630},"obj":"Chemical"},{"id":"T185","span":{"begin":3633,"end":3639},"obj":"Chemical"},{"id":"T186","span":{"begin":3641,"end":3650},"obj":"Chemical"},{"id":"T187","span":{"begin":3652,"end":3659},"obj":"Chemical"},{"id":"T188","span":{"begin":3661,"end":3668},"obj":"Chemical"},{"id":"T190","span":{"begin":3680,"end":3702},"obj":"Chemical"},{"id":"T191","span":{"begin":3747,"end":3758},"obj":"Chemical"},{"id":"T192","span":{"begin":3921,"end":3932},"obj":"Chemical"},{"id":"T193","span":{"begin":3962,"end":3973},"obj":"Chemical"},{"id":"T194","span":{"begin":3982,"end":3990},"obj":"Chemical"},{"id":"T195","span":{"begin":3991,"end":3999},"obj":"Chemical"},{"id":"T196","span":{"begin":4017,"end":4025},"obj":"Chemical"},{"id":"T197","span":{"begin":4272,"end":4280},"obj":"Chemical"},{"id":"T198","span":{"begin":4395,"end":4406},"obj":"Chemical"},{"id":"T199","span":{"begin":4454,"end":4466},"obj":"Chemical"},{"id":"T200","span":{"begin":4550,"end":4563},"obj":"Chemical"},{"id":"T201","span":{"begin":4936,"end":4947},"obj":"Chemical"},{"id":"T202","span":{"begin":4983,"end":4994},"obj":"Chemical"},{"id":"T203","span":{"begin":5032,"end":5045},"obj":"Chemical"}],"attributes":[{"id":"A43","pred":"chebi_id","subj":"T43","obj":"http://purl.obolibrary.org/obo/CHEBI_78665"},{"id":"A44","pred":"chebi_id","subj":"T44","obj":"http://purl.obolibrary.org/obo/CHEBI_15377"},{"id":"A45","pred":"chebi_id","subj":"T45","obj":"http://purl.obolibrary.org/obo/CHEBI_16646"},{"id":"A46","pred":"chebi_id","subj":"T46","obj":"http://purl.obolibrary.org/obo/CHEBI_36080"},{"id":"A47","pred":"chebi_id","subj":"T47","obj":"http://purl.obolibrary.org/obo/CHEBI_33709"},{"id":"A48","pred":"chebi_id","subj":"T48","obj":"http://purl.obolibrary.org/obo/CHEBI_46882"},{"id":"A49","pred":"chebi_id","subj":"T49","obj":"http://purl.obolibrary.org/obo/CHEBI_37527"},{"id":"A50","pred":"chebi_id","subj":"T50","obj":"http://purl.obolibrary.org/obo/CHEBI_78665"},{"id":"A51","pred":"chebi_id","subj":"T51","obj":"http://purl.obolibrary.org/obo/CHEBI_16541"},{"id":"A52","pred":"chebi_id","subj":"T52","obj":"http://purl.obolibrary.org/obo/CHEBI_78665"},{"id":"A53","pred":"chebi_id","subj":"T53","obj":"http://purl.obolibrary.org/obo/CHEBI_15377"},{"id":"A54","pred":"chebi_id","subj":"T54","obj":"http://purl.obolibrary.org/obo/CHEBI_36080"},{"id":"A55","pred":"chebi_id","subj":"T55","obj":"http://purl.obolibrary.org/obo/CHEBI_78665"},{"id":"A56","pred":"chebi_id","subj":"T56","obj":"http://purl.obolibrary.org/obo/CHEBI_36080"},{"id":"A57","pred":"chebi_id","subj":"T57","obj":"http://purl.obolibrary.org/obo/CHEBI_78665"},{"id":"A58","pred":"chebi_id","subj":"T58","obj":"http://purl.obolibrary.org/obo/CHEBI_36080"},{"id":"A59","pred":"chebi_id","subj":"T59","obj":"http://purl.obolibrary.org/obo/CHEBI_33709"},{"id":"A60","pred":"chebi_id","subj":"T60","obj":"http://purl.obolibrary.org/obo/CHEBI_46882"},{"id":"A61","pred":"chebi_id","subj":"T61","obj":"http://purl.obolibrary.org/obo/CHEBI_37527"},{"id":"A62","pred":"chebi_id","subj":"T62","obj":"http://purl.obolibrary.org/obo/CHEBI_22586"},{"id":"A63","pred":"chebi_id","subj":"T63","obj":"http://purl.obolibrary.org/obo/CHEBI_78665"},{"id":"A64","pred":"chebi_id","subj":"T64","obj":"http://purl.obolibrary.org/obo/CHEBI_36080"},{"id":"A65","pred":"chebi_id","subj":"T65","obj":"http://purl.obolibrary.org/obo/CHEBI_36080"},{"id":"A66","pred":"chebi_id","subj":"T66","obj":"http://purl.obolibrary.org/obo/CHEBI_78665"},{"id":"A67","pred":"chebi_id","subj":"T67","obj":"http://purl.obolibrary.org/obo/CHEBI_36080"},{"id":"A68","pred":"chebi_id","subj":"T68","obj":"http://purl.obolibrary.org/obo/CHEBI_33281"},{"id":"A69","pred":"chebi_id","subj":"T69","obj":"http://purl.obolibrary.org/obo/CHEBI_23888"},{"id":"A70","pred":"chebi_id","subj":"T70","obj":"http://purl.obolibrary.org/obo/CHEBI_6827"},{"id":"A71","pred":"chebi_id","subj":"T71","obj":"http://purl.obolibrary.org/obo/CHEBI_28001"},{"id":"A72","pred":"chebi_id","subj":"T71","obj":"http://purl.obolibrary.org/obo/CHEBI_76842"},{"id":"A73","pred":"chebi_id","subj":"T73","obj":"http://purl.obolibrary.org/obo/CHEBI_28757"},{"id":"A74","pred":"chebi_id","subj":"T74","obj":"http://purl.obolibrary.org/obo/CHEBI_17234"},{"id":"A75","pred":"chebi_id","subj":"T74","obj":"http://purl.obolibrary.org/obo/CHEBI_4167"},{"id":"A76","pred":"chebi_id","subj":"T76","obj":"http://purl.obolibrary.org/obo/CHEBI_17306"},{"id":"A77","pred":"chebi_id","subj":"T77","obj":"http://purl.obolibrary.org/obo/CHEBI_27082"},{"id":"A78","pred":"chebi_id","subj":"T78","obj":"http://purl.obolibrary.org/obo/CHEBI_28053"},{"id":"A79","pred":"chebi_id","subj":"T79","obj":"http://purl.obolibrary.org/obo/CHEBI_33942"},{"id":"A80","pred":"chebi_id","subj":"T79","obj":"http://purl.obolibrary.org/obo/CHEBI_47013"},{"id":"A81","pred":"chebi_id","subj":"T81","obj":"http://purl.obolibrary.org/obo/CHEBI_55512"},{"id":"A82","pred":"chebi_id","subj":"T82","obj":"http://purl.obolibrary.org/obo/CHEBI_78665"},{"id":"A83","pred":"chebi_id","subj":"T83","obj":"http://purl.obolibrary.org/obo/CHEBI_78665"},{"id":"A84","pred":"chebi_id","subj":"T84","obj":"http://purl.obolibrary.org/obo/CHEBI_145810"},{"id":"A85","pred":"chebi_id","subj":"T85","obj":"http://purl.obolibrary.org/obo/CHEBI_9168"},{"id":"A86","pred":"chebi_id","subj":"T86","obj":"http://purl.obolibrary.org/obo/CHEBI_33284"},{"id":"A87","pred":"chebi_id","subj":"T87","obj":"http://purl.obolibrary.org/obo/CHEBI_78665"},{"id":"A88","pred":"chebi_id","subj":"T88","obj":"http://purl.obolibrary.org/obo/CHEBI_24433"},{"id":"A89","pred":"chebi_id","subj":"T89","obj":"http://purl.obolibrary.org/obo/CHEBI_59554"},{"id":"A90","pred":"chebi_id","subj":"T90","obj":"http://purl.obolibrary.org/obo/CHEBI_35366"},{"id":"A91","pred":"chebi_id","subj":"T91","obj":"http://purl.obolibrary.org/obo/CHEBI_37527"},{"id":"A92","pred":"chebi_id","subj":"T92","obj":"http://purl.obolibrary.org/obo/CHEBI_35692"},{"id":"A93","pred":"chebi_id","subj":"T93","obj":"http://purl.obolibrary.org/obo/CHEBI_37527"},{"id":"A94","pred":"chebi_id","subj":"T94","obj":"http://purl.obolibrary.org/obo/CHEBI_78665"},{"id":"A95","pred":"chebi_id","subj":"T95","obj":"http://purl.obolibrary.org/obo/CHEBI_29191"},{"id":"A96","pred":"chebi_id","subj":"T95","obj":"http://purl.obolibrary.org/obo/CHEBI_43176"},{"id":"A97","pred":"chebi_id","subj":"T97","obj":"http://purl.obolibrary.org/obo/CHEBI_35366"},{"id":"A98","pred":"chebi_id","subj":"T98","obj":"http://purl.obolibrary.org/obo/CHEBI_37527"},{"id":"A99","pred":"chebi_id","subj":"T99","obj":"http://purl.obolibrary.org/obo/CHEBI_43176"},{"id":"A100","pred":"chebi_id","subj":"T100","obj":"http://purl.obolibrary.org/obo/CHEBI_50465"},{"id":"A101","pred":"chebi_id","subj":"T101","