Shenlian (SL) Decoction, a Traditional Chinese Medicine Compound, May Ameliorate Blood Glucose via Mediating the Gut Microbiota in db/db Mice.

Shenlian (SL) decoction is a herbal formula composed of Coptis and ginseng, of which berberine and ginsenoside are the main constituents. Even though SL decoction is widely used in treating diabetes in China, the mechanism of its antidiabetes function still needs further study. Gut microbiota disorder is one of the important factors that cause diabetes. To explore the effect of SL decoction on intestinal microbiota, gut microbiota of mice was analyzed by sequencing the gut bacterial 16S rRNA V3+V4 region and metagenomics. In this study, results demonstrated that SL decoction had a better hypoglycemic effect and ß cell protection effect than either ginseng or Coptis chinensis. Alpha diversity analysis showed that all interventions with ginseng, Coptis, and SL decoction could reverse the increased diversity and richness of gut microbiota in db/db mice. PCoA analysis showed oral SL decoction significantly alters gut microbiota composition in db/db mice. 395 OTUs showed significant differences after SL treatment, of which 37 OTUs enriched by SL decoction showed a significant negative correlation with FBG, and 204 OTUs decreased by SL decoction showed a significant positive correlation with FBG. Results of KEGG analysis and metagenomic sequencing showed that SL decoction could reduce the Prevotellaceae, Rikenellaceae, and Helicobacteraceae, which were related to lipopolysaccharide biosynthesis, riboflavin metabolism, and peroxisome, respectively. It could also upregulate the abundance of Bacteroidaceae, which contributed to the metabolism of starch and sucrose as well as pentose-glucuronate interconversions. In the species level, SL decoction significantly upregulates the relative abundance of Bacteroides_acidifaciens which showed a significant negative correlation with FBG and was reported to be a potential agent for modulating metabolic disorders such as diabetes and obesity. In conclusion, SL decoction was effective in hypoglycemia and its mechanism may be related to regulating gut microbiota via upregulating Bacteroides_acidifaciens.

Probiotics, prebiotics, and synbiotics for the improvement of metabolic profiles in patients with chronic kidney disease: A systematic review and meta-analysis of randomized controlled trials.

This systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to quantify the effects of probiotic, prebiotic, and synbiotic supplementation on biomarkers of inflammation and oxidative stress, as well as lipid profiles among patients with chronic kidney disease (CKD). Electronic databases, including PubMed, the Cochrane Database, and the Web of Science were searched from January 1, 2000, to May 15, 2019. All RCTs that investigated the effect of prebiotics, probiotics, and synbiotics on a circulating (serum and plasma) inflammatory marker (C-reactive protein [CRP]), oxidative stress indicators (malondialdehyde [MDA], glutathione [GSH], and total anti-oxidant capacity [TAC]); and lipid profiles (total cholesterol [TC], triglycerides [TG], low-density lipoprotein cholesterol [LDL-c], and high-density lipoprotein cholesterol [HDL-c]) among patients with CKD were included. Data were pooled and expressed as a standardized mean difference (SMD) with a 95% confidence interval (CI). The protocol for this meta-analysis is registered with PROSPERO; No. CRD42019139090. Thirteen trials that included 671 patients were identified for analysis. The methodological quality varied across studies. Meta-analysis indicated that microbial therapies significantly reduced CRP (SMD, -0.75; 95% CI, -1.03 to -0.47; p = 0.000), MDA (SMD, -1.06; 95% CI, -1.59 to -0.52; p = 0.000), TC (SMD, -0.33; 95% CI, -0.52 to -0.13; p = 0.000), and LDL-c (SMD, -0.44; 95% CI, -0.86 to -0.02; p = 0.000) levels; they also increased the GSH (SMD, 0.44; 95% CI, 0.25 to 0.65; p = 0.000), TAC (SMD, 0.61; 95% CI, 0.07 to 1.15; p = 0.000), and HDL-c (SMD, 0.45; 95% CI, 0.03 to 0.87; p = 0.000) levels in CKD patients, as compared to the placebo groups; however, there was no statistically significant TG concentration among patients with CKD. Subgroup analyses showed that other key factors, such as the duration of intervention, participants' baseline body mass index (BMI), type of intervention, and age, had an effect of microbial therapies on outcomes. This meta-analysis supports the potential use of probiotic, prebiotic, and synbiotic supplements in the improvement of established biomarkers of inflammation and oxidative stress, as well as lipid profiles among patients with CKD, which are well-known cardiovascular risk factors. Further research into these interventions should consider the limitations of our study to explore the effect of long-term administration of these supplements in the CKD population.

