A Mechanism for the Treatment of Cardiovascular and Renal Disease: TRPV1 and TRPA1.

ABSTRACT: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality globally. CVD and kidney disease are closely related, with kidney injury increasing CVD mortality. The pathogenesis of cardiovascular and renal diseases involves complex and diverse interactions between multiple extracellular and intracellular signaling molecules, among which transient receptor potential vanilloid 1 (TRPV1)/transient receptor potential ankyrin 1 (TRPA1) channels have received increasing attention. TRPV1 belongs to the vanilloid receptor subtype family of transient receptor potential ion channels, and TRPA1 belongs to the transient receptor potential channel superfamily. TRPV1/TRPA1 are jointly involved in the management of cardiovascular and renal diseases and play important roles in regulating vascular tension, promoting angiogenesis, antifibrosis, anti-inflammation, and antioxidation. The mechanism of TRPV1/TRPA1 is mainly related to regulation of intracellular calcium influx and release of nitric oxide and calcitonin gene-related peptide. Therefore, this study takes the TRPV1/TRPA1 channel as the research object, analyzes and summarizes the process and mechanism of TRPV1/TRPA1 affecting cardiovascular and renal diseases, and lays a foundation for the treatment of cardiorenal diseases.

Da-Jian-Zhong decoction alleviates diarrhea-predominant irritable bowel syndrome via modulation of gut microbiota and Th17/Treg balance.

ETHNOPHARMACOLOGICAL RELEVANCE: Da-Jian-Zhong decoction (DJZD) is a herbal formula clinically used for abdominal pain and diarrhea induced by spleen-Yang deficiency syndrome. Recently, treatment of diarrhea-predominant irritable bowel syndrome (IBS-D) with DJZD has received increasing attention, but the underlying mechanism of action remains elusive. AIM OF THE STUDY: We aimed to evaluate the therapeutic effect of DJZD on IBS-D rats and to elucidate the underlying mechanisms. MATERIALS AND METHODS: An IBS-D rats model was constructed using a two-factor superposition method of neonatal maternal separation and Senna folium aqueous extract lavage. Moreover, the effect of DJZD was evaluated based on the body weight, rectal temperature, abdominal withdrawal reflex (AWR), and Bristol stool scale score (BSS). The factors that regulate the DJZD effects on IBS-D were estimated using whole microbial genome, transcriptome sequencing (RNA-Seq), flow cytometry, and quantitative reverse transcription polymerase chain reaction (RT-qPCR) analyses. RESULTS: We found that DJZD alleviated the symptoms of IBS-D rats, with the low-dose (2.4 g/kg) as the better ones, as shown by the higher body weight and lower AWR score and BSS. At the phylum level, the relative abundance of Bacteroidetes was obviously increased, and at the genus level, Lactobacillus and Parabacteroides were increased, while that of Firmicutes_bacterium_424 and Ruminococcus gnavus was decreased in DJZD group. Furthermore, the significantly enriched GO terms after treatment with DJZD mainly included the immune response, positive regulation of activated T cell proliferation, and positive regulation of interleukin-17 (IL-17) production. Importantly, flow cytometry analysis further revealed that the T helper cell type 17/regulatory T cell (Th17/Treg) balance contributed to the DJZD-induced alleviation of IBS-D symptoms, as DJZD downregulated Th17/Treg ratio and Th17 cell-related cytokines IL-17 and IL-6 levels in the colon. CONCLUSIONS: These results demonstrated that DJZD has a good therapeutic effect on IBS-D rats, probably by maintaining the homeostasis of gut microbiota and regulating Th17/Treg balance and its related inflammatory factors.

Meta-Analysis of Clinical Efficacy and Safety of Tripterygium wilfordii Polyglycosides Tablets in the Treatment of Chronic Kidney Disease.