obj":"http://purl.obolibrary.org/obo/CHEBI_36003"},{"id":"A102","pred":"chebi_id","subj":"T102","obj":"http://purl.obolibrary.org/obo/CHEBI_37527"},{"id":"A103","pred":"chebi_id","subj":"T103","obj":"http://purl.obolibrary.org/obo/CHEBI_17314"},{"id":"A104","pred":"chebi_id","subj":"T104","obj":"http://purl.obolibrary.org/obo/CHEBI_78665"},{"id":"A105","pred":"chebi_id","subj":"T105","obj":"http://purl.obolibrary.org/obo/CHEBI_78665"},{"id":"A106","pred":"chebi_id","subj":"T106","obj":"http://purl.obolibrary.org/obo/CHEBI_37527"},{"id":"A107","pred":"chebi_id","subj":"T107","obj":"http://purl.obolibrary.org/obo/CHEBI_37527"},{"id":"A108","pred":"chebi_id","subj":"T108","obj":"http://purl.obolibrary.org/obo/CHEBI_17314"},{"id":"A109","pred":"chebi_id","subj":"T109","obj":"http://purl.obolibrary.org/obo/CHEBI_78665"},{"id":"A110","pred":"chebi_id","subj":"T110","obj":"http://purl.obolibrary.org/obo/CHEBI_33281"},{"id":"A111","pred":"chebi_id","subj":"T111","obj":"http://purl.obolibrary.org/obo/CHEBI_22586"},{"id":"A112","pred":"chebi_id","subj":"T112","obj":"http://purl.obolibrary.org/obo/CHEBI_18059"},{"id":"A113","pred":"chebi_id","subj":"T113","obj":"http://purl.obolibrary.org/obo/CHEBI_78665"},{"id":"A114","pred":"chebi_id","subj":"T114","obj":"http://purl.obolibrary.org/obo/CHEBI_37527"},{"id":"A115","pred":"chebi_id","subj":"T115","obj":"http://purl.obolibrary.org/obo/CHEBI_73702"},{"id":"A116","pred":"chebi_id","subj":"T116","obj":"http://purl.obolibrary.org/obo/CHEBI_35341"},{"id":"A117","pred":"chebi_id","subj":"T117","obj":"http://purl.obolibrary.org/obo/CHEBI_16247"},{"id":"A118","pred":"chebi_id","subj":"T118","obj":"http://purl.obolibrary.org/obo/CHEBI_78665"},{"id":"A119","pred":"chebi_id","subj":"T119","obj":"http://purl.obolibrary.org/obo/CHEBI_15355"},{"id":"A120","pred":"chebi_id","subj":"T120","obj":"http://purl.obolibrary.org/obo/CHEBI_36976"},{"id":"A121","pred":"chebi_id","subj":"T121","obj":"http://purl.obolibrary.org/obo/CHEBI_16335"},{"id":"A122","pred":"chebi_id","subj":"T122","obj":"http://purl.obolibrary.org/obo/CHEBI_16750"},{"id":"A123","pred":"chebi_id","subj":"T123","obj":"http://purl.obolibrary.org/obo/CHEBI_16335"},{"id":"A124","pred":"chebi_id","subj":"T124","obj":"http://purl.obolibrary.org/obo/CHEBI_18367"},{"id":"A125","pred":"chebi_id","subj":"T124","obj":"http://purl.obolibrary.org/obo/CHEBI_26020"},{"id":"A126","pred":"chebi_id","subj":"T124","obj":"http://purl.obolibrary.org/obo/CHEBI_35780"},{"id":"A127","pred":"chebi_id","subj":"T124","obj":"http://purl.obolibrary.org/obo/CHEBI_43474"},{"id":"A128","pred":"chebi_id","subj":"T128","obj":"http://purl.obolibrary.org/obo/CHEBI_15422"},{"id":"A129","pred":"chebi_id","subj":"T128","obj":"http://purl.obolibrary.org/obo/CHEBI_30616"},{"id":"A130","pred":"chebi_id","subj":"T130","obj":"http://purl.obolibrary.org/obo/CHEBI_16335"},{"id":"A131","pred":"chebi_id","subj":"T131","obj":"http://purl.obolibrary.org/obo/CHEBI_16027"},{"id":"A132","pred":"chebi_id","subj":"T131","obj":"http://purl.obolibrary.org/obo/CHEBI_28971"},{"id":"A133","pred":"chebi_id","subj":"T131","obj":"http://purl.obolibrary.org/obo/CHEBI_456215"},{"id":"A134","pred":"chebi_id","subj":"T134","obj":"http://purl.obolibrary.org/obo/CHEBI_46662"},{"id":"A135","pred":"chebi_id","subj":"T135","obj":"http://purl.obolibrary.org/obo/CHEBI_18248"},{"id":"A136","pred":"chebi_id","subj":"T136","obj":"http://purl.obolibrary.org/obo/CHEBI_26708"},{"id":"A137","pred":"chebi_id","subj":"T137","obj":"http://purl.obolibrary.org/obo/CHEBI_22984"},{"id":"A138","pred":"chebi_id","subj":"T137","obj":"http://purl.obolibrary.org/obo/CHEBI_29320"},{"id":"A139","pred":"chebi_id","subj":"T139","obj":"http://purl.obolibrary.org/obo/CHEBI_26216"},{"id":"A140","pred":"chebi_id","subj":"T140","obj":"http://purl.obolibrary.org/obo/CHEBI_27363"},{"id":"A141","pred":"chebi_id","subj":"T140","obj":"http://purl.obolibrary.org/obo/CHEBI_30185"},{"id":"A142","pred":"chebi_id","subj":"T142","obj":"http://purl.obolibrary.org/obo/CHEBI_25107"},{"id":"A143","pred":"chebi_id","subj":"T143","obj":"http://purl.obolibrary.org/obo/CHEBI_18291"},{"id":"A144","pred":"chebi_id","subj":"T143","obj":"http://purl.obolibrary.org/obo/CHEBI_35154"},{"id":"A145","pred":"chebi_id","subj":"T145","obj":"http://purl.obolibrary.org/obo/CHEBI_28694"},{"id":"A146","pred":"chebi_id","subj":"T145","obj":"http://purl.obolibrary.org/obo/CHEBI_30052"},{"id":"A147","pred":"chebi_id","subj":"T147","obj":"http://purl.obolibrary.org/obo/CHEBI_33709"},{"id":"A148","pred":"chebi_id","subj":"T148","obj":"http://purl.obolibrary.org/obo/CHEBI_46882"},{"id":"A149","pred":"chebi_id","subj":"T149","obj":"http://purl.obolibrary.org/obo/CHEBI_37527"},{"id":"A150","pred":"chebi_id","subj":"T150","obj":"http://purl.obolibrary.org/obo/CHEBI_33709"},{"id":"A151","pred":"chebi_id","subj":"T151","obj":"http://purl.obolibrary.org/obo/CHEBI_46882"},{"id":"A152","pred":"chebi_id","subj":"T152","obj":"http://purl.obolibrary.org/obo/CHEBI_37527"},{"id":"A153","pred":"chebi_id","subj":"T153","obj":"http://purl.obolibrary.org/obo/CHEBI_16414"},{"id":"A154","pred":"chebi_id","subj":"T153","obj":"http://purl.obolibrary.org/obo/CHEBI_30015"},{"id":"A155","pred":"chebi_id","subj":"T155","obj":"http://purl.obolibrary.org/obo/CHEBI_15603"},{"id":"A156","pred":"chebi_id","subj":"T155","obj":"http://purl.obolibrary.org/obo/CHEBI_25017"},{"id":"A157","pred":"chebi_id","subj":"T155","obj":"http://purl.obolibrary.org/obo/CHEBI_30006"},{"id":"A158","pred":"chebi_id","subj":"T158","obj":"http://purl.obolibrary.org/obo/CHEBI_17191"},{"id":"A159","pred":"chebi_id","subj":"T158","obj":"http://purl.obolibrary.org/obo/CHEBI_30009"},{"id":"A160","pred":"chebi_id","subj":"T160","obj":"http://purl.obolibrary.org/obo/CHEBI_16857"},{"id":"A161","pred":"chebi_id","subj":"T160","obj":"http://purl.obolibrary.org/obo/CHEBI_30013"},{"id":"A162","pred":"chebi_id","subj":"T162","obj":"http://purl.obolibrary.org/obo/CHEBI_16044"},{"id":"A163","pred":"chebi_id","subj":"T162","obj":"http://purl.obolibrary.org/obo/CHEBI_16643"},{"id":"A164","pred":"chebi_id","subj":"T162","obj":"http://purl.obolibrary.org/obo/CHEBI_16811"},{"id":"A165","pred":"chebi_id","subj":"T165","obj":"http://purl.obolibrary.org/obo/CHEBI_17295"},{"id":"A166","pred":"chebi_id","subj":"T165","obj":"http://purl.obolibrary.org/obo/CHEBI_29997"},{"id":"A167","pred":"chebi_id","subj":"T167","obj":"http://purl.obolibrary.org/obo/CHEBI_133538"},{"id":"A168","pred":"chebi_id","subj":"T167","obj":"http://purl.obolibrary.org/obo/CHEBI_18019"},{"id":"A169","pred":"chebi_id","subj":"T167","obj":"http://purl.obolibrary.org/obo/CHEBI_29967"},{"id":"A170","pred":"chebi_id","subj":"T170","obj":"http://purl.obolibrary.org/obo/CHEBI_16828