Comparison of ginsenosides Rg1 and Rb1 for their effects on improving scopolamine‐induced learning and memory impairment in mice

Rg1 and Rb1 are two major active compounds of ginseng that facilitate learning and memory. The present study aimed to compare the nootropic effects of Rg1 and Rb1 in a scopolamine induced dementia mice model. After 6 and 12 mg/kg of Rg1 and Rb1 intraperitoneal administration to mice for 7 days, their effects were assessed using the step‐down passive avoidance (SD) and the Morris water maze (MWM) tests, the acetylcholinesterase (AChE) activity, acetylcholine (ACh) content and serotonin (5‐HT) level in the hippocampus were analysed after SD and MWM tests. The results showed that Rg1 and Rb1 ameliorated cognition‐deficiency in mice with dementia. Rg1 showed stronger effects than Rb1 on escape acquisition in MWM. Both Rg1 and Rb1 increased ACh levels in the hippocampus, but Rg1 inhibited AChE activity while Rb1 had no effect on AChE activity. Both Rg1 and Rb1 inhibited the decrease of 5‐HT induced by scopolamine, but Rb1 was more active than the same dose of Rg1. These results demonstrate that multiple administrations of Rg1 and Rb1 are effective in improving memory deficiency induced by scopolamine. Rg1 appears to be more potent than Rb1 in improving acquisition impairment, and the two ginsenosides may act through different mechanisms. Copyright © 2010 John Wiley & Sons, Ltd.     

Schizandrin reverses memory impairment in rats

The present study investigated the effect of schizandrin, a component of the fruit of Schizandra chinesis Baill (Fructus Schizandrae), on memory impairment in rats. Scopolamine (0.5 mg/kg, i.p.), a non-selective muscarinic receptor antagonist, markedly impaired spatial memory in an eight-arm radial maze. A higher dose of scopolamine (3 mg/kg, i.p.) also impaired the passive avoidance response. Schizandrin (1 and 10 mg/kg, p.o.) significantly reversed the scopolamine-induced impairment of spatial memory. Similarly, schizandrin (1 mg/kg, p.o.) significantly reversed the scopolamine-induced impairment of the passive avoidance response. Moreover, in mice, schizandrin (1 and 10 mg/kg, p.o.) enhanced tremors induced by oxotremorine, a muscarinic M(1) receptor agonist. Taken together these findings suggest that schizandrin reverses scopolamine-induced memory impairment, in part, by enhancing cholinergic function, and that schizandrin might be useful for treating memory deficits.     

Effects of Kamikihi-To,a traditional Chinese Medicine,on learning and memory performance in mice

The effects of Kamikihi-To (KMK), a traditional Chinese medicine (Chinese name Jia-Wei-Gui-Pi-Tang), on learning and memory performance abilities in normal or memory-impaired mice were studied using step through and step down type passive avoidance tests. The effects were also studied using shuttle box and lever press type conditioned avoidance tests in normal mice. KMK (0.5 and 1.0 g/kg p.o.) showed no influence on the learning abilities in passive and conditioned avoidance tests in normal mice. In contrast, KMK (1.0 g/kg p.o.) exerted ameliorating effects on memory registration impairment induced by ethanol in step through and step down tests. KMK at this dose also significantly improved memory retrieval disability induced by electroconvulsive shock (ECS) in step through test. Moreover, KMK (0.5 g/kg p.o.) ameliorated memory consolidation impairment induced by ECS in step down test. These results suggest that KMK ameliorates the impaired learning performance through its influence on memory registration, consolidation and retrieval.     

