[Effect of Zuogui Jiangtang Qinggan Formula on lipid metabolism in db/db mouse model of type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease].

This study aims to explore the effect of Zuogui Jiangtang Qinggan Formula(ZGJTQGF) on the lipid metabolism in the db/db mouse model of type 2 diabetes mellitus(T2DM) complicated with non-alcoholic fatty liver disease(NAFLD) via the insulin receptor(INSR)/adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)/sterol-regulatory element-binding protein 2(SREBP-2) signaling pathway. Twenty-four db/db mice were randomized into positive drug(metformin, 0.067 g·kg~(-1)) and low-(7.5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) ZGJTQGF groups. Six C57 mice were used as the blank group and administrated with an equal volume of distilled water. The mice in other groups except the blank group were administrated with corresponding drugs by gavage for 6 consecutive weeks. At the end of drug administration, fasting blood glucose(FBG) and blood lipid levels were measured, and oral glucose tolerance test was performed. Compared with the blank group, the mice treated with ZGJTQGF showed decreased body mass and liver weight coefficient, lowered levels of FBG, total cholesterol(TC), triglyceride(TG), and low-density lipoprotein(LDL), and weakened liver function. The pathological changes and lipid accumulation in the liver tissue were examined. Western blot was employed to measure the protein levels of INSR, AMPK, p-AMPK, and SREBP-2. Compared with the blank group, the model group showed down-regulated protein levels of INSR and p-AMPK/AMPK and up-regulated protein level of SREBP-2. Compared with the model group, high-dose ZGJTQGF up-regulated the protein levels of INSR and p-AMPK/AMPK and down-regulated the protein level of SREBP-2. Low-dose ZGJTQGF slightly up-regulated the protein levels of INSR and p-AMPK/AMPK and down-regulated the protein level of SREBP-2, without significant differences. The results suggested that ZGJTQGF may alleviate insulin resistance and improve lipid metabolism in db/db mice by activating the INSR/AMPK/SREBP-2 signaling pathway.

[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.

[Zuogui Jiangtang Qinggan Formula improves glucolipid metabolism in type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease by regulating FoxO1/MTP/APOB signaling pathway].

This study aimed to investigate the effect and mechanism of Zuogui Jiangtang Qinggan Formula(ZGJTQG) on the glucolipid metabolism of type 2 diabetes mellitus(T2DM) complicated with non-alcoholic fatty liver disease(NAFLD). NAFLD was induced by a high-fat diet(HFD) in MKR mice(T2DM mice), and a model of T2DM combined with NAFLD was established. Forty mice were randomly divided into a model group, a metformin group(0.067 g·kg~(-1)), and high-and low-dose ZGJTQG groups(29.64 and 14.82 g·kg~(-1)), with 10 mice in each group. Ten FVB mice of the same age were assigned to the normal group. Serum and liver tissue specimens were collected from mice except for those in the normal and model groups after four weeks of drug administration by gavage, and fasting blood glucose(FBG) and fasting insulin(FINS) levels were measured. The levels of total cholesterol(TC), triglyceride(TG), and low-density lipoprotein(LDL) were detected by the single reagent GPO-PAP method. Very low-density lipoprotein(VLDL) was detected by enzyme-linked immunosorbent assay(ELISA). Alanine aminotransferase(ALT) and aspartate ami-notransferase(AST) were determined by the Reitman-Frankel assay. The pathological changes in the liver were observed by hematoxylin-eosin(HE) staining and oil red O staining. Real-time fluorescence-based quantitative polymerase chain reaction(real-time PCR) and Western blot were adopted to detect the mRNA and protein expression of forkhead transcription factor O1(FoxO1), microsomal triglyceride transfer protein(MTP), and apolipoprotein B(APOB) in the liver. The results showed that high-dose ZGJTQG could signi-ficantly reduce the FBG and FINS levels(P<0.05, P<0.01), improve glucose tolerance and insulin resistance(P<0.05, P<0.01), alleviate the liver damage caused by HFD which was reflected in improving liver steatosis, and reduce the serum levels of TC, TG, LDL, VLDL, ALT, and AST(P<0.05, P<0.01) in T2DM mice combined with NAFLD. The findings also revealed that the mRNA and protein expression of FoxO1, MTP, and APOB in the liver was significantly down-regulated after the intervention of high-dose ZGJTQG(P<0.05, P<0.01). The above study showed that ZGJTQG could effectively improve glucolipid metabolism in T2DM combined with NAFLD, and the mechanism was closely related to the regulation of the FoxO1/MTP/APOB signaling pathway.

