Efficiency of Chinese medicine Bushen Huatan formula for treatment of polycystic ovary syndrome in mice via regulating gut microbiota and PPARγ pathway. / è¡¥è‚¾åŒ–ç—°æ–¹é€šè¿‡è°ƒæŽ§è‚ é“èŒåŠPPARγ通路治疗多囊卵巢综合征的机制.

OBJECTIVES: To explore the effect and mechanism of Chinese medicine Bushen Huatan formula in treatment of polycystic ovary syndrome (PCOS). METHODS: Twenty-four SPF female C57BL/6J mice were randomly divided into 3 groups with 8 animals in each group. Control group was given drinking water ad libitum; PCOS was induced by giving letrozole gavage and high-fat diet in model group and treatment group; treatment group received Bushen Huatan formula suspension for 35 d. The sex hormone levels of mice were detected by enzyme-linked immunosorbent assay. Ovary morphology was observed under light microscope after hematoxylin and eosin staining. The feces in the colon of mice were collected, and the gut microbiota was detected by 16S rRNA sequencing. The short chain fatty acids were detected by gas chromatography-mas spectrometry. The expression of peroxisome proliferator activated receptor (PPARγ) was detected by immunohistochemistry. The mRNA expression of mucin-2, occludin-1, tight junction protein zonula occludens 1 (ZO-1) and PPARγ in intestinal epithelium were detected by realtime RT-PCR. The expression of inducible nitric oxide synthase (iNOS) and PPARγ was detected by Western blotting. RESULTS: Compared with the control group, the body weight, serum levels of follicle stimulating hormone, luteinizing hormone and testosterone in the model group were increased, and serum levels of estradiol were decreased (all P<0.01); the ovarian structure under light microscope was consistent with the characteristics of PCOS. Compared with the model group, the serum levels of sex hormone and ovarian structure in treatment group were improved. The overall structure of gut microbiota in PCOS model mice changed. Compared with control group, there were significantly reduced abundance of Firmicutes, and increased abundance of Verrucomicrobia, Proteobacteria and Actinobacteria inthe model group at phylum level (all P<0.05); there were significantly reduced abundance of Lactobacillus, and increased abundance of Akkermansia, Lachnoclostridium, Lactococcus and Eubacterium_coprostanoligenes at genus level (all P<0.05). The disordered condition of gut microbiota was significantly improved in treatment group. Compared with control group, the contents of acetic acid, propionic acid and butyric acid in feces of model group were significantly decreased (all P<0.05); while the contents of propionic acid and butyric acid in treatment group were significantly increased compared with model control group (both P<0.05). Compared with control group, the mRNA expression of ZO-1 and protein expression of iNOS in model group were significantly increased, and the protein expression of PPARγ and the mRNA expressions of mucin-2 and occludin-1 were significantly decreased (all P<0.05). Compared with model group, the mRNA expression of ZO-1 and protein expression of iNOS in treatment group were decreased, and the protein expression of PPARγ and the mRNA expressions of mucin-2 and occludin-1 were increased. CONCLUSIONS: PCOS induced by letrozole high-fat diet induces microflora imbalance in mice. Chinese medicine Bushen Huatan formula may increase the level of short chain fatty acid by regulating gut microbiota, thereby activating the intestinal PPARγ pathway and improving intestinal barrier function to act as a cure for PCOS.

Therapeutic and prophylactic role of vitamin D and curcumin in acetic acid-induced acute ulcerative colitis model.

Ulcerative Colitis (UC) is a disease that negatively affects quality of life and is associated with sustained oxidative stress, inflammation and intestinal permeability. Vitamin D and Curcumin; It has pharmacological properties beneficial to health, including antioxidant and anti-inflammatory properties. Our study investigates the role of Vitamin D and Curcumin in acetic acid-induced acute colitis model. To investigate the effect of Vitamin D and Curcumin, Wistar-albino rats were given 0.4 mcg/kg Vitamin D (Post-Vit D, Pre-Vit D) and 200 mg/kg Curcumin (Post-Cur, Pre-Cur) for 7 days and acetic acid was injected into all rats except the control group. Our results; colon tissue TNF-α, IL-1ß, IL-6, IFN-γ and MPO levels were found significantly higher and Occludin levels were found significantly lower in the colitis group compared to the control group (p < 0.05). TNF-α and IFN-γ levels decreased and Occludin levels increased in colon tissue of Post-Vit D group compared to colitis group (p < 0.05). IL-1ß, IL-6 and IFN-γ levels were decreased in colon tissue of Post-Cur and Pre-Cur groups (p < 0.05). MPO levels in colon tissue decreased in all treatment groups (p < 0.05). Vitamin D and Curcumin treatment significantly reduced inflammation and restored the normal histoarchitecture of the colon. From the present study findings, we can conclude that Vitamin D and Curcumin protect the colon from acetic acid toxicity with their antioxidant and anti-inflammatory potential.Brief synopsis: In this study; distal colon, distal ileum, jejunum and serum physiopathology in colitis induced by acetic acid and intestinal permeability were investigated. The roles of vitamin D and curcumin in this process were evaluated.

[Zuogui Jiangtang Qinggan Prescription promotes recovery of intestinal mucosal barrier in mice with type 2 diabetes mellitus and nonalcoholic fatty liver disease by improving intestinal flora homeostasis].

