The Combination of Scutellaria baicalensis Georgi and Sophora japonica L. ameliorate Renal Function by Regulating Gut Microbiota in Spontaneously Hypertensive Rats

Abstract

Chronic kidney disease (CKD) is becoming a notable health concern globally. The combination of Scutellaria baicalensis Georgi (SB) and Sophora japonica L. (SJ) has been demonstrated to have anti-hypertensive effects and improve kidney injury clinically. This study aimed to explore the renal protective effect of the combination of SB and SJ against CKD and clarify the potential mechanisms. Male spontaneously hypertensive rats (SHR) were used to induce hypertensive nephropathy and were treated with SB or SJ separately or in combination for 15 weeks, and an antibiotic group was used for a rescue experiment. Blood pressure, serum or urine biochemical markers, serum inflammation factors, short-chain fatty acids (SCFAs), indoxyl sulfate (IS), and oxidative stress indicators were assessed. Western blot analysis was performed to determine the expression of intestinal tight junction proteins, including occludin and ZO-1. The mRNA expression of the SCFAs receptors olfactory 78 (Olfr78) and G protein-coupled receptor 41 (GPR41) was determined by quantitative real-time PCR. Gut microbiota profiles were established via high-throughput sequencing of the V3-V4 region of the bacterial 16S rRNA gene. SB and SJ significantly ameliorated the severity of renal injury induced by hypertension. The combination also decreased the ratio of Firmicutes/Bacteroidetes, increased the relative abundance of Lactobacillus, and reduced that of Clostridiaceae. The intestinal barrier was improved, and the change in dominant bacteria reduced IS accumulation and further inhibited oxidative stress activation in kidneys. SB and SJ increased SCFAs production, inhibited inflammatory factor release, and regulated blood pressure by decreasing the expression of Olfr78 and increasing that of GPR41, then alleviated kidney damage. This research demonstrated the positive effects of SB and SJ in a rat model of hypertensive nephropathy, indicated that the treatment of SB and SJ by improving the intestinal barrier function, increasing SCFAs, reducing inflammation, decreasing IS, and inhibiting oxidative stress reactions.

The Role of Short-Chain Fatty Acids of Gut Microbiota Origin in Hypertension

“…As a specific intestinal growth factor, GLP-2 can promote the growth of normal intestinal mucosa, repair the damaged intestinal epithelium and protect the intestinal mucosal barrier ( Brubaker, 2018 ; Chang et al, 2021 ). Moreover, SCFAs, especially butyrate, can enhance the β-oxidation process of the cells in the intestinal mucosa, consume oxygen in the intestinal lumen and then create a favourable intestinal microenvironment to promote the growth of beneficial bacteria and inhibit the proliferation of potential pathogenic microorganisms; ultimately, the immune inflammatory response related to hypertension is alleviated, and target organ damage is relieved ( Cani, 2017 ; Guan et al, 2020 ). Similarly, Kim et al confirmed that butyrate treatment in mice with Ang II-induced hypertension can ameliorate microbial imbalance and intestinal barrier dysfunction, thereby reducing the mean arterial pressure ( Kim et al, 2018 ).…”

Role of medicinal plants in inhibiting SARS-CoV-2 and in the management of post-COVID-19 complications

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Role of gut microbiota in the immunopathology of atherosclerosis: Focus on immune cells

“…78 Furthermore, SCFAs, particularly butyrate, can alleviate immune inflammatory response and organ damage through enhancing the βoxidation process of cells in the intestinal mucosa and consuming oxygen in the intestinal lumen and then creating a favourable intestinal microenvironment that promotes the proliferation of beneficial bacteria while inhibiting the growth of potentially pathogenic micro-organisms. 80 SCFAs participate in CVD occurrence and development through several pathways; however, most of the studies on SCFAs are phenotypic descriptions, and the specific molecular mechanisms remain unexplained. Further studies are needed to elucidate the potential effects and internal mechanisms of SCFAs on CVD, which could provide fundamental information for the prevention and treatment of CVD.…”

“…Besides, after binding to GPR109A, butyrate can promote anti‐inflammatory properties in colonic macrophages and dendritic cells, leading to differentiation of Tregs and IL‐10‐producing T cells 78 . Furthermore, SCFAs, particularly butyrate, can alleviate immune inflammatory response and organ damage through enhancing the β‐oxidation process of cells in the intestinal mucosa and consuming oxygen in the intestinal lumen and then creating a favourable intestinal microenvironment that promotes the proliferation of beneficial bacteria while inhibiting the growth of potentially pathogenic micro‐organisms 80 . SCFAs participate in CVD occurrence and development through several pathways; however, most of the studies on SCFAs are phenotypic descriptions, and the specific molecular mechanisms remain unexplained.…”