Oral berberine ameliorates high-fat diet-induced obesity by activating TAS2Rs in tuft and endocrine cells in the gut.

BACKGROUND AND AIMS: Although oral berberine, a natural compound extracted from the Chinese herbal medicine curcumin, has low bioavailability, it is still effective in suppressing obesity; however, the underlying mechanism is unclear. Berberine can bind to bitter-taste receptors (TAS2Rs) in intestinal endocrine secretin tumor (STC-1) cells to promote glucagon-like peptide-1 (GLP-1) secretion. Notably, TAS2Rs also exist in the tuft cells of the gut. Therefore, this study aimed to explore whether the beneficial effect of oral berberine on obesity is dependent on bitter-taste signaling in the tuft cells of the gut. METHODS AND RESULTS: Standard chow diet (SCD) or high-fat diet (HFD) was administered to C57BL/6 mice, with or without berberine (100 mg/kg, 200 mg/kg, p. o.). The PLCß2 inhibitor U73122 was used to verify whether the anti-obesity effect of berberine was dependent on the bitter-taste signaling pathway. In this study, we observed that the oral administration of berberine alleviated HFD-induced obesity in mice that U73122 partially inhibited. Both in vivo and ex vivo, berberine upregulated the release of GLP-1, promoted the proliferation of tuft cells and secretion of IL-25 in obesity via the TAS2R signaling pathway. CONCLUSIONS: Oral berberine ameliorated HFD-induced obesity through the TAS2R-IL-25 signaling pathway in tuft cells in the gut. SIGNIFICANCE: We identified and functionally characterized the TAS2Rs and Gα-gustducin/Gß1γ13 signaling pathway utilized by tuft cells in response to oral berberine in obese mice and proposed a new mechanism underlying the anti-obesity effect of berberine.

Ficus hirta Vahl. Ameliorates Nonalcoholic Fatty Liver Disease through Regulating Lipid Metabolism and Gut Microbiota.

Nonalcoholic fatty liver disease (NAFLD) has gradually become one of the most serious liver diseases threatening human health in the world. Currently, Chinese herbal medicine is a potentially important treatment option for NAFLD, and the development of effective Chinese herbal medicine has a good prospect. Previous studies have suggested that Ficus hirta Vahl. (FV) has various protective effects on the liver. In this study, we investigated the therapeutic outcomes of FV treatment for the liver disease and its underlying mechanism using HepG2 cell lines induced by palmitate (PA) and mouse model fed with high-fat diet (HFD). FV mainly exerts pharmacological effects by mediating lipid metabolism and inflammation. During the lipid metabolism regulation process, CD36, SREBP-1, SCD1, PPAR γ, ACOX1, and CPT1α are the key factors related to the healing effects of FV on NAFLD. During the inflammation process, the downregulation of IL-6, IL-1ß, and TNF-α is involved in alleviation of NAFLD. Furthermore, CD36 overexpression promotes lipid abnormal metabolism and inflammation in PA-induced HepG2 cells, while CD36 knockdown and FV supplementation reverse these responses. In addition, FV also modulates gut microbiota composition, such as Allobaculum, Faecalibaculum, and Butyricicoccus in HFD-fed mice. In summary, our findings demonstrated that FV exerted a beneficial preventive and therapeutic effect on NAFLD by improving lipid metabolism and inflammation as well as regulating the structure of gut microbiota, and therefore, FV may be a candidate for the treatment of NAFLD.

Metabolomic Mechanisms of Radix Fici Hirtae against Carbon Tetrachloride-Induced Acute Liver Damage in Mice.

Background: Radix Fici Hirtae (RFH), known as Cantonese ginseng, is an alternative folk medicine that is widely used to treat various diseases in southern China. The aim of this study was to investigate the effect and metabolic mechanisms of pretreatment with RFH on the serum metabolic profiles of carbon tetrachloride (CCl4) induced acute liver injury in mice. Methods: Mice fed with the water extract of RFH at a dose of 1.5 g/kg and 0.75 g/kg for consecutive 7 days, and then serum samples were taken for the metabolomic analysis. Furthermore, the bioinformatics and pathways analysis were measured. Results: The UHPLC-Orbitrap/MS based-metabolomic analysis identified 20 differential metabolic markers in serum of CCl4-induced liver injury mice compared to that of the normal controls, which were mainly related to the metabolism of amino acids and fatty acids. Furthermore, most of these biomarkers contributing to CCl4 induction were ameliorated by RFH, and the bioinformatics and pathways analysis revealed that therapeutic actions of RFH were mainly involved in the regulation of the oxidative stress responses and energy homeostasis. Conclusion: These findings provide potential metabolic mechanism for future study and allow for hypothesis generation about the hepatoprotective effects of Radix Fici Hirtae.

Assessment of evidence on reported non-genetic risk factors of congenital heart defects: the updated umbrella review.