"},{"id":"A171","pred":"chebi_id","subj":"T170","obj":"http://purl.obolibrary.org/obo/CHEBI_27897"},{"id":"A172","pred":"chebi_id","subj":"T170","obj":"http://purl.obolibrary.org/obo/CHEBI_29954"},{"id":"A173","pred":"chebi_id","subj":"T173","obj":"http://purl.obolibrary.org/obo/CHEBI_33229"},{"id":"A174","pred":"chebi_id","subj":"T174","obj":"http://purl.obolibrary.org/obo/CHEBI_50211"},{"id":"A175","pred":"chebi_id","subj":"T175","obj":"http://purl.obolibrary.org/obo/CHEBI_22652"},{"id":"A176","pred":"chebi_id","subj":"T175","obj":"http://purl.obolibrary.org/obo/CHEBI_29073"},{"id":"A177","pred":"chebi_id","subj":"T177","obj":"http://purl.obolibrary.org/obo/CHEBI_37527"},{"id":"A178","pred":"chebi_id","subj":"T178","obj":"http://purl.obolibrary.org/obo/CHEBI_27013"},{"id":"A179","pred":"chebi_id","subj":"T179","obj":"http://purl.obolibrary.org/obo/CHEBI_17015"},{"id":"A180","pred":"chebi_id","subj":"T179","obj":"http://purl.obolibrary.org/obo/CHEBI_57986"},{"id":"A181","pred":"chebi_id","subj":"T181","obj":"http://purl.obolibrary.org/obo/CHEBI_51707"},{"id":"A182","pred":"chebi_id","subj":"T182","obj":"http://purl.obolibrary.org/obo/CHEBI_17154"},{"id":"A183","pred":"chebi_id","subj":"T183","obj":"http://purl.obolibrary.org/obo/CHEBI_75769"},{"id":"A184","pred":"chebi_id","subj":"T184","obj":"http://purl.obolibrary.org/obo/CHEBI_33229"},{"id":"A185","pred":"chebi_id","subj":"T185","obj":"http://purl.obolibrary.org/obo/CHEBI_35701"},{"id":"A186","pred":"chebi_id","subj":"T186","obj":"http://purl.obolibrary.org/obo/CHEBI_17478"},{"id":"A187","pred":"chebi_id","subj":"T187","obj":"http://purl.obolibrary.org/obo/CHEBI_17087"},{"id":"A188","pred":"chebi_id","subj":"T188","obj":"http://purl.obolibrary.org/obo/CHEBI_16236"},{"id":"A189","pred":"chebi_id","subj":"T188","obj":"http://purl.obolibrary.org/obo/CHEBI_30879"},{"id":"A190","pred":"chebi_id","subj":"T190","obj":"http://purl.obolibrary.org/obo/CHEBI_5686"},{"id":"A191","pred":"chebi_id","subj":"T191","obj":"http://purl.obolibrary.org/obo/CHEBI_78665"},{"id":"A192","pred":"chebi_id","subj":"T192","obj":"http://purl.obolibrary.org/obo/CHEBI_78665"},{"id":"A193","pred":"chebi_id","subj":"T193","obj":"http://purl.obolibrary.org/obo/CHEBI_78665"},{"id":"A194","pred":"chebi_id","subj":"T194","obj":"http://purl.obolibrary.org/obo/CHEBI_50904"},{"id":"A195","pred":"chebi_id","subj":"T195","obj":"http://purl.obolibrary.org/obo/CHEBI_36080"},{"id":"A196","pred":"chebi_id","subj":"T196","obj":"http://purl.obolibrary.org/obo/CHEBI_33284"},{"id":"A197","pred":"chebi_id","subj":"T197","obj":"http://purl.obolibrary.org/obo/CHEBI_64857"},{"id":"A198","pred":"chebi_id","subj":"T198","obj":"http://purl.obolibrary.org/obo/CHEBI_22586"},{"id":"A199","pred":"chebi_id","subj":"T199","obj":"http://purl.obolibrary.org/obo/CHEBI_35526"},{"id":"A200","pred":"chebi_id","subj":"T200","obj":"http://purl.obolibrary.org/obo/CHEBI_33281"},{"id":"A201","pred":"chebi_id","subj":"T201","obj":"http://purl.obolibrary.org/obo/CHEBI_78665"},{"id":"A202","pred":"chebi_id","subj":"T202","obj":"http://purl.obolibrary.org/obo/CHEBI_78665"},{"id":"A203","pred":"chebi_id","subj":"T203","obj":"http://purl.obolibrary.org/obo/CHEBI_50733"}],"text":"2.1. Royal Jelly: Its Constituents, Biological, and Pharmacological Activities\nRoyal jelly is a thick, milky, white-yellowish, acidic colloid substance secreted from the hypopharyngeal and mandibular salivary glands of young nurse honey bees (5–15 days old) [32,43]. In general, fresh royal jelly mostly consists of water (67% w/w) in addition to carbohydrates (16%), proteins and amino acids (12.5%), fat (5%), and many other elements [32]. However, royal jelly content of these substances noticeably varies depending on numerous factors like botanical source, bee species, bee artificial feeding, weather, season, location, method of processing, and the like [2,44].\nProtein is the most copious active element in royal jelly, representing half the weight of its dry matter [2]. It vastly comprises nine 49–87 kDa water-insoluble proteins, known as major royal jelly proteins 1–9 (MRJPs1-9) [2,45]. MRJPs constitute more than 80% of royal jelly protein content, and MRJPs1–5 constitute 82–90% of all MRJPs. MRJPs contain 400–578 amino acids that contribute to the antioxidant effect of royal jelly as well as its role in cell proliferation, cell adhesion, cell growth, and immunity [46,47]. Novel non-MRJPs proteins have been newly discovered [48]. Royalisin, jelleines, and aspimin are examples of other proteins that exist in royal jelly, albeit in small amounts. These proteins as well as MRJPs demonstrate strong antimicrobial and bactericidal activities even against the most drug-resistant bacterial strains such as methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, vancomycin-resistant Enterococci, as well as extended-spectrum β-lactamase-producing Proteus mirabilis and Escherichia coli [28,29].\nCarbohydrates (e.g., fructose, glucose maltose, trehalose, melibiose, ribose, and erlose) constitute 7.5–16% or royal jelly content [49]. Reducing sugars in royal jelly are thought to contribute to its epigenetic effect through the activation of insulin-like growth factor 1 (IGF-1) and mammalian target of rapamycin (mTOR) signaling cascades. Thus, they stimulate caste differentiation of Apis mellifera larvae into queens by increasing intake of food and key nutrients [50].\nLipids make up 7–18% of the dry weight of royal jelly. This fraction largely comprises a group of unique and rare saturated or monounsaturated short and medium chain fatty acids that are terminally or internally hydroxylated with terminal mono- or dicarboxylic acid functions [2,28]. The vast majority of royal jelly fat content (80–85%) consists of short hydroxyl fatty acids such as trans-10-hydroxy-2-decenoic acid (10-HDA), which exists only in royal jelly; and therefore, it is known as royal jelly acid or queen bee acid [28,49,51]. 10-HDA is one of the most potent bioactive elements in royal jelly expressing strong anti-aging, neuroprotective, antiproliferative, antimicrobial, antioxidant, anti-inflammatory, and epigenetic effects [52,53,54,55,56,57,58]. In addition, the lipid fraction of royal jelly contains phenolic acids (4–10%), wax (5–6%), steroids (3–4%), and phospholipids (0.4–0.8%) [49].