Complete chloroplast genome sequence of Mucuna prurien and its phylogenetic position.

Mucuna pruriens is traditional medicinal plant originated in South Africa. We characterize the complete plastid genome of M. pruriens, which is a circular-mapping molecule 152,119 bp in length. The genome has a large single-copy region (LSC) of 78,258 bp and a small single-copy region (SSC) of 18,735 bp, respectively. Additionally, the overall GC content of the chloroplast genome was 35.37%. The genome contains 138 genes, including 96 protein-coding, 38 tRNA, and four rRNA genes. The gene content and structure are conserved compared to other species in the genus Glycine. The chloroplast genome and existing data were used to infer its phylogenetic position. The results showed that M. pruriens clustered together with Glycine max and G. soja. These findings provide potential genetic markers that can aid in understanding the genetic diversity of M. pruriens.

Novel Stachydrine-Leonurine Conjugate SL06 as a Potent Neuroprotective Agent for Cerebral Ischemic Stroke.

As major active ingredients of the traditional Chinese medicine motherwort, stachydrine and leonurine were found to have protective effects against cerebral ischemia. However, their bioavailability in vivo was low, and their efficacy was unsatisfactory, which limited their further application. To solve these problems, the conjugates based on the structures of stachydrine and leonurine were designed and synthesized. SL06 was found to have neuronal cell survival improvement, neuronal apoptosis restraining, activation of superoxide dismutase (SOD) activity, and inhibition of lactic dehydrogenase (LDH), reactive oxygen species (ROS), malondialdehyde (MDA) in vitro. In vivo, the infarction size was significantly reduced by SL06 in the middle cerebral artery occlusion rat model. SL06 could also activate protein kinase B (AKT)/glycogen synthase kinase 3ß (GSK-3ß) activity and promoted the expression of antiapoptoticprotein Bcl-2. On the other hand, the expression of the apoptosis-associated protein cleaved caspase-3 would be inhibited as well. Thus, SL06 as the neuroprotective agent has potential for the treatment of cerebral ischemic stroke.

Design, synthesis, and biological evaluation of novel stachydrine derivatives as potent neuroprotective agents for cerebral ischemic stroke.

Stachydrine is a natural product with multiple protective biological activities, including those involved in preventing cancer, ischemia, and cardiovascular disease. However, its use has been limited by low bioavailability and unsatisfactory efficacy. To address this problem, a series of stachydrine derivatives (A1/A2/A3/A4/B1/B2/B3/B4) were designed and synthesized, and biological studies were carried out in vitro and in vivo. When compared with stachydrine, Compound B1 exhibited better neuroprotective effects in vitro, and significantly reduced infarction size in the model of the middle cerebral artery occlusion rat model. Therefore, Compound B1 was selected for further research on ischemic stroke. Graphical abstract.

Seahorse treatment improves depression-like behavior in mice exposed to CUMS through reducing inflammation/oxidants and restoring neurotransmitter and neurotrophin function.

ETHNOPHARMACOLOGICAL RELEVANCE: Seahorses (Hippocampus erectus), belonging to syngnathidae of syngnathiformes, are a traditional Chinese medicine for increasing and balancing vital energy within the body and brain, as well as calming mood and improving sleep. AIM OF THE STUDY: Based on the hypothesis of monoamine neurotransmitter deficiency, current antidepressant treatments, with many side effects, are ineffective. Thus, novel hypotheses, inflammation, oxidative stress and neurotrophin dysfunction were proposed. Since seahorses can modulate immune function, reduce oxidants and nourish brain function, it may effectively treat depression. Therefore, this study aimed to detect the predominant chemical characterization of seahorses and investigate the mechanism by which seahorses exert antidepressant effects by using a chronic unpredictable mild stress (CUMS)-induced model of depression. METHODS: Control and CUMS-exposed mice were fed normal or seahorse diet (0.018 g seahorses power) for 8-weeks. After behavioral tests, serum corticosterone, hippocampal expression of CD11b, glial fibrillary acidic protein (GFAP), and brain derived neurotrophic factor (BDNF), and the concentration of interleukin (IL)-1ß and monoamine neurotransmitters were measured, while amygdala IL-1ß and IL-10, anti-oxidative and oxidative enzyme were also studied. Then main phytoconstituents of seahorses was analyzed using liquid chromatography-mass spectrometry (LC-MS) methods. RESULTS: Compared to controls, sucrose preference, exploration in open field, social interaction, entry numbers into and times spent on the open arms of elevated plus maze were significantly decreased, while immobility times in forced-swimming was increased in CUMS mice. These changes were associated with significantly reduced levels of serotonin, noradrenaline and dopamine, also expressions of GFAP and BDNF. Moreover, CUMS elevated IL-1ß concentrations and reactive oxygen species (ROS), while decreased IL-10 concentration and anti-oxidative super oxide dismutase and glutathione peroxidase. Seahorse diet significantly reversed anxiety- and depression-like behaviors, which were correlated with reducing IL-1ß and ROS, but increasing neurotransmitter concentrations and BDNF expression. Several compounds were found in seahorses, including docosahexaenoic acid, eicosapentaenoic acid, bis(2-ethylheptyl) phthalate, chrysophanol, and hypoxanthine. CONCLUSION: Seahorses could attenuate the CUMS-induced anxiety- and depression-like behaviors by reducing oxidative stress and inflammation, and normalizing neurotransmitter and neurotrophin function, which are possibly due to the activities of one or more or mixture of these identified compounds.

SL1122-37, a novel derivative of sorafenib, has greater effects than sorafenib on the inhibition of human hepatocellular carcinoma (HCC) growth and prevention of angiogenesis.

SL1122-37 is a novel derivative of sorafenib that was characterized by introducing trifluoromethyl on the 4-position of indazole. We aimed to evaluate the effects of SL1122- 37 on human hepatocellular carcinoma (HCC) growth and on umbilical vein vascular endothelial cells (HUVECs) angiogenesis. Its efficacy and mechanisms were compared with sorafenib. SL1122-37 significantly prevented PLC/PRF/5 cell proliferation as estimated by colorimetric assay. Flow cytometry analysis showed the induction of apoptosis and arrest of cell cycle in G1 phase. Western blotting showed the decrease of cyclin D1 and regulation of apoptotic proteins. Further analysis suggested that these effects of SL1122-37 might arise from its roles in the inhibition of multi-kinases, including c-Kit and its downstream targets and the Wnt/ß-catenin pathway in PLC/PRF/5 cells. SL1122-37 also possessed the activity of antiangiogenesis, showing the prevention of HUVEC migration and capillary tube formation. Western blotting indicated the inhibition of VEGF and phosphorylation of VEGFR-2 in HUVECs. Statistical analysis suggested that SL1122-37 might possess greater activities than sorafenib in the prevention of HCC proliferation and HUVEC angiogenesis. Conclusion, SL1122-37 could develop as a potent anticancer agent for the treatment of HCC.