Abstract
The development of anxiety and depression due to chronic exposure to stress is an emerging health problem. NCP formula is a combination of three medicinal herbs: Nelumbo nucifera, Centella asiatica, and Piper nigrum with neuroenhancement properties. The anti-anxiety- and antidepressant-like activities of NCP formula and possible mechanisms were investigated using a chronic mild stress–induced mouse model of depression. Administration of NCP formula to chronic mild stress mice significantly ameliorated anxiety, anhedonia, and hopeless behavior. NCP administration significantly normalized hypothalamic–pituitary–adrenal axis activation by reducing plasma corticosterone levels and downregulating serum- and glucocorticoid-inducible kinase 1 and upregulating glucocorticoid receptor mRNA expression in the frontal cortex and hippocampus of chronic mild stress mice. Moreover, NCP formula upregulated neurogenesis by increasing cyclic AMP-responsive element-binding protein and brain-derived neurotrophic factor mRNA expression in both brain regions. Extracts of each of the NCP herbal constituents inhibited monoamine oxidase A and B activity. The major bioactive compounds identified in the NCP formula extract were piperine, ferulic acid, terpenoids (madecassoside and asiaticoside), and flavonoids (quercetin, kaempferol, kaempferol-3-O-glucoside, rutin, and luteolin-7-O-glucoside).
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The data from this study are available from the corresponding author upon reasonable request.
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Acknowledgements
We thank the Research and Technology Transfer Affairs of Khon Kaen University, the Graduate School of Khon Kaen University, and the Research Program of Khon Kaen University for financial support. YCh. thanks the Faculty of Pharmaceutical Sciences, Khon Kaen University, Thailand, for a Master of Science scholarship and Chao Phya Abhaibhubejhr Hospital for logistical support. The authors thank Glenn Borlace for the English editing of the manuscript.
Funding
This research was supported by the Research and Technology Transfer Affair, Khon Kaen University, partially supported by the Research Program of Khon Kaen University 2021 (RP66-3–003) and Scholarships for the Master degree student, Faculty of Pharmaceutical Sciences, Khon Kaen University (ID: 2(1)/2562).
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OM, YC, SD, and CB conceived and designed the experiments. PK and SP identified the plants and provided the NCP formula. YCh performed the behavioral test, serum CORT assay, and gene expression. JM performed the HPLC analysis. CK performed MAOI assay. YCh and OM wrote the manuscript and assisted in the elaboration of the manuscript.
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The experimental protocol used in the study was following the Guiding Principle for the Care and Use of Animals (NIH Publications #8–23, revised in 2011) and was also approved by the Animal Ethics Committee of Khon Kaen University (approval no. IACUC-KKU-36/61).
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Chotritthirong, Y., Chulikhit, Y., Daodee, S. et al. Possible Mechanisms for the Prevention of Anxiety and Depressive-Like Behavior in a Chronic Mild Stress Mouse Model by the Thai Herbal Medicine with Nelumbo nucifera, Centella asiatica, and Piper nigrum. Rev. Bras. Farmacogn. 33, 756–767 (2023). https://doi.org/10.1007/s43450-023-00401-x
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DOI: https://doi.org/10.1007/s43450-023-00401-x