Orthosiphon stamineus: an Asian tea with substantial anticancer properties
Background: Liver cancer is one of the deadly cancers with high prevalence in the East Asia. Likewise most of diseases, herbs and herbal medicine could be an easy and cost effective tool in prevention and possible cancer treatment. The present study investigated the ability of Orthosiphon stamineus Benth decoction to protect liver against hepatocellular carcinoma in carcinogenesis-induced animal model.
Methods: Forty male Sprague Dawley rats (age: 8±1 weeks, weight: 248.1±7.21g) were obtained and 10 rats were kept as normal group. Hepatocellular carcinoma was induced for the rest 30 of rats by means of intraperitoneal injection of 200mg/kg diethyl nitrosamine (DEN) dissolved in corn oil. Induced cancer rats were under hepatocarcinogenesis promoter diet made from a mixture of standard rat diet (AIN-76) with 2-acetylaminofluorene (0.02% AAF) for two weeks. Two weeks after this diet, left over rats were divided to two groups as control and treatment. Treatment group, were forced feed daily with 0.7 ml O. stamineus decoction.
Results: After 28 weeks treatment with O. stamineus decoction, serum biochemical markers including alpha fetoprotein (AFP), alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT),corticosteroid binding globulin (CBG), gamma glutamyl transferase (GGT), homocysteine (HCY), tumor necrosis factor alpha (TNF-α), and alpha 2 macroglobulin (α2MG) have been regulated favorably. Total antioxidant status (TAS) also has been increased drastically. Liver lesion score in treated groups were reduced and glucocorticoid activity has been amplified significantly.
Conclusion: Our results indicate that O. stamineus decoction might prevent or subdue liver cancer development.
Abdelwahab SI, Mohan S, Mohamed Elhassan M,Al-Mekhlafi N, Mariod AA, Abdul AB, et al.Antiapoptotic and Antioxidant Properties of Orthosiphon stamineus Benth (Cat’s Whiskers): Intervention in the Bcl-2-Mediated Apoptotic Pathway. Evid Based Complement Alternat Med.2011;156765.
Adam Y, Somchit MN, Sulaiman MR, Nasaruddin AA, Zuraini A, Bustamam AA, et al. Diuretic properties of Orthosiphon stamineus Benth. J Ethnopharmacol. 2009; 124(1):154–8.
Bwin DM, Gwan US. Burmese indigenous medicinal plants: I. Plants with reputed hypoglycemic action. Burma Medical Research Institute. Burma Medical Research Institute; 1967.
Sumaryono W, Proksch P, Wray V, Witte L, Hartmann T. Qualitative and Quantitative Analysis of the Phenolic Constituents from Orthosiphon aristatus. Planta Med. 1991;57(2):176–80.
Tezuka Y, Stampoulis P, Banskota AH, Awale S, Tran KQ, Saiki I, et al. Constituents of the Vietnamese medicinal plant Orthosiphon stamineus. Chem Pharm Bull (Tokyo). 2000 ;48(11):1711–9.
Solt D, Farber E. New principle for the analysis of chemical carcinogenesis. Nature 1976;263(5579):701–3.
AIN. Report of the American Institute of Nutrition ad hoc Committee on Standards for Nutritional Studies. J Nutr. 1977;107(7):1340–8.
Stevens A, Lowe JS, Young B, Wheater PR.Wheater’s Basic Histopathology: A Colour Atlas and Text. Churchill Livingstone; 2002.
Batts KP, Ludwig J. Chronic hepatitis. An update on terminology and reporting. Am J Surg Pathol. 1995;19(12):1409–17.
Alshawsh M a, Abdulla MA, Ismail S, Amin Z a. Hepatoprotective Effects of Orthosiphon stamineus Extract on Thioacetamide-Induced Liver Cirrhosis in Rats. Evid Based Complement Alternat Med. 2011;103039.
NCI. Understanding Cancer Series: Cancer - National Cancer Institute. National Institutes of Health. 2013.
Yu MC, Chan KM, Lee CF, Lee YS, Eldeen FZ, Chou HS, et al. Alkaline phosphatase: does it have a role in predicting hepatocellular carcinoma recurrence? J Gastrointest Surg. 2011;15(8):1440–9.
