Dehydrocostuslactone attenuated oxygen and glucose deprivation/reperfusion-induced PC12 cell injury through inhibition of apoptosis and autophagy by activating the PI3K/AKT/mTOR pathway.

The purpose of this study is to investigate the protective effect of dehydrocostuslactone (DHL) on PC12 cells injury induced by oxygen and glucose deprivation/reperfusion (OGD/R) and its possible mechanism on the PI3K/AKT/mTOR pathway. The maestro 11.1 software was used to predict the binding sites of DHL with LC3, Beclin-1, PI3K, AKT, mTOR, Bax, Bcl-2, Caspase-3, Caspase-9, and Caspase-7. We used a cellular model of 2 h of OGD and 24 h of reperfusion to mimic cerebral ischemia-reperfusion injury. Cells were treated with DHL during the reperfusion phase. The docking results showed that DHL had binding sites with LC3, Beclin-1, PI3K, AKT, mTOR, Bax, Bcl-2, Caspase-3, Caspase-9, and Caspase-7. The expression levels of autophagy-related proteins, LC3 and Beclin-1 increased while P-PI3K, P-AKT, and P-mTOR decreased. Apoptosis-related proteins, namely, Bax, Cyto-c, Caspase-3, Caspase-7, Caspase-9 increased, but the anti-apoptosis Bcl-2 protein decreased. However, DHL effectively inhibited these undesirable changes induced by OGD/R in PC12 cells. Our results suggested that DHL attenuated OGD/R-induced neuronal injury by inhibiting apoptosis and autophagy by activating PI3K/AKT/mTOR signaling. This inhibition can improve cell survival and offer evidence for the beneficial effects of DHL on the nervous system.

The role of traditional Chinese medicine in the treatment of cognitive dysfunction in type 2 diabetes.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic cognitive dysfunction (DCD) is mainly one of the complications of type 2 diabetes mellitus (T2DM) with complex and obscure pathogenesis. Extensive evidence has demonstrated the effectiveness and safety of traditional Chinese medicine (TCM) for DCD management. AIM OF THE STUDY: This review attempted to systematically summarize the possible pathogenesis of DCD and the current Chinese medicine on the treatment of DCD. MATERIALS AND METHODS: We acquired information of TCM on DCD treatment from PubMed, Web of Science, Science Direct and CNKI databases. We then dissected the potential mechanisms of currently reported TCMs and their active ingredients for the treatment of DCD by discussing the deficiencies and giving further recommendations. RESULTS: Most TCMs and their active ingredients could improve DCD through alleviating insulin resistance, microvascular dysfunction, abnormal gut microbiota composition, inflammation, and the damages of the blood-brain barrier, cerebrovascular and neurons under hyperglycemia conditions. CONCLUSIONS: TCM is effective in the treatment of DCD with few adverse reactions. A large number of in vivo and in vitro, and clinical trials are still needed to further reveal the potential quality markers of TCM on DCD treatment.

Costunolide attenuates oxygen­glucose deprivation/reperfusion­induced mitochondrial­mediated apoptosis in PC12 cells.

The present study investigated the effect of costunolide (CT), a compound extracted from Aucklandia lappa Decne, to attenuate oxygen­glucose deprivation/reperfusion (OGD/R)­induced mitochondrial­mediated apoptosis in PC12 cells. The present study used molecular docking technology to detect the binding of CT with mitochondrial apoptotic protein targets. A model of oxygen­glucose deprivation for 2 h and reperfusion for 24 h in PC12 cells was used to mimic cerebral ischemic injury. Cell viability and damage were measured using the Cell Counting kit­8 and lactate dehydrogenase (LDH) cytotoxicity assay kits. Cellular apoptosis was analyzed using flow cytometry. A fluorescence microscope determined intracellular [Ca2+] and mitochondrial membrane potential. Furthermore, immunofluorescence and Western blot analyses were used to detect the expression of apoptosis­associated proteins. CT contains binding sites with Caspase­3, Caspase­9 and Caspase­7. CT markedly enhanced cell viability, inhibited LDH leakage, increased intracellular [Ca2+], stabilized the mitochondrial membrane potential, increased the expression of Bcl­2 and inhibited the expression of Apaf­1, Bax, cleaved­caspase­7, cleaved­caspase­9 and cleaved­caspase­3. CT may markedly protect PC12 cells from damage caused by OGD/R, and its mechanism is associated with blocking the calcium channel and inhibiting mitochondrial­mediated apoptosis.