Phytomedicine

Editorial Board

2010-03-01

Phase I study of the botanical formulation PHY906 with capecitabine in advanced pancreatic and other gastrointestinal malignancies

2010-01-21

Abstract: Purpose: The botanical formulation, PHY906, has been used widely in Eastern countries to treat gastrointestinal symptoms including diarrhea, nausea and vomiting. PHY906 may also have anti-tumor properties and may potentiate the action of several chemotherapeutic agents based on pre-clinical studies. We conducted a Phase I study using PHY906 in combination with capecitabine in patients with advanced pancreatic and gastrointestinal malignancies to determine the maximum tolerated dose (MTD) of capecitabine in combination with PHY906.Patients and Methods: This study was a single institution, open-label, Phase I study of PHY906 800mg BID on days 1-4 in combination with escalating doses of capecitabine (1000, 1250, 1500, and 1750mg/m2) orally twice daily on days 1-7 of a 14-day cycle (7/7 schedule). Capecitabine was increased until the appearance of dose limiting toxicities (DLTs). Measurements of efficacy included tumor response by Response Evaluation Criteria in Solid Tumors (RECIST).Results: Twenty-four patients with a median age of 67 years (range 40-84) with pancreatic cancer (15), colon cancer (6), cholangiocarcinoma (1), esophageal cancer (1) and unknown primary (1) received a total of 116 cycles (median 5 cycles; range 1-17 cycles) over 4 dose levels of capecitabine. One DLT (Grade 4 AST/ALT, Grade 3 hyponatremia) was observed in the 1000mg/m2 cohort of patients. No further DLT was observed in the subsequent cohorts and doses of capecitabine were escalated to 1750mg/m2 BID. There were no DLTs at the maximum dose level of 1750mg/m2, however, the delivered dose-intensity of capecitabine was similar at the 1750mg/m2 dose level as the 1500mg/m2 dose level. Therefore, the MTD was defined at 1500mg/m2 of capecitabine in this dosing schedule with PHY906. One patient achieved a partial response, and 13 patients had stable disease that lasted more than six weeks.Conclusion: The MTD of capecitabine was determined to be 1500mg/m2 BID administered in a 7/7 schedule, in combination with PHY906 800mg BID on days 1-4. This combination was well tolerated and warrants further study.

The fixed herbal drug composition “Saikokaryukotsuboreito” prevents bone loss with an association of serum IL-6 reductions in ovariectomized mice model

T. Hattori, W. Fei, T. Kizawa, S. Nishida, H. Yoshikawa, Y. Kishida — 2010-01-25

Abstract: Purpose: Saikokaryukotsuboreito (SRB) is a traditional Japanese herbal medicine that has been used to treat hyperlipidemia. As some studies have shown that lipid-lowering drugs reduce osteoporosis, we investigated the effect of SRB on bone metabolism in the postmenopausal period using an ovariectomized (OVX) murine model.Material and Methods: Fifteen aged 9 weeks female mice were divided into three groups (n=5 each). The OVX group and SRB group underwent bilateral ovariectomy, after which the OVX group was fed a normal diet and the SRB group fed a normal diet containing 2% SRB. The sham group underwent sham surgery and was then fed a normal diet. Eight weeks after surgery, all mice were sacrificed, and bone volume, bone histomorphometric parameters, and bone-associated phenotype were compared among the groups.Results: Compared with the OVX group, the SRB group showed suppression of bone volume loss at the tibia (SRB group: 12.7±0.7%, OVX group: 9.8±0.4%; p=0.005, ANOVA) and lumbar spine (SRB group: 15.1±0.9%, OVX group: 11.3±0.1%; p=0.031, ANOVA). A significant decrease in eroded surface was also observed in SRB-treated ovariectomized mice compared with the OVX group (p=0.022, ANOVA). We also found that serum levels of interleukin (IL)-6, a primary mediator of bone resorption, in the SRB group were significantly lower than in the OVX group (SRB: 52.5±6.8pg/ml; OVX: 138.0±23.1pg/ml; p=0.011, ANOVA). However, unexpectedly, SRB did not affect estradiol and total cholesterol in ovariectomized mice.Conclusion: SRB can prevent loss of bone volume and suppress serum IL-6 levels in this postmenopausal model and is a promising candidate for treatment of postmenopausal osteoporosis.

