Curcumenol mitigates chondrocyte inflammation by inhibiting the NF‑κB and MAPK pathways, and ameliorates DMM‑induced OA in mice

Abstract

At present, an increasing number of individuals are affected by osteoarthritis (OA), resulting in a heavy socioeconomic burden. OA in knee joints is caused by the release of inflammatory cytokines and subsequent biomechanical and structural deterioration. To determine its anti-inflammatory function, the current study investigated the use of the plant-derived medicine, curcumenol, in OA treatment. curcumenol was not cytotoxic to ATdc5 chondrocytes and primary chondrocytes, as determined using a cell viability test. When these cells were treated with TNF-α and IL-1β to induce inflammation, curcumenol treatment inhibited the progression of inflammation by inactivating the NF-κB and MAPK signaling pathways, as well as decreasing the expression levels of MMP3 (as indicated by reverse transcription-quantitative PcR and western blotting). Moreover, to analyze metabolic and catabolic status in high-density and pellet culture, catalytic changes and the degradation of the extracellular matrix induced by TNF-α and IL-1β, were evaluated by alcian blue staining. These catalytic deteriorations were ameliorated by curcumenol. Using curcumenol in disease management, the mechanical and metabolic disruption of cartilage caused in the destabilization of medial meniscus (dMM) model was prevented in vivo. Thus, curcumenol mitigated inflammation in ATdc5 chondrocytes and primary mice chondrocytes, and also ameliorated OA in a dMM-induced mouse model.

Mulberroside A alleviates osteoarthritis via restoring impaired autophagy and suppressing MAPK/NF-κB/PI3K-AKT-mTOR signaling pathways

“…MAPK and NF-κB are signaling pathways closely related to the chondrocyte inflammation, which promotes the occurrence of OA. 9 The former includes the JNK, ERK, and P38 signaling pathways, while P65 is the key regulator downstream of the NF-κB signaling pathway. For the two signaling pathways analysis, IL-1β upregulated the protein expression level of the phosphorylation of JNK, ERK, P38, and P65 ( p -JNK, p -ERK, p-P38, and p-P65) compared with the control group, whereas the administration of MA decreased the expression of p -JNK, p -ERK, p-P38, and p-P65.…”

“…The enhancement of inflammatory response is closely related to the activation of MAPK (mitogen-activated protein kinase) and NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling pathways, and studies have demonstrated that MAPK and NF-κB signaling pathways play an important role in promoting the progression of OA. 9 Furthermore, autophagy process, an intracellular protective mechanism, is regulated by the PI3K-AKT-mTOR signaling pathway and is also considered to be a crucial factor in maintaining the stability of cartilage, as impaired autophagy will contribute to the apoptosis of chondrocytes and the degradation of the ECM. 10 …”

Mangiferin Alleviates Postpartum Depression–Like Behaviors by Inhibiting MAPK Signaling in Microglia

“…Moreover, treatment with MGF significantly inhibited the increase in microglial number in the hippocampus, suggesting that the neuroprotective role of MGF might be associated with its inhibitory effect on microglial activation. To further elucidate the potential targets of MGF, we performed bioinformatics analysis and found that MGF targets MAPK signaling, which regulates cell proliferation, stress response, inflammation, cell differentiation, and apoptosis (Li Z et al, 2021;Qin et al, 2021;Wang et al, 2021;Yang et al, 2021). More importantly, the MAPK signal pathway has been linked to several diseases, including depression (Duman et al, 2007;Wang and Mao, 2019;Humo et al, 2020).…”

Curcumenol Mitigates the Inflammation and Ameliorates the Catabolism Status of the Intervertebral Discs In Vivo and In Vitro via Inhibiting the TNFα/NFκB Pathway

“…A variety of herbs, which are widely used as traditional treatments for inflammatory pain in ancient society, possess this important constituent ( Assis et al, 2013 ; Saikia et al, 2015 ). Recent studies have purified this compound and confirmed that it shows various functions like anti-inflammatory, neuroprotective, and antioxidant activities ( Sun et al, 2010 ; Pintatum et al, 2020 ; Yang et al, 2021 ). Thus, in our study we consider further expanding the application of curcumenol in IVDD.…”