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

Abstract

Low back pain (LBP) caused by intervertebral disc degeneration (IVDD) is accredited to the release of inflammatory cytokines followed by biomechanical and structural deterioration. In our study, we used a plant-derived medicine, curcumenol, to treat IVDD. A cell viability test was carried out to evaluate the possibility of using curcumenol. RNA-seq was used to determine relative pathways involved with curcumenol addition. Using TNFα as a trigger of inflammation, the activation of the NF-κB signaling pathway and expression of the MMP family were determined by qPCR and western blotting. Nucleus pulposus (NP) cells and the rats’ primary NP cells were cultured. The catabolism status was evaluated by an ex vivo model. A lumbar instability mouse model was carried out to show the effects of curcumenol in vivo. In general, RNA-seq revealed that multiple signaling pathways changed with curcumenol addition, especially the TNFα/NF-κB pathway. So, the NP cells and primary NP cells were induced to suffer inflammation with the activated TNFα/NF-κB signaling pathway and increased expression of the MMP family, such as MMP3, MMP9, and MMP13, which would be mitigated by curcumenol. Owing to the protective effects of curcumenol, the height loss and osteophyte formation of the disc could be prevented in the lumbar instability mouse model in vivo.

The antioxidant Glycitin protects against intervertebral disc degeneration through antagonizing inflammation and oxidative stress in nucleus pulposus cells

“…In addition, the NF-κB signaling pathway is a classic downstream inflammatory pathway activated by TNF-α and is closely associated with the development of multiple inflammatory degenerative diseases [46]. In intervertebral disc degeneration, activation of the TNF-α/NF-κB signaling pathway leads to the secretion of inflammatory factors from nucleus pulposus cells, promoting the generation of an inflammatory microenvironment in nucleus pulposus tissue and causing a homeostatic imbalance in the nucleus pulposus tissue internal environment [5,47]. It is widely believed that activation of the NF-κB signaling pathway is related to IVDD; activation of this pathway leads to accelerated disc degeneration, whereas blocking this signaling pathway activation alleviates the aging process [48].…”

Research Progress on Sesquiterpenoids of Curcumae Rhizoma and Their Pharmacological Effects

“…Currently, 54 germacrane sesquiterpenoids have been isolated from Curcumae Rhizoma (Figure 2, Table 2). These natural products frequently engage in the formation of a five-membered ring at C-8 and C-12, yielding diverse structural moieties, such as furan rings (139)(140)(141)(142)(143)(144)(145), lactone rings (146)(147)(148)(149)(150)(151)(152)(153)(154)(155)(156)(157)(158), and lactam rings (161-168). This type of compound is prone to oxidation, which can produce aldehydes, ketones, esters, or oxygen bridges.…”

“…In the context of skin regeneration, it has been discovered that alismoxide (3), isozedoarondiol (20), isoprocurcumenol (43), germacrone (116), and 13-hydroxygermacrone (124) can activate the epidermal growth factor receptor, thereby promoting skin regeneration [142][143][144]. In relation to other activities, procurcumenol (29), germacrone (116), and dehydrocurdione (121) also exhibit neuroprotective effects [143]; curcumanolide A (241) has a relaxant effect on uterine smooth muscle tissue [15]; curdione (117) attenuates sepsis-induced lung injury [145]; curcumenol (61) reduces disc inflammation and improves disc catabolism [146]; zederone (143) has the potential to be a drug for the treatment of dementia [147]; and curcumenone (258) can exert a protective effect against intoxication [148]. These activities are primarily attributed to guaiane-type, germacrane-type, eudesmane-type, and elemane-type sesquiterpenoids.…”