当前位置:首页 期刊杂志

诃子对肝脏保护作用的研究进展

时间:2024-05-15

李贤 苏秀兰

[摘要]诃子是一种广泛记载于中药、蒙药和藏药经典方中的传统植物药物,成分丰富多样,主要含鞣质类、酚酸类和三萜酸类物质,可用于水煎液、提取液以及各种炮制品。诃子具有除传统的抗菌、体外抗氧化、清除自由基和抗肿瘤等功效,还具有保护肝脏的功效。诃子药理作用较多,机制复杂,现代临床研究显示,诃子是通过减毒抗氧化、降酶保肝、抑制肝癌细胞增殖及激活调节核因子红血球相关因子2(Nrf2)、AKT/Nrf2或p53等信号通路来诱导肿瘤细胞凋亡一系列方式来保护肝脏免受损伤。本文对诃子的保肝作用机制进行综述,为诃子的研发和临床应用提供参考。

[关键词]诃子;减毒;保肝作用

[中图分类号] R285.6          [文献标识码] A          [文章编号] 1674-4721(2019)8(c)-0022-04

[Abstract] Terminalia chebula is a kind of traditional plant medicine widely recorded in the classical prescriptions of traditional Chinese medicine, Mongolian medicine and Tibetan medicine. It contains tannins, phenolic acids and triterpene acids. It can be used in water decoction, extracts and various processed products. In addition to traditional antimicrobial, antioxidant, free radical scavenging and anti-cancer effects, Terminalia chebula also has the effect of protecting liver. Terminalia chebula has many pharmacological effects and complex mechanisms. Modern clinical studies have shown that Terminalia chebula can protect the liver from injury by reducing toxicity and antioxidation, reducing enzymes and protecting the liver, inhibiting the proliferation of hepatocellular carcinoma cells and activating signal pathways such as regulating nuclear factor red blood cell related factor 2 (Nrf2), AKT/Nrf2 or p53 to induce apoptosis of tumor cells. In this paper, the mechanism of liver protection of Terminalia chebula was reviewed to provide references for the research and development and clinical application of Terminalia chebula L.

[Key words] Terminolia chebula; Reduce toxicity; Hepatoprotective effect

肝损伤是多种慢性肝病发展的关键过程,严重影响患者的健康。肝病是可以预防的,而寻找安全有效的药物成分是预防肝损伤的关键[1-2]。在医学实践中,诃子作为中草药在肝病的治疗中发挥着重要作用。研究显示,诃子的主要作用是体外抗氧化、清除自由基[3]、抗炎[4]、降血糖[5]和作为强心治疗药物[6]等,也因其具有多重作用,在民间广泛应用,治疗多种疾病[7]。近年来对诃子抗肿瘤和保护肝脏的研究日益增多,对预防肝损伤作用机制的研究尚不完善。因此,本文总结了诃子的化学成分和提取方法,归纳了保护肝脏的作用机制、临床应用情况和未来发展趋势,为诃子的进一步研究和将来的临床应用提供参考。

1诃子概述

诃子(Terminalia chebula),又名诃黎勒,蒙医学上称为阿如拉(Arura),颜色为黄棕色或暗棕色,形状为长圆形或卵圆形,无臭,味道酸涩后甘甜,是一味功效众多,用途广泛的药物。在我国,诃子产量丰富,主要分布在云南、西藏、广东、广西,福建等地,也是中华人民共和国药典收载的传统药物品种[8-9]。诃子中含有脂肪族化合物、酚酸类、鞣质类、三萜类、黄酮类和挥发油等[10],目前已分离得到大约几十种酚酸类及鞣质类化合物。酚酸类成分包括奎宁酸、诃子次酸、没食子酸甲酯、莽草酸等[11]。鞣质成分包括诃子酸、诃黎勒酸、原诃子酸、诃子素、诃子鞣质,1,3,6-三没食子酰葡萄糖等[12]。诃子中的三萜类成分主要是五环三萜,包括阿江榄仁素、马斯里酸[13]、诃子醇、2α-羟基乌苏酸等。黄酮类包括芦丁、槲皮素、槲皮素-3-O-鼠李糖苷等[14]。其他成分有番泻苷、胡萝卜苷、微生物P、微生物C、阿拉伯糖、葡萄糖、谷氨酸、赖氨酸、油酸、亚油酸、多酚氧化酶、过氧化物酶和鞣酸酶等[15]。

