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Anti-inflammatory Modulating Effect of Rengyolone in Rat
Biomed Sci Letters 2019;25:54-59
Published online March 31, 2019;  https://doi.org/10.15616/BSL.2019.25.1.54
© 2019 The Korean Society For Biomedical Laboratory Sciences.

Gil-Hyon Lee1,*, Kyung-Yae Hyun3,* and Yoon-Jung Kang2,†,*

Department of Clinical Laboratory Science, Dong-seo University, Busan 47011, Korea,
Department of Clinical Laboratory Science, Sang-ji University, Wonju 26339, Korea,
Department of Clinical Laboratory Science, Dong-eui University, Busan 47340, Korea
Correspondence to: Yoon-Jung Kang. Department of Clinical Laboratory Science, Sang-ji University, 83 Sangjidaegil, Seo-gu, Wonju 26339, Korea. Tel: +82-33-738-8081, Fax: +82-33-730-0114, e-mail: lvpig@naver.com
Received February 26, 2019; Revised March 26, 2019; Accepted March 27, 2019.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
 Abstract

Hepatitis refers to inflammation of hepatocytes and liver tissue, and is mainly caused by viruses, alcohol, and drugs. Forsythiae Fructus has traditionally been used as a diuretic, anti-inflammatory and antipyretic. Research on rengyolone, a bioactive substance extracted from Forsythiae Fructus, is rarely found in Korea and abroad. First, an acute animal toxicity test for rengyolone was conducted for the animal experiment. 4 week-old SD rats were injected intraperitoneally with acetaminophen for 2 weeks to induce chronic liver inflammation. Rengyolone was orally administered into two groups during 4 weeks: pre-inflammatory group and post-inflammatory group. Oral doses were also divided into 1 mg/kg and 5 mg/kg. Liver function tests (ALT, AST, ALP), western blot analysis of liver tissue, and level of inflammatory cytokine were performed to evaluate the improvement of hepatitis. Experimental results showed that rengyolone inhibited the development of acute inflammation and thus could reduce hepatitis symptoms.

Keywords : Hepatitis, Forsythiae fructus, Rengyolone, Acetaminophen, Liver function tests, iNOS
꽌 濡

媛꾩뿼(hepatitis) 媛꾩꽭룷쓽 넀긽쓣 留먰븯硫 슦由щ굹씪뿉꽌뒗 媛꾩뿼 쓷븳 吏덊솚 以묒뿉 븯굹씠떎. 媛꾩뿼 넻긽 諛붿씠윭뒪뿉 쓽븯뿬 諛쒖깮븳떎怨 븣젮졇 엳쑝굹 븣肄붿삱怨 媛숈 룆꽦臾쇱쭏뿉 쓽븯뿬 諛쒖깮븯뒗 媛꾩뿼룄 엳떎(Tian et al., 2018). 6媛쒖썡 씠긽 吏냽릺뒗 留뚯꽦媛꾩뿼씤 寃쎌슦 쟻젅븳 移섎즺媛 蹂묓뻾릺吏 븡쑝硫 떖媛곹븳 媛꾩넀긽씤 媛꾧꼍蹂쑝濡 吏꾪뻾맂떎(Lightsey and Rockey, 2017; Pérez-Gracia et al., 2017). 媛꾩뿼쓽 씠쑀(諛붿씠윭뒪, 吏諛, 옄媛硫댁뿭, 룆꽦臾쇱쭏 벑)뿉 븳 洹쇱썝쟻씤 移섎즺媛 媛꾩뿼쓽 移섎즺뿉 빑떖씠吏留 빆吏꾨맂 뿼利 긽깭뿉 엳뒗 媛꾩“吏곸뿉 븳 뿼利앸컻쁽 븯瑜 쐞븳 泥섏튂뒗 媛꾩뿼 移섎즺瑜 쐞븯뿬 븘슂븯떎怨 븣젮졇 엳떎(Kanzler et al., 2007). 媛꾧린뒫寃궗(liver function tests, LFT)뒗 asparate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), 븣遺誘(albumin), 鍮뚮━猷⑤퉰(bilirubin)쓽 닔移섎 룊媛븯뒗 寃궗씠떎. 媛꾧린뒫寃궗뒗 媛꾨떞룄怨꾩쭏솚 꽑蹂꾩뿉 슚怨쇱쟻씠硫 媛먮퀎吏꾨떒쓽 諛⑺뼢쓣 젣떆븳떎(Kanzler et al., 2007). 媛꾩넀긽씠 떖빐吏硫 AST, ALT媛 긽듅븯硫 듅엳 媛꾧꼍솕利앹뿉꽌뒗 AST/ALT 鍮꾧 긽듅븳떎怨 븣젮졇 엳떎(Thapa and Walia, 2017; Gressner et al., 2007). ALP뒗 紐⑤뱺 醫낅쪟쓽 媛꾩쭏솚뿉꽌 긽듅븯硫 醫낆뼇뿉 쓽븳 移⑥쑄꽦 媛꾩뿼뿉꽌 쁽엳 利앷븳떎. 씠뱾 媛꾧린뒫寃궗쓽 빆紐⑹쓽 蹂솕뒗 媛꾩쭏솚 꽑蹂꾩뿉 슚怨쇱쟻씠硫 媛꾩쭏솚쓽 以묒쬆룄 移섎즺諛섏쓳룊媛뿉 쑀슜븯떎(Gressner et al., 2007). 留뚯꽦쟻씤 뿼利앹긽깭뿉 엳뒗 留뚯꽦媛꾩뿼솚옄뒗 삁옣뿉꽌 뿼利앹꽦 궗씠넗移댁씤(proinflammatory cytokine) Tumor necrosis factor-alpha (TNF-α), Interleukin-6 (IL-6) 벑씠 利앷릺뼱 엳쑝硫 씠윭븳 궗씠넗移댁씤뿉 쓽븯뿬 inducible NOS (iNOS) 諛쒗쁽씠 利앷릺硫 iNOS뿉 쓽븯뿬 NO媛 떎닔 諛⑹텧맂떎(Brown, 2008; Mariotto et al., 2007). 뵲씪꽌 뿼利앹긽깭媛 샇쟾릺硫 궗씠넗移댁씤쓽 뼇씠 媛먯냼릺硫 iNOS, NO쓽 諛쒗쁽룄 븯맂떎. 떎뿕뿉꽌 留뚯꽦뿼利앹긽깭媛 샇쟾맂떎硫 씠뱾 씤옄뱾쓽 諛쒗쁽룄 옄뿰뒪읇寃 븯맆 寃껋씠씪 삁긽맂떎.

