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Si-Yuan Pan,
Shu-Feng Zhou,
Si-Hua Gao, Zhi-Ling Yu,
Shuo-Feng Zhang,
Min-Ke Tang,
Jian-Ning Sun,
Dik-Lung Ma,
Yi-Fan Han,
Wang-Fun Fong,
Kam-Ming Ko
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ABSTRACT: With tens of thousands of plant species on earth, we are endowed with an enormous wealth of medicinal remedies from Mother Nature. Natural products and their derivatives represent more than 50% of all the drugs in modern therapeutics. Because of the low success rate and huge capital investment need, the research and development of conventional drugs are very costly and difficult. Over the past few decades, researchers have focused on drug discovery from herbal medicines or botanical sources, an important group of complementary and alternative medicine (CAM) therapy. With a long history of herbal usage for the clinical management of a variety of diseases in indigenous cultures, the success rate of developing a new drug from herbal medicinal preparations should, in theory, be higher than that from chemical synthesis. While the endeavor for drug discovery from herbal medicines is "experience driven," the search for a therapeutically useful synthetic drug, like "looking for a needle in a haystack," is a daunting task. In this paper, we first illustrated various approaches of drug discovery from herbal medicines. Typical examples of successful drug discovery from botanical sources were given. In addition, problems in drug discovery from herbal medicines were described and possible solutions were proposed. The prospect of drug discovery from herbal medicines in the postgenomic era was made with the provision of future directions in this area of drug development.
Evidence-based Complementary and Alternative Medicine 01/2013; 2013:627375. · 4.77 Impact Factor
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ABSTRACT: PURPOSE: The aim of this study is to investigate the involvement of DNA-dependent protein kinase (DNA-PK) in palmitate and oleate-induced lipid accumulation in hepatocytes. METHODS: We treated HepG2 with free fatty acids (FFA) (0.33 mM palmitate and 0.66 mM oleate) mixture to induce lipid accumulation. Cellular lipid was determined by Nile Red staining followed by flow cytometry detection as well as phase contrast and fluorescence microscope examination. Cell viability was detected by MTT assay. Apoptosis was detected by DAPI staining. Lipogenic gene expression was examined by real-time PCR at mRNA level and Western blotting at protein level. Promoter transcriptional activity was measured by dual luciferase assay. RESULTS: FFA treatment neither affected HepG2 cells viability nor induced DNA fragmentation, while induced cellular lipid accumulation was associated by the upregulation of sterol regulatory element-binding protein-1 (SREBP1) and fatty acid synthase (FAS) at both mRNA and protein levels. Interestingly, we also found that both the protein phosphatase 2A (PP2A) protein expression and DNA-PK activity were increased in these cells. Inhibition of PP2A by okadaic acid, knockdown of DNA-PK by siRNA or inhibition of DNA-PK by specific DNA-PK inhibitors curtailed the FFA-induced upregulations of the SREBP1 mRNA expression and the nuclear active SREBP1 protein expression, and reduced FFA-induced upregulation of FAS promoter transcriptional activity and lipid accumulation. CONCLUSION: This is the first time suggesting that inhibition of DNA-PK reduced FFA-induced lipid accumulation in hepatocytes. This finding might help us better understand non-alcoholic steatohepatitis pathogenesis.
European Journal of Nutrition 11/2012; · 2.75 Impact Factor
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ABSTRACT: BACKGROUND: Schisandra, a globally distributed plant, has been widely applied to health care products. Here, we investigated the effects of dietary intake of Fructus Schisandrae chinensis (FSC), both aqueous and ethanolic extracts (AqFSC, EtFSC), on serum/hepatic lipid contents in normal diet (ND)- and high-fat/cholesterol/bile salt diet (HFCBD)-fed mice. METHODS: Male ICR mice were fed with ND or HFCBD, supplemented with 1 and 4% of AqFSC and EtFSC, respectively, or 0.1% fenofibrate, for 13 days. Lipids were determined according to the manufacture's instructions. RESULTS: EtFSC, but not AqFSC, significantly elevated hepatic triglyceride (TG) in mice fed with ND. Feeding mice with HFCBD increased serum total cholesterol (TC), high density lipoprotein (HDL) and low density lipoprotein (LDL) levels as well as alanine aminotransferase (ALT) activity. Supplementation with AqFSC, EtFSC or fenofibrate significantly reduced hepatic TC and TG levels. However, AqFSC and EtFSC supplementation increased serum HDL and LDL levels in mice fed with HFCBD. Fenofibrate increased serum HDL and reduced serum LDL contents in hypercholesterolemic mice. EtFSC reduced, but fenofibrate elevated, serum ALT activity in both normal and hypercholesterolemic mice. While fenofibrate reduced serum TC, TG, and HDL levels in mice fed with ND, it increased serum HDL and reduced serum LDL, TC, and TG levels in mice fed with HFCBD. Hepatomegaly was found in normal and hypercholesterolemic mice fed with diet supplemented with fenofibrate. CONCLUSIONS: Feeding mice with AqFSC and EtFSC ameliorated the HFCBD-induced hepatic steatosis. In addition, EtFSC may offer protection against hepatic injury in hypercholesterolemic mice.