2诃子的保肝成分

2.1诃子水煎液

近期研究中,用95%乙醇从诃子干果中提取的水煎液具有明显的抗氧化、保肝和膜稳定作用[16]。有研究显示,以诃子为主要来源的水煎液对小鼠有剂量依赖性的肝损伤风险,但在大鼠亚急性毒性實验中并未显示存在肝毒风险,其可能是给药剂量未达到大鼠的最大给药剂量[17]。室温下浸渍法制备的诃子提取液进一步用乙酸乙酯和水分别进行分馏,得到的产物与粗提物相比,各组分的自由基清除活性较高,且乙酸乙酯分馏组表现出最大的自由基清除活性[18]。

[2]Thawley V.Acute liver injury and failure[J].Vet Clin North Am Small Anim Pract,2017,47(3):617-630.

[3]Rahimi VB,Shirazinia R,Fereydouni N,et al.Comparison of honey and dextrose solution on post-operative peritoneal adhesion in rat model[J].Biomed Pharmacother,2017,92(3):849-855.

[4]Kher MN,Sheth NR,Bhatt VD.In vitro antibacterial evaluation of terminalia chebula as an alternative of antibiotics against bovine subclinical mastitis[J].Anim Biotechnol,2019, 30(2):151-158.

[5]Baradaran RV,Reza AV,Reza S,et al.Protective effects of hydro-ethanolic extract of,terminalia chebula,on primary microglia cells and their polarization(M1/M2, balance)[J].Mult Scler Relat Disord,2018,25(1):5-13.

[6]Thangadurai R,Venilla MA,Shanmugam PS.Management of mastitis in dairy cattle using herbal combination[J].J Krishi Vigyan,2017,5(2):164-167.

[7]Yeasmin,Akhter QS,Tasnim,et al.Hepatoprotective effect of terminalia chebula(haritaki)on serum bilirubin in paracetamol induced liver damage in wister albino rats[J].Dinajpur Med Col J,2016,9(1):78-83.

[8]Kumar R,Arora R,Agarwal A,et al.Protective effect of Terminalia chebula against seizures,seizure-induced cognitive impairment and oxidative stress in experimental models of seizures in rats[J].J Ethnopharmacol,2018,215(1):124-131.

[9]Moavero R,Santarone ME,Galasso C,et al.Cognitive and behavioral effects of new antiepileptic drugs in pediatric epilepsy[J].Brain Dev,2017,39(6):464-469.

[10]王嘉倫,王培杰,易智威,等.诃子的化学成分、药理作用及炮制配伍应用研究进展[J].中医药信息,2016,33(3):123-126.

[11]刘芳,秦红飞,刘松青.诃子化学成分与药理活性研究进展[J].中国药房,2012,23(7):670-672.

[12]周坤,简平,梁文仪,等.藏药大三果化学成分及药理作用研究进展[J].世界科学技术-中医药现代化,2018,20(9):130-136.

[13]杨俊荣,孙芳云,李志宏,等.诃子的化学成分研究[J].天然产物研究与开发,2008,20(3):450-451.

[14]阳小勇,唐荣平.诃子化学成分的研究[J].西昌学院学报,2012,26(2):65-66.

[15]张媛媛,曾慧婷,袁源见,等.藏药诃子的化学成分与药理活性研究进展[J].中国药房,2018,632(14):135-139.

[16]Tasduq SA,Singh K,Satti NK,et al.Terminalia chebula(fruit)prevents liver toxicity caused by sub-chronic administration of rifampicin,isoniazid and pyrazinamide in combination[J].Hum Exp Toxicol,2006,25(3):111-118.

[17]金家金.诃子肝毒性研究及高内涵肝毒性筛选方法的初探[D].北京:北京中医药大学,2015.

[18]Fei W,Liang X,He M.Effects of different processing methods in Tibet on content of chebulinic acid in Terminalia chebula Retz[J].J Chin Pharm Sci,2017,26(3):230-234.

