Effect of picroliv on regeneration of liver after partial hepatectomy in rats

After partial hepatectomy in rats certain biochemical parameters in liver registered a maximal increase at varying periods of time, glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT) (6 h), lipid peroxides (12 h); DNA, RNA (24 h) and acid ribonuclease, acid phosphatase (48 h). In contrast, other parameters registered a maximal decrease after 6 h (glycogen) or 24 h (total proteins, cytochrome P₄₅₀ and cytochrome b₅). Subsequently, all these parameters started recovering towards their normal values which were attained in all parameters measured except RNA, glycogen, cytochrome h₅ and acid ribonuclease. When partial hepatectomy was performed in rats fed 12 mg/kg body wt picroliv (an iridoid glycoside fraction of Picrorhiza kurroa) once daily for 7 days before killing, there was no significant difference in the time or degree of maximal changes but the rate of recovery in most of the biochemical parameters was faster. These results indicate that picroliv stimulated regeneration of liver.     

Effect of picroliv on antioxidant-system in liver of rats,after partial hepatectomy

Levels of glutamate oxaloacetate transaminase, glutamate pyruvate transaminase and alkaline phosphatase in the serum of rats increased maximally at 12 h and bilirubin at 24 h, while total proteins decreased maximally at 48 h after partial hepatectomy. The levels of total lipids, reduced glutathione, glutathione peroxidase and glutathione reductase in liver increased maximally at 12 h and catalase at 24 h, but the activities of peroxidase, glutathione-S-transferase and superoxide dismutase decreased maximally at 12 h. After the period of maximal initial increase/decrease, the changes in these parameters in liver and serum started recovering towards their prehepatectomy levels. When a similar study was performed in rats fed 12 mg/kg body wt picroliv (an iridoid glycoside fraction of Picrorhiza kurroa) once daily for 7 days, the rate of recovery of glutamate oxaloacetate transaminase, glutamate pyruvate transaminase and alkaline phosphatase in serum and total lipids, reduced glutathione, peroxidase, catalase and glutathione-S-transferase in liver was faster.     

Evaluation of antipyretic potential of Nelumbo nucifera stalk extract

The ethanol extract of stalks of Nelumbo nucifera (NNSE) was evaluated for its antipyretic potential on normal body temperature and yeast induced pyrexia in rats. NNSE showed significant activity in both the models at oral doses of 200 and 400 mg/kg. NNSE at a dose of 200 mg/kg was found to produce significant lowering of normal body temperature up to 3 h and at 400 mg/kg it caused significant lowering of body temperature up to 6 h after its administration. In the model of yeast provoked elevation of body temperature NNSE showed dose-dependent lowering of body temperature up to 4 h at both the doses and the results were comparable to that of paracetamol, a standard antipyretic agent.     

Evaluation of antipyretic potential of Leucas lavandulaefolia (Labiatae) aerial part extract

Methanol extract of Leucas lavandulaefolia (LLFE) was subjected to antipyretic evaluation with yeast-induced pyrexia in rats. A yeast suspension (10 mL/kg, s.c.) increased the rectal temperature 19 h after administration. The extract at doses of 100, 200, 400 mg/kg (i.p.) produced significant dose dependent lowering of body temperature in yeast-provoked elevation of body temperature in rats. The antipyretic effect produced was comparable to that of a standard antipyretic drug, paracetamol.     

Protective effect of Lygodium flexuosum (L.) Sw. extract against carbon tetrachloride-induced acute liver injury in rats

The hepatoprotective potential of Lygodium flexuosum (L.) Sw. was evaluated in male Wistar rats against carbon tetrachloride-induced liver damage in preventive and curative models. Toxic control and n-hexane extract-treated rats received a single dose of CCl4 (150 microL/100g, 1:1 in corn oil). Pre-treated rats were given n-hexane extracts at 200 and 100 mg/kg dose 48, 24 and 2 h prior to CCl4 administration. In post-treatment groups, rats were treated with n-hexane extract at a dose of 200 and 100 mg/kg, 2, 24 and 48 h after CCl4 intoxication. Rats pre-treated with Lygodium flexuosum remarkably prevented the elevation of serum AST, ALT, LDH and liver lipid peroxides in CCl4-treated rats. Rats treated with the extract after the establishment of CCl4 induced liver injury showed significant (p < or = 0.05) protection of liver as evidenced from normal AST, ALT, LDH and MDA levels. Hepatic glutathione levels were significantly (p < or = 0.05) increased by the treatment with the extracts in both the experimental groups. Histopathological changes induced by CCl4 were also significantly (p < or = 0.05) reduced by the extract treatment in preventive and curative groups. Phytochemical studies revealed the presence of saponins, triterpenes, sterols and bitter principles in Lygodium flexuosumn-hexane extract which could be responsible for the possible hepatoprotective action.     

