Bioactive Properties of Royal Jelly: History
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Contributor:
Sara Botezan
,
Gabriela-Maria Baci
,
Lilla Bagameri
,
Claudia Pașca
,
Daniel Severus Dezmirean

Royal jelly (RJ) has been one of the most widely used natural products in alternative medicine for centuries. Being produced by both hypopharyngeal and mandibular glands, RJ exhibits an extraordinary complexity in terms of its composition, including proteins, lipids, carbohydrates, polyphenols, vitamins, and hormones. Due to its heterogeneous structure, RJ displays various functional roles for honeybees, including being involved in nutrition, learning, memory, and social behavior. Furthermore, a wide range of studies reported its therapeutic properties, including anticancer, anti-inflammatory, and antioxidant activities, to name a few. In this direction, there is a wide range of health-related problems for which the medical area specialists and researchers are continuously trying to find a cure, such as cancer, atherosclerosis, or infertility. For the mentioned diseases and more, it has been proven that RJ is a key player in finding a valuable treatment. Here, the great impact of RJ as an alternative medicine agent is highlighted. Moreover, researchers link it to its apitherapeutic potential by discussing its composition.

  • apitherapy
  • royal jelly
  • MRJPs
  • 10-HDA
  • anticancer
  • anti-inflammatory
  • antioxidant
  • bioactive components
  • biological functions

1. Introduction

Since ancient times, mankind has taken advantage of the benefits associated with beehive products, such as honey, propolis, bee pollen, beeswax, bee venom, and RJ, and distinct cultures have been using them to treat and prevent diseases [1]. Because of their specific biochemical profile, all of these bee-derived products are highly bioavailable [2].
Royal jelly (RJ), also known as Apilak or Queen Bee Jelly, is a yellowish-white, creamy substance secreted in the hypopharyngeal and mandibular glands of worker bees. It is the only substance fed to the queen larvae and the worker bee larvae are also fed with RJ, but only in the first three days, then a mixture of honey, pollen, and nectar, also called bee bread, constitutes the main diet of the latter [3]. Through its nutrient-rich chemical composition, RJ represents an important source of food for the bee family, playing an essential role in the biology of these insects. For humans, RJ represents a very important nutraceutical, functional food, and nutritional supplement [4] that can efficiently complement a healthy diet. Furthermore, it can also be useful in the diets of various animal species [5].

2. Royal Jelly: Chemical Characterization, Quantitative Determination, and Storage

2.1. General Remarks

RJ represents a rich source of nutrients and bioactive compounds which depends on different factors such as beekeeping season, the geographical orientation of the apiary, chemicals used, meteorological conditions, the ecosystem where the honeybees live, and the plant cultures that the insects have access to. Another parameter that can influence the chemical composition is the race and caste of the honeybees, physiological and metabolic differences between the nurse bees, and the harvest time of RJ [6]. This bee product is a functional food that drives the phenotypic development of the female bee larvae, allowing its transformation into a fertile bee queen instead of a sterile worker bee [7], additionally playing a crucial role in bee brain functions, such as memory, learning, and social behavior [8]. At the same time, RJ can be consumed by humans as a functional food, and it holds a high commercial value for its nutritional and nutraceutical properties [9].
The chemical composition of RJ consists of water (60–78%), proteins (9–18%), carbohydrates (7–18%), lipids (3–8%), mineral salts (0.8–3%), small amounts of polyphenols, vitamins, and enzymes [10][11]. In general, RJ is relatively acidic with a high buffering capacity (pH 3.20–4.01) and the total acidity varies between 2.48–4.66 mL 0.1 N NaOH/g [12]. Sugar composition, moisture, protein, and 10-HDA contents are the most prevalent criteria in the determination of the quality and authenticity of RJ [11][13].

2.2. Sugar Composition

Sugars represent about 30% of the dry matter in RJ [4][14][15]. In general, the main carbohydrates found in RJ are monosaccharides (fructose and glucose) [16] representing 90% of the total sugar fraction of RJ, and sucrose accounts for 0.8–3.6% [17]. RJ contains very small amounts of other sugars such as maltose, trehalose, melibiose, ribose, and erlose. Some authors stated that the determination of sugars could provide important information about RJ’s quality, including the detection of possible adulteration with honey or sugars [15]. Adulteration can also be achieved using corn starch, milk, yoghurt, or egg white [4].

