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Zexieyin formula (ZXYF), a traditional Chinese herbal formula recorded in the Huangdi Neijing to have efficacy in relieving spleen dampness and heat accumulation syndrome, which is also the key pathogenesis of atherosclerosis (AS). The efficacy has demonstrated by our previous studies. However, the intrinsic mechanism of ZXYF for treating vascular inflammation and the effect of inflammatory response on plaque are not known. Currently, plaque stabilization is crucial for the prognosis of AS. Our study mainly focused on the therapeutic effects of ZXYF on high-fat diet (HFD)-induced vascular inflammation and vulnerable plaques (VP) in mice and explored its underlying mechanism. Male apolipoprotein E knockout (APOE−/−) mice were fed HFD for 8 weeks to establish a VP model. During this period, the mice were also administered ZXYF, while atorvastatin (ATO) was used as a positive control. Aortic plaque area and morphology were detected by oil red staining and HE staining. Aortic plaque collagen content was detected by Masson staining. M1/M2 type macrophages were detected using immunofluorescence (IF). The study analyzed the levels of inflammation-related cytokines (IL-1β, IL-10, IL-6), MAPK/NF-κB pathway proteins, and NLRP3 inflammasomes (NLRP3, Caspase-1) using Western blot. Additionally, the levels of matrix metalloproteinase (MMP)-2 and MMP-9 and α-smooth muscle actin (α-SMA) in the aorta were analyzed using immunohistochemistry (IHC). The plaque instability index was calculated for each group using the vulnerable plaque formula. In this study, APOE−/− mice were fed high-fat diet for 8 weeks. The results of oil-red and HE staining indicated a significant increase in the aortic plaque area of the mice, which exhibited a typical VP phenotype. ZXYF and ATO significantly improved AS plaques and prevented plaque rupture. HFD exacerbated vascular inflammation, stimulated macrophage conversion to M1-type through the MAPK/NF-κB signaling pathway, and released pro-inflammatory factors such as interleukin (IL)-1β, IL-1α, and IL-6. These factors activated NLRP3 inflammasome, leading to cellular death. However, ZXYF could reverse this trend and promote the conversion of macrophages to the anti-inflammatory M2 type. The anti-inflammatory effect of ATO was not significant. Moreover, HFD promoted the release of MMP-2 and MMP-9 from macrophages, which degraded plaque collagen, and induced a decrease in plaque SMC content, resulting in a thinning of the plaque fibrous cap. In contrast, ZXYF inhibited the decomposition of plaque collagen and increased the content of plaque smooth muscle cells (SMC) by reducing macrophage secretion of MMPs, thereby stabilizing plaques. Although ATO could reverse the decrease in plaque collagen and SMC content, its effect on MMPs was not significant. Finally, we calculated the vulnerability index to assess the overall risk of the plaque vulnerability phenotype. In line with these findings, ZXYF and ATO were able to effectively reverse the increase in the vulnerability index caused by HFD and lower the risk of adverse cardiovascular events. Our results suggested that ZXYF could reduce inflammation and increase plaque stability by inhibiting the MAPK/NF-κB signaling pathway, which provided a theoretical basis for clinical application and subsequent research. [Display omitted] • Zexieyin formula (ZXYF) has efficacy in the treatment of atherosclerosis (AS). • ZXYF inhibited vascular inflammation by preventing macrophage, decreasing the secretion of MMPs or activation of NLRP3 in aorta. • This study will promote the use of ZXYF in patients with AS. [ABSTRACT FROM AUTHOR]

Zexieyin formula (ZXYF) has been identified to have therapeutic actions of atherosclerosis (AS). It's unknown that whether ZXYF has therapeutic potential of atherosclerosis (AS) with cognitive impairment (CI) and its underlying mechanisms. To elucidate therapeutic effect of ZXYF for AS with CI as well as its underlying mechanisms in AS with CI mice model. To establish AS with CI model, we fed ApoE−/− mice with high-fat diet (HFD) for 8 weeks. Oil red O staining (ORO) and Hematoxylin-eosin staining (HE) were used to detect aortic plaque area. Morris water maze (MWM) and Y-maze were used to measure cognitive function and cognitive improvement after administration of ZXYF and atorvastatin (ATO). Network pharmacology was used to screen for potential mechanisms for improving cognitive function. Western blot was used