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Background: Morin is a flavanoid which exhibits potent antioxidant activity in various oxidative stress related diseases. The current study was attempted to scrutinize the preclinical bio-efficacy of morin on focal ischemia., Methods: The animal model of focal cerebral ischemic injury was done by midbrain carotid artery occlusion (MCAO) method, followed by Morin (30mg/kg) administration for seven days., Results: The outcome of the study showed that treatment with morin displayed positive effects in reducing the focal cerebral ischemia. This effect was evident with the improvements in neurological deficits, reduction in MDA content and elevation of antioxidant levels (SOD, GSH and Gpx). Furthermore, protein expression of Bax and caspase-3 were effectively down-regulated, whilst the expression of Bcl-2 was significantly elevated. On the other hand, the mRNA expression of proinflammatory cytokines was significantly reduced in focal cerebral ischemic rats upon morin intervention., Conclusion: Thus, the beneficial effects of morin on cerebral ischemia assault may result from the reduction of oxidative stress, inhibition of apoptosis and inflammation. The neuroprotective effects of morin supplement may serve as potent adjuvant in the amelioration of ischemic stroke.

This study was designed to investigate the effect of pseudo-G-Rh2, a novel metabolite of ginsenoside Rh2, on the apoptosis of SGC-7901 human gastric cancer cells. Pseudo-G-Rh2 demonstrated antitumor activity and significantly inhibited the proliferation of SGC-7901 cells in a concentration-dependent manner. After treatment with pseudo-G-Rh2, SGC-7901 cells showed typical apoptotic morphological features, such as chromatin condensation and DNA fragmentation. Pseudo-G-Rh2 could induce mitochondrial membrane potential loss, which led to the release of cytochrome c (Cyt c), Smac/Diablo and apoptosis-inducing factor (AIF) to the cell cytoplasm. Furthermore, pseudo-G-Rh2 exposure not only decreased the expression of the Bcl-2 protein but also increased the expression of the Bax protein and the activities of caspase-9 and caspase-3 in SGC-7901 cells. These results demonstrated that pseudo-G-Rh2 inhibited the proliferation of SGC-7901 cells by initiating apoptosis. Pseudo-G-Rh2-induced apoptosis was associated with a drop in the mitochondrial transmembrane potential, down-regulation of Bcl-2, up-regulation of Bax and activation of caspase-9 and caspase-3.

An ETS family member, ETS Related Gene (ERG) is involved in the Ewing family of tumors as well as leukemias. Rearrangement of the ERG gene with the TMPRSS2 gene has been identified in the majority of prostate cancer patients. Additionally, overexpression of ERG is associated with unfavorable prognosis in prostate cancer patients similar to leukemia patients. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) regulate transcription as well as epigenetic status of genes through acetylation of both histones and transcription factors. Deregulation of HATs and HDACs is frequently seen in various cancers, including prostate cancer. Many cellular oncogenes as well as tumor viral proteins are known to target either or both HATs and HDACs. Several studies have demonstrated that there are alterations of HDAC activity in prostate cancer cells. Recently, we found that ERG binds and inhibits HATs, which suggests that ERG is involved in deregulation of protein acetylation. Additionally, it has been shown that ERG is associated with a higher expression of HDACs. In this study, we tested the effect of the HDAC inhibitors valproic acid (VPA) and trichostatin-A (TSA) on ERG-positive prostate cancer cells (VCaP). We found that VPA and TSA induce apoptosis, upregulate p21/Waf1/CIP1, repress TMPRSS2-ERG expression and affect acetylation status of p53 in VCaP cells. These results suggest that HDAC inhibitors might restore HAT activity through two different ways: by inhibiting HDAC activity and by repressing HAT targeting oncoproteins such as ERG.

Ginsenoside Rh2, a major effective constituent of ginseng, has been suggested to have a pro-apoptotic effect in a variety of cancer cells. Pseudo-Ginsenside-Rh2 (pseudo-G-Rh2) is a novel derivative of ginsenoside Rh2. The aim of the present study was to evaluate the effect of pseudo-G-Rh2 on the apoptosis of lung adenocarcinoma A549 cells. The cytotoxicity of pseudo-G-Rh2 on A549 cells was evaluated using an MTT assay. Apoptosis was detected using DAPI staining and flow cytometry. The expression of apoptosis associated proteins was identified by western blot analysis. The results demonstrated that pseudo-G-Rh2 inhibits the proliferation of A549 cells in a dose-dependent manner. DAPI staining revealed topical morphological changes in apoptotic bodies following pseudo-G-Rh2 treatment. Flow cytometric analysis revealed that the percentage of Annexin V-fluorescein isothiocyanate-positive cells, which are apoptotic, increased with pseudo-G-Rh2 treatment in a dose-dependent manner. Furthermore, treatment with pseudo-G-Rh2 increased the level of reactive oxygen species in A549 cells as well as the activation of caspase-9, caspase-3 and poly ADP-ribose polymerase. Pseudo-G-Rh2 treatment was observed to induce mitochondrial membrane potential loss. Furthermore, the results of western blotting revealed that B-cell lymphoma 2 (Bcl-2) expression was significantly decreased while Bcl-2-associated X protein expression was significantly upregulated in A549 cells with pseudo-G-Rh2 treatment. Pseudo-G-Rh2-induced apoptosis was accompanied by sustained phosphorylation of Ras, Raf, extracellular signal-regulated kinase (ERK) and p53. In conclusion, the results of the present study suggest that pseudo-G-Rh2 induces mitochondrial apoptosis in A549 cells and is responsible for excessive activation of the Ras/Raf/ERK/p53 pathway. [ABSTRACT FROM AUTHOR]