[19]Sarkar R,Hazra B,Mandal N.Reducing power and iron chelating property of Terminalia chebula(Retz.)alleviates iron induced liver toxicity in mice[J].BMC Complement Altern Med,2012,12:144.

[20]衣丽娜,尹小英,江一帆,等.分子印迹技术高效分离中药活性成分的应用[J].国际药学研究杂志,2012,39(4):307-310.

[21]李刚,张述禹,王玉华,等.诃子提取物及含药血清对大鼠肝细胞损伤保护作用的研究[J].时珍国医国药,2010,21(7):1707-1709.

[22]Kim JH,Koo YC,Hong CO,et al.Mutagenicity and oral toxicity studies of terminalia chebula[J].Phytother Res,2012,26(1):39-47.

[23]廖礼.诃子不同炮制品对小鼠急性肝损伤保护作用及肠道运动的影响研究[D].成都:四川农业大学,2015.

[24]Kalra P,Karwasra R,Gupta YK,et al.Terminalia chebula supplementation attenuates cisplatin-induced nephrotoxicity in Wistar rats through modulation of apoptotic pathway[J].Nat Prod Res,2019,33(11):1641-1645.

[25]Kim MS,Lee DY,Lee J,et al.Terminalia chebula extract prevents scopolamine-induced amnesia via cholinergic modulation and anti-oxidative effects in mice[J].BMC Complementary Altern Med,2018,18(1):136-146.

[26]Anuradha U.In vitro antioxidant and hepatoprotective effect of leaf galls of terminalia chebula retz,against ccl4 induced oxidative stress in liver slice culture model[J].Indian J Nat Prod Resour,2015,4(1):13-16.

[27]姜慧,李克琴,李旭,等.訶子有效成分组对实验性肝纤维化的影响[J].国际药学研究杂志,2013,40(5):611-614.

[28]Yoskiki K.Antitumor agents,1291 tannins and related compounds as selective cytotoxic agents[J].J Nat Prod,2002,55(8):1033-1043.

[29]连红,黄庆柏,赵余庆.中药诃子的化学成分与生物活性研究进展[J].亚太传统医药,2008,6(4):46-48.

[30]包志强.诃子水提取物对肺癌、肝癌细胞及腹水瘤细胞抑制作用的实验研究[D].呼和浩特:内蒙古医科大学,2011.

[31]Nanda A,Suyila Q,Xian L,et al.Hepatoprotective Mongolian prescription Ⅱ enhances the antitumor effects of chemotherapeutics in hepatocellular carcinoma xenografts[J].Pathol Res Pract,2017,213(5):531-540.

[32]Qi Z,Ci X,Huang J,et al.Asiatic acid enhances Nrf2 signaling to protect HepG2 cells from oxidative damage through Akt and ERK activation[J].Biomed Pharmacother,2017,88(1):252-259.

[33]Jung HL,Yang SY,Pyo MC,et al.Protective effects of chebulic acid from terminalia chebula retz against t-BHP-induced oxidative stress by modulations of Nrf2 and its related enzymes in HepG2 cells[J].Food Sci Biotechnol,2018,28(2):555-562.

[34]Park JY,Kang KS,Lee HJ.Protection effect of cyanidin 3-\r,O\r,-Glucoside against oxidative stress-induced HepG2 cell death through activation of akt and extracellular signal-regulated kinase pathways[J].B Korean Chem Soc,2017,38(11):1316-1320.

[35]Carvalho NCD,Neves SP,Dias RB,et al.A novel ruthenium complex with xanthoxylin induces S-phase arrest and causes ERK1/2-mediated apoptosis in HepG2 cells through a p53-independent pathway[J].Cell Death Dis,2018,9(2):79.

(收稿日期:2019-06-20  本文编辑:刘克明)

免责声明

我们致力于保护作者版权,注重分享,被刊用文章因无法核实真实出处,未能及时与作者取得联系,或有版权异议的,请联系管理员,我们会立即处理! 部分文章是来自各大过期杂志,内容仅供学习参考,不准确地方联系删除处理!