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Antihypertensive Effect of Peptides from Royal Jelly in Spontaneously Hypertensive Rats

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Antihypertensive Effect of Peptides from Royal Jelly in Spontaneously Hypertensive Rats

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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.

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... Dieses Peptid wurde erstmals in der Studie von Saito et al. (1994) über die Struktur und Aktivität ACE-inhibitorischer Peptide von Sake und Sake-Blättern identifiziert. Auch in Algen (Undaria pinnatifida) und Royal Jelly (Apis mellifera), einem als gesundheitsfördernd eingestuften Lebensmittel, wurde das Peptid entdeckt (Sato et al., 2002;Tokunaga et al., 2004). Das Peptid reduziert nach Tokunaga et al. (2004) (Matsui et al., 2002), die jedoch im Widerspruch zu den antihypertensiven Wirkungen in spontan hypertensiven Ratten (Tokunaga et al., 2004) steht. ...
... Auch in Algen (Undaria pinnatifida) und Royal Jelly (Apis mellifera), einem als gesundheitsfördernd eingestuften Lebensmittel, wurde das Peptid entdeckt (Sato et al., 2002;Tokunaga et al., 2004). Das Peptid reduziert nach Tokunaga et al. (2004) (Matsui et al., 2002), die jedoch im Widerspruch zu den antihypertensiven Wirkungen in spontan hypertensiven Ratten (Tokunaga et al., 2004) steht. Peptide, wie das im α S1 -Kasein in Stutenmilch nachgewiesene Peptid EY, sollten deshalb Gegenstand weitergehender Untersuchungen sein, um deren Potential endgültig einschätzen zu können. ...
... Auch in Algen (Undaria pinnatifida) und Royal Jelly (Apis mellifera), einem als gesundheitsfördernd eingestuften Lebensmittel, wurde das Peptid entdeckt (Sato et al., 2002;Tokunaga et al., 2004). Das Peptid reduziert nach Tokunaga et al. (2004) (Matsui et al., 2002), die jedoch im Widerspruch zu den antihypertensiven Wirkungen in spontan hypertensiven Ratten (Tokunaga et al., 2004) steht. Peptide, wie das im α S1 -Kasein in Stutenmilch nachgewiesene Peptid EY, sollten deshalb Gegenstand weitergehender Untersuchungen sein, um deren Potential endgültig einschätzen zu können. ...
Article
Within this study the whey proteins α-lactalbumin, β-lactoglobulin 1 and 2 and the caseins αS1-casein, αS2-casein, β-casein and κ-casein of mare's milk have been processed in silico with the enzymes pepsin (E.C. 3.4.23.1), trypsin (E.C. 3.4.21.4) and chymotrypsin A (E.C. 3.4.21.1) using the programme BIOPEP analyzing the ACE-inhibitory peptides, which evolve an antihypertensive effect. At the same time the effect of genetically variated versions of horse milk proteins on the occurrence of ACE-inhibitory peptides was checked. The in silico analysis of the included milk protein sequences resulted in 17 different bioactive peptides with ACE-inhibitory function. The Peptide IVR out of αS2-Kasein having a very low IC50-value of 0,81 μM demonstrates the high potential of mare's milk. In vivo effects have been already verified for this peptide. Additional highly active peptides are EY (IC50-value = 2,68 μM, αS1-casein), VY (IC50-value = 7,1 μM, β-lactoglobulin 1 and 2), HHL (IC50-value = 21,8 μM, αS2-casein) and NY (IC50-value = 32,6 μM, β-lactoglobulin 1). The genetic variations of the milk proteins α-lactalbumin and αS2-casein did not have any effect on the ACE-inhibitory activity of mare's milk. The incidence of ACE-inhibitory peptides with partly very high activity was demonstrated in this work for the first time showing the opportunity to characterize and quantify the effect of mare's milk on human health-also for use in functional foods - by further analysis.
... 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]. ...
Article
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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) . ...
Article
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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.
