Schisandrin B regulates lipid metabolism in subcutaneous adipocytes.

Subcutaneous adipocytes in obese subjects have a lower sensitivity to catecholamine-induced lipolysis and a higher sensitivity to insulin anti-lipolytic effects compared to adipocytes in other adipose depots. Therefore, increasing lipolysis in subcutaneous adipocytes coupled with enhanced fatty acid oxidation may be an anti-obesity strategy. Schisandrin B (Sch B) is one of the most abundant active dibenzocyclooctadiene derivatives found in the fruit of Schisandra chinensis which is a commonly prescribed Chinese medicinal herb. We found that Sch B reduced glycerolipid contents in 3T3-L1 adipocytes and subcutaneous adipocytes dissected from DIO mice. Sch B also activated hormone sensitive lipase (HSL) and increased lipolysis in these adipocyte in a protein kinase A-dependent manner. Interestingly, Sch B increased fatty acid oxidation gene expressions in these adipocytes, implying an increase in fatty acid oxidation after treatment. In in vivo model, we found that Sch B increased HSL phosphorylation, reduced glycerolipid levels and increased fatty acid oxidation gene expressions in the subcutaneous adipocytes in the DIO mice. More importantly, Sch B significantly reduced the subcutaneous adipocyte sizes, subcutaneous adipose tissue mass and body weight of the mice. Our study provides scientific evidence to suggest a potential therapeutic function of Sch B or Schisandra chinensis seed containing Sch B in reducing obesity.

Cinnamon induces browning in subcutaneous adipocytes.

Browning is the process of increasing the number of brite cells, which helps to increase energy expenditure and reduce obesity. Consumption of natural and non-toxic herbal extracts that possess the browning effect is an attractive anti-obesity strategy. In this study, we examined the browning effect of cinnamon extract. We found that cinnamon extract (CE) induced typical brown adipocyte multiocular phenotype in 3T3-L1 adipocytes. The treatment also increased brown adipocytes markers and reduced white adipocytes markers in the 3T3-L1 adipocytes. In ex vivo studies, we found that CE increased brown adipocytes markers in the subcutaneous adipocytes isolated from db/db mice and diet-induced obesity (DIO) mice. However, CE did not significantly affect UCP1 expression in the adipocytes isolated from perinephric adipose tissue and epididymal adipose tissue. ß3-adernergic receptor (ß3-AR) antagonist reduced the CE-enhanced UCP1 expression, suggesting an involvement of the ß3-AR activity. Oral administration of CE significantly increased UCP1 expression in the subcutaneous adipose tissue in vivo and reduced the body weight of the DIO mice. Taken together, our data suggest that CE has a browning effect in subcutaneous adipocytes. Our study suggests a natural non-toxic herbal remedy to reduce obesity.

Lipidomic-based investigation into the regulatory effect of Schisandrin B on palmitic acid level in non-alcoholic steatotic livers.

Schisandrin B (SchB) is one of the most abundant bioactive dibenzocyclooctadiene derivatives found in the fruit of Schisandra chinensis. Here, we investigated the potential therapeutic effects of SchB on non-alcoholic fatty-liver disease (NAFLD). In lipidomic study, ingenuity pathway analysis highlighted palmitate biosynthesis metabolic pathway in the liver samples of SchB-treated high-fat-diet-fed mice. Further experiments showed that the SchB treatment reduced expression and activity of fatty acid synthase, expressions of hepatic mature sterol regulatory element binding protein-1 and tumor necrosis factor-α, and hepatic level of palmitic acid which is known to promote progression of steatosis to steatohepatitis. Furthermore, the treatment also reduced hepatic fibrosis, activated nuclear factor-erythroid-2-related factor-2 which is known to attenuate the progression of NASH-related fibrosis. Interestingly, in fasting mice, a single high-dose SchB induced transient lipolysis and increased the expressions of adipose triglyceride lipase and phospho-hormone sensitive lipase. The treatment also increased plasma cholesterol levels and 3-hydroxy-3-methylglutaryl-CoA reductase activity, reduced the hepatic low-density-lipoprotein receptor expression in these mice. Our data not only suggest SchB is a potential therapeutic agent for NAFLD, but also provided important information for a safe consumption of SchB because SchB overdosed under fasting condition will have adverse effects on lipid metabolism.

Comparisons of the chemical profiles, cytotoxicities and anti-inflammatory effects of raw and rice wine-processed Herba Siegesbeckiae.

