Xiaoshu Zhang

Novel dammarane-type triterpenes isolated from hydrolyzate of total Gynostemma pentaphyllum saponins

In this study, five novel triterpenes were isolated from hydrolyzate of total saponins from Gynostemma pentaphyllum and identified as gypensapogenin H (1), gypensapogenin I (2), gypensapogenin L (3), gypensapogenin J (4) and gypensapogenin K (5), three of which (1-3) possess unprecedented ring A. All the isolated compounds were evaluated for cytotoxic activities in five cell lines and all the tested compounds showed significant anti-cancer activities against a series of human cancer cell lines, while having much weaker effect on the growth of normal cell. Among them, compound 1 showed strong inhibition toward MCF-7 human breast cancer cells (IC50 values 6.85 μM). Further mechanistic study demonstrated that compound 1 significantly induced MCF-7 cell apoptosis. Our results indicated that compound 1 may be a promising lead agent for further study.

Pharmacokinetics of 20(S)-25-methoxyl-dammarane-3β, 12β, 20-triol and its active metabolite after oral and intravenous administration in rat

The pharmacokinetics behaviour of 20(S)-25-methoxyl-dammarane-3β, 12β, 20-triol (25-OCH3-PPD) and its active metabolite after oral and intravenous administration in rats were studied. Rats were administered 2.5, 5.0, and 10 mg kg−1 25-OCH3-PPD orally after an overnight fasting or by intravenous injection of 5 mg kg−1 25-OCH3-PPD via the tail vein. Plasma concentration–time profiles of 25-OCH3-PPD and its active metabolite 25-O-demethylated (25-OH-PPD) in rats were monitored by liquid chromatography-tandem mass spectroscopy (HPLC-MS-MS). The 25-O-demethylated metabolite appears to be a pathway in the phase I metabolism of 25-OCH3-PPD in rats. The plasma concentration of the metabolite was higher than that of the parent compound.

Flavonoids and its derivatives from Callistephus chinensis flowers and their inhibitory activities against alpha-glucosidase

Inhibitors of carbohydrate-hydrolysing enzymes play an important role for the treatment of diabetes. One of the therapeutic methods for decreasing of postprandial hyperglycemia is to retard absorption of glucose by the inhibition of carbohydrate- hydrolysing enzymes, such as α-glucosidase, in the digestive organs. To investigate the therapeutic potential of compounds from natural sources, Callistephus chinensis flowers (CCF) were tested for inhibition of α-glucosidase, and acarboes was used as the positive control. The 70 % ethanol extract of CCF exhibited significant α-glucosidase inhibitory activities with IC50 value of 8.14 μg/ml. The stepwise polarity fractions of CCF were tested further for in vitro inhibition of α-glucosidase. The ethyl acetate (EtOAc) fraction exhibited the most significant inhibitory activity. Eight pure compounds, apigenin, apigenin-7-O-β-D- glucoside, kaempferol, hyperin, naringenin, quercetin, luteolin, and kaempferol-7-O-β-D- glucoside, were isolated (using enzyme assay-guide fractionation method) from the EtOAc fraction. Among these, quercetin was the most active one (IC50 values 2.04 μg/ml), and it appears that the inhibiting percentages are close to acarbose (IC50 values 2.24 μg/ml), the positive control, on α-glucosidase inhibition. HPLC/UV analysis indicated that the major components of CCF are kaempferol, hyperin and quercetin. The presented results revealed that CCF containing these eight flavonoids could be a useful natural source in the development of a novel α-glucosidase inhibitory agent against diabetic complications.

New cytotoxic compounds from flowers of Lawsonia inermis L.