... significant change; RJ: Royal jelly; SD: Standard deviation; SOD: Superoxide dismutase; CAT: Catalase; GSH-Px: Glutathione peroxidase RJ may have hypoglycemic functions, Münstedt et al. reported that single doses of RJ decreased blood glucose levels in healthy individuals. [13] In addition, findings of in vivo and in vitro studies indicated that RJ has hypotensive, [14] antihypercholesterolemic, [15] anti-inflammatory, [16] antitumor, [17] and antioxidant effects. [18] It has insulin-like activity, which may improve insulin resistance. ...
... The 10-HDA is a special component of a lipid fraction in RJ (Blum et al. 1959;Lercker et al. 1981), which has antibiotic and immunomodulatory activities (Townsend et al. 1959;Vucevic et al. 2007). Some of the RJ proteins such as major royal jelly proteins (MRJPs) (Mairesse et al. 1998), jelleines (Fontana et al. 2004), and royalisin (Fujiwara et al. 1990) are reported to have properties of antimicrobial, antifungal, anti-tumor, anti-diabetic, and anti-hypertensive activities (Bíliková et al. 2001;Oka et al. 2001;Tokunaga et al. 2004). In addition, RJ regulates inflammation, oxidative stress, and vasodilation activity (Okamoto et al. 2003;Liu et al. 2008;Nakajima et al. 2009;Kolayli et al. 2016;Yang et al. 2018). ...
Article
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The genetic selection of a high royal jelly (RJ)-producing strain of bees (RJBs) from Italian bees (ITBs) has been conducted for nearly four decades in China since the 1980s. RJBs are the most important producers of RJ in the world and produce > 90% of the total output with an annual market value of > $40 million. With technological advancements in proteomics, the mechanism underpinning the high RJ production by RJBs has been explored to new depths in the last decades. Here, we give an overview that the mechanism driving the enhanced performance of RJ secretion by RJBs. First, the selection of RJBs, high-efficiency technology for RJ production, and advances in genetic characterization of RJBs are reviewed. Then, proteome and phosphoproteome characterization that decipher the augmented RJ production using honeybee organs and tissues are summarized. This may be potentially useful in gaining a complete mechanistic insight into the high performance of RJ yields in honeybees, and expands understanding of the honeybee biology.
... 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. ...
Preprint
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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.
... Royal jelly is recognized as a milky-white secretion produced by the hypopharyngeal and mandibular glands of young worker bees (Apis mellifera L.) for feeding young larvae and adult queen bee. The chemical composition of royal jelly on a percent weight basis includes water (50-60%), proteins (18%), carbohydrates (15%), lipids (3-6%), mineral ash (1.5%), and vitamins (Nagai and Inoue 2004) in addition to large number of bioactive substances including fatty acids (Vucevic et al. 2007) such as 10-hydroxy-2-decenoic acid (Caparica-Santos and Marcucci 2007), peptides (Tokunaga et al. 2004), and flavonoid phenolics (Kucuk et al. 2007). The variation of bioactive compounds such as peptides and phenolics in royal jelly depends on the floral sources. ...
Chapter
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This chapter presents the potential anticarcinogenic benefits of fermented foods, including the possible anticancer properties of fermented royal jelly and its constituents. Fermented foods and their components have received extensive attention for their potential health benefits. Phenolics and other food-related bioactive phytochemical and zoochemical compounds generated by fermentation have attracted particular attention for their presumed roles in reducing the risk of chronic diseases, including cardiovascular diseases, diabetes, and certain types of cancer. In this regard, the royal jelly produced by honey bees is a rich source of nutrients and bioactives for the development of functional foods because of its established pharmaceutical and nutraceutical properties. Royal jelly contains several essential nutrients and a number of bioactive compounds including peptides, flavonoid phenolics, and fatty acids such as 10-hydroxy-2-decenoic acid. The natural variation in bioactive peptides and phenolics in royal jelly depends on the floral sources and biodiversity of the wild plant species present in various environments. Royal jelly proteins and protein hydrolysates possess anticarcinogenic, antidiabetic, and antihypertensive properties.
... 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]. ...
Article
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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). ...
