Discovery of sesquiterpene from Youngia japonica with antitumor effect.

Fourteen sesquiterpenes, including one undescribed sesquiterpene lactone, were isolated from Youngia japonica, and their structures were identified by NMR, HRESIMS, ECD and calculated ECD. Cytotoxic activities of all isolates against A549, HeLa, and 4 T1 cell lines were detected by CCK8 assay. Among them, 2 showed obvious cytotoxic activity against A549 cells. Subsequently, the production of ROS, and apoptosis of A549 cells treated with 2 were evaluated. The result showed that 2 distinctly increased the ROS level, and induced the apoptosis of A549 cells. Further anticancer mechanism studies showed that 2 increased the expression of cleaved caspase 3. Taken together, our results demonstrated that 2 might become potential leading compounds for the treatment of lung cancer.

Electroacupuncture at "Baihui, Yintang and Shuigou" Acupoints Improves Post-Stroke Cognitive Impairment in Mice.

OBJECTIVE: To study the effect and mechanism of electroacupuncture at "Baihui, Yintang and Shuigou" acupoints on learning and memory in Post-Stroke Cognitive Impairment (PSCI) mice. METHODS: 52 male C57BL/6 mice were used to establish a MACO model by using middle cerebral artery occlusion (n=38), while the Sham only ligated at the distal end of the external carotid artery (n=14). After 28 days, the MCAO was divided into three groups based on the escape latency of Morris water maze: non cognitive impairment (MNP), post-stroke cognitive impairment (MP), and electroacupuncture intervention group (MPEA). In the MPEA, electroacupuncture at "Baihui and Yintang" acupoints was performed for 20 minutes (density wave, 2/15HZ and 1mA) supplemented by acupuncture at "Shuigou" acupoints once a day with a 6-day course of treatment. The intervention last for 2 courses with a 1-day interval. Morris water maze was used to detect the cognitive function of mice in each group; Nissl staining was used to observe hippocampal neurons; Western blot was used to detect the expression of GluA1, Syp, and Syt-1 in the affected hippocampus; IHC was used to detect the expression of Syp in the CA1 region of the contralateral hippocampus. CONCLUSION: Acupuncture at points "Baihui, Yintang, and Shuigou" can improve the learning and memory abilities of PSCI mice, and its mechanism is related to synaptic plasticity of hippocampus.

Neuroprotective Effect of Polyphenol Extracts from Terminalia chebula Retz. against Cerebral Ischemia-Reperfusion Injury.

Current therapies for ischemic stroke are insufficient due to the lack of specific drugs. This study aimed to investigate the protective activity of polyphenol extracts from Terminalia chebula against cerebral ischemia-reperfusion induced damage. Polyphenols of ethyl acetate and n-butanol fractions were extracted from T. chebula. BV2 microglial cells exposed to oxygen-glucose deprivation/reoxygenation and mice subjected to middle cerebral artery occlusion/reperfusion were treated by TPE and TPB. Cell viability, cell morphology, apoptosis, mitochondrial membrane potential, enzyme activity and signaling pathway related to oxidative stress were observed. We found that TPE and TPB showed strong antioxidant activity in vitro. The protective effects of TPE and TPB on cerebral ischemia-reperfusion injury were demonstrated by enhanced antioxidant enzyme activities, elevated level of the nucleus transportation of nuclear factor erythroid 2-related factor 2 and expressions of antioxidant proteins, with a simultaneous reduction in cell apoptosis and reactive oxygen species level. In conclusion, TPE and TPB exert neuroprotective effects by stimulating the Nrf2 signaling pathway, thereby inhibiting apoptosis.

Codonopsis pilosula polysaccharide attenuates Aß toxicity and cognitive defects in APP/PS1 mice.

Codonopsis pilosula Polysaccharides (CPPs), a traditional Chinese medicine used for thousands of years, is a potential neuroprotective polysaccharide via a relatively poorly understood mechanism. We previously reported that CPPs attenuated tau pathology in hTau transfected mice and therefore in the current work investigated the effect of CPPs on Aß toxicity and cognitive defects in APP/PS1 mice model. It was found that one-month intragastric administration of CPPs significantly ameliorated cognitive defects in APP/PS1 mice. In addition, CPPs treatment mitigated the loss of the synaptic plasticity and increased the synaptic proteins including synaptotagmin and PSD95. The expression of Aß42 and Aß40 was remarkably decreased in the hippocampus of APP/PS1 mice after CPPs treatment. We also found that CPPs coincubation significantly reduced the amount of APPß and Aß42 expression in cells. Intriguingly, the activity of BACE1 was decreased following CPPs treatment in both the hippocampus of APP/PS1 mice and in vitro experiments. Collectively, these results indicated that CPPs attenuated Aß pathology in APP/PS1 mice, and down-regulating BACE1 might be the underlaying mechanism which could be a therapeutic target for alleviating cognitive defects in AD pathology.