Si-Miao-Yong-An (SMYA) Decoction May Protect the Renal Function Through Regulating the Autophagy-Mediated Degradation of Ubiquitinated Protein in an Atherosclerosis Model.

Hyperlipidemia is common, and its renal toxicity has attracted a great deal of attention. Si-miao-yong-an (SMYA) is a famous ancient decoction of traditional Chinese medicine (TCM), which is still widely used in clinical treatment. In this study, we observed and explored its efficacy and mechanism in protecting renal function in an atherosclerosis model. The results showed that the serum, Cr urinal KIM-1, and NGAL were significantly decreased in SMYA group. Although SMYA failed to alleviate the lipid accumulation, decrease p-NFκB, or increase SOD in kidney tissue, the levels of ubiquitinated protein and P62 were decreased in SMYA group. What is more, a higher LC3 II level was observed in the SMYA group. In conclusion, these data indicated that SMYA decoction may protect renal function in hyperlipidemia via regulating the autophagy-mediated degradation of ubiquitinated protein.

Tripterygium and its extracts for diabetic nephropathy: Efficacy and pharmacological mechanisms.

Diabetic nephropathy (DN) is a common but intractable diabetic microvascular complication. Tripterygium, a Chinses herb, has been proven to be effective for DN treatment. In this review, the efficacy and pharmacological mechanism of tripterygium and its extracts on DN is elucidated. Tripterygium and its extracts could effectively reduce urine protein and protect renal function. Its pharmacological mechanism involves anti-inflammation, anti-oxidation, anti-glomerulosclerosis and anti-fibrosis, which is achieved by balancing the Th1/Th2 cells, regulating macrophage infiltration, and regulating the following pathways: p38 MAPK, NF-κB, TGF-ß, Wnt/ß-catenin, Akt and Notch1. Although tripterygium and its extracts may result in some adverse effects, including liver-function damage, gastrointestinal reaction, menstrual disorders, and reproductive problems, they are considered good alternative medicines for DN if used with caution and in the proper manner.

The effect of probiotic and synbiotic supplementation on biomarkers of inflammation and oxidative stress in diabetic patients: A systematic review and meta-analysis of randomized controlled trials.

The role of gut microbiota in the management of diabetes has been shown. Several current trials are investigating the effect of probiotics and prebiotics, which are widely used to modulate intestinal microbiota, on inflammatory factors and biomarkers of oxidative stress in diabetic patients; however, their findings are controversial. The aim of the current meta-analysis was to evaluate the effects of probiotic and synbiotic supplementation on levels of serum high-sensitivity C-reactive protein (hs-CRP) and biomarkers of oxidative stress in diabetic patients. We searched the PubMed, Web of Science, and The Cochrane Library databases from the inception to October 31, 2018. Randomized controlled trials (RCTs) which reported the effect of probiotics or synbiotics on circulating (serum and plasma) inflammatory marker (hs-CRP) and oxidative stress indicators (malondialdehyde [MDA], glutathione [GSH], nitric oxide [NO], and total antioxidant capacity [TAC]) among patients with diabetes were included. Eligible studies were assessed for risk of bias and subjected to qualitative and quantitative synthesis using either fixed- or random-effects models accounting for clinical heterogeneity. Our meta-analysis identified 16 eligible RCTs (n = 1060). The methodological quality varied across these trials. Pooled data from these trials demonstrated that probiotic and synbiotic consumption significantly decreased hs-CRP level (standardized mean difference [SMD]=-0.38; 95% confidence interval [CI]:-0.51,-0.24; P = 0.000) and MDA (SMD=-0.61; 95% CI: -0.89, -0.32; P = 0.000) in diabetic patients compared to those in subjects receiving placebos. In addition, probiotic and symbiotic supplementation was found to increase TAC (SMD = 0.31; 95% CI: 0.09, 0.52; P = 0.006), NO (SMD, 0.62; 95% CI, 0.25 to 0.99; P = 0.001) and GSH (SMD = 0.41; 95% CI: 0.26, 0.55, P = 0.000) levels. The results of this systematic review and meta-analysis suggest that probiotic and synbiotic supplementation may help to improve biomarkers of inflammation and oxidative stress in diabetic patients. Further studies are needed to develop clinical practice guidelines for the management of inflammation and oxidative stress in these patients.