\nA wide range of minor constituents and bioactive compounds exist profusely in royal jelly such as acetylcholine, nucleotides (adenosine, guanosine, adenosine tri-phosphate (ATP), adenosine monophosphate (AMP)), minerals (iron, sodium, calcium, potassium, zinc, magnesium, manganese, and copper), amino acids (8 out of 9 essential amino acids Val, Leu, Ile, Thr, Met, Phe, Lys, and Trp), vitamins (retinol (A), ascorbic acid (C), tocopherol (E), riboflavin (B2), niacin (B3), and other B vitamins), esters, aldehydes, ketones, alcohol, and minor heterocyclic compounds [2,28,49,59,60,61]. It is worth noting that royal jelly loses most of its bioactive ingredients and biological properties when stored at a temperature of 5 °C or higher. Therefore, freezing is the best method to store royal jelly [62]. Enzymatic treatment of royal jelly removes allergen proteins and enhances its nutrient content in addition to improving its digestibility and absorption in the gut without altering its freshness [2,59].\nRoyal jelly has been historically used as a beautifying agent by famous queens such as Cleopatra, and it is still involved in the cosmetic industry [29,56]. Its rich content of bioactive compounds grants it a plethora of diverse health benefits such as antioxidant, anti-inflammatory, neurotrophic, hypotensive, antidiabetic, antilipidemic, antirheumatic, anticarcinogenic, anti-fatigue, antiadipogenic, and antimicrobial activities [43,45,63]. Therefore, it is widely used to treat multiple serious conditions including diabetes, hypertension, hyperlipidemia, cancer, skin diseases, and neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease [2,43,46,59,64]. In addition, bee queens (which enjoy long lifespan as well as super fertility and physical qualities) consume royal jelly throughout their entire lives, and royal jelly is considered a promising anti-aging nutraceutical that can positively enhance fertility and improve body composition [2]."}

    LitCovid-PD-GO-BP

    {"project":"LitCovid-PD-GO-BP","denotations":[{"id":"T2268","span":{"begin":1122,"end":1140},"obj":"http://purl.obolibrary.org/obo/GO_0008283"},{"id":"T29579","span":{"begin":1142,"end":1155},"obj":"http://purl.obolibrary.org/obo/GO_0007155"},{"id":"T67133","span":{"begin":1157,"end":1168},"obj":"http://purl.obolibrary.org/obo/GO_0016049"},{"id":"T56275","span":{"begin":1162,"end":1168},"obj":"http://purl.obolibrary.org/obo/GO_0040007"},{"id":"T82150","span":{"begin":2007,"end":2013},"obj":"http://purl.obolibrary.org/obo/GO_0040007"},{"id":"T17533","span":{"begin":2072,"end":2090},"obj":"http://purl.obolibrary.org/obo/GO_0007165"},{"id":"T62332","span":{"begin":2072,"end":2081},"obj":"http://purl.obolibrary.org/obo/GO_0023052"},{"id":"T25963","span":{"begin":2854,"end":2859},"obj":"http://purl.obolibrary.org/obo/GO_0007568"},{"id":"T1068","span":{"begin":5026,"end":5031},"obj":"http://purl.obolibrary.org/obo/GO_0007568"}],"text":"2.1. Royal Jelly: Its Constituents, Biological, and Pharmacological Activities\nRoyal jelly is a thick, milky, white-yellowish, acidic colloid substance secreted from the hypopharyngeal and mandibular salivary glands of young nurse honey bees (5–15 days old) [32,43]. In general, fresh royal jelly mostly consists of water (67% w/w) in addition to carbohydrates (16%), proteins and amino acids (12.5%), fat (5%), and many other elements [32]. However, royal jelly content of these substances noticeably varies depending on numerous factors like botanical source, bee species, bee artificial feeding, weather, season, location, method of processing, and the like [2,44].\nProtein is the most copious active element in royal jelly, representing half the weight of its dry matter [2]. It vastly comprises nine 49–87 kDa water-insoluble proteins, known as major royal jelly proteins 1–9 (MRJPs1-9) [2,45]. MRJPs constitute more than 80% of royal jelly protein content, and MRJPs1–5 constitute 82–90% of all MRJPs. MRJPs contain 400–578 amino acids that contribute to the antioxidant effect of royal jelly as well as its role in cell proliferation, cell adhesion, cell growth, and immunity [46,47]. Novel non-MRJPs proteins have been newly discovered [48]. Royalisin, jelleines, and aspimin are examples of other proteins that exist in royal jelly, albeit in small amounts. These proteins as well as MRJPs demonstrate strong antimicrobial and bactericidal activities even against the most drug-resistant bacterial strains such as methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, vancomycin-resistant Enterococci, as well as extended-spectrum β-lactamase-producing Proteus mirabilis and Escherichia coli [28,29].\nCarbohydrates (e.g., fructose, glucose maltose, trehalose, melibiose, ribose, and erlose) constitute 7.5–16% or royal jelly content [49]. Reducing sugars in royal jelly are thought to contribute to its epigenetic effect through the activation of insulin-like growth factor 1 (IGF-1) and mammalian target of rapamycin (mTOR) signaling cascades. Thus, they stimulate caste differentiation of Apis mellifera larvae into queens by increasing intake of food and key nutrients [50].\nLipids make up 7–18% of the dry weight of royal jelly. This fraction largely comprises a group of unique and rare saturated or monounsaturated short and medium chain fatty acids that are terminally or internally hydroxylated with terminal mono- or dicarboxylic acid functions [2,28]. The vast majority of royal jelly fat content (80–85%) consists of short hydroxyl fatty acids such as trans-10-hydroxy-2-decenoic acid (10-HDA), which exists only in royal jelly; and therefore, it is known as royal jelly acid or queen bee acid [28,49,51]. 10-HDA is one of the most potent bioactive elements in royal jelly expressing strong anti-aging, neuroprotective, antiproliferative, antimicrobial, antioxidant, anti-inflammatory, and epigenetic effects [52,53,54,55,56,57,58]. In addition, the lipid fraction of royal jelly contains phenolic acids (4–10%), wax (5–6%), steroids (3–4%), and phospholipids (0.4–0.8%) [49].\nA wide range of minor constituents and bioactive compounds exist profusely in royal jelly such as acetylcholine, nucleotides (adenosine, guanosine, adenosine tri-phosphate (ATP), adenosine monophosphate (AMP)), minerals (iron, sodium, calcium, potassium, zinc, magnesium, manganese, and copper), amino acids (8 out of 9 essential amino acids Val, Leu, Ile, Thr, Met, Phe, Lys, and Trp), vitamins (retinol (A), ascorbic acid (C), tocopherol (E), riboflavin (B2), niacin (B3), and other B vitamins), esters, aldehydes, ketones, alcohol, and minor heterocyclic compounds [2,28,49,59,60,61]. It is worth noting that royal jelly loses most of its bioactive ingredients and biological properties when stored at a temperature of 5 °C or higher. Therefore, freezing is the best method to store royal jelly [62]. Enzymatic treatment of royal jelly removes allergen proteins and enhances its nutrient content in addition to improving its digestibility and absorption in the gut without altering its freshness [2,59].\nRoyal jelly has been historically used as a beautifying agent by famous queens such as Cleopatra, and it is still involved in the cosmetic industry [29,56]. Its rich content of bioactive compounds grants it a plethora of diverse health benefits such as antioxidant, anti-inflammatory, neurotrophic, hypotensive, antidiabetic, antilipidemic, antirheumatic, anticarcinogenic, anti-fatigue, antiadipogenic, and antimicrobial activities [43,45,63]. Therefore, it is widely used to treat multiple serious conditions including diabetes, hypertension, hyperlipidemia, cancer, skin diseases, and neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease [2,43,46,59,64]. In addition, bee queens (which enjoy long lifespan as well as super fertility and physical qualities) consume royal jelly throughout their entire lives, and royal jelly is considered a promising anti-aging nutraceutical that can positively enhance fertility and improve body composition [2]."}

