Generic placeholder image

Clinical Cancer Drugs

Editor-in-Chief

ISSN (Print): 2212-697X
ISSN (Online): 2212-6988

Research Article

Inonotus obliquus Aqueous Extract Suppresses Carbon Tetrachloride-induced Hepatic Injury through Modulation of Antioxidant Enzyme System and Anti-inflammatory Mechanism

Author(s): Pir Mohammad Ishfaq, Anjali Mishra, Shivani Mishra, Zaved Ahmad, Shovanlal Gayen, Subodh Kumar Jain, Swati Tripathi and Siddhartha Kumar Mishra*

Volume 8, Issue 2, 2021

Published on: 20 December, 2021

Article ID: e301121198423 Pages: 15

DOI: 10.2174/2212697X08666211130130119

Price: $65

Abstract

Background: Chaga mushroom (Inonotus obliquus) is an edible macrofungus used in traditional and folk medicine for the treatment of various gastrointestinal disorders. It has shown potent anti-inflammatory, antioxidant and anticancer effects in several experimental studies, including anti-inflammatory and anticancer effects in colorectal cancer and intestinal inflammation. Whole extract or purified compound ergosterol peroxide from chaga mushroom showed anti-inflammatory mechanism via suppression of NF-κB/iNOS-COX-2 and growth inhibitory mechanism via regulation of apoptosis activation and β-catenin suppression. The diverse inflammatory and carcinogenic agents, like carbon tetrachloride (CCl4), a potent hepatotoxic chemical, cause liver damage by inducing lipid peroxidation and other oxidative damages.

Aims: The study aimed to analyze the biochemical, cellular and molecular mechanisms of CCl4 induced chronic liver inflammation and carcinoma, and to analyze the effect of the extract of chaga mushroom on liver inflammation and cancer by virtue of anti-inflammatory mechanisms.

Method: Physiological, histological and immunohistochemical analyses of the physiological functions and cellular functions were performed. Biochemical assays were conducted for assessing enzymatic changes in tissues. Molecular simulation and docking studies were performed for the evaluation of the molecular interaction.

Results: CCl4-exposed mice exhibited a significant decrease in body weight followed by altered histopathological signatures in the liver. Supplementation of IOAE showed that treatment restored the normal structure of the tissues with large round nuclei in most of the cells. CCl4 caused a steep elevation in the levels of SGOT and SGPT to 2.32- and 1.8-fold as compared to control. The LDH level increased to 447 IU/L in CCl4 treated mice as compared to control (236 IU/L). Analysis of the oxidant enzyme pathway showed that CCl4 reduced the GSH level to 16.5 μM as compared to control (52 μM), and induced the catalase enzyme activity up to 259 U/mL as compared to control (124 U/L). These physiological and biochemical alterations were restored towards normal levels by IOAE administration. Immunohistochemical staining for caspase-3 and p53 showed that CCl4 notably increased their expressions, which were subsequently suppressed by administration of IOAE. The molecular simulation and docking studies using ergosterol peroxide from chaga mushroom with iNOS, COX-2 and TNF-α showed binding energy of -10.5, -8.9 and -9.1 Kcal/mol, respectively. These proteins interacting with ergosterol peroxide exerted an inhibitory effect on these critical proinflammatory signaling proteins.

Conclusion: The results point out that IOAE is able to prevent damage of hepatic cells caused by CCl4 in mouse models through anti-inflammatory and growth inhibitory mechanisms, which can be utilized for natural prevention of liver toxicity.

Keywords: Chaga mushroom, carbon tetrachloride, hepatotoxicity, antiinflammation, antioxidant, immunohistochemicalanalysis.

