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

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          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.

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          Most cited references36

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          Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites.

          Although it has long been recognized that the enteric community of bacteria that inhabit the human distal intestinal track broadly impacts human health, the biochemical details that underlie these effects remain largely undefined. Here, we report a broad MS-based metabolomics study that demonstrates a surprisingly large effect of the gut "microbiome" on mammalian blood metabolites. Plasma extracts from germ-free mice were compared with samples from conventional (conv) animals by using various MS-based methods. Hundreds of features were detected in only 1 sample set, with the majority of these being unique to the conv animals, whereas approximately 10% of all features observed in both sample sets showed significant changes in their relative signal intensity. Amino acid metabolites were particularly affected. For example, the bacterial-mediated production of bioactive indole-containing metabolites derived from tryptophan such as indoxyl sulfate and the antioxidant indole-3-propionic acid (IPA) was impacted. Production of IPA was shown to be completely dependent on the presence of gut microflora and could be established by colonization with the bacterium Clostridium sporogenes. Multiple organic acids containing phenyl groups were also greatly increased in the presence of gut microbes. A broad, drug-like phase II metabolic response of the host to metabolites generated by the microbiome was observed, suggesting that the gut microflora has a direct impact on the drug metabolism capacity of the host. Together, these results suggest a significant interplay between bacterial and mammalian metabolism.
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            The gut microbiota and host health: a new clinical frontier

            Over the last 10–15 years, our understanding of the composition and functions of the human gut microbiota has increased exponentially. To a large extent, this has been due to new ‘omic’ technologies that have facilitated large-scale analysis of the genetic and metabolic profile of this microbial community, revealing it to be comparable in influence to a new organ in the body and offering the possibility of a new route for therapeutic intervention. Moreover, it might be more accurate to think of it like an immune system: a collection of cells that work in unison with the host and that can promote health but sometimes initiate disease. This review gives an update on the current knowledge in the area of gut disorders, in particular metabolic syndrome and obesity-related disease, liver disease, IBD and colorectal cancer. The potential of manipulating the gut microbiota in these disorders is assessed, with an examination of the latest and most relevant evidence relating to antibiotics, probiotics, prebiotics, polyphenols and faecal microbiota transplantation.
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              The Firmicutes/Bacteroidetes ratio of the human microbiota changes with age

              Background In humans, the intestinal microbiota plays an important role in the maintenance of host health by providing energy, nutrients, and immunological protection. Applying current molecular methods is necessary to surmount the limitations of classical culturing techniques in order to obtain an accurate description of the microbiota composition. Results Here we report on the comparative assessment of human fecal microbiota from three age-groups: infants, adults and the elderly. We demonstrate that the human intestinal microbiota undergoes maturation from birth to adulthood and is further altered with ageing. The counts of major bacterial groups Clostridium leptum, Clostridium coccoides, Bacteroidetes, Bifidobacterium, Lactobacillus and Escherichia coli were assessed by quantitative PCR (qPCR). By comparing species diversity profiles, we observed age-related changes in the human fecal microbiota. The microbiota of infants was generally characterized by low levels of total bacteria. C. leptum and C. coccoides species were highly represented in the microbiota of infants, while elderly subjects exhibited high levels of E. coli and Bacteroidetes. We observed that the ratio of Firmicutes to Bacteroidetes evolves during different life stages. For infants, adults and elderly individuals we measured ratios of 0.4, 10.9 and 0.6, respectively. Conclusion In this work we have confirmed that qPCR is a powerful technique in studying the diverse and complex fecal microbiota. Our work demonstrates that the fecal microbiota composition evolves throughout life, from early childhood to old age.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                12 February 2021
                2020
                : 11
                : 575294
                Affiliations
                [ 1 ]School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
                [ 2 ]School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China
                Author notes

                Edited by: Ying-Yong Zhao, Northwest University, China

                Reviewed by: Habib Ur Rehman, University of Veterinary and Animal Sciences, Pakistan

                Rufeng Wang, Beijing University of Chinese Medicine, China

                *Correspondence: Guohua Zhang, zghgz@ 123456163.com ; Lin Lv, lynnlv@ 123456smu.edu.cn

                This article was submitted to Ethnopharmacology, a section of the journal Frontiers in Pharmacology

                Article
                575294
                10.3389/fphar.2020.575294
                7907655
                33643031
                bbda41f7-73e5-409d-aaa9-2c80138f0714
                Copyright © 2021 Guan, Chen, Quan, Kang, Yang, Wu, Yan, Wu, Lv and Zhang.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 23 June 2020
                : 10 December 2020
                Categories
                Pharmacology
                Original Research

                Pharmacology & Pharmaceutical medicine
                scutellaria baicalensis georgi,sophora japonica l,hypertensive nephropathy,gut microbiota,traditional chinese medicine

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