2.3. Proteins, Peptides, and Amino Acids

Proteins, including minor RJ proteins and MRJPs are present in RJ with an average of 9–18% [15][16] and in the International standards ISO 12824 between 11–18%. A total of 80% percent of RJ proteins are represented by the so-called MRJPs, which are playing specific physiological roles in honeybee queen development and include numerous essential amino acids. The MRJP family includes nine members, specifically MRJP1, MRJP2, MRJP3, MRJP4, MRJP5, MRJP6, MRJP7, MRJP8, and MRJP9 [8][15].
Like proteins, peptides represent specific sequences of amino acids in RJ that have biological activities and potential health applications [18]. Among the peptides in RJ, there are: apisimin and jelleines I, II, III, and IV [4]. Royalisin is another peptide from RJ and it was found to have potent antibacterial activity against Gram-positive bacteria, such as Clostridium, at low concentrations [19][20].
RJ is rich in amino acids, including lysine, proline, cysteine, aspartic acid, valine, glutamic acid, serine, glycine, cysteine, threonine, alanine, tyrosine, phenylalanine, hydroxyproline, leucine, isoleucine, and glutamine. These high amounts of amino acids in the MRJP family are essential for the development of both queen bees and larvae [21].

2.4. Lipids and Fatty Acids

Among the main nutritional elements of RJ, lipids constitute 7–18% of RJ content; 90% of these lipids are unique short hydroxy fatty acids with 8–12 carbon atoms in their chain and dicarboxylic acids [17]. The most abundant RJ fatty acids are 32% 10-HDA, 22% 10-hydroxy-trans-2-decenoic acid (10-H2DA), 24% gluconic acid, 5% dicarboxylic acids [18]. Other fatty acids found in RJ are: 10-hydroxydecanoic acid (10-HDAA), 8-hydroxy octanoic acid, 3-hydroxydecanoic acid, 3,10-dihydroxydecanoic acid, 9-hydroxy-2-decenoic acid, 1,10-decanedioic (sebacic) acid, and 2-decenedioic acid [4]. The most important parameter for quality control of RJ is 10-HDA, being an indicator of freshness, quality and authenticity and it is a fatty acid that is present only in RJ [12][22][23].

