Panaxindole, a novel indole alkaloid N-glucoside from the leaves of Panax vietnamensis Ha et Grushv. (Vietnamese ginseng).

Vietnamese ginseng (Panax vietnamensis Ha and Grushv., Araliaceae) is indigenous in the central highlands of Vietnam and the southernmost distribution in the Panax genus. Like other ginseng, Vietnamese ginseng is well known has been used as a tonic and for management of certain diseases in the traditional medicine. Nevertheless, it is noteworthy that in respect to the long history in use and systematic studied on Korean ginseng (P. ginseng), American ginseng (P. quinquefolius), Japanese ginseng (P. japonicus), and Chinese ginseng (P. notoginseng), the up-to-date published database on Vietnamese ginseng is relatively much less extensive. In our ongoing research on the promising Vietnamese medicinal plants, the present phytochemical investigation of the ethanol extract of the leaves of Panax vietnamensis led to the isolation of three compounds (1-3), including a new indole alkaloid N-glycoside (1) and two known compounds. Their structures were elucidated based on extensive physiochemical and chemical methods, especially the interpretation of NMR and MS spectra. The absolute configuration of 1 was determined based on the comparison of its experimental and theoretical ECD spectra along with NMR calculation. Compound 1 is naturally isolated N-glycoside, which is rarely found in natural products. The isolated compounds showed weak or no inhibitory activity against acetylcholinesterase enzyme (AChE).

Neuroprotective Effects of Ethanol Extract of Polyscias fruticosa (EEPF) against Glutamate-Mediated Neuronal Toxicity in HT22 Cells.

In traditional herbal medicine, the Polyscias fruticosa has been frequently used for the treatment of ischemia and inflammation. Oxidative stress mediated by elevated glutamate levels cause neuronal cell death in ischemia and various neurodegenerative diseases. However, so far, the neuroprotective effects of this plant extract against glutamate-mediated cell death have not been investigated in cell models. The current study investigates the neuroprotective effects of ethanol extracts of Polyscias fruticosa (EEPF) and elucidates the underlying molecular mechanisms of EEPFs relevant to neuroprotection against glutamate-mediated cell death. The oxidative stress-mediated cell death was induced by 5 mM glutamate treatment in HT22 cells. The cell viability was measured by a tetrazolium-based EZ-Cytox reagent and Calcein-AM fluorescent dye. Intracellular Ca2+ and ROS levels were measured by fluorescent dyes, fluo-3 AM and 2',7'-dichlorodihydrofluorescein diacetate (DCF-DA), respectively. Protein expressions of p-AKT, BDNF, p-CREB, Bax, Bcl-2, and apoptosis-inducing factor (AIF) were determined by western blot analysis. The apoptotic cell death was measured by flow cytometry. The in vivo efficacy of EEPF was evaluated using the Mongolian gerbil mouse by surgery-induced brain ischemia. EEPF treatment showed a neuroprotective effect against glutamate-induced cell death. The EEPF co-treatment reduced the intracellular Ca2+ and ROS and apoptotic cell death. Furthermore, it recovered the p-AKT, p-CREB, BDNF, and Bcl-2 levels decreased by glutamate. The EEPF co-treatment suppressed the activation of apoptotic Bax, the nuclear translocation of AIF, and mitogen-activated protein kinase (MAPK) pathway proteins (ERK1/2, p38, JNK). Further, EEPF treatment significantly rescued the degenerative neurons in the ischemia-induced Mongolian gerbil in vivo model. EEPF exhibited neuroprotective properties that suppress glutamate-mediated neurotoxicity. The underlying mechanism of EEPF is increasing the level of p-AKT, p-CREB, BDNF, and Bcl-2 associated with cell survival. It has therapeutic potential for the treatment of glutamate-mediated neuropathology.

Unique guanidine-conjugated catechins from the leaves of Alchornea rugosa and their autophagy modulating activity.