뿰援(Forsythiae Fructus)뒗 쓽꽦媛쒕굹由(Forsythia viridissima Lindley) 삉뒗 뿰援(Forsythia suspensa Vahl)씪怨 遺덈━뒗 臾쇳뫖젅굹臾닿낵쓽 뿴留ㅼ씠떎. 뿰援먮뒗 쟾넻쟻쑝濡 씠눊젣, 빆뿼利앹젣, 빐뿴젣濡 쟾넻쟻쑝濡 궗슜릺뼱 솕쑝硫 뿰援ъ뿉 쓽븯硫 빆궛솕(Debnath et al., 2013), 빆洹(Qu et al., 2008), 빆諛붿씠윭뒪(Law et al., 2017) 벑쓽 슚怨쇨 엳떎怨 븣젮졇 엳떎. 洹몃윭굹 쁽옱 뿰援먯쓽 깮由ы솢꽦臾쇱쭏뿉 븳 뿰援щ뒗 嫄곗쓽 吏꾪뻾릺뼱 엳吏 븡쑝硫 洹 以 rengyolone뿉 븳 뿰援щ뒗 쟾臾댄븳 떎젙씠떎. 蹂 뿰援щ뒗 뿰援먯쓽 援ъ꽦꽦遺꾩씤 rengyolone쓣 留뚯꽦뿼利앹긽깭씤 媛꾩뿼룞臾쇰え뜽뿉 寃쎄뎄닾뿬븿쑝濡 떎뿕룞臾쇱뿉꽌 rengyolone 빆뿼利앺슚怨 諛 媛꾩뿼利 媛먯냼슚怨쇰 議곗궗븯떎.

옱猷 諛 諛⑸쾿

떎뿕룞臾

4二쇰졊 Sprague Dawley (SD) rat쓣 以묒븰룞臾쇱꽱꽣(쟾, 븳援)뿉꽌 븫而 60留덈━ 援ъ엯븯쑝硫 硫멸퇏맂 cage뿉꽌 2씪媛 븞젙떆湲곕 媛뽮쾶 븯떎. 룞臾쇱 뒿룄 70±10%, 삩룄 20±5꼦瑜 쑀吏븯쑝硫 癒뱀씠瑜 異⑸텇엳 怨듦툒븯떎. 蹂 뿰援щ뒗 룞쓽븰援 룞臾쇱쑄由ъ떖쓽瑜 以닔븯뿬 떆뻾븯떎.