ETHNOPHARMACOLOGICAL RELEVANCE: Although slightly toxic, the Chinese medicinal herb Herba Siegesbeckiae (HS) has long been used as a remedy for traditional Chinese medicine symptoms that resemble inflammatory joint disorders, because it can eliminate the wind-dampness and soothe painful joints. Proper processing can reduce the toxicity and/or enhance the efficacy of raw herbs. In this study, we aim to examine if processing with rice wine reduces the cytotoxicities and/or enhances the anti-inflammatory effects of HS, and to explore the chemical basis behind the potential changes of medicinal properties caused by the processing. MATERIALS AND METHODS: We used cell models to examine the cytotoxicities and anti-inflammatory effects of HS and rice wine-processed HS (WHS). The chemical profiles of HS and WHS were compared using the ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UPLC/Q-TOF-MS) analysis. RESULTS: We found that WHS was less toxic than HS in cultured cells as shown in the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Both HS and WHS had anti-inflammatory effects as demonstrated by their abilities to reduce nitric oxide (NO) production as well as protein and mRNA expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Interestingly, the anti-inflammatory effects of WHS were more potent than that of HS at the concentration of 100 µg/mL. By comparing the chemical profiles, we found that 19 peaks were lower, while 2 other peaks were higher in WHS than in HS. Four compounds including neo-darutoside, darutoside, stigmasterol and 16-O-acetyldarutoside corresponding to 4 individual changed peaks were tentatively identified by matching with empirical molecular formulae and mass fragments. CONCLUSION: Our study showed that processing with rice wine significantly reduced the cytotoxicities and enhanced the anti-inflammatory effects of HS as demonstrated in cell models. We also developed a UPLC/Q-TOF-MS method to clearly differentiate HS from WHS by their different chemical profiles. Further study is warranted to establish the relationship between the alteration of chemical profiles and the changes of medicinal properties caused by processing with rice wine.

Chemotherapeutic activities of Carthami Flos and its reversal effect on multidrug resistance in cancer cells.

Multidrug-resistance (MDR) represents a major cause of failure in cancer chemotherapy. The need for a reduction in MDR by natural-product-based drugs of low toxicity led to the current investigation of applying medicinal herbs in future cancer adjuvant therapy. Carthami Flos (CF), the dried flower of safflower (Carthamus tinctorius L.), is one of the most popular traditional Chinese medicinal herbs used to alleviate pain, increase circulation, and reduce blood-stasis syndrome. The drug resistance index of the total extract of CF in MDR KB-V1 cells and its synergistic effects with other chemotherapeutic agents were studied. SRB cell viability assays were used to quantify growth inhibition after exposure to single drug and in combinations with other chemotherapeutic agents using the median effect principle. The combination indexes were then calculated according to the classic isobologram equation. The results revealed that CF showed a drug resistance index of 0.096. In combination with other chemotherapeutic agents, it enhanced their chemo-sensitivities by 2.8 to 4.0 folds and gave a general synergism in cytotoxic effect. These results indicate that CF could be a potential alternative adjuvant antitumour herbal medicine representing a promising approach to the treatment of some malignant and MDR cancers in the future.

The herbal compound cryptotanshinone restores sensitivity in cancer cells that are resistant to the tumor necrosis factor-related apoptosis-inducing ligand.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis and kills cancer cells but not normal cells. However, TRAIL resistance due to low level of TRAIL receptor expression is widely found in cancer cells and hampers its development for cancer treatment. Thus, the agents that can sensitize the tumor cells to TRAIL-mediated apoptosis are urgently needed. We investigated whether tanshinones, the major bioactive compounds of Salvia miltiorrhiza (danshen), can up-regulate TRAIL receptor expression. Among the major tanshinones being tested, cryptotanshinone (CT) showed the best ability to induce TRAIL receptor 2 (DR5) expression. We further showed that CT was capable of promoting TRAIL-induced cell death and apoptosis in A375 melanoma cells. CT-induced DR5 induction was not cell type-specific, as DR5 induction was observed in other cancer cell types. DR5 knockdown abolished the enhancing effect of CT on TRAIL responses. Mechanistically, induction of the DR5 by CT was found to be p53-independent but dependent on the induction of CCAAT/enhancer-binding protein-homologous protein (CHOP). Knockdown of CHOP abolished CT-induced DR5 expression and the associated potentiation of TRAIL-mediated cell death. In addition, CT-induced ROS production preceded up-regulation of CHOP and DR5 and consequent sensitization of cells to TRAIL. Interestingly, CT also converted TRAIL-resistant lung A549 cancer cells into TRAIL-sensitive cells. Taken together, our results indicate that CT can potentiate TRAIL-induced apoptosis through up-regulation of DR5.

