RESUMO
Major depressive disorder (MDD) is one life-threatening disorder that is prevalent worldwide. The evident etiology of this disease is still poorly understood. Currently, herbal medicine is gaining more interest as an alternative antidepressant. Oroxylum indicum, which is used in traditional medicine and contains a potential antidepressive compound, baicalein, could have an antidepressive property. An in vitro monoamine oxidase-A (MAO-A) inhibitory assay was used to preliminarily screening for the antidepressant effect of O. indicum seed (OIS) extract. Mice were subjected to unpredictable chronic mild stress (UCMS) for 6 weeks, and the daily administration of OIS extract started from week 4. The mechanisms involved in the antidepressive activity were investigated. The OIS extract significantly alleviated anhedonia and despair behaviors in the UCMS-induced mouse model via two possible pathways: (i) it normalized the HPA axis function via the restoration of negative feedback (decreased FKBP5 and increased GR expressions) and the reduction in the glucocorticoid-related negative gene (SGK-1), and (ii) it improved neurogenesis via the escalation of BDNF and CREB expressions in the hippocampus and the frontal cortex. In addition, an HPLC analysis of the OIS extract showed the presence of baicalin, baicalein, and chrysin as major constituents. All of the results obtained from this study emphasize the potential of OIS extract containing baicalin and baicalein as an effective and novel alternative treatment for MDD.
Assuntos
Transtorno Depressivo Maior , Extratos Vegetais , Camundongos , Animais , Extratos Vegetais/farmacologia , Extratos Vegetais/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Transtorno Depressivo Maior/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Antidepressivos/farmacologia , Sementes , Hipocampo , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/metabolismo , Depressão/metabolismo , Modelos Animais de DoençasRESUMO
Supercritical fluid extraction (SFE) is an innovative green technology for the extraction of phytochemicals from plants. Therefore, this study aimed to evaluate the application of SFE and to optimize the extraction conditions of the Thai herbal formula, Kleeb Bua Daeng (KBD). A Box-Behnken design (BBD) with response surface methodology (RMS) was used to determine the effect of the extraction time (30-90 min), temperature (30-60 °C), and pressure (200-300 bar) on response variables including the extraction yield, total phenolic content (TPC), total flavonoid content (TFC), total carotenoid content (TCC), and total anthocyanin content (TAC) of the KBD formula. The highest percentage extraction yield (3.81%) was achieved at 60 °C, 300 bar, and 60 min of the extraction time. The highest TPC (464.56 mg gallic acid equivalents/g extract), TFC (217.19 mg quercetin equivalents/g extract), and TCC (22.26 mg ß-carotene equivalents/g extract) were all achieved at 60 °C, 250 bar, and 90 min of the extraction time. On the contrary, it was not possible to quantify the total anthocyanin content as anthocyanins were not extracted by this method. The results indicated that SFE-CO2 is a suitable method of extraction for a green recovery of phytochemicals with low and moderate polarity from the KBD formula.
Assuntos
Dióxido de Carbono , Cromatografia com Fluido Supercrítico , Dióxido de Carbono/química , Antocianinas , Carotenoides , Fenóis/análise , Extratos Vegetais/química , Cromatografia com Fluido Supercrítico/métodosRESUMO
Cognitive impairment is a neurological symptom caused by reduced estrogen levels in menopausal women. The Thai traditional medicine, Yakae-Prajamduen-Jamod (YPJ), is a formula consisting of 23 medicinal herbs and has long been used to treat menopausal symptoms in Thailand. In the present study, we investigated the effects of YPJ on cognitive deficits and its underlying mechanisms of action in ovariectomized (OVX) mice, an animal model of menopause. OVX mice showed cognitive deficits in the Y-maze, the novel object recognition test, and the Morris water maze. The serum corticosterone (CORT) level was significantly increased in OVX mice. Superoxide dismutase and catalase activities were reduced, while the mRNA expression of IL-1ß, IL-6, and TNF-α inflammatory cytokines were up-regulated in the frontal cortex and hippocampus of OVX mice. These alterations were attenuated by daily treatment with either YPJ or 17ß-estradiol. HPLC analysis revealed that YPJ contained antioxidant and phytoestrogen constituents including gallic acid, myricetin, quercetin, luteolin, genistein, and coumestrol. These results suggest that YPJ exerts its ameliorative effects on OVX-induced cognitive deficits in part by mitigating HPA axis overactivation, neuroinflammation, and oxidative brain damage. Therefore, YPJ may be a novel alternative therapeutic medicine suitable for the treatment of cognitive deficits during the menopausal transition.