    LitCovid-PD-HP

    {"project":"LitCovid-PD-HP","denotations":[{"id":"T13","span":{"begin":1603,"end":1613},"obj":"Phenotype"},{"id":"T14","span":{"begin":4351,"end":4359},"obj":"Phenotype"},{"id":"T15","span":{"begin":4521,"end":4528},"obj":"Phenotype"},{"id":"T16","span":{"begin":4673,"end":4685},"obj":"Phenotype"},{"id":"T17","span":{"begin":4687,"end":4701},"obj":"Phenotype"},{"id":"T18","span":{"begin":4703,"end":4709},"obj":"Phenotype"},{"id":"T19","span":{"begin":4730,"end":4756},"obj":"Phenotype"},{"id":"T20","span":{"begin":4765,"end":4784},"obj":"Phenotype"}],"attributes":[{"id":"A13","pred":"hp_id","subj":"T13","obj":"http://purl.obolibrary.org/obo/HP_0002090"},{"id":"A14","pred":"hp_id","subj":"T14","obj":"http://purl.obolibrary.org/obo/HP_0001050"},{"id":"A15","pred":"hp_id","subj":"T15","obj":"http://purl.obolibrary.org/obo/HP_0012378"},{"id":"A16","pred":"hp_id","subj":"T16","obj":"http://purl.obolibrary.org/obo/HP_0000822"},{"id":"A17","pred":"hp_id","subj":"T17","obj":"http://purl.obolibrary.org/obo/HP_0003077"},{"id":"A18","pred":"hp_id","subj":"T18","obj":"http://purl.obolibrary.org/obo/HP_0002664"},{"id":"A19","pred":"hp_id","subj":"T19","obj":"http://purl.obolibrary.org/obo/HP_0002180"},{"id":"A20","pred":"hp_id","subj":"T20","obj":"http://purl.obolibrary.org/obo/HP_0002511"}],"text":"2.1. Royal Jelly: Its Constituents, Biological, and Pharmacological Activities\nRoyal jelly is a thick, milky, white-yellowish, acidic colloid substance secreted from the hypopharyngeal and mandibular salivary glands of young nurse honey bees (5–15 days old) [32,43]. In general, fresh royal jelly mostly consists of water (67% w/w) in addition to carbohydrates (16%), proteins and amino acids (12.5%), fat (5%), and many other elements [32]. However, royal jelly content of these substances noticeably varies depending on numerous factors like botanical source, bee species, bee artificial feeding, weather, season, location, method of processing, and the like [2,44].\nProtein is the most copious active element in royal jelly, representing half the weight of its dry matter [2]. It vastly comprises nine 49–87 kDa water-insoluble proteins, known as major royal jelly proteins 1–9 (MRJPs1-9) [2,45]. MRJPs constitute more than 80% of royal jelly protein content, and MRJPs1–5 constitute 82–90% of all MRJPs. MRJPs contain 400–578 amino acids that contribute to the antioxidant effect of royal jelly as well as its role in cell proliferation, cell adhesion, cell growth, and immunity [46,47]. Novel non-MRJPs proteins have been newly discovered [48]. Royalisin, jelleines, and aspimin are examples of other proteins that exist in royal jelly, albeit in small amounts. These proteins as well as MRJPs demonstrate strong antimicrobial and bactericidal activities even against the most drug-resistant bacterial strains such as methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, vancomycin-resistant Enterococci, as well as extended-spectrum β-lactamase-producing Proteus mirabilis and Escherichia coli [28,29].\nCarbohydrates (e.g., fructose, glucose maltose, trehalose, melibiose, ribose, and erlose) constitute 7.5–16% or royal jelly content [49]. Reducing sugars in royal jelly are thought to contribute to its epigenetic effect through the activation of insulin-like growth factor 1 (IGF-1) and mammalian target of rapamycin (mTOR) signaling cascades. Thus, they stimulate caste differentiation of Apis mellifera larvae into queens by increasing intake of food and key nutrients [50].\nLipids make up 7–18% of the dry weight of royal jelly. This fraction largely comprises a group of unique and rare saturated or monounsaturated short and medium chain fatty acids that are terminally or internally hydroxylated with terminal mono- or dicarboxylic acid functions [2,28]. The vast majority of royal jelly fat content (80–85%) consists of short hydroxyl fatty acids such as trans-10-hydroxy-2-decenoic acid (10-HDA), which exists only in royal jelly; and therefore, it is known as royal jelly acid or queen bee acid [28,49,51]. 10-HDA is one of the most potent bioactive elements in royal jelly expressing strong anti-aging, neuroprotective, antiproliferative, antimicrobial, antioxidant, anti-inflammatory, and epigenetic effects [52,53,54,55,56,57,58]. In addition, the lipid fraction of royal jelly contains phenolic acids (4–10%), wax (5–6%), steroids (3–4%), and phospholipids (0.4–0.8%) [49].\nA wide range of minor constituents and bioactive compounds exist profusely in royal jelly such as acetylcholine, nucleotides (adenosine, guanosine, adenosine tri-phosphate (ATP), adenosine monophosphate (AMP)), minerals (iron, sodium, calcium, potassium, zinc, magnesium, manganese, and copper), amino acids (8 out of 9 essential amino acids Val, Leu, Ile, Thr, Met, Phe, Lys, and Trp), vitamins (retinol (A), ascorbic acid (C), tocopherol (E), riboflavin (B2), niacin (B3), and other B vitamins), esters, aldehydes, ketones, alcohol, and minor heterocyclic compounds [2,28,49,59,60,61]. It is worth noting that royal jelly loses most of its bioactive ingredients and biological properties when stored at a temperature of 5 °C or higher. Therefore, freezing is the best method to store royal jelly [62]. Enzymatic treatment of royal jelly removes allergen proteins and enhances its nutrient content in addition to improving its digestibility and absorption in the gut without altering its freshness [2,59].\nRoyal jelly has been historically used as a beautifying agent by famous queens such as Cleopatra, and it is still involved in the cosmetic industry [29,56]. Its rich content of bioactive compounds grants it a plethora of diverse health benefits such as antioxidant, anti-inflammatory, neurotrophic, hypotensive, antidiabetic, antilipidemic, antirheumatic, anticarcinogenic, anti-fatigue, antiadipogenic, and antimicrobial activities [43,45,63]. Therefore, it is widely used to treat multiple serious conditions including diabetes, hypertension, hyperlipidemia, cancer, skin diseases, and neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease [2,43,46,59,64]. In addition, bee queens (which enjoy long lifespan as well as super fertility and physical qualities) consume royal jelly throughout their entire lives, and royal jelly is considered a promising anti-aging nutraceutical that can positively enhance fertility and improve body composition [2]."}

