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Background Chronic stress exposure has been widely recognized as a significant contributor to numerous central nervous system (CNS) disorders, leading to debilitating behavioral changes such as anxiety, depression, and cognitive impairments. The prolonged activation of the hypothalamic–pituitary–adrenal (HPA) axis during chronic stress disrupts the neuroendocrine balance and has detrimental effects on neuronal function and survival. Nelumbo nucifera (N. nucifera) Gaertn., commonly known as the lotus flower, is a traditional medicinal plant consumed for its purported benefits on mental and physical well-being. Despite its traditional use, limited scientific evidence supports these claims. Methods The present study explores the effects of N. nucifera, commonly known as the lotus flower, on cognitive performance and stress resilience in a mouse model subjected to unpredictable chronic mild stress (UCMS). Results Daily treatment significantly improved cognitive performance, alleviated depressive-like behaviors, and normalized hypothalamic–pituitary–adrenal (HPA) axis activity, as indicated by a 60.97% reduction in serum corticosterone. At the molecular level, N. nucifera petals also downregulated serum- and glucocorticoid-inducible kinase 1 (SGK1) mRNA expression while upregulating brain-derived neurotrophic factor (BDNF) mRNA expression and cyclic-adenosine monophosphate (cAMP) responsive element-binding protein (CREB) mRNA expression in the hippocampus and frontal cortex. These normalizations are critical, as chronic stress dysregulates HPA axis function, exacerbating behavioral changes. Furthermore, a phytochemical analysis resulted in the isolation of five major compounds, kaempferol (1), trifolin (2), kaempferol-3-neohesperidoside (3), icariside D2 (4), and β-sitosterol (5), each demonstrating significant monoamine oxidase (MAO) inhibitory activity. Conclusions These compelling findings suggest that N. nucifera petals not only alleviate stress-induced mood and cognitive deficits but also offer a promising avenue for modulating the HPA axis and promoting neuroprotection via essential neurotrophic factors and enzymatic pathways. We advocate for its potential as a complementary and alternative medicine for effective stress management. Future investigations should further explore its mechanisms of action and evaluate its clinical applicability in stress-related disorders. [ABSTRACT FROM AUTHOR]

We previously reported that Ocimum sanctum Linn. (OS) ethanolic extract and its n-butanol fraction (OSB) could improve depression-like behaviour in olfactory bulbectomized mice. The present study aims to clarify the antidepressant-like effects of OS-B and the possible mechanism of its action using mice subjected to unpredictable chronic mild stress (UCMS). UCMS mice were administered daily with OS-B (50 mg/kg, 100 mg/kg, p.o.) or imipramine (IMP, 8 mg/kg, i.p.), a reference drug. The UCMS-induced anhedonia in mice was analysed by the sucrose preference test, while behavioural despair was assessed using the tail suspension test (TST) and forced swimming test (FST). Locomotor activities and grooming behaviour of mice were elucidated using the open-field test (OFT). The UCMS procedure for 5 weeks induced anhedonia, and this symptom was significantly ameliorated by the administration of OS-B (100 mg/kg) as well as IMP during the UCMS period. Moreover, the OS-B and IMP treatment attenuated the UCMS-induced enhancement of behavioural despair in the TST and FST. In OFT, mice subjected to UCMS showed a decrease in grooming behaviour, and the effect of UCMS was reversed by OS-B and IMP administrations. No significant difference in locomotor activities between each animal group was observed. The amelioration effects of OS-B and IMP on UCMS-induced behavioural despair in the TST were abolished by administrating of ρ-chlorophenylalanine (PCPA, 80 mg/kg, i.p), a tryptophan hydroxylase inhibitor, and α-methyl-ρ-tyrosine (AMPT, 100 mg/kg), a tyrosine hydroxylase inhibitor. The present results suggest that OS-B attenuates UCMS-induced depression-like symptoms via monoaminergic systems including in the noradrenergic, dopaminergic, and serotonergic system.

Aim: The purpose of this study was to explore the effects of goreisan (GRS) on rats through the analysis of 1H‐NMR of urine samples, to assess the variations in metabolites affected by GRS, and to gain a new metabolomic understanding of the effects of Kampo medicine. Methods: Male Wistar rats were randomly divided into two groups: a control group that was fed a standard diet, and a GRS group that was fed a 1% GRS diet. The study was conducted over a four‐week period. At the end of the experiment, urine samples were analyzed using 1H‐NMR spectroscopy to evaluate the metabolic changes induced by GRS administration. Additionally, various blood parameters were also analyzed. Results: Administration of GRS resulted in an elevation of lactate, acetate, and other metabolites, such as trimethylamine‐N‐oxide and hippurate, in urine. Additionally, there was a significant decrease in the blood urea nitrogen (BUN) level in the blood of the GRS‐treated group. Conclusion: This study has highlighted the substantial changes in lactate, acetate, and other urine metabolites caused by GRS. The findings demonstrate the effectiveness of 1H‐NMR spectroscopy in assessing metabolic alterations in response to the therapeutic application of a Kampo formula. This research contributes to the knowledge of mechanisms of action from a metabolomic point of view and offers fresh insights into the effects of complex Kampo formulas such as GRS, using 1H‐NMR spectroscopic techniques. [ABSTRACT FROM AUTHOR]