Hindawi Publishing Corporation Evidence-Based Complementary and Alternative Medicine Volume 2012, Article ID 497302, 12 pages doi:10.1155/2012/497302 Research Article Antidepressant-Like Activity of the Ethanolic Extract from Uncaria lanosa Wallich var. appendiculata Ridsd in the Forced Swimming Test and in the Tail Suspension Test in Mice Lieh-Ching Hsu,1 Yu-Jen Ko,1 Hao-Yuan Cheng,2 Ching-Wen Chang,1 Yu-Chin Lin,3 Ying-Hui Cheng,1 Ming-Tsuen Hsieh,1 and Wen Huang Peng1 1 School of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Pharmacy, China Medical University, No. 91 Hsueh-Shih Road, Taichung 404, Taiwan 2 Department of Nursing, Chung Jen College of Nursing, Health Sciences and Management, No. 1-10 Da-Hu, Hu-Bei Village, Da-Lin Township, Chia-Yi 62241, Taiwan 3 Department of Biotechnology, TransWorld University, No. 1221, Jen-Nang Road, Chia-Tong Li, Douliou, Yunlin 64063, Taiwan Correspondence should be addressed to Hao-Yuan Cheng, [email protected] and Wen Huang Peng, [email protected] Received 23 November 2011; Revised 30 January 2012; Accepted 30 January 2012 Academic Editor: Vincenzo De Feo Copyright © 2012 Lieh-Ching Hsu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. This study investigated the antidepressant activity of ethanolic extract of U. lanosa Wallich var. appendiculata Ridsd (ULEtOH)for two-weeks administrations by using FST and TST on mice. In order to understand the probable mechanism of antidepressant-like activity of ULEtOH in FST and TST, the researchers measured the levels of monoamines and monoamine oxidase activities in mice brain, and combined the antidepressant drugs (fluoxetine, imipramine, maprotiline, clorgyline, bupropion and ketanserin). Lastly, the researchers analyzed the content of RHY in the ULEtOH. The results showed that ULEtOH exhibited antidepressant-like activity in FSTandTSTinmice.ULEtOH increased the levels of 5-HT and 5-HIAA in cortex, striatum, hippocampus, and hypothalamus, the levels of NE and MHPG in cortex and hippocampus, the level of NE in striatum, and the level of DOPAC in striatum. Two-week injection of IMI, CLO, FLU and KET enhanced the antidepressant-like activity of ULEtOH.ULEtOH inhibited the activity of MAO- A. The amount of RHY in ULEtOH was 17.12 mg/g extract. Our findings support the view that ULEtOH exerts antidepressant-like activity. The antidepressant-like mechanism of ULEtOH may be related to the increase in monoamines levels in the hippocampus, cortex, striatum, and hypothalamus of mice. 1. Introduction serotonin reuptake inhibitors (SSRIs), monoamine oxi- dase inhibitors (MAOIs), specific serotonin-norepinephrine Depression, a widespread incapacitating psychiatric ailment, reuptake inhibitors (SNRIs), 5-HT2 receptor antagonists, imposes a substantial health burden on society [1]. Affec- and other heterocyclics are clinically employed for drug tive disorder are characterized by a disturbance of mood therapy [5]. However, these drugs can impose a variety associated with alteration in behavior, energy, appetite, of side-effects including sedation, apathy, fatigue, sleep sleep, and weight [2]. According to the most accepted hy- disturbance, cognitive impairment, and sexual dysfunction, pothesis of depression, the monoamine theory, patients and so forth. Hence, there remains a pressing need for new with major depression have symptoms that are reflected effective and better-tolerated antidepressants. changes in brain monoamine neurotransmitters, specifically Herbal therapies may be effective alternatives in the norepinephrine (NE) and serotonin (5-HT) [3]. Clinical treatment of depression, such as HypericumperforatumL. data suggests that dopamine (DA) is also involved in [6], Cordyceps sinensis [7], and Perilla frutescens [8]. The the pathophysiology and treatment of depression [4]. Med- Uncaria species recorded in Chinese Pharmacopoeia and Tai- ications such as tricyclic antidepressants (TCAs), selective wan Herbal Pharmacopoeia include Uncaria rhynchophylla 2 Evidence-Based Complementary and Alternative Medicine (Miquel) Jacks (abbrev. as UR), U. macrophylla Wallich. U. Animals. The experimental protocol was approved by the hirsuta Haviland (UH), U. sinensis (Oliver) Havil, and U. Committee on Animal Research, China Medical University. sessilifructus Roxburgh [9, 10]. According to Flora of Taiwan, The minimum number of animals and duration of observa- there are three different species of Gouteng in Taiwan: UR, tions required to obtain consistent data were used. UH, and U. lanosa Wallich var.appendiculataRidsd (UL) [11]. However, UL is not recorded in Pharmacopoeia. In 2.2. Plant Materials. Uncaria rhynchophylla (Miquel) Jacks traditional Chinese