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Antihypertensive Effect of Peptides from Royal Jelly in Spontaneously Hypertensive Rats
Abstract
We have shown that Protease N treated Royal Jelly (ProRJ) and peptides from ProRJ (Ile-Tyr (IY), Val-Tyr (VY), Ile-Val-Tyr (IVY)) inhibited angiotensin I-converting enzyme (ACE) activity and they have an antihypertensive effect in repeated oral administration for 28 d on spontaneously hypertensive rats (SHR). We investigated the contributive ratio of these peptides in ProRJ for antihypertensive effect in single oral administration on SHR. In single oral administration of each peptide and peptides mixture (MIX; IY, VY and IVY) at doses of 0.5, 1 and 10 mg/kg, systolic blood pressure (SBP) of SHR was reduced dose-dependently. This antihypertensive effect was held for 8 h. These results suggest that peptides contributed to the antihypertensive effect of ProRJ. And the contributive ratio of MIX in ProRJ for antihypertensive effect was computed to be about 38%. Therefore it is considered that intake of peptides, as a functional food would be beneficial for improving blood pressure in people with hypertension.
... The main contents of bee pollen and other bee products are presented in Figure 1. For example, some results [32][33][34] indicate that royal jelly proteins have antihypertensive action and hypocholesterolemic properties. ...
... The main contents of bee pollen and other bee products are presented in Figure 1. For example, some results [32][33][34] indicate that royal jelly proteins have antihypertensive action and hypocholesterolemic properties. The bee pollen of Schisandra chinensis (Turcz.) is often used as a functional food in China. ...
... More details about its chemical components and its biological properties are reviewed by Ahmad et al. [35]. A few experimental papers have examined its cardioprotective properties, including its anti-hypercholesterolemic and anti-hypertension activity [32,33,[43][44][45][46]. ...
Apitherapy is a form of alternative therapy that relies on the use of bee products, i.e., honey, royal jelly, propolis, pollen, and bee venom (known as apitoxin), for the prevention and treatment of various diseases. Various in vitro and in vivo studies suggest that these products may be effective in the prophylaxis and treatment of cardiovascular diseases (CVDs). This mini-review of papers identified in various electronic databases describes new aspects of the bioactivity of certain bee products, viz. bee pollen, royal jelly, bee venom, propolis, and bee bread, as natural interesting products for the prevention and treatment of common CVDs.
... The use of this product as medicine has not yet been approved by the Food and Drug Administration because it is currently uncertain whether it is effective in treating any medical condition. Previous basic studies reported some effects of royal jelly against hypertension, dyslipidemia, and diabetes mellitus 14,15) . Royal jelly is expected to have potential clinical effects on vascular condition and atherosclerosis. ...
... 2.3%, P 0.91). The percentage relative changes in LDL-C, HDL-C, and triglycerides were 14) . However, no clinical studies have clearly shown the blood pressure-lowering effects of royal jelly. ...
... Furthermore, some peptides in royal jelly were reported to inhibit angiotensin-converting enzyme (ACE) activity 14,31) . Sultana et al. reported that pancreatic peptide tyrosine tyrosine (peptide YY), an isolated peptide from royal jelly, inhibits renin activity in vitro 31) . ...
Aims: Royal jelly, a creamy substance secreted by honeybees, has been reported to have beneficial effects against dyslipidemia and metabolic syndrome. However, the effects of royal jelly on atherogenesis remain unknown. Hence, we prospectively evaluated whether royal jelly augments vascular endothelial function, which can reflect early atherogenesis, in healthy volunteers.
Methods: This was a single-center, double-blind, 1:1 randomized placebo-controlled study conducted from October 2018 to December 2019. A total of 100 healthy volunteers were randomly assigned to receive either royal jelly 690 mg or placebo daily for 4 weeks. The primary endpoint was augmentation in vascular endothelial function as assessed using the change in the reactive hyperemia peripheral arterial tonometry index (RH-PAT) index, and the secondary endpoints were the changes in liver function and lipid profiles between baseline and 4 weeks after enrollment.
Results: The mean age of the participants was 35.0±9.3 years in the placebo group and 36.1±9.1 years in the royal jelly groups; 45% and 50% of the placebo and the royal jelly groups, respectively, were male. The percentage relative change in the RH-PAT index was significantly higher in the royal jelly group than in the placebo group (21.4%±53.1% vs. 0.05%±40.9%, P=0.037). The percentage relative changes in alanine aminotransferase and γ-glutamyl transpeptidase were significantly lower in the royal jelly group than in the placebo group (alanine aminotransferase: −6.06%±22.2% vs. 11.6%±46.5%, P=0.02; γ-glutamyl transpeptidase: −3.45%±17.8% vs. 4.62%±19.4%, P=0.045). Lipid profiles were not significantly different between the two groups.
Conclusions: Royal jelly might have antiatherogenic property by improving vascular endothelial function. It also augmented liver functions in healthy volunteers.
... RJ mainly contains water (60-70%), and three major macronutrients including carbohydrates (10-12%), proteins (12-15%), and lipids (3-7%) (Suzuki et al., 2008). In addition to the antioxidant property, previous studies indicated that this functional food has antiinflammatory (Kohno et al., 2004;Pourmobini et al., 2021), vasodilative and hypotensive activity (Tokunaga et al., 2004), anti-hypercholesterolemic (Bahari et al., 2023bGuo et al., 2007), anti-tumor (Townsend et al., 1959), and hypoglycemic functions (Bahari et al., 2023c;Khoshpey et al., 2016). Furthermore, anti-oxidant and anti-inflammatory properties of RJ are attributed to 10-hydroxy-2-decenoic acid (10-HDA), as the primary bioactive element of utmost significance (Honda et al., 2015). ...
Objective: This systematic review and meta-analysis examines the impact of royal jelly (RJ) on inflammation and oxidative stress. By synthesizing existing research, it aims to provide valuable insights into the potential health benefits of RJ. Materials and Methods: PubMed/Medline, Web of Science, and Scopus were searched until the end of December 2023. This meta-analysis included all randomized clinical trials assessing the effect of RJ supplements on serum levels of high-sensitivity C-reactive protein (hs-CRP), total antioxidant capacity (TAC), and malondialdehyde (MDA). A random-effects model was utilized to calculate the pooled mean differences (MD) and 95% confidence interval. Results: Seven suitable datasets from 6 trials were considered eligible. RJ supplementation significantly reduced MDA (WMD,-1.79 (-3.00 to-0.58), p=0.004; I 2 = 97.4%) and increased TAC (WMD, 0.98 (0.24 to 1.71), p=0.009, I 2 = 98.5%), but it did not significantly change hs-CRP levels (WMD:-0.24; 95% CI:-0.60, 0.10; p=0.17). RJ supplementation in higher doses and in participants with normal body mass index (BMI) could induce a greater elevation in TAC, and in participants with normal BMI, a stronger reduction in MDA. Conclusion: Although this meta-analysis confirmed that RJ could be a useful intervention to reduce oxidative stress, this research should be updated in future due to the ietsirtser number of trials.
... These peptides can control the excretion of other active compounds regulating blood pressure, such as NO, endothelin, or prostaglandins. The antihypertensive effect of RJ peptides has been demonstrated by Tokunaga et al. [192] in spontaneously hypertensive rats, indicating that RJ can be appreciated as a functional food for regulating blood pressure in people with hypertension. Moreover, the intake of RJ hydrolysates reduces a high cholesterol level and increases hemoglobin values in humans, thus having a positive effect on organism homeostasis [187,[193][194][195][196][197]. ...
Royal jelly (RJ) is a highly nutritious natural product with great potential for use in medicine, cosmetics, and as a health-promoting food. This bee product is a mixture of important compounds, such as proteins, vitamins, lipids, minerals, hormones, neurotransmitters, flavonoids, and polyphenols, that underlie the remarkable biological and therapeutic activities of RJ. Various bioactive molecules like 10-hydroxy-2-decenoic acid (10-HDA), antibacterial protein, apisin, the major royal jelly proteins, and specific peptides such as apisimin, royalisin, royalactin, apidaecin, defensin-1, and jelleins are characteristic ingredients of RJ. RJ shows numerous physiological and pharmacological properties, including vasodilatory, hypotensive, antihypercholesterolaemic, antidiabetic, immunomodulatory, anti-inflammatory, antioxidant, anti-aging, neuroprotective, antimicrobial, estrogenic, anti-allergic, anti-osteoporotic, and anti-tumor effects. Moreover, RJ may reduce menopause symptoms and improve the health of the reproductive system, liver, and kidneys, and promote wound healing. This article provides an overview of the molecular mechanisms underlying the beneficial effects of RJ in various diseases, aging, and aging-related complications, with special emphasis on the bioactive components of RJ and their health-promoting properties. The data presented should be an incentive for future clinical studies that hopefully will advance our knowledge about the therapeutic potential of RJ and facilitate the development of novel RJ-based therapeutic opportunities for improving human health and well-being.
... Gly-Ala-Ala-Glu-Leu-Pro-Cys-Ser-Ala-Asp-Trp-Trp [40] ...
The most prevalent cardiovascular illness in the world, hypertension, is a significant public health issue in both developed and developing nations. A major risk of cardiovascular disease and high blood pressure is morbidity and mortality. Among all the classes of antihypertensive drugs, angiotensin-converting enzyme (ACE) inhibition has been considered an effective therapeutic approach for the management of hypertension. ACE catalyzes the conversion of inactive angiotensin I into a potent vasoconstrictor, angiotensin II. Angiotensin II results in raising blood pressure by increasing peripheral resistance, heart rate, and cardiac output. There are a number of disorders associated with the cardiovascular system which is frequently treated with ACE inhibitors. Nowadays, various synthetic ACE inhibitors are used in clinical use to treat hypertension. There have been numerous negative side effects related to synthetic ACE inhibitors. Look for natural resources that can be exploited to produce ACE inhibitors that are reliable, safe, benign, and more cost-effective approaches. This review focuses on ACE inhibitors from natural source for the control hypertension. Additionally, a valid statistical analysis of data using a one-sample t -test on data that was collected at random and valued looks at whether the sample's mean is statistically different from or equal to a known or predicted mean value.
... RJ has been demonstrated to possess anti-bacterial [4], anti-diabetic [5], anti-inflammatory [6], anti-cancer [7], anti-hypercholesterolemic [8] and anti-hypertensive properties [9]. RJ has been reported to reduce inflammation [10] and apoptosis [11] in experimental models of neuronal injury. ...
Objectives:
This study aimed to compare the efficacy of royal jelly (RJ) and its major fatty acid 10-hydroxy-2-decenoic acid (10-HDA) on ischemic stroke-related pathologies using histological and molecular approaches.
