A Systematic Pharmacology and In Vitro Study to Identify the Role of the Active Compounds of Achyranthes bidentata in the Treatment of Osteoarthritis

Abstract

Backgrounds Achyranthes bidentata is a Chinese traditional herbal medicine widely used to treat osteoarthritis (OA) . This study aimed to identify active compounds from Achyranthes bidentata through systematic pharmacology and in vitro experiments to find the targets of Achyranthes bidentata in the treatment of OA. Material/Methods We screened the active compounds of Achyranthes bidentata from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Then, we used STITCH and Open Targets Platform databases to screen the active components and predict the potential targets of Achyranthes bidentata in the treatment of OA. Subsequently, we studied the compound-target network and protein interaction network and analyzed the enrichment of potential target proteins. Finally, we used Western blot analysis to verify the therapeutic effect of Achyranthes bidentata extract on the expression of OA-related target proteins. Results There were 7 active components in Achyranthes bidentata , which were strongly related to the 74 targets of OA. Quercetin, baicalein, and berberine are the critical active compounds of Achyranthes bidentata in the treatment of OA. Protein interaction analysis and in vitro experiments suggested that TNF, IL-6, and TP53 are the critical targets of Achyranthes bidentata in the treatment of OA. Functional enrichment analysis showed that Achyranthes bidentata plays a pharmacological role in OA through apoptosis, inflammation, and immune regulation. Conclusions Quercetin, baicalein, and berberine are the critical active compounds of Achyranthes bidentata in the treatment of OA. TNF, IL-6, and TP53 may be potential targets for the treatment of OA.

Inhibitory Effects of IL-6-Mediated Matrix Metalloproteinase-3 and -13 by Achyranthes japonica Nakai Root in Osteoarthritis and Rheumatoid Arthritis Mice Models

“…Because there has been no report of these compounds from AJNR extraction via normal organic solvent extraction methods nor functional research, our current study guaranteed functional studies of these novel compounds in arthritis pathogenesis in the future. As a traditional plant medicine, AJNR has been used in the clinical treatment of OA for many years [ 52 , 57 , 58 ]. Our data indicated the inhibitory effects of AJNR on all OA parameters, e.g., Safranin-O-stained tissue histology, OARSI grade, subchondral bone plate thickness, osteophyte size, osteophyte maturity, and synovitis ( Figure 4 ).…”

Experimental Therapeutics for the Treatment of Osteoarthritis

“…Co-treatment of kaempferol and apigenin: collagen IIa1↑, aggrecan↑, SOX-9↑ gene expression. model: ACLT rat [ 148 , 149 ] Krill oil mixture with astaxanthin and HA Serum levels of articular cartilage degeneration biomarkers cartilage oligomeric matrix protein (COMP)↓ and crosslinked C-telopeptide of type II collagen↓, TNF-α↓, IL-1β↓, IL-6↓, mRNA of iNOS↓, COX-2↓, MMP-2 and −9↓, in knee joint tissue, probably via NF-κB model: MIA rat [ 150 ] Olive-derived polyphenols Olive, contains polyphenols: including hydroxytyrosol, tyrosol, oleocanthal and oleuropein anti-inflammatory, with antioxidant and autophagy-enhancing activities (via SIRT1) models: rabbit articular cartilage defect, human trials [ 151 ] Paeonia (P.) lactiflora and the gum resin of C. myrrha Traditional medicines, P. lactiflora root and C. myrrha gum resin, NO↓, iNOS↓, IL-1β↓, IL-6↓, COX-2↓, cartilage erosion and subchondral bone damage↓ model: MIA rat [ 128 ] Phyllanthus emblica Fruit extract, hyaluronidase and collagenase 2 activity↓, chondroprotection model: human OA articular cartilage explants [ 90 ] Quercetin Achyranthes bidentata , (Quercetin, baicalein, and berberine are contained), inhibitors of TNFα and IL-6 signaling, and tumor suppressor protein (TP)53, inflammation↓, apoptosis↓ model: rat chondrocytes+IL-1β [ 129 ] Resveratrol Grape seed extract, inhibits NF-κB signaling, TNFα↓, IL-1β↓, IL-6↓, IL-18↓, caspase-9/3 activity↓, SIRT1↓, PGE2↓ and NO↓, MMP-1↓, -3↓, -13↓, COX-2↓, collagen type II and ACAN restored, heme oxygenase 1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf-2)↑, hence, it negatively regulates genes involved in apoptosis, cell stress, autophagy, catabolism models: OA articular chondrocytes+IL-1β, MIA rat [ 152 , 153 ] Stinging nettle Stinging nettle, MMP-1↓, MMP-3↓, MMP-9↓ Hypothesized: inhibits NF-κB signaling model: human articular chondrocytes+IL-1β [ 154 ] Sulforaphane …”

“… 8 , 9 , 127 Some agents have been used empirically since centuries, eg, in Chinese traditional medicine (see Table 2 ). 128 More systematical screening has been undertaken to identify novel promising compounds 129 and chemoinformatic recherche exploring suitable compounds based on their putative properties deduced from chemical structure and composition was also applied to identify valuable agents for OA. 8 Nutrigenomics is an additional strategy to find potential therapeutics tailored for individual patients.…”

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

“…Achyranthes bidentate , derived from natural plants, is a common traditional Chinese medicine (TCM) used in treating orthopedics and traumatology, has an anti-inflammatory effect on the articular cartilage of animal models of osteoarthritis [ 15 ]. Reports indicate that Achyranthes bidentata can reduce inflammatory responses by targeting TNF, IL-6, and TP53, suppressing glycolysis and apoptosis by MAPK/AKT signaling pathway, and decreasing osteoclastogenesis and bone resorption by inhibiting RANKL signaling [ 16–18 ]. Achyranthes bidentata contains three active components, including Hydroxyecdysone, Oleanolic acid , and Achyranthes bidentata polysaccharide , the concentration of these three components varies depending on the production area, processing, and testing methods [ 19 ].…”