떎뿕怨꾪쉷 諛 떎뿕援 遺꾨쪟

룞臾 븞젙 씠썑 2二쇱뿉 嫄몄퀜 媛꾩뿼쓣 쑀諛쒗븯쑝硫 rengyolone쓽 븘꽭듃븘誘몃끂렂(acetaminophen)濡 쑀諛쒕릺뒗 媛꾨룆꽦뿉 븳 蹂댄샇슚怨쇰 솗씤븯湲 쐞븳 媛꾩뿼쑀諛 쟾 닾뿬援곌낵 移섎즺슚怨쇰 솗씤븯湲 쐞븳 媛꾩뿼쑀諛 썑 닾뿬援곗쑝濡 꽕젙븯떎(Fig. 1). 媛꾩뿼利 쑀諛 쟾 룞臾쇨뎔怨 쑀諛 썑 룞臾쇨뎔쑝濡 遺꾨━븯뿬 떎뻾븯쑝硫 rengyolone쓽 닾뿬 냽룄 삉븳 5 mg/kg and 1 mg/kg쑝濡 굹늻뼱 寃쎄뎄닾뿬븯떎. 媛꾩뿼쑀諛 떆옉 6二 썑 룞臾쇱쓣 씗깮븯쑝硫 룞臾쇱쓽 삁븸쓣 梨꾩랬븯怨 썝떖遺꾨━븯뿬 삁옣쓣 닔吏묓븯떎. 삉븳 媛꾩“吏곸쓣 옱痍⑦븯떎. 蹂 뿰援ъ뿉꽌 떎뿕援곗 媛 援 10留덈━뵫 떎쓬怨 媛숈씠 遺꾨쪟븯떎. Sham: 젙긽援+깮由ъ떇뿼닔 닾뿬援, Hepatitis-induced Group: 媛꾩뿼利 쑀諛+깮由ъ떇뿼닔 닾뿬, Prelow: 媛꾩뿼利 쑀諛+媛꾩뿼쑀諛 쟾 6二 룞븞 냽룄빟臾쇳닾뿬(1 mg/kg), Pre-high: 媛꾩뿼利 쑀諛+媛꾩뿼利 쑀諛 쟾 6二 룞븞 怨좊냽룄빟臾쇳닾뿬(5 mg/kg), Post-low: 媛꾩뿼利 쑀諛+媛꾩뿼利 쑀諛 썑 4二 룞븞 냽룄빟臾쇳닾뿬(1 mg/kg), Post-high: 媛꾩뿼利 쑀諛+媛꾩뿼利 쑀諛 썑 4二 룞븞 怨좊냽룄빟臾쇳닾뿬(5 mg/kg), Positive control: 媛꾩뿼利 쑀諛+4二쇨컙 Vitamine C, E 蹂듯빀젣(1 mg/kg). 빆궛솕젣뒗 媛꾩뿼쓣 씪쑝궎뒗 궛솕뒪듃젅뒪瑜 媛먯냼떆궎怨 뿼利앹꽦 cytokine쓣 以꾩뿬꽌 媛꾩뿼쓽 移섎즺뿉 궗슜릺뼱 솕쑝硫 몴쟻씤 빆궛솕젣濡쒕뒗 鍮꾪誘 E, 鍮꾪誘 C, 踰좏씤(betaine) 벑씠 엳떎. 씠뿉 蹂 뿰援ъ뿉꽌 鍮꾪誘 C, E 蹂듯빀젣瑜 positive control濡 꽑젙븯떎.

Fig. 1.

Experimental schedule. Acute hepatitis was induced for 2 weeks and then rengyolone was given orally for 4 weeks. Animals were sacrificed after 6 weeks of animal experiment and samples were collected.


湲됱꽦룆꽦떆뿕

泥댁쨷 100~120 g쓽 SD rat쓣 긽쑝濡 냽룄蹂꾨줈 3留덈━쓽 룞臾쇨뎔뿉 rengyolone쓣 寃쎄뎄닾뿬븯떎. Rengyolone쓣 2,000 mg/kg, 3,000 mg/kg 슜웾쑝濡 寃쎄뎄닾뿬 썑 씠 룞븞 뻾룞蹂솕, 泥댁쨷蹂솕, 엫긽利앹긽 諛 궗留앹쓣 愿李고븯쑝硫 떎뿕湲곌컙 以 궗留 諛 愿李곌린媛 醫낅즺 썑 깮議댄븳 룞臾쇨뎔 紐⑤몢 쟾遺 遺寃븯뿬 옣湲곗씠긽뿬遺瑜 愿李고븯떎.