New Perspectives on How to Discover Drugs from Herbal Medicines: CAM's Outstanding Contribution to Modern Therapeutics.

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.

Acylated protopanaxadiol-type ginsenosides from the root of Panax ginseng.

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-{ß-D-6-O-[(E)-but-2-enoyl]glucopyranosyl-(1→2)-ß-D-glucopyranosyl}-20-O-[ß-D-xylopyranosyl-(1→4)-α-L-arabinopyranosyl-(1→6)-ß-D-glucopyranosyl]protopanaxadiol (1), (20S)-3-O-[ß-D-6-O-acetylglucopyranosyl-(1→2)-ß-D-glucopyranosyl]-20-O-[ß-D-xylopyranosyl-(1→4)-α-L-arabinopyranosyl-(1→6)-ß-D-glucopyranosyl]protopanaxadiol (2), (20S)-3-O-{ß-D-6-O-[(E)-but-2-enoyl]glucopyranosyl-(1→2)-ß-D-glucopyranosyl}-20-O-[ß-D-glucopyranosyl-(1→6)-ß-D-glucopyranosyl]protopanaxadiol (3), (20S)-3-O-{ß-D-6-O-[(E)-but-2-enoyl]glucopyranosyl-(1→2)-ß-D-glucopyranosyl}-20-O-[α-L-arabinopyranosyl-(1→6)-ß-D-glucopyranosyl]protopanaxadiol (4), (20S)-3-O-{ß-D-4-O-[(E)-but-2-enoyl]glucopyranosyl-(1→2)-ß-D-glucopyranosyl}-20-O-[α-L-arabinofuranosyl-(1→6)-ß-D-glucopyranosyl]protopanaxadiol (5), (20S)-3-O-{ß-D-6-O-[(E)-but-2-enoyl]glucopyranosyl-(1→2)-ß-D-glucopyranosyl}-20-O-[α-L-arabinofuranosyl-(1→6)-ß-D-glucopyranosyl]protopanaxadiol (6). The sugar moiety at C(3) of the aglycone of each new ginsenoside is butenoylated or acetylated.

New perspectives on chinese herbal medicine (zhong-yao) research and development.

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.

Atractylenolide II induces G1 cell-cycle arrest and apoptosis in B16 melanoma cells.

ETHNOPHARMACOLOGICAL RELEVANCE: 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. MATERIALS AND METHODS: Cell viability was examined by MTT assay. Cell cycle distribution and apoptosis were determined by flow cytometry. Protein expression was determined by Western blotting. RESULTS: 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. CONCLUSIONS: 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.

Baicalein inhibits formation of α-synuclein oligomers within living cells and prevents Aß peptide fibrillation and oligomerisation.

Abnormal protein aggregation in the brain is linked to the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD). Recent studies revealed that the oligomeric form of aggregates is most likely the toxic species, and thus could be a good therapeutic target. To screen for potent inhibitors that can inhibit both oligomerisation and fibrillation of α-synuclein (α-syn), we systematically compared the antioligomeric and antifibrillar activities of eight compounds that were extracted from Chinese herbal medicines through three platforms that can monitor the formation of α-syn fibrils and oligomers in cell-free or cellular systems. Our results revealed that baicalein, a flavonoid extracted from the Chinese herbal medicine Scutellaria baicalensis Georgi ("huang qin" in Chinese), is a potent inhibitor of α-syn oligomerisation both in cell-free and cellular systems, and is also an effective inhibitor of α-syn fibrillation in cell-free systems. We further tested the protective effect of baicalein against α-syn-oligomer-induced toxicity in neuronal cells. Our data showed that baicalein inhibited the formation of α-syn oligomers in SH-SY5Y and Hela cells, and protected SH-SY5Y cells from α-syn-oligomer-induced toxicity. We also explored the effect of baicalein on amyloid-ß peptide (Aß) aggregation and toxicity. We found that baicalein can also inhibit Aß fibrillation and oligomerisation, disaggregate pre-formed Aß amyloid fibrils and prevent Aß fibril-induced toxicity in PC12 cells. Our study indicates that baicalein is a good inhibitor of amyloid protein aggregation and toxicity. Given the role of these processes in neurodegenerative diseases such as AD and PD, our results suggest that baicalein has potential as a therapeutic agent for the treatment of these devastating disorders.

Protopanaxatriol-type ginsenosides from the root of Panax ginseng.