类叶升麻苷对东莨菪碱致小鼠学习记忆障碍的改善作用

目的:探讨类叶升麻苷对痴呆小鼠学习记忆的影响.方法:连续灌服类叶升麻苷10d后,以东莨菪碱建立小鼠记忆获得性障碍模型,采用行为学实验(跳台法)检测动物学习记忆能力,行为学测试结束后,进行小鼠大脑皮层和海马组织中生化指标检测,包括谷胱甘肽过氧化物酶(GSH-Px)、总超氧化物歧化酶(T-SOD)、丙二醛(MDA)、乙酰胆碱酯酶(TChE)以及脑组织蛋白含量的测定.结果:预先给予小鼠类叶升麻苷10 d可以改善东莨菪碱导致的记忆获得性障碍,与模型组比较,类叶升麻苷可显著延长小鼠跳台潜伏期,减少跳台错误次数;类叶升麻苷可使小鼠脑组织中T-SOD,GSH-Px,TChE活性、脑组织蛋白含量升高,MDA含量降低.结论:类叶升麻苷对东莨菪碱致小鼠学习记忆获得性障碍具有显著的改善作用,其作用机制可能与其对抗小鼠体内自由基生成以及改善中枢胆碱能系统功能有关.     

Kalopanaxsaponins A and B isolated from Kalopanax pictus ameliorate memory deficits in mice

The stem-bark of Kalopanax pictus (KP, family Araliaceae), which contains triterpenoid saponins, has been shown to exhibit anticarcinogenic, antiinflammatory, antirheumatoid and antidiabetic activities. In a preliminary study, a KP methanol extract demonstrated acetylcholinesterase activity in vitro and memory enhancement in scopolamine-treated mice. Therefore, we isolated acetylcholinesterase inhibitors, kalopanaxsaponins A and B, from a KP butanol (BuOH) fraction, measured acetylcholinesterase activity in vitro, and investigated their memory-enhancing effects in a passive avoidance test, Y-maze test and Morris water maze test. These constituents inhibited acetylcholinesterase activity and significantly reversed scopolamine-induced deficits. They also increased brain-derived neurotrophic factor (BDNF) and phosphorylated cAMP response element binding (p-CREB) protein expression but reduced TNF-α increased by scopolamine. Based on these findings, kalopanaxsaponins A and B may ameliorate memory deficits by inhibiting acetylcholinesterase activity and inducing BDNF and p-CREB expression.     

Neuroprotective effects of 20(S)‐protopanaxatriol (PPT) on scopolamine‐induced cognitive deficits in mice

20(S)‐protopanaxatriol (PPT), one of the ginsenosides from Panax ginseng, has been reported to have neuroprotective effects and to improve memory. The present study was designed to investigate the protective effect of PPT on scopolamine‐induced cognitive deficits in mice. Male Institute of Cancer Research mice were pretreated with 2 different doses of PPT (20 and 40 μmol/kg) for 27 days by intraperitoneal injection, and scopolamine (0.75 mg/kg) was injected intraperitoneally for 9 days to induce memory impairment. Thirty minutes after the last pretreatment, the locomotor activity was firstly examined to evaluate the motor function of mice. Then, memory‐related behaviors were evaluated, and the related mechanism was further researched. It was founded that PPT treatment significantly reversed scopolamine‐induced cognitive impairment in the object location recognition experiment, the Morris water maze test, and the passive avoidance task, showing memory‐improving effects. PPT also significantly improved cholinergic system reactivity and suppressed oxidative stress, indicated by inhibition of acetylcholinesterase activity, elevation of acetylcholine levels, increasing superoxide dismutase activity and lowering levels of malondialdehyde in the hippocampus. In addition, the expression levels of Egr‐1, c‐Jun, and cAMP responsive element binding in the hippocampus were significantly elevated by PPT administration. These results suggest that PPT may be a potential drug candidate for the treatment of cognitive deficit in Alzheimer's disease.     

Echinacoside alleviates hypobaric hypoxia‐induced memory impairment in C57 mice

Acute hypobaric hypoxia (HH) gives rise to persistent cognitive impairment, influencing memory function specifically. Echinacoside (ECH), one of the phenylethanoids isolated from the stems of Cistanche salsa, has been reported to prevent ischemia induced by neuronal injury traditionally. This study then tried to investigate whether ECH could alleviate HH‐induced memory deficit. Ten C57 mice were used as control, and 50 were exposed to HH equivalent to 6,100 m for 7 days in a decompression chamber and were given ECH daily (50, 75, or 100 mg/kg) through gavage during the period of exposure. Cognitive performance was evaluated by the Morris water maze test. ECH, especially at 100 mg/kg, significantly reduced HH‐induced memory decline. Furthermore, ECH increased the expression of nuclear factor E2 p45‐related factor 2, heme oxygenase‐1, NAD(P)H:quinone oxidoreductase 1, and γ‐glutamyl cysteine synthetase in mRNA and protein levels, suggesting that the Keap1–Nrf2–ARE signaling pathway might be involved in neuronal adaptation. The results indicate that ECH could prevent HH‐induced memory impairment, which is associated with antioxidant effect of ECH in the hippocampus.     

