Compatibility of Achyranthes bidentata components in reducing inflammatory response through Arachidonic acid pathway for treatment of Osteoarthritis.

Achyranthes bidentate is a common traditional Chinese medicine (TCM) used in treating osteoarthritis (OA). The compatibility between effective components has now become a breakthrough in understanding the mechanism of TCM. This study aimed at determining the optimal compatibility and possible mechanism of Achyranthes bidentate for OA treatment. Results showed that the adhesion score of the OA group is higher than NC group, and showed a trend of down-regulation in the intervention group. The CHI3L1 and IL-1ß in joint fluid of the OA group was significantly increased compared to the sham operation group (NC group). Group G, I, and L exhibited significantly down-regulated CHI3L1, while groups C, F, I, K, and L exhibited reduced IL-1ß. Joint adhesion, damage in cartilage, and synovial tissue was found in the OA model, cartilage tissue was found recovered in groups I, J, and L, and synovial tissue was recovered in group G, I, and L. Thus, group I and L were chosen for metabolite analysis, and indole-3-propionic acid was slightly up-regulated, while koeiginequinone A, prostaglandin H2, and 1-hydroxy-3-methoxy-10-methylacridonew were down-regulated in group I and L. According to functional analysis, the arachidonic acid (AA) metabolic pathway is enriched. Down-regulated expression of vital proteins in the AA metabolism pathway, such as PGE2 and COX2 in group I and L were verified. In conclusion, Hydroxyecdysone, Oleanolic acid, Achyranthes bidentata polysaccharide at a compatibility of 0.03-µg/mg, 2.0-µg/mg, 20.0-µg/mg or 0.03-µg/mg, 2.0-µg/mg, 10.0-µg/mg, respectively, may be the optimal compatibility of Achyranthes bidentate.

PIM1, CYP1B1, and HSPA2 Targeted by Quercetin Play Important Roles in Osteoarthritis Treatment by Achyranthes bidentata.

AIM: Achyranthes bidentata is one of the most commonly used Chinese herbal medicines (CHM) that is currently considered for the treatment of osteoarthritis. The purpose of this study was to reveal the mechanism of Achyranthes bidentata in osteoarthritis treatment based on the network pharmacology. METHODS: The effective components of Achyranthes bidentata were firstly screened out from the TCMSP database with ADME property parameters. Then, osteoarthritis-related proteins targeted by the effective components were predicted based on the DrugBank and CTD databases. Subsequently, enrichment analysis and interaction network between targets of effective components and pathways were also studied. In addition, the differentially expressed genes (DEGs) of GSE55457 were used for validation of the osteoarthritis-related target proteins. Finally, the effective components-target molecular docking models were predicted. RESULTS: A total of 10 effective components were identified, of which kaempferol and quercetin had 1 and 29 targets, respectively. There were 26 target proteins of quercetin related to the osteoarthritis. These targets were mainly enriched in mitochondrial ATP synthesis coupled proton transport, cellular response to estradiol stimulus, and nitric oxide biosynthetic process. In addition, there were three common proteins, PIM1, CYP1B1, and HSPA2 based on the DEGs of GSE55457, which were considered as the key targeted proteins of the quercetin. CONCLUSION: The docking of PIM1-quercetin, CYP1B1-quercetin, and HSPA2-quercetin may play important roles during the treatment of osteoarthritis by Achyranthes bidentata.