Hypoglycemic effects of malonyl‐ginsenosides extracted from roots of Panax ginseng on streptozotocin‐induced diabetic mice

Hypoglycemic effects of malonyl‐ginsenosides (MGR), extracted from roots of Panax ginseng, were examined in streptozotocin‐ (STZ‐) induced diabetic mice. Animals received daily intravenous injections of MGR in doses of 30, 60, 120 mg/kg. At a dose of 120 mg/kg, MGR reduced the fasting blood glucose level of diabetic mice by 77.8% (76.7 ± 8.5 mg/dl versus 345.2 ± 35.8 mg/dl, P < 0.01). The same dose also showed a marked improvement in glucose tolerance of 80% (75.3 ± 10.8 mg/dl versus 375.6 ± 43.3 mg/dl, P < 0.01) in diabetic mice after four days. The alkali hydrolysis productions of MGR, ginseng panaxadiol (PDS), malonic acid and a mixture of malonic acid with PDS, showed no effects on fasting blood glucose levels indicated the hypoglycemic effect of MGR relied on their unique esterified chemical structures. The findings from this study suggest that MGR extracted from Panax ginseng may be prescribed as adjunct to drug treatment for controlling diabetes mellitus. Copyright © 2009 John Wiley & Sons, Ltd.     

Neuroprotective Effect of Lycopene Against PTZ‐induced Kindling Seizures in Mice: Possible Behavioural,Biochemical and Mitochondrial Dysfunction

Oxidative stress and mitochondrial dysfunction are the major contributing factors in the pathophysiology of various neurological disorders. Recently, antioxidant therapies aimed at reducing oxidative stress gained a considerable attention in epilepsy treatment. Lycopene, a carotenoid antioxidant, has received scientific interest in recent years. So, the present study has been designed to evaluate the neuroprotective effect of lycopene against the pentylenetetrazol (PTZ)‐induced kindling epilepsy. Laca mice received lycopene (2.5, 5 and 10 mg/kg) and sodium valproate for a period of 29 days and PTZ (40 mg/kg i.p (Intraperitoneal)) injection on alternative days. Various behavioural (kindling score), biochemical parameters (lipid peroxidation, superoxide dismutase, reduced glutathione, catalase and nitrite) and mitochondrial enzyme complex activities (I, II and IV) were assessed in the brain. Results depicted that repeated administration of a sub‐convulsive dose of PTZ (40 mg/kg) significantly increased kindling score, oxidative damage and impaired mitochondrial enzyme complex activities (I, II and IV) as compared with naive animals. Lycopene (5 and 10 mg/kg) and sodium valproate (100 mg/kg) treatment for a duration of 29 days significantly attenuated kindling score, reversed oxidative damage and restored mitochondrial enzyme complex activities (I, II and IV) as compared with control. Thus, present study demonstrates the neuroprotective potential of lycopene in PTZ‐induced kindling in mice. Copyright © 2015 John Wiley & Sons, Ltd.     