BACKGROUND: Congenital heart defect (CHD) is the leading cause of birth defects globally, which results in a great disease burden. It is still imperative to detect the risk factors of CHD. This umbrella review aimed to comprehensively summarize the evidence and grade the evidence of the associations between non-genetic risk factors and CHD. METHODS: Databases including Medline, Embase, Web of Science, Cochrane Library, and four Chinese databases were searched from inception to 18 Jan 2022. The reference lists of systematic reviews (SR) and meta-analyses (MA) were screened, which aimed to explore the non-genetic risk factors of CHD. Subsequently, titles and abstracts of identified records and full texts of selected SR/MA were screened by two independent reviewers based on predefined eligibility criteria. A priori developed extraction form was used to abstract relative data following the PRISMA 2020 and MOOSE guidelines. The risk of bias was assessed with the AMSTAR2 instrument. Data were synthesized using fixed-effects and random-effects meta-analyses, respectively. Finally, the evidence on the association of non-genetic risk factors and CHD was graded using Ioannidis's five-class evidence grade. RESULTS: A total of 56 SRs, encompassing 369 MAs, were identified. The risk factors included relative factors on air pollution, reproductive-related factors, parental age and BMI, parental life habits, working and dwelling environment, maternal drug exposure, and maternal disease. Based on AMSTAR2 criteria, only 16% (9/56) of SRs were classified as "Moderate". One hundred and two traceable positive association MAs involving 949 component individual studies were included in further analysis and grading of evidence. Family genetic history, number of abortions, maternal obesity, especially moderate or severe obesity, decoration materials, harmful chemicals, noise during pregnancy, folic acid supplementation, SSRIs, SNRIs, any antidepressants in the first trimester, maternal DM (including both PGDM and GDM), and gestational hypertension were convincing and highly suggestive factors for CHD. After sensitivity analyses based on cohort studies, some grades of evidence changed. CONCLUSION: The present umbrella review will provide evidence-based information for women of childbearing age before or during pregnancy to prevent CHD. In addition, sensitivity analysis based on cohort studies showed the changed evidence levels. Therefore, future SR/MA should concern the sensitivity analysis based on prospective birth cohort studies and case-control studies.

D-Lactic acid production from agricultural residues by membrane integrated continuous fermentation coupled with B vitamin supplementation.

BACKGROUND: D-Lactic acid played an important role in the establishment of PLA as a substitute for petrochemical plastics. But, so far, the D-lactic acid production was limited in only pilot scale, which was definitely unable to meet the fast growing market demand. To achieve industrial scale D-lactic acid production, the cost-associated problems such as high-cost feedstock, expensive nutrient sources and fermentation technology need to be resolved to establish an economical fermentation process. RESULTS: In the present study, the combined effect of B vitamin supplementation and membrane integrated continuous fermentation on D-lactic acid production from agricultural lignocellulosic biomass by Lactobacillus delbrueckii was investigated. The results indicated the specific addition of vitamins B1, B2, B3 and B5 (VB1, VB2, VB3 and VB5) could reduce the yeast extract (YE) addition from 10 to 3 g/l without obvious influence on fermentation efficiency. By employing cell recycling system in 350 h continuous fermentation with B vitamin supplementation, YE addition was further reduced to 0.5 g/l, which resulted in nutrient source cost reduction of 86%. A maximum D-lactate productivity of 18.56 g/l/h and optical purity of 99.5% were achieved and higher than most recent reports. CONCLUSION: These findings suggested the novel fermentation strategy proposed could effectively reduce the production cost and improve fermentation efficiency, thus exhibiting great potential in promoting industrial scale D-lactic acid production from lignocellulosic biomass.

Therapeutic potential of fucoidan in the reduction of hepatic pathology in murine schistosomiasis japonica.

BACKGROUND: Hepatic granuloma formation and fibrosis as the consequence of tissue entrapped eggs produced by female schistosomes characterize the pathology of Schistosoma japonicum infection. It has been proposed that fucoidan, a sulfated polysaccharide existing naturally in brown seaweed Fucus vesiculosus, plays a diversified role to perform immunomodulatory activities. However, whether fucoidan functions in the host hepatic pathology is unknown and identifying the potential mechanism that is responsible for hepatic improvement is still necessary. METHODS: We evaluated the hepatic pathology from S. japonicum-infected mice after treatment with fucoidan. qRT-PCR and immunofluorescence were used to detect the pro- or anti-inflammatory factors and the phosphorylated p65 in the livers. In addition, flow cytometry was also performed to investigate the T cell subsets in the S. japonicum-infected mice after treatment with fucoidan, and functional molecules relatively specific to Treg cells were detected in vitro. Furthermore, macrophages were treated with fucoidan in vitro and to detect the inflammatory cytokines. RESULTS: Treatment with fucoidan significantly reduced the hepatic granuloma size and fibrosis response during S. japonicum infection. The attenuated phospho-p65 protein levels and the mRNA levels of pro-inflammatory cytokines (IL-6, IL-12 and TNF-α) were observed in the livers from fucoidan-treated S. japonicum-infected mice; however, the mRNA levels of anti-inflammatory cytokines (IL-4 and IL-13) were increased. In addition, the infiltration of Treg cells was significantly enhanced both in the livers and spleens from fucoidan-treated S. japonicum-infected mice. Consistent with this, the mRNA levels of IL-10 and TGF-ß were dramatically increased in the livers from S. japonicum-infected mice after fucoidan treatment. Furthermore, in vitro stimulated splenocytes with fucoidan resulted in increasing Treg cells in splenocytes as well as the functional expression of CC chemokine receptor type 4 (CCR4) and CXC chemokine receptor type 5 (CXCR5) in Treg cells. Additionally, fucoidan promoted the mRNA levels of IL-4 and IL-13 in macrophages. CONCLUSIONS: These findings suggest an important role of natural fucoidan in reducing hepatic pathology in the progress of S. japonicum infection with a stronger Treg response, which may reveal a new potential therapeutic strategy for hepatic disease caused by parasitic chronic infection.