Lipids in Health and Disease 09/2012; 11(1):120. · 2.17 Impact Factor
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ABSTRACT: BACKGROUND: Fatty acid synthase (FAS) inhibitors could be a therapeutic target in cancer treatment. However, only a few FAS inhibitors showing clinical potential have been reported. Oridonin is a diterpenoid isolated from Rabdosia rubescens. Although it has antiproliferative activity in cancers, little was known about its anticancer effect on colorectal cancer. In this regard, we aimed to investigate if oridonin could be a novel FAS inhibitor and its anticancer mechanism in human colorectal cancer cells. METHODS: Two human colorectal cancer cell lines SW480 and SW620 were used as models for this study. RESULTS: We demonstrated that oridonin reduced viability and induced apoptosis in colorectal cancer cells. Knockdown of the expression of FAS in colorectal cancer cells by siRNA induced apoptosis. This led us to examine whether oridonin-induced apoptosis was mediated by FAS suppression in these cells. We found that oridonin effectively inhibited FAS and SREBP1 mRNA and protein expression in human colorectal cancer cells. In a transient reporter assay, oridonin also reduced transcriptional activity of the FAS promoter region containing the SREBP1 binding site. The FAS inhibition was paralleled by reduction in cellular palmitate and stearic acid. Upregulation of SREBP1 and FAS expression by insulin rescued these cells from oridonin-induced apoptosis. CONCLUSION: These results not only provide a novel molecular mechanism for the anticancer effect of oridonin in colorectal cancer, but also suggest oridonin could be a novel FAS inhibitor in cancer treatment. These results strengthen the scientific basis for the therapeutic use of oridonin in colorectal cancer.
Journal of Gastroenterology 06/2012; · 4.16 Impact Factor
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ABSTRACT: Six new protopanaxadiol-type ginsenosides, named ginsenosides Ra(4) -Ra(9) (1-6, resp.), along with 14 known dammarane-type triterpene saponins, were isolated from the root of Panax ginseng, one of the most important Chinese medicinal herbs. The structures of the new compounds were determined by spectroscopic methods, including 1D- and 2D-NMR, HR-MS, and chemical transformation as (20S)- 3-O-{β-D-6-O-[(E)-but-2-enoyl]glucopyranosyl-(1→2)-β-D-glucopyranosyl}-20-O-[β-D-xylopyranosyl-(1→4)-α-L-arabinopyranosyl-(1→6)-β-D-glucopyranosyl]protopanaxadiol (1), (20S)-3-O-[β-D-6-O-acetylglucopyranosyl-(1→2)-β-D-glucopyranosyl]-20-O-[β-D-xylopyranosyl-(1→4)-α-L-arabinopyranosyl-(1→6)-β-D-glucopyranosyl]protopanaxadiol (2), (20S)-3-O-{β-D-6-O-[(E)-but-2-enoyl]glucopyranosyl-(1→2)-β-D-glucopyranosyl}-20-O-[β-D-glucopyranosyl-(1→6)-β-D-glucopyranosyl]protopanaxadiol (3), (20S)-3-O-{β-D-6-O-[(E)-but-2-enoyl]glucopyranosyl-(1→2)-β-D-glucopyranosyl}-20-O-[α-L-arabinopyranosyl-(1→6)-β-D-glucopyranosyl]protopanaxadiol (4), (20S)-3-O-{β-D-4-O-[(E)-but-2-enoyl]glucopyranosyl-(1→2)-β-D-glucopyranosyl}-20-O-[α-L-arabinofuranosyl-(1→6)-β-D-glucopyranosyl]protopanaxadiol (5), (20S)-3-O-{β-D-6-O-[(E)-but-2-enoyl]glucopyranosyl-(1→2)-β-D-glucopyranosyl}-20-O-[α-L-arabinofuranosyl-(1→6)-β-D-glucopyranosyl]protopanaxadiol (6). The sugar moiety at C(3) of the aglycone of each new ginsenoside is butenoylated or acetylated.