媛꾩뿼쑀諛 諛 媛꾧린뒫寃궗

媛꾩뿼쑀諛쒖 Park쓽 諛⑸쾿(Park and Jeong, 1995)쓣 닔젙븯뿬 떎떆븯떎. 븘꽭듃븘誘몃끂렂쓣 룞臾 紐몃Т寃뚯뿉 뵲씪 1 mg/kg 냽룄濡 븯猷⑥뿉 몢 踰 2二 룞븞 蹂듦컯닾뿬븯쑝硫 媛꾩뿼쑀諛 쑀臾대0 媛꾧린뒫寃궗瑜 넻븯뿬 寃利앺븯떎. 媛꾧린뒫룊媛뒗 Hitachi clinical analyzer 7180 (Hitachi Ltd, Tokyo, Japan) 吏꾨떒솕븰遺꾩꽍湲곕 씠슜븯뿬 삁옣뿉 議댁옱븯뒗 ALP, AST, ALP瑜 痢≪젙븯떎.

궗씠넗移댁씤 痢≪젙

씗깮맂 룞臾쇱쓽 삁옣뿉 議댁옱븯뒗 뿼利앹꽦 궗씠넗移댁씤 IL-6 TNF-α쓽 냽룄瑜 痢≪젙븯湲 쐞븯뿬 Quantikine ELISA kit (R&D Ltd, Mineapolis, USA)瑜 궗슜븯쑝硫 떎뿕諛⑸쾿 manufacturer’s instruction쓣 뵲옄떎.

Western blot

쟻異쒗븳 媛꾩“吏곸쓣 臾닿퇏 닔닠슜 移쇰줈 옒寃 떎吏怨, lysis buffer瑜 泥④븯뿬 4꼦뿉꽌 homogenizer瑜 씠슜븯뿬 洹좎쭏솕븯떎. 씠 썑 媛 援곗쓽 媛꾩“吏곸쓣 媛숈 떒諛깆쭏 냽룄濡 젙웾솕븯떎. 以鍮꾨맂 sample 10~12% gel뿉 18.5 μL濡 깦뵆쓣 loading 썑 쟾湲곗쁺룞 븯떎. 援먮컲湲곗뿉꽌 blocking buffer (1X PBST, skim milk, sodium azide)濡 1떆媛꾩뵫, 2踰덉쓽 깉 blocking buffer濡 援먯껜븯뿬 blocking븯怨 iNOS (Ab)瑜 4꼦뿉꽌 over night 떆耳곕떎. 7遺꾧컙 5쉶뿉 嫄몄퀜 1X PBST (10X PBST, D.W, 0.1% Tween 20)濡 닔꽭 썑 2李 Ab瑜 援먮컲湲 쐞뿉꽌 2떆媛 떎삩 諛섏쓳떆궎怨 ECL쓣 씠슜븯뿬 諛쒗쁽, 遺꾩꽍븯떎. 쁺긽遺꾩꽍 Image J Software쓣 씠슜븯뿬 諛쒗쁽 젙룄瑜 痢≪젙븯떎.

옄猷뚮텇꽍 諛 넻怨꾩쿂由

紐⑤뱺 옄猷뚮뱾 媛뒫븳 룊洹좉컪 ± 몴以렪李⑤줈 몴떆븯떎. 떎뿕援 궗씠쓽 젙洹쒖꽦 寃젙쓣 떎떆븯쑝硫 젙洹쒖꽦씠 엳쓣 븣 媛 援 媛꾩쓽 紐⑤뱺 蹂닔 鍮꾧탳뒗 ANOVA(遺꾩궛遺꾩꽍)濡 쑀쓽꽦쓣 寃젙 썑 쑀쓽븳 寃곌낵媛 굹삱 븣 Turkey 踰뺤쑝濡 궗썑寃젙쓣 쟻슜븯떎(SPSS program, Version 12.0).

寃 怨

湲됱꽦룆꽦떆뿕

3留덈━ 룞臾쇱씠 二쎌 븡븯쑝硫 씠 썑 빐遺 寃곌낵 옣湲곗넀긽 諛 蹂깋쁽긽씠 뾾뿀떎. 媛꾧린뒫寃궗 諛 삁븸遺꾩꽍 寃곌낵 紐⑤몢 젙긽移 踰붿쐞 궡떎(寃곌낵瑜 몴 諛 洹몃┝쑝濡 몴떆 븞븿).

