Journal List > J Nutr Health > v.47(2) > 1081327

Yang, Lin, and Kwon: Protective effects of Acanthopanax koreanum Kakai extract against carbon tetrachloride-induced liver injury in Sprague-Dawley rats

Abstract

Purpose

This study was conducted in order to investigate the protective effects of ethanolic extract of Acanthopanax koreanum Nakai (AE) against carbon tetrachloride (CCl4)-induced liver injury in rats.

Methods

Male Sprague-Dawley rats were randomly divided into four groups in order to receive the following experimental diets with intraperitoneal injection of CCl4 (2.0 mL/kg body weight, 20% solution 0.65 mL) for eight weeks (n = 8 per group): CCl4 control (CON), CCl4 + AE 1% (AE1), CCl4 + AE 3% (AE3), or CCl4 + acanthoic acid 0.037%, which is equivalent to AE 3% (AA).

Results

Highest serum ALT activity and albumin level were observed in the CCL4 control group, but showed a significant decrease by either AE or AA supplementation in a dose-dependent manner (p = 0.0063 and 0.0076, respectively). Both hemotoxylin and eosin staining and Masson's staining indicated remarkable prevention of CCl4-induced liver damage in the AE3 group. TNFα and IL-6 production were significantly lowered in the AE treated groups, but not in the AA group (p = 0.0016 and p = 0.0002, respectively). The effects of AE3 were greater than those of AA for inflammation and liver toxicity biomarkers.

Conclusion

Taken together, the results suggested that ethanolic extract of Acanthopanax koreanum Nakai provided hepa-toprotective effects, leading to the reduction of inflammatory response. In addition, the effect of AE was superior to that of single compound AA.

Figures and Tables

Fig. 1
Effects of AE or AA on changes of serum ALT, AST and albumin level in CCl4-induced liver injury rats for 8 weeks. Data are presented as mean ± SE (n = 8/group). Values with different alphabets are significantly different among the groups at p < 0.05 by Duncan's multiple range test. CON, CCl4-induced control; AE1, CCl4 + 1% ethanolic extract of Acanthopanax koreanum Nakai; AE3, CCl4 + 3% ethanolic extract of Acanthopanax koreanum Nakai; AA, CCl4 + acanthoic acid.
jnh-47-106-g001
Fig. 2
Histological findings of the liver tissue; (A) H&E staining, magnification ×200 and (B) Masson's trichrome staining, magnification ×200. CON, CCl4-induced control, AE1, CCl4 + 1% ethanolic extract of Acanthopanax koreanum Nakai, AE3, CCl4 + 3% ethanolic extract of Acanthopanax koreanum Nakai and AA, CCl4 + acanthoic acid. White arrows (A) fatty changes and (B) fibrosis (interbridging septa) Bars: (A)100 µm and (B) 500 µm.
jnh-47-106-g002
Fig. 3
Effects of AE or AA on hepatic TNFα (A) and IL-6 (B) levels in CCl4-induced liver injury rats for 8 weeks. Data are presented as mean ± SE (n = 8/group). Values with different alphabets are significantly different among the groups by post-hoc Duncan's multiple range test at α = 0.05 level after one way ANOVA. CON, CCl4 control; AE1, CCl4 + 1% ethanolic extract of Acanthopanax koreanum Nakai; AE3, CCl4 + 3% ethanolic extract of Acanthopanax koreanum Nakai; AA, CCl4 + acanthoic acid.
jnh-47-106-g003
Fig. 4
Effects of AE or AA on hepatic SOD (A) and CAT (B) activities in CCl4-induced liver injury rats for 8 weeks. Data are presented as mean ± SE (n = 8/group). Values with different alphabets are significantly different among the groups by post-hoc Duncan's multiple range test at α = 0.05 level after One way ANOVA. CON, CCl4-induced control; AE1, CCl4 + 1% ethanolic extract of Acanthopanax koreanum Nakai; AE3, CCl4 + 3% ethanolic extract of Acanthopanax koreanum Nakai; AA, CCl4 + acanthoic acid.
jnh-47-106-g004
Table 1
Composition of experimental diets (unit: g/kg diet)
jnh-47-106-i001