... significant change; RJ: Royal jelly; SD: Standard deviation; SOD: Superoxide dismutase; CAT: Catalase; GSH-Px: Glutathione peroxidase RJ may have hypoglycemic functions, Münstedt et al. reported that single doses of RJ decreased blood glucose levels in healthy individuals. [13] In addition, findings of in vivo and in vitro studies indicated that RJ has hypotensive, [14] antihypercholesterolemic, [15] anti-inflammatory, [16] antitumor, [17] and antioxidant effects. [18] It has insulin-like activity, which may improve insulin resistance. ...
... Recent studies have found that many foods and herbs contain natural ingredients with antihypertensive activities. Therefore, increasing efforts have been devoted to studying the effects of natural foods or their bioactive derivatives, such as garlic (Ried, Frank, & Stocks, 2010), tea (Negishi et al., 2004), peptides (Tokunaga et al., 2004), and vitamin C (McRae, 2006), as functional foods or bioactive compounds for the treatment and prevention of hypertension. ...
Article
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Abstract “Shangshida NO.5” is a giant embryo mutant resulting from giant embryo gene (GE) dysfunction in “Chao2‐10” rice. Here, we compared the antihypertensive effects of “Chao2‐10” brown rice (C2‐10), “Shangshida NO.5” brown rice (GER), and pre‐germinated “Shangshida NO.5” brown rice (PGER) in spontaneously hypertensive rats (SHR). Male SHR at 6 weeks of age were divided into four groups and were fed with (a) a control diet (control), (b) a 40% C2‐10‐supplemented diet (C2‐10), (c) a 40% GER‐supplemented diet (GER), or (d) a 40% PGER‐supplemented diet (PGER) for 8 weeks, and their physiological and biochemical parameters were measured. The results showed that the C2‐10‐, GER‐, and PGER‐supplemented diets significantly decreased systolic blood pressure (SBP) and diastolic blood pressure (DBP) during the experiment. At the end of the experimental period, the SBP and DBP of the C2‐10, GER, and PGER groups were 7.6, 23.3, and 31.1 mmHg and 9.8, 21.1, and 29 mmHg lower than those in the control group, respectively, suggesting the GER and PGER diets were better able to inhibit blood pressure elevation than the C2‐10 diet. The serum creatinine levels in the C2‐10, GER, and PGER groups and the blood urea nitrogen content in the PGER group were significantly lower than those of the control group, indicating that C2‐10‐, GER‐, and especially PGER‐supplemented diets improved renal function. In addition, the antioxidant activity of the C2‐10 group and especially of the GER and PGER groups also improved. The above results suggest that “Shangshida NO.5” rice, particularly pre‐germinated rice, is a good dietary supplement for preventing the development of hypertension.
... Seven kinds of ACE inhibitory peptides were isolated from the hydrolysates of wakame (alga Undaria pinnatifida) by protease [30]. Peptides from bovine lactoferrin [31], wheat gliadin [32], royal jelly [33], casein hydrolysate with an Aspergillus oryzae protease [14], marine shrimps [34], hemoglobin [35], and mung beans were also reported [8], potentiating our results. ...
Article
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Zea mays (maize) leaves (I) and Opuntia tuna (prickly pears) peels (II) were selected as a source of protease enzymes from a programmed screening for casein hydrolysis. These 2 crude enzymes were partially purified by ammo-nium sulphate fractionation and gel filtration on Sephadex G-100 columns. They were purified to final specific activity of 2093 and 593 U/mg protein for I and II, respectively (38 and 119.8-fold that of the crude enzyme, respectively). The prepared enzymes showed optimum activity at pHs 6.0 and 8.5 for enzyme I, and at pHs 6.0 and 7.5 for enzyme II at 37 ºC. The prepared protease (II) has been successfully immobilized by simple adsorption on silica gel (SG) and trical-cium phosphate (TCP) with increasing activity of the immobilized enzyme to free one by 27.1 and 9.6 times, respectively , while protease I has been immobilized on CMC with 1.4 times only. The optimum adsorption ratio was 40/1 (adsorbent/enzyme). Some food proteins (milk, meat powder, Phaseolus vulgaris dried seeds, Faba vulgaris (bean and lentil)) were digested with the two prepared proteases I and II at 37 ºC for 24 h. The digested samples were assayed for the inhibi-tory activity of angiotensin-converting enzyme (ACE). Only the peptides produced from the digested samples of Phase-olus seeds, and lentils by protease I and II showed ACE-inhibiting activity. Also that produced from the digestion of beans by enzyme I showed the same activity. These pep-tides were detected by electrophoresis.