Assuntos
Disfunção Cognitiva , Sistema Hipotálamo-Hipofisário , Animais , Antioxidantes/farmacologia , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Ovariectomia , Sistema Hipófise-Suprarrenal , TailândiaRESUMO
The present study describes investigation of the effects of the bark resin extract of Garcinia nigrolineata (Clusiaceae) on the cognitive function and the induction of oxidative stress in both frontal cortex and hippocampus by unpredictable chronic mild stress (UCMS). By using behavioral mouse models, i.e., the Y-maze test, the Novel Object Recognition Test (NORT), and the Morris Water Maze Test (MWMT), it was found that the negative impact of repeated mild stress-induced learning and memory deficit through brain oxidative stress in the UCMS mice was reversed by treatment with the bark resin extract G. nigrolineata. Moreover, the prenylated xanthones viz. cowagarcinone C, cowaxanthone, α-mangostin, cowaxanthone B, cowanin, fuscaxanthone A, fuscaxanthone B, xanthochymusxanthones A, 7-O-methylgarcinone E, and cowagarcinone A, isolated from the bark resin of G. nigrolineata, were assayed for their inhibitory activities against ß-amyloid (Aß) aggregation and monoamine oxidase enzymes (MAOs).
Assuntos
Garcinia , Xantonas , Peptídeos beta-Amiloides , Animais , Modelos Animais de Doenças , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/etiologia , Camundongos , Monoaminoxidase , Casca de Planta , Extratos Vegetais/farmacologia , Resinas Vegetais , Xantonas/farmacologiaRESUMO
The effects of the phytoestrogen-enriched plant Pueraria mirifica (PM) extract on ovari-ectomy (OVX)-induced cognitive impairment and hippocampal oxidative stress in mice were investigated. Daily treatment with PM and 17ß-estradiol (E2) significantly elevated cognitive behavior as evaluated by using the Y maze test, the novel object recognition test (NORT), and the Morris water maze test (MWM), attenuated atrophic changes in the uterus and decreased serum 17ß-estradiol levels. The treatments significantly ameliorated ovariectomy-induced oxidative stress in the hippocampus and serum by a decrease in malondialdehyde (MDA), an enhancement of superoxide dismutase, and catalase activity, including significantly down-regulated expression of IL-1ß, IL-6 and TNF-α proinflammatory cytokines, while up-regulating expression of PI3K. The present results suggest that PM extract suppresses oxidative brain damage and dysfunctions in the hippocampal antioxidant system, including the neuroinflammatory system in OVX animals, thereby preventing OVX-induced cognitive impairment. The present results indicate that PM exerts beneficial effects on cognitive deficits for which menopause/ovariectomy have been implicated as risk factors.
Assuntos
Disfunção Cognitiva/tratamento farmacológico , Hipocampo/metabolismo , Ovariectomia/efeitos adversos , Fitoestrógenos/administração & dosagem , Pueraria/química , Animais , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Estradiol/administração & dosagem , Estradiol/farmacologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Malondialdeído/sangue , Malondialdeído/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Fitoestrógenos/química , Fitoestrógenos/farmacologiaRESUMO
The crude ethanol extract of the whole plant of Alternanthera philoxeroides (Mart.) Griseb was investigated for its potential as antidementia, induced by estrogen deprivation, based on in vitro antioxidant activity, ß-amyloid aggregation inhibition and cholinesterase inhibitory activity, as well as in vivo Morris water maze task (MWMT), novel object recognition task (NORT), and Y-maze task. To better understand the effect of the extract, oxidative stress-induced brain membrane damage through lipid peroxidation in the whole brain was also investigated. Additionally, expressions of neuroinflammatory cytokines (IL-1ß, IL-6 and TNF-α) and estrogen receptor-mediated facilitation genes such as PI3K and AKT mRNA in the hippocampus and frontal cortex were also evaluated. These effects were confirmed by the determination of its serum metabolites by NMR metabolomic analysis. Both the crude extract of A. philoxeroides and its flavone constituents were found to inhibit ß-amyloid (Aß) aggregation.
Assuntos
Demência/tratamento farmacológico , Espectroscopia de Ressonância Magnética , Metabolômica , Extratos Vegetais/farmacologia , Amaranthaceae/química , Peptídeos beta-Amiloides/química , Animais , Cognição/efeitos dos fármacos , Demência/prevenção & controle , Etanol/química , Etanol/farmacologia , Feminino , Flavonas/química , Sequestradores de Radicais Livres/metabolismo , Lobo Frontal/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Inflamação/tratamento farmacológico , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Medicina Tradicional do Leste Asiático , Metaboloma , Camundongos , Camundongos Endogâmicos ICR , Ovariectomia , Análise de Componente Principal , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Thai traditional herbal formula ''Kleeb Bua Daeng (KBD)''consists of a 1:1:1 ratio (dry weight) of three medicinal plants: Piper nigrum fruit, the aerial part of Centella asiatica and the petals of Nelumbo nucifera. Oral administration of KBD to unpredictable chronic mild stress (UCMS) mice significantly improved their cognitive function caused by chronic mild stress. Daily administration of KBD significantly decreased the serum corticosterone (CORT) and malondialdehyde (MDA) levels but increased the catalase and superoxide dismutase activities in both frontal cortex and hippocampus. The effects of KBD were similar to those caused by oral administration of vitamin E. HPLC analysis of the KBD extract revealed the presence of piperine, madecassoside, asiaticoside, luteolin-7-O-glucoside, rutin, kaempferol-3-glucoside, quercetin, kaempferol and ferulic acid as major constituents.
Assuntos
Cognição/efeitos dos fármacos , Disfunção Cognitiva/tratamento farmacológico , Composição de Medicamentos , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Corticosteroides/sangue , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Cromatografia Líquida de Alta Pressão , Disfunção Cognitiva/etiologia , Peroxidação de Lipídeos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Estrutura Molecular , Estresse Oxidativo/efeitos dos fármacos , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Estresse Psicológico , TailândiaRESUMO
Treatment of the unpredictable chronic mild stress (UCMS) mice with the ethanol extract of Dipterocarpus alatus leaf attenuated anhedonia (increased sucrose preference) and behavioral despair (decreased immobility time in tail suspension test (TST) and forced swimming test (FST)). The extract not only decreased the elevation of serum corticosterone level and the index of over-activation of the hypothalamic-pituitary-adrenal (HPA) axis, caused by UCMS, but also ameliorated UCMS-induced up-regulation of serum- and glucocorticoid-inducible kinase 1 (SGK1) mRNA expression and down-regulation of cyclic AMP-responsive element binding (CREB) and brain-derived neurotrophic factor (BDNF) mRNAs in frontal cortex and hippocampus. In vitro monoamine oxidase (MAO) inhibition assays showed that the extract exhibited the partial selective inhibition on MAO-A. HPLC analysis of the extract showed the presence of flavonoids (luteolin-7-O-glucoside, kaempferol-3-glucoside, rutin) and phenolic acids (gallic acid, ferulic acid, and caffeic acid) as major constituents.
Assuntos
Depressão , Dipterocarpaceae/química , Etanol/química , Extratos Vegetais , Folhas de Planta/química , Estresse Psicológico , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Depressão/tratamento farmacológico , Depressão/metabolismo , Depressão/patologia , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/patologia , Proteínas Imediatamente Precoces/biossíntese , Masculino , Camundongos , Camundongos Endogâmicos ICR , Sistema Hipófise-Suprarrenal/metabolismo , Sistema Hipófise-Suprarrenal/patologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Proteínas Serina-Treonina Quinases/biossíntese , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/metabolismo , Estresse Psicológico/patologiaRESUMO
The previously unreported flavone glycoside, demethyltorosaflavone B (2) and the E-propenoic acid substituted flavone, torosaflavone E (3a), were isolated together with nine previously reported metabolites, including indole-3-carbaldehyde, oleanonic acid, vanillic acid, p-hydroxybenzoic acid, altheranthin (1a), alternanthin B (1b), demethyltorosaflavone D (3b), luteolin 8-C-E-propenoic acid (4) and chrysoeriol 7-O-rhamnoside (5), from the ethanol extract of the aerial part of Althernanthera philoxeroides. The crude ethanol extract was evaluated for its in vitro estrogenic activity in MCF-7 breast cancer cell line. The crude ethanol extract was also investigated in vivo for its antidepressant-like effects on ovariectomized mice using tail suspension and forced swimming tests, while its effect on the locomotor activity was evaluated by a Y-maze test. The effect of the crude extract on the serum corticosterone level, size and volume of uterus of the ovariectomized mice were also investigated. The expression of the mouse cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB), brain-derived neurotrophic factor (BDNF) and ß-actin mRNAs in hippocampus and frontal cortex was also evaluated, using semiquantitative reverse transcription-polymerase chain reaction. The crude extract and the isolated compounds 1a, 1b, 3a, 3b and 5, were evaluated for their inhibitory effects on monoamine oxidases (MAOs)-A and -B.