Diabetic kidney disease (DKD) is a common complication of diabetes and has become the leading cause of end-stage kidney disease. The pathogenesis of DKD is complicated, and oxidative stress is considered as a core of DKD onset. High glucose can lead to increased production of reactive oxygen species (ROS) via the polyol, PKC, AGE/RAGE and hexosamine pathways, resulting in enhanced oxidative stress response. In this way, pathways such as PI3K/Akt, TGF-β1/p38-MAPK and NF-κB are activated, inducing endothelial cell apoptosis, inflammation, autophagy and fibrosis that cause histologic and functional abnormalities of the kidney and finally result in kidney injury. Presently, the treatment for DKD remains an unresolved issue. Traditional Chinese medicine (TCM) has unique advantages for DKD prevention and treatment attributed to its multi-target, multi-component, and multi-pathway characteristics. Numerous studies have proved that Chinese herbs (e.g., Golden Thread, Kudzuvine Root, Tripterygium glycosides, and Ginseng) and patent medicines (e.g., Shenshuaining Tablet, Compound Rhizoma Coptidis Capsule, and Zishen Tongluo Granule) are effective for DKD treatment. The present review described the role of oxidative stress in DKD pathogenesis and the effect of TCM intervention for DKD prevention and treatment, in an attempt to provide evidence for clinical practice.

Cholestasis is a clinical condition resulting from impaired bile flow. Currently, patients with cholestasis face several barriers in seeking diagnosis and treatment. Zhuyu Pill (ZYP) is an ancient classic formula of the Coptis-Evodia herb couples (CEHC), and has been used for cholestasis treatment in the clinic, however, its underlying biological activity in cholestasis remain to be clarified. In this study, an α-naphthyl-isothiocyanate (ANIT, 50 mg/kg)-induced rat model of cholestasis was treated with ZYP. Serum biochemical indices and histopathological evaluation was performed, together with the metabolomics analyses of feces and 16S rDNA sequencing of the fecal microbiota. We evaluated the anti-cholestatic activity of ZYP and investigated the mechanisms underlying its correlation with fecal microbiota and fecal metabolite regulation. The relationships between biochemical indices and changes in gene expression associated with liver injury, levels fecal metabolites, and composition of fecal microbiota were analyzed. The results showed that both high (1.2 g/kg) and low (0.6 g/kg) doses of ZYP could effectively improve biochemical parameters in the blood of cholestasis-induced rat models; the intervention effect of high dose ZYP was superior to that that of lower dose ZYP. Based on a metabolomics test of fecal samples, significantly altered metabolites in the ANIT and ZYP treatment group were identified. In total, 734 metabolites were differentially expressed, and whose biological functions were mainly associated with amino acid metabolism, steroid hormone biosynthesis, and bile secretion. In addition, sequencing of the 16S rDNA unit in fecal samples revealed that the ZYP could improve the fecal microbiota dysbiosis that ANIT had induced. Therefore, we conclude that ANIT altering of blood biochemical and metabolic profiles and of fecal microbiota could effectively be alleviated with ZYP treatment. This study contributes to the “TCM wisdom” applied in clinical diagnosis and treatment of cholestasis.

Nonalcoholic fatty liver disease (NAFLD) is considered to be a manifestation of hepatic metabolic syndrome. Some studies on the pathogenesis of NAFLD by targeting gut microbiota have attracted wide attention. Previous studies have demonstrated the positive effects of berberine and evodiamine on metabolic diseases and gut microbiota dysbiosis. However, it is not known whether the combination of berberine and evodiamine (BE) can prevent the development of high-fat diet (HFD)-induced NAFLD. Therefore, we aimed to explore the protective effects of BE on the development of HFD-induced NAFLD from the perspective of the gut microbiota. Gut microbiota profiles were established by high throughput sequencing of the bacterial 16S ribosomal RNA gene. The effects of BE on liver and intestinal tissue, intestinal barrier integrity, and hepatic inflammation were also investigated. The results showed that the abundance and diversity of gut microbiota were enriched by BE treatment, with an increase in beneficial bacteria, such as Lactobacillus, Ruminococcus, and Prevotella, and a decrease in pathogenic bacteria such as Fusobacterium and Lachnospira. In addition, BE effectively improved liver fat accumulation and tissue damage, inhibited the apoptosis of intestinal epithelial cells, increased the contents of intestinal tight junction proteins, and decreased the expression of pro-inflammatory factors. Consequently, BE treatment could be an effective and alternative strategy for alleviating NAFLD by modulating gut microbiota and safeguarding the intestinal barrier.