... This is in line with the result reported in an earlier study that found no significant changes in the blood pressure of healthy adults who were on royal jelly supplementation at 3000 mg/d for 6 months. 33 Even though the royal jelly in HC has been proven to possess angiotensin I-converting enzyme inhibitory properties, 34,35,36 the insignificant effect of HC on BP warrants further investigation. ...
Article
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Objective: To investigate the long-term effects of Tualang Honey versus Honey Cocktail (mixture of honey, bee bread, and royal jelly) on cardiovascular markers and anthropometric measurements of postmenopausal women. Methods: We conducted a randomised, double blinded, two-armed parallel study comparing 20 g/day of Tualang Honey versus 20 g/day Honey Cocktail among postmenopausal women aged 45–65 years. The cardiovascular parameters and anthropometrics measurements were assessed at baseline, 6 months, and 12 months of the intervention. Results: 100 subjects were successfully randomised into the groups. There was a significant decrease in the diastolic blood pressure from 77.92 mmHg at baseline to 73.45 mmHg at 12 months (F-statistic = 2.55, p-value = 0.047) in the Tualang Honey group compared to Honey Cocktail. There was also a significant decrease in the fasting blood sugar from 6.11 mmol/L at baseline to 5.71 mmol/L at 12 months (F-statistic = 4.03, p-value = 0.021) in the Tualang Honey group compared to the Honey Cocktail group. The body mass index remained unchanged at 27 kg/m2 (F-statistic = 1.60, p-value = 0.010) throughout 12 months of the intervention in the Honey Cocktail group. Conclusion: Subjects who received Honey Cocktail showed remarkable effects on body mass index. However, Tualang Honey supplementation showed superior effect in lowering diastolic blood pressure and fasting blood sugar compared to Honey Cocktail. Further studies are required to ascertain the underlying mechanism(s) of Tualang Honey and Honey Cocktail on each observed parameter.
... [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. ...
Article
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.
... The antioxidant activity of phenolic compounds is mainly due to their redox properties, which can play an important role in absorbing and neutralizing free radicals (Javanmardi et al., 2003). Studies have shown that RJ plays an important role in the immune system (Li et al., 2013), reduces blood pressure (Tokunaga et al., 2004) and has antitumor property (Shirzad et al., 2013). Thus, the aim of the present study was to investigate the protective effect of royal jelly in varicocele-induced oxidative damages and disrupts spermatogenesis cycle of rat testis by biochemical and histopathological methods. ...
Article
Varicocele is one of the most prevalent causes of infertility. It causes induction of oxidative stress, increases lipid peroxidation in the testis and disrupts spermatogenesis cycle. The aim of the study was to investigate the possible protective effects of royal jelly against varicocele induced oxidative stress, biochemical and histological alterations in the experimental varicocele model in rat. Twenty-one adult Wistar rats were divided into three groups. The control group (I), Varicocele and administration of normal saline (II), varicocele and treatment with RJ (III). At the end of the experiment, all the animals were sacrificed and testes excised. The activity of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and MDA levels were measured. Also, histopathological examinations, Johnsen scores and sperm parameters were determined. There was a significant (p<0.05) increase in the activity level of CAT (0.223±0.005), SOD (0.177±0.0062), GPx (9.575±0.318) and a significant (p<0.05) reduction in the MDA level (2.674±0.336) of the experimental varicocele treated with royal jelly when compared to the activity of CAT (0.011±0.004), SOD (0.035±0.0096), GPx (8.864±0.397) and MDA level (4.630±0.579) of the experimental varicocele and administration of normal saline. Results of the Johnsen score showed a significant increase (p<0.05) in the mean score of the RJ group (7.94±1.5) when compared to the normal saline group (6.04±1.4). Therefore, RJ is a potential area for further studies and improving in spermatogenesis cycle after varicocele.