Inhibitory effect of Oren-gedoku-to (Huanglian-Jie-Du-Tang) extract on hepatic triglyceride accumulation with the progression of carbon tetrachloride-induced acute liver injury in rats

The inhibitory effect of Oren-gedoku-to (Huanglian-Jie-Du-Tang) extract (TJ-15) on hepatic triglyceride (TG) accumulation with the progression of acute liver injury was examined in rats intoxicated with carbon tetrachloride (CCl₄). TJ-15 at a dose of 100, 250 or 500 mg/kg body weight (BW) was orally administered to male Wistar rats aged 7 weeks, 6 h after the intraperitoneal injection of CCl₄ (1.0 ml/kg BW) at which time apparent liver injury and hepatic TG accumulation occurred. TJ-15 significantly prevented not only the progression of liver injury but also inhibited hepatic TG accumulation with the progression of the injury in a dose-dependent manner when these effects were examined 24 h after CCl₄ injection. In CCl₄-untreated rats with oral administration of TJ-15 at a dose of 100, 250 or 500 mg/kg BW, liver and serum TG concentrations decreased depending on the dose of the herbal medicine. These results indicate that in rats intoxicated once with CCl₄, orally administered TJ-15 can inhibit hepatic TG accumulation with the progression of acute liver injury by its decreasing action on serum and liver TG levels, leading to a prevention of the progression of the liver injury.     

Cholesterol-lowering activity of the aqueous extract of Spergularia purpurea in normal and recent-onset diabetic rats

The purpose of this study was to examine the effect of single and repeated oral administration of the aqueous extract of Spergularia purpurea (SP) at a dose of 10mg/kg in normal and streptozotocin-induced diabetic rats. In normal rats, the aqueous extract of SP induced a significant decrease of the plasma cholesterol concentrations 6h after a single oral administration (P<0.05) and 2 weeks after repeated oral administration (P<0.05). The plasma triglycerides levels increased significantly 6h after a single oral administration (P<0.05) and decreased 2 weeks after repeated oral administration (P<0.05). In diabetic rats, SP treatment caused a significant decrease of plasma cholesterol levels after a single (P<0.01) and repeated (P<0.01) oral administration. A significant increase of triglycerides levels was observed 6h after a single oral administration of the SP aqueous extract (P<0.01). One week after repeated oral administration of SP aqueous extract, the plasma triglycerides levels were significantly decreased (P<0.005) and still dropped after 2 weeks (P<0.01). On the other hand, the repeated oral administration of SP aqueous extract caused a significant decrease of body weight after 2 weeks of treatment in both normal (P<0.001) and diabetic (P<0.01) rats. We conclude that the aqueous extract of SP exhibits a cholesterol and body weight-lowering activities in both normal and severe hyperglycaemic rats.     

黄芪总黄酮对扑热息痛所致小鼠肝损伤防护作用的研究

目的 :研究黄芪总黄酮 (TFA)对扑热息痛所致肝损伤的防护作用。方法 :用 1%羧甲基纤维素钠 10ml·kg^-1,TFA10 0mg·kg^-1或维生素C (Ascorbicacid ,VC) 1000mg·kg^-1给小鼠灌胃 1h后 ,灌扑热息痛 1000mg·kg^-1,观察小鼠死亡率的变化 ;提前 1h用不同剂量的TFA或VC处理后 ,再灌 400mg·kg^-1的扑热息痛 ,检测血清酶学和肝脏组织学的改变。结果 :给小鼠扑热息痛 1000mg·kg^-1灌胃组 ,24h后可致 80 %小鼠死亡 ;提前 1h用TFA10 0mg·kg^-1或VC灌胃其死亡率可分别下降至 20%和0%。血清转氨酶 (ALT)和病理切片显示当给 400mg·kg^-1扑热息痛灌胃 24h后即可引起严重肝损伤 (ALT升高和肝组织大面积坏死 ,P<0.001)。TFA或VC预防组 (提前1h给药)的肝损伤程度与对照组比较明显减轻 ,其作用强度与药物浓度成正比。结论 :TFA对扑热息痛所致肝损伤有保护作用。     

