毛萼香茶菜醇提物对干酵母致热大鼠解热机制研究
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摘要
为探究毛萼香茶菜醇提物的解热药效及作用机制,采用背部皮下注射干酵母构建SD大鼠发热模型。实验分为空白组、模型组、阳性药扑热息痛组(150 mg/kg)、毛萼香茶菜醇提物低高剂量组(200 mg/kg、800 mg/kg)、迷迭香酸组(150 mg/kg)、蓟黄素组(150 mg/kg)、毛萼晶D组(150 mg/kg)。动物造模4 h后给药治疗,造模8 h后眼眶采血和组织取材。通过测定造模后各组大鼠肛温的变化考察药效,检测血清中肿瘤坏死因子(TNF-α)和精氨酸加压素(AVP)、下丘脑前列腺素E2(PGE2)和环磷酸腺苷(c AMP)和脑腹中隔区精氨酸加压素(AVP)的含量初步探究作用机制。结果显示,总提取物能够显著抑制大鼠肛温的上升,降低血清中TNF-α含量,升高AVP含量,并降低下丘脑中PGE2、c AMP及脑腹中隔区AVP的含量。但迷迭香酸、蓟黄素和毛萼晶D对发热大鼠肛温的上升抑制不明显,且不影响发热大鼠上述生化指标的变化。上述研究结果表明,毛萼香茶菜醇提物具有良好的解热作用,其机制可能与抑制内生致热源TNF-α、中枢体温正调节介质c AMP和PGE2的分泌,以及促进中枢体温负调节介质AVP的分泌有关,但作用物质基础还有待进一步研究。
To investigate the antipyretic effects and potential mechanism of Isodon eriocalyx ethanol extracts,the SD rats was injected by dry yeast subcutaneously to establish the model of fever. Experimental groups were divided into blank,model,positive drug paracetamol( 150 mg/kg),low doses( 200 mg/kg),high doses( 800 mg/kg) of ethanol extracts of I. eriocalyx,rosmarinic acid( 150 mg/kg),cirsimaritin( 150 mg/kg) and maoecrystal D( 150 mg/kg). After 4 hours of model establishment,the drugs were administered orally to each group; the blood and tissue samples were then collected 8 hours affer model establishment. Rectal temperature was detected to evaluate the antipyretic effects. The levels of tumor necrosis factor( TNF-α),arginine vasopressin( AVP),cyclic adenosine monophosphate( cAMP) and prostraglandin E2( PGE2) were measured to explore the potential mechanism. Results showed that the inoreased rectal temperature in rats was ameliorated by ethanol extracts of I. eriocalyx. Moreover,administration of ethanol extracts of I. eriocalyx could reduce the serum TNF-α levels and increase AVP levels in rats,decrease the levels of cAMP and PGE2 in hypothalamus and promote AVP secretion in ventral septal area of rats. However, there were no dramatic changes about rectal temperature and biochemical indicators mentioned above after administration of rosmarinic acid,cirsimaritin and maoecrystal D,respectively. In conclusion,ethanol extracts of I. eriocalyx exerted antipyretic effects on fever rats induced by yeast,which is probably due to the suppression of the secretion of TNF-α,cAMP and PGE2 and promotion of the excretion of AVP. However,the material basis of the antipyretic mechanism of this plant still remains to be further explored.
To investigate the antipyretic effects and potential mechanism of Isodon eriocalyx ethanol extracts,the SD rats was injected by dry yeast subcutaneously to establish the model of fever. Experimental groups were divided into blank,model,positive drug paracetamol( 150 mg/kg),low doses( 200 mg/kg),high doses( 800 mg/kg) of ethanol extracts of I. eriocalyx,rosmarinic acid( 150 mg/kg),cirsimaritin( 150 mg/kg) and maoecrystal D( 150 mg/kg). After 4 hours of model establishment,the drugs were administered orally to each group; the blood and tissue samples were then collected 8 hours affer model establishment. Rectal temperature was detected to evaluate the antipyretic effects. The levels of tumor necrosis factor( TNF-α),arginine vasopressin( AVP),cyclic adenosine monophosphate( cAMP) and prostraglandin E2( PGE2) were measured to explore the potential mechanism. Results showed that the inoreased rectal temperature in rats was ameliorated by ethanol extracts of I. eriocalyx. Moreover,administration of ethanol extracts of I. eriocalyx could reduce the serum TNF-α levels and increase AVP levels in rats,decrease the levels of cAMP and PGE2 in hypothalamus and promote AVP secretion in ventral septal area of rats. However, there were no dramatic changes about rectal temperature and biochemical indicators mentioned above after administration of rosmarinic acid,cirsimaritin and maoecrystal D,respectively. In conclusion,ethanol extracts of I. eriocalyx exerted antipyretic effects on fever rats induced by yeast,which is probably due to the suppression of the secretion of TNF-α,cAMP and PGE2 and promotion of the excretion of AVP. However,the material basis of the antipyretic mechanism of this plant still remains to be further explored.
