Protective effect of free phenolics from Lycopus lucidus Turcz. root on carbon tetrachloride-induced liver injury in vivo and in vitro
Protective effect of free phenolics from Lycopus lucidus Turcz. root (FPLR) on CCl4-induced hepatotoxicity in vivo and in vitro was first evaluated. Oral administration of FPLR (100 mg/kg bw) to mice significantly reduced the CCl4-induced elevation of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, triacylglycerols, total cholesterol, and total bilirubin. FPLR also increased the hepatic GSH contents and antioxidant enzyme activities of SOD and CAT and decreased the hepatic MDA level. Histopathological examinations further confirmed that the FPLR could protect the liver from CCl4-induced damage. Further research indicated that FPLR prevented the DNA fragmentation caused by CCl4 based on TUNEL assay. Moreover, immunohistochemistry staining demonstrated that pretreatment with FPLR significantly inhibited the elevation of hepatic TNF-α, IL-6, IL-8, iNOS, COX-2, and Caspase-3 in CCl4-treated mice. In vitro experiments showed that FPLR remarkably reduced BRL hepatocyte apoptosis and damage caused by CCl4 treatment. These findings indicate that FPLR could be developed as a functional food or medication for therapeutic purpose and prevention of hepatic injury.
- De Abajo FJ, Montero D, Madurga M, Rodriguez LAG. Acute and clinically relevant drug-induced liver injury: a population based case-control study. Br J Clin Pharmacol 2004; 58: 71–80.
- Hoek JB, Pastorino JG. Ethanol, oxidative stress, and cytokine-induced liver cell injury. Alcohol 2002; 27: 63–8.
- Srivastava A, Shivanandappa T. Hepatoprotective effect of the root extract of Decalepis hamiltonii against carbon tetrachloride-induced oxidative stress in rats. Food Chem 2010; 18: 411–17.
- Lin SY, Wang YY, Chen WY, Chuang YH, Pan PH, Chen CJ. Beneficial effect of quercetin on cholestatic liver injury. J Nutr Biochem 2014; 25: 1183–95.
- Yang JY, Li Y, Wang F, Wu CF. Hepatoprotective effects of apple polyphenols on CCl4-induced acute liver damage in mice. J Agr Food Chem 2010; 58: 6525–31.
- Sobeh M, Esmat A, Petruk G, Abdelfattah MAO, Dmirieh M, Monti DM, et al. Phenolic compounds from Syzygium jambos (myrtaceae) exhibit distinct antioxidant and hepatoprotective activities in vivo. J Funct Foods 2018; 41: 223–31.
- Gao CY, Tian CR, Zhou R, Zhang RG, Lu YH. Phenolic composition, DNA damage protective activity and hepatoprotective effect of free phenolic extract from Sphallerocarpus gracilis seeds. Int Immunopharmacol 2014; 20: 238–47.
- Ma TT, Sun XY, Tian CR, Zheng YJ, Zheng CP, Zhan JC. Chemical composition and hepatoprotective effects of polyphenols extracted from the stems and leaves of Sphallerocarpus gracilis. J Funct Foods 2015; 18: 673–83.
- The State Commission of Chinese Pharmacopoeia. Pharmacopoeia of People’s Republic of China, Part I. Beijing: China Medical Science Press; 2015, p. 228.
- Woo ER, Piao MS. Antioxidative constituents from Lycopus Lucidus. Arch Pharm Res 2004; 27: 173–6.
- Ślusarczyk S, Hajnos M, Skalicka-Woźniak K, Matkowski A. Antioxidant activity of polyphenols from Lycopus lucidus Turcz. Food Chem 2009; 113: 134–38.
- Lu YH, Huang JH, Li YC, Ma TT, Sang P, Wang WJ, et al. Variation in nutritional compositions, antioxidant activity and microstructure of Lycopus lucidus Turcz. root at different harvest times. Food Chem 2015; 183: 91–100.
- Lee YJ, Kang DG, Kim JS, Lee HS. Lycopus lucidus inhibits high glucose-induced vascular inflammation in human umbilical vein endothelial cells. Vasc Pharmacol 2008; 48: 38–46.
- Yu JQ, Lei JC, Zhang XQ, Yu HD, Tian DZ, Liao ZX, et al. Anticancer, antioxidant and antimicrobial activities of the essential oil of Lycopus lucidus Turcz. var. hirtus Regel. Food Chem 2011; 126: 1593–8.
- Yang XB, Lv YL, Tian LM, Zhao Y. Composition and systemic immune activity of the polysaccharides from an Herbal Tea (Lycopus Lucidus Turcz). J Agr Food Chem 2010; 58: 6075–80.
- Yang XB, Zhao Y, He NW, Croft KD. Isolation, characterization, and immunological effects of α-galacto-oligosaccharides from a new source, the herb Lycopus lucidus Turcz. J Agr Food Chem 2010; 58: 8253–8.