媛꾧린뒫寃궗

2二 李 媛꾩뿼利앹쓣 쑀諛쒗븳 썑 룞臾쇨컙뿼쓣 寃利앺븯湲 쐞븯뿬 post-treatment 援곗쓣 긽쑝濡 瑗щ━젙留μ뿉꽌 梨꾪삁븳 삁븸쓣 씠슜븯뿬 媛꾧린뒫씤옄(ALT, ALP, AST)瑜 痢≪젙븯떎(Table 1A). 洹몃━怨 4二 룞븞 rengyolone 닾뿬 썑 룞臾쇱쓣 씗깮븯怨 梨꾩랬븳 삁븸뿉꽌 媛꾧린뒫씤옄瑜 遺꾩꽍븯떎(Table 1B). Table 1A 寃곌낵瑜 蹂대㈃ Sham 援곗쓣 젣쇅븳 紐⑤뱺 援곕뱾쓽 媛꾧린뒫씤옄쓽 닔移섍 쁽븯寃 利앷맂 寃쏀뼢쓣 蹂쇱닔 엳뿀떎. Rengyolone쓽 4二 닾엯 썑 媛꾧린뒫씤옄쓽 寃곌낵뒗 Hepatitis-induced group쓣 젣쇅븳 臾쇱쭏닾뿬援곗뿉꽌 媛꾧린뒫씤옄쓽 寃곌낵媛 샇쟾릺뿀쓬쓣 븣 닔 엳뿀떎(Table 1).

Results of liver function test

(A) 1st liver function test

 VariablesExperimental groups

ShamHepatitis-induced groupPost-lowPost-highPositive control
AST (IU/L)144.25±14.51*381.41±11.89355.20±12.65355.87±17.61373.28±12.08
ALT (IU/L)7.25±1.31*28.71±0.8929.89±0.7929.12±1.5930.51±1.62
ALP (IU/L)240.75±10.50*378.10±12.69351.19±13.40337.05±11.89329.02±10.88

(B) 2nd liver function test

 VariablesExperimental groups

ShamHepatitis-induced groupPost-lowPost-highPositive control

AST (IU/L)139.70±9.80261.10±9.85158.78±7.88^178.04±12.60^161.80±10.01^
ALT (IU/L)7.99±1.1020.05±1.9512.88±3.46^10.50±2.51^10.10±1.94^
ALP (IU/L)218.58±11.82278.50±21.54221.40±14.91^225.09±12.97^212.82±13.71^

Liver function tests were performed at 2 (Table 1 A) and 6 (Table 1 B) weeks according to schedule

A)There was a significant difference in the liver function markers in the Sham group compared to the hepatitis-induced groups (Hepatitis-induced group, Post-low, Post-high, Positive control) (*, P<0.05)

B)The results of the liver function tests performed 6 weeks later showed that the hepatic function values of the experimental groups (Post-low, Post-high, Positive control) were significantly lower than those of the hepatitis-induced group (^, P<0.05). Abbreviation: AST, aspartate aminotransferase; ALT, alanine aminotransferase; ALP, alkaline phosphatase


궗씠넗移댁씤 냽룄

Fig. 2쓽 寃곌낵뒗 媛꾩“吏곸뿉꽌쓽 IL-6쓽 諛쒗쁽쓣 蹂댁뿬二쇨퀬 엳떎. Hepatitis-induced group뿉꽌 95.7 ± 17.2 pg/mL濡 怨좊냽룄 諛쒗쁽쓣 蹂댁吏留 굹癒몄 떎뿕援곗뿉꽌뒗 넻怨꾩쟻쑝濡 쑀쓽븳 李⑥씠瑜 蹂댁씠硫 븯맂 寃쏀뼢쓣 蹂 닔 엳뿀떎(P<0.01). 媛꾩“吏곸뿉꽌쓽 TNF-α쓽 냽룄蹂솕瑜 Fig. 3뿉꽌 蹂댁뿬二쇨퀬 엳떎. TNF-α뒗 젙긽援곗뿉꽌뒗 33.2 ± 0.9 pg/mL쓽 냽룄씤 諛섎㈃ Hepatitis-induced group뿉꽌뒗 171.3 ± 11.2 pg/mL濡 솗뿰엳 利앷릺뿀쓬쓣 븣 닔 엳뿀떎. 洹몃윭굹 Hepatitis-induced group뿉 鍮꾪븯뿬 굹癒몄 떎뿕援곗뿉꽌뒗 넻怨꾩쟻쑝濡 쑀쓽븳 李⑥씠瑜 蹂댁씠硫 븯맂 寃쏀뼢쓣 蹂 닔 엳뿀떎(P<0.01). Pre-treatment 援곌낵 post-treatment 援곗쓣 鍮꾧탳빐 蹂 븣 媛 援 媛꾩뿉 쑀쓽븳 李⑥씠媛 뾾쓬쓣 븣 닔 엳뿀떎(P>0.05).