    LitCovid-sentences

    {"project":"LitCovid-sentences","denotations":[{"id":"T59","span":{"begin":0,"end":4},"obj":"Sentence"},{"id":"T60","span":{"begin":5,"end":17},"obj":"Sentence"},{"id":"T61","span":{"begin":18,"end":78},"obj":"Sentence"},{"id":"T62","span":{"begin":79,"end":266},"obj":"Sentence"},{"id":"T63","span":{"begin":267,"end":441},"obj":"Sentence"},{"id":"T64","span":{"begin":442,"end":668},"obj":"Sentence"},{"id":"T65","span":{"begin":669,"end":779},"obj":"Sentence"},{"id":"T66","span":{"begin":780,"end":899},"obj":"Sentence"},{"id":"T67","span":{"begin":900,"end":1007},"obj":"Sentence"},{"id":"T68","span":{"begin":1008,"end":1191},"obj":"Sentence"},{"id":"T69","span":{"begin":1192,"end":1249},"obj":"Sentence"},{"id":"T70","span":{"begin":1250,"end":1366},"obj":"Sentence"},{"id":"T71","span":{"begin":1367,"end":1747},"obj":"Sentence"},{"id":"T72","span":{"begin":1748,"end":1885},"obj":"Sentence"},{"id":"T73","span":{"begin":1886,"end":2091},"obj":"Sentence"},{"id":"T74","span":{"begin":2092,"end":2224},"obj":"Sentence"},{"id":"T75","span":{"begin":2225,"end":2279},"obj":"Sentence"},{"id":"T76","span":{"begin":2280,"end":2508},"obj":"Sentence"},{"id":"T77","span":{"begin":2509,"end":2763},"obj":"Sentence"},{"id":"T78","span":{"begin":2764,"end":2990},"obj":"Sentence"},{"id":"T79","span":{"begin":2991,"end":3134},"obj":"Sentence"},{"id":"T80","span":{"begin":3135,"end":3722},"obj":"Sentence"},{"id":"T81","span":{"begin":3723,"end":3872},"obj":"Sentence"},{"id":"T82","span":{"begin":3873,"end":3938},"obj":"Sentence"},{"id":"T83","span":{"begin":3939,"end":4141},"obj":"Sentence"},{"id":"T84","span":{"begin":4142,"end":4298},"obj":"Sentence"},{"id":"T85","span":{"begin":4299,"end":4586},"obj":"Sentence"},{"id":"T86","span":{"begin":4587,"end":4825},"obj":"Sentence"},{"id":"T87","span":{"begin":4826,"end":5117},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"2.1. Royal Jelly: Its Constituents, Biological, and Pharmacological Activities\nRoyal jelly is a thick, milky, white-yellowish, acidic colloid substance secreted from the hypopharyngeal and mandibular salivary glands of young nurse honey bees (5–15 days old) [32,43]. In general, fresh royal jelly mostly consists of water (67% w/w) in addition to carbohydrates (16%), proteins and amino acids (12.5%), fat (5%), and many other elements [32]. However, royal jelly content of these substances noticeably varies depending on numerous factors like botanical source, bee species, bee artificial feeding, weather, season, location, method of processing, and the like [2,44].\nProtein is the most copious active element in royal jelly, representing half the weight of its dry matter [2]. It vastly comprises nine 49–87 kDa water-insoluble proteins, known as major royal jelly proteins 1–9 (MRJPs1-9) [2,45]. MRJPs constitute more than 80% of royal jelly protein content, and MRJPs1–5 constitute 82–90% of all MRJPs. MRJPs contain 400–578 amino acids that contribute to the antioxidant effect of royal jelly as well as its role in cell proliferation, cell adhesion, cell growth, and immunity [46,47]. Novel non-MRJPs proteins have been newly discovered [48]. Royalisin, jelleines, and aspimin are examples of other proteins that exist in royal jelly, albeit in small amounts. These proteins as well as MRJPs demonstrate strong antimicrobial and bactericidal activities even against the most drug-resistant bacterial strains such as methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, vancomycin-resistant Enterococci, as well as extended-spectrum β-lactamase-producing Proteus mirabilis and Escherichia coli [28,29].\nCarbohydrates (e.g., fructose, glucose maltose, trehalose, melibiose, ribose, and erlose) constitute 7.5–16% or royal jelly content [49]. Reducing sugars in royal jelly are thought to contribute to its epigenetic effect through the activation of insulin-like growth factor 1 (IGF-1) and mammalian target of rapamycin (mTOR) signaling cascades. Thus, they stimulate caste differentiation of Apis mellifera larvae into queens by increasing intake of food and key nutrients [50].\nLipids make up 7–18% of the dry weight of royal jelly. This fraction largely comprises a group of unique and rare saturated or monounsaturated short and medium chain fatty acids that are terminally or internally hydroxylated with terminal mono- or dicarboxylic acid functions [2,28]. The vast majority of royal jelly fat content (80–85%) consists of short hydroxyl fatty acids such as trans-10-hydroxy-2-decenoic acid (10-HDA), which exists only in royal jelly; and therefore, it is known as royal jelly acid or queen bee acid [28,49,51]. 10-HDA is one of the most potent bioactive elements in royal jelly expressing strong anti-aging, neuroprotective, antiproliferative, antimicrobial, antioxidant, anti-inflammatory, and epigenetic effects [52,53,54,55,56,57,58]. In addition, the lipid fraction of royal jelly contains phenolic acids (4–10%), wax (5–6%), steroids (3–4%), and phospholipids (0.4–0.8%) [49].\nA wide range of minor constituents and bioactive compounds exist profusely in royal jelly such as acetylcholine, nucleotides (adenosine, guanosine, adenosine tri-phosphate (ATP), adenosine monophosphate (AMP)), minerals (iron, sodium, calcium, potassium, zinc, magnesium, manganese, and copper), amino acids (8 out of 9 essential amino acids Val, Leu, Ile, Thr, Met, Phe, Lys, and Trp), vitamins (retinol (A), ascorbic acid (C), tocopherol (E), riboflavin (B2), niacin (B3), and other B vitamins), esters, aldehydes, ketones, alcohol, and minor heterocyclic compounds [2,28,49,59,60,61]. It is worth noting that royal jelly loses most of its bioactive ingredients and biological properties when stored at a temperature of 5 °C or higher. Therefore, freezing is the best method to store royal jelly [62]. Enzymatic treatment of royal jelly removes allergen proteins and enhances its nutrient content in addition to improving its digestibility and absorption in the gut without altering its freshness [2,59].\nRoyal jelly has been historically used as a beautifying agent by famous queens such as Cleopatra, and it is still involved in the cosmetic industry [29,56]. Its rich content of bioactive compounds grants it a plethora of diverse health benefits such as antioxidant, anti-inflammatory, neurotrophic, hypotensive, antidiabetic, antilipidemic, antirheumatic, anticarcinogenic, anti-fatigue, antiadipogenic, and antimicrobial activities [43,45,63]. Therefore, it is widely used to treat multiple serious conditions including diabetes, hypertension, hyperlipidemia, cancer, skin diseases, and neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease [2,43,46,59,64]. In addition, bee queens (which enjoy long lifespan as well as super fertility and physical qualities) consume royal jelly throughout their entire lives, and royal jelly is considered a promising anti-aging nutraceutical that can positively enhance fertility and improve body composition [2]."}

