Therapeutic Effect of Buyang Huanwu Decoction on the Gut Microbiota and Hippocampal Metabolism in a Rat Model of Cerebral Ischemia

Abstract

Buyang Huanwu decoction (BHD) is a well-known Chinese herbal prescription. It has been widely used in the clinical treatment of cerebral ischemia (CI) in China. However, the mechanism underlying the treatment of CI with BHD remains to be elucidated. In this study, we combined microbiomic and metabolomic strategies to explore the therapeutic effects of BHD on middle cerebral artery occlusion (MCAO) in rats. Our results showed that BHD could effectively improve neurological severity scores and alleviate neuronal damage in rats with MCAO. BHD could also reduce the level of peripheral proinflammatory cytokines and inhibit neuroinflammation. 16S rRNA sequencing showed that BHD could increase the relative abundances of the genera Lactobacillus, Faecalibacterium, Ruminococcaceae_UCG-002, etc., while decreasing the relative abundances of the genera Escherichia-Shigella, Klebsiella, Streptococcus, Coprococcus_2, Enterococcus, etc. Untargeted metabolomic analysis of hippocampal samples showed that 17 significantly differentially abundant metabolites and 9 enriched metabolic pathways were linked with BHD treatment. We also found that the regulatory effects of BHD on metabolites were correlated with the differentially abundant microbial taxa. The predicted function of the gut microbiota and the metabolic pathway enrichment results showed that purine metabolism, glutamatergic synapses, arginine and proline metabolism, and alanine, aspartic acid and glutamate metabolism were involved in the effects of BHD. These pathways may be related to pathological processes such as excitotoxicity, neuroinflammation, and energy metabolism disorder in CI. In summary, these findings suggest that regulation of hippocampal metabolism and of the composition and function of the gut microbiota may be important mechanisms underlying the effect of BHD in the treatment of CI.

Buyang Huanwu Decoction alleviates cerebral ischemic injury through modulating caveolin-1-mediated mitochondrial quality control

“…Whole-section scans were performed, and images of cortical areas on the ischemic side were selected at ×400 magnification. According to our previous report ( Tang et al, 2022 ), images were analyzed with Image-Pro Plus 6.0, and NeuN expression was assessed using the histochemical score (H-score). The H-score was calculated using the following formula: H-score = (percentage of weakly intense cells ×1) + (percentage of moderately intense cells ×2) + (percentage of strongly intense cells ×3).…”

Gut microbiota, a hidden protagonist of traditional Chinese medicine for acute ischemic stroke

“…In recent years, there has been increasing evidence that the gut microbiota may play a key role in the treatment of AIS with TCM ( Figure 3 ) ( Feng et al, 2019a ; Lin et al, 2021 ; Song et al, 2021 ; Tang et al, 2022 ). AIS can cause disruption of the gut microbiota, which is an important cause of poor prognosis in AIS, and Traditional Chinese herbs can correct this microbiota disorder.…”

Gut brain interaction theory reveals gut microbiota mediated neurogenesis and traditional Chinese medicine research strategies

“…This may be caused by changes in bacterial tryptophan metabolism, reducing peripheral blood 5-HT levels and affecting hippocampal neurotransmitters, thereby regulating NSCs proliferation and differentiation ; however, the specific mechanism warrants further research. Similarly, BHD decreased the abundance of Escherichia-Shigella and Klebsiella (Tang R. et al, 2022). The combination of Puerariae Lobatae Radix (PLR) and Chuanxiong Rhizoma (CXR) could partially r e d u c e t h e e n r i c h m e n t o f i n t e s t i n a l p a t h o g e n s Escherichia_Shigella, Proteus, Klebsiella, etc.…”

“…Using a Buyang Huanwu Decoction (BHD) in cerebellar ischemia model mice significantly down-regulated the relative abundance of Streptococcus , Coprococcus_2 , Enterococcus , etc, and while up-regulating the relative abundance of Lactobacillus , Ruminococcaceae_UCG-002 , etc. ( Tang R. et al., 2022 ). This lowered the levels of proinflammatory cytokines in peripheral blood and inhibited microglial activation ( Tang R. et al., 2022 ).…”

“…( Tang R. et al., 2022 ). This lowered the levels of proinflammatory cytokines in peripheral blood and inhibited microglial activation ( Tang R. et al., 2022 ). At the same time, BHD promoted NSCs proliferation in middle cerebellar artery occlusion mice and promoted astrocyte and neuronal differentiation, which may be related to Jak/Stat3/Cyclin D1 and EGFR/PI3K/Akt/Bad/14-3-3 pathways ( Chen X. et al., 2020 ).…”