Methods:
Male rats were subjected to middle cerebral artery occlusion (MCAo) to induce ischemic stroke and were supplemented daily with either vehicle (control group), RJ or 10-HDA for 7 days starting on the day of surgery. On the eighth day, rats were sacrificed and brain tissue and blood samples were obtained to analyze brain infarct volume, DNA damage as well as apoptotic, inflammatory and epigenetic parameters.
Results:
Both RJ and 10-HDA supplementation significantly reduced brain infarction and decreased weight loss when compared to control animals. These effects were associated with reduced levels of active caspase-3 and PARP-1 and increased levels of acetyl-histone H3 and H4. Although both RJ and 10-HDA treatments significantly increased acetyl-histone H3 levels, the effect of RJ was more potent than that of 10-HDA. RJ and 10-HDA supplementation also alleviated DNA damage by significantly reducing tail length, tail intensity and tail moment in brain tissue and peripheral lymphocytes, except for the RJ treatment which tended to reduce tail moment in lymphocytes without statistical significance.
Conclusions:
Our findings suggest that neuroprotective effects of RJ in experimental stroke can mostly be attributed to 10-HDA.
... The application of RJ resulted in reduced weight gain, alleviated hyperinsulinemia, and improved glucose tolerance. It also lowered liver enzymes and leptin, restored adiponectin levels, and decreased inflammatory markers (IL-6, TNF-α) [23][24][25]. In rats fed a high-fat diet, RJ enhanced their lipid profiles. ...
A natural product is an organic compound from a living organism that can be isolated from natural sources or synthesized [...]
... 6 Consequently, the evidence suggests that RJ serves as an effective therapeutic supplement with diverse pharmacological activities with beneficial effects in hypertension, dyslipidemia, and diabetes mellitus. [7][8][9]56 The current body of evidence does not provide sufficient support to claim that this product effectively treats any medical condition, so the Food and Drug Administration (FDA) has not granted approval for its use as a medicine. ...
Background:
Royal jelly (RJ) may contribute to glycemic control and liver function through various mechanisms. The present study aimed to quantify the effect of RJ supplementation on these outcomes.
Methods:
A literature search of Web of Science, Scopus, and PubMed/Medline, was conducted for RCTs investigating the efficacy of RJ on plasma liver enzymes and glycemic indices. Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated for net changes using a random-effects model.
Results:
Ten RCTs were selected for inclusion in this meta-analysis. Combined estimate of effect sizes for the impact of RJ on neither the plasma liver enzymes nor the glycemic indices were statistically significant. Subgroup analysis showed a significant reduction of serum FPG in trials with intervention duration ≥8 weeks (WMD: -4.28mg/dl, 95% CI -7.41 to -1.14mg/dl, p =0.007), and those conducted in non-healthy populations (WMD: -4.28mg/dl, 95% CI -7.41 to -1.14, p = 0.007).
Conclusion:
RJ does not significantly affect liver function and glycemic profile of adult population. In trials with longer intervention and those conducted in non-healthy populations a significant reduction of serum FBG was observed. This meta-analysis should be repeated in the future, with more primary articles included, in order to provide conclusive results.
... Moreover, propolis' antihypertensive effects have been examined in a range of animal models and have been linked to several biological activities, including vascular reactivity modulation, and anti-inflammatory and antioxidant properties 69 . Vitamins, carbohydrates, peptides, proteins, and fatty acids are abundant in RJ 70,71 , and certain peptides in RJ inhibit the activity of the angiotensin I-converting enzyme (ACE), resulting in hypotension in spontaneously hypertensive rats 72 . OS is another possible mechanism by which glucocorticoids induce hypertension by inhibiting both nitric oxide synthase (NOS) synthesis and transmembrane l-arginine transfer, resulting in increased peripheral resistance. ...
Hypertension-induced ventricular and vascular remodeling causes myocardial infarction, heart failure, and sudden death. Most available pharmaceutical products used to treat hypertension lead to adverse effects on human health. Limited data is available on apitherapy (bee products) combinations for treatment of hypertension. This study aims to evaluate the antihypertensive effects of combinations of natural apitherapy compounds used in the medical sector to treat a variety of diseases. Rats were assigned into six groups consisting of one control group and five hypertensive groups where hypertension (blood pressure > 140/90) was induced with dexamethasone. One of these groups was used as a hypertension model, while the remaining four hypertensive groups were treated with a propolis, royal jelly, and bee venom combination (PRV) at daily oral doses of 0.5, 1.0, and 2.0 mg/ kg, and with losartan 10 mg/kg. The PRV combination at all doses decreased arterial blood pressure below the suboptimal value (p < 0.001), and PRV combination treatment improved dexamethasone-induced-ECG changes. The same treatment decreased angiotensin-II, endothelin-1, and tumor growth factor β serum levels in hypertensive rats. Additionally, PRV combination improved histopathological structure, and decreased serum levels of NF-kB and oxidative stress biomarkers. We concluded that PRV combination therapy may be used as a potential treatment for a variety of cardiovascular diseases. Hypertension is a growing disorder and represents a leading indicator for risk for all cardiovascular diseases and mortality 1. For instance, hypertension-induced left ventricular remodeling causes heart failure, coronary artery diseases, and eventual death 2. Approximately 1.4 billion people worldwide have suffered from hypertension and its complications. Approximately 31.1% of people suffer from primary or secondary hypertension 3. Some medications, such as glucocorticoids which are widely used to treat unrelated medical conditions, may cause iatrogenic hypertension and lead to adverse effects 4. Furthermore, long-term glucocorticoid treatment causes hypertension in 80-90% of patients 5. Dexamethasone (Dex) is the strongest synthetic glucocorticoid, with pure glucocorticoid activity, compared with natural cortisol and corticosterone. These synthetic compounds possess anti-inflammatory and immunosuppressive effects 6 .
... (Kashima et al. 2014). (Tokunaga et al. 2004). ...
... The major constituents of RJ are water, protein, carbohydrates, lipids, polyphenols, and vitamins [19]. RJ is hypotensive and has potent antidiabetic activity due to its ability to stimulate insulin release, improve insulin sensitivity, and control glycemia [18,20,21]. In addition, RJ has been shown to alleviate neural, renal, and hepatic damage in several conditions, and it has potent antibacterial and antiaging effects due to its well-known antioxidant and anti-inflammatory properties [18]. ...
This study examined the mechanism underlying the protective effect of royal jelly (RJ) against high-fat-diet (HFD)-mediated non-alcoholic liver disease (NAFLD) in rats. Adult male rats were divided into five groups (n = 8 each): control fed a standard diet, control + RJ (300 mg/kg), HFD, HFD + RJ (300 mg/kg), and HFD + RJ + CC (0.2 mg/kg). The treatment with RJ reduced weight gain, increased fat pads, and attenuated fasting hyperglycemia, hyperinsulinemia, and glucose tolerance in the HFD-fed rats. It also reduced the serum levels of liver function enzymes, interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and leptin but significantly increased the serum levels of adiponectin. In addition, and with no effect on lipid excretion in stool, RJ significantly decreased the hepatic mRNA expression of SREBP1, serum, hepatic cholesterol, and triglycerides but increased hepatic mRNA levels of PPARα. Furthermore, RJ reduced the hepatic levels of TNF-α, IL-6, and malondialdehyde (MDA) in the livers of these rats. Of note, with no effect on the mRNA levels of AMPK, RJ stimulated the phosphorylation of AMPK and increased the levels of superoxide dismutase (SOD) and total glutathione (GSH) in the livers of the control and HFD-fed rats. In conclusion, RJ attenuates NAFLD via its antioxidant potential and adiponectin-independent activation of liver AMPK.
... However, the changes in the number of EPCs throughout the intervention were similar between them (Table 4). Several peptides in RJ inhibit ACE activity and RJ induces vasorelaxation through nitric oxide production from the vascular endothelium related to improvement of blood pressure in hypertensive rodents and humans, previously reported [38][39][40][41]. On the other hand, RJ consumption did not alter blood pressure in healthy human subjects, although it improved vascular endothelial function as assessed using RH-PAT [10]. ...
Objectives:
Royal jelly (RJ), produced by honeybees, influences stem cell functions, such as pluripotency maintenance of mouse embryonic stem cells and prevention of aging-related muscle stem cell functional deterioration. Thus, we hypothesized that RJ administration has various health-promoting effects based on stem cells. However, its effects are unknown in humans. In this study, we have attempted for the first time to clarify whether the administration of RJ in humans affects stem cells.
Materials and methods:
This randomized, double-blind, placebo-controlled study was performed on healthy subjects (n = 90) who received protease-treated RJ at a dose of 1200 mg/day or placebo daily for four weeks. Also, the participants with a low number of hematopoietic stem cells (HSCs) in peripheral blood were preferentially selected. HSC counts, endothelial progenitor cell (EPC) counts, blood cell counts in peripheral blood, cytokines in serum, and physical conditions were evaluated. Results and Conclusion. Eligible data from 86 subjects (placebo: 42, RJ: 44) who completed the study were analyzed. There were no significant differences between the two groups regarding the changes in peripheral HSC count (p=0.103), while diastolic blood pressure showed a significant improvement in the RJ group compared to that in the placebo group (p=0.032). The subgroup analysis excluded 14 subjects who complained of cold symptoms at baseline or within five days of the four-week study. The changes in the HSC populations were significantly higher in the RJ group than those in the placebo group (p=0.042). No adverse effects were observed in any of the groups. These results suggest that RJ administration affected the peripheral HSC count and may influence stem cell functions. Further research is needed to reveal the various health-promoting benefits of RJ based on stem cells.
... Moreover, propolis' antihypertensive effects have been examined in a range of animal models and have been linked to several biological activities, including vascular reactivity modulation, and anti-inflammatory and antioxidant properties 69 . Vitamins, carbohydrates, peptides, proteins, and fatty acids are abundant in RJ 70,71 , and certain peptides in RJ inhibit the activity of the angiotensin I-converting enzyme (ACE), resulting in hypotension in spontaneously hypertensive rats 72 . OS is another possible mechanism by which glucocorticoids induce hypertension by inhibiting both nitric oxide synthase (NOS) synthesis and transmembrane l-arginine transfer, resulting in increased peripheral resistance. ...