Polysaccharide extracted from Potentilla anserina L ameliorate acute hypobaric hypoxia‐induced brain impairment in rats

High altitude cerebral edema (HACE) is a high altitude malady caused by acute hypobaric hypoxia (AHH), in which pathogenesis is associated with oxidative stress and inflammatory cytokines. Potentilla anserina L is mainly distributed in Tibetan Plateau, and its polysaccharide possesses many physiological and pharmacological properties. In the present study, the protective effect and potential treatment mechanism of Potentilla anserina L polysaccharide (PAP) in HACE were explored. First, we measured the brain water content and observed the pathological changes in brain tissues, furthermore, malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), and glutathione (GSH) were evaluated by kits. Finally, the protein contents and mRNA expressions of pro‐inflammatory (IL‐1β, IL‐6, TNF‐α, vascular endothelial cell growth factor [VEGF], NF‐κB, and hypoxia inducible factor‐1 α [HIF‐1α]) were detected by ELISA kits, RT‐PCR, and western blotting. The results demonstrated that PAP reduced the brain water content, alleviated brain tissue injury, reduce the levels of MDA and NO, and increased the activity of SOD and GSH level. In addition, PAP blocking the NF‐κB and HIF‐1α signaling pathway activation inhibited the generation of downstream pro‐inflammatory cytokines (IL‐1β, IL‐6, TNF‐α, and VEGF). Therefore, PAP has a potential to treat and prevent of HACE by suppression of oxidative stress and inflammatory response.     

Protective effect of ginsenoside Rh2 on scopolamine‐induced memory deficits through regulation of cholinergic transmission,oxidative stress and the ERK‐CREB‐BDNF signaling pathway

Rh2 is a rare ginsenoside and there are few reports of its effect on cognition compared with other similar molecules. This study aimed to establish the impact of Rh2 treatment on improving scopolamine (Scop)‐induced memory deficits in mice and illuminate the underlying mechanisms. First, memory‐related behavior was evaluated using two approaches: object location recognition (OLR), based on spontaneous activity, and a Morris water maze (MWM) task, based on an aversive stimulus. Our results suggested that Rh2 treatment effectively increased the discrimination index of the mice in the OLR test. In addition, Rh2 elevated the crossing numbers and decreased the escape latency during the MWM task. Moreover, Rh2 markedly upregulated the phosphorylation of the extracellular signal‐regulated kinase (ERK)‐cAMP response element binding (CREB)‐brain derived neurotrophic factor (BDNF) pathway in the hippocampus. Meanwhile, the administration of Rh2 significantly promoted the cholinergic system and dramatically suppressed oxidative stress in the hippocampus. Taken together, Rh2 exhibited neuroprotective effects against Scop‐induced memory dysfunction in mice. Rh2 activity might be ascribed to several underlying mechanisms, including its effects on modulating the cholinergic transmission, inhibiting oxidative stress and activating the ERK‐CREB‐BDNF signaling pathway. Consequently, the ginsenoside Rh2 might serve as a promising candidate compound for Alzheimer's disease.     