This study aimed to investigate the recovery effect of Zuogui Jiangtang Qinggan Prescription on intestinal flora homeostasis control and intestinal mucosal barrier in type 2 diabetes mellitus(T2DM) with nonalcoholic fatty liver disease(NAFLD) induced by a high-fat diet. NAFLD was established in MKR transgenic mice(T2DM mice) by a high-fat diet(HFD), and subsequently treated for 8 weeks with Zuogui Jiangtang Qinggan Prescription(7.5, 15 g·kg~(-1)) and metformin(0.067 g·kg~(-1)). Triglyceride and liver function were assessed using serum. The hematoxylin-eosin(HE) staining and Masson staining were used to stain the liver tissue, while HE staining and AB-PAS staining were used to stain the intestine tissue. 16S rRNA sequencing was utilized to track the changes in the intestinal flora of the mice in each group. Polymerase chain reaction(PCR) and immunofluorescence were used to determine the protein and mRNA expression levels of ZO-1, Occludin, and Claudin-1. The results demonstrated that Zuogui Jiangtang Qinggan Prescription increased the body mass of T2DM mice with NAFLD and decreased the hepatic index. It down-regulated the serum biomarkers of liver function and dyslipidemia such as alanine aminotransferase(ALT), aspartate transaminase(AST), and triglycerides(TG), increased insulin sensitivity, and improved glucose tolerance. According to the results of 16S rRNA sequencing, the Zuogui Jiangtang Qinggan Prescription altered the composition and abundance of the intestinal flora, increasing the relative abundances of Muribaculaceae, Lactobacillaceae, Lactobacillus, Akkermansia, and Bacteroidota and decreasing the relative abundances of Lachnospiraceae, Firmicutes, Deslfobacteria, Proteobacteria, and Desulfovibrionaceae. According to the pathological examination of the intestinal mucosa, Zuogui Jiangtang Qinggan Prescritpion increased the expression levels of the tight junction proteins ZO-1, Occludin, and Claudin-1, promoted intestinal mucosa repair, protected intestinal villi, and increased the height of intestinal mucosa villi and the number of goblet cells. By enhancing intestinal mucosal barrier repair and controlling intestinal microbiota homeostasis, Zuogui Jiangtang Qinggan Prescription reduces intestinal mucosal damage induced by T2DM and NAFLD.

The intestinal histopathology, innate immune response and antioxidant capacity of blunt snout bream (Megalobrama amblycephala) in response to Aeromonas hydrophila.

The present study was performed to determine the effects of Aeromonas hydrophila infection on intestinal -histopathology, innate immune response and changes in antioxidant capacity of blunt snout bream (Megalobrama amblycephala). A series of histopathological changes, innate immune enzyme activities, antioxidant enzyme activities, and the corresponding mRNA relative genes expressions in intestines were measured at 0, 1, 2, and 3 weeks post-treatment of Aeromonas hydrophila (1✕107 CFU mL-1) infection. The results showed that Aeromonas hydrophila induced changes in intestinal morphology, including the decreased muscularis thickness, the proliferated goblet cells, and the atrophied intestine villi height. Moreover, the innate immune enzymes activities in serum such as acid phosphatase, alkaline phosphatase, lysozyme activities and immunoglobulin M were significantly reduced after infection at 1week, 2week and 3week. The contents of complement 3 and complement 4 were significantly decreased after infection as well. In addition, the antioxidant enzymes activities, including superoxide dismutase, catalase and glutathione peroxidase in the experimental groups were significantly decreased compared with the control group, whereas the content of malondialdehyde was significantly increased after infection at 1week, 2week and 3week. Furthermore, the mRNA relative expressions of the inflammatory cytokines such as tumor necrosis factor-α, interleukins-1ß, interferon-γ, and interleukins-6 were significantly increased after infection with Aeromonas hydrophila. The TJ-related gene expressions in the intestine of zonula occluden-1, occludin, occludin-1, occludin-2 were significantly reduced throughout the infection period. The mRNA relative expressions of signal transducers and activators of transcription 4 and janus kinase-3 in the intestine were significantly ascended compared with the non-infected group. Overall, the results elucidated that the intestine tissue injury and innate immune response reduction, as well as antioxidant capacity attenuation were occurred against Aeromonas hydrophila infection of the blunt snout bream.

Therapeutic effects of thymoquinone or capsaicin on acrylamide-induced reproductive toxicity in rats mediated by their effect on oxidative stress, inflammation, and tight junction integrity.

In the field of environmental toxicology, endocrine-disrupting effects have become a major concern. The present research set out to investigate the possible reproductive toxicity of acrylamide. The research was also expanded to explore the protective effects of two nutraceuticals, thymoquinone (TQ) and capsaicin, against acrylamide-induced reproductive toxicity. Six groups of sixty male albino rats were created. Group 1 was used as a control. Rats were administered a daily dose of acrylamide and acted as the model in Group 2. TQ was provided to rats once a day in Group 3. Capsaicin was administered to rats once a day in Group 4. TQ was given once daily to rats exposed to acrylamide in Group 5. Rats were given capsaicin once a day for eight weeks after being exposed to acrylamide in Group 6. Acrylamide induced oxidative stress, testicular NF-κB/p65 expression, and down-regulated the expression of occludin, all of which can contribute to its testicular toxicity, while TQ or capsaicin removes all of these toxicity signs. TQ and capsaicin have shown efficacy in alleviating all of the acrylamide's toxic insults in the current reproductive toxicity model. Both nutraceuticals upregulated the expression of occludin in testicular tissue and restored tight junction integrity, in addition to their well-known antioxidant and anti-inflammatory effects, which were confirmed in this study.