to detect expressions of MAPK, Aβ and synaptic proteins in hippocampus. HFD caused and accelerated the AS in ApoE−/− mice, while it was easier able to produce CI than normal mice. Administration of ZXYF or ATO for 8 weeks significantly reduced aortic plaque area in ORO and HE tests, and improved cognitive abilities in MWM and Y-maze tests. Network pharmacology results showed that MAPK or synaptic proteins were highly associated with CI. HFD contributed to abnormal expressions of MAPK (pERK, pP38, pJNK), NF-kB, synaptic proteins (PSD95, synapsin1) and β-amyloid (Aβ) in hippocampus, which were all reversed by ZXYF. However, ERK and PSD95 expressions were not reversed by ATO in hippocampus. ZXYF mitigated AS, further alleviating CI by modulating MAPK signaling, relating to synaptic proteins enhancing and Aβ protein decreasing in the hippocampus. This study firstly lit up the new clinical application of ZXYF, which might promote the use of ZXYF in AS and CI patients. [Display omitted] • Long-term HFD caused atherosclerosis with cognitive impairment only in ApoE−/− mice but not in WT mice. • Zexieyin formula mitigated atherosclerosis to relieve cognitive impairment by modulating MAPK signaling, synaptic proteins and β-amyloid in hippocampus. • This study firstly shed light on clinical application of Zexieyin formula for the treatment of comorbidities such as atherosclerosis with cognitive impairment in patients. [ABSTRACT FROM AUTHOR]

Pyrolae herba (PH), a kind of Chinese herb, has been identified to have an anti-inflammatory effect, while the potential for treating cognitive impairment (CI), as well as the underlying mechanisms, is unclear. Currently, the interaction between neuroinflammation and neural function play a critical role in pathophysiology of CI. To elucidate therapeutic effect of PH for CI as well as its underlying mechanisms with LPS-treated mice model. In this study, male C57BL6/J mice received lipopolysaccharide (LPS) injection for 10 days to establish CI model and were administrated with PH for 14 days. We used piracetam as a positive control. Memory and spatial function was tested by Morris water maze (MWM). The level of inflammation-related cytokines (TNF-α, IL-1β, IL-10, IL-6) were determined by enzyme-linked immunosorbent assay (ELISA) in serum and western blot in hippocampus. Immunofluorescence (IF) was used to measure the levels of ionized calcium binding linker molecule 1 (IBA-1), glial fibrillary acidic protein (GFAP), BrdU, Ki67 and doublecortin (DCX) in hippocampus. The mRNA sequencing was used to screen the potential target of PH with therapeutic CI. Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the gene alteration of triggering receptor expressed on myeloid cells 2 (TREM2) in hippocampus. We used western blot to determine protein expressions of TREM2 and its related signaling, as well as synaptic proteins in hippocampus. The results revealed that LPS contributed to CI, and PH or piracetam treatment significantly ameliorated CI in MWM test. LPS contributed to increasing expressions of TNF-α and IL-1β in serum and hippocampus, which both reversed by PH or piracetam. PH or piracetam could inhibit the activation of glial cells including microglia and astrocyte in the hippocampus in LPS-induced CI model. The mRNA sequencing and RT-PCR results showed that LPS significantly increased the gene expression of TREM2, which was reversed by PH. The alteration of TREM2 expression was the most significant among the 10 genes (TREM2, Slc24a2, Ptch2, Gck, Il1rapl1, Cadps2, Btbd11, Secisbp2l, Tenm3 and Prepl) in hippocampus. Protein results showed that LPS upregulated the expressions of TREM2 and its related proteins including DAP12, spleen tyrosine kinase (SYK) phosphorylation and ADAM 10, which were all reversed by PH or piracetam in hippocampus. Furthermore, LPS was capable of reducing the expression of BrdU and DCX co-labeled positive cells in hippocampal dentate gyrus (DG), which was reversed only by PH. Moreover, PH or piracetam treatment significantly increased the expression of Ki67 and DCX co-labeled positive cells in hippocampal DG. The expression of synapsin1 was obviously decreased by LPS and was significantly reversed by PH or piracetam. PH could alleviate CI by suppressing the secretion of pro-inflammatory cytokines and mitigating astrocyte activity by restraining microglia's activation in hippocampus, further facilitating neurogenesis and proliferation, thereby enhancing pre-synaptic protein. This study highlighted on the clinical application of PH, which might promote the use of phytomedicine in CI patients. [Display omitted] • Pyrolae herba has capable of improving the cognitive impairment in LPS-treated mice. • The effects of Pyrolae herba on improving cognitive impairment by reversing Trem2-related signaling in the hippocampus of LPS-treated mice. • Pyrolae herba enhances neurogenesis, proliferation, and pre-synaptic protein in the hippocampus of LPS-treated mice. • This study shed light on the clinical application of Pyrolae herba, which would promote the use of medicinal herbs in cognitive impairment patients. [ABSTRACT FROM AUTHOR]