2.5. Minerals, Flavonoids, Vitamins, and Other Components

RJ contains small amounts (1.5%) of various minerals and trace elements such as K, Na, Mg, Ca, P, S, Cu, Fe, Zn, Al, Ba, Sr, Bi, Cd, Hg, Pb, Sn, Te, Tl, W, Sb, Cr, Mn, Ni, Ti, V, Co, and Mo. Whereas concentrations of trace and mineral elements in RJ vary according to the botanical origin, they are generally constant [16][24]. The main element is potassium (2462–3120 mg/kg) [4].
The proportion of phenolic components in RJ is 23.3 ± 0.92 gallic acid equivalent (GAE) g/mg; however, these values can change depending on the dietary source. The total flavonoid content in RJ is 1.28 ± 0.09 rutin equivalent (RE) g/mg 32]. Flavonoids are the largest and most important group of phenolic compounds [25]. According to the level of structural complexity, flavonoids of RJ can be differentiated into four groups: (1) flavanones, e.g., hesperetin, isosakuranetin, and naringenin; (2) flavones, e.g., acacetin, apigenin and its glucoside, chrysin, and luteolin glucoside; (3) flavonols, e.g., isorhamnetin and kaempferol glucosides; and (4) isoflavonoids, e.g., coumestrol, formononetin, and genistein [17].
RJ contains small amounts of various B-group vitamins (B1, B2, B6, B8, B9, and B12), ascorbic acid (vitamin C), vitamin E, and vitamin A [16]. Pantothenic acid (vitamin B5) is the most abundant vitamin in RJ (52.8 mg/100 g), followed by niacin (42.42 mg/100 g) [26].
In addition, the interest substance contains other biochemicals, namely adenosine monophosphate (AMP) and its oxide adenosine monophosphate N1 (AMPN1) oxide, acetylcholine, hormones (prolactin, testosterone, estradiol) [3], as well as organic acids and their esters: octanoic acid, benzoic acid, 2-hexenedioic acid and its esters, dodecanoic acid and its ester, known as 1,2-benzenedicarboxylic acid [25]. Moreover, enzymes such as glucose oxidase, alpha-glucosidase and gluco-cerebrosidase are also found in the food of the queens. All these additional components are found in very small amounts [4]. The nutritional requirements for RJ are listed in Table 1.
Table 1. Nutritional requirements for quality assurance of RJ.
Compound Method of Determination Levels [%] References
Water Refractometric analysis min 62.0–max 68.5 [17][18][19]
Lipids Soxhlet method min 2–max 8 [17][20][21]
10-HDA High-performance liquid chromatography (HPLC); ultra-performance liquid chromatography, gas chromatography–mass spectrometry (GC/MS); NIR spectroscopy combined with chemometric methods min 1.4 [4][8][17][19][22]
Proteins
(total protein/soluble protein fraction)		 Bradford assay; bicinchoninic acid (BCA) method min 11–max 18 [17][19]
Nitrogen content using carbon/hydrogen/nitrogen analyzer TruSpec (LECO, Saint Joseph, MI, USA) [23]
Total carbohydrates colorimetric method min 7–max 18 [17][19][26]
Individual carbohydrates Enzymatic method; HPLC method; GC method; Ionic chromatography; Infrared spectroscopy; Nuclear magnetic resonance Fructose (2.3–7.6), glucose (2.9–8.1), sucrose (<0.1–2.1), maltose and maltotriose (0.0–1.0) [19][26][27]
The chemical composition (Table 2) of RJ varies according to different factors, such as honeybee races, floral origin, age of bee larvae and beekeeping practices. There is a regulation of the national and international standards and also in different studies, stating the levels for the quality assurance parameters of fresh RJ. Although RJ is internationally traded for its beneficial properties in the food, cosmetic, and pharmaceuticals industries, there is a major need to establish and adopt consistent quality parameters and standards within producing countries [27], the same as in Argentina, Bulgaria, Turkey, Brazil, Japan, China, and Switzerland.
Table 2. Proximate composition of fresh RJ.
Compound Levels [mg/100 g] References
Minerals    
Macroelements   [28][29]
Na 0.3–13.8
K 321.1–357.4
Ca 22.8–24.0
Mg 44.0–50.4
P 338.4–412.1
S 153.2–169.3
Microelements  
Fe n.d.
Mn 0.01–0.08
Zn 2.07–2.58
Cr 0.03–0.15
Cu 0.31–0.39
Vitamins    
Vitamin A 1.10 [4][30]
Vitamin B1 2.06
Vitamin B2 2.77
Niacin (B3) 42.42
Vitamin B5 (Pantothenic acid) 52.80
Vitamin B6 11.90
Vitamin B9 (Folic acid) 0.40
Vitamin B12 0.15
Vitamin C (Ascorbic acid) 2.00
Vitamin D 0.2
Vitamin E 5.00
Flavonoids    
Quercetin 16.13 [31]
Naringin 0.47
Hesperetin 0.85
Galangin 0.51
Phenolic Acids    
Chlorogenic Acid 37.61 [31]
Caffeic Acid 5.14
Ferulic Acid 68.42

2.6. Conditions for Maintaining RJ Quality

Temperature is an important factor affecting the physicochemical properties of RJ during its maintenance. For this reason, researchers established the storage and shelf life of RJ depending on this parameter. Kausar and More [32] made a comparison between the organoleptic features and the physicochemical properties of fresh and lyophilized RJ, to prove that the latter can also exert the same health benefits as the first. The authors concluded that when lyophilized, RJ is similar in composition to fresh RJ and freeze-drying does not degrade the substance of interest. Therefore, RJ lyophilization can be a useful strategy that enables the storage time to be increased and the RJ to be stored at room temperature, while still maintaining its quality.
Maghsoudlou et al. [33] described the storage stability and shelf life of RJ. Hence, the shelf life for fresh RJ ranges between 6 months (4 °C)–2 years (<−18 °C) and lyophilized RJ can be used for up to 1 year (4 °C) and more than 2 years (<−18 °C). At the same time, RJ can be used in other products (such as honey) and the shelf life in this case is 2 years at room temperature.