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)-ß-D-glucopyranosyl sugar chain, as found in compounds 1 and 2, is reported in the genus Panax for the first time.

Effects of sesquiterpenes isolated from largehead atractylodes rhizome on growth, migration, and differentiation of B16 melanoma cells.

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.

Proteomic and functional analyses reveal the potential involvement of endoplasmic reticulum stress and α-CP1 in the anticancer activities of oridonin in HepG2 cells.

Oridonin has been shown to exhibit therapeutic effects against hepatocellular carcinoma (HCC) in vitro and in vivo. This study aimed to identify the anti-HCC mechanisms of oridonin in HepG2 cells using proteomic and functional analyses. MTT assay showed that oridonin treatment for 24 hours dose-dependently inhibited cell growth with an IC(50) value of 40.4 µM. Treatment with 40 µM oridonin for 24 hours induced apoptosis determined by nuclear morphologic changes of DAPI-stained cells and flow cytometric analysis of annexin V-FITC/PI-stained cells, which was accompanied by Grp78 upregulation and α-CP1 downregulation identified by proteomic analysis. Immunoblot analysis for the endoplasmic reticulum (ER) stress- related proteins demonstrated that the expression levels of phosphorylated PERK (p-PERK) and CHOP were increased, whereas PERK, ATF-6, and IRE-1 expression levels were decreased. Knockdown of α-CP1 expression with siRNA significantly increased cell death and apoptosis in control and oridonin-treated HepG2 cells. Together, these data provide proteomic and functional evidence for the potential involvement of ER stress and α-CP1 in the antiproliferative and apoptotic activities of oridonin in HepG2 cells, which shed new light on the action mechanisms of oridonin in HCC management.

Ethanol extract of fructus schisandrae decreases hepatic triglyceride level in mice fed with a high fat/cholesterol diet, with attention to acute toxicity.

Effects of the ethanol extract of Fructus Schisandrae (EtFSC) on serum and liver lipid contents were investigated in mice fed with high fat/cholesterol (HFC) diet for 8 or 15 days. The induction of hypercholesterolemia by HFC diet caused significant increases in serum and hepatic total cholesterol (TC) levels (up to 62% and 165%, resp.) and hepatic triglyceride (TG) levels (up to 528%) in mice. EtFSC treatment (1 or 5 g/kg/day for 7 days; from Day 1 to 7 or from Day 8 to 14, i.g.) significantly decreased the hepatic TG level (down to 35%) and slightly increased the hepatic index (by 8%) in hypercholesterolemic mice. Whereas fenofibrate treatment (0.1 g/kg/day for 7 days, i.g.) significantly lowered the hepatic TG level (by 61%), it elevated the hepatic index (by 77%) in hypercholesterolemic mice. Acute toxicity test showed that EtFSC was relatively non-toxic, with an LD(50) value of 35.63 ± 6.46 g/kg in mice. The results indicate that EtFSC treatment can invariably decrease hepatic TG in hypercholesterolemic mice, as assessed by both preventive and therapeutic protocols, suggesting its potential use for fatty liver treatment.

New perspectives on innovative drug discovery: an overview.

Despite advances in technology, drug discovery is still a lengthy, expensive, difficult, and inefficient process, with a low rate of success. Today, advances in biomedical science have brought about great strides in therapeutic interventions for a wide spectrum of diseases. The advent of biochemical techniques and cutting-edge bio/chemical technologies has made available a plethora of practical approaches to drug screening and design. In 2010, the total sales of the global pharmaceutical market will reach 600 billion US dollars and expand to over 975 billion dollars by 2013. The aim of this review is to summarize available information on contemporary approaches and strategies in the discovery of novel therapeutic agents, especially from the complementary and alternative medicines, including natural products and traditional remedies such as Chinese herbal medicine.

Involvement of p38 MAPK signaling pathway in the anti-melanogenic effect of San-bai-tang, a Chinese herbal formula, in B16 cells.

AIM OF THE STUDY: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Screening of Chinese herbal medicines for antityrosinase activity in a cell free system and B16 cells.