A randomized double blind placebo controlled clinical evaluation of extract of Andrographis paniculata (KalmCold™) in patients with uncomplicated upper respiratory tract infection

2010-01-22

Abstract: A randomized, double blind placebo controlled clinical study was conducted to evaluate the efficacy of KalmCold™, an extract of Andrographis paniculata, in patients with uncomplicated upper respiratory tract infection (URTI). The assessment involved quantification of symptom scores by Visual Analogue Scale. Nine self evaluated symptoms of cough, expectoration, nasal discharge, headache, fever, sore throat, earache, malaise/fatigue and sleep disturbance were scored. A total of 223 patients of both sexes were randomized in two groups which received either KalmCold™ (200 mg/day) or placebo in a double blind manner. In both the treatments, mean scores of all symptoms showed a decreasing trend from day 1 to day 3 but from day 3 to day 5 most of the symptoms in placebo treated group either remained unchanged (cough, headache and earache) or got aggravated (sore throat and sleep disturbance) whereas in KalmCold™ treated group all symptoms showed a decreasing trend. Within groups, mean scores of symptoms in both the groups decreased significantly (p ≤ 0.05) from day 1 to day 3 and day 5 while from day 3 to day 5 all symptoms except expectoration in placebo group did not improve significantly whereas in KalmCold™ treated group all symptoms improved significantly (p ≤ 0.05) except earache. Comparing mean between both groups, all symptoms at day 1 and day 3 were found to be the same while at day 5 all symptoms except earache in KalmCold™ treated group improved significantly (p ≤ 0.05) than placebo group. Similarly, within groups, overall scores of all symptoms in both the groups decreased significantly (p ≤ 0.05) from day 1 to day 3 and day 5 while from day 3 to day 5 placebo group did not improve significantly whereas KalmCold™ treated group showed significant improvement (p ≤ 0.05). On between groups analysis, KalmCold™ group showed significant reduction (p ≤ 0.05) in overall symptom scores as compared to placebo group. In both placebo and KalmCold™ treated groups, there were only a few minor adverse effects with no significant difference in occurrence (Z = 0.63; p > 0.05). The comparison of overall efficacy of KalmCold™ over placebo was found to be significant (p ≤ 0.05) and it was 2.1 times (52.7%) higher than placebo. The findings of this study revealed that KalmCold™ was effective in reducing symptoms of upper respiratory tract infection.

The aqueous extract of Hibiscus sabdariffa calices modulates the production of monocyte chemoattractant protein-1 in humans

2009-09-22

Abstract: Diet supplementation and/or modulation is an important strategy to significantly improve human health. The search of plants as additional sources of bioactive phenolic compounds is relevant in this context. The aqueous extract of Hibiscus sabdariffa is rich in anthocyanins and other phenolic compounds including hydroxycitric and chlorogenic acids. Using this extract we have shown an effective protection of cultured peripheral blood mononuclear cells from the cellular death induced by H2O2 and a significant role in the production of inflammatory cytokines. In vitro, the extract promotes the production of IL-6 and IL-8 and decreases the concentration of MCP-1 in supernatants in a dose-dependent manner. In humans, the ingestion of an acute dose of the extract (10g) was well tolerated and decreased plasma MCP-1 concentrations significantly without further effects on other cytokines. This effect was not due to a concomitant increase in the antioxidant capacity of plasma. Instead, its mechanisms probably involve a direct inhibition of inflammatory and/or metabolic pathways responsible for MCP-1 production, and may be relevant in inflammatory and chronic conditions in which the role of MCP-1 is well established. If beneficial effects are confirmed in patients, Hibiscus sabdariffa could be considered a valuable traditional herbal medicine for the treatment of chronic inflammatory diseases with the advantage of being devoid of caloric value or potential alcohol toxicity.

Escin improves sperm quality in male patients with varicocele-associated infertility

Yujiang Fang, Lei Zhao, Feng Yan, Xiaoyan Xia, Donghui Xu, Xijun Cui — 2009-08-17

Abstract: Purpose: To evaluate the efficacy of escin to improve sperm quality in Chinese male patients with varicocele-associated infertility.Methods: This study included 219 male patients with varicocele-associated infertility. These patients were randomly assigned into three groups: the control, the surgery and the escin group. 106 patients, with a mean age of 30 years old and a mean period of infertility of 5.0 years, were recruited in the escin group and a daily dose of 60mg (30mg every 12h) of escin was administered orally during an uninterrupted period of 2 months. The diameter of spermatic vein was also measured using color Doppler ultrasonography before and after treatment in the escin group. Patients in all groups took composite medicines favorable for sperm quality and semen were obtained and analyzed before and after treatment.Results: In response to treatment, the improvement rates in sperm density in the control, the surgery and the escin group, were 38.5%, 68.8%, and 57.5%, respectively. The differences in the surgery and the escin groups were significant compared to that in the control group (68.8% or 57.5% vs. 38.5%, P<0.05). The improvement rates in sperm motility in the control, the surgery and the escin group were 46.2%, 77.1%, and 55.7%, respectively. Significant difference was only observed between the surgery and the control group (77.1% vs. 46.2%, P<0.05). In the escin group, when severity of varicocele was classified to mild, moderate or severe degree according to the diameter of the spermatic vein, the improvement rates in disease severity were higher in the mild (41.7% vs. 20.0%, P<0.05) and moderate severity subgroups (64.4% vs. 20.0%, P<0.05) when compared to that in the severe subgroup (20.0%). The improvement rate in disease severity was also higher in the moderate subgroup when compared to that in the mild subgroup (64.4% vs. 41.7%, P<0.05). During the period of treatment, only very low frequencies of mild adverse effects were observed, most of which resolved without further symptomatic drug therapy after advising the patients to take escin after meal. Escin has little effect on vital signs, blood counts, liver or kidney function.Conclusion: Escin is a safe and effective drug to improve sperm quality in Chinese male patients with varicocele-associated infertility.

