Xingzeng Zhao

Macranthoside B, a hederagenin saponin extracted from Lonicera macranthoides and its anti-tumor activities in vitro and in vivo

Macranthoside B (MB) is a hederagenin saponin extracted from the flower bud of Lonicera macranthoides. In this study, we defined the anticancer effect of MB both in vitro and in vivo using cell proliferation assays and xenograft tumor growth assays. Our data indicate that MB inhibits the proliferation of various kinds of cancer cells with IC(50) values in the range of 10-20 microM. Moreover, the volume and weight of xenograft tumors in nude mice treated with 5mg/kgMB were decreased remarkably compared to those of the vehicle control group. Furthermore, DAPI staining and flow cytometry analysis with Annexin V/PI double staining revealed that more apoptotic cells were observed following MB treatment. In addition, degradation of PARP (poly-ADP-ribose polymerase), and activation of the caspase cascade for intrinsic pathways were observed. We also found that the expression of Bcl-2 protein decreased and the protein level of Bax increased which leading to an increase of the Bax/Bcl-2 ratio. Our results showed that MB exhibited strong anti-tumor effect and mitochondrion-mediated apoptosis induction involved in it.

Apoptosis and membrane permeabilisation induced by macranthoside B on HL-60 cells

Triterpene saponins are throught to be potential anti-tumour agents in many cell types. This study aims to evaluate the cytotoxic activity and mechanism of a triterpene saponin, macranthoside B (MB), isolated from Lonicera macranthoides Hand.-Mazz. (Caprifoliaceae). A cell viability assay showed that MB inhibited cell growth of a panel of six cancer cell lines, especially in human acute promyelocytic leukaemia HL-60 cells, with an IC50 value of 3.8 µmol. A hypodiploid cells assay and an annexin-V-FITC/PI double staining assay showed a significant increase of apoptosis in a dose-dependent manner on HL-60 cells both 24 and 48 h after MB treatment. MB-induced apoptosis was through the caspase-mediated pathway, by activation of caspase-3. Furthermore, a lactate dehydrogenase (LDH) release test suggested that an MB–cholesterol interaction led to the rearrangement of the lipid bilayer and to subsequent cell membrane impairment. Taken together, these findings demonstrate that MB may exhibit cytotoxic activity against HL-60 cells by inducing apoptosis via caspase-dependent pathways and also membrane permeabilisation.

New coumarin glucoside from Angelica dahurica

A new linear furanocoumarin glycoside named dahurin B (1) was isolated from the fresh roots and rhizomes of Angelica dahurica. The structure of the new compound was elucidated by spectral techniques including 1H NMR, 13C NMR, as well as HSQC, HMBC, and COSY.

Macranthoside B Induces Apoptosis and Autophagy Via Reactive Oxygen Species Accumulation in Human Ovarian Cancer A2780 Cells

ABSTRACT Macranthoside B (MB), a saponin compound in Lonicera macranthoides, can block cell proliferation and induce cell death in several types of cancer cells; however, the precise mechanisms by which MB exerts its anticancer effects remain poorly understood. MB blocked A2780 human ovarian carcinoma cell proliferation both dose- and time-dependently. MB induced apoptosis, with increased poly (ADP-ribose) polymerase (PARP) and caspase-3/9 cleavage. MB also caused autophagy in A2780 cells, with light chain 3 (LC3)-II elevation. Inhibiting MB-induced autophagy with the autophagy inhibitor 3-methyladenine (3-MA) significantly decreased apoptosis, with a reduction of growth inhibition; inhibiting MB-induced apoptosis with the pan-caspase inhibitor Z-VAD-FMK did not decrease autophagy but elevated LC3-II levels, indicating that MB-induced autophagy is cytotoxic and may be upstream of apoptosis. Furthermore, MB increased intracellular reactive oxygen species (ROS) levels, with activated 5′ adenosine monophosphate-activated protein kinase (AMPK), decreased mammalian target of rapamycin (mTOR) and P70S6 kinase phosphorylation, and increased PARP and caspase-3/9 cleavage, and LC3-II elevation; treatment with the ROS scavenger N-acetyl cysteine and the AMPK inhibitor Compound C diminished this effect. Therefore, the ROS/AMPK/mTOR pathway mediates the effect of MB on induction of apoptosis via autophagy in human ovarian carcinoma cells.