Graphical Abstract

[1]
Ferrell L. Liver pathology: Cirrhosis, hepatitis, and primary liver tumors. Update and diagnostic problems. Mod Pathol 2000; 13(6): 679-704.
[http://dx.doi.org/10.1038/modpathol.3880119] [PMID: 10874674]
[2]
Gu X, Manautou JE. Molecular mechanisms underlying chemical liver injury. Expert Rev Mol Med 2012; 14: e4.
[http://dx.doi.org/10.1017/S1462399411002110] [PMID: 22306029]
[3]
Perez Gutierrez RM, Anaya Sosa I, Hoyo Vadillo C, Victoria TC. Effect of flavonoids from Prosthechea michuacana on carbon tetrachloride induced acute hepatotoxicity in mice. Pharm Biol 2011; 49(11): 1121-7.
[http://dx.doi.org/10.3109/13880209.2011.570766] [PMID: 22014261]
[4]
Bai X, Zhang W, Chen W, Zong W, Guo Z, Liu X. Anti-hepatotoxic and anti-oxidant effects of extracts from Piper nigrum L. root. Afr J Biotechnol 2011; 10: 267-72.
[5]
Tamilarasi R, Sivanesan D, Kanimozhi P. Hepatoprotective and antioxidant efficacy of Anethum graveolens linn in carbon tetrachloride induced hepatotoxicity in albino rats. J Chem Pharm Res 2012; 4: 1885-8.
[6]
Weber LW, Boll M, Stampfl A. Hepatotoxicity and mechanism of action of haloalkanes: Carbon tetrachloride as a toxicological model. Crit Rev Toxicol 2003; 33(2): 105-36.
[http://dx.doi.org/10.1080/713611034] [PMID: 12708612]
[7]
Recknagel RO, Glende EA Jr, Dolak JA, Waller RL. Mechanisms of carbon tetrachloride toxicity. Pharmacol Ther 1989; 43(1): 139-54.
[http://dx.doi.org/10.1016/0163-7258(89)90050-8] [PMID: 2675128]
[8]
Saleem TM, Chetty CM, Ramkanth S, Rajan V, Kumar KM, Gauthaman K. Hepatoprotective herbs-a review. Int J Res Pharma Sci 2010; 1: 1-5.
[9]
Mishra SK, Bae YS, Lee YM, Kim JS, Oh SH, Kim HM. Sesquiterpene alcohol cedrol chemosensitizes human cancer cells and suppresses cell proliferation by destabilizing plasma membrane lipid rafts. Front Cell Dev Biol 2021; 8: 571676.
[http://dx.doi.org/10.3389/fcell.2020.571676] [PMID: 33585438]
[10]
Islam MT, Ali ES, Khan IN, et al. Anticancer perspectives on the fungal-derived polyphenolic hispolon. Anticancer Agents Med Chem 2020; 20(14): 1636-47.
[http://dx.doi.org/10.2174/1871520620666200619164947] [PMID: 32560616]
[11]
Muhammad N, Steele R, Isbell TS, Philips N, Ray RB. Bitter melon extract inhibits breast cancer growth in preclinical model by inducing autophagic cell death. Oncotarget 2017; 8(39): 66226-36.
[http://dx.doi.org/10.18632/oncotarget.19887] [PMID: 29029506]
[12]
Bhattacharya S, Muhammad N, Steele R, Kornbluth J, Ray RB. Bitter melon enhances natural killer-mediated toxicity against head and neck cancer cells. Cancer Prev Res (Phila) 2017; 10(6): 337-44.
[http://dx.doi.org/10.1158/1940-6207.CAPR-17-0046] [PMID: 28465362]
[13]
Bhattacharya S, Muhammad N, Steele R, Peng G, Ray RB. Immunomodulatory role of bitter melon extract in inhibition of head and neck squamous cell carcinoma growth. Oncotarget 2016; 7(22): 33202-9.
[http://dx.doi.org/10.18632/oncotarget.8898] [PMID: 27120805]
[14]
Zhang Z, Guo Y, Zhang S, et al. Curcumin modulates cannabinoid receptors in liver fibrosis in vivo and inhibits extracellular matrix expression in hepatic stellate cells by suppressing cannabinoid receptor type-1 in vitro. Eur J Pharmacol 2013; 721(1-3): 133-40.
[http://dx.doi.org/10.1016/j.ejphar.2013.09.042] [PMID: 24076327]
[15]
Zhao S, Zhang Z, Yao Z, et al. Tetramethylpyrazine attenuates sinusoidal angiogenesis via inhibition of hedgehog signaling in liver fibrosis. IUBMB Life 2017; 69(2): 115-27.
[http://dx.doi.org/10.1002/iub.1598] [PMID: 28112475]