medicine, Gouteng is categorized as a (UR) was collected from SiaoWulai, U. hirsuta Haviland herb to extinguish wind, arrest convulsions, clear heat, and (UH) was collected from Wulai, and U. lanosa Wallich pacify the liver [12]. Gouteng is mainly used to treat cardio- var.appendiculataRidsd (UL) was collected from Xuhai, vascular and central nervous system ailments, including light Mudan Township of Taiwan, and was identified by Dr. Chao- headedness, convulsions, numbness, and hypertension [12]. Lin Kuo, Leader of the School of Chinese Pharmaceutical Several studies demonstrate that the herb extract mainly acts Sciences and Chinese Medicine Resources (CPCR). The ff on neuroprotective e ect used to treat antiepileptic [13–15], voucher specimen (Number: CMU-CPCR-UL-10001) was anti-Parkinsonian [16], anti-Alzheimer’s disease [17, 18], deposited at CPCR. anxiolytic [19], protective action against ischemia-induced neuronal damage [20, 21], anti-inflammation [22]. Alkaloids 2.3. Preparation of Plant Extract. Dried 1 kg of UR, UH, and are the active pharmacological component in Gouteng and UL, made from the stems and hooks of plants, were sliced comprise components include RHY, isorhynchophylline, into small pieces and ground into a powder, and extracted hirsutine, hirsuteine, corynantheine, isocorynoxeine. RHY four times with 5% ammonia solution and 70% ethanol. The exhibited a similar pharmacological activity when compared extracts were filtered, combined, and concentrated under with Gouteng [12]. RHY is an important active compo- reduced pressure at 40◦C to obtain the UR ,UH , nent of alkaloids separated from gambir plant (Gouteng EtOH EtOH UL extracts. The yield ratios of the UR ,UH , in Chinese), RHY exerts the protective action primarily EtOH EtOH EtOH ULEtOH extracts (120 g, 97 g, 115 g) were 12%, 9.7%, 11.5%. by inhibiting of NMDA and 5-HT2 receptor-mediated neurotoxicity during ischemia [21]. RHY also affects the levels of serotonin in cortex, striatum, hippocampus, and 2.4. Drugs and Drug Administration. Imipramine HCl (IMI), hypothalamus [23, 24]. From the above perspectives, we clorgyline HCl (CLO), maprotiline HCl (MAP), fluoxe- inferred that RHY is the key component of antidepressant- tine HCl(FLU), bupropion HCl (BUP), ketanserin (KET), like activity of Gouteng. Gouteng possesses neuroprotective sodium octyl sulfate, norepinephrine HCl (NE), dopamine effect, regulation of monoamine transporters, macrophage HCl (DA), 5-hydroxytryptamine HCl (5-HT), 4-Hydroxy- theory [25], and regulation of glutamatergic system [26]. 3-methoxyphenylglycol (MHPG), 4-dihydroxyphenylacetic Our preliminary test indicated that ethanolic extract of U. acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIAA), as lanosa Wallich var.appendiculataRidsd. (UL ) contained well as horseradish peroxidase (HRP), benzylamine, amplex EtOH ff the largest amount of RHY among Uncaria species in Taiwan. red, and phosphate-bu ered saline (PBS) solution were purchased from Sigma-Aldorich (St. Louis, MO, USA). RHY However, the antidepressant-like activity of ULEtOH has not been investigated, which encouraged us to investigate the was purchased from Matsuura Yakugyo Co., Ltd (Japan). Drugs were dissolved in normal saline, except HRP, benzy- effects of ULEtOH on depression problems. lamine, and amplex red that was diluted in PBS solution. In the present study, we aimed to investigate the effect Citric acid, tri-natriumcitrate-2-hydrate, and EDTA were of UL in FST and TST in mice. The behavioral despair EtOH purchased from Merck. UR ,UH ,UL , or saline tasks have good predictive value for antidepressant potency EtOH EtOH EtOH ff was administered by oral route, whereas the other drugs were in humans [27]. Moreover, we investigated whether the e ect administered by i.p. route. The i.p. or p.o. administrations of ULEtOH in FST and TST is dependent on its interaction were given in a volume of 10 mL/kg body weight. Tests with the 5-HT, NE, and DA receptors, and the brain were performed 1 hr (ULEtOH) and 30 min (imipramine, monoamine neurotransmitter concentration. MAO activity fluoxetine, clorgyline, maprotiline, bupropion, ketanserin) was also tested by neurochemical and biochemical assays after administration. to confirm the participation of monoamine transmitters in treatment involving ULEtOH. 2.5. HPLC Analysis of UREtOH,UHEtOH,andULEtOH. The HPLC system consisted of a Shimadzu (Kyoto, Japan) LC- 2. Materials and Methods 10ATvp liquid chromatograph equipped with a DGU-14A degasser, an FCV-10ALvp low-pressure gradient flow control 2.1. Animals. Male ICR albino mice (weighing around 22 g), valve, an SIL-10ADvp autoinjector, an SPD-M10Avp diode purchased from BioLASCO