Anxiolytic‐like Effect of α‐Asarone in Mice

The effects of α‐asarone in four assays predictive of anxiolytic activity in male mice were studied, with diazepam as a positive anxiolytic control. The use of the elevated plus‐maze test revealed that diazepam (2 mg/kg) or α‐asarone (3.5 mg/kg) increased the percentage of entries into open arms and of the time spent on open arms. In the light/dark transition test, as with 2 mg/kg diazepam, 7 mg/kg α‐asarone increased the time spent in the light area and the number of transitions between the two compartments. In the novel food consumption test, α‐asarone (3.5, 7 and 14 mg/kg) caused significant increases in food intake during 5 min as well as diazepam (0.5 mg/kg). In the marble burying test, α‐asarone also produced a significant inhibition of marble burying at doses of 14 and 28 mg/kg, as did diazepam (5 mg/kg). Thus, these findings indicated that α‐asarone exhibited an anxiolytic‐like effect. Further studies will be required to assess the generality of the present findings to other species and behavioral paradigms. Copyright © 2012 John Wiley & Sons, Ltd.     

Expression of BDNF and TH mRNA in the Brain Following Inhaled Administration of α‐Pinene

Essential oils are mainly administered by inhalation. Administration by inhalation is considered to occur through two pathways, neurological transfer and pharmacological transfer. However, the relationship between the two routes is not clear. To clarify this relationship, we administered α‐pinene, which has an anxiolytic‐like effect, to mice. Emotional behavior and accumulation and expression of relevant mRNAs in the brain (brain‐derived neurotrophic factor (BDNF); tyrosine hydroxylase (TH)) were examined following inhaled administration of α‐pinene (10 μL/L air for 60 or 90 min). To evaluate the anxiolytic‐like effect, the elevated plus maze (EPM) test was used. Inhalation of α‐pinene for 60 min produced a significant increase in the total distance traveled in the EPM test compared with control (water). The concentration of α‐pinene in the brain after 60 min of inhalation was significantly increased compared with that after 90 min of inhalation. The expression of BDNF mRNA in the olfactory bulb and in the hippocampus was almost the same after 60 min of inhalation compared to that after 90 min of inhalation. The expression of TH mRNA in the midbrain after 60 min of inhalation was significantly increased compared with that of the control. Thus, an increase in α‐pinene in the brain induces an increase in TH mRNA expression and increases locomotor activity. The anxiolytic‐like effect may be related to both neurological transfer and pharmacological transfer. Copyright © 2014 John Wiley & Sons, Ltd.     

Daily Inhalation of α‐Pinene in Mice: Effects on Behavior and Organ Accumulation

In phytotherapy, essential oils tend to be used daily for a period of days or weeks, rather than in a single application. However, the literature contains very little information on repeated use of essential oils. In this study, we investigated the effects on behavior and the accumulation in the brain and liver of α‐pinene, an essential oil component, when inhaled by mice. Animals were individually housed in cages for 1 week. Mice inhaled α‐pinene or water vapor (negative control) for 90 min/day for 1 day, 3 days, or 5 days, and they were then submitted to the elevated plus maze test for 10 min. We used gas chromatography with flame ionization detection to quantify concentrations of α‐pinene in the brain and liver. There was significant anxiolytic‐like activity, which remained constant for the 5 days' inhalation of α‐pinene. On the other hand, the accumulation of α‐pinene in the brain and liver peaked on the third day of inhalation. The existence of stress related to the new environment appears to have affected the change in the accumulation of α‐pinene in the internal organs, keeping the anxiolytic‐like action constant. Copyright © 2013 John Wiley & Sons, Ltd.     

