Amelioration of carbon tetrachloride-induced hepatic injury by emulsified Antrodia extract

Document Type: Original Article


1 Graduate Institute of Bioresources, National Pingtung University of Science and Technology, Pingtung, Taiwan

2 Department of Health and Leisure Management, Yuanpei University of Medical Technology, Hsinchu, Taiwan

3 Department of Food Science and Technology, Hungkuang University, Taichung, Taiwan

4 Department of Biotechnology and Pharmaceutical Technology, Yuanpei University of Medical Technology, Hsinchu, Taiwan

5 Department of Plant Industry, National Pingtung University of Science and Technology, Pingtung, Taiwan


Objective(s): Antrodia cinnamomea (AC) is found with anti-inflammatory and immunomodulatory biological activities. In this study, we investigated the anti-hepatitis effect of the emulsified AC extract from RO water or supercritical fluid CO2 with ethanol co-solvent extract methods of AC preparations.
Materials and Methods: Five groups of eight to ten weeks male rats with a count of ten for each group were studied to evaluate the protection of two kinds of AC extract from hepatic injury. Acute liver injury of rats was induced by injecting 40% carbon tetrachloride (CCl4) 1 mg/kg intraperitoneally. Positive and negative control groups rats were perfused with CCl4 or isotonic saline, respectively. Experimental groups received oral administration once/day of AC preparations before CCl4 treatment: water AC extract (WAE group), or emulsified AC extract from supercritical fluid extraction (EAE group) for 5 days, and sacrificed on the 6th day and the blood and liver samples were collected under chloral hydrate anesthesia. The anti-inflammatory, antioxidant markers, and relevant signaling pathways were measured (AST, ALT, ROS, IL-1, IL-6, NO, and COX-2, MAPKs, and caspase-3).
Results: EAE at 50 mg/kg significantly decreased the serum AST, ALT, IL-1, IL-6, NO, and ROS levels. Both extracts reduced the activation of p-ERK in the liver samples, but EAE inhibited COX-2 and caspase-3 protein expression better than WAE. The EAE ameliorated CCl4-induced hepatic injury significantly; as compared with WAE and the positive control.
Conclusion: The hepatoprotection of EAE could be attributed to the antioxidant and anti-inflammatory effects of Antrodia.


Main Subjects

1. Moradpour D, Blum HE. Pathogenesis of hepatocellular carcinoma. Eur J Gastroenterol Hepatol 2005; 17:477-483.

2. Sun H, Che QM, Zhao X, Pu XP. Antifibrotic effects of chronic baicalein administration in a CCl4 liver fibrosis model in rats. Eur J Pharmacol 2010; 631:53-60.

3. Yue PY, Wong YY, Wong KY, Tsoi YK, Leung KS. Current evidence for the hepatoprotective activities of the medicinal mushroom Antrodia cinnamomea. Chin Med 2013; 8:21.

4. Kumar KJ, Chu FH, Hsieh HW, Liao JW, Li WH, Lin JC, et al. Antroquinonol from ethanolic extract of mycelium of Antrodia cinnamomea protects hepatic cells from ethanol-induced oxidative stress through Nrf-2 activation. J Ethnopharmacol 2011; 136:168-177.

5. Gokila Vani M, Kumar KJ, Liao JW, Chien SC, Mau JL, Chiang SS, et al. Antcin c from antrodia cinnamomea protects liver cells against free radical-induced oxidative stress and apoptosis in vitro and in vivo through Nrf2-dependent mechanism. Evid Based Complement Alternat Med 2013; 2013:296082.

6. Han HF, Nakamura N, Zuo F, Hirakawa A, Yokozawa T, Hattori M. Protective effects of a neutral polysaccharide isolated from the mycelium of Antrodia cinnamomea on Propionibacterium acnes and lipopolysaccharide-induced hepatic injury in mice. Chem Pharm Bull (Tokyo) 2006; 54:496-500.

7. Ker YB, Peng CC, Chang WL, Chyau CC, Peng RY. Hepatoprotective bioactivity of the glycoprotein, antrodan, isolated from Antrodia cinnamomea mycelia. PLoS One 2014; 9:e93191.

8. Chen ZQ, Liu Y, Zhao JH, Wang L, Feng NP. Improved oral bioavailability of poorly water-soluble indirubin by a supersaturatable self-microemulsifying drug delivery system. Int J Nanomedicine 2012; 7:1115-1125.

9. Chiu HW, Hua KF. Hepatoprotective effect of wheat-based solid-state fermented Antrodia cinnamomea in carbon tetrachloride-induced liver injury in rat. PLoS One 2016; 11:e0153087.

10. Hsiao G, Shen MY, Lin KH, Lan MH, Wu LY, Chou DS, et al. Antioxidative and hepatoprotective effects of Antrodia camphorata extract. J Agric Food Chem 2003; 51:3302-3308.

11. Hseu YC, Chen SC, Yech YJ, Wang L, Yang HL. Antioxidant activity of Antrodia camphorata on free radical-induced endothelial cell damage. J Ethnopharmacol 2008; 118:237-245.

12. Balakrishnan P, Lee BJ, Oh DH, Kim JO, Lee YI, Kim DD, et al. Enhanced oral bioavailability of Coenzyme Q10 by self-emulsifying drug delivery systems. Int J Pharm 2009; 374:66-72.

13. Gordon G S, Moses A C, Silver R D, Flier J S, Carey M C. Nasal absorption of insulin: enhancement by hydrophobic bile salts. Proc Natl Acad Sci USA 1985; 82:7419-7423.

14. Bowe CL, Mokhtarzadeh L, Venkatesan P, Babu S, Axelrod HR, Sofia MJ, et al. Design of compounds that increase the absorption of polar molecules. Proc Natl Acad Sci USA 1997; 94:12218-12223.

15. Qiao X, Wang Q, Ji S, Huang Y, Liu KD, Zhang ZX, Bo T, Tzeng YM, et al. Metabolites identification and multi-component pharmacokinetics of ergostane and lanostane triterpenoids in the anticancer mushroom Antrodia cinnamomea. J Pharm Biomed Anal 2015; 111:266-276.

16. Wang Q, Qiao X, Qian Y, Li ZW, Tzen YM, Zhou DM, et al. Intestinal absorption of ergostane and lanostane triterpenoids from Antrodia cinnamomea using Caco-2 cell monolayer model. Nat Prod Bioprospect 2015; 5:237-246.

17. Gershanik T, Benita S. Self-dispersing lipid formulations for improving oral absorption of lipophilic drugs. Eur J Pharm Biopharm 2000; 50:179-188.

18. Tien AJ, Chien CY, Chen YH, Lin LC, Chien CT. Fruiting bodies of Antrodia cinnamomea and its active triterpenoid, antcin K, ameliorates N-nitrosodiethylamine-induced hepatic inflammation, fibrosis and carcinogenesis in rats. Am J Chin Med 2017; 45:173-198.