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Regulatory effect of the leaves of Rehmannia glutirtosa Libosch on intestinal microflora in diabetic nephropathy rats
Abstract
The aim of this study was to investigate the regulatory effect of the total glycoside extracted from leaves of Rehmannia (TLR) and Dihuangye total glycoside capsule (DTG) on intestinal microflora in diabetic nephropathy rats. Forty-eight rats were randomly divided into the control group (C), model group (M), Huangkui capsule group (0.75 g kg⁻¹ d⁻¹ HK), irbesartan group (27 mgkg⁻¹.d⁻¹, YX), TLR low dose group (4.3 g-kg⁻¹/d⁻¹, DHYL), TLR high dose group (7.2 g-kg⁻¹.d⁻¹, DHYH), DTG low dose group (216 mg-kg⁻¹ d⁻¹, JNL), DTG high dose group (360 mgkg⁻¹d⁻¹, JNH). Rat model of diabetic nephropathy was induced by intraperitoneal injection of small dose of streptozotocin (45 mg kg⁻¹, STZ) and feeding high-fat diet and 5% glucose drinking water. After oral administration for two weeks, the 16S rDNA sequencing method was used to study the effects of the TLR and DTG on intestinal flora in diabetic nephropathy rats. The results showed that compared with the control group, the intestinal flora of diabetic nephropathy rats had changed from phylum units to the genus units. Moreover, the proportion of lactobacilli in the intestinal bacteria of the model group was significantly decreased, and the proportion of lactobacilli in the administration group was increased, especially the YX group, TLR low dose group and DTG low dose group. The data suggest that the total glycosides of Rehmannia glutinosa improved the disorder of intestinal flora in STZ-induced diabetic nephropathy rats.
... However, the definite association between F/B ratio and biochemical indicators of diabetes is not well established and still needs to be further studied (Mokhtari et al., 2021). On the contrary, the Firmicutes-to-Bacteroidetes ratio was found to have declined significantly in some studies of diabetic nephropathy (Dai et al., and Rehmannia glutinosa leaves total glycoside (Dai et al., 2017;Xu et al., 2020) reduced stimulated blood glucose and increased the F/B ratio in db/db mice. Magnesium lithospermate B did not affect FBG levels and increased the F/B ratio slightly in the streptozotocin (STZ)-induced mice (Zhao et al., 2019). ...
... Frontiers in Pharmacology frontiersin.org total glycoside (Dai et al., 2017;Xu et al., 2020). The Ruminococcus genus (OTU82, OTU230, and OTU51) that increased in the 5/6 Nx group was found to be associated with kidney injury (Zeng et al., 2016;Zhao et al., 2020). ...
Dysbiosis of gut microbiota plays a fundamental role in the pathogenesis and development of chronic kidney disease (CKD) and its complications. Natural products from plants and microorganisms can achieve recognizable improvement in renal function and serve as an alternative treatment for chronic kidney disease patients with a long history, yet less is known on its beneficial effects on kidney injury by targeting the intestinal microbiota. In this review, we summarize studies on the effects of natural products from plants and microorganisms, including herbal medicines and their bioactive extracts, polysaccharides from plants and microorganisms, and phytochemicals, on the prevention and treatment of chronic kidney disease through targeting gut microflora. We describe the strategies of these anti-CKD effects in animal experiments including remodulation of gut microbiota structure, reduction of uremic toxins, enhancement of short-chain fatty acid (SCFA) production, regulation of intestinal inflammatory signaling, and improvement in intestinal integrity. Meanwhile, the clinical trials of different natural products in chronic kidney disease clinical practice were also analyzed and discussed. These provide information to enable a better understanding of the renoprotective effects of these effective natural products from plants and microorganisms in the treatment of chronic kidney disease. Finally, we propose the steps to prove the causal role of the intestinal microflora in the treatment of chronic kidney disease by natural products from plants and microorganisms. We also assess the future perspective that natural active products from plants and microorganisms can beneficially delay the onset and progression of kidney disease by targeting the gut flora and highlight the remaining challenges in this area. With the continuous deepening of studies in recent years, it has been proved that gut microbiota is a potential target of natural active products derived from plants and microorganisms for chronic kidney disease treatment. Fully understanding the functions and mechanisms of gut microbiota in these natural active products from plants and microorganisms is conducive to their application as an alternative therapeutic in the treatment of chronic kidney disease.
... Rhizoma Anemarrhenae was-one of the traditional Chinese medicines-commonly used for nourishing Yin, clearing heat and purging fire, moistening dryness and promoting excretion (15). Recent investigation demonstrated that Anemarrhenae Rhizoma could resist pathogenic microorganism and Rehmanniae Radix could modulate intestinal microflora (12,(16)(17)(18). Ingredients or intestinal metabolites might influence the balance of intestinal bacterial species (19,20). ...