    LitCovid-PubTator

    {"project":"LitCovid-PubTator","denotations":[{"id":"165","span":{"begin":5,"end":16},"obj":"Chemical"},{"id":"171","span":{"begin":402,"end":405},"obj":"Gene"},{"id":"172","span":{"begin":231,"end":241},"obj":"Species"},{"id":"173","span":{"begin":316,"end":321},"obj":"Chemical"},{"id":"174","span":{"begin":329,"end":330},"obj":"Chemical"},{"id":"175","span":{"begin":347,"end":360},"obj":"Chemical"},{"id":"185","span":{"begin":1545,"end":1566},"obj":"Species"},{"id":"186","span":{"begin":1568,"end":1590},"obj":"Species"},{"id":"187","span":{"begin":1592,"end":1613},"obj":"Species"},{"id":"188","span":{"begin":1700,"end":1717},"obj":"Species"},{"id":"189","span":{"begin":1722,"end":1738},"obj":"Species"},{"id":"190","span":{"begin":815,"end":820},"obj":"Chemical"},{"id":"191","span":{"begin":1087,"end":1098},"obj":"Chemical"},{"id":"192","span":{"begin":1523,"end":1534},"obj":"Chemical"},{"id":"193","span":{"begin":1615,"end":1625},"obj":"Chemical"},{"id":"207","span":{"begin":1994,"end":2022},"obj":"Gene"},{"id":"208","span":{"begin":2024,"end":2029},"obj":"Gene"},{"id":"209","span":{"begin":2035,"end":2064},"obj":"Gene"},{"id":"210","span":{"begin":2066,"end":2070},"obj":"Gene"},{"id":"211","span":{"begin":2138,"end":2152},"obj":"Species"},{"id":"212","span":{"begin":1748,"end":1761},"obj":"Chemical"},{"id":"213","span":{"begin":1769,"end":1777},"obj":"Chemical"},{"id":"214","span":{"begin":1779,"end":1786},"obj":"Chemical"},{"id":"215","span":{"begin":1796,"end":1805},"obj":"Chemical"},{"id":"216","span":{"begin":1807,"end":1816},"obj":"Chemical"},{"id":"217","span":{"begin":1818,"end":1824},"obj":"Chemical"},{"id":"218","span":{"begin":1830,"end":1836},"obj":"Chemical"},{"id":"219","span":{"begin":1895,"end":1901},"obj":"Chemical"},{"id":"233","span":{"begin":2542,"end":2545},"obj":"Gene"},{"id":"234","span":{"begin":2225,"end":2231},"obj":"Chemical"},{"id":"235","span":{"begin":2267,"end":2278},"obj":"Chemical"},{"id":"236","span":{"begin":2391,"end":2402},"obj":"Chemical"},{"id":"237","span":{"begin":2464,"end":2490},"obj":"Chemical"},{"id":"238","span":{"begin":2590,"end":2601},"obj":"Chemical"},{"id":"239","span":{"begin":2610,"end":2642},"obj":"Chemical"},{"id":"240","span":{"begin":2644,"end":2650},"obj":"Chemical"},{"id":"241","span":{"begin":2723,"end":2733},"obj":"Chemical"},{"id":"242","span":{"begin":3047,"end":3061},"obj":"Chemical"},{"id":"243","span":{"begin":3071,"end":3074},"obj":"Chemical"},{"id":"244","span":{"begin":3083,"end":3091},"obj":"Chemical"},{"id":"245","span":{"begin":3104,"end":3117},"obj":"Chemical"},{"id":"249","span":{"begin":3261,"end":3270},"obj":"Chemical"},{"id":"250","span":{"begin":3283,"end":3292},"obj":"Chemical"},{"id":"251","span":{"begin":3314,"end":3323},"obj":"Chemical"},{"id":"263","span":{"begin":4142,"end":4153},"obj":"Chemical"},{"id":"264","span":{"begin":4441,"end":4452},"obj":"Disease"},{"id":"265","span":{"begin":4521,"end":4528},"obj":"Disease"},{"id":"266","span":{"begin":4663,"end":4671},"obj":"Disease"},{"id":"267","span":{"begin":4673,"end":4685},"obj":"Disease"},{"id":"268","span":{"begin":4687,"end":4701},"obj":"Disease"},{"id":"269","span":{"begin":4703,"end":4709},"obj":"Disease"},{"id":"270","span":{"begin":4711,"end":4724},"obj":"Disease"},{"id":"271","span":{"begin":4730,"end":4756},"obj":"Disease"},{"id":"272","span":{"begin":4765,"end":4784},"obj":"Disease"},{"id":"273","span":{"begin":4789,"end":4808},"obj":"Disease"}],"attributes":[{"id":"A165","pred":"tao:has_database_id","subj":"165","obj":"MESH:C058787"},{"id":"A171","pred":"tao:has_database_id","subj":"171","obj":"Gene:83720"},{"id":"A172","pred":"tao:has_database_id","subj":"172","obj":"Tax:7460"},{"id":"A173","pred":"tao:has_database_id","subj":"173","obj":"MESH:D014867"},{"id":"A174","pred":"tao:has_database_id","subj":"174","obj":"MESH:D014414"},{"id":"A175","pred":"tao:has_database_id","subj":"175","obj":"MESH:D002241"},{"id":"A185","pred":"tao:has_database_id","subj":"185","obj":"Tax:1280"},{"id":"A186","pred":"tao:has_database_id","subj":"186","obj":"Tax:287"},{"id":"A187","pred":"tao:has_database_id","subj":"187","obj":"Tax:573"},{"id":"A188","pred":"tao:has_database_id","subj":"188","obj":"Tax:584"},{"id":"A189","pred":"tao:has_database_id","subj":"189","obj":"Tax:562"},{"id":"A190","pred":"tao:has_database_id","subj":"190","obj":"MESH:D014867"},{"id":"A191","pred":"tao:has_database_id","subj":"191","obj":"MESH:C058787"},{"id":"A192","pred":"tao:has_database_id","subj":"192","obj":"MESH:D008712"},{"id":"A193","pred":"tao:has_database_id","subj":"193","obj":"MESH:D014640"},{"id":"A207","pred":"tao:has_database_id","subj":"207","obj":"Gene:3479"},{"id":"A208","pred":"tao:has_database_id","subj":"208","obj":"Gene:3479"},{"id":"A209","pred":"tao:has_database_id","subj":"209","obj":"Gene:2475"},{"id":"A210","pred":"tao:has_database_id","subj":"210","obj":"Gene:2475"},{"id":"A211","pred":"tao:has_database_id","subj":"211","obj":"Tax:7460"},{"id":"A212","pred":"tao:has_database_id","subj":"212","obj":"MESH:D002241"},{"id":"A213","pred":"tao:has_database_id","subj":"213","obj":"MESH:D005632"},{"id":"A214","pred":"tao:has_database_id","subj":"214","obj":"MESH:D005947"},{"id":"A215","pred":"tao:has_database_id","subj":"215","obj":"MESH:D014199"},{"id":"A216","pred":"tao:has_database_id","subj":"216","obj":"MESH:D008553"},{"id":"A217","pred":"tao:has_database_id","subj":"217","obj":"MESH:D012266"},{"id":"A218","pred":"tao:has_database_id","subj":"218","obj":"MESH:C026440"},{"id":"A219","pred":"tao:has_database_id","subj":"219","obj":"MESH:D000073893"},{"id":"A233","pred":"tao:has_database_id","subj":"233","obj":"Gene:83720"},{"id":"A234","pred":"tao:has_database_id","subj":"234","obj":"MESH:D008055"},{"id":"A235","pred":"tao:has_database_id","subj":"235","obj":"MESH:C058787"},{"id":"A236","pred":"tao:has_database_id","subj":"236","obj":"MESH:D005227"},{"id":"A238","pred":"tao:has_database_id","subj":"238","obj":"MESH:D005227"},