Hypertension-induced ventricular and vascular remodeling causes myocardial infarction, heart failure, and sudden death. Most available pharmaceutical products used to treat hypertension lead to adverse effects on human health. Limited data is available on apitherapy (bee products) combinations for treatment of hypertension. This study aims to evaluate the antihypertensive effects of combinations of natural apitherapy compounds used in the medical sector to treat a variety of diseases. Rats were assigned into six groups consisting of one control group and five hypertensive groups where hypertension (blood pressure > 140/90) was induced with dexamethasone. One of these groups was used as a hypertension model, while the remaining four hypertensive groups were treated with a propolis, royal jelly, and bee venom combination (PRV) at daily oral doses of 0.5, 1.0, and 2.0 mg/ kg, and with losartan 10 mg/kg. The PRV combination at all doses decreased arterial blood pressure below the suboptimal value (p < 0.001), and PRV combination treatment improved dexamethasone-induced-ECG changes. The same treatment decreased angiotensin-II, endothelin-1, and tumor growth factor β serum levels in hypertensive rats. Additionally, PRV combination improved histopathological structure, and decreased serum levels of NF-kB and oxidative stress biomarkers. We concluded that PRV combination therapy may be used as a potential treatment for a variety of cardiovascular diseases. Hypertension is a growing disorder and represents a leading indicator for risk for all cardiovascular diseases and mortality 1. For instance, hypertension-induced left ventricular remodeling causes heart failure, coronary artery diseases, and eventual death 2. Approximately 1.4 billion people worldwide have suffered from hypertension and its complications. Approximately 31.1% of people suffer from primary or secondary hypertension 3. Some medications, such as glucocorticoids which are widely used to treat unrelated medical conditions, may cause iatrogenic hypertension and lead to adverse effects 4. Furthermore, long-term glucocorticoid treatment causes hypertension in 80-90% of patients 5. Dexamethasone (Dex) is the strongest synthetic glucocorticoid, with pure glucocorticoid activity, compared with natural cortisol and corticosterone. These synthetic compounds possess anti-inflammatory and immunosuppressive effects 6 .
... The most frequent compounds in royal jelly are proteins (12%-15%), sugars (10%-16%), lipids (3%-6%), vitamins, free amino acids, and minerals (8). Investigations carried out on experimental animals exhibited many pharmacological functions of royal jelly including antibacterial (8), antioxidant (9), antitumor (10), anti-inflammatory (8), antiallergic (11), anti-aging (12), wound healing (10), and antihypertensive functions (13). In addition, the improved lipoprotein metabolism, reduced serum total cholesterol, and low-density lipoprotein levels were also observed following the consumption of royal jelly by humans (14). ...
Background and aims: Highly active oxygen causes DNA or protein damage. This study aimed to determine the effect of the extract of three medicinal plants, royal jelly, and metformin on the survival of human dermal fibroblast (HDF) cells under oxidative stress induced by H2 O2 . Methods: Hydroalcoholic extracts were prepared from Nigella sativa, Carum carvi seeds, and Taraxacum officinale flower. The growth curve of HDF cells was plotted in Dulbecco’s modified eagle medium (DMEM). The cells were exposed to H2 O2 stress and treated with different concentrations of the extracts, royal jelly, and metformin. The cells viability was then calorimetrically analyzed during different times in 69-well plates. Results: The exponential growth phase of HDF cells was observed during 24–72-hour growth. High cell survivals were seen during 72 hours of exposure to 25 mg/mL royal jelly (99.13±3.22%), 15 mg/mL C. carvi extracts and N. sativa (97.87±3.25% and 96.22±5.47%, respectively), 10 mg/mL royal jelly (96.14±4.72%), 16 mg/mL metformin (91.23±5.34%), and 8 mg/mL T. officinale (86.31±7.44%), respectively. These results were significantly higher than the results of 48 and 24 hours of exposure to 15 mg/mL N. sativa (P=0.013), 15 mg/mL C. carvi (P=0.019), and 16 mg/mL metformin (P=0.027). Moreover, royal jelly (25 mg/mL) significantly indicated greater effect on the cell survival compared with the highest concentrations of the extracts and metformin at different exposure times (P=0.016-0.032). Conclusion: Royal jelly, N. sativa, and T. officinale extracts revealed remarkable effects on the stressed HDF cells; therefore, they can be proposed for treatment of wounds and burns after clinical analysis.
... RJ hydrolyzed with protease N and the resulting peptides (Ile-Tyr, Val-Tyr, and Ile-Val-Tyr) were able to inhibit angiotensin-converting enzyme (ACE) activity and had anti-hypertensive effects by decreasing systolic blood pressure in a dose-dependent manner after 28-days oral treatment in spontaneously hypertensive rats. Therefore, the peptides resulting from RJ hydrolysis may be useful for ameliorating blood pressure in patients with hypertension (Tokunaga et al., 2004). ...
Royal jelly (RJ) is a complex beehive product that is important for larval development and queen nutrition in the hive and may also have beneficial effects on human health, according to in vitro and in vivo studies. The main proteins in RJ belong to the Major royal jelly proteins family (MRJPs), representing up to 90% of the total proteins. This narrative review aims to compile the results of studies on MRJPs and their derived peptides to understand their biological effects better, their most important activities being antioxidant, antimicrobial, anti-tumor, hypotensive, hypolipidemic, cell growth promoting, wound healing, anti-aging, neuroprotective, anti-inflammatory and immune-modulatory.
... Also RJ contains bioactive components such as biologically active peptides that help decrease levels of blood pressure (BP) through inhibiting vasoactive enzymes such as Angiotensin Converting Enzyme (ACE), responsible for increasing BP by converting angiotensin I to angiotensin II, which is a strong vasoconstrictor (Bhat et al., 2017). The following peptides with antihypertensive activity have been identified within the RJ: Trp-Val-Leu, Tyr-Tyr-Ser-Pro (Matsui et al., 2006), Ile-Tyr, Val-Tyr, Ile-Val-Tyr, Tyr-Tyr, Ile-Phe, Lys-Ser (Maruyama et al., 2003;Tokunaga et al., 2004), Asp-Gly-Leu and Leu-Thr-Phe (Matsui et al., 2002). ...
Royal jelly is a glandular secretion produced by Apis mellifera L. bees, and it is considered as a functional food with the ability to control and prevent chronic diseases such as high blood pressure, because in their composition there are peptides with biological activity. The objective of this study was to evaluate the effect of the food consumed by honey bees on the antihypertensive potential of the royal jelly produced. Honey bee colonies were fed with three different diet treatments: Mucuna pruriens flour and honey; pollen and honey and free feeding. The amino acid content was determined in the proteic ingredients and the royal jelly obtained by every feed treatment. The antihypertensive activity was evaluated in vitro by the angiotensin converting enzyme technique. To assess the antihypertensive activity in vivo, Wistar rats were subjected to a biological model of metabolic syndrome model, the rats were dosed with royal jelly and the blood pressure were measured every week. No significant differences (P>0.05) were found between the jellies regarding the presence of amino acids associated with antihypertensive activity. The angiotensin converting enzyme inhibition values were less than 25%; however the blood pressure in the groups of rats that received the royal jelly treatments was similar to the control group (P>0.05). The amino acid composition in royal jelly can be related with the feed consumed by the nurse bees. This results indicates that the consumption of royal jelly prevent the elevation in the blood pressure values, demonstrating an antihypertensive effect.
... The antioxidant activity of royal jelly (RJ), one of the products of the honey bee, prevents oxidative stress, lipid peroxidation, and protection of the DNA from oxidative damage. The results of studies showed that RJ is a highly potent antioxidant and acts as an antiinflammatory and antimicrobial agent (9,10). The beneficial effects of RJ can be attributed to the antioxidant properties of its tri-D peptide (Tyr-Tyr, Arg-Tyr, Lys-Tyr). ...
Background and purpose: Dichlorvos, an organophosphate insecticide, induces side effects on normal tissues. On the other hand, Royal jelly (RJ) with antioxidant activities has many medical benefits including liver toxicity. In this study, we investigated the role of RJ in improving dichlorvos adverse impact on the liver of male rats.
Experimental approach: Forty-eight male rats were randomly divided into 8 groups (n = 6); receiving by gavage normal saline (0.09%), dichlorvos (4 mg/kg/day), RJ (50, 100, 150 mg/kg/day; RJ 1, 2, 3) or dichlorvos + RJs, daily for 28 consecutive days. At the end of experiments, histopathology alterations, apoptosis induction, and biochemical factors related to the liver were evaluated.
Findings/Results: There was a significant reduction in the number of hepatocytes and total antioxidant capacity (TAC) levels in the dichlorvos group compared to the control group, whereas these parameters in the dichlorvos + RJs groups, were significantly increased compared to the dichlorvos group. Central vein diameter, liver enzymes (aspartate transaminase, alanine transaminase, and alkaline phosphatase) serum levels of nitric oxide, and apoptotic index were significantly higher in the dichlorvos group than in the control, while these parameters were decreased in the dichlorvos + RJs groups versus the dichlorvos group.
Conclusion and implications: RJ at 50 mg/kg protected dichlorvos-induced liver damage in rats. Dichlorvos- hepatitis mechanism could be oxidative induction as long as antioxidant reduction leads to apoptosis in this organ, while RJ due to its antioxidant potential suppresses this hazardous cellular and molecular process.
... Royal jelly (RJ) is a natural bee product that is widely used as a health food and supplement worldwide because of its anti-inflammatory, antioxidative, antibacterial, and anticancer effects [18,19]. In addition, RJ has been reported to be associated with vasorelaxation and antihypertensive effects via vascular endothelial cell activity, angiogenesis, and nitric oxide production at the molecular level [20][21][22][23]. Moreover, several in vitro studies have shown that RJ affects the secretion of inflammationrelated cytokines from activated macrophages [24,25]. ...
Background
Hemodialysis (HD) is a common renal replacement therapy for patients with renal failure. Cardiovascular and cerebrovascular diseases are known to shorten survival periods and worsen the quality of life of HD patients. Atherosclerosis is a major cause of vascular diseases, and various factors such as abnormality of lipid metabolism and increased macrophage activity, oxidative stress, and endothelial dysfunction are associated with its pathogenesis and progression. Further, endothelial stem cells (ESCs) have been reported to play important roles in endothelial functions. Royal jelly (RJ) affects atherosclerosis- and endothelial function-related factors. The main aim of this trial is to investigate whether oral intake of RJ can maintain endothelial function in HD patients. In addition, the effects of RJ intake on atherosclerosis, ESC count, inflammation, and oxidative stress will be analyzed.
Methods
This will be a multicenter, prospective, double-blind, randomized controlled trial. We will enroll 270 participants at Nagasaki Jin Hospital, Shinzato Clinic Urakami, and Maeda Clinic, Japan. The participants will be randomized into RJ and placebo groups. The trial will be conducted according to the principles of the Declaration of Helsinki, and all participants will be required to provide written informed consent. The RJ group will be treated with 3600 mg/day of RJ for 24 months, and the placebo group will be treated with starch for 24 months. The primary endpoint will be the change in flow-mediated dilation (FMD), a parameter of endothelium function, from the time before treatment initiation to 24 months after treatment initiation. The secondary and other endpoints will be changes in FMD; ESC count; serum levels of vascular endothelial cell growth factor, macrophage colony-stimulating factor, 8-hydroxydeoxyguanosine, and malondialdehyde; the incidence of cardiovascular diseases, cerebrovascular diseases, and stenosis of blood access; and safety.
