Possible effects of royal jelly against neuronal injury in the hippocampus of ovariectomized rats with pentylenetetrazol-induced seizures: Role of luteinizing and follicle-stimulating hormones.

697 Background: Royal jelly (RJ) is a honey bee product secreted from the mandibular glands and hypopharyngeal glands of worker honeybees. RJ has anti-allergy, anti-inflammatory, and immunomodulatory effects. RJ has been reported to improve the anti-cancer effects and suppress the adverse effects of chemotherapeutic agents. The main aim is to clarify the clinical effects of oral intake of RJ in renal cell carcinoma (RCC) patients treated with tyrosine kinase inhibitors (TKIs). Methods: A randomized, controlled, double-blinded clinical trial with reduction of tumor size and frequencies of adverse events as endpoints was performed in 33 RCC patients who received TKIs in Nagasaki University Hospital. Patients were divided into RJ (n = 16) and placebo (n = 17) groups, and there was no significant difference in all clinical and pathological parameters between the two groups. RJ and placebo were orally administered for 3 months. Results: In this study, 21, 8, and 3 patients were treated with sunitinib, pazopanib, and axitinib, respectively; only 1 patient was treated with sorafenib. Frequencies and severities of fatigue and anorexia in the RJ group was significantly lower than those in the placebo group ( P = 0.003 and 0.015, respectively). Such significant differences between the 2 groups were detected in patients treated with sunitinib, but not in those treated with other TKIs. The number of patients who were given an initial dose of TKIs in the RJ and placebo groups were 7 (43.8%) and 2 (11.8%), respectively, and the relative dose intensity (RDI) of the RJ group (88.6%) was significantly higher ( P = 0.016) than that in the placebo group (68.6%). Regarding anti-cancer effects, the frequency of partial response in the RJ group (n = 5; 41.7%) was higher than that in the placebo group (2; 18.2%); however, such difference was not significant ( P = 0.056). Conclusions: RJ intake can increase RDI. Although a significant difference was not observed, RJ intake observed a trend for improving anti-cancer effects by increasing RDI and maintaining quality of life.

BackgroundHemodialysis (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.MethodsThis 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.DiscussionThis 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 registrationThe Japan Registry of Clinical Trials jRCTs071200031. Registered on 7 December 2020.

Royal jelly (RJ) is a honey bee product for which, anti-inflammatory properties were shown in vitro. Nanoparticles, including nano-silver (NS), are plausible inflammation inducers that act by activation of immune cells and consequent production of pro-inflammatory cytokines. This project aimed to explore immunomodulatory effects of royal jelly and nano-silver on the kidney and liver. In this project, 40 male rats were grouped as follows: 10 rats as controls, 10 rats treated with RJ; 10 rats treated with both NS and RJ and 10 rats treated with NS. Liver and kidney interleukin (IL)-1β, -2, -6, and -33 levels were determined using commercial ELISA kits. RJ reduced kidney IL-6 levels in comparison to control and NS--RJ groups. RJ and NS reduced kidney and liver IL-1β levels. Kidney IL-33 levels were decreased in the RJ and nano-silver groups in comparison to the NS--RJ group. Based on this study, it may be concluded that RJ together with NS can play anti-inflammatory roles and may affect the function of immune cells.

Background: Both coding and long non-coding RNAs (lncRNAs) have emerged as vital regulators in almost every cellular process, and their expression can be modulated by external stimuli, such as physical exercise. Objectives: The current research aimed to investigate the effects of different volumes of TABATA-high-intensity interval training (HIIT) exercises combined with royal jelly (RJ) supplementation on the NLRP3 inflammasome and lncRNA-H19 expression in obese males. Methods: Forty-two healthy men [Body Mass Index (BMI) = 30 kg/m², waist-to-hip ratio = 0.95, age range: 40 - 60 years] volunteered to participate in the study. The individuals were randomly divided into five experimental groups (N = 35) and one control + placebo group (N = 7). The high-volume (HV) or low-volume (LV) TABATA exercise programs were performed twice a week for 8 weeks. Participants in the RJ supplementation groups received a 1000 mg capsule once a day for 8 weeks. The expression of NLRP3 and lncRNA-H19 genes was evaluated using the real-time PCR method. Results: The NLRP3 gene expression in the Bruce test, measured before and after the 8-week exercise interventions and RJ supplementation, showed insignificant changes across the different groups. However, the H19 gene expression in the Bruce test showed a significant reduction in the HV-TABATA HIIT intervention groups, which was more pronounced than in the LV groups after 8 weeks: HV group (P = 0.004), RJ group (P = 0.001), HV + RJ group (P = 0.007), and LV + RJ group (P = 0.002). After 8 weeks of non-pharmacological interventions involving exercise training and supplementation, a significant decrease in NLRP3 and a significant increase in H19 gene expression were detected in the HV group compared to the LV group (P = 0.05 and P = 0.010). Significant improvement was also found in the resting H19 levels between the RJ and LV groups (P = 0.011) and the LV + RJ group (P = 0.44). Moreover, a significant reduction in resting NLRP3 gene expression was observed between the RJ + LV and LV groups (P = 0.038). Conclusions: Chronic HV TABATA HIIT exercise, when combined with RJ supplementation, is effective in attenuating inflammatory responses to acute stress.