AIM OF THE STUDY: Tyrosinase inhibitors are becoming increasingly important in controlling skin hyperpigmentation. We aimed to screen 50 extracts from traditional Chinese medicines (TCM) for tyrosinase activity-inhibiting agents. MATERIALS AND METHODS: The 50 herbal extracts were prepared from 32 herbs and 18 TCM formulas, which are used as folk skin whiteners in China and have not been investigated for their skin-whitening mechanisms. Each herb and formula was extracted with 30% ethanol and water, respectively, and followed by column chromatography for isolating bioactive substances such as saponins, flavonoids and alkaloids for the antityrosinase activity study. Every extract was tested using the cell free mushroom tyrosinase inhibitory assay at 2 mg/ml for the single herb extracts and 1mg/ml for formula extracts. Extracts showing greater than 50% inhibition against mushroom tyrosinase activity were further examined by cellular tyrosinase assay in mouse B16 cells. The cytotoxicity in B16 cells was measured by methyl thiazolyl tetrazolium bromide (MTT) assay. RESULTS: In the cell-free assay, 10 out of the 50 extracts demonstrated more than 50% inhibition against mushroom tyrosinase activity. These 10 extracts were further assessed by cellular tyrosinase assay, and 6 showed>50% inhibition with IC(50) values <1 mg/ml. The 6 extracts are from 3 herbs namely Ampelopsis japonica, Lindera aggregata, and Polygonatum odoratum, and 3 formulas namely Qian-wang-hong-bai-san, Qiong-yu-gao, and San-bai-tang. As compared with vitamin C, these 6 extracts showed similar or greater ratio of cell growth IC(50) to cellular tyrosinase IC(50). As compared with arbutin, extract from Ampelopsis japonica, Lindera aggregata, Qian-wang-hong-bai-san, or San-bai-tang had a similar, although extract from Polygonatum odoratum or Qiong-yu-gao had a greater, IC(50) value against murine tyrosinase activity. CONCLUSIONS: From the screening assays we identified three Chinese medicinal herbs and three TCM formulas that have appreciable antityrosinase activity. Further studies are warranted to develop them as skin-whitening agents with convenient dosage forms or to identify active constituents from the extracts as useful leads for the development of skin whiteners.

Long-term treatment with a Chinese herbal formula, Sheng-Mai-San, improves cardiac contractile function in aged rats: the role of Ca(2+) homeostasis.

A Chinese herbal formula Sheng-Mai-Yin (SMY), the liquid dosage form of Sheng-Mai-San, has been used clinically for treating heart failure, particularly in aged patients. To investigate the effect of SMY treatment on the contractile function of aged hearts, we first examined cardiac hemodynamics in aged rats. To define the mechanism involved in the enhancement of cardiac function, we investigated the effect of SMY treatment on Ca(2+) homeostasis in ventricular cardiomyocytes isolated from aged rats. Ca(2+) release was assessed by measurements of changes in cardiac Ca(2+) transients and Ca(2+) sparks, using laser scanning confocal microscopy. The functional status of Ca(2+)-release regulators, including L-type Ca(2+) channels, sarcoplasmic reticulum (SR) Ca(2+)-adenosine triphosphatase (ATPase), and ryanodine receptors (RyRs), was also assessed. The results indicated that SMY treatment (2 g/kg per day for 30 doses within 6 weeks, intragastically) significantly improved hemodynamic parameters in aged rats. SMY treatment markedly increased the amplitude and shortened the duration of Ca(2+) transients in aged cardiomyocytes, and reversed the age-related increase in frequency, decrease in amplitude, and changes in spatiotemporal properties of Ca(2+) sparks in cardiomyocytes. In addition, SMY treatment increased the L-type Ca(2+) current density, SR Ca(2+) content, and SR Ca(2+)-ATPase expression, and decreased the sensitivity of RyRs to Ca(2+), all of which are causally related to increases in the amplitude of Ca(2+) transients and the size of Ca(2+) sparks. In conclusion, the improvement in cardiac contractile function afforded by SMY treatment in aged rats is likely mediated by an increase in Ca(2+) release from the SR through L-type Ca(2+) current-activated RyRs.

Tenacigenin B derivatives reverse P-glycoprotein-mediated multidrug resistance inHepG2/Dox cells.

Tenacissimoside A (1) and 11alpha-O-benzoyl-12beta- O-acetyltenacigenin B (2), two derivatives of tenacigenin B (3) from the plant Marsdenia tenacissima, reversed multidrug resistance in P-glycoprotein (Pgp)-overexpressing multidrug-resistant cancer cells. The sensitivity of HepG2/Dox cells to the antitumor drugs doxorubicin, vinblastine, puromycin, and paclitexel was increased by 18-, 10-, 11-, and 6-fold by 20 microg/mL (or 25 microM) of 1 and 16-, 53-, 16-, and 326-fold by 20 microg/mL (or 39 microM) of 2, respectively. A preliminary mechanistic study has suggested that 1 might modulate Pgp-mediated multidrug resistance through directly interacting with the Pgp substrate site.