Chemistry & Biodiversity 10/2011; 8(10):1853-63. · 1.80 Impact Factor
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ABSTRACT: Qian-wang-hong-bai-san (QW), a Chinese herbal formula, is traditionally used as a skin whitening agent in China. Aim of study: In our previous screening assays, QW was identified as an effective tyrosinase inhibitor. In this study, we aim to investigate the underlying mechanism of the anti-melanogenic effect of QW in B16 cells.
Cytotoxicity of QW in B16 cell line was examined by MTT assay. Cellular tyrosinase activity was determined based on the melanin content measured at 475 nm with a microplate spectrophotometer. Protein expression was analyzed by Western blotting and quantified by Quantity One.
QW dose-dependently inhibited tyrosinase activity and decreased melanin content at 48 h without significant cytotoxicity in B16 cells. Western blot analysis showed that QW treatment down-regulated the expression levels of phospho-p38, phospho-CREB, MITF, tyrosinase, TRP-1 and TRP-2 in a dose-dependent manner. At the same time, QW treatment for 48 h inhibited IBMX-induced elevation of cellular melanin content and tyrosinase activity. However, the attenuation of IBMX-mediated up-regulations of phospho-CREB and phospho-PKA was readily observed with 60 min of QW treatment.
The anti-melanogenic activity of QW in B16 melanoma cells can be attributed, at least in part, to the inhibition of the p38 MAPK and PKA signaling pathways. These findings shed new light on the molecular mechanisms of the skin-whitening property of QW.
Journal of ethnopharmacology 08/2011; 141(2):622-8. · 2.32 Impact Factor
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ABSTRACT: 20(S)-Protopanaxadiol (PPD), a metabolite of ginsenosides, has been demonstrated to possess cytotoxic effects on several cancer cell lines. The molecular mechanism is, however, not well understood. In this study, we have shown that PPD inhibits cell growth and induces apoptosis in human hepatocarcinoma HepG2 cells. PPD-treated cells showed a massive cytoplasmic vacuolization and a dramatic change of endoplasmic reticulum (ER) morphology. The induction of ER stress is associated with the upregulation of ER stress-associated genes and proteins. PPD activates the unfolded protein response (UPR) through the phosphorylation of PERK and eIF2α, the splicing of XBP1 mRNA, and the cleavage of AFT6. PPD also induces the intrinsic and extrinsic apoptotic pathways. It activates DR5, caspase-8, -9, -3, and promotes the cleavage of PARP while it downregulates Bcl-2, Bcl-x(L) and mitochondrial membrane potential. Knockdown of one of the three UPR limbs by specific siRNAs did not affect PPD-induced apoptosis, which was however, significantly suppressed by the downregulation of CHOP. Western blot analysis showed that PPD-stimulated downregulation of Bcl-2 protein, increase of DR5 protein, activation of caspase-8 and cleavage of PARP were significantly inhibited in CHOP siRNA-transfected cells. Taken together, we have identified ER as a molecular target of PPD and our data support the hypothesis that PPD induces HepG2 cell apoptosis through the ER stress pathway.
European journal of pharmacology 06/2011; 668(1-2):88-98. · 2.59 Impact Factor
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ABSTRACT: Atractylenolide II (AT-II) is a sesquiterpene compound isolated from the dried rhizome of Atractylodes macrocephala (Baizhu in Chinese), which is traditionally prescribed for melanoma treatment by Chinese medicine practitioners. Our previous study showed that AT-II can inhibit B16 cells proliferation. Here we investigate the mechanistic basis for the anti-proliferative activity of AT-II in B16 melanoma cells.
Cell viability was examined by MTT assay. Cell cycle distribution and apoptosis were determined by flow cytometry. Protein expression was determined by Western blotting.