Natural guanidines, molecules that contain the guanidine moiety, are structurally unique and often exhibit potent biological activities. A phytochemical investigation of the leaves of Alchornea rugosa (Lour.) Müll.Arg. by MS/MS-based molecular networking revealed eight undescribed guanidine-flavanol conjugates named rugonines A-H. The chemical structures of the isolated compounds were comprehensively elucidated by NMR spectroscopy, HRESIMS, and circular dichroism (CD) analysis. All isolated compounds were tested for autophagosome formation in HEK293 cells stably expressing GFP-LC3. The results revealed that compounds rugonines D-G showed potential autophagy inhibitory activity.

Antidiabetic Activity of Gomphogyne bonii Gagnep. Extract against High-Fat Diet and Alloxan-Induced Type 2 Diabetes in Mice.

So far, diabetes mellitus has become a health threat to society all over the world. Especially, people with diabetes have always coped with complications related to this disease and unexpected side effects of synthetic drugs. Thus, there has been a current trend for researchers to find out new natural ingredients which were safer and still effective in the treatment of diabetes. Gomphogyne bonii Gagnep. extract (G. bonii extract) was an herbal-derived product of the Pharmacy Department, Vietnam University of Traditional Medicine. This study was designed to assess the antidiabetic effect of G. bonii extract on a high-fat diet (HFD) and alloxan-induced diabetes in mice. Mice were first fed a high-fat diet for 8 weeks and then given an intraperitoneal injection of alloxan (ALX) at the dose of 180 mg/kg b.w. After the diabetic mice model was successfully established, mice were administered orally with G. bonii extract at two doses of 4 mL/kg b.w/day and 12 mL/kg b.w/day for 2 weeks. The results revealed that G. bonii extract at both doses ameliorated the effects of ALX on the concentration of glucose, total cholesterol (TC), triglyceride (TG), and low-density lipoprotein-cholesterol (LDL-C) and microhistological images of livers. Besides, the antidiabetic effect of G. bonii extract at the dose of 12 mL/kg b.w/day was better than that at the dose of 4 mL/kg b.w/day. This suggested that G. bonii extract could be a potential agent for treating diabetes mellitus in clinical practice.

Chemical constituents from the roots of Kadsura coccinea with their protein tyrosine phosphatase 1B and acetylcholinesterase inhibitory activities.

Kadsura coccinea (Lem.) A. C. Smith has been used as a tonic, decongestant, and digestive agent. The roots are also employed in traditional medicine to treat chronic enteritis, acute gastritis, duodenal ulcers, rheumatic pain in bone, and traumatic injuries. In the present study, we have described the biological evaluation of constituents from the roots of K. coccinea with PTP1B and AChE inhibitory activities for the first time in literature. A new compound (1), kadcoccilactone T, and 24 known ones (2‒25) were isolated and identified using spectroscopic methods. All the isolates were examined for PTP1B and AChE inhibitory activities. Compounds 4 and 8 expressed strong PTP1B inhibition with IC50 values of 1.57 ± 0.11 and 3.99 ± 1.08 µM, respectively. Apparently, these compounds were further studied for PTP1B enzyme kinetic analysis. The result indicated that compounds 4 and 8 exhibited mixed-type inhibition with the Κi values of 4.97 and 3.26 µM, respectively.

Oligosaccharide and glucose esters from the roots of Polygala arillata.

The root of plant Polygala arillata has been used in the Oriental medicine as a tonic and for the treatment of certain diseases. Our current research on phytochemical profile of the roots of P. arillata led to the isolation of a new oligosaccharide ester (1, polygaloside), a new glucose ester (7, arillatoside), along with five known sucrose esters (2-6). Their structures were elucidated on the basis of extensive chemical and spectroscopic methods as well as comparison with those reported in the literature. The occurence of various oligosaccharide esters in P. arillata including unique compounds plays taxonomical impact and suggests potential in medicinal uses of the title plant.

A natural ent­kaurane diterpenoid induces antiproliferation in ovarian cancer cells via ERK1/2 regulation and inhibition of cellular migration and invasion.