Discussion
This trial will clarify whether oral intake of RJ can maintain endothelial function and suppress the progression of atherosclerosis in HD patients. In addition, it will clarify the effects of RJ on ESCs, oxidative stress, and angiogenic activity in blood samples.
Trial registration
The Japan Registry of Clinical Trials jRCTs071200031 . Registered on 7 December 2020.
... Se han identificado que los tripéptidos ác. aspártico-glicina-leucina e isoleucina-valina-tirosina poseen la capacidad de disminuir la presión sanguínea (Matsui et al. 2002); además, los péptidos isoleucina-tirosina y valina-tirosina también han demostrado actividad antihipertensiva (Tokunaga et al., 2004). Al analizar la presencia de los aminoácidos ác. ...
La jalea real (JR) es una secreción de las abejas, considerada como un alimento funcional debido a que posee una gran cantidad de nutrientes y propiedades bioactivas, muchas de estas atribuidas a péptidos con actividad biológica; sin embargo, se desconoce el efecto que puede tener la alimentación de las obreras en la presencia y concentración de los aminoácidos que conforman a los péptidos. El objetivo del trabajo fue determinar el perfil de aminoácidos de dos diferentes fuentes proteicas usadas para alimentar a las abejas y de la JR producida, con el fin de conocer el impacto que puede tener el alimento consumido en la presencia de los aminoácidos que conforman la JR. Se utilizaron tres tratamientos diferentes para alimentar a las abejas (Dieta 1: harina de Mucuna pruriens y miel; dieta 2: polen y miel; dieta 3: alimentación libre). El perfil de aminoácidos se realizó para conocer la concentración de cada uno de los aminoácidos esenciales y no esenciales que conformaban los ingredientes proteicos de las dietas, así como de la JR producida. Los resultados indicaron que los ingredientes proteicos y las jaleas, poseen todos los aminoácidos esenciales. La presencia de todos los aminoácidos en las jaleas sirve como un indicador de que el alimento consumido por las abejas es de calidad y que probablemente, parte de la actividad biológica de la JR se debe a la presencia de péptidos bioactivos.
... With its rich content, this product, which provides food for worker bees for a short time and the queen bee for a lifetime, has also attracted the attention of humans. Studies increasing day by day include anti-aging, anti-inflammatory, antioxidant, antibacterial, antifungal, antiviral, antihypertensive, immunomodulatory, preventing osteoporosis risk, hepatoprotective, cardioprotective, antiulcer, neuroprotective, anticancer, growth promoting, wound healing, stated that it has antirheumatic, antidepressant, antiallergic, and balancing effects of high cholesterol levels [68][69][70][71][72][73][74][75] . Since it has estrogen-like activity, current studies are investigating that it can be a traditional solution for postmenopausal symptoms and reduce complaints 76 . ...
While Brazil and the United States of America are in the first place in world Apitherapy research, our country is in the fifth place after Japan and China. While the studies on apitherapy are continuing rapidly in the world, it has started to become widespread in our country especially in 2014 with the regulation of traditional and complementary medicine practices, and Apitherapy units and application centers have started to be established. Apitherapy is the use of bee products to protect and improve health, to strengthen the immune system and to complement the treatment process of some diseases. While bee products such as honey, propolis, bee pollen have been known and used for a long time, studies on apilarnil, royal jelly and bee venom have started to increase in recent years. These products have been used both as foodstuffs and as a source of healing from wound healing to anticancer effect for many years due to their rich content. With scientific studies, the interest in apitherapy products has increased even more. Cancer is known as the leading cause of death in our country and all over the world. Side effects, costs, etc. Such adverse conditions have led researchers to research natural treatment methods. These natural treatments are used to increase the effectiveness of existing traditional treatments. In this review, literature information about Apitherapy, which is one of the traditional and complementary medicine applications, chemical content and physiological effects of bee products, is given and the therapeutic effect of bee venom on cancer is mentioned. Studies on the anticancer activity of bee venom in almost all types of cancer have been conducted and promising results have been obtained. This situation indicates that this apitherapeutic product will take place as a supplement in cancer treatment in the near future.
... However, the actual compositions may vary depending on pollen source, climate, environmental conditions and the processing methods [127][128]. Royal jelly also includes carbohydrates, lipids, proteins and vitamins but with a large number of bioactive components such as 10hydroxy decanoic acid, several peptides and proteins (MRJPs-Major royal jelly proteins, Apismin, Royalactina, Roalisin, Jelleines, Glucose oxidase, Apolippophorin III like) [62,118,126,[130][131][132]. Honey and royal jelly may be considered as functional foods because of having naturally high an-tioxidant potential in them [126]. ...
Being one of the most important insect pollinators, honey bee plays a great role
in the livelihood of mankind. It pollinates flowers during foraging and shares a
great contribution in agriculture and horticulture towards the yield of fruits and
crops. Interestingly, this tiny insect has very sophisticated machines hidden
inside its’ body that produce honey, royal jelly, wax and propolis etc.
Considering the great number of exocrine glands present in their bodies, honey
bee body may be considered as a chemical factory. Honey bees produce these
products through a sophisticated machinery mechanism involving regurgitation,
enzymatic activity and water evaporation. Honey bees prepared these products
for various purposes such as to feed queens/workers/drones, making honey
combs, hive construction and colony maintenance etc. On the other hand these
bee products are highly benefited to human as nutritional food supplements and
medicine. This article narrates the summary of honey and royal jelly and their
medicinal benefits to human.
... It has a yellowish-white color, a gelatinous-viscous sour taste, with a slight characteristic odor of phenol (which gives it a distinct odor) (Fratinia et al., 2016), and relatively acid (pH 3.6-4.2) (Seven et al., 2014;Fratinia et al., 2016). It is rich in vitamins, proteins, enzymes, fatty acids, peptides, and flavonoids (Tokunaga et al., 2004;Melliou and Chinou, 2005;Vucevic et al., 2007). Hence, the intellectual property of RJ has been adopted since ancient times in folk medicine, especially in Asian apitherapy, but also in ancient Egypt. ...
For sustainable and organic farming, organic manures such as cattle manure (CMn) and bio-nutritious substances such as royal jelly (RJ) should be used as complete or at least partial alternatives to chemical fertilizers (CFs). Therefore, two consecutive trial seasons (2018 and 2019) were conducted to study the effect of soil fertilization with CMn and/or CFs in combination with foliar spraying with RJ on growth, yield, and chemical composition of roselle (Hibiscus sabdariffa L.) plant and seed. The results indicated that spraying roselle plants with RJ resulted in a significant increase in all parameters studied over the control; however, this increase was enhanced when RJ was combined with soil fertilization. The highest values for most of the growth traits, chemical composition of seeds, sepal anthocyanin and vitamin C contents, and sepal acidity were obtained by applying 2 or 4 g RJ L⁻¹ + (30 m³ CMn ha⁻¹ + 50% dose CFs). In addition, the highest values for yield components and plant chemical composition were obtained by applying 2 or 4 g RJ L⁻¹ + (0 m³ CMn ha⁻¹ + full dose CFs). The results also indicated that applying CMn in combination with RJ gave values mostly close to those of CFs treatment. In conclusion, the results recommend the use of RJ (2 g L⁻¹ as a foliar feeding) along with CMn (30 m³ ha⁻¹) as a partial alternative to chemical fertilizers for sustainably producing healthy roselle sepals.
... The blood pressure lowering capacity of the ACE-I inhibitory peptides is varied from 1 to 9 h after oral administration. A dipeptide (IY, VY) the maximum reduction of SBP (16.8, 14.8 mmHg) was found in the 1 h of oral administration (Tokunaga et al. 2004). In contrast, Alashi et al. (2014) reported that crude peptides from canola protein hydrolysates reduced SBP (-31 mmHg) at 4 h of oral administration in SHR. ...
Food proteins are sources for ACE-I inhibitory peptides that can be extracted by enzymatic hydrolysis exhibiting anti-hypertensive activity. However, these peptides are prone to further degradation by gastrointestinal enzymes during oral consumption. Bio-activity of these peptides is dependent on the resultant peptide post gastrointestinal digestion. To exhibit the bio-activity, they need to be absorbed in intact form. Although studies suggest di and tri-peptides show better ACE-I inhibitory activity, few peptides show altered IC50 values under simulated gastrointestinal digestion. Moreover, ACE-I inhibitory peptides with low IC50 values have not shown effective anti-hypertensive activity in spontaneously hypertensive rats when administered orally. Few ACE-I inhibitory peptides have reported effective reduction in systolic blood-pressure when administered through intravenously. During oral consumption of such peptides, the actual peptide sequence responsible for reducing blood-pressure is a result of breakdown in gastrointestinal tract. The fate of targeted peptides during digestion depends on amino acid sequence of the protein containing the specific site for cleavage where the action of digestive enzymes takes place. Therefore, this review attempts to explain the factors that affect the anti-hypertensive activity of ACE-I inhibitory peptides during oral consumption. It also highlights subsequent absorption of ACE-I inhibitory peptides after gastrointestinal digestion.
... RJ is reported to be composed of water (60%-70%), proteins (27%-41% of the dry matter), carbohydrates (up to 30% of the dry matter), fatty acids and lipids (3%-8% of the fresh matter and 8%-19% of the lyophilized form), 10-hydroxy-2-decenoic acid (10-HDA) (>1.4% of the fresh matter and >3.5% of the lyophilized form), and trace amounts of vitamins and minerals (Sabatini et al., 2009). Because of the high abundance of organic fatty acids and oligosaccharides, RJs possess moisturizing, emulsifying, and stabilizing properties, and several pharmacological activities are also present, including antioxidative, antimicrobial, anti-inflammatory, antitumor, anti-hypertensive, anti-photoaging, and wound-healing properties (Pavel et al., 2011;Townsend et al., 1960;Tokunaga et al., 2004;Park et al. 2011Park et al. , 2012, which make them an ideal constituent for cosmetic and skin care products. ...