柴胡疏肝散对抑郁症模型小鼠行为学改变影响的实验研究

目的：观察中药复方柴胡疏肝散对抑郁模型小鼠行为学变化的影响。方法：采取小鼠强迫游泳实验复制抑郁症模型。除正常组外所有动物均灌胃给药,连续给药21 d。采用高架十字迷宫,观察实验小鼠行为学变化。结果：柴胡疏肝散低、高剂量、盐酸氯丙咪嗪均能明显缩短小鼠强迫游泳的不动时间（P〈0.05）,并明显增加小鼠进入开放臂的次数及时间百分比（P〈0.01）,并增加小鼠向下探究次数和封闭臂后腿直立次数,其中柴胡疏肝散高剂量作用最为显著。结论：中药复方柴胡疏肝散高、低剂量均具有一定的抗抑郁作用。     

牡丹皮中丹皮酚的抗焦虑作用

目的:探讨中药牡丹皮抗焦虑作用物质基础.方法:80只成年雄性昆明种小鼠随机分为空白组(Control),阳性药组(地西泮,BZ,1 mg·kg-1),牡丹皮水蒸气蒸馏馏分低、中、高剂量组(Px,50,100,200 mg· kg-1),牡丹皮蒸馏剩余药渣水提物低、中、高剂量组(Wx,100,200,400 mg· kg-1);实验依次进行自由探索模型实验(FEP)、旷场实验(OFT)、高架十字迷宫实验(EPM)、高架○迷宫实验(EZM)和明暗箱实验(LDB);FEP实验参数包括陌生区时间百分率(Ntime％)、陌生区水平运动百分率(Ncross％)、陌生区垂直运动百分率(Nrear％)、总水平运动(Cross)和总垂直运动(Rear);OFT实验参数包括中央区时间百分率(Ctime％)、中央区水平运动百分率(Ccross％)、总水平运动(Cross)和总垂直运动(Rear);EPM和EZM实验参数包括开臂时间百分率(Otime％)、开臂进入次数百分率(Oentries％)和两臂总进入次数(Entries);LDB实验参数包括明区停留时间百分率(Ltime％)、明区水平运动百分率(Lcross％)、明区垂直运动百分率(Lrear％)、穿梭次数(Transition)、总水平运动(Cross)和总垂直运动(Rear).结果:与Control组比较,BZ及Px低、中、高剂量可显著增加FEP_Ntime％,FEP_Ncross％,FEP_Nrear％,OFT_Ctime％,OFT_ Ccross％,EPM_Otime％,EPM_Oentries％,EZM_Otime％,EZM_Oentries％,LDB_ Ltime％,LDB_Lcross％,LDB_Lrear％(P＜0.05);Wx仅高剂量可显著增加OFT_Ccross％,EZM_Otime％,LDB_Lrear(P＜0.05);BZ及Px,Wx低、中、高剂量对FEP_Cross,FEP_Rear,OFT_Cross,OFT_Rear,EPM/EZM_Entries,LDB_Transition,LDB_Cross,LDB_Rear实验参数影响均无统计学差异.结论:牡丹皮抗焦虑作用有效部位是水蒸气蒸馏馏分(Px),即丹皮酚类成分,其可能的作用靶点是γ-氨基丁酸A受体(GABAAR).     

The anxiolytic effect of Sho-ju-sen, a Japanese herbal medicine, assessed by an elevated plus-maze test in mice

Sho-ju-sen (SK), a Japanese herbal medicine with a nourishing tonic action, is composed of a water extract of Kumazasa leaves (Sasa kurinensis Makino et Sibata) (SS), and ethanol extracts of Japanese red pine needles (Pinus densiflora Sieb. et Zucc) (PN) and Ginseng roots (Panax ginseng C. A. Meyer) (PX) in the ratio 8:1:1. In this study, an elevated plus-maze test in mice was carried out to assess whether SK had an anxiolytic effect. No significant change was observed in either the plus-maze or activity test following a single administration of SK (10 and 20 mL/kg p.o.). However, mice allowed a free intake of SK (10% solution) for 5 days and longer showed a significant prolongation of the time spent in the open arms (an anxiolytic effect), as long as that caused by the benzodiazepine anxiolytic diazepam (1 mg/kg p.o.). SK (1%, 3% and 30% solutions for 7 days) tended to develop the anxiolytic effect. Of the constituents of SK, SS (8% solution), but not PN (1% solution) or PX (1% solution), resulted in the anxiolytic effect. Except for a slight acceleration in the motor activity by PN (1% solution), no significant change in the motor activity was produced by any treatment with SK, SS or PX. The combined treatment of SK (10% solution) or SS (8% solution) with 1 mg/kg diazepam enhanced the anxiolytic effect. Flumazenil (0.1 mg/kg s.c.), a benzodiazepine receptor antagonist, alone did not change the time spent in the open arms. However, it completely reversed the anxiolytic effect of SK, SS and diazepam. The present results suggest that: (1) long-term treatment with SK develops an anxiolytic effect, (2) SS is the main constituent for the anxiolytic effect of SK, and (3) benzodiazepine receptors are involved in the anxiolytic effect of SK and SS.     