Three new compounds, a bicoumarin A (1), a biflavonoid A (2), and a biquinone A (3), as well as 12 other known compounds, were isolated from the flower of Lawsonia inermis L. The structures were elucidated by spectral analysis and new compounds 2 and 3 then were further confirmed by ECD calculations and single-crystal X-ray diffraction crystallography respectively. The cytotoxicity of the compounds against four cancer cell lines, including MCF-7, Hela, HCT-116, and HT-29 were evaluated using MTT assay. The IC50 values of compounds 3 and 5 against MCF-7, Hela, HCT-116, and HT-29 were 2.24, 1.42, 24.29, and 7.02 μM and 6.1, 2.44, 5.58, and 10.21 μM respectively. The two compounds exhibited stronger inhibitory activities than the positive control 5-fluorouracil (IC50=7.34, 11.50, 36.17, 18.83 μM) against the four tested cell lines. These results demonstrated that compounds from the flowers of L. inermis L. showed cytotoxic activity on MCF-7, Hela, HCT-116, and HT-29 cell lines.

Protein tyrosine phosphatase 1B inhibitory effect by dammarane-type triterpenes from hydrolyzate of total Gynostemma pentaphyllum saponins

Protein tyrosine phosphatase 1B (PTP1B) is an important factor in non-insulin-dependent diabetes mellitus (type-2 diabetes), and a promising target for treatment of diabetes and obesity. Therefore, the aim of this study is to investigate the inhibitory activities of constituents (three new together with twelve known triterpenes compounds) isolated from the hydrolyzate of total saponins from Gynostemma pentaphyllum. Their structures were accomplished mainly base on the spectroscopic methods, and then were further confirmed by X-ray crystal diffraction. All the compounds were evaluated for inhibitory activity against PTP1B. Current data suggested that the compounds 1, 3, 12, 13 and 14 were considered to be potential as antidiabetic agents, in which they could significantly inhibit the PTP1B enzyme activity in a dose-dependent manner.

Antitumor activity of ginseng sapogenins, 25-OH-PPD and 25-OCH3-PPD, on gastric cancer cells

Objectives25-Hydroxyprotopanaxadiol (25-OH-PPD) and 25-methoxylprotopanaxadiol (25-OCH3-PPD), two ginseng sapogenins, have potent antitumor activity and their effects on gastric cancer (BGC-823, SGC-7901, MKN-28) cells and a gastric mucosa (GES-1) cell line are reported.ResultsBoth compounds significantly inhibited the growth of gastric cancer cells, while having lesser inhibitory effects on GES-1 cells by MTT assay. A mechanistic study revealed that the two ginseng sapogenins could induce apoptosis in BGC-823 cells by morphological observation, DNA fragmentation, flow cytometry and western blot analysis. Besides, the apoptosis was inhibited by Ac-DEVD-CHO, a caspase 3 inhibitor, which was confirmed by cell viability analysis.ConclusionsThese results indicate that 25-OH-PPD and 25-OCH3-PPD have potential to be promising agents for the treatment of gastric cancer.

Depside derivatives with anti-hepatic fibrosis and anti-diabetic activities from Impatiens balsamina L. flowers.

Eighteen compounds (1-18), seven new (3-9) and eleven previously reported (1, 2, and 10-18), were isolated from the flowers of Impatiens balsamina (Linn). The structures of the isolated compounds were elucidated using different spectroscopic methods, including NMR (1D and 2D), UV, IR, and HR-ESI-MS. Analysis of the bioassay results showed the compounds had notable anti-hepatic fibrosis activity against murine Hepatic Stellate Cells (t-HSC/Cl-6) and anti-diabetics activity against α-glucosidase. Specifically, new compounds 7, 8, 9 showed significant inhibitory activity on t-HSC/Cl-6 cells with IC50 values of 42.12, 109.2, and 34.04 μg/mL respectively, while the IC50 values of positive control Silymarin and Fufang Biejia Ruangan Pian were 202.34 and 231.56 μg/mL, respectively. In addition, compounds 2, 4, 7, 8, 10, 11, 17, and 18 exhibited excellent α-glucosidase inhibitory activity. Among these compounds, 7 exhibited the highest activity with an IC50 value of 0.72 μg/mL, while the IC50 value of the positive control acarbose was 3.36 μg/mL. This is the first study evaluating the anti-hepatic fibrosis and anti-diabetic activities of compounds isolated from the flowers of I. balsamina.