Jiawei-Xiaoyao pill (JWX), a traditional Chinese medicine, was recorded in ancient Chinese medicine pharmacopoeia using for treatment of various diseases, including mood disorders. Current mainstream antidepressants have a disadvantage in delayed onset of action. The rapid antidepressant potential of JWX and the underlying mechanisms remain unclear. We aimed to assess the rapid antidepressant potential of JWX, within the prescription dose range, and the distinct underlying neuroplasticity signaling mechanism. The rapid antidepressant response of JWX were determined using various behavioral paradigms, and in a corticosterone (CORT)-induced depression model in mice. The molecular neuroplasticity signaling and the expression of BDNF in the hippocampus was evaluated using immunoblotting and immunostaining. The contribution of specific signaling was investigated using pharmacological interventions. A single dose of JWX induced rapid and persistent antidepressant effects in both the normal and chronic CORT-exposed mice. The phosphorylation of CaMKII, mTOR, ERK and the expressions of BDNF, synapsin1 and PSD95 increased at 30 min post JWX. JWX restored the expression of BDNF in the hippocampal dentate gyrus reduced by CORT-exposure. The rapid antidepressant effect and upregulation of BDNF expression by JWX was blunted by a mTOR antagonist, rapamycin, or a CaMKII antagonist, KN-93. CaMKII signaling blockade blunted mTOR signaling activated by JWX, but not vice versa. JWX elicits a rapid antidepressant effect, via quickly stimulating CaMKII signaling, subsequently activating mTOR-BDNF signaling pathway, and thus enhancing hippocampal neuroplasticity. [Display omitted] • Jiawei-Xiaoyao pill (JWX) elicits rapid anxiolytic and antidepressant effects. • JWX-activated hippocampal mTOR-BDNF signaling regulates rapid antidepressant effects. • JWX-activated mTOR-BDNF signaling relied on stimulation of CaMKII signaling. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: The combination of Radix Angelicae sinensis (Oliv.) Diels and Radix Sophora flavescens Ait. was extensively used in traditional Chinese medicine to treat inflammatory diseases, such as acne, heart disease, and hepatitis. Sodium ferulate (SF) and oxymatrine (OMT) were effective component of Radix Angelicae sinensis (Oliv.) Diels and Radix Sophora flavescens Ait., respectively. Aim of the study: In this study, we investigated the synergistic anti-inflammatory effect of the combination of SF and OMT, and its modulation on inflammation-associated mediators in RAW 264.7 cells. Materials and methods: In vivo, the anti-inflammatory effects of the combination of SF and OMT were evaluated with the xylene-induced mouse ear edema model and the carrageenan-induced rat paw edema model. In vitro, chemokines and cytokines mRNA expressions in lipopolysaccharide (LPS)-activated RAW 264.7 cells were determined by real-time PCR (RT-PCR) microarray analysis. The levels of interleukin-11 (IL-11), C-reactive protein (CRP) and interferon-γ (INF-γ) in the supernatant of LPS-stimulated RAW 264.7 cells were measured by enzyme-linked immune-sorbent assay (ELISA). Results: The combination of SF and OMT could significantly inhibit the edema in the xylene-induced mouse ear edema and carrageenan-induced rat paw edema, but no effect was found when each drug was used alone according to above doses. The combination exhibited a better effect in down-regulating mRNA expressions of inflammation-associated mediators in LPS-stimulated RAW 264.7 cells than SF or OMT alone. The ELISA results showed that the combination synergistically inhibited LPS-induced IL-11, CRP and INF-γ production in a dose-dependent manner. Conclusion: The combination of SF and OMT showed synergistic anti-inflammatory effect, and the activity was probably related to its modulation on inflammation-associated mediators, especially IL-11, CRP and INF-γ. [Copyright &y& Elsevier]