Royal jellies (RJs) possess moisturizing, emulsifying, and stabilizing properties, and several pharmacological activities have also been found to be present, which make them an ideal component for cosmetic and skin care products. However, despite the abundant efficacies, there is a lack of studies that explore the chemical composition of RJ using metabolome analysis. Furthermore, an evaluation of the chemical composition of Indonesian RJs collected from different regions has yet to be carried out. Therefore, the main objective of this study was to identify any differences in the chemical composition of such RJs. Chemical profiling was also carried out to enable more targeted utilization based on the actual compositions. Chemical profiling is also important given the rich Indonesian biodiversity and the high dependence of the RJ compositions on the botanical source. In this research, ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used as part of an untargeted metabolomics approach. From the chemical profiling, >30 compounds were identified across four RJ samples. The major constituents of the samples were found to be oligosaccharides, fatty acids, and adenosine monophosphate derivatives. Meanwhile, sucrose and planteose were found to be highest in the samples from Banjarnegara and Kediri, whereas dimethyloctanoic acid was found to be unique to the sample from Banjarnegara. It was also discovered that the RJs from Demak and Tuban contained more organic fatty acids and oligosaccharides than the other samples. Although the sample from Demak demonstrated good potential for use in the cosmetic, skin care, and bio-supplement industries, the higher abundance of fatty acids and oligosaccharides in the sample from Tuban indicated that it is perhaps the most suitable RJ for use in this field.
... [12] In laboratory animals, RJ has been shown to have several pharmacological functions, like antitumor, [13] antioxidant, [4] anti-inflammatory, [14] antibacterial, [15] anti-allergic, [16] anti-aging [17] and anti-hypertensive properties. [18] For humans, its oral consumption facilitates the metabolism of lipoproteins and decreases the levels of total serum cholesterol (TC) and low density lipoprotein (LDL). In postmenopausal women, a mixture of four natural components, including RJ, promoted health and well-being. ...
Royal Jelly (RJ) is most wanted healthy food supplement that makes lots of health benefits. One of the benefits include that it can act as potent supplement for healthy egg to help women with infertility. This review is focused on the recent developments in use of RJ in the treatment of infertility and boon for them to give a dream child. The healthy egg is very phenomenal key factor for the in vitro fertilization to be successful in sexing with sperm. RJ is traditionally used as health supplement for infertility treatment from the ancient time in Indian traditional system. The recent literature revealed that, scientific and traditional findings are proven it RJ is one of the therapeutic molecule and act as a food supplements that can be used it in to improve egg cell physiology. Although, there is no clinical research studies have been reported yet on RJ. Hence, in this review explored the comprehensive report on health benefits of RJ and its impact on reproductive aspects in particular in egg development of women during ovulation. This article will be the key step to the researchers and scientists who are involved in searching alternative, cost effective and without side effect for treating infertility in global scenario.
... Yang et al. (2018) also reported that10-HAD found in royal jelly shows bactericide and antiinflammatory activity in human colon cancer cells. Furthermore, royal jelly also shows multiple pharmacological activities as antitumor (Townsend et al., 1960), anti-oxidant (Nakajima et al., 2009), anti-inflammatory (Kohno et al., 2004), antibacterial (Tseng et al., 2011), anti-allergic (Okamoto et al., 2003), anti-aging (Park et al., 2012), and antihypertensive properties (Tokunaga et al., 2004). ...
Honey bees play significant role in crop pollination. As, honeybee nutrition is raising global topic in beekeeping, it's essential nutrients, nutrient sources and role in honey bees are reviewed in this paper. Like other animals, honeybees also need carbohydrate, protein, vitamins, minerals and water. These nutrients are primarily supplemented by pollen, nectar, royal jelly or water. Adequate supplement of these nutrients play significant role in growth and development in honeybees and also development of immunity in honeybees. Knowledge of bee nutrition helps to manage nutrient in bee colony and prevents them from different diseases and pests.
... It may cause myocardial infarction, heart failure, cerebral stroke, and it is usually associated with metabolic syndrome. Three peptides contained in royal jelly (Ile-Val-Tyr, Val-Tyr, and Ile-Tyr) were reported to inhibit the activity of angiotensin I-converting enzyme and to normalize the systolic blood pressure after only 28 days of treatment in hypertensive rats [62]. ...
Women’s life stages are based on their reproductive cycle. This cycle begins with menstruation and ends with menopause. Aging is a natural phenomenon that affects all humans, and it is associated with a decrease in the overall function of the organism. In women, aging is related with and starts with menopause. Also, during menopause and postmenopausal period, the risk of various age-related diseases and complaints is higher. For this reason, researchers were pushed to find effective remedies that could promote healthy aging and extended lifespan. Apitherapy is a type of alternative medicine that uses natural products from honeybees, such as honey, propolis, royal jelly, etc. Royal jelly is a natural yellowish-white substance, secreted by both hypopharyngeal and mandibular glands of nurse bees, usually used to feed the queen bees and young worker larvae. Over the centuries, this natural product was considered a gold mine for traditional and natural medicine, due to its miraculous effects. Royal jelly has been used for a long time in commercial medical products. It has been demonstrated to possess a wide range of functional properties, such as: antibacterial, anti-inflammatory, vasodilatative, hypotensive, anticancer, estrogen-like, antihypercholesterolemic, and antioxidant activities. This product is usually used to supplement various diseases such as cardiovascular disease, Alzheimer’s disease, sexual dysfunctions, diabetes or cancer. The main objective of this study is to highlight the effectiveness of royal jelly supplementation in relieving menopause symptoms and aging-related diseases. We also aimed to review the most recent research advances regarding the composition of royal jelly for a better understanding of the effects on human health promotion.
... [28] These findings indicate the adverse effects of Dich on endocrine system activity. [29] The results of some studies have emphasized adrenocorticotropic hormone (ACTH) increment following the destructive role of organophosphorus administration that finally amplifies the protein catabolism and weight loss. [30] IA has substantial biocompatible mixture such as sugars, fatty acids, minerals, and vitamins. ...
... [28] These findings indicate the adverse effects of Dich on endocrine system activity. [29] The results of some studies have emphasized adrenocorticotropic hormone (ACTH) increment following the destructive role of organophosphorus administration that finally amplifies the protein catabolism and weight loss. [30] IA has substantial biocompatible mixture such as sugars, fatty acids, minerals, and vitamins. ...
... [28] These findings indicate the adverse effects of Dich on endocrine system activity. [29] The results of some studies have emphasized adrenocorticotropic hormone (ACTH) increment following the destructive role of organophosphorus administration that finally amplifies the protein catabolism and weight loss. [30] IA has substantial biocompatible mixture such as sugars, fatty acids, minerals, and vitamins. ...
... [28] These findings indicate the adverse effects of Dich on endocrine system activity. [29] The results of some studies have emphasized adrenocorticotropic hormone (ACTH) increment following the destructive role of organophosphorus administration that finally amplifies the protein catabolism and weight loss. [30] IA has substantial biocompatible mixture such as sugars, fatty acids, minerals, and vitamins. ...
Ipomoea aquatica (IA) with antioxidant properties is used in therapeutic trends. An organophosphate, dichlorvos (Dich), is a common insecticide with various side effects on living tissues. This study examines the role of IA on Dich-induced hepatotoxicity in male rats. Sixty-four male rats were divided into eight groups including sham, Dich (4 mg/kg/day, intraperitoneally), IA 1, 2, and 3 (250, 500, and 1000 mg/kg/day, respectively, orally), and Dich + IA 1, 2, and 3. All treatments were applied daily for 60 days. At the end of the treatment, the animals were sacrificed. The histopathological changes, leukocyte infiltration, and apoptosis were assessed by light and fluorescent microscopy. The serum levels of hepatic enzymes, nitrite oxide (NO), and total antioxidant capacity (TAC) were evaluated biochemically. Dich statistically significantly increased the NO level, hepatic enzyme activity, apoptosis, leukocyte infiltration, the mean diameter of hepatocytes (DHs), and central hepatic vein diameter (CHVD) and also decreased the TAC, mean weight of liver, and the total weight of rats compared to the sham group (P < 0.01). In all IA and Dich + IA groups, a statistically significant decrease was detected in apoptosis, leukocyte infiltration, hepatic enzyme activity, NO level, mean DH, and CHVD, whereas an increase in TAC level, mean liver weight, and total weight was detected compared to the Dich group (P < 0.01). IA, due to the antioxidant property, recovers the Dich-related catastrophic changes in liver.
... These were IW (isoleucine-tryptophan), VY (valine-tyrosine), IY isoleucine-tyrosine, EY (glutamate-tyrosine), and DG (aspartate-glycine). Except for EY, all peptides presented in vivo activity despite being hydrophobic [20][21][22][23]. These have been described as unstable during gastrointestinal digestion [24]. ...
Metabolic syndrome comprises a cluster of diseases like hypertension, dyslipidemia, and insulin resistance, among others. Its treatment is based on lifestyle modification; however, this treatment often fails to improve metabolic syndrome indicators over the long term. In this work, sequences of some representative vegetable proteins were explored to find bioactive peptides with activity toward metabolic disorders of metabolic syndrome. Five proteins, i.e., legumin (chickpea), glutelin type A-2 (chickpea), glutelin type B-2 (rice), prolamin PPROL 17 (maize), and glutelin (rice) revealed a high potential to be effective against metabolic syndrome. We designed and evaluated in silico modifications to their amino acid sequence to release bioactive peptides after simulating gastrointestinal digestion (SGD). The approach presented here allows the design of proteins that could combat metabolic syndrome, for later production and study. In the future, these proteins can be used as functional foods.
... Bu nedenle pek çok biyolojik aktivite gösterdiği bildirilmiştir. Yapılan çalışmalarda arı sütünün; nörogenik aktivitesi (Zamanı, 2012;Hashimoto, 2005;morita, 2012), anti tümör (Ka radeniz,2011;Tamura,1987;Izuta, 2009), antimikrobiyel (Tseng, 2011;Boukraa, 2009),antihypertensive (Tokunaga, 2004;Takaki-Doi, 2009) aktivite, kan kolesterolü ve şeker düzenliyeci (Guo, 2007;Münstedt, 2009) ve anti-inflammatuar etki (Kohno, 2004;Yanagita, 2011), antioxidan (Nakajima, 2009;Silici, 2010;Cemek, 2010), immunmodulator (Okamoto, 2003;şimşek, 2009;Gasic,2007;Sugiyama, 2012) ve östrojenik (Suzuki,2006) aktivite gösterdiği bildirilmiştir. ...