Antihepatic Fibrosis Effect of Active Components Isolated from Green Asparagus (Asparagus officinalis L.) Involves the Inactivation of Hepatic Stellate Cells.

Green asparagus (Asparagus officinalis L.) is a vegetable with numerous nutritional properties. In the current study, a total of 23 compounds were isolated from green asparagus, and 9 of these compounds were obtained from this genus for the first time. Preliminary data showed that the ethyl acetate (EtOAc)-extracted fraction of green asparagus exerted a stronger inhibitory effect on the growth of t-HSC/Cl-6 cells, giving an IC50 value of 45.52 μg/mL. The biological activities of the different compounds isolated from the EtOAc-extracted fraction with respect to antihepatic fibrosis were investigated further. Four compounds, C3, C4, C10, and C12, exhibited profound inhibitory effect on the activation of t-HSC/Cl-6 cells induced by TNF-α. The activation t-HSC/Cl-6 cells, which led to the production of fibrotic matrix (TGF-β1, activin C) and accumulation of TNF-α, was dramatically decreased by these compounds. The mechanisms by which these compounds inhibited the activation of hepatic stellate cells appeared to be associated with the inactivation of TGF-β1/Smad signaling and c-Jun N-terminal kinases, as well as the ERK phosphorylation cascade.

Dammarane triterpenoids for pharmaceutical use: a patent review (2005 – 2014)

Introduction: Dammarane triterpenoids, the main secondary metabolites of Panax ginseng, are very important natural compounds with remarkable biological activity. They could be isolated from the plants of Panax or other genus, as well as through the modifications of certain natural products. This review is a collection of a number of patents (2005 – 2014) that describe the dammarane triterpenoids for therapeutic or preventive uses on numerous common diseases. Areas covered: In this review, patents from 2005 to 2014 on chemical structures and treatment of different diseases by dammarane triterpenoids have been summarized. The SciFinder and the World Intellectual Property Organisation databases have been used as main sources for the search. Expert opinion: In the last decade, over 90 patents concerning dammarane derivatives for pharmaceutical have been published. These types of compounds could be used as agents for prevention and treatment of various kinds of diseases, such as cancer, diabetes mellitus and metabolic syndrome, hyperlipidemia, cardiovascular and cerebrovascular disease, aging, neurodegenerative disease, bone disease, liver disease, kidney disease, gastrointestinal disease, depression-type mental illness and skin aging. Rare plants, except for Panax genus, which contain dammarane triterpenoids should be studied extensively. In addition, more dammarane triterpenoids with good biological activity, especially the aglycones possessing novel side chain, should be prepared using chemical modification. Finally, pharmacological effects of dammarane triterpenoids should be further studied.

Design, characterization, and in vitro antiproliferative efficacy of gemcitabine conjugates based on carboxymethyl glucan

Gemcitabine (GEM) is widely used in clinical practice in the treatment of cancer and several other solid tumors. Nevertheless, the antitumor effect of GEM is partially prevented by some limitations including short half life, and lack of tumor localizing. Carboxymethyl glucan (CMG), a carboxymethylated derivative of β-(1-3)-glucan, shows biocompatibility and biodegradability as well as a potential anticarcinogenic effect. To enhance the antiproliferative activity of GEM, four water soluble conjugates of GEM bound to CMG via diverse amino acid linkers were designed and synthesized. 1H NMR, FT IR, elementary analysis and RP-HPLC chromatography were employed to verify the correct achievement of the conjugates. In vitro release study indicated that conjugates presented slower release in physiological buffer (pH 7.4) than acidic buffer (pH 5.5) mimicking the acidic tumor microenvironment. Moreover, A549, HeLa and Caco-2 cancer cell lines were used to evaluate the in vitro cytotoxicity of conjugates and the results showed that binding GEM to CMG significantly enhanced antiproliferative activity of GEM on A549 cells. Therefore, these conjugates may be potentially useful as a delivery vehicle in cancer therapy and worthy of further study on structure-activity relationship and antiproliferative activity in vitro and in vivo, especially for lung tumor.