A Comparative Study on the Inhibitory Effects of Different Parts and Chemical Constituents of Pomegranate on α‐Amylase and α‐Glucosidase

Pomegranate has been documented for the management of diabetes in Unani and Chinese medicine. This study compared the effects of the extracts of different pomegranate parts, including juice, peels, seeds and flowers, on carbohydrate digestive enzymes (α‐amylase and α‐glucosidase) in vitro. The methanolic flower extract inhibited α‐amylase and α‐glucosidase, while the methanolic peel extract inhibited α‐glucosidase selectively. The most active flower extract was subjected to water‐ethyl acetate partition. The ethyl acetate fraction was more potent than the water fraction in inhibiting both enzymes. Gallic acid and ellagic acid also showed selective inhibition against α‐glucosidase, and their presence in the ethyl acetate fraction was confirmed by HPLC‐DAD and HPLC‐HESI‐MS. Our findings suggest that the inhibition of carbohydrate digestive enzymes and their phenolic content may contribute to the anti‐hyperglycaemic effects of pomegranate flower and peel, and support their claims in diabetes. Copyright © 2012 John Wiley & Sons, Ltd.     

Suppression of Lipopolysaccharide‐stimulated Cytokine/Chemokine Production in Skin Cells by Sandalwood Oils and Purified α‐santalol and β‐santalol

Medicinally, sandalwood oil (SO) has been attributed with antiinflammatory properties; however, mechanism(s) for this activity have not been elucidated. To examine how SOs affect inflammation, cytokine antibody arrays and enzyme‐linked immunosorbent assays were used to assess changes in production of cytokines and chemokines by co‐cultured human dermal fibroblasts and neo‐epidermal keratinocytes exposed to lipopolysaccharides and SOs from Western Australian and East Indian sandalwood trees or to the primary SO components, α‐santalol and β‐santalol. Lipopolysaccharides stimulated the release of 26 cytokines and chemokines, 20 of which were substantially suppressed by simultaneous exposure to either of the two sandalwood essential oils and to ibuprofen. The increased activity of East Indian SO correlated with increased santalol concentrations. Purified α‐santalol and β‐santalol equivalently suppressed production of five indicator cytokines/chemokines at concentrations proportional to the santalol concentrations of the oils. Purified α‐santalol and β‐santalol also suppressed lipopolysaccharide‐induced production of the arachidonic acid metabolites, prostaglandin E2, and thromboxane B2, by the skin cell co‐cultures. The ability of SOs to mimic ibuprofen non‐steroidal antiinflammatory drugs that act by inhibiting cyclooxygenases suggests a possible mechanism for the observed antiinflammatory properties of topically applied SOs and provides a rationale for use in products requiring antiinflammatory effects. Copyright © 2013 John Wiley & Sons, Ltd.     

α‐Glucosidase Inhibitors from the Stems of Embelia ribes

From the ethyl acetate extract of the stems of Embelia ribes (Myrsinaceae), a new alkenylresorcinol, embeliphenol A (1), together with 11 known compounds have been isolated. Their structures were elucidated on the basis of spectroscopic data. All compounds possessed significant α‐glucosidase inhibitory activity in a concentration‐dependent manner, except for 2 and 9. Compounds 1, 3–6, 8, and 12 showed more potent inhibitory activity, with IC₅₀ values ranging from 10.4 to 116.7 μM, than that of a positive control acarbose (IC₅₀, 214.5 μM). Copyright © 2014 John Wiley & Sons, Ltd.     