- Shin TY, Kim SH, Suk K, Ha JH, Kim I, Lee MG, et al. Anti-allergic effects of Lycopus lucidus on mast cell-mediated allergy model. Toxicol Appl Pharmacol 2005; 209: 255–62.
- Xiong W, Chen G, Tan D, Zuo S. Hypoglycemic and hypolipidemic effect of polysaccharide from wild plant Lycopus lucidus Turcz. on alloxan-induced diabetic mice. Chin J Bioprocess Eng 2011; 9: 45–8.
- Yao Y, Yang J, Wang D, Zhou F, Cai X, Lu W, et al. The aqueous extract of Lycopus lucidus turcz, ameliorates streptozotocin-induced diabetic renal damage via inhibiting TGF-β1 signaling pathway. Phytomedicine 2013; 20: 1160–7.
- Lu YH, Tian CR, Gao CY, Zhang RG, Guo Q, Mu CL. Nutritional profiles, phenolics, and DNA damage protective effect of Lycopus lucidus Turcz. root at different harvest times. Int J Food Prop 2018; 20: 1–16.
- Cho BO, Ryu HW, So Y, Jin CH, Baek JY, Park KH, et al. Hepatoprotective effect of 2,3-dehydrosilybin on carbon tetrachloride-induced liver injury in rats. Food Chem 2013; 138: 107–15.
- Weber LW, Boll M, Stampfl A. Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model. Crc Crit Rev Toxicol 2003; 33: 105–36.
- Naik SR. Antioxidants and their role in biological functions: an overview, Indian Drugs 2003; 40: 501–16.
- Szymonik-Lesiuk S, Czechowska G, Stryjecka-Zimmer M, Slomka M, Madro A, Celinski K, et al. Catalase, superoxide dismutase, and glutathione peroxidase activities in various rat tissues after carbon tetrachloride intoxication. J Hepato-Bil-Pan Sci 2003; 10: 309–15.
- Lee KJ, Choi HJ, Jeong HG. Hepatoprotective and antioxidant effects of the coffee diterpenes kahweol and cafestol on carbon tetrachloride-induced liver damage in mice. Food Chem Toxicol 2007; 45: 2118–25.
- Zhang S, Lu BN, Han X, Xu LN, Qi Y, Yin LH, et al. Protection of the flavonoid fraction from Rosa laevigata Michx fruit against carbon tetrachloride-induced acute liver injury in mice. Food Chem Toxicol 2013; 55: 60–9.
- Niu XF, Liu F, Li WF, Zhi WB, Yao Q, Zhao JM, et al. Hepatoprotective effect of fraxin against carbon tetrachloride-induced hepatotoxicity in vitro and in vivo through regulating hepatic antioxidant, inflammation response and the MAPK-NF-κB signaling pathway. Biomed Pharmacoth 2017; 95: 1091–102.
- Kim H, Park J, Lee K, Lee D, Kwak J, Kim YS, et al. Ferulic acid protects against carbon tetrachloride-induced liver injury in mice. Toxicol 2011; 282: 104–11.
- Ko J, Lee S, Lim K. Rhus verniciflua Stokes glycoprotein (36 kDa) has protective activity on carbon tetrachloride-induced liver injury in mice. Environ Toxicol Phar 2006; 22: 8–14.
- Giudice A, Montella M. Activation of the Nrf2-ARE signaling pathway: a promising strategy in cancer prevention. Bioessays 2006; 28: 169–81.
- Rubiolo JA, Mithieux G, Vega FV. Resveratrol protects primary rat hepatocytes against oxidative stress damage: activation of the Nrf2 transcription factor and augmented activities of antioxidant enzyme. Eur J Pharmacol 2008; 591: 66–72.
- Wang X, Hai CX, Liang X, Yu SX, Zhang W, Li YL. The protective effects of Acanthopanax senticosus Harms aqueous extracts against oxidative stress: role of Nrf2 and antioxidant enzymes. J Ethnopharmacol 2010; 127: 424–32.
- Morio LA, Chiu H, Sprowles KA, Zhou P, Heck DE, Gordon MK, et al. Distinct roles of tumor necrosis factor-alpha and nitric oxide in acute liver injury induced by carbon tetrachloride in mice. Toxicol Appl Pharm 2001; 172: 44–51.
- Domitrović R, Škoda M, Marchesi VV, Cvijanović O, Pugel EP, Štefan MB. Rosmarinic acid ameliorates acute liver damage and fibrogenesis in carbon tetrachloride-intoxicated mice. Food Chem Toxicol 2013; 51: 370–8.
- Yang SY, Hong CO, Lee GP, Kim CT, Lee KW. The hepatoprotection of caffeic acid and rosmarinic acid, major compounds of Perilla frutescens, against t-BHP-induced oxidative liver damage. Food Chem Toxicol 2013; 55: 92–9.
This work is licensed under a Creative Commons Attribution 4.0 International License
Authors retain copyright of their work, with first publication rights granted to SNF Swedish Nutrition Foundation.