冰片配伍黄芪甲苷和三七总皂苷通过Notch信号通路对大鼠脑缺血再灌注损伤模型的神经保护作用

目的 从Notch信号通路探讨冰片配伍黄芪甲苷（astragaloside IV,AST IV）和三七总皂苷（Panax notoginseng saponins,PNS）对大鼠脑缺血再灌注损伤（cerebral ischemia reperfusion injury,CIRI）模型的神经保护作用。方法 SD大鼠随机分为假手术组、模型组、冰片（7.5 mg/kg）组、PNS（25 mg/kg）组、AST IV（10 mg/kg）组、AST IV（10 mg/kg）+PNS（25 mg/kg）组、冰片（7.5 mg/kg）+AST IV（10 mg/kg）+PNS（25 mg/kg）低剂量组、冰片（15 mg/kg）+AST IV（20 mg/kg）+PNS（50 mg/kg）高剂量组、依达拉奉（4 mg/kg）组。假手术组、模型组ig 0.5% CMC-Na,依达拉奉组ip相应药物,其余各组ig相应药物,2次/d,间隔12 h。末次给药后2 h采用线栓法阻断大鼠右侧大脑中动脉,建立CIRI模型。缺血2 h,再灌注22 h后,进行神经功能缺损评分;HE染色法观察缺血皮质区病理变化;免疫组化法检测神经元特异性核蛋白（neuron specific nuclear,NeuN）、内皮屏障抗原蛋白（endothelial barrier antigen,EBA）表达;Western blotting法检测血管内皮生长因子（vascular endothelial growth factor,VEGF）、Notch1、Notch胞内域（intracellular domain of Notch,NICD）蛋白表达。结果 模型组大鼠神经功能缺损评分和细胞损伤率显著增加（P<0.01）;各给药组大鼠神经功能缺损评分和细胞损伤率显著降低（P<0.05、0.01）,冰片+AST IV+PNS组的效应强于各药物单用及AST IV+PNS组（P<0.05、0.01）。模型组大鼠缺血皮质区NeuN、EBA蛋白表达均显著降低（P<0.01）;各给药组NeuN、EBA蛋白表达显著增加（P<0.05、0.01）,冰片+AST IV+PNS组的效应强于各药物单用及AST IV+PNS组（P<0.05、0.01）。模型组大鼠缺血皮质区VEGF蛋白表达显著增加（P<0.05）,NICD、Notch1蛋白表达无显著变化;冰片+AST IV+PNS组VEGF、NICD、Notch1蛋白表达显著上调（P<0.01）,且3种药物配伍的效应强于各药物单用及AST IV+PNS（P<0.05、0.01）。结论 冰片、AST IV、PNS具有抗脑缺血再灌注后神经元和脑微血管损伤的作用,3种药物配伍的作用强于各药物单用及AST IV+PNS,其作用可能与激活Notch信号通路、上调VEGF表达,从而发挥对缺血脑组织的保护作用有关。     

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.     

胃肠安丸对功能性消化不良肝郁脾虚大鼠胃动素的影响

目的观察胃肠安丸对肝郁脾虚型功能性消化不良(FD)模型大鼠胃肠动力及血浆胃动素(MTL)水平的影响。方法将60只实验大鼠随机分为6组(每组10只):对照组,模型组,胃肠安丸高、中、低剂量(50.4、25.2、12.6 mg/kg,中剂量为临床等效剂量)组及多潘立酮片阳性对照组,各组均ig给药,连续7d。给药后测定每组大鼠胃残留率及血浆MTL水平。结果与模型组相比,胃肠安丸高、中剂量组及多潘立酮片组大鼠胃内残留率显著降低(P0.05);胃肠安丸高剂量组血浆MTL水平与对照组、模型组相比均显著提高(P0.05);胃肠安丸中剂量组血浆MTL水平显著高于模型组(P0.05)。结论胃肠安丸可能通过调节MTL水平,改善胃动力,进而发挥对FD的治疗作用。     

基于均匀设计法对酸枣仁镇静催眠有效组分的配伍研究

目的 优选酸枣仁中3种具有镇静催眠作用的主要有效组分(总皂苷、总黄酮、总生物碱)最佳配伍.方法 采用均匀设计法将70只小鼠随机分为7组,分别为对照组及给药A～F组,观察各组小鼠自主活动情况;采用阈上剂量戊巴比妥钠(45 mg/kg)协同睡眠试验,以小鼠的睡眠潜伏期和睡眠时间为评价指标,筛选酸枣仁镇静催眠有效组分的最佳配伍.对所得有效组分最佳配伍的药效进行比较和验证实验.结果 与对照组比较,给药A、C、E组小鼠自主活动减少(P＜0.05、0.01),C、D组小鼠站立次数略有减少(P＜0.05).在阈上剂量戊巴比妥钠协同试验中,给药组C～F睡眠潜伏期显著缩短(P＜0.01),B～F组睡眠时间显著延长(P＜0.01).经多元统计分析,酸枣仁镇静催眠有效组分的最佳配伍组合为总皂苷200mg/kg、总黄酮0 mg/kg、总生物碱20 mg/kg.结论 应用均匀设计与药效学相结合确定中药有效组分配伍的方法是可行的.验证实验表明,酸枣仁有效组分的最佳配伍组合可以达到与原药材相同的疗效.     