The antioxidant effect of green tea catechin ameliorates experimental liver injury

2010-01-21

Abstract: Purpose: Several studies have reported green tea catechin to have both antifibrotic and anti-oxidative effects. The goal of this study was to evaluate the effect of green tea cathechin therapy in hepatic tissue injury using cholestatic rats with bile duct ligation.Materials and methods: We performed bile duct ligation on cholestatic seven-week-old male Wistar rats and classified them into three groups according to the method of treatment. The groups comprised the SHAM group, the NT-group (no-treatment-group), and the T-group (treatment-group). The rats were orally administered green tea catechin at a dose of 50mg/kg/day and were sacrificed on the 17th postoperative day. We subsequently investigated the levels of fibrosis and antioxidant activity associated with various clinical markers. We evaluated the serum AST and ALT levels and performed immunohistochemical analyses for 4-hydroxynonenal (4-HNE), 8-oxo-2′deoxyguanosine (8-OHdG) and transforming growth factor-β1 (TGF-β1). We also evaluated the levels of activator protein-1 m-RNA (AP-1 m-RNA) and tissue inhibitor metalloproteinase-1 m-RNA (TIMP-1 m-RNA) by Real Time PCR. Finally, we performed Azan staining and immunohistochemical staining of α-smooth muscle actin (α‐SMA) to evaluate the degree of fibrosis.Results: The values of serum AST, serum ALT, AP-1 m-RNA, α‐SMA, TGF-β1, 4-HNE, and 8-OHdG in the T-Group were significantly lower than those in NT-Group. Therefore, the administration of green tea catechin might have suppressed the oxidative stress, controlled the stellate cell activation and consequently reduced the fibrosis.Conclusion: Green tea catechin may reduce hepatic fibrosis by suppressing oxidative stress and controlling the transcription factor expression involved in stellate cell activation.

Pharmacokinetic interaction studies of tanshinones with tolbutamide, a model CYP2C11 probe substrate, using liver microsomes, primary hepatocytes and in vivo in the rat

X. Wang, W.Y.W. Lee, P.M.Y. Or, J.H.K. Yeung — 2009-08-13

Abstract: The effects of Danshen and its active components (tanshinone I, tanshinone IIA, dihydrotanshinone and cryptotanshinone) on tolbutamide 4-hydroxylation was investigated in the rat. Danshen (0.125–2mg/ml) decreased 4-hydroxy-tolbutamide formation in vitro and in vivo. Enzyme kinetics studies showed that inhibition of tolbutamide 4-hydroxylase activity was competitive and concentration-dependent. The Ki values of the tanshinones were: dihydrotanshinone (8.92μM), cryptotanshinone (24.5μM), tanshinone I (80.3μM) and tanshinone IIA (242.9μM). In freshly prepared primary rat hepatocytes, tanshinones inhibited tolbutamide 4-hydroxylation in a concentration-dependent manner, with EC40 values in the order: cryptotanshinone (15.8μM), tanshinone IIA (16.2μM), dihydrotanshinone (20.1μM) and tanshinone I (48.2μM). In whole animal studies, single dose Danshen treatment (50 or 200mg/kg, i.p.) increased tolbutamide clearance (17–26.9%), decreased AUC (14.4–20.9%) and increased the Vd (7.26%). Three-day Danshen treatment (200mg/kg/day, i.p.) decreased the Cinitial, increased T1/2 and Vd but did not affect tolbutamide clearance and AUC. Tolbutamide-4-hydroxylation in vivo was decreased by Danshen after acute and after 3-day treatment, with decreases in the AUC of 4-hydroxy-tolbutamide (15–28%) over the time period studied. Despite competitive inhibition of rat CYP2C11 in vitro and in vivo, as shown by the decrease in tolbutamide 4-hydroxylation, only minor changes in tolbutamide pharmacokinetics was observed. This study illustrated that the herb-drug interaction potential should be monitored by both in vitro and in vivo biotransformation/ pharmacokinetic parameters.