Ovarian cancer is one of the most common causes of female mortalities from gynecological tumors. An ent­kaurane diterpenoid compound CRT1 (ent­18­acetoxy­7ß­hydroxy kaur­15­oxo­16­ene), mainly isolated from the Vietnamese herb Croton tonkinesis has been used in folk medicine in Vietnam for cancer treatment. However, the effect of this compound on human ovarian cancer cells has not yet been reported. The objective of the present study was to determine the effect of CRT1 on the cell viability, apoptosis and metastasis of SKOV3 human ovarian cancer cells using a Cell Counting Kit­8 assay, flow cytometric analysis of Annexin V­fluorescein isothiocyanate/propidium iodide staining, western blot analysis, soft agar colony forming assay, wound healing assay and Matrigel invasion assay. The results revealed that CRT1 possessed significant anti­proliferative effects on SKOV3 cells. CRT1 treatment at 25 and 50 µM induced apoptosis, enhanced the percentage of Annexin V­positive cells, increased the expression of pro­apoptotic protein B­cell lymphoma 2 (Bcl­2)­associated X protein, cytochrome c release from the mitochondria to the cytosol, cleaved caspase­3, caspase­7, caspase­9, and poly (adenosine diphosphate­ribose) polymerase. However, it decreased the expression of Bcl­2 in a dose­dependent manner. The percentage of necrotic cells increased following CRT1 treatment at <10 µM. CRT1 at 50 µM significantly induced the phosphorylation of extracellular signal­regulated kinase (ERK). Growth inhibition and the apoptotic effects of CRT1 could be reversed by PD98059, an ERK inhibitor. Additionally, CRT1 inhibited cell migration and invasion via ERK1/2 activation in SKOV3 cells. These results indicated that CRT1, an ent­kaurane diterpenoid, may be a potential inhibitor of ovarian cancer by the activating ERK1/2/p90 ribosomal S6 kinase signaling pathway.

Antiproliferative activity and apoptosis induction by trijuganone C isolated from the root of Salvia miltiorrhiza Bunge (Danshen).

In this study, we found that the hexane fraction of Danshen, the dried root of Salvia miltiorrhiza (Lamiaceae), exerted antiproliferative effects on human leukemia cells. Phytochemical investigation of the hexane fraction achieved the isolation of the tanshinone diterpenes: dihydrotanshinone I (1), trijuganone C (2), trijuganone B (3), cryptotanshinone (4), tanshinone IIA (5), and tanshinone I (6). Compound 2 showed significant antiproliferative activities against human leukemia cells HL-60, Jurkat, and U937. The antiproliferative activities of 2 against human cancer and normal cells indicated that 2 exhibited potent antiproliferative activities with IC50 values less than 10 µM against HL-60 and Jurkat cells as well as on the colon cancer cells DLD-1, COLO 205, and Caco-2. Compound 2 induced chromatin condensation, DNA fragmentation, activation of caspase-3, -8, and -9, and the cleavage of poly (ADP-ribose) polymerase (PARP) in HL-60 cells. Moreover, 2 activated Bid and Bax, leading to the loss of mitochondrial membrane potential, and 2 induced the cytochrome c release from mitochondria into cytosol. In contrast, Bcl-2 and Bcl-xL were unaffected by 2. These results suggest that 2 exerts antiproliferative effects via apoptosis induction mediated by mitochondrial dysfunction and caspase activation. Compound 2 may serve as a candidate of potential chemotherapeutic agent for human leukemia.

Xanthine oxidase inhibitors from Archidendron clypearia (Jack.) I.C. Nielsen: Results from systematic screening of Vietnamese medicinal plants.