Hypoglycaemic activity of Geranium core-core,Oxalis rosea and Plantago major extract in rats

The hypoglycaemic activity of ‘Core-core’ (Geranium core-core, Geraniaceae), ‘Culle’ (Oxalis rosea, Oxalidaceae) and ‘Llantén’ (Plantago major, Plantaginaceae) crude extracts was assessed in normoglycaemic rats. Furthermore, the hypoglycaemic activity of Core-core extract was evaluated in alloxan-diabetic rats. A single oral dose of 500 mg/kg Core-core extract significantly reduced glycaemia in normal rats under glucose tolerance test conditions (p < 0.01), while Culle and Llantén were devoid of activity. The effect was lower than a single oral dose of 100 mg/kg tolbutamide. After 7 days oral treatment at 250 mg extract/kg body weight, Core-core significantly reduced glycaemia (p<0.01) in normal rats under oral glucose tolerance conditions. In alloxan-diabetic rats, a single oral dose of 500 mg/kg and chronic treatment at 250 mg/kg Core-core extract significantly reduced glycaemia in glucose tolerance test conditions at p < 0.05 and p < 0.01, respectively. During the acute oral toxicity study, animals treated with Core-core extract exhibited no symptoms of drug-induced toxicity with doses up to 5 g/kg.     

Protective effect of Morinda citrifolia fruits on β‐amyloid (25–35) induced cognitive dysfunction in mice: An experimental and biochemical study

The neuroprotective effect of an ethyl acetate extract of Morinda citrifolia (Rubiaceae) Linn. fruits (EMC, ethyl acetate extract of Morinda citrifolia) at doses of 200 and 400 mg/kg, p.o. was studied on β‐amyloid (25–35) peptide induced cognitive dysfunction in mice. In the step‐down inhibitory avoidance, EMC exhibited a significant increase in short‐term memory and long‐term memory (p < 0.05). A significant decrease (p < 0.01) in escape latency was noticed in the animals in the water maze. A significant increase (p < 0.01) in alteration of behavior was exhibited upon administration of EMC 200 and 400 mg/kg on the Y maze. Exploratory parameters such as line crossings, head dipping and rearing were increased significantly in EMC treated groups in a dose‐dependent manner (p < 0.05 and p < 0.01). A significant reduction (p < 0.05) in acetyl cholinesterase activity was noticed in the EMC 200 and 400 mg/kg treated groups. The level of monoamine oxidase‐A was decreased by the administration of EMC 200 and 400 mg/kg (p < 0.05 and p < 0.01, respectively). EMC at a dose of 400 mg/kg exhibited a significant increase (p < 0.01) in the levels of serotonin and dopamine. Antioxidant enzymes such as superoxide dismutase, glutathione reductase, glutathione peroxidase and ascorbic acid were decreased significantly in the b‐amyloid peptide injected group, whose levels were restored significantly (p < 0.01) by the administration of EMC (400 mg/kg). Copyright © 2009 John Wiley & Sons, Ltd.     

松萝酸磷脂复合物在大鼠体内的药动学及组织分布研究

目的研究大鼠ig松萝酸磷脂复合物(UAPC)的药动学和组织分布特征。方法建立大鼠血浆和各组织中松萝酸(UA)的HPLC测定方法,大鼠分别单次ig给予UA和UAPC(35.0、17.5、11.7 mg/kg,以UA计)后,测定不同时间点大鼠血浆和各组织中的UA质量浓度,采用药动学程序软件DAS 2.0计算药动学参数。结果与UA相比,UAPC的主要药动学参数:高剂量35.0 mg/kg时C_(max)、AUC_(0~t)显著增大(P0.05),CL显著降低(P0.01),相对生物利用度为177.83%;中剂量17.5 mg/kg时C_(max)、AUC_(0~t)显著增大(P0.05),CL降低明显(P0.05),相对生物利用度为150.27%;低剂量11.7 mg/kg时C_(max)、AUC0~t增大,CL降低,无显著性差异(P0.05),相对生物利用度为109.67%。UAPC的组织分布特征:高剂量35.0mg/kg时在肝、脾、脑组织中分布较高;中剂量17.5 mg/kg时在肺、脑组织中分布较高;低剂量11.7 mg/kg时在肝、肾组织中分布较高。结论将UA制成UAPC后提高了UA的口服生物利用度,改变了其在大鼠某些脏器组织中的分布。     

Effect of crocin on the morphine‐induced antinociception in the formalin test in rats

