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A comprehensive identification of sphingoid bases and ceramides in wild Cordyceps was performed by integrating a sequential chromatographic enrichment procedure and an UHPLC-ultrahigh definition-Q-TOF-MS based sphingolipidomic approach. A total of 43 sphingoid bases and 303 ceramides were identified from wild Cordyceps, including 12 new sphingoid base analogues and 159 new ceramide analogues based on high-resolution MS and MS/MS data, isotope distribution, matching with the comprehensive personal sphingolipid database, confirmation by sphingolipid standards and chromatographic retention time rule. The immunosuppressive bioassay results demonstrated that Cordyceps sphingoid base fraction exhibits more potent immunosuppressive activity than ceramide fraction, elucidating the immunosuppressive ingredients of wild Cordyceps. This study represented the most comprehensive identification of sphingoid bases and ceramides from a natural source. The findings of this study provided an insight into therapeutic application of wild Cordyceps.

Oxidative stress is an early major pathological feature after subarachnoid hemorrhage (SAH) and involves in the development of acute brain injury, neuronal apoptosis and cerebral vasospasm following SAH. Antioxidant stress is an effective way to improve the prognosis of SAH. Oleanolic acid is a widely used triterpenoid from plants, which has strong antioxidant activities, hepatoprotective, anti‐inflammatory and anti‐cancer activities. However, whether oleanolic acid exerts its anti‐oxidant effect after SAH and the underlying mechanisms involved in it is unclear. In current study, the SAH model was established on Sprague Dawley rats using a standard intravascular puncture model. We found OA treatment significantly reduced malondialdehyde levels, and increased the levels of superoxide dismutase, catalase and GSH‐Px after SAH, and reduced many EBI‐related indicators, including brain edema, BBB disruption, SAH grades, and neurological score. In addition, the activation of Nrf2/HO‐1 pathway after SAH was also detected. And by using Nrf2 siRNA intracerebroventricular injections, apoptosis related factors downstream of Nrf2/HO‐1 pathway were detected. By TUNEL staining, OA treatment obviously reduced neuronal apoptosis. Therefore, we suggest that OA could alleviate oxidative stress and reduce neuronal apoptosis through activating Nrf 2/HO‐1 pathway.

YiQiFuMai (YQFM) powder injection as a modern preparation derived from Sheng Mai San, a traditional Chinese medicine, has been widely used in the treatment of cardiovascular and cerebrovascular diseases. However, its neuroprotective effect and underlying mechanism in cerebral ischemia remain to be explored. The present study was designed to investigate the neuroprotective effect of YQFM on endoplasmic reticulum (ER) stress-mediated neuronal apoptosis in the permanent middle cerebral artery occlusion- (MCAO-) injured mice and the oxygen-glucose deprivation- (OGD-) induced pheochromocytoma (PC12) cells. The results showed that single administration of YQFM (1.342 g/kg, i.p.) could reduce the brain infarction and improve the neurological deficits and the cerebral blood flow (CBF) after MCAO for 24 h in mice. Moreover, incubation with YQFM (100, 200, and 400 μg/mL) could increase the cell viability, decrease the caspase-3 activity, and inhibit the cell apoptosis in OGD-induced PC12 cells for 12 h. In addition, YQFM treatment could significantly modulate cleaved caspase-3 and Bcl-2 expressions and inhibit the expressions of ER stress-related marker proteins and signaling pathways in vivo and in vitro. In conclusion, our findings provide the first evidence that YQFM ameliorates cerebral ischemic injury linked with modulating ER stress-related signaling pathways, which provided some new insights for its prevention and treatment of cerebral ischemia diseases.