Renal protective effects of astragaloside IV, in diabetes mellitus kidney damage animal models: A systematic review, meta-analysis.

Astragaloside IV (ASIV) is the essential active component of astragalus that has diverse biological activities. Previous research has suggested its potentially beneficial effects on diabetic nephropathies. However, its effects and protective mechanism remain unclear. In this study, we conducted a preclinical systematic review to evaluate the efficacy and potential mechanisms of ASIV in reducing kidney damage in diabetes mellitus (DM) models. Studies were searched from nine databases until January 2020. A random-effects model was used to calculate combined standardised mean difference estimates and 95 % confidence intervals. Risk of bias of studies was assessed using the Systematic Review Center for Laboratory Animal Experimentation risk of bias tool 10-item checklist. RevMan 5.3 software was used for statistical analysis. Twenty-three studies involving 562 animals were included in the meta-analysis. Studies quality scores ranged from 2 to 5. The ASIV group induced a marked decrease in serum creatinine (P < 0.00001), blood urea nitrogen (P < 0.00001), 24-h urine protein (P < 0.00001) and pathological score (P < 0.001) compared with the control group. The determined potential mechanisms of ASIV action were relieving oxidative stress, delaying renal fibrosis, anti-apoptosis and anti-inflammatory action. We conclude that ASIV exerts renal protective effects in animals with DM through multiple signalling pathways.

Global status and trends of metabolomics in diabetes: A literature visualization knowledge graph study.

BACKGROUND: Diabetes is a metabolic disease characterized by hyperglycemia, which has increased the global medical burden and is also the main cause of death in most countries. AIM: To understand the knowledge structure of global development status, research focus, and future trend of the relationship between diabetes and metabolomics in the past 20 years. METHODS: The articles about the relationship between diabetes and metabolomics in the Web of Science Core Collection were retrieved from 2002 to October 23, 2023, and the relevant information was analyzed using CiteSpace6.2.2R (CiteSpace), VOSviewer6.1.18 (VOSviewer), and Bibliometrix software under R language. RESULTS: A total of 3123 publications were included from 2002 to 2022. In the past two decades, the number of publications and citations in this field has continued to increase. The United States, China, Germany, the United Kingdom, and other relevant funds, institutions, and authors have significantly contributed to this field. Scientific Reports and PLoS One are the journals with the most publications and the most citations. Through keyword co-occurrence and cluster analysis, the closely related keywords are "insulin resistance", "risk", "obesity", "oxidative stress", "metabolomics", "metabolites" and "biomarkers". Keyword clustering included cardiovascular disease, gut microbiota, metabonomics, diabetic nephropathy, molecular docking, gestational diabetes mellitus, oxidative stress, and insulin resistance. Burst detection analysis of keyword depicted that "Gene", "microbiota", "validation", "kidney disease", "antioxidant activity", "untargeted metabolomics", "management", and "accumulation" are knowledge frontiers in recent years. CONCLUSION: The relationship between metabolomics and diabetes is receiving extensive attention. Diabetic nephropathy, diabetic cardiovascular disease, and kidney disease are key diseases for future research in this field. Gut microbiota, molecular docking, and untargeted metabolomics are key research directions in the future. Antioxidant activity, gene, validation, mass spectrometry, management, and accumulation are at the forefront of knowledge frontiers in this field.

Zuogui Jiangtang Shuxin formula Ameliorates diabetic cardiomyopathy mice via modulating gut-heart axis.