In this study, the effects of intraperitoneal (i.p.) injection of crocin in the absence and presence of subcutaneous (s.c.) injections of morphine and naloxone were investigated on the formalin test in rats. The formalin test was induced by intra‐plantar (i.pl.) injection of formalin (50 μL, 1%), and the time spent licking and biting of the injected paw was measured for 1 h. Formalin induced a marked biphasic (first phase: 0–5 min and second phase: 15–45 min) pain response. Morphine (1 mg/kg, s.c.) significantly (p < 0.05) suppressed both phases of pain. Naloxone (2 mg/kg, s.c.) alone did not change the intensity of pain, but pretreatment with naloxone (2 mg/kg) significantly (p < 0.05) prevented morphine (1 mg/kg)‐induced antinociception. Crocin at doses of 50, 100 and 200 mg/kg significantly (p < 0.05) attenuated pain. Crocin (100 mg/kg, i.p.) significantly (p < 0.05) increased the morphine (1 mg/kg, s.c.)‐induced antinociception. Naloxone (2 mg/kg) did not reverse the suppressive effect of crocin (100 mg/kg) on pain. Crocin at a dose of 400 mg/kg significantly (p < 0.05) suppressed locomotor activities. These findings indicate that morphine through a naloxone‐sensitive mechanism produced analgesia. Crocin produced a dose‐dependent antinociceptive effect. In addition, crocin increased morphine‐induced antinociception, but naloxone did not change the antinociceptive effect of crocin. Copyright © 2009 John Wiley & Sons, Ltd.     

Effects of Salvia lavandulifolia Vahl. ssp. Oxyodon extract on pancreatic endocrine tissue in streptozotocin-diabetic rats

We have investigated the antidiabetic activity of Salvia lavandulifolia ssp. oxyodon extract on rats pancreotomized by streptozotocin (STZ). At a dose of 10 mg dry residue/kg the extract produced: an increase in Langerhans islet number and size; an increase in pancreatic insulin content. When both Salvia extract (10 mg/kg) and glibenclamide (1 mg/kg) were administered concurrently to STZ-diabetic rats, a significant decrease in glycaemic level (>40%) and mortality index was achieved.     

Antidepressant profile of Ptychopetalum olacoides Bentham (Marapuama) in mice

Depression has become of universal major importance, and it is therefore vital to expand the armamentarium for treating the condition. Lack of motivation and lassitude are major symptoms treated with the use of Marapuama (Ptychopetalum olacoides, PO) remedies by communities in the Brazilian Amazon. Considering the prominence of such symptoms in depression, the present study was designed to verify the effects of a standardized PO ethanol extract (POEE) on the forced swimming (FST) and tail suspension tests (TST). POEE i.p. (15–100 mg/kg) and oral (300 mg/kg) resulted in a significant and dose‐related anti‐immobility effect. We further examined the involvement of dopamine, noradrenaline and serotonin in these antidepressant‐like effects. POEE effects were prevented when catecholamine synthesis was inhibited by ‐α‐methyl‐ρ‐tyrosine (AMPT) (100 mg/kg, i.p.), while inhibition of serotonin synthesis with ρ‐chlorophenylalanine methyl ester hydrochloride (PCPA) (100 mg/kg, i.p.) was devoid of effect. The blockade of β‐adrenergic (propranolol 2 mg/kg, i.p.) and D₁ dopamine (SCH 23390 0.5 mg/kg, i.p.) receptors prevented POEE anti‐immobility effects; by contrast, blockade of D₂ dopamine (sulpiride 2 and 50 mg/kg, i.p.) receptors was ineffective. Consistent with traditional use, the results indicate that POEE possesses antidepressant‐like effects, possibly mediated by β‐adrenergic and D₁ dopamine receptors. Copyright © 2008 John Wiley & Sons, Ltd.     

Bacopa monnieri Increases Cerebral Blood Flow in Rat Independent of Blood Pressure

Bacopa monnieri (L.) Wettst. (Brahmi in India and Thailand) is an ayurvedic dementia treatment, but its effect on cerebral blood flow (CBF) is still unknown. We sought to test its chronic and acute effects on CBF compared with Ginkgo biloba and donepezil. CBF was measured by laser Doppler from rat cerebral cortex after 8 weeks of daily oral dosing of these drugs. Systolic blood pressure was also measured using the tail cuff method or via arterial cannulation. In rats treated with B. monnieri (40 mg/kg), CBF was 25% increased [2927 ± 123 perfusion units, (PU)] compared with shams (2337 ± 217 PU, p < 0.05, nine rats). G. biloba (60 mg/kg) also increased CBF (by 29% to 3019 ± 208 PU, p < 0.05, nine rats). No clear effect was obtained with donepezil (1 mg/kg). Chronic administration of the preparations had no effect on blood pressure. In contrast, intravenous acute infusion of these herbals (20–60 mg/kg) had marked dose‐dependent hypotensive actions (diastolic ~31 mmHg lower with 40 mg/kg of either extract), which correspondingly reduced CBF by ~15%. Likewise, CBF fell slightly with acute intravenous sodium nitroprusside and rose with noradrenaline. Donepezil (1 mg/kg) was slightly hypotensive without affecting CBF. Increased CBF with B. monnieri may account for its reported procognitive effect, and its further exploration as an alternative nootropic drug is worthwhile. Copyright © 2012 John Wiley & Sons, Ltd.     