Tanshinone II A attenuates inflammatory responses of rats with myocardial infarction by reducing MCP-1 expression

Z.H. Ren, Y.H. Tong, W. Xu, J. Ma, Y. Chen — 2009-10-05

Abstract: The root of Salvia miltiorrhiza Bunge, a well-known traditional Chinese medicine, has been used effectively for the treatment of cardiovascular diseases for a long time. The mechanisms underlying this therapeutic effect are not, however, fully understood. Tanshinone IIA (Tan IIA) is one of the major active components of this Chinese medicine. Therefore, the present study was performed to investigate whether Tan IIA, which has shown a cardio-protective capacity in myocardial ischemia, has an inhibitory effect on the inflammatory responses following myocardial infarction (MI) and its potential mechanisms. In an in vivo study, rat MI model was induced by permanent left anterior descending coronary artery (LAD) ligation. After the operation rats were divided into three groups (sham, MI and Tan IIA). Tan IIA was administered intragastrically at a dose of 60mg/kg body wt./day. One week later, rats were sacrificed and the hemodynamic, pathological and molecular biological indices were examined. In an in vitro study, the inflammatory model was established by TNF-α stimuli on cardiacmyocyte and cardiac fibroblasts. Tan IIA attenuates the MI pathological changes and improves heart function, and reduces expression of MCP-1, TGF-β1 and macrophage infiltration. Furthermore, Tan IIA could also decrease the expression of TNF-α and activation of nuclear transcription factor-kappa B (NF-κB). In vitro, Tan IIA could reduce MCP-1 and TGF-β1secretion of cardiac fibroblasts. The present study demonstrated that the cardioprotective effects of Tan IIA might be attributed to its capacity for inhibiting inflammatory responses.

Inhibition of warfarin hydroxylation by major tanshinones of Danshen (Salvia miltiorrhiza) in the rat in vitro and in vivo

Windy W.P. Wu, John H.K. Yeung — 2009-07-24

Abstract: Danshen (Salvia miltiorrhiza) is commonly used in the treatment of cardiovascular and cerebrovascular diseases. In this study, the effects of a Danshen ethyl acetate extract containing the major tanshinones, an aqueous extract containing salvianolic acid B and danshensu, and individual tanshinones (tanshinone I, tanshinone IIA and cryptotanshinone) on warfarin hydroxylation was investigated. In rat liver microsomes study, the ethyl acetate extract of Danshen, tanshinone I, tanshinone IIA and cryptotanshinone decreased the formation of 4′-, 6- and 7-hydroxy-warfarin, mediated by CYP1A1, CYP2C6 and CYP2C11 activities, respectively. The aqueous extract of Danshen had no effect on warfarin hydroxylation. Both acute and 3-day Danshen treatment significantly decreased Cmax and prolonged Tmax of warfarin in the rats. The formation of 4′- and 7-hydroxywarfarin in vivo was decreased significantly after 3-day danshen treatment. In steady state study in vivo, the steady state plasma warfarin concentration was increased by 23% when Danshen was co-administered. The results suggest that tanshinones inhibited CYP1A1, CYP2C6 and CYP2C11-mediated warfarin metabolism both in vitro and in vivo in the rats. The timing of Danshen intake relative to warfarin contributed to different pharmacokinetics of the free warfarin concentration.

Preventive effect of crocin of Crocus sativus on hemodynamic, biochemical, histopathological and ultrastuctural alterations in isoproterenol-induced cardiotoxicity in rats

2009-09-11

Abstract: We investigated the effects of crocin, a pharmacologically active constituent of Crocus sativus L., in isoproterenol (ISO)-induced cardiotoxicity with reference to hemodynamic, antioxidant, histopathological and ultrastructural parameters. Rats were administered crocin (5, 10 and 20mg/kg/day) or vehicle orally for 21 days along with ISO (85mg/kg, subcutaneously, at 24h interval) on 20th and 21st day. On 22nd day ISO-control rats showed cardiac dysfunction as indicated by lowering of systolic, diastolic and mean arterial blood pressures. In addition, a significant decrease in maximum positive and negative rate of developed left ventricular pressure (±LVdp/dtmax) and an increase in left ventricular end-diastolic pressure (LVEDP) were observed. Furthermore, a marked reduction in the activities of myocardial creatine kinase-MB (CK-MB) isoenzyme, lactate dehydrogenase (LDH), superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) levels along with an increase in content of malondialdehyde (MDA) were observed. Myocardial necrosis, edema and inflammation were evident from the light microscopic and ultrastructural changes. Crocin at the dose of 20mg/kg/day significantly modulated hemodynamic and antioxidant derangements. The preventive role of crocin on ISO-induced MI was reconfirmed by histopathological and ultrastructural examinations. The effect at the dose of 20mg/kg/day of crocin was more pronounced than that of other two doses (5 and 10mg/kg/day). The results suggest that crocin may have cardioprotective effect in ISO-induced cardiac toxicity through modulation of oxidative stress in such a way that maintains the redox status of the cell.