... Besides, it is also noted that RJ contains rennin and angiotensin I-con- verting enzyme (ACE) dual inhibitory peptides, which can lower blood pressure in spontaneously hypertensive rats (SHR) ( Sultana et al., 2008;Takakidoi, Hashimoto, Yamamura, & Kamei, 2009;Tokunaga et al., 2004). Moreover, RJ causes temporary vasodilation on dog's femo- ral arteries (Shinoda et al., 1978). ...
Article
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Among royal jelly’s (RJ) various biological activities, its possible antihypertension and vasorelaxation effects deserve particular attention, but the underlying mechanisms of action remain unclear. Therefore, this study used the spontaneously hypertensive rats (SHR) hypertension model and the isolated rabbit thoracic aorta rings model to explore the mechanisms underlying the hypotension and vasorelaxation effects of RJ. Rats were divided into the following groups (n = 6): WKY‐control group, SHR‐control group, and SHR‐RJ group. SHR‐RJ group was received 1 g/kg of RJ via oral administration daily for 4 weeks. Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and nitric oxide (NO) level were detected. In addition, the mechanism of vasodilation of RJ was investigated using an isolated rabbit aortic ring technique. RJ significantly reduced SBP and DBP as well as increased NO levels of SHR in vivo. RJ caused vasorelaxation of the isolated aorta rings, and this effect was inhibited by atropine (M3 receptor blocker), L‐NAME (nitric oxide synthase inhibitor), methylene blue (guanylate cyclase inhibitor), and indomethacin (cyclooxygenase inhibitor). Moreover, RJ could markedly suppress the NE‐induced intracellular Ca2+ releases and high K+‐induced extracellular Ca2+ influx in denuded aortic rings. In addition, RJ can also increase cGMP levels and the production of NO in isolated aortic rings. The present study showed that RJ has antihypertensive effects and was associated with increased NO production. In addition, RJ contains muscarinic receptor agonist, possibly an acetylcholine‐like substance, and induces vasodilation through NO/cGMP pathway and calcium channels. RJ has antihypertensive effects and is associated with increased NO production. In addition, RJ contains muscarinic receptor agonists and induces vasorelaxation through NO/cGMP pathway and calcium channels.
... significant change. RJ: Royal jelly; SD: Standard deviation; SOD: Superoxide dismutase; CAT: Catalase; GSH-Px : Glutathione peroxidase 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 [13] In addition, findings of in vivo and in vitro studies indicated that RJ has hypotensive, [14] antihypercholesterolemic, [15] anti-inflammatory, [16] antitumor, [17] and antioxidant effects. [18] It has insulin-like activity, which may improve insulin resistance. ...
Article
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Context: Diabetes mellitus and its increasing effect on endocrine functionality have been widely observed. Aims: The present study aims at investigating the histopathological changes of splenic cells in diabetic rats. Subjects and Methods: The experiment was conducted on adult male albino rats. They were categorized into four groups: Group I (negative control; fed with standard basal diet [SBD]), Group II (positive control; fed with SBD), Group III (fed on SBD + dose of 50 mg/kg of body weight royal jelly [RJ]) and Group IV were given orally RJ 100 mg/kg of b.wt. The food intake ratio and body weight gain were monitored on a weekly basis. The blood sample and organ tissue samples were collected at the end of feeding and biochemical and immunological analysis was performed for determining the blood glucose level and immune status of the investigated rats. Superoxide dismutase activity was also determined. Results: The results showed increased antioxidant enzymes and lowered glucose levels in diabetic rats fed with RJ. Conclusion: Histopathology tissues indicated moderate to extreme cellular transformations upon treated rats. The histopathological variations in treated rat cells were found to be evident. For this reason, there is likelihood that RJ may have an effect on splenic tissue repair in diabetic rats. SUMMARY • Diabetes mellitus and its increasing effect on endocrine functionality have been widely observed. Recent studies indicate that developing nations in Asia and Middle East will experience a surge in the incidences of diabetes by 2030. The present study aims at investigating the functions of royal jelly (RJ) in overcoming insulin resistance through enzyme function modification leading to prevention of lipid aggregation. The results showed enhanced immunity indices, antioxidant enzymes, and lowered glucose levels in diabetic rats fed with RJ.