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.

Backgrounds: Royal jelly is a creamy substance secreted by honeybees. It has been reported that royal jelly has benefits on dyslipidemia and metabolic syndrome. However, the effects of royal jelly on atherogenesis remains unknown. We prospectively evaluated the effects of royal jelly on endothelial function, which can reflect early atherogenesis, in healthy volunteers. Methods: This was a single center, double-blind, 1:1 randomized placebo-controlled study. One-hundred healthy volunteers were randomly assigned to receive royal jelly 690 mg daily (equivalent 2040 mg of fresh royal jelly) or placebo from October 2018 and December 2019. Royal jelly or placebo were administered for 28 days. Endothelial function assessed by reactive hyperemia peripheral arterial tonometry (RH-PAT) and blood chemistries were compared between baseline and 28 days after enrollment. Primary endpoint was the change of RH-PAT index. Secondary endpoint was the change of liver function and lipid profiles. Results: The mean (SD) age of the participants was 35.0 (9.3) and 36.1 (9.1) years, and male was 45% and 50% in the placebo and the royal jelly group, respectively. The relative change of RH-PAT index was significantly higher in the royal jelly group compared with placebo control (21.4 ± 53.1% vs. 0.05 ± 40.9%, P = 0.037). The relative change of alanine aminotransferase and γ-glutamyl transpeptidase were significantly lower in the royal jelly group than 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 two study groups. Conclusions: Royal jelly improved endothelial function assessed by RH-PAT and liver function in healthy volunteer. It can be expected that royal jelly has anti-atherogenic property through improving endothelial function.

Objectives This study aimed to evaluate the effects of royal jelly (RJ) supplementation on bone metabolism in postmenopausal women. Methods This was a randomized, double-blind, placebo-controlled clinical trial. Seventy-two healthy postmenopausal women aged 45–60 years within 5 years after menopause were randomized into two groups: women in the RJ group (n = 36) received capsules containing dried RJ (equivalent to 3000 mg of fresh RJ); and women in the placebo group (n = 36) received placebo daily for 6 months. Bone mineral density (BMD) of the lumbar spine (L2–L4) and left proximal femur, hip structural analysis (HSA) of the left hip, and bone turnover markers were measured. Results Although women in the placebo group experienced a significant loss of BMD and deterioration in HSA parameters of the femur, no significant differences were found in these parameters in women in the RJ group. The levels of total procollagen type 1 N-terminal propeptide (P1NP) and tartrate-resistant acid phosphatase decreased significantly in the placebo group; however, the total P1NP level, a marker of bone formation, was not significantly different in the RJ group at postintervention compared with baseline. Conclusion RJ consumption may ameliorate decreases in femoral BMD and strength in postmenopausal women.

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.

ABSTRACTWe investigated microtubule-associated protein 2 (MAP-2) immunoreactivity of hippocampal neurons and the potential role of royal jelly (RJ) in regulating MAP-2 during experimental hypothyroidism (HT). Thirty adult female Wistar albino rats were randomized into five groups: the control group was untreated, the sham control group was treated with 10 mg/kg 0.9% sterile saline injected intraperitoneally (i.p.), The RJ group was treated with 100 mg/kg RJ by oral gavage, the HT group was treated with 10 mg/kg propylthiouracil (PTU) i.p. to induce experimental hypothyroidism, and the HT + RJ group was treated with 10 mg/kg PTU i.p. + 100 mg/kg RJ by oral gavage. Oral and i.p. administrations were performed once daily for 20 days. Thyroid stimulating hormone (TSH) and free thyroxine (fT4) levels in the serum were measured biochemically, MAP-2 was measured immunohistochemically in the hippocampus and an immunohistochemical H score was calculated. MAP-2 immunoreactivity appeared in the cytoplasm of neuron cell bodies and dendrites in the hippocampal CA3 and CA1 regions in the control, sham control and RJ groups. MAP-2 immunoreactivity decreased significiantly in the HT group compared to control, sham control and RJ groups. Also, vascular dilation and swollen cells were observed following PTU administration. The degeneration that was observed in the HT group decreased by RJ administration. By contrast, MAP-2 immunoreactivity increased following administration of RJ. Experimental hypothyroidism reduced significiantly MAP-2 immunoreactivity in both the CA3 and CA1 regions and caused degeneration, including edema and vascular dilation, in the hippocampus. RJ increased MAP-2 expression and exhibited a therapeutic effect on the degenerative changes.