3. Main Bioactive Compounds in Royal Jelly

3.1. Major Royal Jelly Proteins (MRJPs) Family

In terms of RJ’s soluble protein content, over 80% is represented by MRJPs. Containing a wide range of essential amino acids, such as arginine, histidine, or lysine, these proteins play a key role in the process of honeybee queen’s development. It is well documented that for each of the target proteins, MRJP 1-9, the honeybee’s genome harbors a distinct gene [34], which are located on chromosome 11 [35]. These proteins exhibit a high amino acid homology of up to 70% [3]. In addition, it has been reported that the Yellow proteins are found in Drosophila and other insects, but also in some bacteria and share MRJP’s evolutionary origin [36][37]. Furthermore, it has been shown that the MRJPs evolved from the yellow-e3 gene, which exhibits a key role in early bee brain development [38]. The MRJPs are synthesized in honeybee cephalic glands, hypopharyngeal and mandibular; each of the nine members was identified in RJ.

3.1.1. MRJP1

Among the members of this protein family, the dominant glycoprotein in RJ is MRJP1, reaching up to 66% of the total amount of MRJPs [18][34][37]. MRJP1′s architecture involves a chain of 413 amino acids, mainly valine and leucine, [18][39][40] and its secondary structure mainly implies β-sheets (38.3%), followed by 20% β-turns, and 9.6% α-helices [17]. In RJ this specific glycoprotein is found in a monomeric state, royalactin (55 kDa), but also in an oligomeric form, apisin (280–450 kDa) [37][39]. Royalactin increases body and ovary size, and triggers physiological changes that play an important role in the queen bee differentiation. The second-mentioned state represents a complex formed by royalactin, 24-methylenecholesterol, and apisimin, a serine-valine-rich protein [39]. The MRJP1 oligomer exhibits great biochemical heat resistance, but also long storage stability compared to royalactin [37][40]. It creates a pH-dependent fibrillary network, which achieves the necessary viscosity to this bee product, stopping the larvae from falling from the queen cells [41][42]. Moriyama et al. (2015) [40] investigated the MRJP1 heat-resistant features by exposing the glycoprotein to 56, 65, and 96 °C; more specifically, the proliferative activity was assessed. The results showed that until 56 °C, the oligomer’s molecular state was maintained. On the other hand, at 65 °C and 96 °C, the molecular forms transformed in macromolecular aggregates. Interestingly, even if the growth activity was attenuated at 96 °C, the cell proliferation activity was not impacted.
The mrjp1 gene consists of 3038 bp and includes six exons and five introns [43], and it has been reported that mrpj1 is expressed in prominent structures of the bee brain, suggesting that MRJPs’ role is not limited to nutrition, but these proteins are also involved in bees’ social behavior, memory, and learning [37][44]. In this direction, tremendous effort is being made to perform functional analyses on target genes, such as mrjp1. For instance, Kohno et al. (2016) [45] used the clustered regularly interspaced short palindromic repeats (CRISPR)-cas9 system to knock out the mrjp1 gene in order to investigate its dispensable status in the honeybee, Apis mellifera. The authors used a Cas9 expression vector and designed a single-guide RNA (sgRNA) based on a target sequence of 20-base, and an NGG sequence was added following the sgRNA, as protospacer adjacent motif. After the eggs were laid, for up to three hours, the injection was performed into the egg’s dorsal posterior side. By injecting 57 fertilized embryos, they obtained six queens, and two of them laid eggs under laboratory conditions. From two queens, one of them led to genome-manipulated drones, and 20 drones of the total of 161 produced, were genome-edited (12.4% efficiency). Their results revealed that the mrjp1 gene exhibits no impact on normal drone development, at least until the pupal phase.
Although MRJP1 is the pivotal protein of this group, the other members also play crucial roles for honeybees (Table 3). The post-translational modifications, such as phosphorylation, N-glycosylation, or methylation, directly impact the function of each MRJP.
Table 3. MRJP 1-9 brief description.
MRJP
Member		 Alternative Name Amino
Acids Number		 Expression Function Reference
MRJP1 Royalactin, apalbumin 1, D III 413 Upregulated in nurse bee’s head compared to foragers; Upregulated in mated queen spermathecal fluid and spermatheca of the mated queen Essential amino acids absorption; Source of energy for stored sperm; Worker honeybees’ temporal polytheism and phenotypic plasticity’s regulation; Social behavior; Learning; Memory [44][46][47][48]
MRJP2 Apalbumin 2 435 Upregulated in nurse bee’s head compared to foragers Nitrogen reserve; Worker honeybees temporal polytheism and phenotypic plasticity’s regulation [47][49]
MRJP3 RJ protein RJP57-1 524 Upregulated in nurse bee’s head compared to foragers Nitrogen supply; Worker honeybees temporal polytheism and phenotypic plasticity’s regulation [46][47][48][49]
MRJP4 RJ protein RJP57-2 444 Upregulated in nurse bee’s head compared to foragers; Upregulated in mated queen spermathecal fluid and spermatheca of mated queen Essential amino acids absorption; Source of energy for stored sperm; Worker honeybees temporal polytheism and phenotypic plasticity’s regulation [44][46][47]
MRJP5   578 Upregulated in foragers’ head compared to nurses Essential amino acids absorption; nitrogen reserve; Worker honeybees temporal polytheism and phenotypic plasticity’s regulation [46][47]
MRJP6 Not applicable 417 Upregulated in foragers’ head compared to nurses; Upregulated in mated queen spermathecal fluid and spermatheca of the mated queen Source of energy for stored sperm; Worker honeybees temporal polytheism and phenotypic plasticity’s regulation [44][47]
MRJP7 Not applicable 426 Upregulated in nurse bee’s head compared to foragers Worker honeybees’ temporal polytheism and phenotypic plasticity’s regulation [47]
MRJP8 Not applicable 400 Evenly expressed in head, thorax, abdomen of all groups Honeybee worker’s defense; queen’s long life span maintenance [50][51]
MRJP9 Not applicable 403 Upregulated in virgin queens and workers bees General philological role [35]