Anti‐inflammatory Effects of Ginsenosides Rg5, Rz1, and Rk1: Inhibition of TNF‐α‐induced NF‐κB,COX‐2, and iNOS transcriptional expression

In the course of this experiment on the anti‐inflammatory effect of ginsenosides, protopanaxdiol ginsenosides have shown inhibition activities in inflammatory responses: NF‐κB, COX‐2, and iNOS were induced by TNF‐α. The responses of this experiment were evaluated by NF‐κB‐luciferase assay and RT‐PCR experiment of COX‐2 and iNOS genes. The NF‐κB expressions were inhibited by ginsenosides Rd, Rg₅, Rz₁, and Rk₁ in a dose‐dependent manner. The IC₅₀ values were 3.47, 0.61, 0.63, and 0.75 μM, respectively. Particularly, ginsenosides Rg₅, Rz₁, and Rk₁ as converted ginsenosides from primary protopanaxdiol ginsenosidess significantly inhibited COX‐2 and iNOS gene expression. These inhibition levels were similar to sulfasalazine as reference material. Copyright © 2014 John Wiley & Sons, Ltd.     

Antioxidant and Anti‐α‐glucosidase Compounds from the Rhizome of Peltiphyllum peltatum (Torr.) Engl

The antioxidant, anti‐α‐glucosidase and anticholinesterase effects of the alcohol extract of fresh underground rhizomes of Peltiphyllum peltatum were studied. A potent antioxidant activity accompanied by a selective α‐glucosidase effect was observed for the crude extract. Further activity‐guided fractionation (petroleum ether, chloroform, ethyl acetate, n‐butanol and water) resulted in the identification of the ethyl acetate fraction with the highest antioxidant effect. Gallic acid, methyl‐3‐O‐methyl gallate, catechin, gallocatechin, bergenin and 11‐O‐galloylbergenin were isolated from the ethyl acetate fraction. While all the isolated compounds did show a variable degree of radical scavenging effect, 11‐O‐galloylbergenin was identified as the selective α‐glucosidase inhibitor. The isolation, structural elucidation and biological effects of these compounds are discussed. Copyright © 2012 John Wiley & Sons, Ltd.     

Antiviral and anticancer activities of 13(E)‐labd‐13‐ene‐8α,15‐diol isolated from Brachyglottis monroi

The antiviral activity of 13(E)‐labd‐13‐ene‐8α,15‐diol (1), isolated from Brachyglottis monroi, was examined against human rhinovirus 2 (HRV2) and 3 (HRV3), and the anticancer activity on human cancer cells (A549 and Hep2). Compound (1) showed strong anti‐HRV2 and HRV3 activity with a 50% inhibitory concentration (IC₅₀) of 2.68 and 0.87 µg/mL, respectively, and a 50% cytotoxicity concentration (CC₅₀) of 59.45 µg/mL. Ribavirin only showed anti‐HRV3 activity with an IC₅₀ of 30.48 µg/mL and a CC₅₀ > 100 µg/mL. The addition of compound (1) to HRV‐infected HeLa cells directly reduced the formation of visible cytopathic effect (CPE) and it directly interacted with HRV particles. Furthermore, A549 and Hep2 cells incubated with 32 µg/mL of compound (1) for 48 h exhibited antilung and antilaryngeal cancer activities, with a viability of less than 50%. These results suggest that compound (1) may be used as a potential antiviral and anticancer agent. Copyright © 2009 John Wiley & Sons, Ltd.     

In vivo Antimalarial Activity of α‐Mangostin and the New Xanthone δ‐Mangostin

Based on the previously reported in vitro antiplasmodial activity of several xanthones from Garcinia mangostana, two xanthones, α‐mangostin and a new compound, δ‐mangostin, were isolated from mangosteen husk, and the in vitro antiplasmodial and cytotoxic effects were determined. α‐Mangostin was more active against the resistant Plasmodium falciparum chloroquine‐resistant (FCR3) strain (IC₅₀ = 0.2 ± 0.01 μM) than δ‐mangostin (IC₅₀ = 121.2 ± 1.0 μM). Furthermore, the therapeutic response according to the administration route was evaluated in a Plasmodium berghei malarial murine model. The greatest therapeutic response was obtained with intraperitoneal administration; these xanthones reduced parasitemia by approximately 80% with a daily dose of 100 mg/kg administered twice a day for 7 days of treatment. Neither compound was effective by oral administration. Noticeable toxicological effects were not observed. In addition to the antimalarial effect of these xanthones isolated from G. mangostana husk, the availability of larger amounts of husk raw material to purify the bioactive xanthones is advantageous, permitting additional preclinical assays or chemical transformations to enhance the biological activity of these substances. Copyright © 2015 John Wiley & Sons, Ltd.     