Yueju-Ganmaidazao Decoction (YG) is a multiherbal medicine prescribed for treatment of mood disorder, consisting of two classical traditional Chinese herbal medicine Yueju and Ganmaidazao. Yueju and Ganmaidazao both are used for depression treatment. The combined decoction of Yueju and Ganmaidazao is prescribed to achieve optimal clinical outcomes by dealing with different symptoms of depression. Recent studies indicated ethanol extract of Yueju was capable to confer rapid antidepressant-like response. The antidepressant activity of YG decoction with fast-onset feature remains to be investigated. Rapid and safe antidepressant treatment is urgently needed. This study aimed to assess the rapid antidepressant-like activity of YG and the underlying mechanism, focusing on NMDA/NO/cGMP signaling. The optimal doses for immediate and persistent antidepressant-like response were first screened using tail suspension test (TST) and forced swimming test (FST) post a single administration of YG. The rapid action was further confirmed by using the chronic mild stress (CMS) and learned helplessness (LH) paradigms. The expressions of NMDA receptor subunits were evaluated post stress and YG. The contributions of NMDA, NO, and cGMP signaling to the antidepressant effect of YG were investigated systematically using pharmacological interventions. The optimal dose for immediate and persistent antidepressant potential, evidenced with reduced immobility times in TST or FST from 30 min to 7 days, was determined. The rapid antidepressant-like effect was confirmed in CMS and LH paradigms, including instant normalization of sucrose preference behavior. The expression of NMDA subunit NR1 in the hippocampus was reduced from 30 min to 5 days post YG. In animals subjected to CMS and LH, hippocampal NR1 expression increased, reversed by YG. YG's antidepressant-like effect was blunted by pretreatment with the agonists along the signalings including NMDA (75 mg/kg), L-arginine (750 mg/kg) and sildenafil (5 mg/kg) in TST or FST. Conversely, administration of subeffective dose of individual antagonists, including MK-801 (0.05 mg/kg), 7-nitroindazole (30 mg/kg), methylene blue (10 mg/kg), in combination with a subeffective dose of YG, elicited antidepressant effects. YG conferred rapid antidepressant-like effects, and the antidepressant response was essentially dependent on suppression of NMDA/NO/cGMP signaling. Image 1 [ABSTRACT FROM AUTHOR]

Viscum coloratum (Kom.) Nakai has been traditionally used in China for nearly a thousand years to treat rheumatic diseases. However, its efficacy and mechanisms in treating rheumatoid arthritis (RA) have not been demonstrated. To investigate the anti-arthritic effects and molecular mechanisms of Viscum coloratum (Kom.) Nakai on collagen-induced arthritic mice through network pharmacology technology and experimental validation. First, the main ingredients of the extract of Viscum coloratum (Kom.) Nakai (EVC) were identified through chemical composition characterization using Ultra Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS). Then, the collagen-induced arthritis (CIA) model was established in DBA/1 J mice and the ameliorative effects of EVC on the progression of CIA mice were evaluated by oral treatment with different doses of the EVC for 28 days. After that, cytokine antibody microarray assay was used to detect the levels of multiple inflammation-related cytokines and chemokines in each group, and performed Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) enrichment analysis. Subsequently, the potential target for the effective chemical components of EVC in treating RA was identified using various databases. Additionally, a drug-disease target protein-protein interaction network (PPI) was conducted using Cytoscape for visualization and clustering, while GO and KEGG enrichment analyses were performed with the Metascape database. Finally, identified phenotypes and targets by network pharmacology analysis were experimentally validated in vivo. Treatment with EVC significantly suppressed the severity of CIA with a dramatic reduction of paw swelling, arthritis index, levels of IgGs (IgG, IgG1, IgG2a, and IgG2b), multi-inflammation-related cytokines and chemokines on the progression of CIA. Histopathological examinations showed EVC could markedly inhibit inflammatory cell infiltration, tartrate-resistant acid phosphatase (TRAP) activity of osteoclast, and bone