3.1.2. Therapeutic Impact of MRJPs

Among the crucial roles that RJ exhibits for the honeybee, a wide range of researchers across the world demonstrated its beneficial effects for human health, including its antitumor, antiviral, anti-inflammatory, antioxidant, or antimicrobial activities. Even if the most important member of MRJP’s family is MRJP1, numerous studies reported the therapeutic value of other members of the MRJP family and underlined its role as key active components [39]. There is a wide range of novel studies that reported the MRJPs’ beneficial role for human health [44][49][52][53][54][55][56][57][58].
In terms of its pharmacological effects on human health, MRJP1 has a wide range of pharmacological properties, including wound healing, antibacterial, antitumor, antihypertensive, antifungal activities, hypocholesterolemic effects, immune enhancement, as well as cell growth-promoting activities. In studies involving rat hepatocytes, MRJP1 was found to promote cell proliferation and induce albumin synthesis even in the absence of fetal bovine serum, potentially by functioning as biosimilars [7][59]. In mouse macrophages, MRJP2 promoted the release of the anticancer compound tumor necrosis factor-α (TNF-α) [60]. Moreover, through the inhibition of TNF-α, intracellular reactive species, and mixed lineage kinase domain-like protein, MRJP2 might alleviate hepatic necrosis against carbon tetrachloride-induced hepatotoxicity. MRJP2 could be a trustworthy treatment strategy for hepatic disorders. Additionally, recombinant MRJP2 and MRJP4 can kill various microorganisms by adhering to the cell walls of fungus, yeast, and bacteria, causing cell wall destruction [61].
As MRJP3 binds to and stabilizes ribonucleic acid (RNA), it is hypothesized that bees are able to transmit RNA across individuals, through secretion and consumption. It is also believed that this RNA transfer from worker bees to larvae may promote social immunity against diseases [38]. Kohno et al. (2004) discovered that MRJP3 impacts the immunological responses of T-cells by downregulating the production of interleukin (IL)-4, IL-2, and interferon (IFN) in research on the health aspects of MRJP3. Moreover, they reported that MRJP3 acts as an anti-allergic agent by reducing immunoglobulin (Ig)E and IgG1 synthesis. According to the authors, this protein inhibits the production of pro-inflammatory cytokines, such as TNF-, IL-6, and IL-1, in activated mouse macrophages, acting as an anti-inflammatory drug both in vivo and in vitro [45].

3.1.3. Purification of MRJPs

Regarding MRJP purification approaches, chromatography is the primary technique used for protein purification, based on extracting the substances of interest by using the interactions between a mobile and stationary phase. Using chromatographic procedures, molecules are separated from mixtures based on their characteristics, such as size, hydrophobicity, electric charge, and affinity to ligands. Among chromatographic methods, ion exchange (adsorption), hydrophobic interaction, affinity, molecular exclusion (gel filtering) are the most used for protein purification. MRJP1, MRJP2, MRJP3, and MRJP5 have a positive electrical charge due to RJ’s natural pH value of about 4.0, having isoelectric points (pI) between 5.03 and 6.65 [62].