Aim. The prevalenceof nonalcoholic fatty liver disease (NAFLD)is increasing worldwide, but there are currently limited treatmentoptions available. Therefore, it is necessary to research new treatmentstrategies. Zhuyu Pill (ZYP) is a well-known herbal recipe consistingof Huanglian (Coptidis rhizoma) and Wuzhuyu (Evodiae Fructus) thathas been clinically used to treat NAFLD. This study aimed to investigatethe impact of ZYP on NAFLD induced by a high-fat diet (HFD) and toidentify its potential mechanism. Methods. In this investigation,we used ZYP to treat a mouse model of NAFLD induced by an HFD. Weconducted various analyses including assessment of serum biochemicalindices, histological evaluation, fecal metabonomics analysis, westernblot, and quantitative real-time polymerase chain reaction. Results.ZYP effectively improved blood lipid levels and reduced inflammatoryresponse in HFD mice, while also alleviating liver cell damage andlipid accumulation. Additionally, ZYP influenced the fecal bile acid(BA) metabolism profiles of HFD mice by inhibiting the signal transductionof ileal farnesoid X receptor (FXR) fibroblast growth factor 15 (FGF15),enhancing the expression of cytochrome P450 family 7 subfamily A member1(CYP7A1), promoting BA synthesis and increasing the metabolic eliminationof cholesterol. Conclusion. ZYP shows promise as a potential treatmentfor alleviating NAFLD by modulating BA metabolism through the FXR-FGF15-CYP7A1pathway.

This study aimed to identify potential pharmacological targets of triptolide regulating the tumor microenvironment (TME) of stomach adenocarcinoma (STAD) patients. A total of 343 STAD cases from The Cancer Genome Atlas (TCGA) were assigned into high- or low-score groups applying Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE). Hub genes were identified from differentially expressed genes (DEGs) shared by stromal- and immune-related components in the TME of STAD patients using R software. Cox regression analysis was used to identify genes significantly correlated with STAD patient survival. Triptolide target genes were predicted from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Top 30 genes filtered by Cytohubba from 734 DEGs were screened as hub genes. Forty-two genes were found to be at high risk for STAD prognosis. Thirty-four targets of triptolide were predicted using the TCMSP database. Importantly, C-X-C chemokine receptor type 4 (CXCR4) was identified as a potential target of triptolide associated with the TME in STAD. Analysis of survival highlighted the association between CXCR4 upregulation with STAD progression and poor prognosis. Gene Set Enrichment Analysis (GSEA) confirmed that genes in the CXCR4- upregulated group had significant enrichment in immune-linked pathways. Additionally, triptolide targets were found to be significantly enriched in CXCR4-related chemokine and cancer-related p53 signaling pathways. Molecular docking demonstrated a high affinity between triptolide and CXCR4. In conclusion, CXCR4 may be a therapeutic target of triptolide in the treatment of STAD patients by modulating the TME. Graphical Abstract

Chronic obstructive pulmonary disease (COPD) is a severe condition that leads to premature mortality and places a significant financial burden on healthcare systems. An adjunctive therapy in COPD includes the simultaneous administration of astragalus injection and ambroxol hydrochloride. Despite its widespread use, the effectiveness of this combined approach in COPD treatment has not been systematically evaluated. Thus, we conducted a systematic review and meta-analysis to assess the efficacy of combining astragalus injection with ambroxol hydrochloride as an adjuvant treatment for COPD. Six electronic databases were used to search for relevant randomized controlled trials, and data analysis was conducted using Review Manager 5.4. A total of 14 randomized controlled trials were included, involving 1070 patients who met the criteria. The results of the meta-analysis indicated that the combination of astragalus injection with ambroxol hydrochloride as an adjuvant treatment can improve various clinical parameters in patients with COPD compared to conventional treatment alone. These parameters include the clinical effective rate (OR = 5.44, 95% CI 3.51–8.43, I² = 0%), partial pressure of oxygen in artery (MD = 1.12, 95% CI 0.87–1.36, I² = 5%), partial pressure of carbon dioxide in artery (MD = − 1.43, 95% CI − 1.65 to − 1.21, I² = 0%), forced expiratory volume in one second (MD = 0.30, 95% CI 0.18–0.42, I² = 0%), percentage of forced expiratory volume in one second (MD = 16.18, 95% CI 12.60–19.76, I² = 82%), forced vital capacity (MD = 0.33, 95% CI 0.21–0.45, I² = 36%), hemoglobin (MD = − 16.17, 95% CI − 20.84 to − 11.51, I² = 29%), and the ratio of forced expiratory volume in one second to forced vital capacity (MD = 2.51, 95% CI − 0.05 to 5.06, I² = 0%). The combination of astragalus injection and ambroxol hydrochloride could be a selection of COPD patients as an adjuvant treatment. However, further validation is required to evaluate the effectiveness of combining astragalus injection and ambroxol hydrochloride as an adjunctive treatment for patients with COPD.