OBJECTIVE: To screen Vietnamese medicinal plants for xanthine oxidase (XO) inhibitory activity and to isolate XO inhibitor(s) from the most active plant. METHODS: The plants materials were extracted by methanol. The active plant materials were fractionated using different organic solvents, including n-hexane, ethyl acetate, and n-butanol. Bioassay-guided fractionation and column chromatography were used to isolate compounds. The compounds structures were elucidated by analysis of spectroscopic data, including IR, MS, and NMR. RESULTS: Three hundreds and eleven methanol extracts (CME) belonging to 301 Vietnamese herbs were screened for XO inhibitory activity. Among these plants, 57 extracts displayed XO inhibitory activity at 100 µg/mL with inhibition rates of over 50%. The extracts of Archidendron clypearia (A. clypearia), Smilax poilanei, Linociera ramiflora and Passiflora foetida exhibited the greatest potency with IC50 values below 30 µg/mL. Chemical study performed on the extract of A. clypearia resulted in the isolation of six compounds, including 1-octacosanol, docosenoic acid, daucosterol, methyl gallate, quercitrin and (-)-7-O-galloyltricetiflavan. The compound (-)-7-O-galloyltricetiflavan showed the most potent XO inhibitory activity with an IC50 value of 25.5 µmol/L. CONCLUSIONS: From this investigation, four Vietnamese medicinal plants were identified to have XO inhibitory effects with IC50 values of the methanol extracts below 30 µg/mL. Compound (-)-7-O- galloyltricetiflavan was identified as an XO inhibitor from A. clypearia with IC50 value of 25.5 µmol/L.

Anti-Hyperuricemic, Anti-Inflammatory and Analgesic Effects of Siegesbeckia orientalis L. Resulting from the Fraction with High Phenolic Content.

BACKGROUND: The medicinal plant Siegesbeckia orientalis L. has been commonly used for the treatment of acute arthritis, rheumatism, and gout in Vietnam. However, pharmacological research of this plant associated with gout has not been reported. Anti-hyperuricemic and anti-inflammatory effects were evaluated and observed for the crude ethanol extract (CEE) of S. orientalis. Retention of these biological properties was found in a n-butanol-soluble fraction (BuOH fr.) of the extract, and therefore further biological and chemical investigations were undertaken on the BuOH fr. to support the medical relevance of this plant. METHODS: The aerial part of S. orientalis was obtained in the mountainous region of Vietnam. The crude ethanol extract (CEE) and its BuOH fr. were prepared from the plant materials. Anti-hyperuricemic activities of the CEE and BuOH fr. were tested in vivo using the model oxonate-induced hyperuricemia rats through determination of serum uric acid levels and inhibitory effects on xanthine oxidase (XO) in the rat liver. Anti-inflammatory activities of the BuOH fr. were also evaluated in vivo using carrageenan-induced paw edema and urate-induced synovitis in rats. Active components of the BuOH fr. were characterized by comparison of HPLC retention time (t R) and spectroscopic data (UV, 1H-NMR) with those of reference compounds. RESULTS: The CEE of S. orientalis displayed anti-hyperuricemic activity, and the BuOH fr. was found to be the most active portion of the extract. Further in vivo studies on this fraction showed 31.4% decrease of serum uric acid levels, 32.7% inhibition of xanthine oxidase (XO), 30.4% reduction of paw edema volume, symptomatic relief in urate-induced synovitis and significant analgesic effect at the dose of 120 mg/kg, as compared to the corresponding values of the control groups. Chemical analysis of the BuOH fr. revealed high phenolic content, identified as caffeic acid analogues and flavonones. CONCLUSIONS: This study suggested that anti-hyperuricemic and anti-inflammatory mechanism of S. orientalis is related to XO inhibitory effect of the phenolic components. Our findings support the use of this plant as the treatment of gout and other inflammatory diseases.

Anticancer activity of pristimerin in epidermal growth factor receptor 2-positive SKBR3 human breast cancer cells.