Background: There is growing evidence demonstrating that the gut microbiota plays a crucial role in multiple endocrine disorders, including diabetic cardiomyopathy (DCM). Research shows that the Chinese herb reduces disease occurrence by regulating gut microbiota. Zuogui Jiangtang Shuxin formula (ZGJTSXF), a Chinese medicinal formula, has been clinically used for treatment of DCM for many years. However, there is still no clear understanding of how ZGJTSXF treatment contributes to the prevention and treatment of DCM through its interaction with gut microbiota and metabolism. Methods: In this study, mice models of DCM were established, and ZGJTSXF's therapeutic effects were assessed. Specifically, serum glycolipid, echocardiography, histological staining, myocardial apoptosis rate were assessed. Using 16s rRNA sequencing and high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), we determined the impact of ZGJTSXF on the structure of gut microbiota and content of its metabolite TMAO. The mechanism of ZGJTSXF action on DCM was analyzed using quantitative real-time PCR and western blots. Results: We found that ZGJTSXF significantly ameliorated DCM mice by modulating gut-heart axis: ZGJTSXF administration improved glycolipid levels, heart function, cardiac morphological changes, inhibited cardiomyocytes apoptosis, and regulate the gut microbiota in DCM mice. Specifically, ZGJTSXF treatment reverse the significant changes in the abundance of certain genera closely related to DCM phenotype, including Lactobacillus, Alloprevotella and Alistipes. Furthermore, ZGJTSXF alleviated DCM in mice by blunting TMAO/PERK/FoxO1 signaling pathway genes and proteins. Conclusion: ZGJTSXF administration could ameliorate DCM mice by remodeling gut microbiota structure, reducing serum TMAO generation and suppressing TMAO/PERK/FoxO1 signaling pathway.

Association of FcγRIIA-R/H131 polymorphism and systemic lupus erythematosus lupus nephritis risk: A meta-analysis.

AIM: Previous studies have discussed association of FcγRIIA-R/H131 polymorphism and systemic lupus erythematosus (SLE), lupus nephritis (LN) risk. However, conclusions were inconsistent. METHODS: A meta-analysis was performed in this study with allelic contrast (allele R vs H), additive model (genotype RR vs HH), recessive model (genotype RR vs RH + HH), and dominant model (genotype RR + RH vs HH). RESULTS: A total of 33 studies discussed the correlation between FcγRIIA-R/H131 polymorphism and SLE, involving 5652 SLE patients and 6322 controls. Allele R was significantly related to SLE in the overall population (odds ratio [OR] = 1.238, P < .001), Asian (OR = 1.237, P < .001) and European population (OR = 1.212, P = .012). Additive, recessive and dominant models were correlating with SLE in the overall population (OR = 1.448, P < .001; OR = 1.303, P < .001; OR = 1.310, P < .001), Asian population (OR = 1.640, P = .001; OR = 1.437, P < .001; OR = 1.344, P = .005), respectively. In addition, 22 studies evaluated relation of FcγRIIA-R/H131 polymorphism with LN, involving 2065 patients with LN, and 2023 patients without LN. Results showed that allele R and the other 3 models related to LN susceptibility in the overall population when discussing differences of polymorphism between patients with/without LN. We further compared differences of polymorphism between patients with LN and controls, showing that additive and recessive models related to LN risk in the overall population, Asian, European and North American populations. CONCLUSION: In summary, FcγRIIA-R/H131 polymorphism is associated with SLE and LN.

A review on the efficacy and mechanism of action of Shenkang injection against chronic kidney disease.

Chronic kidney disease (CKD) is one of the most common conditions which significantly increases the risk for serious health outcomes. Epidemiological investigations have shown that CKD has become a serious global health problem. At present, there are no treatments for CKD, thus the need for an effective and safe treatment for this condition. Shenkang Injection (SKI), which is an herbal medication in Chinese Medicine, has been used in the management and treatment of CKD and has achieved favorable therapeutic effects. The purpose of this paper is to review the clinical efficacy, mechanism of action, and safety profile of SKI when used in CKD, and to provide comprehensive potential evidence for its clinical application.