1) CON: CCl4-induced control, AE: ethanolic extract of Acanthopanax Koreanum Nakai, AE1: CCl4 + 1%AE, AE3: CCl4 + 3%AE, AA: CCl4 + Acanthoic acid 2) AIN-93G-MX (g/kg mixture): Anhydrous calcium carbonate, 357; monobasic potassium phosphate, 196; sodium chloride, 74; potassium sulfate, 46.6; Potassium citrate, tri-potassium monohydrate, 70.78; Magnesium oxide 24, ferric citrate, 6.06; Zinc carbonate,1.65; manganous carbonate, 0.63; cupric carbonate, 0.3; potassium iodate, 0.01; anhydrous sodium selenate, 0.01025; ammoniumparamolydrate 4-hydrate, 0.000795; sodium meta-silicate, 9-hydrate, 1.45; chromium potassium sulfate, 12-hydrate, 0.275; boric acid, 0.0815; sodium fluoride, 0.0635; nickel carbonate, 0.0318; lithium chloride, 0.0174; ammonium vanadate, 0.0066; powdered sucrose, 221.026 3) AIN-93-VX (g/kg mixture): nicotinic acid, 3; Ca-pantothenate 1.6; pyridoxine-HCl, 0.7; thiamin-HCl, 0.6; riboflavin, 0.6; folic acid, 0.2; D-Biotin, 0.02; Vitamin B12 (cyonocobalamin)(0.1% A in mannitol), 2.5; Vitamin E (all-rac-a-tocopheryl acetate)(500 IU/g), 15; Vitamin A (all-trans-retinylpalmitate; 500,000 IU/g), 0.8; Vitamin D3 (cholecalciferol; 400,000 IU/g), 0.25; Vitamin K/dextrose mix (10 mg/g), 7.5; Powdered sucrose 967.23 4) Contents of AE: Carbohydrate, 60.44%; Crude protein, 11.97%; Crude fat, 1.70%; Calories, 304.94 kcal/100 g

Notes

This study was supported by the Ministry of Knowledge Economy [Regional Innovation System support program B0012328 supervised by the KIAT (Korea Institute for Advancement of Technology)].