Effect of total saponins of “panax notoginseng root” on aortic intimal hyperplasia and the expressions of cell cycle protein and extracellular matrix in rats

2009-09-14

Abstract: Aim of the study: the effect of total saponins of “panax notoginseng root” on aortic intimal hyperplasia and the expressions of cell cycle protein and extracellular matrix in ratsMaterials and methods: Sprague-Dawley rats were randomly divided into sham-operated, control, TSPN and atorvastatin group. Rat aorta intima in all groups were injured by insertion of domestic balloon catheter into the aortae except sham-operated rats. Drugs were administrated orally from the second day after vascular injury and continued for 14 days. The injured segments of aortae were collected on the sixteenth day after operation to observe the morphological changes of vascular structure and to examine the expressions of proliferating cell nuclear antigen(PCNA), cyclinD1, cyclinE, collagen I(Col-I), fibronect(FN), matrix metalloproteinase-9(MMP-9) and tissue inhibitor metalloproteinase-1(TIMP-1). Results: TPNS significantly inhibited the vascular intimal hyperplasia. TPNS significantly lowered the expression of PCNA, cyclinE, cyclinD1, FN and MMP-9. TPNS had no significant impacts on the expression of Col-I and TIMP-1.Conclusions: Our studies indicated that TSPN could inhibit vessel restenosis after vascular intimal injury, and its mechanisms may be related to the blockage of the excessive proliferation of VSMC, the reduction of ECM protein deposition in the endometrium, and the degradation of ECM protein.

Aged garlic extract delays the appearance of infarct area in a cerebral ischemia model, an effect likely conditioned by the cellular antioxidant systems

2009-07-24

Abstract: Experimental evidence has shown that some garlic-derived products have a protective effect against ischemic brain injury. The present study was designed to investigate the effect of aged garlic extract (AGE), establish the therapeutic window, and determine its protective mechanism in a cerebral ischemia model. Animals were subjected to middle cerebral artery occlusion (MCAO) for 2h and treated with 1.2ml/kg body wt.(i.p.) of AGE 30min before, at the beginning of (0R), or 1h after reperfusion. The 0R treatment significantly reduced the size of the infarct area after 2h of reperfusion. Repeated doses subsequent to the 0R treatment (at 1, 2, or 3h after reperfusion) had no effect on the temporal window of protection. The protective 0R treatment with AGE prevented the increase in nitrotyrosine and the decrease in total superoxide dismutase, glutathione peroxidase, and extracellular superoxide dismutase activities induced by MCAO. These data indicate that AGE delays the effects of ischemia/reperfusion-induced neuronal injury. However, this treatment itself was not associated with a noticeable improvement in the neurological outcome, or with an effect on the inflammatory response. We conclude that the neuroprotective effect of AGE in the 0R treatment might be associated with control of the free-radical burst induced by reperfusion, preservation of antioxidant enzyme activity, and the delay of other pathophysiological processes.

Anti-stress effects of the “tonic” Ptychopetalum olacoides (Marapuama) in mice

A.L. Piato, B.C. Detanico, V.M. Linck, A.P. Herrmann, D.S. Nunes, E. Elisabetsky — 2009-08-17

Abstract: With the recognition that high levels of sustained stress are associated with the natural course of countless illnesses, effective anti-stress agents have gained importance. Improved endurance to particularly stressful periods is one of the medicinal claims for Marapuama (Ptychopetalum olacoides Bentham, PO), a popular Amazonian herbal. The purpose of this study was to evaluate if PO possesses anti-stress properties. To this end, an extract from PO (POEE) was evaluated on anxiety and glucose levels in mice submitted to the unpredictable chronic mild stress (UCMS) paradigm. POEE did not present anxiolytic effects, but was able to prevent (p<0.01) the UCMS-induced anxiety as assessed by the light/dark test (time spent in the lit area, POEE 100 and 300mg/kg 235.9±20.6s and 250.4±17.4s, respectively, compared to DMSO 104.7±24.4s). Likewise, although POEE did not induce noticeable effects on glycemia, it effectively (p<0.01) prevented the UCMS-induced hyperglycemia (POEE 100 and 300mg/kg 106.4±6.7mg/dl and 107.3±3.3mg/dl, respectively, compared to DMSO 134.6±5.9mg/dl). Additionally, POEE (50-200mg/kg i.p. and 800mg/kg p.o.) significantly (p<0.01 and p<0.05, respectively) increased the time to hypoxia-induced convulsion (by 38%, 51%, 59% and 27%, respectively for i.p. and p.o. treatments). The data indicate that POEE counteracts some of the effects brought about by chronic stress. This study combined with the identified antioxidant and neuroprotective properties, as well as the claimed benefits associated with stressful periods suggest that Ptychopetalum olacoides (Marapuama) might possess adaptogen-like properties.