Xian-Ling-Gu-Bao (XLGB), a famous traditional Chinese medicine prescription consisted of six herbal medicines, was used for prevention and treatment of osteoporosis in China. As an oral formulation, the multiple components contained in XLGB were inevitably biotransformed by the intestinal microflora before absorption via the gastrointestinal tract. However, the dynamic profiles of biotransformation products of XLGB remain unknown. In this paper, a rapid and sensitive ultra-performance liquid chromatography tandem triple quadrupole mass spectrometry method was developed for the simultaneous quantitative analysis of multiple biotransformation products of XLGB with rat intestinal microflora. For 10 selected quantitative compounds, all calibration curves revealed good linearity (r2 > 0.99) within the sampling ranges considered. The whole intra- and inter-day precisions (as relative standard deviation) of all analytes were <13.5%, and the accuracies (as relative error) were in the range from -11.3 to 11.2%. The lower limits of quantification were 20, 10, 5, 20, 2, 2, 2, 5, 2 and 2 ng/mL for sweroside, timosaponin BII, epimedin C, asperosaponin VI, psoralen, isobavachin, icariside II, timosaponin AIII, isobavachalcone and icaritin, respectively. The matrix effects, extraction recoveries and stabilities were all satisfactory. Meanwhile, dynamic profiles of 21 additional biotransformation products were also monitored by their area-time curves. The analytical method was successfully applied to describe dynamic profiles of 31 biotransformation products of XLGB and the recipes with removal of a definite composed herbal medicine (Anemarrhenae Rhizoma or Rehmanniae Radix).
... Rehmannia glutinosa leaves total glycoside (DHY) is mainly composed of iridoid glycosides (catalpol, ajugol, etc.) and phenylethanoid glycosides (acteoside, etc.) extracted from RGL. Previous studies have exhibited that DHY has been used in the clinical treatment of various kidney diseases, it can protect kidney by improving glomerular permeability and reducing proteinuria and improve the effect of STZ-induced intestinal flora imbalance in diabetic nephropathy rats [8][9][10]. Dihuangye total glycoside capsule (JN) is a proprietary Chinese medicine extracted from DHY. Clinical experimental studies have shown that JN combined with conventional treatment or other western drugs such as irbesartan and nephritis rehabilitation tablet, can effectively reduce proteinuria in patients with DN clinical stage, improve the hypercoagulability of blood, and have a better renal protection effect [11][12][13]. ...
The spontaneous db/db mice were used to elucidate the biological effects and mechanisms of Rehmannia glutinosa leaves total glycoside (DHY) on kidney injury through biochemical indicators, kidney pathological section analysis, metabolic profiling, intestinal flora analysis and in vitro Human renal tubular epithelial (HK-2) cell model induced by high glucose. It was found that DHY can decrease the blood sugar level (insulin, INS; fasting blood glucose, FBG), blood lipid level (Total Cholesterol, T-CHO; Triglyceride, TG) significantly and improve kidney injury level (blood urea nitrogen, BUN; urine microalbumin, mALB; serum creatinine, Scr). It can also alleviate kidney tubular epithelial cell oedema and reduce interstitial connective tissue hyperplasia of the injury kidney induced by high glucose. 13 endogenous metabolites were identified in serum, which involved of ether lipid metabolism, sphingolipid metabolism, glyoxylic acid and dicarboxylic acid metabolism and arachidonic acid metabolism. High glucose can also lead to the disorder of intestinal flora, especially Firmicutes and Bacteroides. Meanwhile, DHY also inhibited the expression of α-SMA, TGF- β1, Smad3 and Smad4 in the kidney tissues of db/db mice and HK-2 cells. To sum up, DHY may restore the dysfunctional intestinal flora to normal and regulate glycolipid level of db/db mice as well as TGF-β/Smad signalling pathway regulation to improve early kidney damage caused by diabetes.
... DJ could strengthen the intestinal barrier integrity in T2DM mice and restore the gut microbiota dysbiosis, as indicated by the decreased F/B ratio and the increased A. muciniphila, Anaerotruncus colihominis, Mucispirillum schaedleri and Butyricimonas virosa [74]. Similarly, we demonstrated the beneficial effects of the total glycoside extract of the leaves of Rehmannia glutinosa Libosch instead of the medicinal tuberous roots in diabetic nephropathy rats, followed with the significantly increased proportion of Lactobacilli in the gut [75]. Recently, a novel polysaccharide was isolated from the industrial Astragalus membranaceus-extracted waste dregs, which improved diabetes-related cognitive dysfunction by decreasing the fecal F/B ratio, Oscillospira and Mucispirillum but increasing Lactobacillus and Sutterella as well as butyrate production [76]. ...
With the development of system biology, traditional Chinese medicine (TCM) is drawing more and more attention nowadays. However, there are still many enigmas behind this ancient medical system because of the arcane theory and complex mechanism of actions. In recent decades, advancements in genome sequencing technologies, bioinformatics and culturomics have led to the groundbreaking characterization of the gut microbiota, a 'forgotten organ', and its role in host health and disease. Notably, gut microbiota has been emerging as a new avenue to understanding TCM. In this review, we will focus on the structure, composition, functionality and metabolites of gut microbiota affected by TCM so as to conversely understand its theory and mechanisms. We will also discuss the potential areas of gut microbiota for exploring Chinese material medica waste, Chinese marine material medica, add-on therapy and personalized precise medication of TCM. The review will conclude with future perspectives and challenges of gut microbiota in TCM intervention.
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