Protective Effects of a Purified Saponin Mixture from Astragalus corniculatus Bieb., in vivo Hepatotoxicity Models

In this study, the in vivo effects of a purified saponin mixture (PSM), obtained from Astragalus corniculatus Bieb., were investigated using two in vivo hepatotoxicity models based on liver damage caused by paracetamol (PC) and carbon tetrachloride (CCl₄). The effects of PSM were compared with silymarin. Male Wistar rats were challenged orally with 20% CCl₄ or PC (2 g/kg) four days after being pre‐treated with PSM (100 mg/kg) or silymarin (200 mg/kg). A significant decrease of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase (LDH) activities and glutathione (GSH) levels and an increase of malondialdehyde (MDA) quantity was observed after CCl₄ and PC administration alone. PSM pre‐treatment decreased serum transaminases and LDH activities and MDA levels and increased the levels of cell protector GSH. Biotransformation phase I enzymes were also assessed in both models. In the CCl₄ hepatotoxicity model, pre‐treatment with PSM or silymarin resulted in significantly increased activities of ethylmorphine‐N‐demethylase and aniline 4‐hydroxylase activity and cytochrome P450, compared to the CCl₄ only group. Neither silymarin nor PSM influenced PC biotransformation. Our results suggest that PSM, obtained from A. corniculatus, Bieb. showed in vivo hepatoprotective and antioxidant activities against CCl₄ and PC‐induced liver damage comparable to that of silymarin. Copyright © 2012 John Wiley & Sons, Ltd.     

Hepatoprotective effects of Taiwan folk medicine: Alternanthera sessilis on liver damage induced by various hepatotoxins

The hepatoprotective effects of the Taiwanese herb ‘Horngtyan-wu’ (Alternanthera sessilis (L.) DC.) were investigated in three kinds of experimental animal model. Acute hepatitis was induced by various chemicals such as carbon tetrachloride (31.25 μL/kg, i.p.) or acetaminophen (paracetamol; 600 mg/kg, i.p.) in mice and D(+)-galactosamine (188 mg/kg, i.p.) in rats. When treated with A. sessilis (300 mg/kg, p.o.) at 2, 6 and 10 h, a reduction in elevation of serum glutamate oxaloacetic transaminase (SGOT) and glutamate pyruvic transaminase (SGPT) levels could be observed at 24 h after administration of the three hepatotoxins. These serological observations were also confirmed by histopathological examinations including centrilobular necrosis, eosinophilic bodies, pyknotic nuclei, microvesicular degeneration of hepatocytes and others. The liver microscopic examination showed a noted improvement in groups receiving A. sessilis. All pharmacological and histopathological effects were compared with observations using the hepatoprotective Chinese herb, Bupleurum chinense (Family Umbelliferae). It was confirmed that A. sessilis has hepatoprotective effects against liver injuries induced by hepatotoxins with different mechanisms.     

Quercetin reduced the formation of N‐acetyl‐p‐benzoquinoneimine,a toxic metabolite of paracetamol in rats and isolated rat hepatocytes

N‐acetyl‐p‐benzoquinoneimine (NAPQI) is toxic metabolite of paracetamol formed primarily by cytochrome P4502E1 (CYP2E1) metabolic pathway when administered at therapeutic doses or overdose. The influence of quercetin (flavonoid) on the bioactivation of paracetamol to NAPQI was investigated using rat liver microsomes and rats in vivo. Paracetamol (80 mg/kg) was administered orally without or with silymarin (100 mg/kg), a known inhibitor of CYP2E1, CYP3A4 and quercetin (10 and 20 mg/kg) to rats for 15 consecutive days. Area under the plasma concentration–time curve (AUC_0‐∞) and the peakplasma concentration (C_max) of paracetamol were dose‐dependently increased with quercetin (10 and 20 mg/kg) compared to paracetamol control group (p < 0.001). On the other hand, the AUC_0‐∞ and C_max of NAPQI were decreased significantly with quercetin. The same results were observed with silymarin also. The elevated liver and kidney functional enzymes/compounds were significantly reduced by quercetin and silymarin compared to paracetamol control group. The formation of NAPQI was reduced in the incubation samples in presence of quercetin in experiment using isolated rat hepatocytes. The presentstudy results revealed that quercetin might be inhibited the CYP2E1‐mediated metabolism of paracetamol; thereby decreased the formation of NAPQI and protected the liver and kidney.     