Fig. 2.

Concentration of IL-6 in serum. The concentration of IL-6 tends to decrease in a concentration-dependent manner. There was a significant difference in the treatment groups compared to hepatitisinduced group (**, P<0.01).


Fig. 3.

Concentration of TNF-α in serum. The concentration of TNF-α was significantly increased in the hepatitis-induced group. There was a significant difference in the treatment groups compared to the hepatitis-induced group (**, P<0.01).


iNOS 諛쒗쁽

Fig. 4쓽 寃곌낵뒗 媛꾩“吏곸쓣 洹좎쭏솕븳 썑 痢≪젙븳 iNOS 諛쒗쁽쓣 痢≪젙븳 寃곌낵씠떎. 씠 寃곌낵 뿭떆 Hepatitis-induced group뿉 鍮꾪븯뿬 굹癒몄 떎뿕援곗뿉꽌 넻怨꾩쟻쑝濡 쑀쓽븳 李⑥씠瑜 蹂댁씠硫 븯맂 寃쏀뼢쓣 蹂 닔 엳뿀쑝硫(P<0.01) 듅엳 Sham 援곗뿉꽌뒗 iNOS 諛쒗쁽씠 嫄곗쓽 씠猷⑥뼱吏吏 븡븯쓬쓣 븣 닔 엳뿀떎. 궗씠넗移댁씤 遺꾩꽍 寃곌낵 留덉갔媛吏濡 iNOS 諛쒗쁽 뿭떆 Pre-treatment 援곌낵 post-treatment 援 궗씠뿉 쑀쓽븳 李⑥씠瑜 蹂 닔 뾾뿀떎(P>0.05).

Fig. 4.

Expression of iNOS in liver tissue. The protein concentration of iNOS was significantly increased in the hepatitis-induced group. There was a significant difference in the treatment groups compared to the hepatitis-induced group (**, P<0.01).


