Royal Jelly Attenuates LPS-Induced Inflammation in BV-2 Microglial Cells through Modulating NF-κB and p38/JNK Signaling Pathways.

Royal jelly (RJ), a hive product with versatile pharmacological activities, has been used as a traditional functional food to prevent or treat inflammatory diseases. However, little is known about the anti-inflammatory effect of RJ in microglial cells. The aim of this study is to assess the anti-inflammatory effects of RJ in lipopolysaccharide- (LPS-) induced murine immortalized BV-2 cells and to explore the underlying molecular mechanisms. Our results showed that in LPS-stimulated BV-2 cells, RJ significantly inhibited iNOS and COX-2 expression at mRNA and protein levels. The mRNA expression of IL-6, IL-1ß, and TNF-α was also downregulated by RJ in a concentration-dependent manner. Additionally, RJ protected BV-2 cells against oxidative stress by upregulating heme oxygenase-1 (HO-1) expression and by reducing reactive oxygen species (ROS) and nitric oxide (NO) production. Mechanistically, we found that RJ could alleviate inflammatory response in microglia by suppressing the phosphorylation of IκBα, p38, and JNK and by inhibiting the nucleus translocation of NF-κB p65. These findings suggest that RJ might be a promising functional food to delay inflammatory progress by influencing the microglia function.

[Expression of Sirtuin 1 in visceral adipose tissue in Tibetan mini-pigs with obesity and insulin resistance induced by high fat/cholesterol diet].

OBJECTIVE: To investigate the role of Sirt1 in visceral adipose tissue in Tibetan mini-pigs with obesity and insulin resistance induced by high fat/cholesterol diet. METHODS: Twelve male Tibetan mini-pigs were divided into 2 groups randomly: normal control (NC) group, high-fat/cholesterol (HFC) diet group, 6 in each group. After 16 weeks of modeling, fasting body weight and body mass index (BMI) were measured. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were measured in anterior venous blood, and atherosclerosis index (AI) was calculated. Meanwhile, intravenous glucose tolerance test was conducted to observe the changes of blood glucose and insulin, and the area under the curve (AUC) was calculated. After euthanasia, visceral fat rate was detected, and visceral fat tissue was taken for histopathological observation and fat cell diameter analysis. RT-PCR was used to observe the mRNA expression levels of Sirtuin1 (Sirt1), insulin-like growth factor-1 (IGF-1), glucose transporter 4 (GLUT4), peroxisome proliferator-activated receptor γ (PPARγ), peroxisome proliferator-activated receptor γ-assisted activator 1α (PGC-1α), forkhead box protein O1 (FoxO1), lipolysis-related gene hormone-sensitive lipase (HSL), and fat synthesis-related gene fatty acid synthase (FASN)changes in adipose tissue. RESULTS: Compared with the NC group, the body weight, BMI, TC, LDL-C, HDL-C, AI and visceral fat rate were significantly increased after 16 weeks of high-fat/cholesterol induction in Tibetan mini-pigs(P＜0.05,P＜0.01). Meanwhile, the glucose tolerance curve was significantly delayed and the area under the curve of blood glucose and insulin was significantly increased (P＜0.05). HE pathological observation and quantitative analysis showed that fat cells were hypertrophy and the average cell diameter was increased significantly (P＜0.01). In addition, the mRNA expression levels of Sirt1,PGC-1α, GLUT4, and HSL were all decreased in varying degrees in adipose tissue, among which the mRNA expressions of Sirt1 and HSL were significantly decreased (P＜0.05), while the mRNA expressions of FOXO1, IGF-1, PPARγ, and FASN were significantly increased (P＜0.05, P＜0.01). CONCLUSION: Tibetan mini-pigs were induced by high fat/cholesterol diet to form obesity model with phenotypic characteristics such as lipid disorder and insulin resistance, whereas Sirt1 plays a key role in visceral fat deposition and insulin sensitivity reduction in obese Tibetan mini-pigs.

Royal jelly attenuates nonalcoholic fatty liver disease by inhibiting oxidative stress and regulating the expression of circadian genes in ovariectomized rats.

