Drug Design, Development and Therapy (Dec 2023)

Naotaifang III Protects Against Cerebral Ischemia Injury Through LPS/TLR4 Signaling Pathway in the Microbiota–Gut–Brain Axis

  • Nie H,
  • Ge J,
  • Yang K,
  • Peng Z,
  • Wu H,
  • Yang T,
  • Mei Z

Journal volume & issue
Vol. Volume 17
pp. 3571 – 3588

Abstract

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Huifang Nie,1 Jinwen Ge,1,2 Kailin Yang,1 Zhuli Peng,1 Haihui Wu,1 Tong Yang,1 Zhigang Mei1 1Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, People’s Republic of China; 2Hunan Academy of Chinese Medicine, Changsha, Hunan, 410006, People’s Republic of ChinaCorrespondence: Zhigang Mei; Jinwen Ge, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, People’s Republic of China, Email [email protected]; [email protected]: Ischemic stroke (IS) is a leading cause of mortality worldwide. Naotaifang III is a new Chinese herbal formula to treat IS. Previous studies have shown that Astragali Radix, Puerariae Lobatae Radix, Chuanxiong Rhizoma, and Rhei Radix Et Rhizoma in Naotaifang III were able to regulate the imbalance of intestinal microbiota during cerebral ischemia injury.Methods: Rats were randomly divided into sham operation group, normal control group, middle cerebral artery occlusion (MCAO) group, intestinal microbiota imbalance MCAO group, Naotaifang III group, and normal bacteria transplantation group, with 15 rats in each group. Then, neurological function scores and cerebral infarction volume were detected; haematoxylin and eosin staining and Golgi silver staining were used to observe morphological changes in brain tissue. Meanwhile, the lipopolysaccharide (LPS) and cerebral cortex interleukin (IL)-1β were detected by enzyme-linked immunosorbent assay (ELISA); the expressions of Toll-like receptor (TLR)-4 and nuclear factor kappa-B (NF-κB) proteins were detected by immunofluorescence and Western blot. The cecal flora was detected by 16S rDNA. The results showed that gut dysbiosis aggravated cerebral ischemic injury and significantly increased the expression of LPS, TLR4, NF-κB, and IL-1β, which could be significantly reversed by Naotaifang III or normal bacterial transplantation. Naotaifang III may exert a protective effect on neuroinflammatory injury after MCAO through the LPS/TLR4 signaling pathway in the microbe-gut-brain axis. In summary, Naotaifang III may induce anti-neuroinflammatory molecular mechanisms and signaling pathways through the microbe-gut-brain axis.Results: The results showed that gut dysbiosis aggravated cerebral ischemic injury and significantly increased the expression of LPS, TLR4, NF-κB, and IL-1β, which could be significantly reversed by Naotaifang III or normal bacterial transplantation. Naotaifang III may exert a protective effect on neuroinflammatory injury after MCAO through the LPS/TLR4 signaling pathway in the microbe-gut-brain axis.Conclusion: Naotaifang III may induce anti-neuroinflammatory molecular mechanisms and signaling pathways through the microbe-gut-brain axis. Keywords: Naotaifang III, ischemic stroke, intestinal microbiota, LPS/TLR4 signaling pathway, microbiota–gut–brain axis

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