Effects of total glucosides of paeony on oxidative stress in the kidney from diabetic rats

2009-09-16

Abstract: TGP, extracted from the traditional Chinese herb root of Paeonia lactiflora pall, has been shown to have therapeutic effect in experimental diabetic nephropathy. However, its mechanism is not fully understood. In this study, the effects of TGP on oxidative stress were investigated in the kidney of diabetic rats induced by streptozotocin. TGP (50, 100, 200mg/kg) was orally administered once a day for 8 weeks. TGP treatment in all three doses significantly lowered 24 h urinary albumin excretion rate in diabetic rats and attenuated glomerular volume. TGP treatment with 100 and 200mg/kg significantly reduced indices for tubulointerstitial injury in diabetic rats. The level of MDA was significantly increased in the kidney of diabetic rats and attenuated by TGP treatment at the dose of 200mg/kg. TGP treatment in a dose-dependent manner decreased the level of 3-NT protein of the kidney which increased under diabetes. T-AOC was significantly reduced in diabetic rat kidney and remarkably increased by TGP treatment at the dose of 100 and 200mg/kg. Activity of antioxidant enzyme such as SOD, CAT was markedly elevated by TGP treatment with 200mg/kg. Western blot analysis showed that p-p38 MAPK and NF-κB p65 protein expression increased in diabetic rat kidney, which were significantly decreased by TGP treatment. It seems likely that oxidative stress is increased in the diabetic rat kidneys, while TGP can prevent diabetes-associated renal damage against oxidative stress.

Role of cyclin inhibitor protein p21 in the inhibition of HCT116 human colon cancer cell proliferation by American ginseng (Panax quinquefolius) and its constituents

M.L. King, L.L. Murphy — 2009-08-12

Abstract: American ginseng and its ginsenoside constituents have been shown to exert anti-cancer effects although the mechanism of action remains unclear. The present study determined the effects of water-extracted ginseng (GE) or its ginsenoside (GF) and polysaccharide (PS) fractions on the proliferation of human colon cancer cells and examined the role of p21 in mediating these effects using wild-type and p21-/- HCT116 human colon carcinoma cells. Proliferation was inhibited by GE, GF, and PS in wild-type and p21-/- cells, and the p21-/- cells were more sensitive to these treatments. Wild type cells treated with GE were arrested in the G0/G1 phase of the cell cycle and the expression of p53 and p21 proteins was increased while phospho-MEK levels decreased. In contrast, cells deficient in p21 displayed reduced cell viability, elevated number of dead cells, and increased expression of Bax and cleaved caspase-3 proteins. Both polysaccharides and ginsenosides appear to be responsible for the anti-proliferative and proapoptotic effects of GE. This study suggests that p21 functions to arrest HCT116 wild-type cells treated with GE, while p21-deficient cells undergo cell death in a ginseng constituent-dependent manner.

Cancer chemopreventive activity of diversin from Ferula diversivittata in vitro and in vivo

M. Iranshahi, A. Sahebkar, S.T. Hosseini, M. Takasaki, T. Konoshima, H. Tokuda — 2009-07-24

Abstract: A prenylated coumarin (diversin, 1) together with four new sesquiterpene lactones (diversolides A, D, F and G, 2-5) isolated from the roots of Ferula diversivittata were studied for their possible inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). All of the tested compounds were active against EBV-EA activation. Among these compounds diversin (IC50: 7.7) exhibited the strongest inhibitory effect and was selected to examine its effects on in vivo two-stage mouse skin carcinogenesis induced by 7,12-dimethylbenz[a]anthracene (DMBA) as initiator and TPA as promoter. Treatment with compound 1 (85nmol) along with DMBA/TPA inhibited papilloma formation up to week 7 and the percentage of papilloma bearers was approximately 93.3% at week 20. The average number of papillomas formed per mouse was only 5.5 even at week 20. The results of the present investigation indicated that diversin might be valuable as a potent cancer chemopreventive agent and its potency was comparable with those of curcumin and quercetin, two well-known cancer chemopreventive agents.