Hepatoblastoma is the most common primary liver tumor for children aged <5 years old. 20(S)-Protopanaxadiol (PPD) is a ginsenoside extracted from Pananx quinquefolium L., which inhibits tumor growth in several cancer cell lines. The purpose of the present study was to assess the anticancer activities of 20(S)-PPD in human hepatoblastoma HepG2 cells. The cytotoxicity of 20(S)-PPD on HepG2 cells was evaluated using an MTT assay. Apoptosis was detected using DAPI staining and flow cytometry. The expression of apoptosis-associated proteins was identified by western blotting. The results demonstrated that 20(S)-PPD inhibited the viability of HepG2 cell in a dose and time-dependent manner. The IC50 values were 81.35, 73.5, 48.79 µM at 24, 48 and 72 h, respectively. Topical morphological changes of apoptotic body formation following 20(S)-PPD treatment were detected by DAPI staining. The percentage of Annexin V-fluoroscein isothyiocyanate positive cells were 3.73, 17.61, 23.44 and 65.43% in HepG2 cells treated with 0, 40, 50 and 60 µM of 20(S)-PPD, respectively. Furthermore, 20(S)-PPD upregulated the expression of Bax and downregulated the expression of Bcl-2 and also activated caspases-3 and -9, and Poly [ADP-ribose] polymerase cleavage. In addition, 20(S)-PPD inhibited the phosphorylation of protein kinase B (Akt; Ser473). The results indicate that 20(S)-PPD inhibits the viability of HepG2 cells and induces apoptosis in HepG2 cells by inhibiting the phosphoinositide-3-kinase/Akt pathway. [ABSTRACT FROM AUTHOR]

In the present study, we aim to evaluate the potential neuroprotective effect and the underlying mechanism of Kaempferide-7-O-(4″-O-acetylrhamnosyl)-3-O-rutinoside (A-F-B) against cerebral I/R injury. Adult male rats were pretreated with A-F-B by intragastric administration once a day for 3 days. One hour after the third day administration, animals were subjected to 2 h of transient middle cerebral artery occlusion (MCAO) followed by 24 h of reperfusion. Neurological deficit, infarct volume, histopathological changes, oxidative stress-related biochemical parameters, neuronal apoptosis, apoptosis-related proteins and the expression of pro-inflammator cytokines genes were measured. A-F-B significantly decreased neurological and histological deficits, reduced the infarct volume, and decreased neuroapoptosis. Meanwhile, A-F-B inhibited the expression of Bax, cleaved caspase-3, cleaved caspase-9, and promoted Bcl-2 expression. In addition, the expression of pro-inflammator cytokines, including phospho-NF-kBp65, interleukin-1β, interleukin-6, tumor necrosis factor-α, intercellular adhesion molecule-1, cyclooxygenase-2 and inducible nitric oxide synthase, were also suppressed by A-F-B pretreatment. Furthermore, pretreatment with A-F-B could significantly increase the activities of superoxide dismutase, glutathione peroxidase, but decrease the content of malondiadehyde in blood serum. These results suggest that A-F-B has the neuroprotective effect in ischemic stroke by suppressing neuroinflammation, reactive oxygen species and neuroapoptosis. [ABSTRACT FROM AUTHOR]

• The results of the first study on Resveratrol-primed exosomes on autophagy and apoptosis after spinal cord injury likely via PI3K signaling pathway. • The reduction in the level of apoptosis-related protein is inhibited after the exosome treatment in SCI model. • The discoveries jointly infer that Resveratrol-primed exosomes might affect autophagy and apoptosis and Mediated to the neuroprotection in SCI. Spinal cord injury (SCI) is a traumatic condition of the central nervous system (CNS) that can cause paralysis of the limbs. The molecular mechanisms of neural repair following SCI remain unclear and no effective treatment for SCI currently exists, since drugs have difficulty crossing the blood-brain barrier (BBB). The present study aimed to investigate whether exosomes could be used as specific carriers of resveratrol for induction of neuronal autophagy both in vitro and in vivo for the treatment of SCI. The results indicate that exosomes are able to enhance the solubility of resveratrol and enhance penetration of the drug through the BBB, thereby increasing its concentration in the CNS. Exosomes derived from resveratrol-treated primary microglia (Exo + Res) assisted the rehabilitation of paralyzed limbs in rats. Restoration of neural function following SCI was mediated through increased induction of autophagy and inhibition of apoptosis of neurons both in vitro and in vivo via activation of the PI3K signaling pathway. The mechanism of action of Exo + Res may be associated with the PI3K inhibitor 3-methyladenine (3-MA) in primary spinal neurons. The results suggest that Exo + Res are highly effective at crossing the BBB with good stability, suggesting they have potential for enhancing targeted drug delivery and the recovery of neuronal function in SCI therapy, likely associated with the induction of autophagy and inhibition of apoptosis via the PI3K signaling pathway. [ABSTRACT FROM AUTHOR]