Lupeol

1 Ailanthus sp. 2 Antennaria sp. 3 Arbutus sp. 4 Arctium sp. 5 Asclepias sp. 6 Asphodelus sp. 7 Betula sp. 8 Boswellia sp. 9 Bowdichia sp. 10 Carlina sp. 11 Castanea sp. 12 Catalpa sp. 13 Crataeva sp. 14 Dendranthema sp. 15 Euphorbia sp. 16 Ficus sp. 17 Flueggea sp. 18 Fraxinus sp. 19 Glycyrrhiza sp. 20 Lavandula sp. 21 Mallotus sp. 22 Phyllanthus sp. 23 Pistacia sp. 24 Pterocarpus sp. 25 Quercus sp. 26 Rhododendron sp. 27 Ricinus sp. 28 Rudbeckia sp. 29 Sambucus sp. 30 Shorea sp. 31 Sorbus sp. 32 Sterculia sp. 33 Tussilago sp. 34 Zanthoxylum sp.

Lupeol enhances radiosensitivity of human hepatocellular carcinoma cell line SMMC-7721 in vitro and in vivo.[Pubmed:25241960]

Int J Radiat Biol. 2015 Feb;91(2):202-8.

PURPOSE: To investigate the effect of Lupeol, a pentacyclictriterpene, on the radiosensitivity of a human hepatocellular carcinoma (HCC) in vitro and in vivo xenografts. METHODS: SMMC-7721 cells were exposed to gamma-radiation with or without Lupeol and assayed for proliferation, clonogenic survival, apoptosis and cell cycle distribution. The cells were also analyzed by Western blotting for the expression levels of the proteins involved in apoptosis. Finally radiosensitization by Lupeol was assessed in HCC xenograft model. RESULTS: Lupeol further suppressed the proliferation and colonogenic survival of the SMMC-7721 cells exposed to gamma-radiation. It could also induce the accumulation of cells in G2/M phase together with gamma-radiation. The data also indicated that Lupeol sensitized SMMC-7721 cells exposed to gamma-radiation to apoptosis and activated the apoptotic proteins including caspase-9 and PARP. Administration of Lupeol with radiation in HCC xenograft model produced a significant tumor growth delay compared with radiation or Lupeol alone and was well tolerated. CONCLUSION: Lupeol significantly enhanced the radiosensitivity of SMMC-7721 cells in vitro and in vivo. The mechanisms involved could be cell cycle arrest and induction of apoptosis. Our studies suggest that Lupeol has the potential to be developed as an adjuvant for radiotherapy in HCC.

A novel mechanism of hepatocellular carcinoma cell apoptosis induced by lupeol via Brain-Derived Neurotrophic Factor Inhibition and Glycogen Synthase Kinase 3 beta reactivation.[Pubmed:26004524]

Eur J Pharmacol. 2015 Sep 5;762:55-62.

Lupeol is a naturally available triterpenoid with selective anticancerous potential on various human cancer cells. The present study shows that Lupeol can inhibit cell proliferation of hepatocellular carcinoma (HCC) HCCLM3 cells in a time- and dose-dependent manner, through caspase-3 dependent activation and Poly ADP-Ribose Polymerase (PARP) cleavage. Lupeol-induced cell death is associated with a marked decrease in the protein expression of Brain-Derived Neurotrophic Factor (BDNF) and ser-9-phosphoryltion of Glycogen Synthase Kinase 3 Beta (GSK-3beta), with concomitant suppression of Akt1, phosphatidyl inositol 3-kinase (PI3K), beta-catenin, c-Myc and Cyclin D1 mRNA expression. Suppressing overexpression of BDNF by Lupeol results in decreased protein expression of p-Akt and PI3K (p110alpha), as well as reactivation of GSK-3beta function in HepG2 cells. Lupeol treatment also inhibits LiCl-induced activation of Wnt signaling pathway and exerts the in vitro anti-invasive activity in Huh-7 cells. LiCl-triggered high expression of beta-catenin, c-Myc and Cyclin D1 protein is reduced followed by Lupeol exposure. The findings suggest a mechanistic link between caspase dependent pathway, BDNF secretion and Akt/PI3K/GSK-3beta in HCC cells. These results indicate that Lupeol can suppress HCC cell proliferation by inhibiting BDNF secretion and phosphorylation of GSK-3beta(Ser-9), cooperated with blockade of Akt/PI3K and Wnt signaling pathway.

Beneficial health effects of lupeol triterpene: a review of preclinical studies.[Pubmed:21118697]

Life Sci. 2011 Feb 14;88(7-8):285-93.