Pristimerin is a naturally occurring triterpenoid that causes cytotoxicity in several cancer cell lines. However, the mechanism of action for the cytotoxic effect of pristimerin has not been unexplored. The purpose of this study was to investigate the effect of pristimerin on cytotoxicity using the epidermal growth factor receptor 2 (HER2)-positive SKBR3 human breast cancer cell line. Pristimerin inhibited proliferation in dose- and time-dependent manners in cells. We found it to be effective for suppressing HER2 protein and mRNA expression. Fatty acid synthase (FASN) expression and FASN activity were downregulated by pristimerin. Adding of exogenous palmitate, the end product of de novo fatty acid synthesis, reduced the proliferation activity of pristimerin. The changes in HER2 and FASN expression induced by pristimerin altered the levels of Akt and mitogen-activated protein kinase (MAPK) phosphorylation (Erk1/2, p38, and c-Jun N-terminal kinase (JNK)). Pristimerin lowered the levels of phosphorylated mammalian target of rapamycin (mTOR) and its downstream targets such as phosphoprotein 70 ribosomal protein S6 kinase and 4E binding protein1. Pristimerin inhibited migration and invasion of cells, and co-treatment with the mTOR inhibitor rapamycin additionally suppressed these activities. Pristimerin-induced apoptosis was evaluated using Western blotting for caspase-3, -8, -9, and poly (ADP-ribose) polymerase expression and flow cytometric analysis for propidium iodide labeling. These results suggest that pristimerin is a novel HER2-downregulated compound that is able to decrease fatty acid synthase and modulate the Akt, MAPK, and mTOR signaling pathways to influence metastasis and apoptosis. Pristimerin may be further evaluated as a chemotherapeutic agent for HER2-positive breast cancers.

An ent-kaurane diterpenoid from Croton tonkinensis induces apoptosis by regulating AMP-activated protein kinase in SK-HEP1 human hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer with high mortality worldwide. Traditional chemotherapy for HCC is not widely accepted by clinical practitioners because of its toxic side effects. Thus, there is a need to identify chemotherapeutic drugs against HCC. AMP-activated protein kinase (AMPK) is a biologic sensor for cellular energy status that acts a tumor suppressor and a potential cancer therapeutic target. The traditional Vietnamese medicinal plant Croton tonkinensis shows cytotoxicity in various cancer cells; however, its anticancer mechanism remains unclear. In this study, we determined whether the ent-kaurane diterpenoid ent-18-acetoxy-7ß-hydroxy kaur-15-oxo-16-ene (CrT1) isolated from this plant plays a role as a chemotherapeutic drug targeting AMPK. CrT1 blocked proliferation in dose- and time-dependent manners in human hepatocellular carcinoma SK-HEP1 cells. CrT1 induced sub-G(1) arrest and caspase-dependent apoptosis. CrT1 activated caspase-3, -7, -8, -9, and poly(ADP-ribose) polymerase, and its effect was inhibited by z-VAD-fmk suppressing caspase-3 cleavage. CrT1 induced increases in p53 and Bax levels but decreased Bcl(2) levels. In addition, CrT1 resulted in increased translocation of cytochrome c into the cytoplasm. We showed that CrT1-activated AMPK activation was followed by modulating the mammalian target of rapamycin/p70S6K pathway and was inactivated by treating cells with compound C. Treatment with CrT1 and aminoimidazole carboxamide ribonucleotide (AICAR) synergistically activated AMPK. CrT1-induced AMPK activation regulated cell viability and apoptosis. These results suggest that CrT1 is a novel AMPK activator and that AMPK activation in SK-HEP1 cells is responsible for CrT1-induced anticancer activity including apoptosis.

Anticancer properties of pomolic acid-induced AMP-activated protein kinase activation in MCF7 human breast cancer cells.

AMP-activated protein kinase (AMPK) is a sensor of cellular energy status found in all eukaryotes. Recent studies indicate that AMPK activation strongly suppresses cell proliferation in tumor cells, which requires high rates of protein synthesis and de novo fatty acid synthesis for their rapid growth. Pomolic acid (PA) has been previously described as being active in inhibiting the growth of cancer cells. In this study, we investigated PA activated AMPK, and this activity was related to proliferation and apoptosis in MCF7 breast cancer cells. PA inhibited cell proliferation and induced sub-G(1) arrest, elevating the mRNA levels of the apoptotic genes p53 and p21. PA activated caspase-3, -9, and poly(ADP-ribose) polymerase, and this effect was inhibited by z-VAD-fmk. AMPK activation was increased by treating cells with PA, inactivated by treating cells with a compound C, and co-treatment consisting of PA and aminoimidazole carboxamide ribonucleotide (AICAR) synergistically activated AMPK. These anti-cancer potentials of PA were accompanied by effects on de novo fatty acid synthesis as shown by the decreased expression of fatty acid synthase, and decreased acetyl-CoA carboxylase activation and incorporation of [(3)H]acetyl-CoA into fatty acids. In addition, PA inhibited key enzymes involved in protein synthesis such as mammalian target of rapamycin (mTOR), 70 kDa ribosomal protein S6 kinase (p70S6K), and eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1). These results suggest that PA exerts anti-cancer properties through the modulation of AMPK pathways and its value as an anti-cancer agent in breast cancer therapy.