The honeybee production is to come into question as one of the most important economical sources in our country as being in the world. Up to date, twentyseven honeybee breeds are used for this purposes in the world. In Turkey, it is known that honeybee breeds are spreaded according to regions; Apis mellifera anatolica at the sea side of Trakya, Eagen, Anatolia ve Mediterranean; A. m. caucasica at the sea side of Northeast of Anatolia and east blacksea; A.m. meda (iranian honeybee) at eastsouth of Anatolia region. In addition, it is talked about the exist of honeybee breeds of east Eagen islands, Muğla and Thrace and Syria (A.m. syriaca). On these honeybee breeds as enunciative of genetic resources, a lot of various were done studies as consisting of high value of information on the yield, genetic distances etc. The results of these studies are not said all Turkey honeybee populations are identical because of the regional different honeybee clonies. However, the solution of the problems occuring at the
honeybee production is related to unsufficent usage
of the genetic resources. Recently, biotechnological
advances as parallel into morphological studies done
on the other organisms are hoped to show valuable
developments at the honeybee breeding for higher
yield. At the honeybee breeding, the importance of
honeybee genetic resources is thought to come from
the genes related to resistance to diseases, yield
etc. Using these genes can be possible to solve the
problems of honeybee production such as breeding
resistance breeds against American foulbrood and
varroa problems. In our country, there is no any
comprehensive study exhibiting the genome profile of
honeybee genotypes, yet. From the angle of utilization
of genetic resources, molecular techniques are used
to get more genetic information about genomes. The
widest used molecular techniques are microsatellite,
RFLP, mtDNA studies and SNP sequences. We need
more bioinformatics on Turkish honeybee breeds
making genome DNA sequence mapping.
... Iron (Li, Huang, & Xue, 2013;Shirzad, Kordyazdi, Shahinfard, & Nikokar, 2013;Tokunaga et al., 2004). revealed that the RJ has many protein fractions that possess the scavenging capability against reactive oxygen species (ROS) and high antioxidant activity. ...
Royal jelly (RJ) is one of the furthermost valuable curative products mentioned by natural medicine scientists due to its promising medical and nutritional purposes. It possesses many impacts, including antioxidants, antimicrobial, antitumor, anti‐inflammatory and immunomodulatory functions in human and animal that benefit their health and welfare, resulting in its widespread use in medical and commercial products and healthy food. Recently, favourable functions of RJ on male fertility have been reported in different animals. According to earlier literatures, the level of RJ supplementation in animal diet ranged from 100 to 200 mg/kg. Oral exposure to RJ has been reported to have oestrogenic influences in the adult female rats. Also, RJ may be influential in improvement of pregnancy and lambing rates of ewes. Oral administration of RJ at 100 mg/kg diet before sexual maturity enhanced sexual behaviour and semen quality of male rabbits. Moreover, RJ administration (up to 400 mg/kg diet once weekly) for male rabbits exposed to heat stress can counteract “summer infertility” and improve physiological responses. Furthermore, supplementation of freezing extender media with 0.1 or 3% RJ had a protective influence on cryopreserved and chilled spermatozoa of buffalo and ram respectively. However, the high dose of RJ oral administration (800 mg/kg) by pubescent male rats for 1 month had an undesirable effect on the reproductive system; however, the somewhat unfavourable influences were mitigated by the discontinuation of the administration. This review shows the chemical composition, favourable applications and health benefits of RJ and its effects on reproductive aspects, semen quality and in vitro fertilization outcomes which are advantageous for scientists, researchers, nutritionists, physiologists, embryologists, pharmacists, veterinarians, pharmaceutical industries and animal's breeders.
... However, ERJ and its peptides (Ile-Tyr, Val-Tyr, and Ile-Val-Tyr) stop ACN activities and exhibited anti-hypertensive effects after oral treatment for 28 days in the SHR. Systolic blood pressure decreases in SHR depending upon the quantity of oral administration of these peptides, which may be beneficial for improving blood pressure in people with hypertension [91]. ...
Royal jelly (RJ) is a yellowish-white and acidic secretion of hypopharyngeal and mandibular glands of nurse bees used to feed young worker larvae during the first three days and the entire life of queen bees. RJ is one of the most appreciated and valued natural product which has been mainly used in traditional medicines, health foods, and cosmetics for a long time in different parts of the world. It is also the most studied bee product, aimed at unravelling its bioactivities, such as antimicrobial, antioxidant, anti-aging, immunomodulatory, and general tonic action against laboratory animals, microbial organisms, farm animals, and clinical trials. It is commonly used to supplement various diseases, including cancer, diabetes, cardiovascular, and Alzheimer's disease. Here, we highlight the recent research advances on the main bioactive compounds of RJ, such as proteins, peptides, fatty acids, and phenolics, for a comprehensive understanding of the biochemistry, biological, and pharmaceutical responses to human health promotion and life benefits. This is potentially important to gain novel insight into the biological and pharmaceutical properties of RJ.
... In addition to its use as a dietary supplement, RJ has been reported to be associated with many health-promoting properties, such as cancer prevention, cholesterol reduction and wound healing, as well as antifatigue, antihypertensive and antibacterial effects. In addition to these physical effects, several reports have also interestingly postulated that RJ has immunomodulatory activities (Fujii et al., 1990;Vittek, 1995;Kamakura et al., 2001;Tokunaga et al., 2004). ...
This study was conducted at a laboratory in the Biology, College of Education, University of Salahaddin, from February to May 2022 to investigate propolis, honey and royal jelly’s chemical composition, antioxidant and antibacterial activities. The honeybee production extract showed that Gram (+) bacteria were more resistant to the antibacterial compounds of honey and propolis than Gram (-) bacteria and fungi. E. coli was a more sensitive isolate than all the other bacteria examined against the honey types tested. At the same time, it revealed more resistance against all types of propolis. Royal jelly with honey displayed more antimicrobial activity than other bee products and exhibited superior activity; the minimum inhibitory concentration of honey and propolis samples ranged from 32 to 512µg/mL. The MIC value of the most effective honey (Honey 1, Honey 2 and Royal jelly) was 32µg/mL. The lowest concentration of Qaladze propolis was (32µg/mL) for E. coli ATCC 25922, followed by 128µg/mL in some other propolis types. Keywords: Apis mellifera; antimicrobial activities; honey; propolis; royal jelly.
Inconsistent data are available about the effect of royal jelly supplementation on anthropometric indices in humans. This systematic review and meta-analysis was done to summarize data from available randomized controlled trials (RCTs) on the effect of royal jelly supplementation on anthropometric indices such as body weight (BW), body mass index (BMI), and fat mass (FM) in adults. We systematically searched Embase, PubMed, Web of Science, and Scopus databases up to March 2023. All RCTs assessing the effect of royal jelly on anthropometric indices were included. Data were pooled using the random-effects method and were expressed as weighted mean difference (WMD) and 95% confidence intervals (CIs). Sensitivity and subgroup analyses were also performed. Out of 1,492 records, 10 studies that enrolled 512 participants were included. There was no significant effect on BW (WMD: −0.29 kg, 95% CI: −1.24, 0.65, p = 0.543), BMI (WMD: 0.11 kg/m², 95% CI: −0.29, 0.52, p = 0.583), and FM (WMD: 0.02%, 95% CI: −0.41, 0.46, p = 0.84). However, we observed a reduction in BW and BMI following royal jelly intake in subgroup of royal jelly dosage <3,000 mg/day. Although the royal jelly supplementation significantly reduced BW and BMI at the dosages <3,000 mg/day, until additional trials have been conducted to assess the effects on obesity measures, it is best to prescribe royal jelly with caution.
Diabetes Mellitus (DM) is considered a very common health problem today. It causes many acute and chronic complications and negatively affects the quality of life of patients. It is known that diabetes has an impact on many biochemical processes. This study aimed to evaluate the interaction between royal jelly (RJ) and diabetes with irisin, a parameter that has not been investigated before. The study was planned with 3 groups: control group, DM group, DM+350 mg/kg RJ group. In the experiments, 18 female Wistar albino rats were studied. Irisin levels in rat blood serum were determined using the ELISA (Enzyme-Linked Immuno Sorbent Assay) method. Glucose levels in blood taken from the tail vein were determined with a glucometer. As a result of the experimental study, a statistically significant difference was found in the DM+350 mg/kg RJ group compared to the control group (p
Royal jelly (RJ) is a bee product produced by young adult worker bees, composed of water, proteins, carbohydrates and lipids, rich in bioactive components with therapeutic properties, such as free fatty acids, mainly 10-hydroxy-trans-2-decenoic acid (10-H2DA) and 10-hydroxydecanoic acid (10-HDA), and major royal jelly proteins (MRJPs), as well as flavonoids, most flavones and flavonols, hormones, vitamins and minerals. In vitro, non-clinical and clinical studies have confirmed its vital role as an antioxidant and anti-inflammatory. This narrative review discusses the possible effects of royal jelly on preventing common complications of non-communicable diseases (NCDs), such as inflammation, oxidative stress and intestinal dysbiosis, from the viewpoint of predictive, preventive and personalised medicine (PPPM/3PM). It is concluded that RJ, predictively, can be used as a non-pharmacological therapy to prevent and mitigate complications related to NCDs, and the treatment must be personalised.
Food protein-derived antihypertensive peptides are a representative type of bioactive peptides. Several models based on partial least squares regression have been constructed to delineate the relationship between the structure and activity of the peptides. Machine-learning-based models have been applied in broad areas, which also indicates their potential to be incorporated into the field of bioactive peptides. In this study, a long short-term memory (LSTM) algorithm-based deep learning model was constructed, which could predict the IC50 value of the peptide in inhibiting ACE activity. In addition to the test dataset, the model was also validated using randomly synthesized peptides. The LSTM-based model constructed in this study provides an efficient and simplified method for screening antihypertensive peptides from food proteins.
Hiç şüphe yoktur ki arı sütü önemli bir doğal arı ürünüdür ve popülaritesi her geçen gün artmaktadır. İşçi arıların hipofarengial ile mandibular bezlerinden salgılanır ve biyolojik aktiviteye sahiptir. Yaşlanma karşıtı, antioksidan, antibakteriyel, antitümöral, antihipertansif, immünomodülatör, antiinflamatuar, karaciğer koruyucu ve kemik erimesini (osteoporoz) önleyici özellikleri son yıllarda dikkat çekmektedir. Bu çalışmanın amacı, makine öğrenmesi yoluyla arı sütünün bölgesini belirlemek için ayırt edici kimyasal faktörleri keşfetmektir. Çalışmada, Türkiye'nin 13 farklı bölgesinden 84 numune kullanılmış ve nem, pH, asitlik ve 10-hidroksi-2-dekenoik asit (10-HDA) kimyasal parametreleri incelenmiştir. 13 yerden toplanan arı sütleri arasında dört kimyasal değer açısından farklılık olup olmadığı ANOVA testi ile incelenmiştir. İstatistiksel testlere ek olarak, arı sütlerini birbirinden neyin ayırdığını keşfetmek için bir makine öğrenimi modeli kullanılmıştır. Arı sütü, kimyasal analiz sonuçlarının tanımlayıcı istatistikleri sırasıyla, nem %63.05±2.99, pH 3.67±0.08, asitlik 45.32±3.55 ve 10-HDA 2.40±0.24 olarak bulunmuştur. Şaşırtıcı bir şekilde, makine öğrenimi modeli, 10-HDA'nın arı sütünün bölgesini belirlemek için en belirgin parametre olabileceğini öne sürmektedir. Bu bilgi, arı sütünün doğruluğunun tespitini daha kolay öğrenmemize yardımcı olacaktır.