AT-II treatment for 48 h dose-dependently inhibited cell proliferation with an IC(50) of 82.3 μM, and induced G1 phase cell cycle arrest. Moreover, treatment with 75 μM AT-II induced apoptosis. These observations were associated with the decrease of the expression of Cdk2, phosphorylated-Akt, phosphorylated-ERK and Bcl-2, the increase of the expression of phosphorylated-p38, phosphorylated-p53, p21, p27, and activation of caspases-8, -9 and -3. In addition, a chemical inhibitor of p53, PFTα, significantly decreased AT-II-mediated growth inhibition and apoptosis.
We demonstrated that the G1-arresting and apoptotic effects of AT-II in B16 cells involve p38 activation as well as ERK and Akt inactivation, and the cytotoxic/apoptotic effects of AT-II are potentially p53 dependent. These findings provided chemical and pharmacological basis for the traditional application of Baizhu in melanoma treatment.
Journal of ethnopharmacology 06/2011; 136(1):279-82. · 2.32 Impact Factor
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ABSTRACT: Bioconversion of timosaponin A-III (TA-III), one of the major steroidal saponins isolated from the rhizomes of Anemarrhenae asphodeloides Bunge (Liliaceae), was investigated in Saccharomyces cerevisiae. Five bioconversion products, denoted compounds 2-6, were obtained. Biotransformation metabolite 2 was a stereoisomer of TAIII with a specific isotype F-ring and beta-ranged CH3-21, which rarely occurs in nature. The structure of 2 was elucidated by extensive spectroscopic analysis (H-H COSY, HSQC, HMBC), as well as by high-resolution mass spectral analysis. The growth inhibitory activity of compounds 1-6 was assayed against four human cancer cell lines, HepG2, H-1299, HT-29, and HCT-116. Compounds 1 and 2 obviously inhibited the growth of the four types of cancer cells with IC50 values being less than 19 micrometer. A structure-activity relationship is discussed, and the spirostane-ring F in compounds 1 and 2 appears to be the critical bioactive moiety for the cell growth inhibitory property.
Journal of Microbiology and Biotechnology 06/2011; 21(6):582-9. · 1.38 Impact Factor
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ABSTRACT: Schisandrin B, an active ingredient isolated from the fruit of Schisandra chinensis, increased serum and hepatic triglyceride levels in mice. In the present study, the effective kinetics of schisandrin B on serum/hepatic triglyceride and total cholesterol levels in mice without and with the influence of fenofibrate were investigated. Parameters on hepatic index (the ratio of liver weight to body weight × 100) were also analyzed. Mice were intragastrically treated with schisandrin B at a single dose of 0.2, 0.4, 0.8, or 1.6 g/kg, without or with fenofibrate pretreatment (0.1 g/kg/day for 4 days, p.o.). Twenty-four hours after schisandrin B treatment, serum/hepatic triglyceride and total cholesterol levels were measured. Schisandrin B treatment dose-dependently increased serum and hepatic triglyceride levels as well as hepatic index in mice. In contrast, hepatic total cholesterol levels were decreased in a dose-dependent manner in schisandrin B-treated mice. Data obtained from effective kinetics analysis indicated that the action of schisandrin B on serum triglyceride had a higher specificity than those on hepatic total cholesterol and hepatic index. While fenofibrate pretreatment inhibited the schisandrin B-induced elevation in serum triglyceride levels, it completely abrogated the elevation of hepatic triglyceride levels in schisandrin B-treated mice. The combined treatment with schisandrin B and fenofibrate decreased hepatic total cholesterol level and increased the hepatic index in an additive or semi-additive manner, respectively. In conclusion, the results of effective kinetics analysis indicated that the schisandrin B-induced hypertriglyceridemia was competitively inhibited by fenofibrate. Schisandrin B may offer the prospect of setting up a mouse model of hypertriglyceridemia and fatty liver for screening triglyceride-lowering drug candidates.
Archiv für Experimentelle Pathologie und Pharmakologie 06/2011; 383(6):585-91. · 2.65 Impact Factor
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ABSTRACT: We investigated the involvement of MAPK pathways in the melanogenic effect of apigenin in B16 cells. Apigenin treatment for 48 h dose (5-20 μm)-dependently up-regulated protein expression levels of microphthalmia-associated transcription factor (MITF) and melanogenic enzymes including tyrosinase, tyrosinase-related protein-1 (TRP-1) and TRP-2 and enhanced the phosphorylation of p38 MAPK, without affecting the phosphorylation of JNK or ERK MAPK. Treatment with 10 μm apigenin time (6-48 h)-dependently elevated the protein expressions of p-p38, MITF and melanogenic enzymes. Moreover, PD169316, a selective inhibitor of p38 kinase, suppressed the stimulatory effects of apigenin on tyrosinase activity and melanin synthesis, which were accompanied by decreased MITF protein expression. In conclusion, apigenin increased melanogenesis in B16 cells, at least in part, by activating the p38 MAPK pathway. The novel findings of this study shed light on the molecular mechanisms underlying the melanogenic activity of apigenin and suggest that apigenin/its derivatives may be potentially used for treating hypopigmentation disorders.