Since ancient times, natural products have been used as remedies to treat human diseases. Lupeol, a phytosterol and triterpene, is widely found in edible fruits, and vegetables. Extensive research over the last three decades has revealed several important pharmacological activities of Lupeol. Various in vitro and preclinical animal studies suggest that Lupeol has a potential to act as an anti-inflammatory, anti-microbial, anti-protozoal, anti-proliferative, anti-invasive, anti-angiogenic and cholesterol lowering agent. Employing various in vitro and in vivo models, Lupeol has also been tested for its therapeutic efficiency against conditions including wound healing, diabetes, cardiovascular disease, kidney disease, and arthritis. Lupeol has been found to be pharmacologically effective in treating various diseases under preclinical settings (in animal models) irrespective of varying routes of administration viz; topical, oral, intra-peritoneal and intravenous. It is noteworthy that Lupeol has been reported to selectively target diseased and unhealthy human cells, while sparing normal and healthy cells. Published studies provide evidence that Lupeol modulates the expression or activity of several molecules such as cytokines IL-2, IL4, IL5, ILbeta, proteases, alpha-glucosidase, cFLIP, Bcl-2 and NFkappaB. This minireview discusses in detail the preclinical studies conducted with Lupeol and provides an insight into its mechanisms of action.

Evaluation of antidiabetic and antioxidant potential of lupeol in experimental hyperglycaemia.[Pubmed:22043924]

Nat Prod Res. 2012;26(12):1125-9.

Oxidative stress, produced under diabetic conditions, is a possible cause of various forms of tissue damage. The concentrations of antioxidant enzymes in cases of diabetes are significantly decreased, with a concomitant increase in lipid peroxidation. In this study, Lupeol, a phytoconstituent from Solanum xanthocarpum, is shown to suppress the progression of diabetes after 21 days. Lupeol treatment caused decreases in glycated haemoglobin, serum glucose and nitric oxide, with a concomitant increase in serum insulin level. Furthermore, treatment with Lupeol also increased antioxidant levels, with a decrease in the level of thiobarbituric acid-reactive oxygen species.

Lupeol prevents acetaminophen-induced in vivo hepatotoxicity by altering the Bax/Bcl-2 and oxidative stress-mediated mitochondrial signaling cascade.[Pubmed:22326499]

Life Sci. 2012 Apr 20;90(15-16):561-70.

AIMS: Lupeol, a triterpene, possesses numerous pharmacological activities, including anti-malarial, anti-arthritic and anti-carcinogenic properties. The present study was conducted to explore the hepatoprotective potential of Lupeol against acetaminophen (AAP)-induced hepatotoxicity in Wistar rats. MAIN METHODS: Rats were given a prophylactic treatment of Lupeol (150 mg/kg body weight, p.o., for 30 consecutive days) with a co-administration of AAP (1 g/kg body weight). The modulatory effects of Lupeol on AAP-induced hepatotoxicity were investigated by assaying oxidative stress biomarkers, serum liver toxicity markers, pro/anti apoptotic proteins, DNA fragmentation and by the histopathological examination of the liver. KEY FINDINGS: Lupeol significantly prevented hepatic damage as evident from the histopathological studies and significant decline in serum trans-aminases. The alterations in cellular redox status (p<0.01) and antioxidant enzyme activities together with the enhanced lipid peroxidation and protein carbonyl levels were also observed in the AAP-treated rats. In addition, significant ROS generation and mitochondrial depolarization were observed in this group. Co-administration of Lupeol significantly decreased the level of serum transaminases, MDA and protein carbonyl content. It also prevented ROS generation and mitochondrial depolarization. Furthermore, Lupeol enhanced the mitochondrial antioxidant and redox status and inhibited DNA damage and cell death by preventing the downregulation of Bcl-2, upregulation of Bax, release of cytochrome c and the activation of caspase 9/3. SIGNIFICANCE: The conclusion of this study is that Lupeol when co-administered with AAP effectively reduces oxidative stress and prevents AAP-induced hepatotoxicity by inhibiting critical control points of apoptosis.

Antiangiogenic activity of lupeol from Bombax ceiba.[Pubmed:12722136]

Phytother Res. 2003 Apr;17(4):341-4.

In the search for antiangiogenic agents from medicinal plants used in Vietnam, a methanol extract of the stem barks of Bombax ceiba was found to exhibit a significant antiangiogenic activity on in vitro tube formation of human umbilical venous endothelial cells (HUVEC). Bioactivity-guided fractionation and isolation carried out on this extract afforded Lupeol as an active principle. At 50 and 30 microg/mL Lupeol showed a marked inhibitory activity on HUVEC tube formation while it did not affect the growth of tumor cell lines such as SK-MEL-2, A549, and B16-F10 melanoma.

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