Chin J, Hussin A, Ismail S. Hepatoprotective effect of Orthosiphon stamineus Benth against acetaminophen intoxication in rats. J Nat Remedies. 2009;9(2):177–84.
Yang R-Z, Park S, Reagan WJ, Goldstein R, Zhong S, Lawton M, et al. Alanine aminotransferase isoenzymes: molecular cloning and quantitative analysis of tissue expression in rats and serum elevation in liver toxicity. Hepatology. 2009;49(2):598–607.
Green RM, Flamm S. AGA technical review on the evaluation of liver chemistry tests.Gastroenterology. 2002;123(4):1367–84.
Maheswari C. Hepatoprotective activity of “Orthosiphon stamineus” on liver damage caused by paracetamol in rats. Jordan J Biol Sci. 2008;1(3):6673.
Gowda S, Desai PB, Hull V V, Math AAK, Vernekar SN, Kulkarni SS. A review on laboratory liver function tests. Pan Afr Med J.2009;3:17.
Kucharczak J, Simmons MJ, Fan Y, Gélinas C.To be, or not to be: NF-kappaB is the answer--role of Rel/NF-kappaB in the regulation of apoptosis. Oncogene. 2003;22(56):8961–82.
Sethi G, Sung B, Aggarwal BB. TNF: a master switch for inflammation to cancer. Front Biosci.2008;13:5094–107.
Mocellin S, Nitti D. TNF and cancer: the two sides of the coin. Front Biosci. 2008;13:2774–83.
Laavola M, Nieminen R, Yam MF, Sadikun A, Asmawi MZ, Basir R, et al. Flavonoids eupatorin and sinensetin present in Orthosiphon stamineus leaves inhibit inflammatory gene expression and STAT1 activation. Planta Med. 2012;78(8):779–86.
Sukata T, Uwagawa S, Ozaki K, Sumida K, Kikuchi K, Kushida M, et al. alpha(2)- Macroglobulin: a novel cytochemical marker characterizing preneoplastic and neoplastic rat liver lesions negative for hitherto established cytochemical markers. Am J Pathol. 2004;165 (5):1479–88.
Kotaka M, Chen GG, Lai PBS, Lau WY, Chan PKS, Leung TWT, et al. Analysis of differentially expressed genes in hepatocellular carcinoma with hepatitis C virus by suppression subtractive hybridization. Oncol Res. 2002;13(3):161–7.
Smorenburg SM, Griffini P, Tiggelman AB, Moorman AF, Boers W, Van Noorden JF. alpha2- Macroglobulin is mainly produced by cancer cells and not by hepatocytes in rats with colon carcinoma metastases in liver. Hepatology.1996;23(3):560–70.
Wu LL, Wu JT. Hyperhomocysteinemia is a risk factor for cancer and a new potential tumor marker. Clin Chim Acta.;322(1-2):21–8.
De Carvalho SCR, Muniz MTC, Siqueira MDV, Siqueira ERF, Gomes AV, Silva KA, et al. Plasmatic higher levels of homocysteine in non- alcoholic fatty liver disease (NAFLD). Nutr J. 2013;12:37.
Sakuta H, Suzuki T. Alcohol consumption and plasma homocysteine. Alcohol. 2005;37(2):73–7.
Hu Z, Zhao W. Novel insights into the molecular mechanisms of α-fetoprotein expression and malignant phenotypes of hepatocellular carcinoma. Cell Mol Immunol. 2012;9(1):7–8.
Ruoslahti E, Seppälä M. Studies of carcino-fetal proteins. 3. Development of a radioimmunoassay for -fetoprotein. Demonstration of -fetoprotein in serum of healthy human adults. Int J Cancer.
Yam MF, Lim CP, Fung Ang L, Por LY, Wong ST, Asmawi MZ, et al. Antioxidant and Toxicity Studies of 50% Methanolic Extract of Orthosiphon stamineus Benth. Biomed Res Int. Hindawi Publishing Corporation.2013:1–10.