In this study, 42 Wistar albino male rats (n = 42, 8 weeks old) were used. Rats were divided into 6 groups and 7 rats included each group. Groups: (i) Control group: Standard diet; (ii) RJ (royal jelly) group: Standard diet + royal jelly; (iii) F50 group: Standard diet + 50 mg/kg fluoride; (iv): F100 group: Standard diet + 100 mg/kg fluoride; (v) F50+RJ group: Standard diet + 50 mg/kg fluoride + royal jelly; (vi): F100+RJ group: Standard diet + 100 mg/kg fluoride + royal jelly. After 8 weeks, the rats were decapitated, and their muscle tissues were removed. Expression levels of Caspase-3, Caspase-6, Bax, tumor necrosis factor-α (TNF-α), interleukin 1 alpha (IL1-α) and Bcl-2 proteins in muscle tissue were determined by western blotting method. Histopathological analyses were also performed on the muscle tissue. Malondialdehyde (MDA), glutathione (GSH) and catalase (CAT) analyses were determined by a spectrophotometer. According to the obtained results, Bcl-2, TNF-α and IL1-α protein expression was increased in damage groups compared to the control and royal jelly groups, while Caspase-3, Caspase-6 and Bax protein expression levels decreased in damage groups. MDA level increased in damage groups compared to the control and royal jelly groups, while CAT and GSH levels increased with royal jelly application in royal jelly-given group in comparison to the flouride-exposed group. According to histopathological analysis results, edema and inflammatory cell formations were found in the injury groups, a tendency to decrease in these injuries was observed in the treatment groups. Based on these results, we can say that royal jelly has protective effects on muscle tissue against fluoride damage.Graphical abstract

Royal jelly is known to strengthen memory, provide antioxidative, antidiabetic, antitumor, anticancer, antibacterial, antiinflammatory, antihypertensive. In this study, 42 rats (n = 42) were used, and these rats were divided into 6 groups of 7 rats each. Groups: (i) Control Group: Group fed with standard diet; (ii) Royal Jelly (RJ) Group: RJ (100 mg/kg bw, gavage); (iii) F50 Group: Fluoride (50 mg/kg bw, drinking water); (iv) F100 Group: F (100 mg/kg bw, drinking water); (v) F50 + RJ Group: F (50 mg/kg bw, drinking water) + RJ (100 mg/kg bw, gavage); (vi) F100 + RJ Group: F (100 mg/kg bw, drinking water) + RJ (100 mg/kg bw, gavage). The rats were decapitated after 8 weeks, and their heart tissues were taken and examined. Lipid peroxidation by MDA (malondialdehyde) analyzes, GSH (glutathione) level and catalase activity were determined by spectrophotometer. Protein expression levels of caspase-3, caspase-6, caspase-9, Bcl-2, Bax, BDNF, Gsk-3, Nrf-2 and NF-κB proteins in heart tissue were determined by western blotting technique and hearth tissue evaluated by histopathologically. As a result, MDA levels, Bcl-2, Gsk-3 and NF-κB protein expression levels were reduced, whereas GSH levels, caspase-3, caspase-9, caspase-6, Bax, BDNF and Nrf-2 protein levels were increased in the F50 + RJ and F100 + RJ groups compared to the F50 and F100 groups. According to the results of this study, it has been concluded that Royal jelly has the potential to be developed in to a drug for treatment of heart diseases in addition to providing protection against heart damage.

Introduction: Royal jelly (RJ) is a honey bee secretion with numerous medicinal properties and antioxidant activities. Morphine is a major risk factor in the development of functional disorders in several organ systems. This study was designed to evaluate the effects of RJ against morphine-induced damage to the prefrontal cortex of rats. Materials and Methods: In this study, 48 male Wistar rats were randomly assigned into 6 groups: sham group, morphine group, RJ groups (100, and 200 mg/kg), and morphine + RJ groups. Treatments were administered intraperitoneally and orally for 20 days on a daily basis. Ferric reducing/antioxidant power (FRAP) method was applied to determine the total antioxidant capacity. The number of neurons and, dendritic spines were investigated by Golgi technique, and Griess technique was employed to determine the serum nitrite oxide level. Results: Morphine administration significantly increased the nitrite oxide level and total antioxidant capacity, and reduced neuronal dendritic spines and neurons compared to the sham group (P < 0.05). In all RJ and Morphine + RJ groups, the number of neurons and neuronal dendritic spines were elevated significantly, while nitrite oxide level and total antioxidant capacity were reduced compared to the morphine group (P < 0.05). Conclusions: RJ administration protected animals against oxidative stress and nitrite oxide. It also improves some prefrontal cortex parameters including number of neurons and dendritic spines because of the morphine.