Background
Panax ginseng (Gin) potentiates the immune system via its antioxidant properties. Royal jelly (RJ), as an antioxidant, has been shown to attenuate oxidative stress damage in several vital organs. The current study aimed to determine whether Gin and RJ can ameliorate the toxic effects of diabetes on the hepatic and renal functions of male rats.MethodsA total of 40 Wistar male albino rats were randomly divided into five groups, namely the control, diabetes (STZ), diabetes + Gin (STZ+Gin), diabetes + RJ (STZ+RJ), and diabetes + Gin + RJ (STZ+Gin+RJ) groups.ResultsThe ability of RJ and Gin treatment to ameliorate liver injury was substantiated by the significant improvement in liver and kidney functions verified by lowered activity levels of liver function enzymes and improved renal biomarkers and lipid profile. The results revealed that RJ and Gin significantly reduced STZ-induced diabetes and increased liver malondialdehyde, accompanied by significant elevations in glutathione content (GSH) and superoxide dismutase, catalase, and glutathione peroxidase activities. Both Gin and RJ mitigated the distortion in hepatic histology and fibrosis, as well as the expression of TNF-α and TGF-β, with no significant difference between them. No significant benefit was observed with the concomitant use of Gin and RJ.Conclusion
Our findings concluded that RJ and Gin might alleviate the progression of STZ-induced diabetic liver and kidney injury by suppressing oxidative stress and decreasing apoptosis, inflammatory and fibrotic markers.
Hypertension-induced ventricular and vascular remodeling causes myocardial infarction, heart failure, and sudden death. Most available pharmaceutical products used to treat hypertension lead to adverse effects on human health. Limited data is available on apitherapy (bee products) combinations for treatment of hypertension. This study aims to evaluate the antihypertensive effects of combinations of natural apitherapy compounds used in the medical sector to treat a variety of diseases. Rats were assigned into six groups consisting of one control group and five hypertensive groups where hypertension (blood pressure > 140/90) was induced with dexamethasone. One of these groups was used as a hypertension model, while the remaining four hypertensive groups were treated with a propolis, royal jelly, and bee venom combination (PRV) at daily oral doses of 0.5, 1.0, and 2.0 mg/kg, and with losartan 10 mg/kg. The PRV combination at all doses decreased arterial blood pressure below the suboptimal value ( p < 0.001), and PRV combination treatment improved dexamethasone-induced-ECG changes. The same treatment decreased angiotensin-II, endothelin-1, and tumor growth factor β serum levels in hypertensive rats. Additionally, PRV combination improved histopathological structure, and decreased serum levels of NF-kB and oxidative stress biomarkers. We concluded that PRV combination therapy may be used as a potential treatment for a variety of cardiovascular diseases.
Royal jelly (RJ) is a creamy white-yellow liquid that is secreted by the mandibular and hypopharyngeal glands of bees to nourish the larvae. RJ has gained increasing interest in recent years owing to its antioxidant potential. However, little is known about adequate RJ dosing and its effects on genetic material. Thus, the aim of this study was to evaluate the in vivo effects of RJ on genotoxicity and mutagenicity induced by the alkylating agent methyl methanesulfonate (MMS). In this study, 3-month-old Swiss albino male mice (N=66) were divided into 11 groups for experimentation. Experiments were performed by administering lyophilized RJ (150 mg/kg, 300 mg/kg, and 1000 mg/kg) or water via gavage as pre- and posttreatment processes with the alkylating agent MMS. After treatment, blood samples were collected from the mice via an incision at the end of the tail to conduct comet assays at times of 24 h and 48 h posttreatment. The mice were then euthanized to remove the bone marrow for a micronucleus test. Overall, regardless of dose, RJ did not exhibit genotoxic, mutagenic activity and the administration of high doses, mainly in the form of posttreatment, presented antigenotoxic and antimutagenic actions. Further, a dose-response correlation was observed in the RJ posttreatment groups. These results demonstrate that RJ administration was effective in reversing the damage caused by the alkylating agent MMS.
Beside honey, honeybees (Apis mellifera L.) are able to produce many byproducts, including bee pollen, propolis, bee bread, royal jelly, and beeswax. Even if the medicinal properties of these byproducts have been recognized for thousands of years by the ancient civilizations, in the modern era, they have a limited use, essentially as nutritional supplements or health products. However, these natural products are excellent sources of bioactive compounds, macro- and micronutrients, that, in a synergistic way, confer multiple biological activities to these byproducts, such as, for example, antimicrobial, antioxidant, and anti-inflammatory properties. This work aims to update the chemical and phytochemical composition of bee pollen, propolis, bee bread, royal jelly, and beeswax and to summarize the main effects exerted by these byproducts on human health, from the anticancer and immune-modulatory activities to the antidiabetic, hypolipidemic, hypotensive, and anti-allergic properties.
Royal jelly (RJ) is a highly valued natural product which has long been used as a functional food in various parts of the world. The aim of this study was to evaluate the effects of RJ supplementation (0.5%, 1%, and 1.5%, w/w) on physicochemical properties (i.e., viscosity, chemical composition, water holding capacity, antioxidant activity), organoleptic characteristics, culture viability, and biological activities (i.e., anticancer and antibacterial activities) of fermented milk. Results showed RJ supplementation could reduce the fermentation time, increase the viscosity and water holding capacity, and also enhance the antioxidant acitivity of fermented milk. Compared to the fermented milk without RJ addition, fermented milk with 1% RJ had significantly more probiotics Lactobacillus helveticus Lh-B02, approximately 9.73 log CFU/g during 21 days of cold storage. Additionally, RJ supplementation could greatly boost the bioactivities of fermented milk. Fermented milk with 1.5% RJ had the highest anticancer and antibacterial properties, whereas the one with 1% RJ had the best sensory attribute score. Overall, RJ has a great potential to be a viable dietary additive for the development of innovative dairy products with multifacet nutritional and bioactive properties.
A 30 cm segment of the duodenum, jejunum, or ileum of normal human volunteers was perfused, on separate occasions, with test solutions containing either glycylglycine, free glycine, glycylleucine, or equimolar amounts of free glycine and free leucine. Luminal fluid contained no hydrolytic activity against glycylglycine and minimal activity against glycylleucine. In each intestinal segment, amino acid absorption rates were significantly greater from the test solutions containing the same amount of amino acids in dipeptide than in free form(as high as 185% increase). Perfusion of each intestinal segment with a test solution containing the equimolar mixture of free glycine and free leucine always resulted in a greater leucine than glycine absorption rate. This preferential absorption of leucine, however, was either diminished (jejunum) or almost abolished (duodenum and ileum) when the glycylleucine solution instead of the equimolar mixture was presented to the intestinal mucosa. Among the three segments, the duodenum exhibited the least potential for the disappearance of dipeptides. The jejunal and ileal dipeptide disappearance rates were either similar for glycylleucine (94% vs. 92%) or slightly different for glycylglycine (92% vs. 79%). Despite lack of a remarkable difference in the disappearance rates, absorption rates of constituent amino acids were markedly greater in the jejunum than in the ileum. This reduced amino acid absorption was brought about by a greater accumulation of free amino acids in the lumen of the ileal segment (3 to 10-fold difference). Inhibition of free glycine absorption by leucine during the perfusion of the intestine with a test solution containing glycylglycine and leucine did not result in any greater concentration of free glycine in the lumen than when the glycylglycine test solution did not contain free leucine. Similarly, inhibition of free glycine and free leucine absorption by isoleucine was not accompanied by any remarkable alteration of absorption rates of the constituent amino acids of glycylleucine. The results of these studies suggest that: (a) dipeptide disappearance in the gut lumen is principally accomplished by intact absorption and not by hydrolysis; (b) intracellular hydrolysis of dipeptides is markedly greater in the ileum than in the jejunum, while dipeptide absorption rates are either similar or only slightly different in these two segments; (c) there is no appreciable hydrolysis of glycylglycine by the membrane-bound enzymes and only a small fraction of glycylleucine is hydrolyzed by these enzymes.
The intestinal absorption of small peptides was investigated in rats under unrestrained conditions. The peptide utilized in the experiment was hydrolysate of egg white protein with an average molecular weight of about 350 and containing less than 10% of free amino acids. We compared the intestinal absorption of these small peptides with that of an amino acid mixture with the same small peptide amino acid composition by determining the concentration of individual amino acids in portal blood after a single administration of a nitrogen source. The absorptive intensity of each amino acid was calculated from its rate of elevation in the portal blood; it was higher in the small peptides. The proportion of the amount of each amino acid absorbed in portal blood from small peptides was much more like the composition of the administered amino acids than like that from the amino acid mixture. Among the amino acids administered in the mixture, some amino acids such as L-tyrosine, L-threonine, L-serine and L-histidine increased more slowly in the blood than others. These results suggested that the small peptide formula was utilized more effectively than the amino acid mixture and had higher nutritive value.
Supplementing diets with nondigestible fibers that are fermented by the gastrointestinal tract bacteria increases the dimension and absorptive capacities of the small intestine; we hypothesized that this would increase the accumulation of environmental contaminants. This was tested by feeding mice for 6-8 wk diets with fiber at two levels (0 and 100 g/kg) and from different sources (cellulose, lactosucrose, polydextrose, indigestible dextrin, inulin) before a 2-wk oral exposure to (14)C-labeled mirex or methylmercury in combination with (3)H-labeled retinol. Concentrations of contaminants and retinol were measured in urine and feces collected for the last 2 d of exposure and in seven tissues (small and large intestine, brain, liver, kidneys, gastrointestinal tract mesentery, gall bladder). Mice fed the same diets, but not exposed to the contaminants, were used for routine microbiology of alimentary canal contents, measurements of intestinal dimensions and in vitro rates of glucose, mirex, methylmercury and retinol absorption by the small intestine. Mice fed the diets with nondigestible oligosaccharides had higher densities of anaerobic bacteria and larger small and large intestines, but did not have greater rates of contaminant absorption or accumulation. Mice exposed to methylmercury accumulated less retinol than mice exposed to mirex. Although diets with nondigestible oligosaccharides fibers reduce accumulation of environmental contaminants, but not retinol, the specific responses vary among tissues, sources of fiber and contaminants. The mechanisms responsible for the influence of nondigestible oligosaccharides can include reduced absorption, increased fecal elimination and transformation to forms that are excreted in the urine.