Symmetric dimers of ent-kaurane diterpenoids with cytotoxic activity from Croton tonkinensis.

Breast cancer is the most common malignant tumor in women these days accounting for approximately 24% of all cancer. During our screening program searching for cytotoxic materials from natural products, two new symmetric dimers of ent-kaurane diterpenoid, crotonkinensins C (1) and D (2), with connectivity at C-17 were isolated from the leaves of the Vietnamese endemic medicinal plant Croton tonkinensis. Their structures were determined on the basis of physicochemical and spectroscopic data. Compound 2 showed a potent cytotoxic activity against MCF-7, tamoxifen-resistant MCF-7 (MCF-7/TAMR), adriamycin-resistant MCF-7 (MCF-7/ADR), and MDA-MB-231 breast cancer cell lines.

Activation of AMP-activated protein kinase on human gastric cancer cells by apoptosis induced by corosolic acid isolated from Weigela subsessilis.

Corosolic acid is one of the triterpenoids present in the leaves of Weigela subsessilis. The antidiabetic activity of corosolic acid has been reported previously, but to date, the anticancer effects on gastric cancer have been poorly studied. In this study, corosolic acid showed growth inhibition on SNU-601 human gastric cancer cells, with an IC50 value of 16.9 ± 2.9 µM. Corosolic acid also triggered the activation of caspase-3 and poly (ADP-ribose) polymerase, while it was recovered by Z-VAD-FMK. Moreover, the cell growth/apoptosis activities of corosolic acid were regulated by the AMP-activated protein kinase-mammalian target of rapamycin (AMPK-mTOR) signals. These results showed that corosolic acid-mediated AMPK activation leads to inhibition of mTOR, thus providing a possible mechanism of action of corosolic acid in the inhibition of cancer cell growth and the induction of apoptosis.

Protein tyrosine phosphatase 1B inhibitory activity of 24-norursane triterpenes isolated from Weigela subsessilis.

During the screening effort to discover new types of protein tyrosine phosphatase 1B (PTP1B) inhibitors, it was found that a MeOH extract of the leaves and stems of Weigela subsessilis (Caprifoliaceae) inhibited the enzyme activity. By means of an in vitro bioassay-guided fractionation on the MeOH extract, two 24-norursane triterpenes, ilekudinol A (1) and ilekudinol B (2), were isolated as active metabolites. Compounds 1 and 2 inhibited PTP1B with IC(50) values of 29.1 ± 2.8 and 5.3 ± 0.5 µM, respectively. Kinetic studies suggest that both 1 and 2 are non-competitive inhibitors of PTP1B. The findings indicate that the free carboxyl group at C-28 in this type of triterpenes plays a critical role in the inhibition of PTP1B.

Down-regulation of human epidermal growth factor receptor 2/neu oncogene by corosolic acid induces cell cycle arrest and apoptosis in NCI-N87 human gastric cancer cells.