The aim was to study the possible effects of royal jelly (RJ) supplementation on milk fat content and fatty acids (FA) profile of ewes during the early stage of lactation. Randomly, thirty-six Ossimi ewes were divided into two groups (18 animals each). The first group was offered the basal diet which was considered as a control group, whereas the second group was fed the basal diet, in addition to a supplement of a single bolus of RJ (1000 mg/head) every two days as a treated group. Regardless the effect of time, the RJ-supplemented group recorded a non-significant increase in daily milk yield (1.22 kg) when compared with the control (1.08 kg) group (P<0.063). While, the RJ-supplemented ewes showed significantly increase in milk fat percentage (P<0.008) as compared to control group. Lactating ewes in the control group produced significantly higher contents of milk C14:0 (P<0.036) and C18:0 (P<0.027) saturated FA than that in the RJ group. However, the contents of milk C6:0 and C17:0 in the RJ group were significantly greater than that estimated in the control (P<0.050 and 0.041, respectively). Furthermore, Lactating ewes supplemented with RJ produced significantly higher contents of milk C16:1 (P<0.001), C18:1 (P<0.001) and C18:2 (P<0.046) unsaturated FA than the control group. It can be concluded that supplementation of ewes during the early stage of lactation with RJ can improve the nutritive value of milk fat, and appears to be an opportunity to modify the concentrations of certain milk fatty acids.

Background: Alzheimer’s disease (AD) is a common disease in the elderly that is associated with impaired metabolism and biology of the hippocampus. Although the role of exercise and natural antioxidants in improving the disease has been reported, the role of muscle contraction-related physical activity along with royal jelly (RJ) consumption is not yet well understood. Objectives: This study aimed to investigate the effect of eight weeks of training on positive slope (ETPS) and negative slope (ETNS) with royal jelly (RJ) consumption on O-6-methylguanine DNA methyltransferase (MGMT) and ATPase gene expression levels in the hippocampus tissue of trimethyltin (TMT)-induced AD rats. Methods: In this experimental trial, 36 male Sprague-Dawley AD rats (induced with 8 mg/kg TMT) were divided into (1) control + normal saline/royal jelly solvent) (Sh); (2) ETPS; (3) ETNS; (4) ETPS + RJ; (5) ETNS + RJ, and (6) RJ groups. Six rats were placed in the healthy control (HC) group. Then the training groups trained on ( + 15 and -15) slopes for eight weeks, five sessions per week, and each session lasted 60 minutes at a speed of 16 m/min. The royal jelly (RJ) groups received 100 mg/kg royal jelly per day by intraperitoneal injection. Results: ETNS, ETPS, ETPS + RJ, and ETNS + RJ increased MGMT gene expression (P ≤ 0.05). ETPS and ETPS + RJ also increased ATPase gene expression (P ≤ 0.05). However, RJ had no significant effect on increasing MGMT and ATPase gene expression in the hippocampus tissue of AD rats (P ≥ 0.05). Conclusions: It seems that the improvement of DNA damage markers and energy levels depends on the type of contraction. Although training on positive and negative slopes with royal jelly consumption has an interactive effect on DNA repair markers, training on a positive slope and royal jelly consumption has an interactive effect on ATPase gene expression.

Purpose: Cadmium (Cd) is a toxic metal that seriously threatens human health due to environmental pollution, is widely used in industry and agriculture, and causes oxidative stress and tissue damage. This study aims to examine the effect of royal jelly (RJ) on oxidative status and telomerase enzyme activity in tissue damage induced by Cd. Materials and Methods: The experimental design was made with 6 rats in each group. A total of 6 groups were created: control group, Cd group, 250 mg/kg RJ group, Cd + 250 mg/kg RJ group, 400 mg/kg RJ group, Cd + 400 mg/kg RJ group. In the study, total oxidant status and total antioxidant status in blood serum were investigated by colorimetric method, and telomerase enzyme activity in ovarian tissue was investigated by ELISA method. Results: Cd caused an increase in oxidative capacity (23.80 ± 2.4) and a significant decrease was determined after RJ applications compared to the control group. After RJ application, the best total antioxidant response was observed in the 250 mg/kg RJ and Cd + 250 mg/kg RJ groups. Cd significantly reduced telomerase enzyme activity (0.90 ± 0.13). RJ administered for treatment after Cd application increased telomerase levels up to the control level (1.40 ± 0.05). The best treatment response was observed in the Cd + 250 mg/kg RJ group (1.42 ± 0.05). Conclusion: Cd causes oxidative stress and that RJ may have curative effects by increasing the antioxidant capacity and telomerase enzyme activity RJ is a promising natural product and can contribute to recovery.