Chun-Tao Che

Anti-proliferative effect of ginseng saponins on human prostate cancer cell line

Ginseng is a medicinal herb widely used in Asian countries, and many of its pharmacological actions are attributed to the ginsenosides. In a study of the anti-proliferative activity of ginsenosides using human prostate carcinoma LNCaP cell line, ginsenoside Rg3 displayed growth inhibitory activity. The cells lost its adherent property after incubation in the presence of 250 microM of ginsenoside for 48h. The expression of biomarker genes, including prostate specific antigen (PSA), androgen receptor (AR) and 5alpha-reductase (5alphaR), and that of the proliferating cell nuclear antigen (PCNA), were suppressed. Ginsenoside Rg3 induced classic apoptotic morphology and interfered with the expression of apoptosis-related genes, bcl-2 and caspase-3, in LNCaP cells, as demonstrated by fluorescence microscopy, flow cytometry and reverse transcriptase-polymerase chain reaction. Taken our results together, we suggested that ginsenoside Rg3 activated the expression of cyclin-kinase inhibitors, p21 and p27, arrested LNCaP cells at G1 phase, and subsequently inhibited cell growth through a caspase3-mediated apoptosis mechanism.

Peony glycosides produce antidepressant-like action in mice exposed to chronic unpredictable mild stress: effects on hypothalamic-pituitary-adrenal function and brain-derived neurotrophic factor.

The root part of Paeonia lactiflora Pall. (Ranunculaceae), commonly known as peony, is a commonly used Chinese herb for the treatment of depression-like disorders. Previous studies in our laboratory have demonstrated that total glycosides of peony (TGP) produced antidepressant-like action in various mouse models of behavioral despair. The present study aimed to examine whether TGP could affect the chronic unpredictable mild stress (CUMS)-induced depression in mice. The mechanism(s) underlying the antidepressant-like action was investigated by measuring serum corticosterone level, glucocorticoid receptor (GR) and brain-derived neurotrophic factor (BDNF) mRNA levels in brain tissues. CUMS, being lasted for 6 weeks, caused depression-like behavior in mice, as indicated by the significant decrease in sucrose consumption and increase in immobility time in the forced swim test. Whereas serum corticosterone level was significantly increased in mice exposed to CUMS, expressions of GR mRNA in hippocampus, and BDNF mRNA in hippocampus and frontal cortex, were decreased in CUMS-treated mice. Daily intragastric administration of TGP (80 or 160 mg/kg/day) during the six weeks of CUMS significantly suppressed behavioral and biochemical changes induced by CUMS. The results suggest that the antidepressant-like action of TPG is likely mediated by modulating the function of hypothalamic-pituitary-adrenal axis and increasing the expression of BDNF in brain tissues.

Treatment of Diarrhea-Predominant Irritable Bowel Syndrome with Traditional Chinese Herbal Medicine: A Randomized Placebo-Controlled Trial

BACKGROUND:As there is no effective treatment for irritable bowel syndrome (IBS), many patients turn to traditional Chinese medicine (TCM) for possible cure. We investigated the therapeutic efficacy of an ancient herbal Chinese formula in patients with diarrhea-predominant IBS.METHODS:This was a randomized double-blinded placebo-controlled trial. Chinese IBS patients with predominant diarrhea symptoms that fulfilled Rome II criteria were recruited. The diagnosis was verified by a TCM herbalist using TCM criteria. Eligible patients were randomized to receive a standard preparation of TCM extracts that contained 11 herbs or placebo with similar appearance and taste for 8 wk after a 2-wk run-in period. Patients were followed up for an additional 8 wk post-treatment. Primary outcome was patients global symptom assessment. Other outcome measures included individual IBS symptom scores and health-related quality of life (short form 36).RESULTS:One hundred nineteen patients were randomized: 60 to receive TCM and 59 to receive placebo. There was no significant difference in the proportion of patients with global symptom improvement between the TCM and placebo groups at week 8 (35% vs 44.1%, p = 0.38) and at week 16 (31.7% vs 33.9%, p = 0.62). Moreover, there was no difference in individual symptom scores and the quality-of-life assessment between the two groups at all time points.BACKGROUND:The use of this herbal formulation for diarrhea-predominant IBS did not lead to global symptom improvement. Further controlled clinical studies may be necessary to characterize the role of TCM in the management of IBS.