Experimental Dermatology 05/2011; 20(9):755-7. · 3.54 Impact Factor
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ABSTRACT: To investigate the effects of schisandrin B (Sch B) on free fatty acid (FFA)-induced steatosis in L-02 cells.
Cellular steatosis was induced by incubating L-02 cells with a FFA mixture (oleate and palmitate at the ratio of 2:1) for 24 h. Cytotoxicity and apoptosis were evaluated by 3-(4, 5-dmethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay and Annexin V/propidium iodide staining, respectively. Cellular total lipid was determined using a photocolorimetric method after Nile red staining, and triglyceride content was measured using an enzymatic kit. To study the effects of Sch B on steatosis, L-02 cells were treated with Sch B (1-100 μmol/L) in the absence or presence of 1 mmol/L FFA for 24 h, and cellular total lipid and triglyceride levels were measured. To explore the mechanisms of action of Sch B in the steatotic L-02 cells, mRNA levels of several regulators of hepatic lipid metabolism including adipose differentiation related protein (ADRP), sterol regulatory element binding protein 1 (SREBP-1), peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ were measured by quantitative real-time polymerase chain reaction (PCR), and protein levels of ADRP and SREBP-1 were measured by immunoblotting.
Treatment with 1 mmol/L FFA for 24 h induced intracellular lipid accumulation in L-02 cells comparable to that in human steatotic livers without causing apparent apoptosis and cytotoxicity. Sch B mitigated cellular total lipid and triglyceride accumulations in the steatotic L-02 cells in a dose-dependent manner. Quantitative real-time PCR and Western blot analyses revealed that treatment of L-02 cells with 100 μmol/L Sch B reverted the FFA-stimulated up-regulation of ADRP and SREBP-1.
Sch B inhibits FFA-induced steatosis in L-02 cells by, at least in part, reversing the up-regulation of ADRP and SREBP-1.
World Journal of Gastroenterology 05/2011; 17(19):2379-88. · 2.47 Impact Factor
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ABSTRACT: Overexpression of EGFR and HER2 is seen in breast cancers and results in poor prognosis and decreased patient survival. Clinically, EGFR and HER2 are effective therapeutic targets. The objective of this study is to investigate the in vitro effects of furanodienone, an active chemical component isolated from Rhizoma Curcumae, on the activation of EGFR/HER2 signaling, cell cycle, and apoptosis in HER2-overexpressing BT474 and SKBR3 cells.
Cell growth was assessed by SRB protein assay. Cell cycle analysis was carried out by flow cytometry, and apoptosis was observed by Annexin V and DAPI staining. Effects of furanodienone on the activation of EGFR/HER2 signaling-related proteins were analyzed by western blotting.
Furanodienone inhibited cell growth in BT474 and SKBR3 cells. Furanodienone caused G1 arrest in BT474 cells and induced apoptosis in SKBR3 cells. Furanodienone interfered with EGFR/HER2 signaling in treated cells as shown by decreases in phosphorylated EGFR, HER2, Akt, Gsk3β and an increase in p27(kip1) protein. Accordingly, furanodienone inhibited EGF-induced phosphorylation of EGFR, HER2, Akt, and Gsk3β. EGFR-specific siRNA knockdown did not affect the cell growth inhibitory effect of furanodienone. On the contrary, specific siRNA knockdown of HER2 increased cellular resistance to furanodienone toxicity. In HER-2-deficient MDA-MB-231 cells, the transfection and expression of HER2 increased the sensitivity of cells to furanodienone toxicity.
Furanodienone inhibited EGFR/HER2 signaling pathway in BT474 and SKBR3 cells. More importantly, the effect of furanodienone was specifically dependent on HER2, but not EGFR, expression.