Parthenolide Inhibits the LPS‐induced Secretion of IL‐6 and TNF‐α and NF‐κB Nuclear Translocation in BV‐2 Microglia

Feverfew (Tanacetum parthenium [L.] Sch. Bip. [Asteraceae]) is a popular herbal treatment used to prevent and treat headache and migraine. Parthenolide (PTN), the sesquiterpene lactonic derivative that is the plant's major component, might be one of the ingredients that act on mediators of inflammation. In the present study, in cultured lipopolysaccharide (LPS)‐stimulated BV‐2 microglia pretreatment with PTN caused a dose‐dependent reduction of interleukin‐6 (IL‐6) secretion (29% by 200 nm, p < 0.001; 45% by 1 µm, p < 0.001; 98% by 5 µm, p < 0.001); at 5 µm, the highest concentration tested, it also reduced the secretion of TNF‐α (54%, p < 0.001). Western blotting analysis on separate cytoplasmic and nuclear extracts showed that PTN strongly reduced the translocation of nuclear factor (NF)‐κB to the cell nucleus. The reduction of microglial activation by inhibition of proinflammatory agents may help attenuate the onset and intensity of acute migraine attacks. These in vitro results provide an additional explanation for the efficacy of orally administered T. parthenium as an antimigraine agent. Copyright © 2012 John Wiley & Sons, Ltd.     

Analgesic and diuretic properties of α‐santalone from Polygonum flaccidum

Polygonum flaccidum Meissn. is an annual herb, native to Bangladesh, and well known for its analgesic, anti‐inflammatory, diuretic, purgative and insecticidal properties, and also for its use against snake‐bites. The analgesic and the diuretic properties of α‐santalone (1), isolated from the aerial parts of Polygonum flaccidum, were assessed by the acetic‐acid‐induced writhing method and the Lipschitz test, respectively. Complete ¹H and ¹³C NMR data of 1 are also presented. Copyright © 2010 John Wiley & Sons, Ltd.     

Zerumbone Suppresses IL‐1β‐induced Cell Migration and Invasion by Inhibiting IL‐8 and MMP‐3 Expression in Human Triple‐negative Breast Cancer Cells

Inflammation is a key regulatory process in cancer development. Prolonged exposure of breast tumor cells to inflammatory cytokines leads to epithelial‐mesenchymal transition, which is the principal mechanism involved in metastasis and tumor invasion. Interleukin (IL)‐1β is a major inflammatory cytokine in a variety of tumors. To date, the regulatory mechanism of IL‐1β‐induced cell migration and invasion has not been fully elucidated. Here, we investigated the effect of zerumbone (ZER) on IL‐1β‐induced cell migration and invasion in breast cancer cells. The levels of IL‐8 and matrix metalloproteinase (MMP)‐3 mRNA were analyzed by real‐time polymerase chain reaction. The levels of secreted IL‐8 and MMP‐3 protein were analyzed by enzyme‐linked immunosorbent assay and western blot analysis, respectively. Cell invasion and migration was detected by Boyden chamber assay. The levels of IL‐8 and MMP‐3 expression were significantly increased by IL‐1β treatment in Hs578T and MDA‐MB231 cells. On the other hand, IL‐1β‐induced IL‐8 and MMP‐3 expression was decreased by ZER. Finally, IL‐1β‐induced cell migration and invasion were decreased by ZER in Hs578T and MDA‐MB231 cells. ZER suppresses IL‐1β‐induced cell migration and invasion by inhibiting IL‐8 expression and MMP‐3 expression in TNBC cells. ZER could be a promising therapeutic drug for treatment of triple‐negative breast cancer patients. Copyright © 2014 John Wiley & Sons, Ltd.     