Effect of xanthone from Kielmeyera coriacea stems on serotonergic neurons of the median raphe nucleus

2009-08-12

Abstract: Kielmeyera coriacea Mart. (Clusiaceae), known as “Pau Santo”, is used to treat several tropical diseases. The hydroethanolic extract (HE) of Kielmeyera coriacea stems and its semi-pure dichloromethane constituent (DCM) produced an anti-immobility effect in rats submitted to the forced swimming test (FST), suggesting a antidepressant-like profile. This study evaluated the effect of intra-median raphe nucleus (MRN) microinjection of 1,3,7-trihydroxy-2-(3-methylbut-2-enyl)-xanthone, present in large quantity in the HE from Kielmeyera coriacea stems, on immobility behaviour in the FST in rats. The effects of xanthone were compared with intra-MRN microinjections of Way100635 (5-HT1A antagonist) or (+) 8-OH-DPAT (5-HT1A agonist).Locomotor activity in the open-field test (OFT) was evaluated as a complementary measure. Xanthone (0.3ng) or Way100635 (2.5μg) reduced, whereas (+) 8-OH-DPAT (5.0μg) increased immobility time in the FST. Way100635 (2.5 or 5.0μg) completely reversed the effects of (+) 8-OHDPAT (5.0μg), and potentiated the anti-immobility effect of the ineffective dose of xanthone (0.2ng) in the FST. The association of effective doses of (+) 8-OH-DPAT (5.0μg) and xanthone (0.3ng) annulled the effect of each compound on immobility time. These results suggest that xanthone acts as an antagonist at 5-HT1A autoreceptors in MRN and increases serotonin (5-HT) availability in projection regions, proving to be a prototype drug that may be useful in mood isorders such as depression, or indeed be a beneficial adjunctive treatment improving the efficacy and/or accelerating the effects of antidepressant drugs in patients with major depression.

Activity of (-)α-bisabolol against Leishmania infantum promastigotes

2009-07-24

Abstract: Many of the drugs used to treat leishmaniasis are associated with numerous adverse effects. Agents of natural origin have shown activity against different parasites. With this background, an in vitro study was conducted on the activity of (-)α-bisabolol, the principal component of Chamomilla recutita essential oil, against Leishmania infantum promastigotes, the main species responsible for human leishmaniasis in Spain. At the two highest concentrations tested (1000 and 500μg/ml), (-)α-bisabolol and pentamidine (control agent) achieved 100% inhibition of L. infantum promastigote. These in vitro data can be considered promising in support of the therapeutic use of (-)α-bisabolol preparations to treat leishmaniasis caused by L. infantum species.

In vitro and in vivo antifibrotic effects of rosmarinic acid on experimental liver fibrosis

Gui-Sheng Li, Wang-Lin Jiang, Jing-Wei Tian, Gui-Wu Qu, Hai-Bo Zhu, Feng-Hua Fu — 2009-07-24

Abstract: This study was carried out to investigate whether rosmarinic acid (RA) has antifibrotic effect on experimental liver fibrosis in vitro and in vivo and its possible mechanism. Culture of hepatic stellate cells (HSCs) determine proliferation and expression of transforming growth factor-β1 (TGF-β1), connective transforming growth factor (CTGF) and α-smooth muscle actin (α-SMA). In carbon tetrachloride (CCL4)-induced rat liver fibrosis model, determined biochemical indicator, liver fibrosis grade and histopathological changes, immunohistochemical detected liver TGF-β1 and CTGF expression. The results indicated that RA could inhibit HSCs proliferation, inhibit TGF-β1, CTGF and α-SMA expression in cultured HSCs. It has marked evident in reducing fibrosis grade, ameliorating biochemical indicator and histopathological morphology, reducing liver TGF-β1 and CTGF expression in CCL4-induced liver fibrosis. These findings suggest that RA has potentially conferring antifibrogenic effects.

Monoamine levels in rat striatum after acute intraperitoneal injection of strictosidinic acid isolated from Psychotria myriantha Mull. Arg. (Rubiaceae)

2009-07-24

Abstract: Strictosidinic acid 10mg/kg, isolated from Psychotria myriantha leaves, were administered intraperitoneally to Wistar male rats (n=5-6). After 60minutes, striatum was dissected, homogenized and injected onto HPLC-ED chromatographic system. It was observed a 28.7% reduction in the 5-HT levels followed up by an increase of 5-HIAA levels (29.4%). Furthermore there was a decrease of 8.0% in DA levels and an increase in the levels of metabolites DOPAC (21.5%) and HVA (52.5%). The results indicate that strictosidinic acid has a promising effect in the central nervous system, justifying more studies about the central actions of Psychotria compounds.