A biflavonoid from stems and leaves of Lonicera macranthoides

A new biflavonoid, 3′′′-O-methylamentoflavone (1), as well as a known biflavonoid, amentoflavone (2), was isolated from the stems and leaves of Lonicera macranthoides Hand.-Mazz.Their structures were established on the basis of 1D, 2D NMR (HSQC and HMBC), and ESI-TOF-MS spectroscopic methods and chemical evidence.

Two new linear furanocoumarin glycosides from Angelica dahurica

Two new linear furanocoumarin glycosides, tert-O-β-D-apiofuranosyl-(1→6)-O-β-D-glucopyranosyl-oxypeucedanin hydrate (1) and sec-O-β-D-apiofuranosyl-(1→6)-O-β-D-glucopyranosyl-oxypeucedanin hydrate (2), were isolated from the fresh roots of Angelica dahurica. The structures of new compounds were elucidated on the basis of spectral analysis.

Two new coumarin biosides from Angelica dahurica

Two new coumarin biosides, tert-O-β-D-apiofuranosyl-(1→6)-O-β-D-glucopyranosyl-byakangelicin (1) and 2′-O-β-D-apiofuranosyl-(1→6)-β-D-glucopyranosyl-peucedanol (2), were isolated from the fresh roots of Angelica dahurica. The structures of the new compounds were elucidated on the basis of spectral analysis.

Fungicidal activity of 10-deacetylbacatin III against Phytophthora capsici via inhibiting lysine biosynthesis

10-deacetyl-bacatin III (10-DAB) is a natural plant-derived taxane diterpene, whose antimicrobial activity against phytopathogens remains unknown. In this study, we demonstrated the antimicrobial effect of 10-DAB on plant-pathogenic oomycetes. Our results revealed that 10-DAB exhibited significant antimicrobial activities against test oomycetes, especially against Phytophthora capsici, with a median effective concentration (EC50) of 1.46 μg/mL, but had no effect on test fungi. Under 10-DAB treatment, mycelia of P. capsici were contorted with an increased number of top branches, and the production and germination of zoospores were inhibited and delayed, respectively. In addition, 10-DAB had favorable protective and curative activities with control efficacies of 63.90% and 74.81% at 200 μg/mL on detached pepper leaves. Furthermore, 10-DAB caused a significant decrease in soluble protein, lysine, and α, ε-diaminopimelic acid content of P. capsici, which suggested that 10-DAB inhibited the lysine biosynthesis. On the contrary, treatment with exogenous lysine effectively counteracted 10-DABs inhibition activity on P. capsici. Moreover, relative expression of four key lysine biosynthesis-related genes of P. capsici were decreased upon 10-DAB treatment. Taken together, our findings suggest a lysine biosynthesis inhibiting-dependent antimicrobial activity of 10-DAB against P. capsici, which contributes to accelerating the application of 10-DAB for successful management of phytophthora blight disease in agricultural production.

Crucial role of oxidative stress in bactericidal effect of parthenolide against Xanthomonas oryzae pv. oryzae : Role of oxidative stress in bactericidal effect of parthenolide

BACKGROUND Xanthomonas oryzae pv. oryzae (Xoo) causes rice bacterial blight, which is one of the most devastating diseases on rice. Parthenolide (PTL) is a sesquiterpene lactone possessing multiple bioactivities. In the preliminary study, we found PTL can totally inhibit the growth of Xoo at 10 mg L-1 in vitro. In this study, we aim to further evaluate the anti-bacterial activity of PTL against Xoo and discern the role of oxidative stress in its bactericidal effect. RESULTS PTL was effective against Xoo both in vitro and in vivo. PTL induced reactive oxygen species (ROS) accumulation in Xoo, leading to cell death, while exogenous catalase can fully abolish its bactericidal effect. PTL sensitivity of catalase deletion mutants of Xoo increased significantly compared with that of wild-type Xoo strain. In addition, PTL treatment increased glutathione peroxidase activity and decreased glutathione (GSH) reductase activity in Xoo, but had no effect on its catalase and superoxide dismutase activities. Interestingly, PTL dramatically reduced the GSH level in Xoo, resulting in disturbed GSH/GSSG balance. Moreover, PTL rapidly reacted with GSH by a nucleophilic addition reaction. CONCLUSION PTL is a promising lead compound for developing bactericide against Xoo. PTL rapidly reacts with GSH, resulting in disturbed GSH/GSSG balance in Xoo, which causes ROS accumulation, leading to cell death. Oxidative stress plays a critical role in the bactericidal effect of PTL against Xoo.