NMPA Key Laboratory for Quality Control of Traditional Chinese Medicine (Mongolian Medicine), School of Mongolian Medicine, Inner Mongolia Minzu University, Tongliao, China; Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Provincial Key Laboratory for Research and Development of Tropical Herbs, School of Pharmacy, Hainan Medical University, Haikou, China.
NMPA Key Laboratory for Quality Control of Traditional Chinese Medicine (Mongolian Medicine), School of Mongolian Medicine, Inner Mongolia Minzu University, Tongliao, China.
J Ethnopharmacol. 2023 Oct 5;314:116545. doi: 10.1016/j.jep.2023.116545. Epub 2023 May 17.
Ruda-6 (RD-6), a typical traditional Mongolian medicine formulae consisting of 6 herbs, has been traditionally used in treating gastric disorders. Even though it has been shown to protect against gastric ulcers (GU) in animal models, the gut microbiome and serum metabololite-related mechanisms that prevent GU are not well understood.
This study was conducted to evaluate the gastroprotective mechanism of RD-6 associated with the alteration of the gut microbiome and serum metabolic profiles in GU rats.
RD-6 (0.27, 1.35 and 2.7 g/kg) or ranitidine (40 mg/kg) were orally administered in rats for three weeks before the induction of gastric ulcer using indomethacin (30 mg/kg, single oral dose). The gastric ulcer index, ulcer area, H&E staining, and the levels of TNF-α, iNOS, MPO and MDA were quantified to evaluate the ulcer inhibitory effects of RD-6. Then, 16S rRNA gene sequencing combined with LC-MS metabolic profiling was performed to investigate the effect of RD-6 on the gut microbiota and serum metabolites in rats. Moreover, a spearman analysis was used to calculate the correlation coefficient between the different microbiota and the metabolites.
RD-6 inhibited the gastric lesion damage caused by indomethacin in rats, decreased the ulcer index by 50.29% (p < 0.05), reduced the levels of TNF-α, iNOS, MDA and MPO in gastric tissue. Additionally, RD-6 reshaped the diversity and microbial composition, and reversed the reduced bacteria including [Eubacterium]_xylanophilum group, Sellimonas, Desulfovibrio, and UCG-009, and the increased bacteria Aquamicrobium caused by indomethacin induction. Furthermore, RD-6 regulated the levels of metabolites including amino acids and organic acids, and these affected metabolites were involved in taurine and hypotaurine metabolism and tryptophan metabolism. Spearman analysis revealed that the perturbed gut microbiota were closely related to the changes in differential serum metabolites.
In view of the 16S rRNA gene sequencing and LC-MS metabolic results, the present study suggests the mechanism of RD-6 ameliorating GU via modulating intestinal microbiota and their metabolites.
Ruda-6（RD-6）是一种由 6 种草药组成的典型传统蒙药配方，传统上用于治疗胃部疾病。尽管它已被证明可在动物模型中预防胃溃疡（GU），但预防 GU 的肠道微生物组和血清代谢物相关机制尚不清楚。
本研究旨在评估 RD-6 对 GU 大鼠肠道微生物组和血清代谢谱的改变与胃保护机制相关。
在使用消炎痛（30mg/kg，单次口服剂量）诱导胃溃疡之前，RD-6（0.27、1.35 和 2.7g/kg）或雷尼替丁（40mg/kg）以口服方式连续三周给予大鼠。通过胃溃疡指数、溃疡面积、H&E 染色以及 TNF-α、iNOS、MPO 和 MDA 水平来评估 RD-6 的溃疡抑制作用。然后，进行 16S rRNA 基因测序结合 LC-MS 代谢谱分析，以研究 RD-6 对大鼠肠道微生物组和血清代谢物的影响。此外，使用 Spearman 分析计算不同微生物组和代谢物之间的相关系数。
RD-6 抑制了消炎痛引起的大鼠胃损伤，使溃疡指数降低了 50.29%（p<0.05），降低了胃组织中 TNF-α、iNOS、MDA 和 MPO 的水平。此外，RD-6 重塑了多样性和微生物组成，并逆转了消炎痛诱导的减少的细菌，包括[Eubacterium]_xylanophilum 组、Sellimonas、Desulfovibrio 和 UCG-009，以及增加的细菌 Aquamicrobium。此外，RD-6 调节了包括氨基酸和有机酸在内的代谢物水平，这些受影响的代谢物参与了牛磺酸和次牛磺酸代谢和色氨酸代谢。Spearman 分析显示，失调的肠道微生物组与差异血清代谢物的变化密切相关。
根据 16S rRNA 基因测序和 LC-MS 代谢结果，本研究表明 RD-6 通过调节肠道微生物组及其代谢物来改善 GU 的机制。