[16]
Zhang C, Bian M, Chen X, et al. Oroxylin A prevents angiogenesis of LSECs in liver fibrosis via inhibition of YAP/HIF-1α signaling. J Cell Biochem 2018; 119(2): 2258-68.
[http://dx.doi.org/10.1002/jcb.26388] [PMID: 28857294]
[17]
Shashkina MY, Shashkin PN, Sergeev AV. Chemical and medicobiological properties of chaga. Pharm Chem J 2006; 40: 560-8.
[http://dx.doi.org/10.1007/s11094-006-0194-4]
[18]
Wasser SP, Weis AL. Medicinal properties of substances occurring in higher basidiomycetes mushrooms: Current perspectives. Int J Med Mushrooms 1999; 19(1): 65-96.
[http://dx.doi.org/10.1615/IntJMedMushrooms.v1.i1.30]
[19]
Balandaykin ME, Zmitrovich IV. Review on Chaga medicinal mushroom, Inonotus obliquus (higher basidiomycetes): Realm of medicinal applications and approaches on estimating its resource potential. Int J Med Mushrooms 2015; 17(2): 95-104.
[http://dx.doi.org/10.1615/IntJMedMushrooms.v17.i2.10] [PMID: 25746615]
[20]
Wasser SP. Medicinal mushrooms as a source of antitumor and immunomodulating polysaccharides. Appl Microbiol Biotechnol 2002; 60(3): 258-74.
[http://dx.doi.org/10.1007/s00253-002-1076-7] [PMID: 12436306]
[21]
Amin SA, Bhattacharya P, Basak S, Gayen S, Nandy A, Saha A. Pharmacoinformatics study of piperolactam a from piper betle root as new lead for non steroidal anti fertility drug development. Comput Biol Chem 2017; 67: 213-24.
[http://dx.doi.org/10.1016/j.compbiolchem.2017.01.004] [PMID: 28160639]
[22]
Mishra S, Kang J, Song K, et al. Inonotus obliquus suppresses proliferation of colorectal cancer cells and tumor growth in mice models by downregulation of β-catenin/NF-κB-signaling pathways. Eur J Inflamm 2013; 11: 615-29.
[http://dx.doi.org/10.1177/1721727X1301100306]
[23]
Mishra SK, Kang JH, Kim DK, Oh SH, Kim MK. Orally administered aqueous extract of Inonotus obliquus ameliorates acute inflammation in dextran sulfate sodium (DSS)-induced colitis in mice. J Ethnopharmacol 2012; 143(2): 524-32.
[http://dx.doi.org/10.1016/j.jep.2012.07.008] [PMID: 22819687]
[24]
Kang J-H, Jang J-E, Mishra SK, et al. Ergosterol peroxide from Chaga mushroom (Inonotus obliquus) exhibits anti-cancer activity by down-regulation of the β-catenin pathway in colorectal cancer. J Ethnopharmacol 2015; 173: 303-12.
[http://dx.doi.org/10.1016/j.jep.2015.07.030] [PMID: 26210065]
[25]
Rosenfeld RJ, Garcin ED, Panda K, et al. Conformational changes in nitric oxide synthases induced by chlorzoxazone and nitroindazoles: Crystallographic and computational analyses of inhibitor potency. Biochemistry 2002; 41(47): 13915-25.
[http://dx.doi.org/10.1021/bi026313j] [PMID: 12437348]
[26]
Kurumbail RG, Stevens AM, Gierse JK, et al. Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents. Nature 1996; 384(6610): 644-8.
[http://dx.doi.org/10.1038/384644a0] [PMID: 8967954]
[27]
He MM, Smith AS, Oslob JD, et al. Small-molecule inhibition of TNF-alpha. Science 2005; 310(5750): 1022-5.
[http://dx.doi.org/10.1126/science.1116304] [PMID: 16284179]
[28]
Al-Dbass AM, Al-Daihan SK, Bhat RS. Agaricus blazei Murill as an efficient hepatoprotective and antioxidant agent against CCl4-induced liver injury in rats. Saudi J Biol Sci 2012; 19(3): 303-9.
[http://dx.doi.org/10.1016/j.sjbs.2012.03.004] [PMID: 23961190]
[29]
Marchesini G, Petta S, Dalle Grave R. Diet, weight loss, and liver health in nonalcoholic fatty liver disease: Pathophysiology, evidence, and practice. Hepatology 2016; 63(6): 2032-43.
[http://dx.doi.org/10.1002/hep.28392] [PMID: 26663351]
[30]