基于制马钱子在大鼠体内药动学行为的蓄积可能性研究

目的研究临床剂量下制马钱子在大鼠体内多次给药的药动学过程及各组织脏器中的含量,探讨马钱子在体内蓄积的可能性。方法大鼠分别单次、多次ig给予制马钱子,采用UPLC-Q-Orbitrap HRMS法测定大鼠血浆和组织中马钱子碱和士的宁的血药浓度,比较不同给药次数下2种成分的药动学和组织分布差异,探讨其在体内是否存在蓄积。结果制马钱子单次给药后,马钱子碱和士的宁的主要药动学参数半衰期(t_(1/2))为10.59、8.39 h,达峰时间(t_(max))为0.77、0.64 h,t_(1/2Ka)为5.38、2.63 h,峰浓度(C_(max))为2.97、10.83 ng/L,药时曲线下面积(AUC_(0～t))为87.36、172.24 ng·h/L,药物消除率(CL/F)为40 637.08、38 370.26 L/(h·kg);制马钱子中马钱子碱与士的宁的血药浓度在大鼠给药3 d后达到稳态。末次给药后,制马钱子中马钱子碱和士的宁的主要药动学参数分别为:t_(1/2)为7.07、4.75 h,t_(max)为0.48、0.46 h,t_(1/2Ka)为3.23、1.09 h,C_(max)为5.77、34.83 ng/L,AUC_(0～t)为32.80、107.86 ng·h/L,CL/F为75 920.52、43 871.54 L/(h·kg)。与单次给药比较,马钱子碱和士的宁在多次给药后,肝、肾组织中的含量明显减少,其他组织无明显变化。结论制马钱子中马钱子碱与士的宁在大鼠体内单次、多次给药的药动学过程均符合一室模型,体内血药浓度变化过程趋势基本一致。两者在大鼠体内具有吸收速度快的药动学特征。给药3 d后,马钱子碱与士的宁血药浓度达到稳态,并未出现随着给药次数的增加,血药浓度持续增加的现象。单次和多次给药后的各组织含量并未增高。提示在安全给药剂量下,多次给予制马钱子,不会引起马钱子碱与士的宁在大鼠体内血药浓度的持续叠加升高,导致中毒现象的发生。     

栀子苷对正常大鼠急性肝、肾毒性的时-毒关系分析

目的:考察栀子苷对正常大鼠急性肝、肾毒性的时-毒关系,为栀子临床安全应用提供科学依据。方法:Wistar大鼠110只,随机分为正常组,给药后不同时间组(0.5,1,2,4,8,12,24,48,72 h组),除正常组灌服生理盐水外,其余组按剂量1.2 g·kg-1灌服栀子苷。按组在灌胃后相应时间眼眶静脉取血,离心取血清,检测血清天门冬氨酸氨基转移酶(AST),碱性磷酸酶(ALP),丙氨酸氨基转移酶(ALT),总胆红素(TBIL),尿素氮(BUN),肌酐(Cr)活性,观察肝肾毒性损伤情况。结果:与正常组比较,在给药12 h后AST,ALP,ALT,TBIL,BUN,Cr明显升高(P0.05,P0.01),在给药24,48 h后AST,ALP,ALT,TBIL,BUN,Cr出现峰值,72 h后明显下降,240 h可见基本恢复正常。病理组织学检查出现不同程度的汇管区炎细胞浸润、肝细胞坏死、汇管区胆管轻度增生、纤维组织增生等病理变化。结论:栀子苷(1.2 g·kg-1)对正常大鼠存在急性肝、肾毒性且存在一定的时-毒关系。     

Anti-diabetic activity of green tea polyphenols and their role in reducing oxidative stress in experimental diabetes