... This is accomplished by modification of the epigenetic state of the genome and gene expression by regulating DNA methylation, thus resulting in genetic morphology development (23). For humans, RJ is widely used in nutraceuticals and cosmetics (20,24) for its antibacterial and antioxidative properties, and possible anticancer effects (19,21,(25)(26)(27). To increase RJ yields, beekeepers in China have been selecting a stock of high royal jelly producing bees (RJBs) from Italian bees (ITBs, Apis mellifera ligustica) since the 1980s. ...
Article
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Royal jelly (RJ) is a secretion of the hypopharyngeal glands (HGs) of honeybee workers. High royal jelly producing bees (RJBs), a stock of honeybees selected from Italian bees (ITBs), have developed a stronger ability to produce RJ than ITBs. However, the mechanism underpinning the high RJ-producing performance in RJBs is still poorly understood. We have comprehensively characterized and compared the proteome across the life span of worker bees between the ITBs and RJBs. Our data uncover distinct molecular landscapes that regulate the gland ontogeny and activity corresponding with age-specific tasks. Nurse bees (NBs) have a well-developed acini morphology and cytoskeleton of secretory cells in HGs to prime the gland activities of RJ secretion. In RJB NBs, pathways involved in protein synthesis and energy metabolism are functionally induced to cement the enhanced RJ secretion compared with ITBs. In behavior-manipulated RJB NBs, the strongly expressed proteins implicated in protein synthesis and energy metabolism further demonstrate their critical roles in the regulation of RJ secretion. Our findings provide a novel understanding of the mechanism consolidating the high RJ-output in RJBs.
... 17 In addition, RJ has various biological activities such as insulin-like, anti-hypercholesterolemic, hypotensive and anti-tumor functions. [18][19][20][21] Also, several studies have revealed some pharmacologic, antioxidant and anti-inflammatory properties for RJ in both human and animal models. [21][22][23] Despite the several studies that investigated the effects of RJ on metabolic variables such as glycemic status, lipid profile, oxidative stress and inflammation in diabetes mellitus, [24][25][26][27][28][29][30][31][32][33][34][35] no comprehensive study has been conducted to summarize the findings yet. ...
Article
Diabetes mellitus is one of the most common endocrine disorders in the world. This systematic review was conducted with focus on the current knowledge on the effect of royal jelly on metabolic variables in diabetes mellitus. PubMed, Scopus, Embase, ProQuest and Google Scholar databases were searched from inception until June 2018. All clinical trials and animal studies that evaluated the effects of royal jelly on diabetes mellitus, and were published in English-language journals were eligible. Studies that provided insufficient outcomes were excluded. Out of 522 articles found in the search, only twelve articles were eligible for analysis. Seven studies showed a significant reduction in FBS, and one reported HbA1c decrease following royal jelly supplementation. Although royal jelly supplementation resulted in significant reductions in HOM A-I R in three studies, the findings on insulin levels were controversial. In addition, royal jelly substantially improved serum levels of triglycerides, cholesterol, HDL, LDL, VLDL and Apo-A1 in diabetes mellitus. In addition, royal jelly resulted in a decrease oxidative stress indicators and increase antioxidant enzymes levels. In conclusion, royal jelly could improve glycemic status, lipid profiles and oxidative stress in diabetes mellitus. However, exploring the underlying mechanisms warrants further studies.
... 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]. ...
Article
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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.
... 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. ...
Article
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.
... [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. ...
... 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. ...
Article
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.
... 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. ...
Conference Paper
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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.
... 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]. ...
Article
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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.
... 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]. ...
Article
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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.
... [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. ...
... 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. ...
Article
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 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). ...
Article
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.
... 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. ...
Article
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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. ...
Article
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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.
... 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). ...
Article
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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.
... 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). ...
Article
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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]. ...
Article
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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. ...
... 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 . ...
Article
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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.