Xiao J, Liong EC, Ching YP, et al. Lycium barbarum polysaccharides protect mice liver from carbon tetrachloride-induced oxidative stress and necroinflammation. J Ethnopharmacol 2012; 139(2): 462-70.
[http://dx.doi.org/10.1016/j.jep.2011.11.033] [PMID: 22138659]
[31]
El-Tawil O, Moussa SZ. Antioxidant and hepatoprotective effects of thymoquinone against carbon tetrachloride-induced hepatotoxicity in isolated rat hepatocyte. J Egypt Soc Toxicol 2006; 34: 33-41.
[32]
Hsu YW, Tsai CF, Chang WH, Ho YC, Chen WK, Lu FJ. Protective effects of Dunaliella salina-a carotenoids-rich alga, against carbon tetrachloride-induced hepatotoxicity in mice. Food Chem Toxicol 2008; 46(10): 3311-7.
[http://dx.doi.org/10.1016/j.fct.2008.07.027] [PMID: 18761048]
[33]
Ogaly HA, Eltablawy NA, El-Behairy AM, El-Hindi H, Abd-Elsalam RM. Hepatocyte growth factor mediates the antifibrogenic action of Ocimum bacilicum essential oil against CCl4-induced liver fibrosis in rats. Molecules 2015; 20(8): 13518-35.
[http://dx.doi.org/10.3390/molecules200813518] [PMID: 26213907]
[34]
Wang T, Sun N-L, Zhang W-D, et al. Protective effects of dehydrocavidine on carbon tetrachloride-induced acute hepatotoxicity in rats. J Ethnopharmacol 2008; 117(2): 300-8.
[http://dx.doi.org/10.1016/j.jep.2008.02.010] [PMID: 18358653]
[35]
Ou Y, Zheng S, Lin L, Jiang Q, Yang X. Protective effect of C phycocyanin against carbon tetrachloride-induced hepatocyte damage in vitro and in vivo. Chem Biol Interact 2010; 185(2): 94-100.
[http://dx.doi.org/10.1016/j.cbi.2010.03.013] [PMID: 20227401]
[36]
Dutta S, Chakraborty AK, Dey P, et al. Amelioration of CCl4 induced liver injury in swiss albino mice by antioxidant rich leaf extract of Croton bonplandianus Baill. PLoS One 2018; 13(4): e0196411.
[http://dx.doi.org/10.1371/journal.pone.0196411] [PMID: 29709010]
[37]
Song T-Y, Yen G-C. Protective effects of fermented filtrate from Antrodia camphorata in submerged culture against CCl4-induced hepatic toxicity in rats. J Agric Food Chem 2003; 51(6): 1571-7.
[http://dx.doi.org/10.1021/jf0209701] [PMID: 12617586]
[38]
Bansal MB, Kovalovich K, Gupta R, et al. Interleukin-6 protects hepatocytes from CCl4-mediated necrosis and apoptosis in mice by reducing MMP-2 expression. J Hepatol 2005; 42(4): 548-56.
[http://dx.doi.org/10.1016/j.jhep.2004.11.043] [PMID: 15763341]
[39]
Johnston DE. Special considerations in interpreting liver function tests. Am Fam Physician 1999; 59(8): 2223-30.
[PMID: 10221307]
[40]
Nyblom H, Björnsson E, Simrén M, Aldenborg F, Almer S, Olsson R. The AST/ALT ratio as an indicator of cirrhosis in patients with PBC. Liver Int 2006; 26(7): 840-5.
[http://dx.doi.org/10.1111/j.1478-3231.2006.01304.x] [PMID: 16911467]
[41]
Hong KB, Noh DO, Park Y, Suh HJ. Hepatoprotective activity of water extracts from Inonotus obliquus (higher basidiomycetes) against tert-butyl hydroperoxide-induced oxidative liver injury in primary cultured rat hepatocytes. Int J Med Mushrooms 2015; 17(11): 1069-76.
[http://dx.doi.org/10.1615/IntJMedMushrooms.v17.i11.70] [PMID: 26853962]
[42]
Kotoh K, Kato M, Kohjima M, et al. Lactate dehydrogenase production in hepatocytes is increased at an early stage of acute liver failure. Exp Ther Med 2011; 2(2): 195-9.
[http://dx.doi.org/10.3892/etm.2011.197] [PMID: 22977488]
[43]
Faloppi L, Bianconi M, Memeo R, et al. Lactate dehydrogenase in hepatocellular carcinoma: Something old, something new. BioMed Res Int 2016; 2016: 7196280.
[http://dx.doi.org/10.1155/2016/7196280] [PMID: 27314036]
