The Xiaogu San Attenuates Pain and Cartilage Damage in Rats with Monosodium Iodoacetate Induced Osteoarthritis

Comb Chem High Throughput Screen. 2022;25(11):1914-1951. doi: 10.2174/1386207325666211008130312.

Abstract

Background: Osteoarthritis (OA) is a degenerative joint disease with an increasing incidence associated with increased life expectancy. The application of traditional Chinese medicine in the treatment of OA has become a research hotspot.

Objective: This study investigated the effects of XGS externally applied to osteoarthritic joints and analyze its effect on pain in monosodium iodoacetate (MIA)-induced OA rats. This study also evaluates potential mechanisms behind the anti-osteoarthritic effects of XGS.

Methods: A total of 24 Sprague Dawley rats were evenly and randomly divided into three separate groups, including the normal control (NC), OA and XGS groups. MIA (50 μL, 10 mg/mL) was injected into the left knee joints of the rats to induce OA. After 7 days, The rats of XGS group were given XGS (0.45 g) that was externally applied to the left knee joint, were fixed with gauze, and continuously administered XGS for 28 days. Morphological changes in tissues and organs were examined using H&E staining. Biochemical indicators were measured using an automatic biochemical analyzer. Inflammatory cytokines were detected using ELISA kits and immunohistochemistry. RNA-based high-throughput sequencing (RNA-seq) was performed to detect differential expression of mRNAs in normal and MIA-induced OA rats.

Results: Stride of the left leg was extended in rats, matrix increased on cartilage tissue surfaces, and inflammatory cytokines were reduced when treated with XGS. RNA-seq results revealed that the PI3K-Akt signaling pathway is activated in the OA model. The qRT-PCR showed that the expression levels of Tnn, Col6a6, Igf1 and Lamb1 were up-regulated by XGS.

Conclusion: Altogether, this work demonstrated the potential therapeutic effects of XGS in rats with OA induced by MIA. The XGS may be considered an alternative therapy to manage OA.

Keywords: Osteoarthritis; PI3K/AKT signaling pathway; Xiaogu San; cartilage damage; knee joint; pain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cartilage, Articular* / metabolism
  • Cytokines / metabolism
  • Disease Models, Animal
  • Iodoacetic Acid / toxicity
  • Osteoarthritis* / chemically induced
  • Osteoarthritis* / drug therapy
  • Osteoarthritis* / metabolism
  • Pain / chemically induced
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA / metabolism
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Cytokines
  • RNA
  • Proto-Oncogene Proteins c-akt
  • Iodoacetic Acid