The mechanism by which Naru 3 pill protects against intervertebral disc cartilage endplate degeneration based on network pharmacology and experimental verification

Abstract

Context Naru 3 pill is a traditional Mongolian medicine for the treatment of intervertebral disc degeneration (IDD), but the mechanism is not yet clear. Objective This study investigated the mechanism of Naru 3 pill in the treatment of IDD. Materials and methods Active ingredients and related targets of Naru 3 pill, as well as IDD-related genes, were collected from public databases. The analysis was performed by protein‒protein interaction network analysis, gene ontology and Kyoto Gene and Genome Encyclopedia (KEGG) functional enrichment analysis, molecular docking and molecular dynamics simulations. Finally, the network pharmacology results were validated by in vitro experiments. Results Network analysis showed that sesamin, piperine and ellagic acid were potential key components and CASP3, BAX and BCL2 were key targets. KEGG analysis indicated the apoptotic pathway as a potential pathway. Molecular docking showed that sesamin interacted better with the targets than the other components. The results of molecular dynamics simulations indicated that the three systems BAX-sesamin, BCL2-sesamin and CASP3-sesamin were stable and reasonable during the simulation. In vitro experiments showed that sesamin had the least effect on cell growth and the most pronounced proliferation-promoting effect, and so sesamin was considered the key component. The experiments confirmed that sesamin had antiapoptotic effects and reversed the expression of CASP3, BAX and BCL2 in degeneration models, which was consistent with the network pharmacology results. Furthermore, sesamin alleviated extracellular matrix (ECM) degeneration and promoted cell proliferation in the IDD model. Conclusion The present study suggested that Naru 3 pill might exert its therapeutic and antiapoptotic effects on IDD by delaying ECM degradation and promoting cell proliferation, which provides a new strategy for the treatment of IDD.

Plant-Derived Senotherapeutics for the Prevention and Treatment of Intervertebral Disc Degeneration and Aging

“…Rat caudal vertebrae needle-stab model activity in ionizing radiation-induced senescent normal human WI-38 fibroblasts [150] and having emerged as the top-runner in a computational screening for natural senotherapeutic repurposing candidates that mimic dasatinib based on gene expression data [282]-has been reported to rescue IL1β-induced elevated levels of oxidative stress in cartilage explants and to reduce the expression of major inflammatory markers in a goat ex vivo OA model [283]; (x) sesamin has been found to protect against IDD based on a network pharmacology analysis [284] and to inhibit LPS-induced inflammation and ECM catabolism in the rat IVD in vitro and ex vivo [285], while its intradiscal injection in a rat tail disc has been shown to protect from lesion-induced IDD in vivo [286]; (xi) wogonin has been reported to suppress inflammatory mediators and ECM-degrading enzymes and to up-regulate type II collagen in IL-1β-stimulated rat NP IVD cells and to ameliorate IDD in an in vivo rat caudal vertebrae needle-stab model [287].…”

Integrated virtual screening and in vitro studies for exploring the mechanism of triterpenoids in Chebulae Fructus alleviating mesaconitine-induced cardiotoxicity via TRPV1 channel

“…In the use habits of ethnic minorities, it is more commonly used together with the aconitum herbs, such as Aconitum pendulum Busch, Aconiti kusnezoffii radix. In order to reduce the toxicity or preservation effect, CF decoction processing aconitums or compatibility aconitums with CF are popular methods in clinical practice ( Li et al, 2019 ; Li et al, 2021 ), and they are often used in the form of pills or powders, such as Naru Sanwei Wan ( Guo et al, 2023 ). However, the mechanism behind the attenuation toxicity remains unclear and requires further exploration.…”