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  2. Network analysis of microbiome and metabolome to explore the mechanism of raw rhubarb in the protection against ischemic stroke via microbiota-gut-brain axis

Network analysis of microbiome and metabolome to explore the mechanism of raw rhubarb in the protection against ischemic stroke via microbiota-gut-brain axis

  • Fitoterapia. 2024 Apr 20:175:105969. doi: 10.1016/j.fitote.2024.105969.
Minghua Xian 1 Zuqing Ma 2 Sikai Zhan 2 Lin Shen 2 Ting Li 2 Huiting Lin 2 Mingmin Huang 2 Jiale Cai 2 Tao Hu 2 Jiaying Liang 2 Shengwang Liang 2 Shumei Wang 3
Affiliations

Affiliations

  • 1 Guangdong Pharmaceutical University, Guangzhou 510006, China; Traditional Chinese Medicine Resource Germplasm Bank Management Center, Yunfu 527322, China; Key Laboratory of Digital Quality Evaluation of Chinese Materia Medica of State Administration of TCM, School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou 510006, China; Engineering & Technology Research Center for Chinese Materia Medica Quality of the Universities of Guangdong Province, School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou 510006, China. Electronic address: xmh360@163.com.
  • 2 Guangdong Pharmaceutical University, Guangzhou 510006, China; Key Laboratory of Digital Quality Evaluation of Chinese Materia Medica of State Administration of TCM, School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou 510006, China; Engineering & Technology Research Center for Chinese Materia Medica Quality of the Universities of Guangdong Province, School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou 510006, China.
  • 3 Guangdong Pharmaceutical University, Guangzhou 510006, China; Traditional Chinese Medicine Resource Germplasm Bank Management Center, Yunfu 527322, China; Key Laboratory of Digital Quality Evaluation of Chinese Materia Medica of State Administration of TCM, School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou 510006, China; Engineering & Technology Research Center for Chinese Materia Medica Quality of the Universities of Guangdong Province, School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou 510006, China. Electronic address: gdpuwsm@126.com.
Abstract

Ischemic stroke (IS) has attracted worldwide attention due to the high mortality and disability rate. Raw rhubarb (RR) is a traditional medicinal plant and whole-food that has been used in China for its various pharmacological activities, such as antioxidant and anti-inflammatory properties. Recent pharmacological research has shown the role of RR against IS, but its mechanism of action remains unclear, particularly in the context of the brain-gut axis. To address this gap in knowledge, the present study was conducted in the middle cerebral artery occlusion/reperfusion (MCAO/R) model with the aim of investigating the effects of RR on regulating the intestinal microbiota barrier and metabolism and thereby reducing inflammatory response so as to improve the IS. The results showed that pre-treatment of RR attenuated cerebral infarct area and inflammation response in MCAO rats. Furthermore, RR also improved intestinal barrier function, including the integrity and permeability of the intestinal barrier. Additionally, RR intervention significantly attenuated gut microbiota dysbiosis caused by ischemic stroke, especially the increased Firmicutes. Notably, the pseudo-germ-free (PGF) rats further demonstrated that the anti-stroke effect of RR might rely on intestinal microbiota. In addition, the UPLC/Q-Orbitrap-MS-Based metabolomics revealed the disrupted metabolic profiles caused by MCAO/R, and a total of 11 differential metabolites were modulated by RR administration, especially bile acids. Further correlation analysis and network pharmacology analysis also demonstrated a strong association between specific bacteria, such as Firmicutes and bile acids. In conclusion, our work demonstrated that RR could effectively ameliorate ischemic stroke by modulating the microbiota and metabolic disorders.

Keywords

Intestinal microflora; Ischemic stroke; Metabolomics; Netwok pharmacology; Raw rhubarb.

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