We have previously shown using in vitro and in vivo experimental systems that Perilla frutescens leaf extract (PFE) exhibits anti-allergic functions through inhibiting IgE production by way of down-regulating the production of the Th2 cytokines IL-4, IL-5, and IL-10, but not that of the Th1 cytokine IFN-γ. Th2 cytokines play important roles in allergic responses. In this study, we have examined whether royal jelly (RJ) exhibits anti-allergic functions similar to those of PFE using an immediate hypersensitivity model, in which BALB/c mice were immunized with ovalbumin (OVA)-Alum. In a manner similar to that observed with PFE, intraperitoneal administration of RJ significantly inhibited both OVA-specific IgG1 and IgE production, and IL-4, IL-5, and IL-10 production by spleen cells stimulated with OVA. In contrast to PFE, however, administration of RJ also inhibited IFN-γ production by OVA-stimulated spleen cells, and tended to down-regulate OVA-specific IgG2a production. IL-2 production by OVA-stimulated spleen cells was unaffected by the administration of RJ and there were no significant changes in cytokine production by spleen cells in response to concanavalin A (Con A) among the experimental groups. Similar findings were observed when lymph node cells from OVA-Alum-immunized mice were stimulated with OVA in the presence of RJ. Furthermore, oral administration of RJ also resulted in a significant inhibition of both OVA-specific IgE and total IgE production. These results suggest that RJ exhibits anti-allergic functions through a different mechanism from that of PFE.
It has been reported that Royal Jelly (RJ) treated with protease N (ProRJ) contained three ACE inhibitory peptides (IY, VY and IVY) and that three peptides have an antihypertensive effect on spontaneously hypertensive rats (SHR). We examined the mechanism by which ProRJ decreased blood pressure in SHR. In single oral administration of ProRJ at a dose of 2.0g/kg in SHR, the systolic blood pressure was significantly decreased 6 hours after administration. And the angiotensin I converting enzyme (ACE) activities in the abdominal aorta and lungs of SHR administration of ProRJ were decreased compared to those of control at 6 hours after administration. IY, VY and IVY were detected in the abdominal aorta and lungs of SHR, and also in plasma by the HPLC method. The amount of aldosterone in plasma was significantly decreased from 1 hour to 4 hours after administration of ProRJ in SHR. According to these results, it was suggested that the antihypertensive effect of ProRJ in SHR is responsible for ACE inhibitory activity of IY, VY and IVY in ProRJ.
Protease digested royal jelly (ProRJ) proved to inhibit angiotensin I converting enzyme (ACE) activity in vitro. And we have demonstrated that peptides isolated from ProRJ (Ile-Tyr (IY), Val-Tyr (VY)) also inhibited ACE activity. We examined an antihypertensive effect of RJ, ProRJ and RJ peptides (IY and VY) on spontaneously hypertensive rat (SHR). In chronic oral administration of ProRJ and RJ at the dose of 10 mg/kg/day for 28 days, the systolic blood pressure (SBP) of SHR was significantly decreased against the control. The blood pressure of normotensive rat (Wistar Kyoto rat) did not changed on the repeated administration of ProRJ. In repeated oral administration of RJ peptides at the dose of 10 mg/kg/day for 28 days, SBP was significantly reduced against the control. These results suggest that the hypotensive effect of ProRJ is correlated with ACE inhibitory activity of RJ peptides, and ProRJ would be beneficial for improving blood pressure in hypertension.
This study was designed to isolate and analyze inhibitory peptides against angiotensin I-converting enzyme (ACE) from protease treated Royal Jelly (RJ) hydrolysate. We obtained the fractions which inhibited ACE from the RJ hydrolysate treated with protease N using octadecyl silica gel (ODS) and Superdex™-peptide 10/30 (GPC) colums. In ODS column chromatography, an ACE inhibitory fraction was recovered after elution with 10% ethanol in water. And from it the most active fraction was obtained through 3 step high performance liquid chromatographies. As a result, two different ACE inhibitory peptides were purified. On the other hand, the RJ hydrolysate was fractionated with Superdex™-peptide 10/30 GPC column chromatography to obtain di- and tri-peptide fractions which processed marked inhibitory activity against ACE. And we carried out another 2 or 3 step HPLC of the fraction, obtaining 4 different peptides. By analysis of these 6 peptides using an amino acid sequencer, we could obtain Ile-Tyr (IY), Val-Tyr (VY), Ile-Val-Tyr (IVY), Tyr-Tyr (YY), Ile-Phe (IF), and Lys-Ser (LS); IC 50 values for ACE inhibition were 0.008, 0.02, 0.018, 0.028, 0.034, and 1.55 mg/ml, respectively. Especially, IY, YY, and LS were isolated first time from the RJ. In conclusion, this study elucidated that novel ACE inhibitory peptides were contained in RJ hydrolysate, and these might play an important role in ability of the RJ hydrolysate to depress the blood pressure via ACE inhibition.
Angiotensin I-converting enzyme (ACE)-inhibitory peptides from the thermolysin digest of chicken muscle and the peptic digest of ovalbumin were isolated. However, some of them failed to show antihypertensive activity in spontaneously hypertensive rats (SHR). To clarify this discrepancy, ACE-inhibitory peptides from various sources were preincubated with ACE before measurement of ACE-inhibitory activity and classified into 3 groups: (1) inhibitor type, IC50 values of peptides that are not affected after preincubation with ACE; (2) substrate type, peptides that are hydrolyzed by ACE to give peptides with weaker activity; and (3) prodrug-type inhibitor, these peptides are converted to true inhibitors by ACE or gastrointestinal proteases. Peptides belonging to the 1st and the 3rd groups exert antihypertensive activities even after oral administration in SHR.
It was found that the water-soluble fraction of royal jelly contained a factor which had a vasodilating activity on dog femoral artery. This activity was transitory, was present in 100- to 200-fold of that in honey, and the activity was rapidly lost in alkaline aqueous solution. This active factor was partially purified by Sephadex G-25 chromatography, and various examinations were made to elucidate its principle. It was thereby found that this factor was inactivated by the protease treatment, was antagonized by atropine, and was inactivated by the true cholinesterase. Consequently, this vasodilating factor was considered to be a cholinergic substance, and was determined as acetylcholine by paper chromatography.
The inhibitory activity of angiotensin I-converting enzyme in milk increased during fermentation with the Calpis sour milk starter containing Lactobacillus helveticus and Saccharomyces cerevisiae. Two kinds of peptides inhibitory to angiotensin I-converting enzyme were purified from the sour milk by using four-step HPLC. The amino acid sequences of these inhibitors were identified as Val-Pro-Pro and Ile-Pro-Pro. The concentrations of peptides providing 50% inhibition of angiotensin I-converting enzyme were 9 and 5 microM, respectively. Most of the inhibitory activity in sour milk was attributed to these two peptides.
Absorption of inhibitory peptides to angiotensin I-converting enzyme, L-valyl-L-prolyl-L-proline and L-isoleucyl-L-prolyl-L-proline, was studied in spontaneously hypertensive rats and normotensive Wistar-Kyoto rats after an oral administration of Calpis sour milk, which contains these peptides. Six hours after the administration of Calpis sour milk or saline to spontaneously hypertensive rats or normotensive Wistar-Kyoto rats, the blood pressure was measured and rats were killed. Abdominal aorta, lung, kidney, heart and brain were excised, homogenized and solubilized by detergent treatments. Angiotensin I-converting enzyme activity in the solubilized fractions from the abdominal aorta was significantly lower in spontaneously hypertensive rats given the sour milk than in the rats given saline. L-Valyl-L-prolyl-L-proline and L-isoleucyl-L-prolyl-L-proline were detected by HPLC in the heat-treated solubilized fraction from the abdominal aorta of spontaneously hypertensive rats given the sour milk. In contrast, the tripeptides were not detected in rats given saline, or in normotensive Wistar-Kyoto rats given the sour milk or saline. These data suggest that L-valyl-L-prolyl-L-proline and L-isoleucyl-L-prolyl-L-proline in the Calpis sour milk are absorbed directly without being decomposed by digestive enzymes, reach the abdominal aorta, inhibit the angiotensin I-converting enzyme, and show antihypertensive effects in spontaneously hypertensive rats.
In order to clarify the potential physiological function of royal jelly (RJ), we report here the gastrointestinal enzyme production of antihypertensive peptides from RJ. Intact RJ and its protein fraction did not retard the action of angiotensin I-converting enzyme (ACE) activity at all. However, development of ACE inhibition power of RJ was newly observed by pepsin hydrolysis (IC(50)=0.358 mg protein/mL), and the subsequent trypsin and chymotrypsin hydrolyses (IC(50)=0.099 mg protein/mL). Single oral administration of this gastrointestinal RJ hydrolysate (1 g/kg dose) in 10-week spontaneously hypertensive rat resulted in a significant reduction of systolic blood pressure of 22.7 plus minus 3.6 mmHg at 2 hr (P<0.05 vs. 0 hr by one-way ANOVA, n=7). Then, the RJ hydrolysate was fractionated with gel permeation chromatography to obtain the di- and tri-peptides (DTP) fraction. As a result of isolation from the DTP fraction by reversed phase-high performance liquid chromatography, eleven ACE inhibitory peptides were isolated from the DTP-RJ hydrolysate. Some of the ACE inhibitors were derived from the RJ-glycoprotein; eight peptides with the IC(50) value of <10 &mgr;M were identified from natural resources for the first time. Consequently, RJ protein was thought to be a good resource of ACE inhibitory peptides produced by the gastrointestinal enzyme hydrolyses.
Seven kinds of angiotensin I-converting enzyme (ACE) inhibitory peptides were isolated from the hydrolysates of wakame (Undaria pinnatifida) by Protease S "Amano" (from Bacillus stearothermophilus) by using three-step high-performance liquid chromatography (HPLC) on a reverse-phase column. These peptides were identified by amino acid composition analysis, sequence analysis, and liquid chromatography-mass spectrometry (LC-MS), as Val-Tyr (IC(50) = 35.2 microM), Ile-Tyr (6.1 microM), Ala-Trp (18.8 microM), Phe-Tyr (42.3 microM), Val-Trp (3.3 microM), Ile-Trp (1.5 microM), and Leu-Trp (23.6 microM). These peptides have resistance against gastrointestinal proteases in vitro. Each peptide was determined to have an antihypertensive effect after a single oral administration in spontaneously hypertensive rats (SHR). Among them, the blood pressure significantly decreased by Val-Tyr, Ile-Tyr, Phe-Tyr, and Ile-Trp in a dose of 1 mg/kg of body weight (BW). The present study showed that antihypertensive effect in the hydrolysates of wakame by Protease S "Amano" was attributed to these peptides.
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