destruction. Furthermore, GO and KEGG enrichment analyses revealed that EVC could ameliorate RA by inhibiting osteoclast differentiation and regulating multiple signaling pathways including Osteoclast differentiation, IL-17, and TNF. PPI network analysis demonstrated that AKT1, MMP9, MAPK3, and other genes were highly related to EVC in treating RA. Finally, we proved that EVC could inhibit the expression of NFTAc1, MMP9, Cathepsin K, and AKT which were closely related to osteoclast activity. EVC could treat RA through multiple components, multiple targets, and multiple pathways. The present study demonstrated the therapeutic efficacy of EVC and its molecular mechanisms in treating RA, indicating that it would be a potent candidate as a novel botanical drug for further investigation. [Display omitted] • EVC has similar therapeutic effects as Chinese medicinal formulae in treating RA. • EVC can treat RA by inhibiting multiple inflammatory cytokines and chemokines. • EVC contains a rare class of diphenylheptanes. [ABSTRACT FROM AUTHOR]

Treating cognitive impairment is a challenging and necessary research topic. ZeXieYin Formula (ZXYF), is a traditional herbal formula documented in the book of HuangDiNeiJing. Our previous studies demonstrated the ameliorative effects of ZXYF on atherosclerosis by reducing the plasma trimethylamine oxide (TMAO) level. TMAO is a metabolite of gut microorganisms, our recent research found that the increasing level of TMAO may have adverse effects on cognitive functions. Our study mainly focused on the therapeutic effects of ZXYF on TMAO-induced cognitive impairment in mice and explored its underlying mechanism. After the TMAO-induced cognitive impairment mice models were established, we applied behavioral tests to estimate the learning and memory ability of the ZXYF intervention mice. Liquid chromatography-mass spectrometry (LC-MS) was used to quantify the TMAO levels in plasma and the brain. The effects of ZXYF on the hippocampal synaptic structure and the neurons were observed by transmission electron microscopy (TEM) and Nissl staining. In addition, western-blotting (WB) and immunohistochemical (IHC) staining were used to detect the level of related proteins in the synaptic structure and further verify the changes in synaptic plasticity and the mTOR pathway after ZXYF administration. Behavioral tests showed that the learning and memory ability of mice impaired after a period of TMAO intervention and ZXYF could alleviate these changes. A series of results showed that ZXYF partly restored the damage of hippocampal synapse and neurons in TMAO-induced mice, at the same time, the expression of synapse-related proteins and mTOR pathway-related proteins were significantly regulated compared with the damage caused by TMAO. ZXYF could alleviate TMAO-induced cognitive impairment by improving synaptic function, reducing neuronal damage, regulating synapse-associated proteins, and regulating the mTOR signaling pathway. Graphical abstract: Schematic diagram of the mechanism by which ZXYF affects cognitive impairment. ZXYF as a Traditional Chinese Medicine can effectively reduce the synthesis of TMAO, modulate the mTOR signaling pathway and improve synaptic plasticity to reduce cognitive impairment caused by TMAO. [Display omitted] • ZXYF could be a novel therapeutic approach for TMAO-related cognitive impairment. • The ZXYF treatment reduced the elevation of TMAO levels in both plasma and brain. • Treatment with ZXYF for TMAO-induced cognitive disorder led to alterations in both synaptic plasticity and the mTOR pathway. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Suanzaorenhehuan Formula (SHF) has been used for treating depression-like disorders for many years in China. The saponins part of the SHF (SSHF) extract was the antidepressant effective component. Aim of study To investigate the antidepressant-like effect of SSHF and its possible mechanisms. Materials and methods Experimental approaches including the forced swim test (FST), the tail suspension test (TST) and unpredictable chronic mild stress (UCMS) were used to evaluate the effects of SSHF. The possible mechanisms were explored by measuring monoamine neurotransmitter in mice frontal cortex and hippocampus, testing monoamine oxidase enzyme (MAO) activities, antioxidant enzyme activities and free radicals levels in the brains of UCMS-exposed mice. Results The results showed that SSHF (10, 20, 40 mg/kg) significantly decreased the immobility period in FST and