Yiqihuoxue Formula Activates Autophagy and Offers Renoprotection in a Rat Model of Adenine-Induced Kidney Disease.

Chronic kidney disease (CKD) is a worldwide health problem for which effective therapeutic methods are still lacking. Traditional Chinese medicine (TCM) has been indicated as an effective alternative treatment for kidney disease. In this study, a clinically effective therapy, yiqihuoxue (YQHX) formula, was administrated to adenine-induced kidney disease rats for 6 weeks. We found that the adenine rats displayed a significant reduction in renal function as evidenced by the increased levels of serum creatinine (Scr), blood urea nitrogen (BUN), and 24-h urinary albumin level, which were attenuated by the YQHX treatment. The glomerulosclerosis, interstitial fibrosis, arteriolosclerosis, interstitial inflammation, and tubular dilatation were reversed by the YQHX treatment in the adenine rats. Furthermore, the hepatic damage characterized by increased levels of aspartate aminotransferase and alanine aminotransferase and inflammatory cell infiltration was improved by YQHX. In addition, the number of apoptotic cells in the adenine rats was obviously reduced by the YQHX treatment as manifested by the lower expression level of cleaved caspase-3 protein. Moreover, the YQHX treatment downregulated the expression levels of fibronectin, type I collagen, α-smooth muscle actin, and TGF-ß1 in the adenine rats. Furthermore, autophagy was activated by the YQHX treatment, which manifested as an increased LC3-II and Beclin-1 expression levels and a decreased p62 level. In conclusion, the YQHX formula might retard the progression of kidney disease by activating autophagy.

Effect of Qufengtongluo Decoction on PI3K/Akt Signaling Pathway in the Kidney of Type 2 Diabetes Mellitus Rat (GK Rat) with Diabetic Nephropathy.

Qufengtongluo (QFTL) decoction is an effective treatment for diabetic nephropathy (DN). However, the underlying molecular mechanism is still unclear. In this study, we try to investigate whether QFTL decoction acts via inhibiting PI3K/Akt signaling pathway. Twenty-four GK rats were randomly divided into 3 groups: blank group, sham-operated group, and QFTL group. After model establishment, rats in QFTL group were given QFTL decoction by gavage, while the rest were given pure water. During the 8-week intervention, 24 hr urinal protein was measured every 2-3 weeks. After intervention, kidneys were removed for pathological smear, quantitative real-time PCR, and western blotting to detect expression levels of p-PI3K, p-Akt, PTEN, TGF-ß, PI3K mRNA, Akt mRNA, PTEN mRNA, and TGF-ß mRNA. QFTL group showed a slighter degree of renal fibrosis in Masson and PASM staining and a greater reduction of 24 hr urinal protein than blank group. Compared to blank group, expression levels of p-PI3K, p-Akt, PI3K mRNA, and Akt mRNA were lower in QFTL group, while expression levels of PTEN and PTEN mRNA were higher. Besides, TGF-ß was downregulated by QFTL decoction. In conclusion, this study suggests that QFTL decoction might inhibit PI3K/Akt signaling pathway via activating PTEN and inhibiting TGF-ß.

[Synthesis and biological evaluation of novel chalcone aromatic oxygen alkyl acids compounds].

Six novel ligustrazine chalcone aromatic oxygen alkyl acids compounds and two pyridine chalcone aromatic oxygen alkyl acids ester compounds were synthesized according to the traditional Chinese medicine theory removing blood stasis. The structures of target compounds were identified by IR, NMR and ESI-MS. The inhibitory activities of platelet aggregation induced by adenosine diphosphate (ADP) and arachidonic acid(AA) were measured by the liver microsomal incubation method in vitro. Hypolipidemic activities of compounds were tested in vivo for better inhibitory activities of platelet aggregation. Preliminary pharmacological results showed that compounds 7c, 8a and 11 a had potent inhibitory activity against platelet aggregation induced by AA, compounds 7c, 7d, 8a and 11 b showed significant inhibitory activity against platelet aggregation induced by ADP. Compounds 7c and 8a exhibited good hypolipidemic activities in high-fat-diet(HFD) induced hyperlipidemia C57/BL6 mice and worthy for further investigation.