[44]
Rogatzki MJ, Ferguson BS, Goodwin ML, Gladden LB. Lactate is always the end product of glycolysis. Front Neurosci 2015; 9: 22-2.
[http://dx.doi.org/10.3389/fnins.2015.00022] [PMID: 25774123]
[45]
Liu Y, Wang X, Liu Y. Protective effects of tanshinone IIA on injured primary cultured rat hepatocytes induced by CCl4. Zhong Yao Cai 2003; 26(6): 415-7.
[PMID: 14528681]
[46]
Singab ANB, Youssef DT, Noaman E, Kotb S. Hepatoprotective effect of flavonol glycosides rich fraction from Egyptian Vicia calcarata Desf. against CCl4-induced liver damage in rats. Arch Pharm Res 2005; 28(7): 791-8.
[http://dx.doi.org/10.1007/BF02977344] [PMID: 16114493]
[47]
Nagano K, Umeda Y, Saito M, et al. Thirteen-week inhalation toxicity of carbon tetrachloride in rats and mice. J Occup Health 2007; 49(4): 249-59.
[http://dx.doi.org/10.1539/joh.49.249] [PMID: 17690517]
[48]
Ozer J, Ratner M, Shaw M, Bailey W, Schomaker S. The current state of serum biomarkers of hepatotoxicity. Toxicology 2008; 245(3): 194-205.
[http://dx.doi.org/10.1016/j.tox.2007.11.021] [PMID: 18291570]
[49]
Cahill A, Cunningham CC, Adachi M, et al. Effects of alcohol and oxidative stress on liver pathology: The role of the mitochondrion. Alcohol Clin Exp Res 2002; 26(6): 907-15.
[http://dx.doi.org/10.1111/j.1530-0277.2002.tb02621.x] [PMID: 12068261]
[50]
Szymonik-Lesiuk S, Czechowska G, Stryjecka-Zimmer M, et al. Catalase, superoxide dismutase, and glutathione peroxidase activities in various rat tissues after carbon tetrachloride intoxication. J Hepatobiliary Pancreat Surg 2003; 10(4): 309-15.
[http://dx.doi.org/10.1007/s00534-002-0824-5] [PMID: 14598152]
[51]
Sheweita SA, El-Gabar MA, Bastawy M. Carbon tetrachloride changes the activity of cytochrome P450 system in the liver of male rats: role of antioxidants. Toxicology 2001; 169(2): 83-92.
[http://dx.doi.org/10.1016/S0300-483X(01)00473-5] [PMID: 11718950]
[52]
Sun F, Hamagawa E, Tsutsui C, Ono Y, Ogiri Y, Kojo S. Evaluation of oxidative stress during apoptosis and necrosis caused by carbon tetrachloride in rat liver. Biochim Biophys Acta 2001; 1535(2): 186-91.
[http://dx.doi.org/10.1016/S0925-4439(00)00098-3] [PMID: 11342007]
[53]
Shah MD, Gnanaraj C, Haque AT, Iqbal M. Antioxidative and chemopreventive effects of Nephrolepis biserrata against carbon tetrachloride (CCl4)-induced oxidative stress and hepatic dysfunction in rats. Pharm Biol 2015; 53(1): 31-9.
[http://dx.doi.org/10.3109/13880209.2014.909502] [PMID: 25243876]
[54]
Mahmoud AM, Hozayen WG, Ramadan SM. Berberine ameliorates methotrexate-induced liver injury by activating Nrf2/HO-1 pathway and PPARγ, and suppressing oxidative stress and apoptosis in rats. Biomed Pharmacother 2017; 94: 280-91.
[http://dx.doi.org/10.1016/j.biopha.2017.07.101] [PMID: 28763751]
[55]
Shi J, Aisaki K, Ikawa Y, Wake K. Evidence of hepatocyte apoptosis in rat liver after the administration of carbon tetrachloride. Am J Pathol 1998; 153(2): 515-25.
[http://dx.doi.org/10.1016/S0002-9440(10)65594-0] [PMID: 9708811]
[56]
Wang L, Zhang Z, Li M, et al. P53-dependent induction of ferroptosis is required for artemether to alleviate carbon tetrachloride-induced liver fibrosis and hepatic stellate cell activation. IUBMB Life 2019; 71(1): 45-56.
[http://dx.doi.org/10.1002/iub.1895] [PMID: 30321484]
[57]
Prives C, Lowe SW. Cancer: Mutant p53 and chromatin regulation. Nature 2015; 525(7568): 199-200.
[http://dx.doi.org/10.1038/nature15212] [PMID: 26331537]
[58]
