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 β-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.

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.

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Daily treatment of ovariectomized (OVX) ICR mice with puerarin, a glycosyl isoflavone isolated from the root bark of Pueraria candollei var. mirifica, and 17β-estradiol attenuated ovariectomy-induced depression-like behavior, as indicated by a decrease in immobility times in the tail suspension test (TST) and the forced swimming test (FST), an increase in the uterine weight and volume, a decrease in serum corticosterone levels, and dose-dependently normalized the downregulated transcription of the brain-derived neurotrophic factor (BDNF) and estrogen receptor (Erβ and Erα) mRNAs. Like 17β-estradiol, puerarin also inhibited ovariectomy-induced suppression of neurogenesis in the dentate gyrus of the hippocampus (increased the number of doublecortin (DCX)-immunosuppressive cells). These results suggest that puerarin exerts antidepressant-like effects in OVX animals, possibly by attenuating the OVX-induced hyperactivation of the HPA axis and/or normalizing the downregulated transcription of BDNF and ER mRNA in the brain.Molecules 2019, 24, 4569 2 of 15 depression. These symptoms can be reversed by supplementation with estrogen. A body of evidence suggests that such estrogen replacement therapy (ERT) can exert anxiolytic and antidepressant effects in menopausal females by modulating the hypothalamic-pituitary-adrenal (HPA) axis functions [3,4]. However, the drawback of ERT is its adverse effects, such as an increased risk of breast and endometrial cancers, as well as thromboembolic events [5,6]. Consequently, the long-term usage of ERT to ameliorate emotional and cognitive deficits has an obvious limitation in women. Thus, the search for new phytoestrogens, with a weak effect on reproductive organs, from natural sources continues to be an important field of research.Pueraria candollei var. mirifica is a medicinal plant used in Thai traditional medicine for its rejuvenating and estrogenic effects [7]. For this reason, this plant has been widely investigated for its constituents and pharmacological activities. Peerakam et al. [8] found that the 95% ethanol extract of this plant contained puerarin (1), as a major compound, and other isoflavonoids, such as daidzin, daidzein, genistin, and genistein, in addition to the phytoestrogens miroestrol and deoxymiroestrol. Suthon et al.[9] evaluated the anti-osteoporotic effects of the crude extract of P. candollei var. mirifica and puerarin (1) in ovariectomized (OVX) mice and found that only the crude extract at 50 mg/kg (body weight) per day caused a significant increase in the trabecular bone mineral densities of tibia metaphysis when compared to the control group. On the other hand, the pharmacological activities of puerarin (1) (Figure 1), a major isoflavonoid from P. candollei var. mirifica, have been extensively investigated. Puerarin (1) has been widely used in the treatment of diabetes, dyslipidemia, liver fibrosis, cardiovascular diseases, neurotoxicity, and Alzheimer's disease [10]. This compound was also found to exhibit various protective effects against fever, hyper...