Article
Aims: Royal jelly (RJ) has a variety of reported biological activities, including vasorelaxation and blood pressure-lowering effects. Although functional foods are positively used for health, the effects of RJ on the cardiovascular system in healthy individuals have not been well studied. Therefore, we investigated the mechanisms underlying the vasorelaxation effects of RJ in healthy control rats to evaluate whether the peripheral circulation was increased. Main methods: We used fresh RJ to examine the vasorelaxation effects and related mechanisms in Wistar rats using organ bath techniques. Furthermore, we measured changes in tail blood circulation, systolic blood pressure (sBP), and heart rate (HR) after the oral administration of RJ to control rats and nitro-l-arginine methyl ester (l-NAME)-treated rats (0.5 mg/ml dissolved in distilled drinking water for 1 week). Concentrations of acetylcholine (ACh) in the RJ were measured using a commercial kit. Key findings: RJ caused vasorelaxation of isolated rat aortas and superior mesenteric arteries, and this effect was inhibited by atropine (10-5 M, 15 min) or L-NAME (10-4 M, 20 min) and endothelium-denuded arterial ring preparations. Oral RJ increased tail blood flow and mass in control rats 1 h after treatment without affecting velocity, sBP, or HR. These effects were not observed in L-NAME-treated rats. RJ contained approximately 1000 μg/g of ACh. Significance: The present study demonstrated that RJ is composed of muscarinic receptor agonist(s), likely ACh, and induces vasorelaxation through nitric oxide (NO) production from the vascular endothelium of healthy rats, leading to increased tail blood circulation. Thus, fresh RJ may improve peripheral circulation in healthy individuals.
Article
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.
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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.
Article
Objective: Royal jelly (RJ) has been used for medical and nutritional purposes, and previous studies have indicated that it may have estrogenic activity. The present study investigated the effects of RJ on bone metabolism in ovariectomized (OVX) rats. Methods: Rats (12 weeks old) were randomly divided into four groups, namely Baseline, Sham, OVX, and OVX + RJ groups. Rats in the Baseline group were killed immediately, whereas rats in the OVX and OVX + RJ groups underwent bilateral ovariectomy and those in the Sham group underwent sham operation. RJ was administered to rats in the OVX + RJ group daily for 12 weeks. At the end of the 12-week period, bone mass, bone histomorphometry, and bone mechanics were analyzed. Results: Femur bone mineral density (BMD) was significantly lower in the OVX group than in the Sham group, and this decrease in BMD was not ameliorated by RJ administration. However, femur stiffness, as evaluated by a three-point bending test, was significantly higher in the OVX + RJ group than in the OVX group. Conclusion: The findings of the present study suggest that RJ does not prevent bone loss, but does improve bone strength in OVX rats.
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With increasing age, humans and animals suffer from partial or complete loss of cognition and memory. As a result, quality of life declines significantly. Among many underlying mechanisms, a significant decline in the neurotransmitter acetylcholine (ACh), an increase in N-methyl-d-aspartate (NMDA), and oxidative stress are the most recognized events involved in cognition impairment, especially memory and learning. Like chronic neurodegenerative Alzheimer’s disease (AD) in humans, canines and felines suffer from memory loss as they become older. Currently, for AD treatment in humans, an NMDA receptor antagonist memantine in combination with the acetylcholinesterase (AChE) inhibitor donepezil, rivastigmine, or galantamine appears to be the best option. A number of therapeutic drugs (selegiline, gabapentin, buspirone, memantine, etc.) are also available for treatment of canine cognition dysfunction (CCD)/cognitive dysfunction syndrome (CDS). A large number of plant extracts, their ingredients, and bioactive compounds of animal origin have been investigated for anticholinesterase (anti-ChE), antioxidative, anti-inflammatory, and immunomodulatory activities, as well as anti-Aβ aggregation and deposition in the brain. Some of these substances have also been shown to normalize the blood-brain barrier permeability and integrity, while others have been demonstrated to restore mitochondrial function. A small number of plant extracts have also shown MAO-B inhibitory property. Currently, dementic dogs and cats are given nutraceuticals and/or a therapeutic diet to improve their cognition and memory. This chapter describes various nutraceuticals and substances that have potential to improve cognition and memory in senior dogs and cats.