白边岛衣多糖抗肿瘤作用的研究

白边岛衣多糖腹腔注射200mg/kg(1/5LD₅₀)能显著抑制小鼠肉瘤180、艾氏腹水癌和宫颈癌-u14等肿瘤的生长,但不能延长白血病L7217小鼠的存活时间,50mg/kg和100mg/kg(1/10和1/20 LD₅₀)能增加小鼠网状内皮系统的吞噬功能。     

Muscarinic agonist properties of the hydrobutanol extract from aerial parts of Waltheria viscosissima St. Hil. (Sterculiaceae) in Rats†

The cardiovascular effects of the hydrobutanol phase of the ethanolíc extract from the aerial parts (HBWV) of Waltheria viscosissima A. St. Hil. (Sterculiaceae) were tested in rats by using a combined (in vivo and in vitro) approach. HBWV (5, 7.5, 10, 15 and 20 mg/kg, randomly) induced a significant and dose‐dependent hypotension and bradycardia in conscious freely moving normotensive rats. Both hypotensive and bradycardic effects evoked by a submaximal dose of HBWV (10 mg/kg) were inhibited by pre‐treatment of the animals with atropine (2 mg/kg, i.v.). In anaesthetized animals, electrocardiogram recordings revealed second and third degree sinoatrial and atrioventricular blockade induced by the extract (10 mg/kg, i.v.), which were inhibited by cardiac muscarinic blockade (atropine, 2 mg/kg, i.v.). In isolated rat aortic rings, increasing concentrations of HBWV (50, 100, 200 and 400 µg/mL) were able to antagonize the contractile effects of noradrenaline (1 µM ). This effect was inhibited by pre‐incubation of the aortic rings with atropine (1 µM ), by removal of the vascular endothelial tissue or by nitric oxide synthase blockade. These results suggest that both cardiac and peripheral actions induced by HBWV are probably mediated by stimulation of cardiac and endothelial muscarinic receptors, respectively. Copyright © 1999 John Wiley & Sons, Ltd.     

Hypoglycaemic activity of Hexachlamys edulis (‘Yvahai’) extract in rats

The hypoglycaemic activity of the extract of the crude drug ‘Yvahai’ (Hexachlamys edulis, Myrtaceae) was assessed on normoglycaemic and alloxan-diabetic rats. After 7 days of oral treatment at 100 mg extract/kg body weight, Yvahai significantly reduced glycaemia in normal (p<0.02) and diabetic (p<0.05) rats during an oral glucose tolerance test. The maximum effect was observed between 1.5 and 2.5 h after glucose administration in normoglycaemic rats, and at 1.0 h in diabetic animals. The extract, however, did not have a statistically significant effect on the basal glycaemia of untreated compared with treated rats. A single oral dose of 500 mg extract/kg administered to normoglycaemic rats 1 h before glucose, elicited a significant reduction (p < 0.02) in the percent increase in glycaemia compared with vehicle-treated animals. The effect was comparable to a single oral dose of 100 mg/kg tolbutamide. During the oral toxicity study, animals exhibited no symptoms of drug-induced toxicity with doses up to 5 g/kg.     

Hypotensive and diuretic effect of Equisetum bogotense and Fuchsia magellanica and micropropagation of E. bogotense

Equisetum bogotense (Equisetaceae) and Fuchsia magellanica (Onagraceae) were used by the Mapuche Amerindians as diuretics. Intravenous administration of hydroalcoholic extracts to rats elicited a hypotensive response of ?29.0% ±4.5% and ?24.2% ±0.5% respectively in the mean blood pressure of normotensive animals at a dose of 5 mg crude extract/kg body weight. The activity was found to be related with polar compounds. For Fuchsia, the active principles are related to tannins. A single oral dose of 500 mg/kg body weight Equisetum extract produced a significant increase (p < 0.05) in the urine output in rats, while in Fuchsia a reduction in diuresis was observed. The diuretic effect of the Equisetum extract was weak compared with hydrochlorothiazide at 25 mg/kg body weight. The data presented support the use of E. bogotense in Chilean traditional medicine. A micropropagation method for E. bogotense was established by culturing shoot tips in Murashige-Skoog medium with macro and micronutrients diluted 4-fold and containing 0.1 mg/L thiamine, 100 mg/L myoinositol, 1.0 mg/L NAA and 0.1 mg/L BAP.     