3.2. 10-Hydroxy-2-Decenoic Acid (10-HDA)

More than 50% of the free fatty acid content of RJ is represented by 10-HDA, which has not been found in any other natural product, not even in another bee-related product [12]. Several studies have demonstrated that 10-HDA has a wide range of health-promoting activities, including immunoregulatory [3], anti-inflammatory, antioxidant [12], antidiabetic, antibacterial [63], and antitumor [18][63]. Four unsaturated fatty acids (10-H2DA, 10-HDAA, trans-2-decenoic acid, and 24-methylenecholesterol) found in RJ were demonstrated to have estrogen receptor (ER)-binding activity [64]. The interaction of these substances with ERs resulted in changes in gene expression and cell growth [65]. Recent research revealed that its antitumor properties have not been precisely outlined. However, Lin et al. (2020) [64] investigated the mechanisms behind 10-HDA’s action in A549 human lung cancer cells. According to their findings, 10-HDA exhibited no harmful effects on healthy cells while inhibiting the growth of three human lung cancer cell lines, namely A549, NCI-H23, and NCI-H460.
A study conducted by Albalawi et al. (2021) [66] aimed to examine the antitumor effect of this natural product, alone and in combination with cyclophosphamide (CP), an alkylating drug frequently used in neoplastic tumor treatment. Mice with Ehrlich solid tumors were enrolled in this research, all of them treated with 10-HDA (2.5 and 5 mg/kg) alone and combined with CP (25 mg/kg), once a day, during a 2-week period. However, more research, particularly in a clinical context, is necessary to validate these findings, the fatty acid at the dosages of 2.5 and 5 mg/kg, especially in conjunction with CP, exhibited potential antitumor effects against EST in mice.
Peng et al. (2017) [67] investigated the anti-melanogenic and depigmenting activity of 10-HDA. The skin whitening effect was monitored by applying 0.5%, 1%, and 2% of 10-HDA-based cream on mouse skin (C57BL/6 J strain) for a period of three weeks. 10-HDA, even at a dosage of 0.5%, was able to considerably stimulate skin whitening. Moreover, 10-HDA decreased the tyrosinase activity, along with the production of melanogenic enzymes, by inhibiting the microphthalmia-associated transcription factor (MITF) protein expression in B16F10 melanoma cells. These findings showed that this fatty acid has the potential to serve as a natural, effective, and safe melanogenesis inhibitor in the health and cosmetic industry.
In vitro anti-inflammatory effects of 10-HDA in lipoteichoic acid (LTA) from Staphylococcus aureus stimulated RAW 264.7 cells were evaluated by Chen et al. (2018) [68]. They observed a decrease in the number of important inflammatory genes, such as IL-1, IL-6, cyclooxygenase-2 (COX-2), and monocyte chemoattractant protein-1 (MCP-1). Furthermore, 10-HDA’s impact on lung damage caused by LTA was tested on mice. Results showed that 100 mg/kg of 10-HDA can have protective properties by controlling the release of inflammatory cytokines including IL-10, MCP-1, and TNF-α. They provide evidence that this fatty acid had significant, dose-dependent inhibitory effects. The results demonstrate 10-HDA’s powerful anti-inflammatory effects; however, authors suggest further research to fully understand this fatty acid’s mechanisms of action.

3.3. Hormones

As for the hormone content of RJ, it contains testosterone, progesterone, prolactin, estrogen [69], and estradiol [3]. Due to its resemblance to estrogens, RJ is widely used by women in order to relieve and treat menopause, as well as aging-related diseases. Clinical trials demonstrated that oral administration of 1g of RJ per day has a decreasing effect on the severity of the premenstrual syndrome. Moreover, by using this natural substance, a life quality improvement was observed amongst the reproductive-aged women [70].
RJ is supposed to play an important role in the hormonal balance, by increasing testosterone production, along with the synthesis of estrogen. 10-HDA improves hormonal balance by increasing the production of ovulation hormones and preventing the depletion of the follicular pool [71].
Other findings indicate that, when given to adult male rabbits at a dose of 150 mg/kg body weight, RJ has a beneficial impact on libido, glucose, blood testosterone concentration, total proteins, fertility, as well as sperm production and quality. It was found that RJ supplementation can enhance the physiological state of heat-stressed rabbits and it can also prevent summer infertility [72]. However, more studies on RJ hormones are needed to better understand their way of action.

This entry is adapted from the peer-reviewed paper 10.3390/molecules28031510

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