Article
Food Yellow 4 (FY4) is a lemon-yellow-colored synthetic organic azo dye, which is used widely for imparting pleasant and attractive appearance to foods and cosmetics. The present study aimed at evaluating the possible mechanism underlying the FY4-induced reprotoxicity in rats, and the potential supportive role of royal jelly (RJ) or cod liver oil (CLO), which is a natural remedy with several pharmacological benefits, against induced toxicity. Forty-eight male rats were divided into different groups-the control group, the CLO group (0.4 mL/kg), the RJ group (300 mg/kg), the FY4 group (500 mg/kg b.w.), and the co-treated groups (FY4 + CLO or FY4 + RJ). Semen analysis, serum hormones, and enzyme activities were estimated. Immunohistochemical staining was performed using anti-PCNA, anti-Sox 9, anti-STRA8, anti-DMC1, and anti-ssDNA antibody. The FY4 group exhibited a significant decrease in sperm concentration and motility percentage (%) and a substantial reduction in the TES and LH levels. Testicular LDH, ACP, and SDH were observed to be inhibited. Furthermore, co-localization of DMC1 and ssDNA, which reflected apoptotic induction in the leptotene and zygotene spermatocytes, respectively, was observed to have markedly elevated in the FY4 treated rats, with fewer PCNA-positive and SOX9-positive cells and higher ssDNA-positive cells in the seminiferous epithelium in comparison to the control groups. Interestingly, co-treatment with CLO or RJ exhibited healthy sperms and restored their features, activated the enzyme production, and raised the levels of sexual hormones. In addition, both RJ and CLO restored the features of the testicular tissue as observed under a light microscope, and limited the apoptosis as observed through antibody staining. Collectively, the results of the present study revealed that the co-administration of RJ or CLO with FY4 improved the biochemical, hormonal, and structural aspects of the testicular tissue in rats. Therefore, CLO and RJ may be considered promising agents that would be able to improve the testicular structure and function in the FY4-exposed individuals.
Article
Royal jelly (RJ) is a well-known functional and medicinal food for human health promotion. Major royal jelly proteins (MRJPs), which are the major protein components in RJ, exhibit antimicrobial activities. However, the identities of the MRJPs of RJ responsible for its antioxidant effects have remained unclear. Here, we report that honeybee (Apis cerana) MRJP 2 (AcMRJP2) acts as an antimicrobial and antioxidant agent in RJ. Using recombinant AcMRJP2, which was produced in baculovirus-infected insect cells, we established the antimicrobial and antioxidant roles of MRJP 2. AcMRJP2 bound to the surfaces of bacteria, fungi, and yeast, which then induced structural damage in the microbial cell walls and led to a broad spectrum of antimicrobial activities. AcMRJP2 protected mammalian and insect cells via the direct shielding of the cell against oxidative stress, which led to reduced levels of caspase-3 activity and oxidative stress-induced cell apoptosis, followed by increased cell viability. Moreover, AcMRJP2 exhibited DNA protection activity against reactive oxygen species (ROS). Our data indicate that AcMRJP2 could play a crucial role as an antimicrobial agent and antioxidant in RJ, suggesting that MRJP 2 is a component responsible for the antimicrobial and antioxidant activities of RJ.
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The production of tropical fruits is a great business opportunity in Brazil, including in Tocantins state. Among the species belonging to the family Cucurbitaceae, the melon, Cucumis melo L., and the watermelon, Citrullus lanatus (Thunb.) Matsum. & Nakai, occupy a rominent position. Melon and watermelon are highly dependent on bee pollination services to produce fruits. If there is no bee articipation in the pollination of the flowers, there will be no fruit production or if this participation of these beneficial insects is insufficient, the revenge fruits will be deformed, with reduced mass and poor in sugar content and consequently of no commercial value. Although beemediated pollination is a crucial issue for the production of various crops, it is often confined to a few lines in the available technical publications. Therefore, this work aimed to describe the characteristics of the melon and watermelon plant that must be observed for a better adaptation of the management practices of the crops in order to favor the pollination services performed by the bees and to present directed pollination with Africanized bees, Apis mellifera L., reporting technical aspects needed to optimize this activity in melon and watermelon crops in Tocantins and in other Brazilian states.
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Article
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.
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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.
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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.
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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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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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