怨 李

怨좊룄솕맂 쁽궗쉶뿉꽌 옦 쓬二쇰Ц솕 뒪듃젅뒪濡 씤븳 媛꾩쭏솚 諛쒕퀝 뜑슧 떖솕릺뼱媛怨 엳떎. 넻긽 媛꾩뿼쓽 썝씤 諛붿씠윭뒪媛먯뿼씠 二쇱슂 썝씤씠怨 洹 쇅 룆洹밸Ъ, 吏諛⑹텞泥, 뵾濡 벑 떎뼇븳 썝씤뿉 쓽빐꽌 諛쒕퀝븯硫 넻긽 6媛쒖썡 씠긽 留뚯꽦쟻씤 뿼利앹긽깭媛 吏냽릺硫 젙긽議곗쭅씠 꽟쑀솕릺硫 媛꾧린뒫씠 궗씪吏뒗 媛꾧꼍솕濡 吏꾪뻾븯寃 맂떎. 씠젅씠씪뒗 긽몴紐낆쑝濡 옒 븣젮吏 븘꽭듃븘誘몃끂렂 쟾 꽭怨꾩쟻쑝濡 궗슜릺뒗 빐뿴吏꾪넻젣씠硫 移섎즺 슜웾쓽 踰붿쐞媛 삊냼븳 옞옱쟻씤 궡씤꽦 媛꾨룆냼(intrinsic hepatoxin)씠떎. 꽦씤궓꽦쓽 寃쎌슦 븘꽭듃븘誘몃끂렂쓣 20 mg 씠긽쓽 슜웾뿉꽌 솴떖怨 븿猿 湲됱냽엳 媛꾨쟾씠 씠뻾븳떎怨 븣젮졇 엳쑝硫 湲됱꽦 媛꾨쟾 씠썑 12~24떆媛 궡뿉 媛 슚냼(ALT, AST, ALT 벑)쓽 닔移섍 긽듅븳떎怨 븣젮졇 엳떎(Ahn, 2006). 媛꾩꽭룷쓽 넀긽쓣 遺꾩꽍븯湲 쐞븯뿬 엫긽쟻쑝濡 삁泥 궡쓽 AST, ALT, ALP 媛숈 슚냼쓽 솢꽦룄瑜 寃궗븳떎. A 삁泥뿉꽌쓽 AST, ALT 솢꽦移 利앷뒗 媛꾩꽭룷쓽 뙆愿 諛 옣븷젙룄 넂 긽愿꽦쓣 媛吏怨 엳쑝硫 媛꾩뿉꽌 삁븸뿉꽌 쑀異쒕릺뒗 떎瑜 슚냼뿉 鍮꾪븯뿬 삁誘쇳븯寃 蹂룞맂떎. ALP뒗 媛꾨떞愿긽뵾꽭룷, 堉, 냼옣 벑 뿬윭 옣湲곗뿉 遺꾪룷븯뒗 슚냼씠硫 뿭떆 씠 슚냼쓽 湲됱냽븳 利앷뒗 媛꾩넀긽쓣 쓽誘명븳떎. 蹂 뿰援ъ뿉꽌뒗 꽦씤뿉寃뚯꽌 湲됱냽븳 媛꾨쟾쓣 씪쑝궓떎怨 븣젮吏 슜웾蹂대떎 넂 슜웾쓣 SD rat뿉寃 닾뿬븯뿬 湲됱냽 媛꾩뿼利앹쓣 씪쑝耳곕떎. 븘꽭듃븘誘몃끂렂뿉 쓽븳 媛꾩넀긽씠 젙긽쟻쑝濡 씠猷⑥뼱議뚮뒗吏瑜 궡뵾湲 쐞븯뿬 1李 媛꾧린뒫寃궗瑜 떎떆븳 寃곌낵 븘꽭듃븘誘몃끂렂 닾뿬援곗뿉꽌 鍮꾩젙긽쟻씤 媛꾧린뒫 닔移섎 蹂댁엫쓣 븣 닔 엳뿀떎(Table 1A). Rengyolone 닾뿬 썑 媛꾧린뒫 닔移섎뒗 rengyolone 닾뿬援곌낵 鍮꾪닾뿬援 媛꾩쓽 솗뿰엳 李⑥씠瑜 蹂 닔 엳뿀쑝硫 씠뒗 rengyolone 닾뿬媛 留뚯꽦쟻씤 媛꾩뿼쓣 샇쟾떆궎뒗뜲 湲곗뿬븯쓬쓣 븣 닔 엳뒗 紐⑹씠떎(Table 1). Rengyolone쓽 寃쎄뎄닾뿬媛 媛꾩넀긽쓣 移섎즺븿뿉 엳뼱 뿼利앸컻쁽吏뿉 븳 룊媛瑜 쐞븯뿬 떎쓬 뿰援щ 吏꾪뻾븯떎.

