Danggui Sini decoction alleviates oxaliplatin-induced peripheral neuropathy by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder

• Published in: Chinese medicine Vol. 19; no. 1; p. 58
• Main Authors: Chen, Chen, Xu, Jian-Lin, Gu, Zhan-Cheng, Zhou, Shan-Shan, Wei, Guo-Li, Gu, Jia-Lin, Ma, Hai-Long, Feng, Yan-Qi, Song, Zi-Wei, Yan, Zhan-Peng, Deng, Shan, Ding, Rong, Li, Song-Lin, Huo, Jie-Ge
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 07-04-2024; BioMed Central; BMC
• Subjects: Analysis; Antibiotics; Bacteria; Chinese medicine; Correlation analysis; Danggui Sini decoction; Digestive system; Dorsal root ganglia; Drug dosages; Dysbacteriosis; Fatty acids; Fecal microbiota transplantation; Fecal microflora; Feces; Gastrointestinal tract; Glutamine; Gut microbiota; Homovanillic acid; Inflammation; Intestinal microflora; Laboratory animals; Lipopolysaccharides; Medicine, Chinese; Metabolic disorder; Metabolic disorders; Metabolism; Metabolites; Metabolomics; Metronidazole; Microbiota; Microbiota (Symbiotic organisms); Neomycin; Nervous system; Neuroinflammation; Neuroprotection; Oxalic acid; Oxaliplatin; Oxaliplatin-induced peripheral neuropathy; Pain perception; Peripheral neuropathy; Physiological aspects; rRNA 16S; Sphingomyelin; Traditional Chinese medicine; Transplantation; Tumor necrosis factor-α; China; Jiangsu China; United States > US; Gut microbiota; Neuroinflammation; Metabolic disorder; Danggui Sini decoction; Oxaliplatin-induced peripheral neuropathy; Fecal microbiota transplantation
• ISSN: 1749-8546; 1749-8546
• DOI: 10.1186/s13020-024-00929-7

Danggui Sini decoction (DSD), a traditional Chinese medicine formula, has the function of nourishing blood, warming meridians, and unblocking collaterals. Our clinical and animal studies had shown that DSD can effectively protect against oxaliplatin (OXA)-induced peripheral neuropathy (OIPN), but the detailed mechanisms remain uncertain. Multiple studies have confirmed that gut microbiota plays a crucial role in the development of OIPN. In this study, the potential mechanism of protective effect of DSD against OIPN by regulating gut microbiota was investigated.
The neuroprotective effects of DSD against OIPN were examined on a rat model of OIPN by determining mechanical allodynia, biological features of dorsal root ganglia (DRG) as well as proinflammatory indicators. Gut microbiota dysbiosis was characterized using 16S rDNA gene sequencing and metabolism disorders were evaluated using untargeted and targeted metabolomics. Moreover the gut microbiota mediated mechanisms were validated by antibiotic intervention and fecal microbiota transplantation.
DSD treatment significantly alleviated OIPN symptoms by relieving mechanical allodynia, preserving DRG integrity and reducing proinflammatory indicators lipopolysaccharide (LPS), IL-6 and TNF-α. Besides, DSD restored OXA induced intestinal barrier disruption, gut microbiota dysbiosis as well as systemic metabolic disorders. Correlation analysis revealed that DSD increased bacterial genera such as Faecalibaculum, Allobaculum, Dubosiella and Rhodospirillales_unclassified were closely associated with neuroinflammation related metabolites, including positively with short-chain fatty acids (SCFAs) and sphingomyelin (d18:1/16:0), and negatively with pi-methylimidazoleacetic acid, L-glutamine and homovanillic acid. Meanwhile, antibiotic intervention apparently relieved OIPN symptoms. Furthermore, fecal microbiota transplantation further confirmed the mediated effects of gut microbiota.
DSD alleviates OIPN by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder.