Objective. Rhizoma Coptidis is an herb that has been frequently used in many traditional formulas for the treatment of diabetic mellitus (DM) over thousands of years. Berberine, the main active component of Rhizoma Coptidis, has been demonstrated to have the potential effect of hypoglycemia. To determine the potential advantages of berberine for diabetic care, we conducted this systematic review and meta-analysis to examine the efficacy and safety of berberine in the treatment of patients with type 2 DM. Methods. Eight databases including PubMed, Embase, Web of Science, the Cochrane library, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Database (SinoMed), Wanfang Database, and Chinese VIP Information was searched for randomized controlled trials (RCTs) reporting clinical data regarding the use of berberine for the treatment of DM. Publication qualities were also considered to augment the credibility of the evidence. Glycemic metabolisms were the main factors studied, including glycosylated hemoglobin (HbA1c), fasting plasm glucose (FPG), and 2-hour postprandial blood glucose (2hPG). Insulin resistance was estimated by fasting blood insulin (FINS), homeostasis model assessment-insulin resistance (HOMA-IR), and body mass index (BMI). Lipid profiles were also assessed, including triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), along with inflammation factors such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Serum creatinine (Scr), blood urea nitrogen (BUN), and adverse events were applied to evaluate the safety of berberine. Results. Forty-six trials were assessed. Analysis of berberine applied alone or with standard diabetic therapies versus the control group revealed significant reductions in HbA1c ( MD = − 0.73 ; 95% CI (−0.97, −0.51)), FPG ( MD = − 0.86 , 95% CI (−1.10, −0.62)), and 2hPG ( MD = − 1.26 , 95% CI (−1.64, −0.89)). Improved insulin resistance was assessed by lowering FINS ( MD = − 2.05 , 95% CI (−2.62, −1.48)), HOMA-IR ( MD = − 0.71 , 95% CI (−1.03, −0.39)), and BMI ( MD = − 1.07 , 95% CI (−1.76, −0.37)). Lipid metabolisms were also ameliorated via the reduction of TG ( MD = − 0.5 , 95% CI (−0.61, −0.39)), TC ( MD = 0.64 , 95% CI (−0.78, −0.49)), and LDL ( MD = 0.86 , 95% CI (−1.06, −0.65)) and the upregulation of HDL ( MD = 0.17 , 95% CI (0.09, 0.25)). Additionally, berberine improved the inflammation factor. Conclusion. There is strong evidence supporting the clinical efficacy and safety of berberine in the treatment of DM, especially as an adjunctive therapy. In the future, this may be used to guide targeted clinical use of berberine and the development of medications seeking to treat patients with T2DM and dyslipidemia.

Hypertensive renal injury is a complication of hypertension. Cordyceps cicadae (C. cicadae) is a traditional Chinese medicine used to treat chronic kidney diseases especially renal fibrosis. Autophagy is described as a cell self-renewal process that requires lysosomal degradation and is utilized for the maintenance of cellular energy homeostasis. The present study explores the mechanism underlying C. cicadae’s renoprotection on hypertensive nephropathy (HN). First, HN rat models were established on spontaneously hypertensive rats (SHRs). The expression of fibrosis-related protein and autophagy-associated protein was detected in vivo. NRK-52E cells exposed to AngII were chosen to observe the potential health benefits of C. cicadae on renal damage. The level of extracellular matrix accumulation was detected using capillary electrophoresis immunoquantification and immunohistochemistry. After treatment with lysosomal inhibitors (chloroquine) or an autophagy activator (rapamycin), the expression of Beclin-1, LC3II, and SQSTM1/p62 was further investigated. The study also investigated the change in sirtuin1 (SIRT1), fork head box O3a (FOXO3a), and peroxidation (superoxide dismutase (SOD) and malondialdehyde (MDA)) expression when intervened by resveratrol. The changes in SIRT1 and FOXO3a were measured in patients and the SHRs. Here, we observed that C. cicadae significantly decreased damage to renal tubular epithelial cells and TGFβ1, α-smooth muscle actin (α-SMA), collagen I (Col-1), and fibronectin expression. Meanwhile, autophagy defects were observed both in vivo and in vitro. C. cicadae intervention significantly downregulated Beclin-1 and LC3II and decreased SQSTM1/p62, showing an inhibition of autophagic vesicles and the alleviation of autophagy stress. These functions were suppressed by rapamycin, and the results were just as effective as the resveratrol treatment. HN patients and the SHRs exhibited decreased levels of SIRT1 and FOXO3a. We also observed a positive correlation between SIRT1/FOXO3a and antifibrotic effects. Similar to the resveratrol group, the expression of SIRT1/FOXO3a and oxidative stress were elevated by C. cicadae in vivo. Taken together, our findings show that C. cicadae ameliorates tubulointerstitial fibrosis and delays HN progression. Renoprotection was likely attributable to the regulation of autophagic stress mediated by the SIRT1 pathway and achieved by regulating FOXO3a and oxidative stress.

