Danggui Niantong granules ameliorate rheumatoid arthritis by regulating intestinal flora and promoting mitochondrial apoptosis

Pharm Biol. 2022 Dec;60(1):1606-1615. doi: 10.1080/13880209.2022.2107018.

Abstract

Context: Danggui Niantong Granules (DGNTG) are a valid and reliable traditional herbal formula, commonly used in clinical practice to treat rheumatoid arthritis (RA). However, the mechanism of its effect on RA remains unclear.

Objective: An investigation of the therapeutic effects of DGNTG on RA.

Materials and methods: Twenty-four male Sprague-Dawley (SD) rats were divided into four groups: control, model, DGNTG (2.16 g/kg, gavage), methotrexate (MTX) (1.35 mg/kg, gavage) for 28 days. The morphology of synovial and ankle tissues was observed by haematoxylin-eosin staining. The responses of mitochondrial apoptosis were assessed by qPCR, Western blotting and immunohistochemical staining. Rat faeces were analysed by 16S rRNA sequencing.

Results: Our results showed that DGNTG treatment reduced AI scores (7.83 ± 0.37 vs. 4.67 ± 0.47, p < 0.01) and paw volumes (7.63 ± 0.17 vs. 6.13 ± 0.11, p < 0.01) compared with the model group. DGNTG also increased the expression of Bax (0.34 ± 0.03 vs. 0.73 ± 0.03, p < 0.01), cytochrome c (CYTC) (0.24 ± 0.02 vs. 0.64 ± 0.01, p < 0.01) and cleaved caspase-9 (0.24 ± 0.04 vs. 0.83 ± 0.08, p < 0.01), and decreased bcl-2 (1.70 ± 0.11 vs. 0.60 ± 0.09, p < 0.01) expression. DGNTG treatment regulated the structure of gut microbiota.

Discussion and conclusions: DGNTG ameliorated RA by promoting mitochondrial apoptosis, which may be associated with regulating gut microbiota structure. DGNTG can be used as a supplement and alternative drug for the treatment of RA; its ability to prevent RA deserves further study.

Keywords: Adjuvant-induced arthritis rats; fibroblast-like synovial cells; gut microbiota; traditional Chinese medicine.

MeSH terms

  • Animals
  • Apoptosis* / drug effects
  • Arthritis, Experimental* / drug therapy
  • Arthritis, Rheumatoid* / drug therapy
  • Arthritis, Rheumatoid* / metabolism
  • Drugs, Chinese Herbal* / pharmacology
  • Gastrointestinal Microbiome* / drug effects
  • Male
  • RNA, Ribosomal, 16S / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Synovial Membrane / metabolism

Substances

  • Drugs, Chinese Herbal
  • RNA, Ribosomal, 16S

Grants and funding

This work was supported by the Natural Science Foundation of Guangdong Province [grant number 2022A1515011681], Natural Science Foundation of China (NSFC) [grant number 8167151349] and Natural Science Foundation of China (NSFC) [grant number 8177150993].