桂枝汤苯丙烯类化合物对APP转基因AD小鼠学习记忆障碍的影响

目的:探讨桂枝汤苯丙烯类化合物(PCGZT)对APP转基因阿尔茨海默病(AD)小鼠模型记忆障碍影响及其部分作用机制。方法:按体重随机将3月龄APP695V717转基因小鼠随机分为模型组,阿司匹林组(20 mg·kg-1·d-1),脑复康组(600 mg·kg-1·d-1),石杉碱甲组(0.3 mg·kg-1·d-1)和PCGZT大、中、小剂量(64.4,32.2,16.1 mg·kg-1·d-1)组,每组10只;另取C57BL/6J小鼠10只作为空白组。各组小鼠每天给药1次,约10月龄时,进行Morris水迷宫实验和跳台实验,测定小鼠脑组织丙二醛(MDA)含量,血清中基质金属蛋白酶-2(MMP-2)和MMP-9含量。结果:与模型组比较,PCGZT可以减少APP转基因AD小鼠跳台反应时间,降低错误期总时间和错误次数,提高安全期总时间(P0.05);PCGZT小剂量组提高APP转基因AD小鼠在Morris迷宫实验中站台象限路程比率(P0.01)和站台象限时间比率(P0.05)。同时,PCGZT可以降低AD小鼠脑MDA含量(P0.05)和血清中MMP-9含量(P0.05),对MMP-2含量无影响。结论:PCGZT能够明显改善APP转基因AD小鼠学习记忆障碍,其作用机制可能涉及多个药物靶点。     

Neuroprotective effects of Triticum aestivum L. against β‐Amyloid‐induced cell death and memory impairments

β‐Amyloid (Aβ) is a key component of senile plaques, neuropathological hallmarks of Alzheimer's disease (AD) and has been reported to induce cell death via oxidative stress. This study investigated the protective effects of Triticum aestivum L. (TAL) on Aβ‐induced apoptosis in SH‐SY5Y cells and cognitive dysfunctions in Sprague‐Dawley (SD) rats. Cells treated with Aβ exhibited decreased viability and apoptotic features, such as DNA fragmentation, alterations in mitochondria and an increased Bax/Bcl‐2 ratio, which were attenuated by TAL extract (TALE) pretreatment. To elucidate the neuroprotective mechanisms of TALE, the study examined Aβ‐induced oxidative stress and cellular defense. TALE pretreatment suppressed Aβ‐increased intracellular accumulation of reactive oxygen species (ROS) via up‐regulation of glutathione, an essential endogenous antioxidant. To further verify the effect of TALE on memory impairments, Aβ or scopolamine was injected in SD rats and a water maze task conducted as a spatial memory test. Aβ or scopolamine treatment increased the time taken to find the platform during training trials, which was decreased by TALE pretreatment. Furthermore, one of the active components of TALE, total dietary fiber also effectively inhibited Aβ‐induced cytotoxicity and scopolamine‐caused memory deficits. These results suggest that TALE may have preventive and/or therapeutic potential in the management of AD. Copyright © 2009 John Wiley & Sons, Ltd.     

Effects of acute administration of the hydroalcoholic extract of mate tea leaves (Ilex paraguariensis) in animal models of learning and memory

Aim of the study

Ilex paraguariensis St. Hilaire (Aquifoliaceae) is a plant widely cultivated in South America that is used to prepare a tea-like beverage with a reputation to improve cognitive function, a response that has been attributed to the constituents of the leaves, especially caffeine. Our previous study indicated that the hydroalcoholic extract of Ilex paraguariensis presents an antiparkinsonian profile in reserpine- and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-treated rodents.

Materials and methods

In the present study, the effects of the hydroalcoholic extract of Ilex paraguariensis on the short- and long-term learning and memory of rats were assessed with the social recognition, Morris water maze, and step-down inhibitory avoidance tasks.

Results

A preliminary HPLC fingerprint of the plant extract confirmed the presence of caffeine (the major compound), rutin and kaemperol, and revealed the absence of detectable concentrations of caffeic acid, quercetin and ursolic acid. Acute pre-training intraperitoneal (i.p.) or oral administration of the extract of Ilex paraguariensis improved the short-term social memory in a specific manner as well as facilitated the step-down inhibitory avoidance short-term memory evaluated 1.5 h after training. Moreover, a synergistic response was observed following the co-administration of ‘non-effective’ doses of caffeine and Ilex paraguariensis in the social memory. In contrast, pre-training administration of hydroalcoholic extract of Ilex paraguariensis did not alter the step-down inhibitory avoidance long-term memory evaluated 24 h after training, while the highest dose tested (250 mg/kg, i.p.) disrupted the animals’ performance in a cued version of the Morris water maze.