Identification of higenamine as a novel α1‐adrenergic receptor antagonist

The α₁‐adrenoceptor (α₁‐AR) antagonists are potential candidates for the treatment of blood pressure. Higenamine (HG) is a novel α₁‐AR antagonist. In this study, we investigated the effects of HG in HEK293A cells transfected with α_1A‐, α_1B‐, and α_1D‐AR in vitro, rat mesenteric artery ex vivo, Wistar–Kyoto rats and spontaneously hypertensive rats in vivo. The radioligand binding assay showed that HG competitively inhibited the binding of [³H]‐prazosin to α₁‐AR in a concentration‐dependent manner. The affinities (pKi) of HG for the cloned α_1A‐, α_1B‐, and α_1D‐AR were 6.57, 6.48, and 6.35, respectively, indicating that HG displayed no selectivity for the three α₁‐AR subtypes. In in vitro studies, HG was able to blunt inositol monophosphate production. It also displayed an inhibitory effect on the influx and entry of calcium ions and phosphorylation of extracellular signal‐regulated kinase 1 and 2 induced by phenylephrine (PE). In ex vivo studies, PE caused a dose‐dependent inotropic response curve, and the pA₂ value for HG was 6.86 ± 0.29. In addition, the in vivo results showed that HG could decrease the blood pressure in normotension, spontaneous hypertension, and PE‐induced hypertension models. These results indicate that HG can directly bind to α₁‐AR and it appears to be a novel antagonist for α₁‐AR, which may contribute to its hypotensive effect.     

Schisandrin C Ameliorates Learning and Memory Deficits by Aβ1–42‐induced Oxidative Stress and Neurotoxicity in Mice

Schisandrin C (SCH‐C) is a main and typical antioxidative lignan isolated from the fruits of Schisandra chinensis (Trucz.) Baill (a widely used traditional Chinese medicine). The present study aimed to characterize the effect of SCH‐C on memory impairment and further research on pathological changes in Aβ_1–42‐induced Alzheimer's disease mice. Mice were administration with SCH‐C daily for 5 days in the lateral cerebral ventricles using sterotaxically implanted cannula. Cognitive functions were assessed by Y‐maze test, active avoidance test and Morris water maze test in all groups, and the level of Aβ_1–42 and neuronal injury induced by Aβ_1–42 were reversed remarkably following SCH‐C treatment compared with sham group; meanwhile the impairment of short‐term or working memory was dramatically improved. In addition, SCH‐C significantly inhibited total cholinesterase (ChEtotal), and increased superoxide dismutase (SOD) and glutathione peroxidase (GSH‐px) activity glutathione (GSH) levels in the hippocampus and cerebral cortex. It can be speculated that SCH‐C offers protection against Aβ_1–42‐induced dysfunction in learning and memory by inhibiting ChEtotal and its antioxidant action. Copyright © 2015 John Wiley & Sons, Ltd.     

Chelidonine inhibits TNF‐α‐induced inflammation by suppressing the NF‐κB pathways in HCT116 cells

Nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) is a complex that regulates several hundreds of genes, including those involved in immunity and inflammation, survival, proliferation, and the negative feedback of NF‐κB signaling. Chelidonine, a major bioactive, isoquinoline alkaloid ingredient in Chelidonium majus, exhibits antiinflammatory pharmacological properties. However, its antiinflammatory molecular mechanisms remain unclear. In this work, we explored the effect of chelidonine on TNF‐induced NF‐κB activation in HCT116 cells. We found chelidonine inhibited the phosphorylation and degradation of the inhibitor of NF‐κB alpha and nuclear translocation of RELA. Furthermore, by inhibiting the activation of NF‐κB, chelidonine downregulated target genes involved in inflammation, proliferation, and apoptosis. Chelidonine also inhibited mitogen‐activated protein kinase pathway activation by blocking c‐Jun N‐terminal kinase and p38 phosphorylation. These results suggest that chelidonine may be a potential therapeutic agent against inflammatory diseases in which inhibition of NF‐κB activity plays an important role.