{"id":"A242","pred":"tao:has_database_id","subj":"242","obj":"MESH:C017616"},{"id":"A243","pred":"tao:has_database_id","subj":"243","obj":"MESH:D014885"},{"id":"A244","pred":"tao:has_database_id","subj":"244","obj":"MESH:D013256"},{"id":"A245","pred":"tao:has_database_id","subj":"245","obj":"MESH:D010743"},{"id":"A249","pred":"tao:has_database_id","subj":"249","obj":"MESH:D000241"},{"id":"A250","pred":"tao:has_database_id","subj":"250","obj":"MESH:D000241"},{"id":"A251","pred":"tao:has_database_id","subj":"251","obj":"MESH:D000241"},{"id":"A263","pred":"tao:has_database_id","subj":"263","obj":"MESH:C058787"},{"id":"A264","pred":"tao:has_database_id","subj":"264","obj":"MESH:D007022"},{"id":"A265","pred":"tao:has_database_id","subj":"265","obj":"MESH:D005221"},{"id":"A266","pred":"tao:has_database_id","subj":"266","obj":"MESH:D003920"},{"id":"A267","pred":"tao:has_database_id","subj":"267","obj":"MESH:D006973"},{"id":"A268","pred":"tao:has_database_id","subj":"268","obj":"MESH:D006949"},{"id":"A269","pred":"tao:has_database_id","subj":"269","obj":"MESH:D009369"},{"id":"A270","pred":"tao:has_database_id","subj":"270","obj":"MESH:D012871"},{"id":"A271","pred":"tao:has_database_id","subj":"271","obj":"MESH:D019636"},{"id":"A272","pred":"tao:has_database_id","subj":"272","obj":"MESH:D000544"},{"id":"A273","pred":"tao:has_database_id","subj":"273","obj":"MESH:D010300"}],"namespaces":[{"prefix":"Tax","uri":"https://www.ncbi.nlm.nih.gov/taxonomy/"},{"prefix":"MESH","uri":"https://id.nlm.nih.gov/mesh/"},{"prefix":"Gene","uri":"https://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"CVCL","uri":"https://web.expasy.org/cellosaurus/CVCL_"}],"text":"2.1. Royal Jelly: Its Constituents, Biological, and Pharmacological Activities\nRoyal jelly is a thick, milky, white-yellowish, acidic colloid substance secreted from the hypopharyngeal and mandibular salivary glands of young nurse honey bees (5–15 days old) [32,43]. In general, fresh royal jelly mostly consists of water (67% w/w) in addition to carbohydrates (16%), proteins and amino acids (12.5%), fat (5%), and many other elements [32]. However, royal jelly content of these substances noticeably varies depending on numerous factors like botanical source, bee species, bee artificial feeding, weather, season, location, method of processing, and the like [2,44].\nProtein is the most copious active element in royal jelly, representing half the weight of its dry matter [2]. It vastly comprises nine 49–87 kDa water-insoluble proteins, known as major royal jelly proteins 1–9 (MRJPs1-9) [2,45]. MRJPs constitute more than 80% of royal jelly protein content, and MRJPs1–5 constitute 82–90% of all MRJPs. MRJPs contain 400–578 amino acids that contribute to the antioxidant effect of royal jelly as well as its role in cell proliferation, cell adhesion, cell growth, and immunity [46,47]. Novel non-MRJPs proteins have been newly discovered [48]. Royalisin, jelleines, and aspimin are examples of other proteins that exist in royal jelly, albeit in small amounts. These proteins as well as MRJPs demonstrate strong antimicrobial and bactericidal activities even against the most drug-resistant bacterial strains such as methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, vancomycin-resistant Enterococci, as well as extended-spectrum β-lactamase-producing Proteus mirabilis and Escherichia coli [28,29].\nCarbohydrates (e.g., fructose, glucose maltose, trehalose, melibiose, ribose, and erlose) constitute 7.5–16% or royal jelly content [49]. Reducing sugars in royal jelly are thought to contribute to its epigenetic effect through the activation of insulin-like growth factor 1 (IGF-1) and mammalian target of rapamycin (mTOR) signaling cascades. Thus, they stimulate caste differentiation of Apis mellifera larvae into queens by increasing intake of food and key nutrients [50].\nLipids make up 7–18% of the dry weight of royal jelly. This fraction largely comprises a group of unique and rare saturated or monounsaturated short and medium chain fatty acids that are terminally or internally hydroxylated with terminal mono- or dicarboxylic acid functions [2,28]. The vast majority of royal jelly fat content (80–85%) consists of short hydroxyl fatty acids such as trans-10-hydroxy-2-decenoic acid (10-HDA), which exists only in royal jelly; and therefore, it is known as royal jelly acid or queen bee acid [28,49,51]. 10-HDA is one of the most potent bioactive elements in royal jelly expressing strong anti-aging, neuroprotective, antiproliferative, antimicrobial, antioxidant, anti-inflammatory, and epigenetic effects [52,53,54,55,56,57,58]. In addition, the lipid fraction of royal jelly contains phenolic acids (4–10%), wax (5–6%), steroids (3–4%), and phospholipids (0.4–0.8%) [49].\nA wide range of minor constituents and bioactive compounds exist profusely in royal jelly such as acetylcholine, nucleotides (adenosine, guanosine, adenosine tri-phosphate (ATP), adenosine monophosphate (AMP)), minerals (iron, sodium, calcium, potassium, zinc, magnesium, manganese, and copper), amino acids (8 out of 9 essential amino acids Val, Leu, Ile, Thr, Met, Phe, Lys, and Trp), vitamins (retinol (A), ascorbic acid (C), tocopherol (E), riboflavin (B2), niacin (B3), and other B vitamins), esters, aldehydes, ketones, alcohol, and minor heterocyclic compounds [2,28,49,59,60,61]. It is worth noting that royal jelly loses most of its bioactive ingredients and biological properties when stored at a temperature of 5 °C or higher. Therefore, freezing is the best method to store royal jelly [62]. Enzymatic treatment of royal jelly removes allergen proteins and enhances its nutrient content in addition to improving its digestibility and absorption in the gut without altering its freshness [2,59].\nRoyal jelly has been historically used as a beautifying agent by famous queens such as Cleopatra, and it is still involved in the cosmetic industry [29,56]. Its rich content of bioactive compounds grants it a plethora of diverse health benefits such as antioxidant, anti-inflammatory, neurotrophic, hypotensive, antidiabetic, antilipidemic, antirheumatic, anticarcinogenic, anti-fatigue, antiadipogenic, and antimicrobial activities [43,45,63]. Therefore, it is widely used to treat multiple serious conditions including diabetes, hypertension, hyperlipidemia, cancer, skin diseases, and neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease [2,43,46,59,64]. In addition, bee queens (which enjoy long lifespan as well as super fertility and physical qualities) consume royal jelly throughout their entire lives, and royal jelly is considered a promising anti-aging nutraceutical that can positively enhance fertility and improve body composition [2]."}