Acetylcholinesterase enzyme inhibitory potential of standardized extract of Trigonella foenum graecum L and its constituents

N. SatheeshKumar, Pulok K. Mukherjee, S. Bhadra, B.P. Saha — 2009-07-24

Abstract: Ethno pharmacological approach has provided several leads to identify potential new drugs from plant sources, including those for memory disorders. Acetylcholinesterase inhibitors (AChEI) give a symptomatic relief to some of the clinical manifestations of the disease. The main objective of this study is to standardize the extract of Trigonella foenum graecum L with trigonelline by HPTLC method and determine the in vitro AChE inhibitory activity of Trigonella foenum graecum L and its constituents using galanthamine as a reference. Different concentrations of hydro alcoholic extract of Trigonella foenum graecum and trigonelline were subjected to HPTLC analysis using the mobile phase n propanol, methanol and water (4:1:2, v/v). The Rf of trigonelline was found to be 0.43, and the correlation coefficient of 0.99 was indicative of good linear dependence of peak area on concentration. The concentration of trigonelline was found to be 13mgg−1w/w in the hydro alcoholic extract of Trigonella foenum graecum. The AChE inhibitory activity of crude fenugreek seed extracts, fractions and trigonelline was evaluated using Ellman's method in 96-well micro plate's assay and TLC bioassay detection. The ethyl acetate fraction of the alcohol extract (IC50 53.00 ± 17.33μg/ml), and total alkaloid fraction (IC50 9.23±6.08μg/ml) showed potential AChE inhibition. Trigonelline showed IC50 233±0.12μM. Galanthamine was used as standard and it showed inhibition of acetyl cholinesterase with an IC50 value of 1.27±0.21μM.

The effect of mastic gum on Helicobacter pylori: A randomized pilot study

K.J. Dabos, E. Sfika, L.J. Vlatta, G. Giannikopoulos — 2009-10-30

Abstract: Our aim was to study the effect of pure mastic gum on Helicobacter pylori (H. pylori) eradication in patients suffering from an H. pylori infectionFifty two patients were randomized to receive either 350mg three times a day (tid) of pure mastic gum for 14 days (Group A), or 1,05g tid of pure mastic gum (Group B) for 14 days, or pantoprazole 20mg twice a day (bd) plus pure mastic gum 350mg tid for 14 days (Group C) or pantoprazole 20mg bd plus amoxicillin 1g bd plus clarithromycin 500mg bd for 10 days (Group D). All patients harboured H. pylori before entering the study and that was confirmed by a 13C urea breath test (UBT). H. pylori eradication was tested by a UBT 5 weeks after completion of the eradication regime.Eradication of H. pylori was confirmed in 4/13 patients in Group A and in 5/13 in Grour B. No patient in Group C achieved eradication whereas 10/13 patients in Group D had a negative UBT. There were no statistically significant differences in mean UBT values in Groups A, B, C although there was a trend in Group A (p=0.08) and in Group B (p=0.064). The difference was significant in Group D (p=0.01). All patients tolerated mastic gum well and no serious adverse events were reported. Mastic gum has bactericidal activity on H. pylori in vivo.

Immunomodulatory, analgesic and antipyretic effects of violacein isolated from Chromobacterium violaceum

P. Antonisamy, S. Ignacimuthu — 2009-07-24

Abstract: Violacein was isolated from Chromobacterium violaceum, a soil Gram negative bacterium collected from the forest water body soil sample of Kolli Hills; Tamil Nadu, India. In the present study the immunomodulatory, analgesic and antipyretic activities of violacein were investigated in wistar rats and mice. Analgesic effect was evaluated by acetic acid- induced writhing, formalin induced paw licking and hotplate tests. Immunomodulatory effect was investigated by using ovalbumin- induced active paw anaphylaxis and sheep red blood cells (SRBC)-induced DTH tests. Antipyretic activity was evaluated by yeast- induced hyperpyrexia in rats. The anti- oedema effect was compared with indomethacin. Violacein inhibited 42.9% of ovalbumin- induced edema. Further we found that violacein (40mg/kg b.w.) reduced the edema induced by sheep red blood cells. Violacein also produced significant (p<0.05) analgesic activity in acetic acid induced writhing response, formalin induced paw licking response and hot plate analysis. Treatment with violacein showed a significant (p<0.05) dose-dependent reduction in pyrexia in rats. The results suggest that violacein possesses potent immunomodulatory, analgesic and antipyretic activities.

Announcement

2010-03-01