Nonalcoholic fatty liver disease (NAFLD) has a high incidence in postmenopausal women and is accompanied by insulin resistance, obesity, and dyslipidemia. Royal jelly (RJ), a natural substance derived from hive, possesses numerous health-beneficial properties. Here, we evaluated the effects of RJ (150, 300, and 450 mg kg-1  day-1 , 8 weeks) on NAFLD in ovariectomized (OVX) rats. Based on the results, RJ ameliorated the degree of anxiety, improved serum lipid profile, and attenuated the hepatic steatosis and liver injury in OVX rats. Furthermore, the protective effects of RJ could be attributed to its antioxidant properties, which enhance the levels of hepatic antioxidant enzymes. The qRT-PCR results also suggest that RJ improves the disturbances of circadian genes by downregulating their expression, including that of Per1 and Per 2, in the liver of OVX rats. Altogether, our findings suggest that RJ may be a promising agent for the treatment of NAFLD. PRACTICAL APPLICATIONS: Postmenopausal women are at an increased risk of NAFLD. Currently, there are no licensed therapies for NAFLD. Although hormone replacement therapy (HRT) is reported to inhibit the development of NAFLD, it causes unexpected adverse effects. As HRT is controversial, the use of natural supplements to counteract the detrimental effects of menopause has recently attracted more attention. RJ is a natural product secreted from the hypopharyngeal and mandibular glands of worker bees. The present study illustrates the protective effect of the natural product, RJ, and its underlying mechanisms on NAFLD. This is the first study to assess the effect of RJ on NAFLD under estrogen deficiency. Such findings contribute to the further utilization of RJ, which might serve as a promising therapeutic option and natural food for the treatment of NAFLD.

Differential expression of microRNA related to irritable bowel syndrome in a rabbit model.

OBJECTIVE: This study aimed to evaluate the differential expressions of microRNAs (miRNAs) in white hair black eye (WHBE) rabbits of irritable bowel syndrome (IBS). METHODS: WHBE and Japanese white (JW) rabbits were divided into the control and IBS groups. The IBS groups were exposed to moist heat, stress and low-dose laxatives. Their intestinal movement rate was measured. Blood samples were taken to detect serum 5-hydroxytryptamine (5-HT) and dopamine levels and colonic tissues were obtained to detect c-Fos expression by immunohistochemistry. Deep sequencing technology was used to obtain miRNA sequences in the intestinal tissues of WHBE and JW control groups. Expressions of 14 miRNAs were measured by real-time polymerase chain reaction in both the control and the IBS model groups. RESULTS: Serum 5-HT and dopamine levels, intestinal movement rate and c-Fos expressions in the WHBE rabbits were significantly increased compared with the control group. MiR-29a-3p, miR-24-3p, miR-221-3p, let-7f-5p, let-7g-5p, let-7i-5p, miR-192-5p, miR-126-3p and miR-130b-3p expressions in WHBE IBS rabbits at day 14 were significantly higher than those in the control group while miR-324-3p and miR-132 were downregulated. MiR-29a-3p, let-7i-5p, miR-192-5p and miR-126-3p were significantly upregulated only in JW IBS rabbits at day 14 and miR-324-3p, miR-223-3p and miR-132 were significantly downregulated in JW IBS group. MiR-24-3p, miR-221-3p, let-7f-5p, miR-126-3p and miR-130b-3p expressions in WHBE IBS rabbits were higher than that in JW IBS rabbits. CONCLUSIONS: Twelve miRNAs were differentially expressed in IBS rabbits. Five are specific in WHBE IBS rabbits, suggesting that they play a role in increased sensitivity to IBS.

[Monitoring inbreeding of WHBE rabbits using microsatellites].

Microsatellite polymorphisms were analyzed in F5, F6 and F7 WHBE rabbits (Oryctolagus cuniculus) to monitor inbreeding. Out of 21 microsatellite loci, 11 were successfully amplified and showed polymorphic. For the F5 WHBE rabbits, the number of alleles per locus (Na) ranged from 3 to 9 and the mean effective number of alleles (Ne) was 1.81. The mean value of observed heterozygosity (Ho) and polymorphism information content (PIC) of the 11 polymorphic loci were 0.381 and 0.524, respectively. The power of cumulative discrimination (CDP) was 1.0. The value of cumulative exclusion probability of the 11 polymorphic loci in the absence (CPE-1) or in the presence of genetic information on the first parent (CPE-2) was 0.926 and 0.993, respectively. For the F6 WHBE rabbits, Na per locus ranged from 3 to 8 and the mean value of Ne was 1.68. The mean value of Ho, PIC, CDP, CPE-1, CPE-2 of the 11 polymorphic loci were 0.356, 0.548, 1.0, 0.931, 0.994 respectively. For the F7 WHBE rabbits, Na per locus ranged from 2 to 6 and the mean value of Ne was 1.51. The mean value of Ho, PIC, CDP, CPE-1, CPE-2 of the 11 polymorphic loci were 0.287, 0.498, 1.0, 0.891, 0.986 respectively. The average number of effective alleles and the average observed heterozygosity were decreasing continuously in F5, F6 and F7, suggesting that the purity of WHBE rabbits was increasing continuously.