Uncaria tomentosa (Willd. ex. Roem. & Schult.) DC. and Eucalyptus globulus Labill. interactions when administered with diazepam

The safety of natural drugs is defined by their side effects and toxicity as well as any interactions that may occur if taken together with other drugs. In particular, it is essential to identify synergies, antagonisms and other types of interference with other drugs so that the correct choice can be made from the range of phytomedicines available. The aim of this work was to investigate changes in the pharmacological effect of diazepam (2 mg/kg) on the CNS when administered together with a medicinal plant: Eucalyptus globulus Labill. (eucalyptus 6 mg/kg and 3.25 mg/kg) or Uncaria tomentosa (Willd. ex Roem. & Schult). DC. (cat's claw, 7.14 mg/kg and 3.54 mg/kg). Various different psychopharmacological effects were evaluated through assessing exploratory behavior, muscle relaxation and spontaneous motor activity. Both phytodrugs interacted with the benzodiazepine. Eucalyptus had an inhibitory effect at both doses and could be useful at the highest dose in cases where the desired effect of the depressant is moderate anxiolytic activity without marked muscle relaxation. Cat's claw, at both doses, enhanced the action of diazepam on spontaneous motor activity and, at the lowest dose, exploratory ability. These herbal drugs could be useful for their antiinflammatory activity in musculoskeletal pathologies treated with benzodiazepines. Copyright © 2011 John Wiley & Sons, Ltd.     

Terpenoid content of Valeriana wallichii extracts and antidepressant‐like response profiles

Three extracts of Valeriana wallichii DC (Valerianaceae) rhizome and fluoxetine were studied for antidepressant‐like activity in two behavioral models, namely the forced swim test (FST) and the tail suspension test (TST). Fluoxetine as well as methanolic and aqueous extracts of V. wallichii induced monophasic dose‐related decrements in immobility times in both tests. However, the aqueous‐ethanolic fraction induced a biphasic dose‐response profile since it produced a graded effect up to 200 mg/kg but the highest dose (250 mg/kg) was inactive in the FST. This extract also exhibited significantly reduced activity at 200 mg/kg compared to lower doses in the TST. The highest doses of aqueous‐ethanolic extract also reduced locomotor activity which will have led to a negative functional interaction with antidepressant‐like effects. Qualitative phytochemical analysis revealed that the aqueous‐ethanolic extract of V. wallichii was the only separated rhizome fraction containing terpenoids. Furthermore, since the methanolic and aqueous extracts were active in the tests, it is suggested that the antidepressant‐like action of this herbal plant is not contingent upon its terpenoid constituents. Copyright © 2009 John Wiley & Sons, Ltd.     

Influence of piperine on nimesulide induced antinociception

Piperine (1-peperoyl piperidine), an alkaloid extracted from Piper nigrum Linn is an inhibitor of hepatic and other enzymes involved in the biotransformation of drugs. In the present study piperine showed a dose dependent synergistic effect on nimesulide induced antinociception, in the acetic acid induced writhing test in mice. Piperine at a dose of 10 mg/kg significantly (p < 0.001) increased the analgesic activity of nimesulide administered at a submaximal dose of 6.5 mg/kg. In the formalin test, nimesulide alone (10 mg/kg, oral) did not modify phase I or nociceptor mediated pain while a combination of nimesulide (10 mg/kg) with piperine (10 mg/kg) significantly decreased it. In phase II or inflammatory pain, duration of formalin induced behaviour was 80 ± 7 s, 61 ± 7.3 s and 5.33 ± 3.3 s in control, nimesulide treated and piperine plus nimesulide treated groups respectively, indicating a synergistic activity of piperine with nimesulide. The antinociceptive effect correlated well with increased plasma concentration of nimesulide. The plasma concentration after oral administration of nimesulide (10 mg/kg) alone was 8.03 ± 0.99 ug/mL. However, when it was administered with piperine (10 mg/kg), the plasma concentration of nimesulide increased to 11.9 ± 0.23 ug/mL. This indicates that piperine inhibits the biotransformation and metabolism of nimesulide leading to significantly (p < 0.05) higher levels of drug in the systemic circulation. The findings of the present study suggest that piperine could be used as a biological enhancer when coadministered with nimesulide. © 1998 John Wiley & Sons, Ltd.