Loon YH, Wong JW, Yap SP, Yuen KH.Determination of flavonoids from Orthosiphon stamineus in plasma using a simple HPLC method with ultraviolet detection. J Chromatogr B Analyt Technol Biomed Life Sci. 2005;816(1-2):161–6.
Pan Y, Abd-Rashid BA, Ismail Z, Ismail R, Mak JW, Pook PCK, et al. In vitro effects of active constituents and extracts of Orthosiphon stamineus on the activities of three major human cDNA-expressed cytochrome P450 enzymes. Chem Biol Interact. Elsevier Ireland Ltd;2011;190(1):1–8.
Hu G, Tuomilehto J, Pukkala E, Hakulinen T, Antikainen R, Vartiainen E, et al. Joint effects of coffee consumption and serum gamma- glutamyltransferase on the risk of liver cancer. Hepatology. 2008;48(1):129–36.
Lim J-S, Yang J-H, Chun B-Y, Kam S, Jacobs DR, Lee D-H. Is serum gamma- glutamyltransferase inversely associated with serum antioxidants as a marker of oxidative stress? Free Radic Biol Med. 2004;37(7):1018–23.
Cooke MS, Evans MD, Dizdaroglu M, Lunec J.Oxidative DNA damage: mechanisms, mutation, and disease. FASEB J. 2003 Jul;17(10):1195–214.
Schlossmacher G, Stevens A, White A.Glucocorticoid receptor-mediated apoptosis: mechanisms of resistance in cancer cells. J Endocrinol. 2011;211(1):17–25.
Smith KG, Strasser A, Vaux DL. CrmA expression in T lymphocytes of transgenic mice inhibits CD95 (Fas/APO-1)-transduced apoptosis, but does not cause lymphadenopathy or autoimmune disease. EMBO J. 1996;15(19):5167–76.
Planey SL, Abrams MT, Robertson NM, Litwack G. Role of apical caspases and glucocorticoid- regulated genes in glucocorticoid-induced apoptosis of pre-B leukemic cells. Cancer Res. 2003;63(1):172–8.
Kofler R. The molecular basis of glucocorticoid- induced apoptosis of lymphoblastic leukemia cells. Histochem Cell Biol. 2000;114(1):1–7.
Tonko M, Ausserlechner MJ, Bernhard D, Helmberg A, Kofler R. Gene expression profiles of proliferating vs. G1/G0 arrested human leukemia cells suggest a mechanism for glucocorticoid-induced apoptosis. FASEB J.2001;15(3):693–9.
Obexer P, Certa U, Kofler R, Helmberg A.Expression profiling of glucocorticoid-treated T- ALL cell lines: rapid repression of multiple genes involved in RNA-, protein- and nucleotide synthesis. Oncogene. 2001;20(32):4324–36.
Fernandez A, Kiefer J, Fosdick L, McConkey DJ.Oxygen radical production and thiol depletion are required for Ca(2+)-mediated endogenous endonuclease activation in apoptotic thymocytes. J Immunol. 1995;155(11):5133–9.
Tome ME, Briehl MM. Thymocytes selected for resistance to hydrogen peroxide show altered antioxidant enzyme profiles and resistance to dexamethasone-induced apoptosis. Cell Death Differ. 2001;8(9):953–61.
Goppelt-Struebe M, Wolter D, Resch K.Glucocorticoids inhibit prostaglandin synthesis not only at the level of phospholipase A2 but also at the level of cyclo-oxygenase/PGE isomerase.Br J Pharmacol. 1989;98(4):1287–95.
Hoellen F, Kelling K, Dittmer C, Diedrich K, Friedrich M, Thill M. Impact of cyclooxygenase-2 in breast cancer. Anticancer Res. 2011;31(12):4359–67.
Larkins TL, Nowell M, Singh S, Sanford GL.Inhibition of cyclooxygenase-2 decreases breast cancer cell motility, invasion and matrix metalloproteinase expression. BMC Cancer. 2006;6(1):181.
Schmidt S, Rainer J, Ploner C, Presul E, Riml S, Kofler R. Glucocorticoid-induced apoptosis and glucocorticoid resistance: molecular mechanisms and clinical relevance. Cell Death Differ. 2004;11 Suppl 1(S1):S45–55.
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