Thevetiaflavone from Wikstroemia indica ameliorates PC12 cells injury induced by OGD/R via improving ROS-mediated mitochondrial dysfunction

Abstract

Cerebral ischemia and following reperfusion affects many people worldwide. To discover efficient therapeutic approaches, numerous natural products have been investigated. The current study investigated the protective effects of thevetiaflavone, a natural flavonoid obtained from Wikstroemia indica, and the associated mechanisms using PC12 cells induced by oxygen and glucose deprivation. As a result, thevetiaflavone improves cell viability and suppresses the leakage of lactate dehydrogenase from the cytoplasm. Further investigation of the mechanisms demonstrated that thevetiaflavone decreases overproduction of ROS and ameliorates ROS‑mediated mitochondrial dysfunction, including collapse of mitochondrial membrane potential and mitochondrial permeability transition pore opening. Thevetiaflavone reduces the intracellular Ca2+ level, which is closely associated with mitochondrial function and interplays with ROS. Furthermore, thevetiaflavone inhibits apoptosis in PC12 cells through upregulating the expression of Bcl‑2 and downregulating that of Bax and caspase‑3 in addition to increasing the activity of caspase‑3. These results further indicate the protective effects of thevetiaflavone in vivo and its application in the clinic.

Protective Effects of Oroxylin A on Oxygen-Glucose Deprivation/Reperfusion-Induced PC12 Cells by Activating the Sonic Hedgehog Signal Pathway

“…It has been reported that OGD/R resulted in cell apoptosis. 39 Consistent with that study, our data showed that cell viability was decreased by OGD/R compared with the control group, whilst, cell apoptosis decreased by OGD/R was reversed by oroxylin A pretreatment in a dose-dependent manner, which confirmed that oroxylin A protected the cells from the injury induced by insufficient oxygen-glucose. ROS levels in the different groups ( # P < 0.05, ### P < 0.001 vs DMSO 1% + OGD/R; ***P < 0.001 vs control).…”

“…As ischemic stroke is accompanied by insufficient oxygen-glucose, PC12 cells induced by oxygen-glucose deprivation/reperfusion, which has frequently served as the cell model of cerebral ischemia reperfusion, was used as the cell model in this study. [37][38][39] Oroxylin A, a flavonoid, possesses low toxicity in vivo and in vitro and is a promising compound. It possesses many functions, including anti-inflammation, neuroprotective, and oxidation resistance.…”

SWELL1 promotes cell growth and metastasis of hepatocellular carcinoma in vitro and in vivo

“…The results showed that SWELL1 protected HCC cells from apoptosis. Apoptotic cells generate excess ROS and lose MMP, which in turn reduce the production of ATP [12,36]. In this study, the results of the ROS measurements also indicated the anti-apoptotic role of SWELL1 in HCC.…”

“…5a). ROS production correlates closely with mitochondrial dysfunction, and mitochondrial dysfunction can be indicated by changes in mitochondrial membrane potential (MMP) [11,12]. As shown in Fig.…”

Compounds Isolated from Wikstroemia taiwanensis Regulate Bone Remodeling by Modulating Osteoblast and Osteoclast Activities

“…Besides, compounds isolated from the Wikstroemia genus of plants exhibited antiviral activities against the hepatitis B virus and hepatitis C virus ( Khong et al, 2012 ; Li et al, 2018 ). They also protected PC12 neuronal cells against oxygen and glucose deprivation/restoration-induced injury ( Yao et al, 2017 ; Yao et al, 2019 ). These studies provided compelling evidence for the medicinal properties of Wikstroemia genus plants.…”