引文
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[17] Zuo ZP,Wang ZB,Guo YD,et al. Fever process and characteris-tics in commonly used rat fever models[J]. Chin J Comp Med(中国比较医学杂志),2012,22(2):52-57.
[18] Zhang F,Wang D,Li X,et al. Metabolomic study of the fevermodel induced by baker's yeast and the antipyretic effects ofaspirin in rats using nuclear magnetic resonance and gas chroma-tography-mass spectrometry[J]. J Pharmaceut Biomed,2013,81/82:168-177.
[19] Wan YX. The research of Yinlai Decoction on antipyretic mecha-nism of yeast-induced rats(银莱汤对干酵母致热大鼠的解热机制研究)[D]. Beijing:Beijing University of Chinese Medi-cine,2017.
[2] Dinarello CA. Infection,fever,and exogenous and endogenouspyrogens:some concepts have changed[J]. J Endotoxin Res,2004,10(4):201-222.
[3] Liu X,Tang YP,Liu R,et al. Antipyretic and anti-inflammatoryactivities of Thais luteostoma extracts and underlying mechanisms[J]. Chin J Nat Med,2015,13(3):192-198.
[4] Panthong A,Norkaew P,Kanjanapothi D,et al. Anti-inflammatory,analgesic and antipyretic activities of the extract of gamboge fromGarcinia hanburyi Hook F[J]. J Ethnopharmacol,2007,111(2):335-340.
[5] Tao C,Li QJ,Ye LH,et al. Diterpenoids from Isodon erioealyx inGuizhou[J]. Nat Prod Res Dev(天然产物研究与开发),2015,27(1):26-30.
[6] Editorial Board of the Flora of China. Flora of China(中国植物志)[M]. Beijing:Science Press,1977,66(22):439.
[7] Sun HD,Huang SX,Han QB. Diterpenoids from Isodon speciesand their biological activities[J]. J Cheminformatics,2007,38(5):673-698.
[8] Liu M,Wang WG,Sun HD,et al. Diterpenoids from Isodon spe-cies:an update[J]. Nat Prod Rep,2017,34(9):1090-1140.
[9] Leung CH,Grill SP,Lam W,et al. Novel mechanism of inhibitionof nuclear factor-kappaB DNA-binding activity by diterpenoidsisolated from Isodon rubescens[J]. Mol Pharmacol,2005,68(2):286.
[10] Lee JH,Koo TH,Hwang BY,et al. Kaurane diterpene,kame-bakaurin,inhibits NF-kappa B by directly targeting the DNA-binding activity of p50 and blocks the expression of antiapoptoticNF-kappa B target genes[J]. J Biol Chem,2002,277(21):18411-18420.
[11] Kong LM,Deng X,Zuo ZL,et al. Identification and validation ofp50 as the cellular target of eriocalyxin B[J]. Oncotarget,2014,5(22):11354-11364.
[12] Jayanthy G,Roshana Devi V,Ilango K,et al. Rosmarinic acidmediates mitochondrial biogenesis in insulin resistant skeletalmuscle through activation of AMPK[J]. J Cellular Biochem,2017,118(7):1839-1848.
[13] Lee D,Kim KH,Lee J,et al. Protective effect of cirsimaritinagainst streptozotocin-induced apoptosis in pancreatic beta cells[J]. J Pharm Pharmacol,2017,69(7):875-883.
[14] Lu QD. Research on material basis and mechanism of BupleuriRadix,s antipyretic effects(柴胡解热作用的物质基础及作用机制的实验研究)[D]. Jinan:Shandong University of TraditionalChinese Medicine,2013.
[15] Wu YL. Antiptretic effect of modified Baihu Decoction on yeast-induced fever in rats(加减白虎汤对酵母引起大鼠发热的解热作用研究)[D]. Changchun:Jilin University,2016.
[16] Wu LL. The research of Dr Zhang's Gypsum Rice Decoction onantipyretic mechanism of yeast-induced rats(张氏石膏粳米汤对干酵母致热大鼠解热机制研究)[D]. Nanning:GuangxiUniversity of Chinese Medicine,2018.
[17] Zuo ZP,Wang ZB,Guo YD,et al. Fever process and characteris-tics in commonly used rat fever models[J]. Chin J Comp Med(中国比较医学杂志),2012,22(2):52-57.
[18] Zhang F,Wang D,Li X,et al. Metabolomic study of the fevermodel induced by baker's yeast and the antipyretic effects ofaspirin in rats using nuclear magnetic resonance and gas chroma-tography-mass spectrometry[J]. J Pharmaceut Biomed,2013,81/82:168-177.
[19] Wan YX. The research of Yinlai Decoction on antipyretic mecha-nism of yeast-induced rats(银莱汤对干酵母致热大鼠的解热机制研究)[D]. Beijing:Beijing University of Chinese Medi-cine,2017.