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47 records · Page 3Linked to original sources
PubMed2006

The course of uncarinic acid E-induced apoptosis of HepG2 cells from damage to DNA and p53 activation to mitochondrial release of cytochrome c.

Uncarinic acid E, an active component isolated from Gelsemium elegans BENTH, has been reported to exhibit antitumor effects, but little is known about its molecular mechanisms of action. In this study, the growth-inhibitory activity of uncarinic acid E for HepG2 cells is in time- and dose-dependent manner. HepG2 cells treated with uncarinic acid E exhibited several typical characteristics of apoptosis through photomicroscopical observation, DNA agarose gel electrophoresis. The inhibitory effect of uncarinic acid E on HepG2 cells was partially reversed by the inhibitors of pan-caspase, caspase-3 and caspase-6. The protein expression ratio of Bcl-xL/Bax and Bcl-2/Bax was down-regulated and uncarinic acid E-induced apoptosis involves the initial phase mediated by the balance among Bcl-xL, Bcl-2 and Bax proteins, resulting in cytochrome c release from the mitochondria. Uncarinic acid E significantly increased the expression of p53 proteins indicates that p53 plays a pivotal role in the initiation phase of uncarinic acid E-induced HepG2 cell apoptosis. The phoshatidylinositol 3-kinase (PI3-K) family inhibitor wortmanin and the MEK inhibitor (PD98059) rescued the viability loss induced by uncarinic acid E through the expression of p53. Taken together, uncarinic acid E induces apoptosis in HepG2 cells via accumulation of p53, alters the Bax/Bcl-2 ratio, and activates caspases, resulting in cytochrome c release from the mitochondria.

Apoptosis↗
PubMed1995

[Chemical studies of indole alkaloids].

Up to now, more than two thousands indole alkaloids having structural variety have been found from the three families of Gentianales: Loganiaceae, Apocynaceae, and Rubiaceae plants. These compounds generally possess characteristic biological activities and many of them are utilized for the medicinal purpose and for the lead-compounds to develop new synthetic drugs. The author of this review has been investigated the alkaloidal constituents of the above mentioned plants native to Japan and overseas countries. Especially, a cooperative work with Thai researchers concerning the plants in Thailand was developed. On the basis of biogenetic consideration of the structures of monoterpenoid indole alkaloids, chemical bond cleavage between the C3-N4 linkage in the C/D ring of indole alkaloids was discovered. It was speculated that, either in biogenesis, the flexibility of the ring-opening compounds having ten membered ring enabled the construction of indole alkaloids having highly strained polycyclic structures. Along with this conception, the syntheses of structurally complex indole alkaloids utilizing a biomimetic procedure have been investigated. In this review, recent results on the chemical synthesis of many skeletally varied Gelsemium alkaloids (Loganiaceae plant) are mainly described.

Alkaloids↗
PubMed2004

Enantioselective total synthesis of semperoside a.

A versatile and concise strategy has been developed (Scheme 1) for the enantioselective synthesis of semperoside A 1 which is endowed with an unusually glucosylated iridane structure. The crucial step was a Hg(II)-mediated electrophilic heteroatom cyclization of beta-glucoside 4 that readily led to the iridane skeleton while installing the C-2 and C-3 stereocenters with complete stereocontrol. This expeditious route is unprecedented among synthetic approaches to iridoid glycosides and smoothly overcomes the hemiacetals glucosidation issue. The present inaugural total synthesis of semperoside A was achieved in 10 steps and 17% overall yield from the enantiomerically pure lactone 8, thus proving the absolute stereochemistry of 1 unequivocally.

Cyclization↗
PubMed2003

[Study of koumine-induced apoptosis of human colon adenocarcinoma LoVo cells in vitro].

OBJECTIVE: To study the apoptosis-inducing effect of koumine on human colon adenocarcinoma LoVo cells in vitro. METHODS: After koumine (50 mmol/L) treatment in vitro, the LoVo cells were examined under light microscope, transmission electron microscope and fluoroscope respectively for apoptosis, and the cell cycle distribution was analyzed using flow cytometry. RESULTS: The percentage of apoptotic cells increased in a time-dependent manner after the cells were treated with koumine, whose action exhibited remarkable cell cycle specificity. The percentage of LoVo cells in G(0)/G(1) phase rose from 31.3% to 42.3% and the percentage of cells in S phase fells from 62.0% to 38.7%. CONCLUSION: Koumine can induce apoptosis of LoVo cells in a time-dependent manner and inhibit the DNA synthesis in LoVo cells, thereby blocking the cell cycle from G1 to S phase.