TST in mice after two-week treatment. Whereas, SSHF had no significant effect on locomotor activity in mice. It was also found that the serotonin (5-HT) and noradrenaline (NE) levels in the hippocampus and frontal cortex were significantly increased only in 40 mg/kg SSHF treated mice. In addition, SSHF (10, 20, 40 mg/kg) significantly inhibited monoamine oxidase-A (MAO-A) and monoamine oxidase-B (MAO-B) after 21-day UCMS exposure. SSHF (10, 20, 40 mg/kg) significantly decreased the nitrous oxide (NO) levels, and increased the activities of total antioxidant capability (T-AOC), glutathione peroxidase (GSH-PX), and catalase (CAT) in different degrees in the brains of UCMS-exposed mice. Conclusions Our results suggested that SSHF may effectively produce an antidepressant-like effect, which appeared to involve the serotonergic, noradrenergic, monoamine oxidase enzyme and antioxidant systems. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Cyclocarya paliurus Batal., a Chinese native plant, is the sole species in its genus and its leaves have been widely used as a remedy for diabetes in traditional folk medicine. The study was undertaken to evaluate the effects of Cyclocarya paliurus leaves extracts (CPE) on adipokine expression and insulin sensitivity in mice. Materials and methods: Mice were stimulated with conditioned medium (prepared from activated macrophages, Mac-CM) to induce adipose dysfunction and insulin resistance. Then mice were treated with CPE (100, 200 and 500mg/kg, ig.) or metformin (200mg/kg, ig.), followed by glucose and insulin intolerance, adipokine expression, phosphorylation of insulin receptor substrate (IRS-1) and glucose consumption measurement. Results: CPE, as well as metformin effectively promoted glucose disposal in oral glucose tolerance test in normal mice. Mac-CM challenge induced glucose and insulin intolerance, but CPE reversed these alternations with increased glycogen content in muscle and liver, well demonstrating its beneficial effects on glucose homeostasis. RT-qPCR analysis showed that CPE inhibited TNF-a, IL-6, MCP-1 and resistin overexpression and effectively enhanced adiponectin expression in adipose tissue when mice were exposed to Mac-CM stimulation. Inflammation impaired insulin signaling in muscle, whereas CPE inhibited inflammation-induced serine phosphorylation of IRS-1 and effectively restored the phosphorylation of both IRS-1 at tyrosine residues and downstream Akt phosphorylation in response to insulin. Moreover, independently of insulin, CPE promoted glucose consumption in adipocytes under normal and inflammatory conditions. Conclusion: Above-mentioned results demonstrated that CPE beneficially regulated adipokines expression and ameliorated insulin resistance through inhibition of inflammation in mice. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Suanzaorenhehuan Formula (SHF) is a Chinese herbal formula for the treatment of depression-like disorders. It contains four herbs: Semen Ziziphi spinosae, Cortex Albiziae, Radix Paeoniae Alba and Semen Platycladi. The present study is to investigate the antidepressant-like effect of the ethanolic extract of SHF and its possible mechanisms. Materials and methods: Mouse models of depression including the tail suspension test (TST), forced swimming test (FST) and chronic unpredicted mild stress (CUMS) were used to evaluate the effects of SHF extract. The mechanisms were examined by measuring monoamine neurotransmitters in mice hippocampus and frontal cortex, testing monoamine oxidase enzyme (MAO) activities in brain of CUMS-exposed mice. Results: After one-week treatment, SHF extract (50, 100 and 200mg/kg) induced a significant decrease on immobility time in TST. After two-week treatment, SHF extract (50, 100 and 200mg/kg) led to a reduction in the immobility period in TST and FST. The 5-HT levels in mice hippocampus were increased only after 200mg/kg SHF extract treatment. The noradrenaline (NE) levels were increased after 200mg/kg SHF extract treatment in mice hippocampus and frontal cortex. SHF extract (50, 100 and 200mg/kg) significantly inhibited monoamine oxidase-A (MAO-A) and monoamine oxidase-B (MAO-B) after 21-day CUMS exposure. Conclusion: These findings demonstrated that ethanolic SHF extract produced an antidepressant-like effect and the mechanism of action involves the serotonergic, noradrenergic and monoamine oxidase enzyme systems although underlying mechanism still remains to be further elucidated. [Copyright &y& Elsevier]