Long-term treatment with peony glycosides reverses chronic unpredictable mild stress-induced depressive-like behavior via increasing expression of neurotrophins in rat brain

The root part of Paeonia lactiflora Pall., commonly known as peony, is a commonly used Chinese herb for the treatment of depression-like disorders. Previous studies in our laboratory have showed that total glycosides of peony (TGP) produced antidepressant-like action in various mouse models of behavioral despair. The present study aimed to investigate the mechanism(s) underlying the antidepressant-like action of TGP by measuring neurotrophins including brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in non-stressed and chronic unpredictable mild stress (CUMS)-treated rats. TGP (80 or 160 mg/kg/day) was administered by oral gavage to the animals for 5 weeks. The results showed that CUMS caused depression-like behavior in rats, as indicated by the significant decreases in sucrose consumption and locomotor activity (assessed by open-field test). In addition, it was found that BDNF contents in the hippocampus and frontal cortex were significantly decreased in CUMS-treated rats. CUMS treatment also significantly decreased the level of NGF in the frontal cortex of the animals. Daily intragastric administration of TGP (80 or 160 mg/kg/day) during the five weeks of CUMS significantly suppressed behavioral and biochemical changes induced by CUMS. Treating non-stressed animals with TGP (160 mg/kg) for 5 weeks also significantly increased BDNF contents in the hippocampus and frontal cortex, and NGF contents in the frontal cortex. The results suggest that the antidepressant-like action of TGP is mediated, at least in part, by increasing the expression of BDNF and NGF in selective brain tissues.

Antidepressant-like effect of ethanol extract from Paeonia lactiflora in mice.

The present study investigated the antidepressant effect of ethanol extract of Paeonia lactiflora (EPL) in mice using forced swim test, tail suspension test, open‐field test and reserpine test. Our results showed that intragastric administration of EPL at the doses of 250 and 500 mg/kg for seven days significantly reduced the duration of immobility in both forced swim test and tail suspension test. EPL at the dose of 500 mg/kg was as effective as the positive control (chlorimipramine, 20 mg/kg) in these tests. However, these treatments did not affect the number of crossing and rearing in the open‐field test. Treating mice with EPL at the doses of 250 and 500 mg/kg significantly antagonized reserpine‐induced ptosis and hypothermia. However, at the dose of 125 mg/kg, EPL antagonized only the hypothermia but not ptosis induced by reserpine. The results clearly demonstrated the antidepressant effect of Paeonia lactiflora in animal models of depression. The action of Paeonia lactiflora may be mediated via the central monoaminergic neurotransmitter system. Copyright

Flueggines A and B, Two New Dimeric Indolizidine Alkaloids from Flueggea virosa

Two unprecedented C,C-linked dimeric indolizidine alkaloids, flueggines A (1) and B (2), were isolated from the twigs and leaves of Flueggea virosa. The structures and absolute configurations were elucidated by means of NMR, single-crystal X-ray diffraction, and CD analyses. Compound 1 is the first example of Securinega alkaloids bearing an isoxazolidine ring, the plausible biogenetic pathway of which is also proposed. Compound 2 exhibited growth inhibitory activity against MCF-7 and MDA-MB-231 human breast cancer cells.

Antidepressant-like effect of peony glycosides in mice.

AIM OF THE STUDY The root part of Paeonia lactiflora Pall. (Ranunculaceae), known as peony, is often used in Chinese herbal formulae for the treatment of depression-like disorders. Previous studies in our laboratory have shown that an ethanol extract of peony produced antidepressive effects in mouse models of depression. It is well known that peony contains glycosides such as paeoniflorin and albiflorin, yet it remains unclear whether the total glycosides of peony (TGP) are effective. The present study aims to evaluate the antidepressant-like effects of TGP. MATERIALS AND METHODS The antidepressant-like effects of TGP was determined by using animal models of depression including forced swim and tail suspension tests. The acting mechanism was explored by determining the effect of TGP on the activities of monoamine oxidases. RESULTS Intragastric administration of TGP at 80 and 160 mg/kg for seven days caused a significant reduction of immobility time in both forced swim and tail suspension tests, yet TGP did not stimulate locomotor activity in the open-field test. In addition, TGP treatment antagonized reserpine-induced ptosis and inhibited the activities of monoamine oxidases in mouse cerebrum. CONCLUSION These results suggest that the antidepressive effects of TGP are mediated, at least in part, by the inhibition of monoamine oxidases.

Effects of peony glycosides on mice exposed to chronic unpredictable stress: further evidence for antidepressant-like activity.