떎뼇븳 썝씤뿉 쓽븯뿬 諛쒖깮븯뒗 뿼利앸컲쓳 洹 썝씤怨 諛섏쓳븯뒗 議곗쭅쓽 李⑥씠뿉 긽愿뾾씠 쑀궗븳 蹂솕瑜 蹂댁씤떎怨 븣젮졇 엳떎. 씠윭븳 쑀궗븳 뿼利앷낵젙쓣 怨듯넻쟻쑝濡 留ㅺ컻븯뒗 臾쇱쭏뱾濡 뿼利앹꽦 궗씠넗移댁씤, NO, prostaglandin 벑씠 엳떎(Noh and Baek, 2009). 쟾뿼利앹꽦 궗씠넗移댁씤씤 IL-1, TNF-α, IL-6 벑쓽 옄洹뱀뿉 쓽빐 iNOS쓽 怨쇰룄븳 솢꽦솕濡 떇꽭룷, 媛꾩꽭룷, 궡뵾꽭룷, 떖洹쇱꽭룷 벑뿉꽌 옣떆媛 떎웾쓽 NO瑜 깮꽦븯寃 븯뒗 寃껋쑝濡 븣젮졇 엳떎. 깮泥대궡 怨좊냽룄쓽 NO 깮꽦 닕二쇱꽭룷쓽 뙆愿, 뿼利앸컲쓳 쑀諛쒖쓣 留ㅺ컻븯뿬 議곗쭅쓣 긽빐븳떎(Tian et al., 2018). 뵲씪꽌 NO 깮꽦 빐젣뒗 떎뼇븳 뿼利앹꽦 吏덊솚쓽 뿼利앸컲쓳議곗젅젣濡쒖꽌쓽 媛뒫꽦뿉 븳 뿰援ш 솢諛쒗엳 씠猷⑥뼱吏怨 엳떎. 뵲씪꽌 Rengyolone쓽 뿼利앸컻쁽 吏瑜 솗씤븯湲 쐞븯뿬 뿼利앹꽦 궗씠넗移댁씤 IL-6, TNF-α怨 洹몄뿉 뵲瑜대뒗 뿼利앸컻쁽씤옄 iNOS 諛쒗쁽쓣 궡렣蹂댁븯떎(Fig. 2-4). 癒쇱 Fig. 2, 3쓽 삁泥 궗씠넗移댁씤 諛쒗쁽 寃곌낵瑜 蹂대㈃ IL-6, TNF-α쓽 諛쒗쁽씠 Hepatitis-induced Group뿉 鍮꾧탳븯뿬 Rengyolone 닾뿬援곕뱾뿉꽌 쁽븯寃 궙 냽룄瑜 蹂댁엫쓣 븣 닔 엳뿀떎. 몢 궗씠 넗移댁씤쓽 뼇긽 씠 썑 留ㅺ컻臾쇱쭏 iNOS쓽 諛쒗쁽怨쇰룄 愿怨꾧 엳뿀쑝硫 洹 寃곌낵뒗 Fig. 4뿉 蹂댁뿬二쇨퀬 엳떎. 뿼利앹꽦 궗씠넗移댁씤 寃곌낵 쑀궗븯寃 iNOS 寃곌낵 뿭떆 궗씠넗移댁씤쓽 寃곌낵 쑀궗븳 寃쏀뼢쓣 蹂댁엫쓣 蹂댁씠怨 엳쑝硫 씠뒗 궗씠넗移댁씤쓽 냽룄쓽議댁쟻쑝濡 Rengyolone 닾뿬援곗뿉꽌 iNOS 떒諛깅컻쁽씠 븯븯쓬쓣 븣 닔 엳뿀쑝硫 씠뒗 IL-6 TNF-α뿉 쓽빐 議곗젅릺뒗 씠 떒諛깅컻쁽쓽 湲곗쟾쓣 怨좊젮븯怨 蹂 븣 빀떦븯떎怨 蹂 닔 엳떎. 긽꽭븳 뿼利앹븯湲곗쟾뿉 븯뿬꽌 썑 뿰援ш 븘슂븯硫 븘留덈룄 rengyolone媛 씪젴쓽 뿼利앸컻쁽떊샇泥닿퀎뿉꽌 빐젣 뿭븷쓣 뻽뿀쓣 寃껋씠씪뒗 궗猷뚮맂떎. 븯吏留 Rengyolone쓽 媛꾩뿼利 諛쒗쁽 삁諛⑺슚怨쇰 궡렣蹂닿린 쐞븯뿬 吏꾪뻾븳 pre 援(6二 닾뿬)怨 post 援(4二 닾뿬) 궗씠뿉 뿼利앹씤옄뱾 媛꾩뿉 넻怨꾪븰쟻쑝濡 쑀쓽븳 李⑥씠뒗 뾾뿀떎.

蹂 뿰援ъ뿉꽌 留뚯꽦뿼利 룞臾쇰え뜽뿉꽌 rengyolone 닾뿬뒗 넂븘吏 궗씠넗移댁씤쓽 냽룄瑜 븯떆궎硫 愿젴뿼利앹씤옄쓽 諛쒗쁽쓣 吏븿쓣 븣 닔 엳뿀떎. Rengyolone 닾뿬媛 뿼利앹븯뿉 슚怨쇨 엳쓬쓣 븣 닔 엳뿀吏留 뿼利 cascade 궡뿉꽌 젙솗븳 湲곗쟾뿉 븳 遺꾩꽍 뼢썑 뿰援ш낵젣씠떎. 蹂 뿰援ш껐怨쇰뒗 誘몃옒뿉 rengyolone쓽 솢슜뿉 엳뼱 以묒슂븳 옄猷뚮줈 솢슜맆 닔 엳쓣 寃껋씠硫 媛꾩뿼利앷낵 愿젴맂 썑蹂댁빟젣濡 궗슜맆 닔 엳쓣 寃껋씠씪怨 궗猷뚮맂떎.

ACKNOWLEDGEMENT

This research was supported by the Korea Research Foundation (NRF-2017R1C1B5076959).

CONFLICT OF INTEREST

No potential conflict of interest relevant to this article was reported.

Acknowledgments
This research was supported by the Korea Research Foundation (NRF-2017R1C1B5076959).
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