>> Gynostemma Pentaphyllum
1. Inhibition of melanogenesis and melanin transportation.
Gynostemma pentaphyllum, Hye In Lee, Byoung Sam Yoo, Mi Ae Yoo and Sang Yo Byun. Department of Molecular Science & Technology, Ajou
University, Suwon, Kyunggi 443-749, Korea.
"The extract of Gynostemma pentaphyllum was tested to control the melanogenesis in B16 melanoma. Cytotoxic effect by the extract was
observed when the dose concentration was higher than 2 mg/L. Most of the inhibitory effect was obtained by the reduced accumulation of
extra-cellular melanin. When the extract was dosed as 2 mg/L, the extra-cellular melanin produced was only 24% of the control. Proteome
analysis with 2-D PAGE showed that various proteins involved in melanogenesis were down-regulated by Gynostemma pentaphyllum. In
addition to other proteins related to the intra-cellular melanogenesis, Rab-27b and Rab-38 could explain the remarkable decrease in extra-cellular
melanin accumulation by reduced melanin transfer to keratinocyte."
2. Gypenosides derived from Gynostemma pentaphyllum suppress NO synthesis in murine macrophages by inhibiting iNOS enzymatic activity and
attenuating NF-kappaB-mediated iNOS protein expression.
Aktan F, Henness S, Roufogalis BD, Ammit AJ., Faculty of Pharmacy, University of Sydney.
"Gypenosides isolated from Gynostemma pentaphyllum are widely used in traditional Chinese medicine, with beneficial effects reported in
numerous diseases, including inflammation and atherosclerosis, although the mechanism underlying these therapeutic effects is unknown.
Because increased nitric oxide (NO) plays a role in these pathological conditions, we investigated whether the pharmacological activity of
gypenosides is due to suppression of NO synthesis. The markedly increased production of nitrite by stimulation of RAW 264.7 murine
macrophages with 1 microg/mL lipopolysaccharide (LPS) for 20 h (unstimulated: 0.3+/-0.3 microM vs. LPS: 32.5+/-1.2 microM) was dose-
dependently inhibited by gypenosides (0.1-100 microg/mL). When cells were pretreated with gypenosides (for 1h) prior to LPS stimulation,
subsequent NO production was significantly attenuated (IC(50) of 3.1+/-0.4 microg/mL) (P<0.05)."
3. Protective effect of gypenosides against oxidative stress in phagocytes, vascular endothelial cells and liver microsomes.
Li L, Jiao L, Lau BH., "Department of Microbiology, School of Medicine, Loma Linda University, CA.
"The action of gypenosides (GP, saponins of Gynostemma pentaphyllum, a Chinese medicinal herb) as an antioxidant was studied using various
models of oxidant stress in phagocytes, liver microsomes and vascular endothelial cells. The results show that GP decreased superoxide anion
and hydrogen peroxide content in human neutrophils and diminished chemiluminescent oxidative burst triggered by zymosan in human
monocytes and murine macrophages. An increase of lipid peroxidation induced by Fe2+/cysteine, ascorbate/NADPH or hydrogen peroxide in
liver microsomes and vascular endothelial cells was inhibited by GP. It was also found that GP protected biomembranes from oxidative injury by
reversing the decreased membrane fluidity of liver microsomes and mitochondria, increasing mitochondrial enzyme activity in vascular
endothelial cells and decreasing intracellular lactate dehydrogenase leakage from these cells. The extensive antioxidant effect of GP may be
valuable to the prevention and treatment of various diseases such as atherosclerosis, liver disease and inflammation."
4. Protection of vascular endothelial cells from hydrogen peroxide-induced oxidant injury by gypenosides, saponins of Gynostemma pentaphyllum.
Lin Li, Benjamin H. S. Lau, Department of Microbiology, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USA.Funded by: Chan Shun Research Fund for AIDS and Cancer (Chan Shun International Foundation, Burlingame, CA, USA).
"Lipid peroxidation and toxicity associated with oxygen radicals have been suggested as major causes of cancer, atherosclerosis and the aging process. Damage of endothelial cells may lead to cardiovascular and cerebrovascular diseases. Endothelial cells are susceptible to oxidant insult. In the present study, the antioxidant effect of a Chinese medicinal herb, Gynostemma pentaphyllum Makino (Chinese name, Jiaogulan), was investigated in vitro using vascular endothelial cells. Confluent monolayers of bovine pulmonary artery endothelial cells (PAEC) were preincubated with different concentrations of gypenosides (GP, total saponins of Gynostemma pentaphyllum) for 16 h, then washed and incubated with hydrogen peroxide (H2O2) for 4 h. Cell injury was assessed by measuring the release of intracellular lactate dehydrogenase(LDH), and cell viability with tetrazolium (MTT) assay. Lipid peroxidation products of PAEC were monitored as thiobarbituric acid-reactive substances (TBARS) with a fluorometric assay. The results showed that 62.5 M H2O2 incubated with PAEC for 4 h increased the percentage of LDH release, decreased cell viability manifested by MTT absorbance at 620 nm, and elevated TBARS. Preincubation of GP (25-150 g/mL) with PAEC for 16 h before H2O2 exposure significantly declined LDH release, increased cell viability, and reduced TBARS. These results demonstrate that gypenosides can protect vascular endothelial cells from oxidant injury. The data thus suggest that gypenosides may be beneficial for the prevention and treatment of atherosclerosis and for retardation of the aging process."
5. Gypenosides induce apoptosis in human hepatoma Huh-7 cells through a calcium/reactive oxygen species-dependent mitochondrial pathway.
Qwa-Fun Wang,Chi-Wu Chiang,Chun-Chi Wu,Chi-Chih Cheng,Shur-Jong Hsieh,Jung-Chou Chen,Yun-Chih Hsieh,Shih-Lan Hsu.
"We have previously reported that gypenosides induce apoptosis in human hepatocarcinoma Huh-7 cells through a mitochondria-dependent
caspase-9 activation cascade. In order to further explore the critical events leading to apoptosis in gypenosides-treated cells, the following
effects of gypenosides on components of the mitochondrial apoptotic pathway were examined: generation of reactive oxygen species (ROS),
alteration of the mitochondrial membrane potential (MPT), and the subcellular distribution of Bcl-2 and Bax. We show that gypenosides-induced
apoptosis was accompanied by the generation of intracellular ROS, disruption of MPT, and inactivation of ERK, as well as an increase in
mitochondrial Bax and a decrease of mitochondrial Bcl-2 levels. Ectopic expression of Bcl-2 or treatment with furosemide attenuated
gypenosides-triggered apoptosis. Treatment with ATA caused a drastic prevention of apoptosis and the gypenosides-mediated mitochondrial
Bcl-2 decrease and Bax increase, but failed to inhibit ROS generation and MPT dysfunction. Incubation with antioxidants significantly inhibited
gypenosides-mediated ROS generation, ERK inactivation, MPT and apoptosis. Moreover, an increase of the intracellular calcium ion (Ca(2+))
concentration rapidly occurred in gypenosides-treated Huh-7 cells. Buffering of the intracellular Ca(2+) increase with a Ca(2+) chelator
BAMTA/AM blocked the gypenosides-elicited ERK inactivation, ROS generation, Bcl-2/Bax redistribution, mitochondrial dysfunction, and
apoptosis. Based on these results, we propose that the rise in intracellular Ca(2+) concentration plays a pivotal role in the initiation of
gypenosides-triggered apoptotic death."