Li T, Liu X, Jiang L, Manfredi J, Zha S, Gu W. Loss of p53-mediated cell-cycle arrest, senescence and apoptosis promotes genomic instability and premature aging. Oncotarget 2016; 7(11): 11838-49.
[http://dx.doi.org/10.18632/oncotarget.7864] [PMID: 26943586]
[59]
Krzyczkowski W, Malinowska E, Suchocki P, Kleps J, Olejnik M, Herold F. Isolation and quantitative determination of ergosterol peroxide in various edible mushroom species. Food Chem 2009; 113: 351-5.
[http://dx.doi.org/10.1016/j.foodchem.2008.06.075]
[60]
Li X, Wu Q, Bu M, et al. Ergosterol peroxide activates Foxo3-mediated cell death signaling by inhibiting AKT and c-Myc in human hepatocellular carcinoma cells. Oncotarget 2016; 7(23): 33948-59.
[http://dx.doi.org/10.18632/oncotarget.8608] [PMID: 27058618]
[61]
Breinig M, Schirmacher P, Kern MA. Cyclooxygenase-2 (COX-2)-a therapeutic target in liver cancer? Curr Pharm Des 2007; 13(32): 3305-15.
[http://dx.doi.org/10.2174/138161207782360627] [PMID: 18045183]
[62]
Osawa Y, Nagaki M. Cyclooxygenase-2: Its paradoxical roles in liver inflammation and fibrosis. Hepatol Res 2008; 38(8): 772-4.
[http://dx.doi.org/10.1111/j.1872-034X.2008.00379.x] [PMID: 18705763]
[63]
Simeonova PP, Gallucci RM, Hulderman T, et al. The role of tumor necrosis factor-alpha in liver toxicity, inflammation, and fibrosis induced by carbon tetrachloride. Toxicol Appl Pharmacol 2001; 177(2): 112-20.
[http://dx.doi.org/10.1006/taap.2001.9304] [PMID: 11740910]
[64]
Terzić J, Grivennikov S, Karin E, Karin M. Inflammation and colon cancer. Gastroenterology 2010; 138(6): 2101-2114.e5.
[http://dx.doi.org/10.1053/j.gastro.2010.01.058] [PMID: 20420949]
[65]
Boland CR, Luciani MG, Gasche C, Goel A. Infection, inflammation, and gastrointestinal cancer. Gut 2005; 54(9): 1321-31.
[http://dx.doi.org/10.1136/gut.2004.060079] [PMID: 16099799]
[66]
Wang MT, Honn KV, Nie D. Cyclooxygenases, prostanoids, and tumor progression. Cancer Metastasis Rev 2007; 26(3-4): 525-34.
[http://dx.doi.org/10.1007/s10555-007-9096-5] [PMID: 17763971]
[67]
Wang S, Liu Z, Wang L, Zhang X. NF-kappaB signaling pathway, inflammation and colorectal cancer. Cell Mol Immunol 2009; 6(5): 327-34.
[http://dx.doi.org/10.1038/cmi.2009.43] [PMID: 19887045]
[68]
Surh YJ, Chun KS, Cha HH, et al. Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: Down-regulation of COX-2 and iNOS through suppression of NF-kappa B activation. Mutat Res 2001; 480-481: 243-68.
[http://dx.doi.org/10.1016/S0027-5107(01)00183-X] [PMID: 11506818]
[69]
Lee SH, Hwang HS, Yun JW. Antitumor activity of water extract of a mushroom, Inonotus obliquus, against HT-29 human colon cancer cells. Phytother Res 2009; 23(12): 1784-9.
[http://dx.doi.org/10.1002/ptr.2836] [PMID: 19367670]
[70]
Najafzadeh M, Reynolds PD, Baumgartner A, Jerwood D, Anderson D. Chaga mushroom extract inhibits oxidative DNA damage in lymphocytes of patients with inflammatory bowel disease. Biofactors 2007; 31(3-4): 191-200.
[http://dx.doi.org/10.1002/biof.5520310306] [PMID: 18997282]
[71]
Choi J-H, Kim D-W, Yun N, et al. Protective effects of hyperoside against carbon tetrachloride-induced liver damage in mice. J Nat Prod 2011; 74(5): 1055-60.
[http://dx.doi.org/10.1021/np200001x] [PMID: 21428416]
[72]
Kim YO, Park HW, Kim JH, Lee JY, Moon SH, Shin CS. Anti- cancer effect and structural characterization of endo-polysaccharide from cultivated mycelia of Inonotus obliquus. Life Sci 2006; 79(1): 72-80.
[http://dx.doi.org/10.1016/j.lfs.2005.12.047] [PMID: 16458328]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy