Garlic essential oil ameliorates depression-like behaviors in unpredictable chronic mild stress by modulating the brain NLRP3 inflammasome pathway and influencing the gut barrier and microbiota.

Depression is a severe mental disorder, with approximately 300 million people suffering from it. Recent studies have demonstrated that chronic neuroinflammation is significantly associated with intestinal flora and barrier function in depression. As a therapeutic herb, garlic (Allium sativum L.) has detoxification, antibacterial activity, and antiinflammatory functions; however, its antidepressant effect through gut microbiota and barrier function has not been reported yet. The present study investigated the effect of garlic essential oil (GEO) and its active constituent diallyl disulfide (DADS) on depressive behavior by attenuating the NLRP3 inflammasome, alternating intestinal barrier function and gut microbiota in an unpredictable chronic mild stress (US) model in rats. This study found that dopamine and serotonin turnover rates were reduced significantly with a low dose of GEO (25 mg per kg bw). The GEO groups effectively reversed sucrose preference and increased the total distance traveled in the behavioral test. Moreover, 25 mg per kg bw GEO inhibited the UCMS-induced activated inflammatory response, reflected by reduced expression in the frontal cortex of NLRP3, ASC, caspase-1, and its downstream IL-1ß proteins, as well as the concentration of IL-1ß and TNF-α in the serum. Supplementation with GEO increased the expression of occludin and ZO-1 and the concentration of short-chain fatty acids to influence the impact of intestinal permeability in depressive conditions. The results revealed that GEO administration caused significant changes in the α and ß diversity and abundance of certain bacteria. At the genus level, GEO administration significantly increased the relative abundance, particularly beneficial SCFA-producing bacteria, and may improve depression-like behavior. In conclusion, these results indicated the antidepressant effects of GEO involved in the inflammatory pathway, short-chain fatty acids, intestinal integrity, and intestinal composition.

Anti-depressive-like and cognitive impairment alleviation effects of Gastrodia elata Blume water extract is related to gut microbiome remodeling in ApoE-/- mice exposed to unpredictable chronic mild stress.

ETHNOPHARMACOLOGY RELEVANCE: Gastrodia elata Blume (GE) is a traditional Chinese dietary therapy used to treat neurological disorders. Gastrodia elata Blume water extract (WGE) has been shown to ameliorate inflammation and improve social frustration in mice in a chronic social defeat model. However, studies on the anti-depressive-like effects and cognitive impairment alleviation related to the impact of WGE on the gut microbiome of ApoE-/- mice remain elusive. AIM OF THE STUDY: The present study aimed to investigate the anti-depressive-like effect and cognitive impairment alleviation and mechanisms of WGE in ApoE-/- mice subjected to unpredictable chronic mild stress (UCMS), as well as its impact on the gut microbiome of the mice. MATERIALS AND METHODS: Sixty ApoE-/- mice (6 months old) were randomly grouped into six groups: control, UCMS, WGE groups [5, 10, 20 mL WGE/kg body weight (bw) + UCMS], and a positive group (fluoxetine 20 mg/kg bw + UCMS). After four weeks of the UCMS paradigm, the sucrose preference, novel object recognition, and open field tests were conducted. The neurotransmitters serotonin (5-HT), dopamine (DA) and their metabolites were measured in the prefrontal cortex. Serum was collected to measure corticosterone and amyloid-42 (Aß-42) levels. Feces were collected, and the gut microbiome was analyzed. RESULTS: WGE restored sucrose preference, exploratory behavior, recognition ability, and decreased the levels of serum corticosterone and Aß-42 in ApoE-/- mice to alleviate depressive-like behavior and cognitive impairment. Furthermore, WGE regulated the monoamine neurotransmitter via reduced the 5-HT and DA turnover rates in the prefrontal cortex. Moreover, WGE elevated the levels of potentially beneficial bacteria such as Bifidobacterium, Akkermansia, Alloprevotella, Defluviitaleaceae_UCG-011, and Bifidobacterium pseudolongum as well as balanced fecal short-chain fatty acids (SCFAs). CONCLUSION: WGE demonstrates anti-depressive-like effects, cognitive impairment alleviation, and gut microbiome and metabolite regulation in ApoE-/- mice. Our results support the possibility of developing a functional and complementary medicine to prevent or alleviate depression and cognitive decline using WGE in CVDs patients.

Genotoxicity and 28-day repeated dose oral toxicity study of garlic essential oil in mice.

Background and aim: Garlic essential oil (GEO) isolated from Garlic (Allium sativum L.) exerts biological activities in disease prevention, particularly in metabolic and liver diseases, and is used for a dietary therapy for centuries. However, due to the side effects associated with the excessive consumption of GEO, there is a need to evaluate the safety of the GEO. Experimental procedure: Ames test using five Salmonella typhimurium strains (TA98, TA100, TA102, TA1535, and TA1537) and Chinese hamster ovary (CHO-K1) cells with or without metabolic activation (S9 system), and mammalian erythrocyte micronucleus test were used to assess the genotoxicity and clastogenic effects of GEO. A repeated dose of GEO (15, 25, and 50 mg/kg body weight, p.o.) were administrated to ICR mice for 28 days to ascertain the subacute toxicity of GEO. Results and conclusions: The results of the Ames test with or without S9 system indicated that GEO did not induce mutagenicity nor have clastogenic effects in CHO-K1 cells with or without S9 activation. Furthermore, GEO did not affect the ratio of immature to total erythrocytes or the number of micronuclei in immature erythrocytes of ICR mice after 24 and 48 h. In a 28-day oral toxicity assessment, GEO (15, 25, and 50 mg/kg body weight, p.o.)-fed ICR mice exhibited normal behaviors, mortality, body weight, daily intake, hematology, clinical biochemistry, and organ weight. GEO shows no genotoxicity, and the no-observed-adverse-effect level (NOAEL) for GEO is considered to be greater than 50 mg/kg bw/day orally for 28 days in mice.

Gastrodia elata Blume water extract modulates neurotransmitters and alters the gut microbiota in a mild social defeat stress-induced depression mouse model.

Gastrodia elata Blume has multiple bioactive functions, such as antioxidant and antidepressant activities, immune modulation, neuroplasticity, and neuroprotection. We previously found that the water extract of G. elata exerts antidepressant-like effects in unpredictable chronic mild stress models and animals exposed to the forced swimming test. We aimed to investigate the mechanisms by which the water extract of G. elata protects against subchronic- and mild-social defeat-stress-induced dysbiosis. After a 10-day subchronic and mild-social-defeat-stress program, oral treatment with the water extract of G. elata (500 mg/kg bw) resulted in reversal of depression-like behavior. In addition, monoamine analyses showed that the water extract of G. elata normalized the 5-hydroxyindoleacetic acid:5-HT ratio in the prefrontal cortex and colon and reduced the defeat-stress-induced kynurenine:tryptophan ratio in the colon. After the 10-day subchronic and mild social-defeat-stress program, the water extract of G. elata altered the intestinal microbiome by increasing Actinobacteria levels, modulating intestinal inflammation, and shifting the relative abundances of multiple bacterial groups in the gut. Our results suggest that the water extract of G. elata exhibits a potent antidepressant-like effect via the regulation of monoaminergic neurotransmission and alteration of gut microbiota composition and function, and that it may be an effective prevention for depression.

Antidepressant-like effects of water extract of Cordyceps militaris (Linn.) Link by modulation of ROCK2/PTEN/Akt signaling in an unpredictable chronic mild stress-induced animal model.

ETHNOPHARMACOLOGY RELEVANCE: Cordyceps militaris (Linn.) Link (CM) is a medicinal mushroom traditionally used in tonics for treating several neurological disorders, including epilepsy and anxiety, in Asia. Reports have shown that CM has anti-inflammatory and anti-oxidative effects and may be beneficial for depression management. AIM OF THE STUDY: This study aimed to investigate the potential of CM as an antidepressant for a long-term unpredictable chronic mild stress (UCMS) rodent models and explore its underlying mechanisms. MATERIALS AND METHODS: Rats were orally administered with 125 (low, L), 250 (medium, M), and 500 (high, H) mg/kg bodyweight (bw) of the water extract of CM (WCM) for 35 consecutive days in the UCMS protocol. The levels of cerebral serotonin (5-HT), dopamine (DA), and metabolites in the frontal cortex of the rats were measured. Blood was collected to investigate the levels of proinflammatory cytokines, and the brain was dissected to assay the stress-associated ROCK2/PTEN/Akt signaling. RESULTS: All doses of the WCM prevented abnormal behaviors induced by UCMS, including anhedonia and hypoactivity. The LWCM treatment reduced the turnover rate of 5-HT, and all doses of the WCM reduced the turnover rate of DA in the frontal cortex. The LWCM also attenuated the elevation of serum IL-1ß induced by chronic stress. All doses of the WCM attenuated the ROCK2 protein hyperactivation, and the LWCM further increased the down-regulation of p-Akt/Akt signaling. CONCLUSION: The WCM has antidepressant-like effects, which may result from the regulation of the stress-related ROCK2/PTEN/Akt pathway. Therefore, the WCM may be developed and used for the complementary treatment of depression.

Water extract of Armillaria mellea (Vahl) P. Kumm. Alleviates the depression-like behaviors in acute- and chronic mild stress-induced rodent models via anti-inflammatory action.

ETHNOPHARMACOLOGY RELEVANCE: Armillaria mellea (Vahl) P. Kumm. (AM) is an edible mushroom that has been reported as treatment for several neurological disorders, such as dizziness and epilepsy in Asia. Importantly, AM shares a symbiotic relationship with Gastrodia elata Blume (GE), a medicinal herb with antidepressant-like properties. Researchers believe that AM may possess pharmacological properties similar to GE due to their symbiosis, however, few studies have investigated the pharmacological effect of AM. AIM OF THE STUDY: The aim of this study was to explore the potential of AM as an antidepressant in forced-swimming test (FST) and unpredictable chronic mild stress (UCMS) rodent models and investigate its possible underlying mechanism. MATERIALS AND METHODS: Rats were orally administrated with 250, 500, and 1000 mg/kg body weight (bw) water extract of AM (WAM) for 28 and 35 consecutive days prior to the FST and UCMS protocols, respectively. The cerebral serotonin (5-HT) and the metabolites in the frontal cortex of rats were measured. The brain was dissected and the blood was collected to investigate the levels of inflammatory-related signaling pathway. RESULTS: All doses of WAM reduced the immobility time in the FST without disturbing autonomic locomotion. All doses of WAM prevented stress-induced abnormal behaviors in the UCMS model, including decreased sucrose preference and hypoactivity. 500 and 1000 mg/kg bw WAM attenuated the stress-induced increases in IL-1ß and TNF-α in the serum and cerebrum. 1000 mg/kg bw WAM alleviated brain inflammation by reducing the protein expression of ionized calcium binding adaptor molecule 1. CONCLUSION: WAM exhibited acute and chronic antidepressant-like effects, and may result from the anti-inflammatory actions. Therefore, the development of AM as a dietary therapy or adjuvant for depression treatment should be considered.

Safety evaluation of water extract of Gastrodia elata Blume: Genotoxicity and 28-day oral toxicity studies.

Water extract of Gastrodia elata Blume (WGE) has great potential as an anti-depressant and could be developed as a functional food. This study aims to assess the safety of WGE using in vitro and in vivo genotoxicity assays and a 28-day oral toxicity study. Results from a bacterial reverse mutation assay (Ames test) using five Salmonella typhimurium strains (TA98, TA100, TA102, TA1535, and TA1537) with or without metabolic activation (S9 system) showed that WGE did not induce mutagenicity. Nor did it induce clastogenic effects in Chinese hamster ovary (CHO-K1) cells with or without S9 activation. Moreover, WGE did not affect the proportion of immature to total erythrocytes or the number of micronuclei in immature erythrocytes of ICR mice. Finally, a dose-dependent 28-day repeated dose toxicity assessment of WGE (2040, 4080, and 8065 mg/kg body weight, p.o.) in mice revealed no adverse effects on behavior, mortality, body weight, haematology, clinical biochemistry, or organ weight. No toxicopathologic lesions were detected following administration of high-dose WGE compared to controls. In conclusion, WGE has no significant mutagenic or toxic properties, and the no-observed-adverse-effect level (NOAEL) of WGE can be defined as at least 8065 mg/kg/day orally for 28 days for male and female mice.

Combination of cut-log cultivated fruiting body and solid-state cultured mycelia of Taiwanofungus camphoratus ameliorates CCl4-induced liver injury in rats.

Taiwanofungus camphoratus, a medicinal mushroom indigenous to Taiwan, possesses various pharmacological functions. The most recognized ethnopharmacological relevance of T. camphoratus is hepatoprotection since it was traditionally used for treating liver disorders by Taiwan aborigines. The aim of this study is to evaluate the hepatoprotective effect of the combination of fruiting body and solid-state cultured mycelia of T. camphoratus (LDAC) on carbon tetrachloride (CCl4)-induced chronic liver damage in rats. We treated Wistar rats daily with low, medium and high [87.5, 175 and 437.5 mg/kg body weight (bw), respectively] doses of LDAC for 9 weeks. After the first week of treatment, rats were administered 20% CCl4 (0.5 mL/0.3 kg bw) twice a week to induce liver damage until the treatment ended. The results showed that administration of LDAC by oral gavage significantly reduced the absolute weight of the liver and the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in CCl4-treated rats. The activities of the antioxidant enzymes glutathione peroxidase (GPx), glutathione reductase (GRd) and catalase (CAT) were increased by LDAC treatment. Moreover, LDAC improved CCl4-induced hepatic vacuolization, necrosis and fibrosis in a dose-dependent manner, and no adverse effects were observed in the LDAC-treated groups. Based on the results, LDAC is a promising hepatoprotective agent for preventing and ameliorating CCl4-induced chronic liver injury, and this effect might be exerted through activation of the antioxidant defense system.

Poria cocos water extract ameliorates the behavioral deficits induced by unpredictable chronic mild stress in rats by down-regulating inflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: Poria cocos is a medicinal mushroom of the Polyporaceae family with antioxidant and anti-inflammatory activities, which has been used for its sedative, diuretic and tonic effects in traditional medicine for several hundred years. AIM OF STUDY: Considering that depression is an inflammatory related mental disease, this study investigated the antidepressant-like effects of water extract of P. cocos in a rodent animal model. MATERIALS AND METHODS: Rats that were exposed to a forced swimming test (FST) for 28 consecutive days, and unpredictable chronic mild stress (UCMS) for five weeks underwent treatment with P. cocos water extract (PCW) (doses: 100, 300 and 900 mg/kg body weight [bw]; administered by gavage). Dopamine (DA), serotonin (5-HT) and their metabolites in the frontal cortex of rats were measured. RESULTS: Our results firstly showed that sucrose preference during the UCMS paradigm was increased and immobility time in the FST was reduced with administration of PCW. In addition, PCW significantly attenuated UCMS-induced turnover rate of DA and 5-HT in the frontal cortex. Moreover, PCW inhibited UCMS-induced activated inflammatory response, reflected by reduced expression in the frontal cortex of p38, NF-κB and TNF-α. CONCLUSIONS: Our results strongly suggest that PCW exhibits a potent antidepressant-like effect via regulation of monoaminergic neurotransmission and inactivation of inflammation, and that P. cocos may be considered as a traditional herbal potential medicine for the treatment of depression.

Garlic essential oil mediates acute and chronic mild stress-induced depression in rats via modulation of monoaminergic neurotransmission and brain-derived neurotrophic factor levels.

Garlic essential oil (GEO) and its major organosulfur component (diallyl disulfide, DADS) possess diverse biological properties; however, limited information on their antidepressant-like effects is available. This study is the first to investigate these effects of GEO using the forced swimming test (FST) and unpredictable chronic mild stress (UCMS) induced depression in rats. After oral administration for 28 consecutive days, GEO (25 and 50 mg per kg bw) significantly reduced the immobility time in the FST. Additionally, GEO and DADS significantly reversed the sucrose preference index decrease induced by 5 weeks of UCMS. GEO (25 mg per kg bw) effectively decreased the frontal cortex turnover ratio of serotonin (5-HT) and dopamine (DA), thus increasing the 5-HT and DA levels, with no hippocampal effects. Chronic GEO treatment increased hippocampal brain-derived neurotrophic factor (BDNF), c-AMP response element binding protein (CREB), and protein kinase B (AKT) expression, exhibiting its effects via monoamine neurotransmitter modulation and the BDNF-related signaling pathway.

Antidepressant-like effects of Gan-Mai-Dazao-Tang via monoamine regulatory pathways on forced swimming test in rats.

Depression is a highly prevalent and recurrent mental disorder that impacts all aspects of human life. Undesirable effects of the antidepressant drugs led to the development of complementary and alternative therapies. Gan-Mai-Da-Zao-Tang (, gan mài dà zǎo tang) is a traditional herbal formula commonly used for the treatment of depression, but lack of scientific proof on its mechanism. It consisted of Glycyrrhiza uralensis Fisch. (licorice), Triticum aestivum L. (wheat) and Zizphus jujuba Mill. (jujube). The objective of this study is to investigate the antidepressant effects of Gan-Mai-Dazao-Tang and its ingredients in rats exposed to forced swimming test (FST). The 72 of male Nerl: Wistar rats (8 weeks old) were randomized into control (10 mL/kg bw H2O), licorice (0.4 g/kg bw), wheat (1.6 g/kg bw), jujube (0.5 g/kg bw), Gan-Mai-Da-Zao-Tang (2.5 g/kg bw of licorice: wheat: jujube in ratio of 5:20:6) and Prozac (18 mg/kg bw) groups. Samples were administered by oral gavage for 21 days. FST was performed on 21st day, with 15 min for pretest followed by 5 min for real test. Then, the animals were sacrificed and brain tissues were collected for monoamines analyses. The Gan-Mai-Da-Zao-Tang (LWJ) showed significantly down-regulation of immobility time, 3,4-dihydroxyphenylacetic acid (DOPAC) and DOPAC/dopamine (DA) turnover rates, and also enhanced the concentration of serotonin (5-HT) and DA in brain tissues, as compared with the control. The LWJ stated the potent antidepressant-like effect by modulating these monoamines concentration, while the licorice, wheat and jujube did not reported significant results as compared with control group. The positive control (Prozac) was noted with significantly reduction in body weight and appetite. In conclusion, the antidepressant-like effects of LWJ might be mediated by the regulation of monoamine neurotransmitters. Thus, it could beneficial in depression treatment as a complementary approach.

Antidepressant-like effects of water extract of Gastrodia elata Blume on neurotrophic regulation in a chronic social defeat stress model.

ETHNOPHARMACOLOGY RELEVANCE: Gastrodia elata Blume (GE) is a traditional Chinese medicine commonly used to treat dizziness, epilepsy, paralysis and some emotional symptoms in east Asia. We previously showed that the water extract of Gastrodia elata Blume (WGE) possesses anti-depression like effects in a forced swimming test and chronic mild stress model. AIM OF THE STUDY: The aim of this study was to investigate the antidepressant-like effects of WGE and potential mechanisms related to brain-derived neurotrophic factor (BDNF) regulation in mice exposed to chronic social defeat stress (CSDS) model. MATERIALS AND METHODS: Fifty C57BL/6 mice were divided into 5 groups as follows: a control (CTL) group, CSDS group, and 3 WGE groups receiving 250, 500 or 1000mg/kg body weight in the CSDS model. Mice were administered WGE for 24 days by oral gavage, and the social defeat stress paradigm began on day 14, except for the control group. A social interaction test was conducted to evaluate the antidepressant-like effects of WGE. Blood samples were collected to measure serum corticosterone levels, and the brain was dissected to investigate the expression of BDNF-related signaling pathway proteins using western blotting. RESULTS: Oral administration of WGE improved depression-like behaviors and stress-induced elevations of corticosterone. Further, WGE increased the protein expression of BDNF and promoted the hippocampal protein phosphorylation ratio of cAMP response element binding protein (CREB) and protein kinase B (Akt). CONCLUSION: WGE exerts antidepressant-like effects on mice in a CSDS model, likely through activating of the BDNF/CREB/Akt pathway. Therefore, WGE has potential as a supplement or an adjuvant to prevent or treat clinical depressive disorders.

Ginseng essence, a medicinal and edible herbal formulation, ameliorates carbon tetrachloride-induced oxidative stress and liver injury in rats.

BACKGROUND: Ginseng essence (GE) is a formulation comprising four medicinal and edible herbs including ginseng (Panax ginseng), American ginseng (Panax quinquefolius), lotus seed (Nelumbo nucifera), and lily bulb (Lilium longiflorum). This study was aimed at investigating the hepatoprotective effect of GE against carbon tetrachloride (CCl4)-induced liver injury in rats. METHODS: We treated Wistar rats daily with low, medium, and high [0.625 g/kg body weight (bw), 1.25 g/kg bw, and 3.125 g/kg bw, respectively] doses of GE for 9 wk. After the 1st wk of treatment, rats were administered 20% CCl4 (1.5 mL/kg bw) two times a week to induce liver damage until the treatment ended. RESULTS: Serum biochemical analysis indicated that GE ameliorated the elevation of aspartate aminotransferase and alanine aminotransferase and albumin decline in CCl4-treated rats. Moreover, CCl4-induced accumulation of hepatic total cholesterol and triglyceride was inhibited. The hepatoprotective effects of GE involved enhancing the hepatic antioxidant defense system including glutathione, glutathione peroxidase, glutathione reductase, glutathione S-transferase, superoxide dismutase, and catalase. In addition, histological analysis using hematoxylin and eosin and Masson's trichrome staining showed that GE inhibited CCl4-induced hepatic inflammation and fibrosis. Furthermore, immunohistochemical staining of alpha-smooth muscle actin indicated that CCl4-triggered activation of hepatic stellate cells was reduced. CONCLUSION: These findings demonstrate that GE improves CCl4-induced liver inflammation and fibrosis by attenuating oxidative stress. Therefore, GE could be a promising hepatoprotective herbal formulation for future development of phytotherapy.

Diet Supplementation with Allicin Protects against Alcoholic Fatty Liver Disease in Mice by Improving Anti-inflammation and Antioxidative Functions.

This study investigated the liver-protective effects of allicin, an active compound in fresh garlic, against alcoholic fatty liver disease (AFLD) and liver inflammation. Its effects were investigated in an AFLD model in male C57BL/6 mice, which were fed Lieber-DeCarli liquid diet containing ethanol. Allicin (5 and 20 mg/kg bw/day) was orally administered daily in the AFLD mice for 4 weeks. The results indicate that allicin promotes hepatoprotection by significantly reducing aspartate transaminase (AST) and alanine transaminase (ALT) levels (p < 0.05) in the plasma, which are key indicators of liver damage. Allicin reduced fat accumulation, increased glutathione and catalase levels, and decreased microsomal protein cytochrome P450 2E1 (CYP2E1) expression (p < 0.05) in the livers of the AFLD mice. Furthermore, allicin supplementation significantly decreased the levels of proinflammatory tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 and suppressed the expression of sterol regulatory element-binding protein-1 (SREBP-1) (p < 0.05). Additionally, it improved the hepatic alcohol dehydrogenase (ADH) activity (p < 0.05). Collectively, these findings demonstrate that allicin attenuates liver oxidative stress and inflammation.

Ginger Essential Oil Ameliorates Hepatic Injury and Lipid Accumulation in High Fat Diet-Induced Nonalcoholic Fatty Liver Disease.

The objective of this study was to investigate the hepatoprotective efficacy and mechanism of action of ginger essential oil (GEO) against the development of nonalcoholic fatty liver disease (NAFLD). Mice were maintained on either a control diet or high-fat diet (HFD) supplemented with GEO (12.5, 62.5, and 125 mg/kg) or citral (2.5 and 25 mg/kg) for 12 weeks. We demonstrated that GEO and its major component (citral) lowered HFD-induced obesity in a dose-dependent manner, accompanied by anti-hyperlipidemic effects by reducing serum free fatty acid, triglyceride, and total cholesterol levels. Moreover, liver histological results showed that administration of 62.5 and 125 mg/kg GEO and 25 mg/kg citral significantly reduced hepatic lipid accumulation. Further assessment by Western blotting and investigation of the lipid metabolism revealed that hepatic protein expression of sterol regulatory element-binding protein-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), and cytochrome P450 2E1 (CYP2E1) were down-regulated by GEO and citral, indicating that GEO and citral suppressed HFD-stimulated lipid biosynthesis and oxidative stress. Furthermore, GEO and citral effectively enhanced the antioxidant capacities and reduced inflammatory response in mouse liver, which exerted protective effects against steatohepatitis. Collectively, GEO and citral exhibited potent hepatoprotective effects against NAFLD induced by HFD in obese mice. Thus, GEO might be an effective dietary supplement to ameliorate NAFLD-related metabolic diseases, and citral could play a vital role in its management.

Anti-depressant effects of Gastrodia elata Blume and its compounds gastrodin and 4-hydroxybenzyl alcohol, via the monoaminergic system and neuronal cytoskeletal remodeling.

ETHNOPHARMACOLOGY RELEVANCE: Gastrodia elata Blume is a highly valuable traditional Chinese medicine used in the treatment of depression. However, compounds with antidepressant effects in water extracts of G. elata Bl. (WGE) have not been identified. The aims of this study were to determine the major antidepressant compound in WGE and to evaluate the antidepressant effects of WGE and its active compounds which involved the monoaminergic system and neuronal cytoskeletal remodeling. MATERIALS AND METHODS: Gastrodin (GAS) and 4-hydroxybenzyl alcohol (HBA) in WGE, were analyzed with high-performance liquid chromatography (HPLC)-ultraviolet detection. The forced swimming test (FST) was used to induce depression-like symptoms in 9 weeks old male Sprague-Dawley rats. The open field test (OFT) was used to measure anxiety after WGE, GAS, and HBA treatments. The levels of monoamine such as serotonin (5-HT), dopamine (DA), and their metabolites 5-hydroxyindoleacetic acid (5-HIAA), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) were measured using HPLC-electrochemical detection. Western blotting was used to examine the 5-HT1A receptor and the neuronal cytoskeleton remodeling-related proteins, Slit, dihydropyrimidinase-related protein 2 (DPYSL2, also called CRMP2), Ras homologous member A (RhoA), and profilin 1 (PFN1) in vivo. Slit1 expression was evaluated in Hs683 cell line after treated with WGE (0.5mg/mL), GAS (50, 100 and 100µM), and HBA (50, 100 and 100µM). RESULTS: Oral administration of WGE (500mg/kg bw), GAS (100mg/kg bw), and HBA (100mg/kg bw) exhibited the anti-depressant effect by significantly reducing the immobility time in FST, monoamine metabolism including the 5-HT to 5-HIAA in the hippocampus and DA to DOPAC and HVA ratios in the frontal cortex, amygdala, and hippocampus. In the hippocampus, the expression of the neuronal cytoskeleton remodeling-related negative regulators Slit1 and RhoA were significantly down-regulated. In addition, the positive regulators CRMP2 and PFN1 were significantly up-regulated following GAS, HBA, and WGE treatments. Moreover, WGE, GAS, and HBA were directly down-regulated Slit1 expression in Hs683 cells. CONCLUSION: WGE, GAS, and HBA exhibited potential anti-depressant effects in rats by decreasing monoamine metabolism and modulated cytoskeleton remodeling-related protein expression in the Slit-Robo pathway. These results suggest that WGE can be used as agent for depressive prevention.

A medicinal herb, Melissa officinalis L. ameliorates depressive-like behavior of rats in the forced swimming test via regulating the serotonergic neurotransmitter.

ETHNOPHARMACOLOGICAL RELEVANCE: Depression is a serious psychological disorder that causes extreme economic loss and social problems. However, the conventional medications typically cause side effects that result in patients opting to out of therapy. Lemon balm (Melissa officinalis L., MO) is an old and particularly reliable medicinal herb for relieving feelings of melancholy, depression and anxiety. The present study aims to investigate the antidepressant-like activity of water extract of MO (WMO) by evaluating its influence on the behaviors and the relevant neurotransmitters of rats performed to forced swimming test. MATERIALS AND METHODS: Two phases of the experiment were conducted. In the acute model, rats were administered ultrapure water (control), fluoxetine, WMO, or the indicated active compound (rosmarinic acid, RA) three times in one day. In the sub-acute model, rats were respectively administered ultrapure water (control), fluoxetine, or three dosages of WMO once a day for 10 days. Locomotor activity and depression-like behavior were examined using the open field test and the forced swimming test, respectively. The levels of relevant neurotransmitters and their metabolites in the frontal cortex, amygdala, hippocampus, and striatum were analyzed by high performance liquid chromatography. RESULTS: In the acute model, WMO and RA significantly reduced depressive-like behavior but the type of related neurotransmitter could not be determined. The results indicated that the effect of WMO administration on the reduction of immobility time was associated with an increase in swimming time of the rats, indicative of serotonergic neurotransmission modulation. Chromatography data validated that the activity of WMO was associated with a reduction in the serotonin turnover rate. CONCLUSION: The present study shows the serotonergic antidepressant-like activity of WMO. Hence, WMO may offer a serotonergic antidepressant activity to prevent depression and to assist in conventional therapies.

Down-regulation of Slit-Robo pathway mediating neuronal cytoskeletal remodeling processes facilitates the antidepressive-like activity of Gastrodia elata Blume.

Nowadays, depression is a serious psychological disorder that causes extreme economic loss and social problems. Previously, we discovered that the water extract of Gastrodia elata Blume (WGE) improved depressive-like behavior by influencing neurotransmitters in rats subjected to the forced swimming test. To elucidate possible mechanisms, in the present study, we performed a proteomics and bioinformatics analysis to identify the related pathways. Western blot-validated results indicated that the core protein network modulated by WGE administration was closely associated with down-regulation of the Slit-Robo pathway, which modulates neuronal cytoskeletal remodeling processes. Although Slit-Robo signaling has been well investigated in neuronal development, its relationship with depression is not fully understood. We provide a potential hint on the mechanism responsible for the antidepressive-like activity of WGE. In conclusion, we suggest that the Slit-Robo pathway and neuronal cytoskeleton remodeling are possibly one of the pathways associated with the antidepressive-like effects of WGE.

Garlic essential oil protects against obesity-triggered nonalcoholic fatty liver disease through modulation of lipid metabolism and oxidative stress.

This study investigated the protective properties of garlic essential oil (GEO) and its major organosulfur component (diallyl disulfide, DADS) against the development of nonalcoholic fatty liver disease (NAFLD). C57BL/6J mice were fed a normal or high-fat diet (HFD) with/without GEO (25, 50, and 100 mg/kg) or DADS (10 and 20 mg/kg) for 12 weeks. GEO and DADS dose-dependently exerted antiobesity and antihyperlipidemic effects by reducing HFD-induced body weight gain, adipose tissue weight, and serum biochemical parameters. Administration of 50 and 100 mg/kg GEO and 20 mg/kg DADS significantly decreased the release of pro-inflammatory cytokines in liver, accompanied by elevated antioxidant capacity via inhibition of cytochrome P450 2E1 expression during NAFLD development. The anti-NAFLD effects of GEO and DADS were mediated through down-regulation of sterol regulatory element binding protein-1c, acetyl-CoA carboxylase, fatty acid synthase, and 3-hydroxy-3-methylglutaryl-coenzyme A reductase, as well as stimulation of peroxisome proliferator-activated receptor α and carnitine palmitoyltransferase-1. These results demonstrate that GEO and DADS dose-dependently protected obese mice with long-term HFD-induced NAFLD from lipid accumulation, inflammation, and oxidative damage by ameliorating lipid metabolic disorders and oxidative stress. The dose of 20 mg/kg DADS was equally as effective in preventing NAFLD as 50 mg/kg GEO containing the same amount of DADS, which demonstrates that DADS may be the main bioactive component in GEO.

Wild bitter gourd protects against alcoholic fatty liver in mice by attenuating oxidative stress and inflammatory responses.

Bitter gourd (Momordica charantia L.) is a common vegetable grown widely in Asia that is used as a traditional medicine. The objective of this study was to investigate whether wild bitter gourd possessed protective effects against chronic alcohol-induced liver injury in mice. C57BL/6 mice were fed an alcohol-containing liquid diet for 4 weeks to induce alcoholic fatty liver. Meanwhile, mice were treated with ethanol extracts from four different wild bitter gourd cultivars: Hualien No. 1', Hualien No. 2', Hualien No. 3' and Hualien No. 4'. The results indicated that the daily administration of 500 mg kg body weight(-1) of a Hualien No. 3' extract (H3E) or a Hualien No. 4' extract (H4E) markedly reduced the steatotic alternation of liver histopathology. In addition, the activation of serum aminotransferases (AST and ALT) and the accumulation of hepatic TG content caused by alcohol were ameliorated. The hepatoprotective effects of H3E and H4E involved the enhancement of the antioxidant defence system (GSH, GPx, GRd, CAT and SOD), inhibition of lipid peroxidation (MDA) and reduction of pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6) in the liver. Moreover, H3E and H4E supplementation suppressed the alcohol-induced elevation of CYP2E1, SREBP-1, FAS and ACC protein expression. These results demonstrated that ethanol extracts of Hualien No. 3' and Hualien No. 4' have beneficial effects against alcoholic fatty liver, in which they attenuate oxidative stress and inflammatory responses.