OBJECTIVE: Tripterygium wilfordii polyglycosides tablet (TGt) is an oral preparation extracted from plant Tripterygium wilfordii. It has the effects of anti-inflammation and inhibition of cellular and humoral immunity. However, many reports of adverse reactions caused by TGt have limited its application. In this paper, the clinical efficacy and safety of TGt in the treatment of chronic kidney disease (CKD) were verified by data mining and analysis, so as to provide theoretical data support for the application and development of TGt. METHODS: A computer search of the following databases was conducted: PubMed, Web of Science, CBM, VIP, Wanfang Data, and CNKI. The search time limit is from the establishment of the database to September 2020. We searched for clinical randomized controlled trials of TGt in the treatment of CKD. The main types of CKD involved are nephrotic syndrome (NS), primary nephrotic syndrome (PNS), refractory nephrotic syndrome (RNS), and IgA nephropathy (IgAN). RevMan 5.2 and Stata 12.0 software were used to evaluate the literature quality and analyze the data. Finally, GRADEpro software was used to evaluate the quality of evidence. RESULTS: According to the inclusion and exclusion criteria, 75 articles with a total of 6418 subjects were included. The results of the meta-analysis showed that TGt could reduce 24-hour urinary protein, increase serum albumin, improve clinical efficacy, and reduce disease recurrence rate in patients (P < 0.05) with CKD compared with adrenocortical hormones or immunosuppressants. TGt could significantly reduce the level of serum creatinine (Scr) in patients with CKD (P < 0.05), but it was not significant in reducing the level of blood urea nitrogen (P > 0.05). In terms of safety evaluation, in patients with CKD, it could significantly reduce the incidence of gastrointestinal adverse reactions and neurogenic dizziness and headache (P < 0.05). However, in terms of adverse reactions such as liver injury, respiratory infection, and leukopenia, TGt was as harmful as corticosteroids or immunosuppressants (P < 0.05). The quality of the evidence was evaluated with GRADEpro software, and the results showed that TGt was strongly recommended for the treatment of CKD. CONCLUSION: TGt has certain efficacy in the treatment of CKD and has fewer side effects in certain types of diseases. The effect of TGt combined with other drugs is better than that of single use. This paper also has some limitations. Due to the limited number of the included studies, with all being from China, there may be methodological differences. Therefore, more high-quality literature data from different countries are needed.

Meta-Analysis of Randomized Controlled Trials of Xueshuantong Injection in Prevention of Deep Venous Thrombosis of Lower Extremity after Orthopedic Surgery.

OBJECTIVE: To systematically evaluate the clinical efficacy of Xueshuantong injection (Panax notoginseng saponins) in preventing deep venous thrombosis (DVT) of lower extremity after orthopedic surgery. METHODS: The randomized controlled trials (RCTs) of Xueshuantong injection in prevention of lower extremity DVT after orthopedic surgery were retrieved from CNKI, Wanfang database, VIP, PubMed, and Cochrane Library by August 2020. Revman5.2 was used to analyze the results. RESULTS: A total of 20 articles including 2336 patients were included. The results of meta-analysis showed that the incidence of DVT in the experimental group was lower than that in the control group; after operation, the D-dimer (Ddimer), thrombin time (APTT), and prothrombin time (PT) in the experimental group were significantly improved compared with those in the control group, and the difference between the two groups was statistically significant. CONCLUSION: Xueshuantong injection can effectively prevent the formation of lower extremity DVT after orthopedic surgery and antagonize the postoperative hypercoagulable state of blood, which has high clinical value.

Meta-Analysis of the Therapeutic Effect of Shenqi Jiangtang Granule on Type 2 Diabetes Mellitus.

OBJECTIVE: To systematically evaluate the effectiveness of Shenqi Jiangtang granule (SQJT) in the treatment of type 2 diabetes. METHODS: We searched CNKI, Wanfang Data, VIP, and PubMed databases to collect randomized controlled trials (RCT) of Shenqi Jiangtang granules in the treatment of type 2 diabetes. The search time was from January 2014 to the present. Data were extracted, and quality was evaluated. Metadata analysis of the extracted data was carried out using RevMa5.2 software. The final results are expressed in relative risk (RR), mean difference (MD), and 95% CI. RESULTS: This study included a total of 13 studies, 1160 subjects. Meta-analysis results showed that the test group was better than the control group (RR = 1.26, 95% CI 1.18-1.34, P < 0.00001). The fasting blood glucose, postprandial blood glucose, and glycated hemoglobin of the test group were also significantly better than those of the control group. CONCLUSION: Shenqi Jiangtang granules have a certain clinical effect and low adverse reaction rate for the treatment or adjuvant treatment of type 2 diabetes. At present, the drug has been widely used in clinical practice, but a large number of large-sample clinical trials are needed to further verify its specific efficacy and safety.