Antidepressant-like Effect of Oroxylum indicum Seed Extract in Mice Model of Unpredictable Chronic Mild Stress.

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.

Approach of Supercritical Carbon Dioxide for the Extraction of Kleeb Bua Daeng Formula.

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.

Effect of Yakae-Prajamduen-Jamod Traditional Thai Remedy on Cognitive Impairment in an Ovariectomized Mouse Model and Its Mechanism of Action.

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.

Effects of the Bark Resin Extract of Garcinia nigrolineata on Chronic Stress-Induced Memory Deficit in Mice Model and the In Vitro Monoamine Oxidases and ß-Amyloid Aggregation Inhibitory Activities of Its Prenylated Xanthone Constituents.

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).

Merging the Multi-Target Effects of Kleeb Bua Daeng, a Thai Traditional Herbal Formula in Unpredictable Chronic Mild Stress-Induced Depression.

Major depressive disorder (MDD) is a common and debilitating psychiatric disease characterized by persistent low mood, lack of energy, hypoactivity, anhedonia, decreased libido, and impaired cognitive and social functions. However, the multifactorial etiology of MDD remains largely unknown due the complex interaction between genetics and environment involved. Kleeb Bua Daeng (KBD) is a Thai traditional herbal formula that has been used to promote brain health. It consists of a 1:1:1 ratio of the aerial part of Centella asiatica, Piper nigrum fruit, and the petals of Nelumbo nucifera. According to the pharmacological activities of the individual medicinal plants, KBD has good potential as a treatment for MDD. The present study investigated the antidepressant activity of KBD in an unpredictable chronic mild stress (UCMS) mouse model. Daily administration of KBD to UCMS mice ameliorated both anhedonia, by increasing 2% sucrose intake, and hopeless behavior, by reducing immobility times in the forced swimming test (FST) and tail suspension test (TST) without any effect on locomotor activity. The mechanism of KBD activity was multi-modal. KBD promoted neurogenesis by upregulation of brain-derived neurotrophic factor (BDNF) and cyclic AMP-responsive element binding (CREB) mRNA expression in the frontal cortex and hippocampus. Daily treatment with KBD significantly reversed UCMS-induced HPA axis dysregulation by upregulating the glucocorticoid receptor (GR) while downregulating serum- and glucocorticoid-inducible kinase 1 (SGK1) and FK506 binding protein 5 (FKBP5) mRNA expression. KBD treatment also normalized proinflammatory cytokine expression including tumor necrosis factor-alpha (TNF-α), and interleukin (IL)-1ß and IL-6. KBD and its component extracts also exhibited an inhibitory effect in vitro on monoamine oxidase (MAO) A and B. The multiple antidepressant actions of KBD emphasize its potential as an effective, novel treatment for MDD.

Antidementia Effects of Alternanthera philoxeroides in Ovariectomized Mice Supported by NMR-Based Metabolomic Analysis.

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.