References

1. Statistics Korea. Cause of death statistics [Internet]. Daejeon: Statistics Korea;2012. cited 2013 Dec 23. Available from: http://kostat.go.kr/portal/korea/kor_nw/2/6/2/index.board?bmode=read&bSeq=&aSeq=308559&pageNo=1&rowNum=10&navCount=10&currPg=&sTarget=title&sTxt=.
2. Lee JH, Kim EM, Park YK, Park EJ, Sung MK, Sohn JM, Shin DY, Shin MJ, Lee HM. Pathophysiology for clinical nutrition. 1st edition. Seoul: Kyomoonsa;2013.
3. Park DY, Suh KS. Experimental liver disease models of rats - morphological characteristics. Korean J Pathol. 2003; 37(3):151–158.
4. McCay PB, Lai EK, Poyer JL, DuBose CM, Janzen EG. Oxygen- and carbon-centered free radical formation during carbon tetrachloride metabolism. Observation of lipid radicals in vivo and in vitro. J Biol Chem. 1984; 259(4):2135–2143.
crossref
5. Edwards MJ, Keller BJ, Kauffman FC, Thurman RG. The involvement of Kupffer cells in carbon tetrachloride toxicity. Toxicol Appl Pharmacol. 1993; 119(2):275–279.
crossref
6. Nan JX, Park EJ, Nam JB, Zhao YZ, Cai XF, Kim YH, Sohn DH, Lee JJ. Effect of Acanthopanax koreanum Nakai (Araliaceae) on D-galactosamine and lipopolysaccharide-induced fulminant hepatitis. J Ethnopharmacol. 2004; 92(1):71–77.
crossref
7. Nan JX, Jin XJ, Lian LH, Cai XF, Jiang YZ, Jin HR, Lee JJ. A diterpenoid acanthoic acid from Acanthopanax koreanum protects against D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure in mice. Biol Pharm Bull. 2008; 31(4):738–742.
crossref
8. Jeong JE, Baek HE, Oh DS, Wi AJ, Yoon BS. Functional properties and biological activity of breeding lines, parts, and various solvents from Acanthopanax. Korean J Pharmacogn. 2013; 44(3):242–252.
9. Brekhman II, Kirillov OI. Effect of eleutherococcus on alarmphase of stress. Life Sci. 1969; 8(3):113–121.
crossref
10. Brekhman II, Dardymov IV. New substances of plant origin which increase nonspecific resistance. Annu Rev Pharmacol. 1969; 9:419–430.
crossref
11. Ko ST, Kim SW, Lim DY. A study on the hypotensive action of Acanthopanax extract in rabbit. J Korean Pharm Sci. 1978; 8(1):6–16.
12. Lim JK, Seo YB, Kim DH, Seol IC. The experimental studies on the reinforcemental effects of Acanthopanax Radicis cortex about immunity hematogenic action. Korean J Herbol. 2000; 15(1):1–17.
13. Lee YS, Jung SH, Lim SS, Ji J, Lee SH, Shin KH. Effects of the water extract from the stem bark of Acanthopanax senticosus on hyperlipidemia in rats. Korean J Pharmacogn. 2001; 32(2):103–107.
14. Wu YL, Jiang YZ, Jin XJ, Lian LH, Piao JY, Wan Y, Jin HR, Joon Lee J, Nan JX. Acanthoic acid, a diterpene in Acanthopanax koreanum, protects acetaminophen-induced hepatic toxicity in mice. Phytomedicine. 2010; 17(6):475–479.
crossref
15. Kang OH, Kim DK, Cai XF, Kim YH, Lee YM. Attenuation of experimental murine colitis by acanthoic acid from Acanthopanax koreanum. Arch Pharm Res. 2010; 33(1):87–93.
crossref
16. Kang HS, Kim YH, Lee CS, Lee JJ, Choi I, Pyun KH. Suppression of interleukin-1 and tumor necrosis factor-alpha production by acanthoic acid, (-)-pimara-9(11),15-dien-19-oic acid, and it antifibrotic effects in vivo. Cell Immunol. 1996; 170(2):212–221.
17. Jung MG, Do GM, Shin JH, Ham YM, Park SY, Kwon O. Acanthopanax koreanum Nakai modulates the immune response by inhibiting TLR 4-dependent cytokine production in rat model of endotoxic shock. Nutr Res Pract. 2013; 7(6):460–465.
18. Choi YH, Kim JW. Quantitative analysis of eleutherosides B and E using HPLC-ESI/MS. Korean J Pharmacogn. 2002; 33(2):88–91.
19. Lim JH, Lee SH, Jun BS, Yang YT, Koh JS. Changes in major constituents by soaking of Acanthopanax koreanum with spirit solution. J Korean Soc Appl Biol Chem. 2005; 48(2):166–172.
20. Song IH, Kim BH, Kim YK, Dong SH, Kim HJ, Lee JI, Chang YW, Chang R. Carbon tetrachloride (CCl4)-induced hepatic fibrosis in the rat. Korean J Gastroenterol. 1992; 24(6):1330–1339.
21. Kim JY, Kwon O. Culinary plants and their potential impact on metabolic overload. Ann N Y Acad Sci. 2011; 1229:133–139.
crossref
22. Jang WJ, Kim YS, Ha YL, Park CW, Ha YK, Kim JO. Optimal level for the protection of carbon tetrachloride-induced Sprague-Dawley rat liver damage by mycelial cultures of lentinus edodes. J Life Sci. 2010; 20(5):782–788.
TOOLS
Similar articles