ETHNOPHARMACOLOGY RELEVANCE Peony, the processed root of Paeonia lactiflora Pall. (Ranunculaceae), is a component herb of many traditional formulae for the treatment of depression-like disorders. AIM OF THE STUDY The present study aimed to investigate whether the total glycosides of peony (TGP) could prevent depression induced by chronic stress. MATERIALS AND METHODS Mice were subjected to an experimental setting of chronic unpredictable stress (CUS). The effect of TGP treatment on CUS-induced depression was examined by measuring behavioral and neurochemical parameters of depression and the antioxidant status of brain tissue. RESULTS CUS-induced depression, as indicated by a significant increase in immobility time in the tail suspension test, was associated with increases in the activities of monoamine oxidases, depletion of reduced glutathione, and an increase in malondialdehyde level, in mice brains. TGP treatment alleviated the extent of CUS-induced depression and the associated impairment of antioxidant status in the mouse brain. CONCLUSION The results suggest that TGP alleviates depression induced by chronic unpredictable stress. The antidepressant-like activity of TGP is probably mediated by inhibition of monoamine oxidases and the attenuation of oxidative stress in mouse brain.

Differential effects of saralasin and ramiprilat, the inhibitors of renin–angiotensin system, on cerulein-induced acute pancreatitis

Acute pancreatitis is an inflammatory disease characterized by pancreatic tissue edema, acinar cell necrosis, hemorrhage and inflammation of the damaged gland. It is believed that acinar cell injury is initiated by the activation of digestive zymogens inside the acinar cells, leading finally to the autodigestion of the pancreas. Previous study in our laboratory demonstrated that cerulein-induced acute pancreatitis was associated with an up-regulation of local renin-angiotensin system (RAS) in rat pancreas. Therefore, the utilization of RAS inhibitors may provide a novel and alternative treatment for acute pancreatitis. By means of a rat model of cerulein-induced acute pancreatitis, results from the present study showed that an intravenous injection of saralasin, an antagonist for angiotensin II receptors, at a dose of 40 microg/kg 30 min before the induction of acute pancreatitis significantly attenuated pancreatic edema. Results from the biochemical measurements showed that pretreatment with saralasin at a dose of 20 microg/kg markedly reduced pancreatic injury, as evidenced by the decreased activities of alpha-amylase and lipase in plasma. However, the same recipe of ramiprilat, a specific inhibitor for angiotensin-converting enzyme, at a dose of 20 microg/kg did not provide any protective effect against acute pancreatitis. On the contrary, pretreatment with ramiprilat at a dose 40 microg/kg enhanced cerulein-induced pancreatic injury. Results from histopathological analysis of these RAS inhibitors further confirmed with those results as obtained from biochemical analysis. These data indicate that administration of saralasin but not ramiprilat could be protective against acute pancreatitis and that activation of pancreatic RAS in acute pancreatitis may play a role in pancreatic tissue injury.

Bioassay-Guided Isolation of Neuroprotective Compounds from Uncaria rhynchophylla against Beta-Amyloid-Induced Neurotoxicity.

Uncaria rhynchophylla is a component herb of many Chinese herbal formulae for the treatment of neurodegenerative diseases. Previous study in our laboratory has demonstrated that an ethanol extract of Uncaria rhynchophylla ameliorated cognitive deficits in a mouse model of Alzheimers disease induced by D-galactose. However, the active ingredients of Uncaria rhynchophylla responsible for the anti-Alzheimers disease activity have not been identified. This study aims to identify the active ingredients of Uncaria rhynchophylla by a bioassay-guided fractionation approach and explore the acting mechanism of these active ingredients by using a well-established cellular model of Alzheimers disease, beta-amyloid- (Aβ-) induced neurotoxicity in PC12 cells. The results showed that six alkaloids, namely, corynoxine, corynoxine B, corynoxeine, isorhynchophylline, isocorynoxeine, and rhynchophylline were isolated from the extract of Uncaria rhynchophylla. Among them, rhynchophylline and isorhynchophylline significantly decreased Aβ-induced cell death, intracellular calcium overloading, and tau protein hyperphosphorylation in PC12 cells. These results suggest that rhynchophylline and isorhynchophylline are the major active ingredients responsible for the protective action of Uncaria rhynchophylla against Aβ-induced neuronal toxicity, and their neuroprotective effect may be mediated, at least in part, by inhibiting intracellular calcium overloading and tau protein hyperphosphorylation.