An aqueous solution of green tea polyphenols (GTP) was found to inhibit lipid peroxidation (LP), scavenge hydroxyl and superoxide radicals in vitro. Concentration needed for 50% inhibition of superoxide, hydroxyl and LP radicals were 10, 52.5 and 136 micro g/ml, respectively. Administration of GTP (500 mg/kg b.wt.) to normal rats increased glucose tolerance significantly (P<0.005) at 60 min. GTP was also found to reduce serum glucose level in alloxan diabetic rats significantly at a dose level of 100 mg/kg b.wt. Continued daily administration (15 days) of the extract 50, 100 mg/kg b.wt. produced 29 and 44% reduction in the elevated serum glucose level produced by alloxan administration. Elevated hepatic and renal enzymes produced by alloxan were found to be reduced (P<0.001) by GTP. The serum LP levels which was increased by alloxan and was reduced by significantly (P<0.001) by the administration of 100 mg/kg b.wt. of GTP. Decreased liver glycogen, after alloxan administration showed a significant (P<0.001) increase after GTP treatment. GTP treated group showed increased antioxidant potential as seen from improvements in superoxide dismutase and glutathione levels. However catalase, LP and glutathione peroxidase levels were unchanged. These results indicate that alterations in the glucose utilizing system and oxidation status in rats increased by alloxan were partially reversed by the administration of the glutamate pyruvate transaminase.     

Preventive and curative effects of Berberis aristata Fruit extract on paracetamol- and CCl4-induced hepatotoxicity

The effect of an aqueous-methanol extract of Berberis aristata fruits (Berberidaceae) was investigated against paracetamol- and CCl₄-induced hepatic damage. Paracetamol produced 100% mortality at a dose of 1 g/kg in mice while pre-treatment of animals with crude extract (500 mg/kg) reduced the death rate to 10%. Pre-treatment of rats with fruit extract (500 mg/kg, orally twice daily for 2 days) prevented (p<0.05) the paracetamol (640 mg/kg) as well as CCl₄ (1.5 mL/kg)-induced rise in serum transaminases (GOT and GPT). Post-treatment with three successive doses of extract (500 mg/kg, 6h) restricted the hepatic damage induced by acetaminophen (p<0.01) but CCl₄-induced hepatotoxicity was not altered (p>0.05). Plant extract (500 mg/kg) caused significant prolongation (p<0.01) in pentobarbital (75 mg/kg)-induced sleep as well as increased strychnine-induced lethality in mice suggestive of inhibitory effect on microsomal drug metabolizing enzymes (MDME). These results indicate that the crude extract of Berberis aristata fruits exhibits hepatoprotective action partly through MDME inhibitory action.     

Hypoglycaemic activity of Anthocleista vogelii (Planch) aqueous extract in rodents

The hypoglycaemic effect of Anthocleista vogelii was studied in mice, rats and rabbits. Aqueous extract of the plant obtained by infusion from finely pulverized root was used. The extract (100, 400 and 800 mg/kg) induced significant hypoglycaemic activity in a dose-related fashion at 2 h after oral administration in mice and rats with ED₂₅ of 250 mg/kg and 350 mg/kg respectively. The extract (800 mg/kg, orally) similarly induced statistically significant lowering of blood glucose levels at 8 h in normoglycaemic rabbits. The extract (400 mg/kg and 800 mg/kg, orally) also caused reduction of blood glucose levels in alloxan-induced diabetic animals. The results of this study indicate that the aqueous extract of the roots of Anthocleista vogelii possess favourable hypoglycaemic activity both in normo and hyperglycaemic animals compared to chlorpropamide as a standard.     