Conclusion

These results partly substantiate the traditional use of mate tea for improvement of cognition indicating that acute administration of hydroalcoholic extract of Ilex paraguariensis differentially modulates short- and long-term learning and memory in rats probably through its antagonist's action on adenosine receptors.     

Effects of Hypericum perforatum extract on diabetes‐induced learning and memory impairment in rats

Cognitive impairment occurs in diabetes mellitus. Hypericum perforatum has been used in folk medicine to improve mental performance. Here it is hypothesized that chronic treatment with an extract of Hypericum perforatum (6, 12 and 25 mg/kg, p.o.) would have effects on passive avoidance learning (PAL) and memory in control and streptozotocin‐induced diabetic rats. Treatments were begun at the onset of hyperglycaemia. PAL was assessed 30 days later. A retention test was done 24 h after training. At the end, the animals were weighed and blood samples were drawn for plasma glucose measurement. Diabetes caused impairment in acquisition and retrieval processes of PAL and memory. Hypericum treatment (12 and 25 mg/kg) improved learning and memory in control rats and reversed learning and memory deficits in diabetic rats. A dose of 6 mg/kg did not affect cognitive function. Hypericum administration did not alter the body weight and plasma glucose levels. Antioxidant properties and cholinergic facilitatory effects of Hypericum may be involved in its nootropic effects. These results show that Hypericum perforatum prevented the deleterious effects of diabetes on PAL and memory. As Hypericum would be free of major side effects compared with other nootropic medications, it may provide a new potential alternative for demented diabetic patients. Copyright © 2010 John Wiley & Sons, Ltd.     

地黄饮子对痴呆小鼠脑功能及乙酰胆碱酯酶活性的影响

研究地黄饮子对痴呆小鼠学习记忆的影响及其部分作用机理。以氯化铝诱导痴呆小鼠模型 ,观察地黄饮子对小鼠在跳台实验、水迷宫实验中学习记忆能力及脑组织中乙酰胆碱酯酶活性的影响。结果 ,地黄饮子可以减少小鼠跳台错误反应次数 ,延长测验期跳台潜伏期 ,缩短小鼠寻找平台潜伏期 ,增加测验期跨越平台次数 ,降低乙酰胆碱酯酶活性。地黄饮子可以提高痴呆小鼠学习记忆能力 ,其作用机理可能与降低小鼠脑组织中乙酰胆碱酯酶活性有关。     

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 effects of Dioscorea opposita on scopolamine-induced memory impairment in in vivo behavioral tests and in vitro assays

Ethnopharmacological relevance

Plants belong to the genus Dioscorea have long been used as edible tuber crops in many tropical and subtropical areas and as a traditional herbal medicine in oriental countries including China, Japan and Korea.

Aim of the study

In this study, in vivo and in vitro tests were carried out to evaluate the cognitive enhancing effects of CHCl₃-soluble extract from Dioscorea opposita against scopolamine-induced amnesic mice and glutamate- and H₂O₂-treated cortical neurons of rats.

Materials, methods and results

Acute treatment (200 mg/kg body weight, p.o.) and 10 days’ daily administration (50 mg/kg body weight, p.o.) of CHCl₃-soluble extract showed significant spatial learning and memory improvement on mice. Furthermore, the neuroprotective effects on glutamate- and H₂O₂-induced neurotoxicity in primary cultured cortical neurons of rats were assessed. Pretreatment with the extract was found to impart significant protection against neurotoxicity.

Conclusions

These in vivo and in vitro results suggest that the Dioscorea opposita has neuroprotective effects on memory impairment related neurodegenerative diseases.     