Adenocarcinoma↗
PubMed2004

[General pharmacology of koumine parenteral solution].

OBJECTIVE: To determine the effect of koumine parenteral solution on the nervous, respiratory and cardiovascular systems of experimental animals. METHODS: Mouse spontaneous activities under the influence of the koumine injection were recorded with a photoelectric counter, and canine femoral artery pressure was determined by CYS-0.5 pressure transducer, respiratory curve described with TB-611 tension transducer and electrocardiogram (ECG) recorded with subcutaneous electrodes in the extremities after the injection. The above indices were automatically sampled and processed by multifunctional signal processor after being inputt to a computer. In this experiment, we observed the changes in the general behavior of the mice and their spontaneous activities within 15 min, along with the heart rate, maximum, minimum, and mean value of cardiac electric voltage, mean arterial pressure, respiratory rate and respiratory depth of the dogs before and at 10, 20, 30, 60, 90, 120 min after koumine injection. RESULTS: Koumine injection significantly decreased mouse spontaneous activities in moderate and high-dose groups, but did not produce obvious effect on the respiratory system, mean arterial pressure, and maximum, minimum, and mean values of cardiac electric voltage in dogs. The heart rate of the dogs did not undergo obvious changes in response to the injection at a low dose, but median and high doses of the injection produced obvious effects. CONCLUSION: Koumine injection has definite sedative effect in mice, and does not affect the respiratory and cardiovascular systems of dogs with the exception of the heart rate.

Animals↗
PubMed2005

[Therapeutic effects of koumine on psoriasis: an experimental study in mice].

OBJECTIVE: To study the therapeutic effects of koumine on psoriasis in mouse models. METHODS: The effects of koumine on epithelial cell mitosis and epidermal cell differentiation was evaluated by collecting the samples of the vaginal mucous and squamous epidermis at the tail of mice treated with methotrexate or koumine at different doses. The levels of interleukin (IL)-2 were detected with enzyme-linked immunosorbent assay. RESULTS: High and intermediate doses of koumine showed remarkable inhibitory effect on mouse vaginal epithelial cell mitosis and promoted the formation of epidermal granular layer in the scales at the mouse tail. Three concentrations at 6, 30, 150 mg/kg of koumine decreased serum IL-2 level in the mice. CONCLUSION: The therapeutic effect of koumine against psoriasis is related to the inhibition of epidermal cell proliferation, promoting the formation of granular cells and decreasing the serum level of IL-2.

Animals↗
PubMed2005

[Effect of koumine on proliferation of murine CD4+ T cells purified by magnetic-activated cell sorting in vitro].

OBJECTIVE: To assess the separation efficiency of magnetic-activated cell sorting in the purification of CD4+ T cells from murine spleen, and observe the effects of koumine on the proliferation of the separated cells. METHODS: CD4+ T cells were isolated from murine spleen by magnetic-activated cell sorting (MiniMACS). Fluorescence-activated cell sortering was employed to determine the purity of CD4+ T cells before and after the separation procedure followed by evaluation of the cell viability using trypan blue staining. Concanavalin A- (ConA, 5 microg/ml) or phytahematoagglutinin (PHA,1 mg/ml)-induced murine T cells were treated with different concentrations of koumine (10-320 microg/ml), and their proliferation was determined by MTT colorimetry, and enzyme-linked immunosorbent assay was used to measure IL-2 level in the cell culture supernatant. RESULTS: The purity of CD4+ T cells reached (90.3+/-5.8)% after the purification with a cell viability of (94.9+/-3.6)%. Koumine (20-320 microg/ml) dose-dependently inhibited ConA- or PHA-induced proliferation of murine lymphocytes as compared with the controls (P<0.05). Koumine (20, 100, and 200 microg/ml) significantly decreased the level of IL-2 in comparison with the control group (P<0.05). CONCLUSIONS: CD4+ T cells of high purity can be obtained from murine spleen using MiniMACS without impairing the viability of the cells. Koumine significantly inhibits the proliferation of murine CD4+ T cells due to its immunosuppressive effect and inhibition of IL-2 secretion.

Animals↗