桃仁承气汤治疗百草枯中毒肺损伤的实验研究

目的观察桃仁承气汤治疗百草枯(PQ)中毒大鼠肺损伤的效果,探讨其保护作用及机制,为临床治疗百草枯中毒提供依据。方法1)清洁级雄性Wistar大鼠40只,随机分为空白对照组、桃仁承气汤对照组、PQ模型组、桃仁承气汤治疗组。PQ模型组、桃仁承气汤治疗组予PQ溶液(100 mg/kg)灌胃染毒;桃仁承气汤治疗组染毒后3、9、24、48 h予桃仁承气汤灌胃(5.13 g/kg);空白对照组以等量0.9%氯化钠注射液灌胃;桃仁承气汤对照组予桃仁承气汤3、9、24、48 h灌胃。PQ灌胃后72 h,处死大鼠,用酶联免疫吸附(ELISA)方法检测大鼠血清肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、超氧化物歧化酶(SOD)、丙二醛(MDA)、高迁移族蛋白(HMGB1)变化情况;开胸取肺组织,测肺干/湿重比(D/W)比值;观察肺病理变化并评分。2)同样方法构建模型和分组,观察并记录PQ中毒大鼠一般状况;30 min后观察记录染毒后72 h各组死亡数,计算各组大鼠生存曲线。结果与PQ模型组比较,桃仁承气汤治疗组D/W比值明显上升,肺病理学评分下降,TNF-α、IL-6、HMGB1水平明显下降,SOD水平明显升高,MDA水平明显下降(P<0.05)。PQ模型组大鼠中毒后72 h存活率为60%,低于桃仁承气汤治疗组的90%(P<0.05)。结论桃仁承气汤能延长PQ中毒大鼠的生存时间,降低炎症反应、过氧化损伤等,抑制HMGB1,减轻PQ中毒肺损伤。     

清热化湿疏肝祛瘀法对急性肝内胆汁淤积大鼠的防治作用

目的:观察清热化湿疏肝祛瘀法组成之中药复方对急性肝内胆汁淤积大鼠肝功能的影响。方法:采用异硫氰酸萘酯(ANIT)诱导大鼠急性肝内胆汁淤积,同时以5g/(kg.d)的中药复方进行干预,熊去氧胆酸[90mg/(kg.d)]为对照,于给ANIT后24、48、72h随机处死模型组及各药物干预组1/3数量的大鼠,取肝组织行HE染色在光镜下观察病理学变化,取血清以全自动生化仪检测肝功能。结果:模型组大鼠肝组织损伤及肝功能所测各项指标在应用ANIT后24h、48h及72h均明显增高,并以48h时为高峰;应用中药复方及熊去氧胆酸干预组大鼠的肝功能各项指标在应用ANIT后24h及48h时较相对应的模型组显著下降,72h时则与对应的模型组无统计学差异。结论:清热化湿疏肝祛瘀法中药可明显改善急性肝内胆汁淤积大鼠肝组织损伤及肝功能状况。     

Blood chemistry of rats pretreated with Mucuna pruriens seed aqueous extract MP101UJ after Echis carinatus venom challenge.

The effect of a lethal Echis carinatus venom on serum enzyme levels and blood plasma coagulation parameters in rats pretreated with Mucuna pruriens seed aqueous extract MP101UJ (21 mg/kg body wt) 24 h and 3 wk before i.p venom injection (0.50 mg/kg rat) and rats injected with venom alone (0.50 mg/kg body wt) was investigated. The enzyme levels and coagulation parameter levels were measured 4 h after venom administration. The results showed that the increased enzymes lactate dehydrogenase (LDH), glutamic pyruvic transaminase (SGPT), creatinine kinase (CK) and changed coagulation parameters D-Dimer and Quick levels due to the venom effect were inhibited by M. pruriens seed aqueous extract MP101UJ in pretreated rats. Rats pretreated with a single dose (21 mg/kg and multiple doses 21 mg/kg rat) of extract MP101UJ maintained the normal enzyme levels and showed an anticoagulant effect as evidenced by the high PTT level which was also observed in venom treated animals. D-Dimer and Quick values were normal. However, the extract MP101UJ appeared to significantly inhibit the lethal venom induced myotoxic, cytotoxic and coagulation activities in experimental animals.     

Evaluation of antipyretic potential of Cleome viscosa Linn. (Capparidaceae) extract in rats

The antipyretic activity of a methanol extract of Cleome viscosa Linn. (CVME) was investigated for its potential on normal body temperature and yeast-induced pyrexia in albino rats. The CVME, at doses of 200, 300, and 400mg/kg BW p.o., showed significant reduction in normal body temperature and yeast-provoked elevated temperature in a dose-dependent manner. The effect also extended upto 5h after the drug administration. The anti-pyretic effect of CVME was comparable to that of paracetamol (150mg/kg p.o.), a standard anti-pyretic agent.