Cajaninstilbene Acid Prevents Corticosterone-Induced Apoptosis in PC12 Cells by Inhibiting the Mitochondrial Apoptotic Pathway

Abstract

Background/Aims: Cajaninstilbene acid (3-hydroxy-4-prenyl-5-methoxystilben-2 -carboxylic acid, CSA), a natural stilbene isolated from the leaves of Cajanus cajan, has attracted considerable attention for its wide range of pharmacological activities. This study investigated whether CSA protects against corticosterone (CORT)-induced injury in PC12 cells and examined the potential mechanisms underlying this protective effect. Methods: Cell viability and cytotoxicity were detected using a 3-(4,5-desethyithiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and a lactate dehydrogenase (LDH) assay kit, respectively. PC12 cell apoptosis was measured using Hoechst 33342 staining and a DNA fragmentation assay kit, and intracellular Ca²⁺ concentrations were assessed by fluorescent labelling. Next, the mitochondrial permeability transition pores (mPTPs) and mitochondrial membrane potentials (∆Ψm) were detected using a colorimetric mPTP detection kit and a 5,5',6,6'-tetrachloro-1,1',3,3'- tetraethylbenzimidazolyl-carbocyanine iodide (JC-1) kit, respectively. Finally, cytochrome c, caspase-3 and inhibitor of caspase-activated deoxyribonuclease (ICAD) expression levels were monitored by western blot analysis. Results: Treatment with 100 µmol/l CORT induced cytotoxicity in PC12 cells. However, CSA dose-dependently increased cell viability and decreased LDH release as well as CORT-induced apoptosis. Mechanistically, compared with the CORT-treated group, CSA strongly attenuated intracellular Ca²⁺ overload and restored mitochondrial functions, including mPTPs and ∆Ψm. Furthermore, the down-regulation of cytochrome c and ICAD protein expression and the blockage of caspase-3 activity were observed upon CSA treatment. Conclusions: In summary, our data are the first to show that the in vitro antidepressant-like effect of CSA may be attributed to the cytoprotection of neurons and that such neuroprotective mechanisms are correlated with intracellular Ca²⁺ homeostasis and mitochondrial apoptotic pathways.

H<sub>2</sub>S protects PC12 cells against toxicity of corticosterone by modulation of BDNF-TrkB pathway

“…Numerous findings have demonstrated that corticosterone causes neurotoxicity, apoptosis [13,42,53], and oxidative stress [54,55]. Based on these findings, our present study was designed to detect the toxicity of corticosterone to PC12 cells.…”

“…Taken together, these findings reveal that BDNF-TrkB pathway mediates the protective effect of H 2 S against the corticosteroneinduced neurotoxicity. Corticosterone, a principal corticosteroid, has been shown to elicit toxic effects on neurons [13,42,43]. Increasing data revealed that increase in brain corticosterone concentration is associated with depression [44][45][46].…”

Metabolomics reveals the protective of Dihydromyricetin on glucose homeostasis by enhancing insulin sensitivity

“…The spectral data were analyzed as ourprevious reports43. The resulting data were mean-centered and pareto-scaled prior to the statistical analysis via supervised partial least-squares discriminant analysis (PLS-DA) to differentiate each group.…”

Cajaninstilbene acid inhibits osteoporosis through suppressing osteoclast formation and RANKL‐induced signaling pathways

“…CSA is a natural compound extracted from cajan (a perennial legume from the family Fabaceae), with roles in the treatment of diabetes (Grover et al, ), measles (Nwodo et al, ), as an antifungal (Brito et al, ) and as an antioxidant (Wang et al, ; Wei et al, ; Zhang et al, ). CSA itself was reported as being an active anti‐inflammatory agent in RAW264.7 cells (Huang et al, ), antibacterial against methicillin‐resistant staphylococcus aureus (MRSA) (Geng et al, ), antioxidative and antiapoptotic in PC12 cells (Jiang et al, ; Y. Liu et al, ), antihepatitis (X. Y. Ji et al, ), and anticancer in MCF7 cells (Kadioglu et al, ). The present study examined CSA's influence on osteoclast activity and formation and on OVX‐induced bone loss in mice.…”