Membranous nephropathy (MN) is an organ-restricted autoimmune disease mainly caused by circulating autoantibodies against podocyte antigens, including the M-type phospholipase A2 receptor (PLA2R) and thrombospondin domain-containing 7A (THSD7A). Antibodies against PLA2R are present in 70%–80% and against THSD7A in 2% of adult patients, which provides a paradigm shift in molecular diagnosis and management monitoring. Both antigens share some similar characteristics: they are expressed by podocytes and have wide tissue distributions; they are bound by autoantibodies only under nonreducing conditions, and the subtype of most autoantibodies is IgG4. However, the factors triggering autoantibody production as well as the association among air pollution, malignancy, and the pathogenesis of MN remain unclear. In this review, we discuss the similarity between the pathological mechanisms triggered by disparate antigens and their associated diseases. Furthermore, we demonstrated the possibility that PM2.5, malignancy, and gene expression specifically induce exposure of these antigens through conformational changes, molecular mimicry, or increased expression eliciting autoimmune responses. Thus, this review provides novel insights into the pathological mechanism of MN.

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Haikun Shenxi capsule was widely used for patients with chronic kidney disease (CKD) stages 3-5. This study aimed to systematically evaluate the efficacy and adverse effects of the Haikun Shenxi capsule in the treatment of patients with CKD stages 3-5 (nondialysis-dependent) and provide a reference for clinical application. The Cochrane Library, PubMed, EMBASE, Web of Science, Chinese National Knowledge Infrastructure (CNKI), Wanfang Database, Chongqing VIP Database, and SinoMed Database were searched for randomized-controlled trials applying Haikun Shenxi capsule to treat CKD from their inception date to February 2022. Data extraction and quality assessment were assigned to two researchers, respectively. The risk of bias was assessed by the Cochrane handbook, and Revman5.3 was used for data statistics and analysis. Heterogeneity tests were conducted, and the mean difference (MD) or relative risk (RR) with a 95% confidence interval (95% CI) of the outcomes was presented. Eight randomized controlled trials with 522 patients diagnosed with CKD stages 3-5 (nondialysis-dependent) treated with Haikun Shenxi capsules were included. Compared with the control group, the Haikun Shenxi capsule group showed lower levels of serum creatinine (Scr; MD = -61.14, 95% CI = -68.13 to -54.16, P < 0.00001) and blood urea nitrogen (BUN; MD = -4.21, 95% CI = -5.59 to -2.84, P < 0.00001) and higher creatinine clearance (Ccr; MD = 3.94, 95% CI = 1.47 to 6.42, P = 0.002). No drug-related adverse effects of Haikun Shenxi were found in these studies. The Haikun Shenxi capsule could reduce Scr and BUN levels and increase the Ccr level, thereby improving renal functions of CKD stages 3-5 (nondialysis-dependent) patients without drug-related adverse effects based on conventional therapy.

Diabetic kidney disease (DKD), a severe and common microvascular complication of diabetes mellitus, has become a major cause of end-stage renal disease. Huangkui capsule (HKC) has been widely used to treat DKD. This meta-analysis aimed to provide high-quality evidence for the clinical application of HKC in DKD. The following databases: China National Knowledge Infrastructure, Wanfang Database, Chongqing VIP, SinoMed, Web of Science, EMBASE, PubMed, and The Cochrane Library, were searched for randomized controlled trials using the search theme: "angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) combined with HKC for treatment of DKD" from their inception dates till August 2022. Studies were selected following our inclusion and exclusion criteria, and we extracted the required data. RevMan 5.3 was used for data statistics and analysis. Based on the main components identified by high performance liquid chromatography, the SwissADME, SwissTarget-Prediction, and UniProt databases were used to predict the target genes of HKC. OMIM, DrugBank, GeneCards, and DisGeNet databases were used to predict DKD-related target genes. Venny 2.0 was then used to find the common targets in HKC and DKD. We conducted an HKC-ingredients-targets-DKD network using Cytoscape and a protein-protein interaction (PPI) network using the STRING database. Finally, we performed a Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis using the DAVID database. Exactly 15 studies were included in this meta-analysis. Compared with the control group using ACEI/ARB only, ACEI/ARB combined with HKC was found to significantly lower the urine albumin excretion rate (UAER; standard mean difference [SMD] = -1.