Overexpression/amplification of human epidermal growth factor receptor (HER)2/neu (erbB-2) oncogene plays a causal role in carcinogenesis and correlates with a poor clinical prognosis. However, little is known about HER2 in gastric cancer. In this study, we explored the pharmacological activities of natural triterpenoid corosolic acid (CRA) in HER2 signaling and its role in gastric cancer development and progression. In this study, CRA dramatically inhibited HER2 expression in a dose- and time-dependent manner, effectively inhibited cell proliferation, and induced G(0)/G(1) arrest through the induction of p27(kip1) and cyclin D(1) down-regulation. CRA exposure enhanced apoptotic cell death, as confirmed by caspase-3 and poly (ADP-ribose) polymerase cleavage activities. CRA inhibited signaling pathways downstream of HER2, including phospho-proteins such as Akt and Erk. In addition, CRA combined with adriamycin and 5-fluorouracil enhanced this growth inhibition, but not with docetaxel and paclitaxel. These findings demonstrate that CRA suppresses HER2 expression, which in turn promotes cell cycle arrest and apoptotic cell death of gastric cancer cells, providing a rationale for future clinical trials of CRA in the treatment of HER2-positive gastric cancers.

Synthesis and Biological Evaluation of A Series of (Benzo[d]thiazol-2-yl)cyclohexanecarboxamides and (Benzo[d]thiazol-2-yl)cyclohexanecarbothioamides.

A series of benzothiazole derivatives including N-(benzo[d]thiazol-2-yl)cyclohexanecarboxamides (2a-g) and N-(benzo[d]thiazol-2-yl)cyclohexancarbothioamides (3b-d) have been synthesized and evaluated for cytotoxic and antimicrobial activities. Two compounds including N-(6-ethoxybenzo[d]thiazol-2-yl)cyclohexanecarboxamide (2c) and N-(6-ethoxybenzo[d]thiazol-2-yl)cyclohexanecarbothiamide (3c) demonstrated significant cytotoxicity against three cancer cell lines (A549, MCF7-MDR and HT1080) while most of compounds exhibited moderate inhibitory effects on the growth of Staphyllococcus aureus and some other fungi.

SIRT1 inhibitory diterpenoids from the Vietnamese medicinal plant Croton tonkinensis.

Silent information regulator two ortholog 1 (SIRT1) is a member of the sirtuin deacetylase family of enzymes that removes acetyl groups from the lysine residues in histones and other proteins. It has been suggested that SIRT1 inhibitors might be beneficial in the treatment of cancer and neurodegenerative diseases. Bioassay-guided fractionation of the MeOH extract of the leaves of CROTON TONKINENSIS resulted in the isolation of a new ENT-kaurane diterpenoid (1) along with 11 known compounds (2- 12). The structure of the new compound 1 was determined to be ENT-11 alpha-acetoxy-7 beta-hydroxykaur-16-en-15-one based on spectroscopic analyses. Compounds 3, 4, 6- 9, 11, and 12 exhibited SIRT1 inhibitory activity in an IN VITRO assay, with IC (50) values ranging from 16.08 +/- 0.11 to 44.34 +/- 2.32 microM. This is the first report showing the potential of ENT-kaurane diterpenoids as a new class of natural SIRT1 inhibitors.

Stimulation of glucose uptake by triterpenoids from Weigela subsessilis.

Four ursane-type triterpenoids, corosolic acid (1), ilekudinol B (2), ursolic acid (3) and pomolic acid (4), were isolated from an EtOAc-soluble extract of the leaves of Weigela subsessilis. These bioactive compounds were evaluated for their glucose uptake activity and produced moderate to strong enhancement both in basal- and insulin-stimulated L6 muscle cells. In particular, corosolic acid exhibited the most potent activity, increasing uptake by basal- and insulin-stimulated myotubes by 2.63- and 3.33-fold, respectively; ilekudinol B produced 1.6- and 2.9-fold, ursolic acid produced 1.84- and 2.64-fold, and pomolic acid produced 1.6- and 2.8-fold increases. No cytotoxicities were observed for corosolic acid, ursolic acid and ilekudinol B in myoblasts, while pomolic acid at doses of 25 and 50 microm reduced cell viability by 19% and 21.8% upon 24 h treatment and by 48.6% and 54.1% upon 48 h treatment, respectively. These results suggest that ursane-type triterpenoids from W. subsessilis might enhance glucose uptake by acting as insulin mimics and as insulin sensitizers and that they could be useful as nontoxic diabetes treatment agents.