Memory Enhancement of Acteoside (Verbascoside) in a Senescent Mice Model Induced by a Combination of d‐gal and AlCl3

Acteoside, also known as verbascoside or orobanchin, is a common compound found in many important medicinal plants including the Chinese herb Cistanche deserticola Y. C. Ma, which is used for its neuroprotective and memory enhancement properties. We have investigated the effects of acteoside using a senescent mouse model induced by a combination of chronic intraperitoneal administration of d ‐gal (60 mg/kg/day) and oral administration AlCl₃ (5 mg/kg/day) once daily for 90 days. After 60 days, acteoside (30, 60, and 120 mg/kg/day) was orally administered once daily for 30 days. The memory enhancing effects of acteoside were evaluated using the Morris water maze test. The results showed that 30–120 mg/kg/day of acteoside reduced the escape latency in finding the platform, and increased the number of crossings of the platform. A 30–120 mg/kg/day of acteoside increased significantly the expression of nerve growth factor and tropomycin receptor kinase A mRNA and protein in the hippocampus, measured using real‐time RT‐PCR, immunohistochemical analysis, and western blotting. These results support the use of C. deserticola for memory enhancement and indicate that the effects of acteoside are induced via promotion of nerve growth factor and tropomycin receptor kinase A expression. Copyright © 2015 John Wiley & Sons, Ltd.     

Relationship Between Emotional Behavior in Mice and the Concentration of (+)‐α‐Santalol in the Brain

We previously reported finding anxiolytic‐like activity for sandalwood oil after administration in mice. In this report, we further investigated the emotional behavior associated with inhaled or intraperitoneally administered (+)‐α‐santalol, the main component of sandalwood oil, in addition to examining whether pharmacological or neurological transfers are responsible for this behavior. After administration of (+)‐α‐santalol by inhalation or intraperitoneal injection, we assessed anxiolytic‐like and locomotor activities using elevated‐plus maze tests. We also examined the relationship between the emotional behavior and the (+)‐α‐santalol brain concentration. Anxiolytic‐like activity was not observed immediately after administration or after water‐immersion stress for 24 h for either the (+)‐α‐santalol 2 μL/L air inhalation or the (+)‐α‐santalol 0.03 mL/kg (i.p.) administration. However, mice administered (+)‐α‐santalol 0.03 mL/kg intraperitoneally exhibited a significant decrease in the locomotor activity after exposure to water‐immersion stress for 24 h. The brain (+)‐α‐santalol concentration was 2.6 µg/g tissue after (+)‐α‐santalol 0.03 mL/kg (i.p.) administration. The observed shift of (+)‐α‐santalol to the brain suggests that this component acts via pharmacological transfer and is responsible for the sedative effect but not the anxiolytic‐like activity. Copyright © 2015 John Wiley & Sons, Ltd.     

Effect of Choto‐san,a Kampo medicine,on impairment of passive avoidance performance in mice

In mice with procephalic ischaemia loading, disrupted passive avoidance retention performance was dose‐dependently improved by Choto‐san, but this effect was antagonized by NAN‐190, a serotonin_1A­receptor antagonist. In mice with decreased intracerebral serotonin concentration, Choto‐san prevented disturbance in acquiring a passive avoidance response after scopolamine administration, but did not­influence the decreased serotonin concentration. These results suggested that Choto‐san showed the­anti‐amnestic effect based on the stimulation of serotonin_1A receptors. Copyright © 1999 John Wiley & Sons, Ltd.     

Essential Oil from Citrus aurantifolia prevents ketotifen‐induced weight‐gain in mice

Obesity is a major health problem world‐wide. Medical intervention is often needed to tackle this problem, and accordingly the need for developing more effective, safer and cheaper weight reducing drugs has become paramount in recent years. In the present study, the effects of lime (Citrus aurantifolia) essential oils in reducing body weight, individually and in co‐administration with ketotifen, an antihistaminic drug that causes weight‐gain, has been investigated using a mouse model. During the 45 days experimental period, the mice that received ketotifen demonstrated an enhancement both in the amount of food intake and body weight compared with the control group. Groups treated with lime essential oil displayed a reduction in body weight and food consumption in mice, possibly through promoting anorexia which might have played a role in weight loss. Interestingly, co‐administration of the lime essential oil and ketotifen caused significant suppression in gaining weight, as well as decreased body weights of mice. The data obtained in this study suggested that lime essential oil plays an important role in weight loss and could be useful in the treatment of drug‐induced obesity and related diseases. The GC‐MS analysis of the essential oils of C. aurantifolia was also performed and approximately 22 main components, with limonene (28.27%) being the principal one, were identified and quantified. Copyright © 2010 John Wiley & Sons, Ltd.