Cancer Chemotherapy and Pharmacology 04/2011; 68(5):1315-23. · 2.83 Impact Factor
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ABSTRACT: The aims of this study were to isolate sesquiterpene compounds from the largehead atractylodes rhizome (LAR) and to investigate their effects on B16 cancer cells. A total of 8 sesquiterpenes from LAR were identified, of which eudesm-4 (15), 7-diene-9α, 11-diol (7) was isolated for the first time. All 8 compounds inhibited growth of B16 cells, and atractylenolide I (AT-I), atractylenolide II (AT-II), and atractylenolactam (ATR) were the most potent, with IC(50) values of 76.46, 84.02, and 54.88 μΜ, respectively. Monomer lactone or lactam structures in the 8 compounds appeared to be critical for their antiproliferative activities. In addition, AT-I, AT-II, and ATR could induce cell differentiation and inhibit cell migration. Western blot analysis indicated that 2 of the compounds, AT-I and AT-II, could inactivate ERK, where all 3 inhibited AKT activation, suggesting that Ras/ERK and PI3K/AKT signaling pathways are involved in the action mechanisms of the LAR sesquiterpene compounds.
Integrative Cancer Therapies 03/2011; 10(1):92-100. · 2.14 Impact Factor
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ABSTRACT: Oridonin is the main bioactive constituent of the Chinese medicinal herb Isodon rubescens and has been shown to have anti-neoplastic effects against a number of cancers in vitro and in vivo. Here we report the proteomic identification of proteins involved in the anticancer properties of oridonin in hepatocarcinoma HepG2 cells. Cell viability assay showed that oridonin dose-dependently inhibited cell growth with an IC(50) of 41.77μM. Treatment with oridonin at 44μM for 24h induced apoptosis and G2/M cell cycle arrest, which were associated with nine differentially expressed proteins identified by proteomic analysis. The proteomic expression patterns of Hsp70.1, Sti1 and hnRNP-E1 were confirmed by quantitative real-time PCR and/or immunoblotting. Eight of the nine identified proteins are shown, for the first time, to be involved in the anticancer activities of oridonin. Up-regulation of Hsp70.1, STRAP, TCTP, Sti1 and PPase, as well as the down-regulation of hnRNP-E1 could be responsible for the apoptotic and G2/M-arresting effects of oridonin observed in this study. Up-regulation of HP1 beta and GlyRS might contribute to inhibitory effects of oridonin on telomerase and tyrosine kinase, respectively. These findings shed new insights into the molecular mechanisms underlying the anticancer properties of oridonin in liver cancer cells.
Phytomedicine: international journal of phytotherapy and phytopharmacology 01/2011; 18(2-3):163-9. · 2.17 Impact Factor
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ABSTRACT: It is well established that cholinergic over-stimulation can interfere with memory processes. The aim of this study was to evaluate the effect of tacrine, an acetylcholinesterase inhibitor, on recognition memory as well as the associated hepatotoxicity in juvenile (20-day-old) and adult (100-day-old) ICR male mice. Recognition memory was assessed by open-field test and step-through task without footshocks for three sessions between 08:00 and 13:00, with a 24-hr retention interval. Tacrine (10 or 40 μmol/kg) or vehicle was administered (s.c.) 20 min. prior to the first session. During the acquisition session, tacrine suppressed the open-field behaviours, including locomotor activity, rearing, grooming and defecation (by 77-100%) in mice of both ages. During the recall (observable in both ages) and re-recall (observable in juvenile mice) session, the locomotor activity and rearing number were significantly increased, indicative of impairment in recognition memory, in mice treated with tacrine 40 μmol/kg. During the training trial, tacrine decreased the step-through number in mice of both ages. In contrast, during the retention and re-retention trials, the step-through number was increased (by 92% and 93%, respectively), indicative of impairment in step-through memory, in juvenile but not adult mice treated with tacrine 40 μmol/kg. Tacrine 40 μmol/kg elevated the serum alanine aminotransferase (ALT) activity (by 135%) in juvenile mice, but reduced the ALT activity (by 42%) in adult mice. The results indicated that 20-day-old mice seemed to be more sensitive than 100-day-old mice to tacrine-induced impairment in recognition memory and the associated liver damage.
Basic & Clinical Pharmacology & Toxicology 01/2011; 108(6):421-7. · 2.18 Impact Factor
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ABSTRACT: Synthetic chemical drugs, while being efficacious in the clinical management of many diseases, are often associated with undesirable side effects in patients. It is now clear that the need of therapeutic intervention in many clinical conditions cannot be satisfactorily met by synthetic chemical drugs. Since the research and development of new chemical drugs remain time-consuming, capital-intensive and risky, much effort has been put in the search for alternative routes for drug discovery in China. This narrative review illustrates various approaches to the research and drug discovery in Chinese herbal medicine. Although this article focuses on Chinese traditional drugs, it is also conducive to the development of other traditional remedies and innovative drug discovery.
Evidence-based Complementary and Alternative Medicine 01/2011; 2011:403709. · 4.77 Impact Factor
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ABSTRACT: Ginseng, the root of Panax ginseng C. A. Meyer (Araliaceae), is one of the most important traditional medicines and functional foods. A detailed phytochemical investigation on the roots of P. ginseng led to the isolation of 6 new natural protopanaxatriol (PPT)-type ginsenosides, ginsenosides Re(1)-Re(6) (compounds 1-6), along with 10 known PPT-type ginsenosides. Their structures were elucidated on the basis of chemical and spectroscopic analyses, including high-resolution mass spectrometry (HRMS) and 1D and 2D nuclear magnetic resonance (NMR). The unusual α-D-glucopyranosyl-(1→3)-β-D-glucopyranosyl sugar chain, as found in compounds 1 and 2, is reported in the genus Panax for the first time.
Journal of Agricultural and Food Chemistry 01/2011; 59(1):200-5. · 2.82 Impact Factor
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ABSTRACT: We aimed to screen for melanogenic agents among 35 botanical compounds. The compounds were first assessed with regard to their effects on tyrosinase activity in B16 cells. At 100 μM, 13 compounds showed tyrosinase activity-enhancing effects, ranging from 2.6 to 372.8% activation. Five of them showed more than 50% enhancement and were further tested for their EC(50) values. Compared with 8-Methoxypsoralen, an effective tyrosinase activator with an EC(50) of 7.26 μM, 3 compounds exhibited smaller EC(50) values (apigenin, 0.45 μM; hyperosid, 0.92 μM; and icariin, 1.01 μM for enhancing tyrosinase activity). The 3 compounds significantly increased cellular melanin contents without affecting cell proliferation. Compared with 8-Methoxypsoralen (EC(50), 35.94 μM for stimulating pigmentation), apigenin (EC(50), 17.46 μM) and icariin (EC(50), 32.77 μM) showed better melanogenic activity, while hyperosid (EC(50), 70.4 μM) was less potent. Western blot analysis demonstrated that the 3 compounds could differentially increase the expression levels of tyrosinase, and tyrosinase-related proteins 1 and 2. Together these data suggest that apigenin and icariin exert potent melanogenic activities through, at least in part, upregulating the protein expression levels of melanogenic enzymes in B16 cells. Thus, further investigations are merited to ascertain their potential application in treating hypopigmentation disorders.
Phytomedicine: international journal of phytotherapy and phytopharmacology 12/2010; 18(1):32-5. · 2.17 Impact Factor
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ABSTRACT: San-bai-tang (SBT), a Chinese herbal formula, is traditionally used as a skin whitener in China. In our previous screening assays, SBT was identified as an effective tyrosinase inhibitor. In this study, we aim to investigate the anti-melanogenic effect and mechanisms of SBT in B16 cells.
Cell viability was examined by the MTT assay. Cellular tyrosinase activity and melanin content were determined using spectrophotographic methods. Protein expression was analyzed by immunoblotting.
SBT inhibited tyrosinase activity with an IC(50) of 215.6 ± 10.3 μg/ml, and decreased cellular melanin content with an IC(50) of 254.8 ± 14.5 μg/ml at 48 h. MTT assay demonstrated that 48-h SBT (50-400 μg/ml) treatment did not show obvious cytotoxicity. Immunoblot analysis showed that SBT (100, 200 or 400 μg/ml) treatment for 48 h down-regulated the expression levels of phosphorylated-p38, MITF, tyrosinase, TRP-1 and TRP-2 in a dose-dependent manner.
SBT inhibited melanogenesis in B16 cells, and suppression of p38 MAPK signaling pathway contributed to the anti-melanogenic effect of SBT by down-regulating the expression of MITF and melanogenic enzymes. These novel findings demonstrated the anti-melanogenic effect and mechanisms of SBT, and provide pharmacological basis for the traditional use of SBT.
Journal of ethnopharmacology 11/2010; 132(2):533-5. · 2.32 Impact Factor
