Merging the Multi-Target Effects of Kleeb Bua Daeng, a Thai Traditional Herbal Formula in Unpredictable Chronic Mild Stress-Induced Depression
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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)-1β 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.
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Psychedelics facilitate altered states of consciousness characterized by heightened introspection and diminished ego boundaries through influence on 5-HT1A, 5-HT2B, dopaminergic, and glutamatergic systems.
“The other explanation of psychedelics' ability to facilitate altered states of consciousness characterized by heightened introspection and diminished ego boundaries is their influence on 5-HT1A [64] and 5-HT2B [65], and interacting with the dopaminergic [66] and glutamatergic systems [67].”
From Mindfulness meditation and psychedelics: potential synergies and commonalities (2023) · cites this paper as [65]
The Introduction and Discussion address depression, chronic stress, and the antidepressant effects of Kleeb Bua Daeng, not psychedelic-induced states of consciousness. Searches for psychedelics, altered states, ego boundaries, and 5-HT1A found no passage linking those effects to the cited receptor or neurotransmitter systems. Page numbers are not available in our copy. (LLM, conf=0.78)
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- Authors
- Maneenet, J., Monthakantirat, O., Daodee, S., Boonyarat, C., Chotritthirong, Y., Kwankhao, P., Pitiporn, S., Awale, S., & Chulikhit, Y.
- Affiliations
- Khon Kaen University (TH)
- Ministry of Public Health (TH)
- University of Toyama (JP)
- Corresponding author
- Chulikhit, Yaowared
- ORCID
- Venue
- Pharmaceuticals
- Publisher
- MDPI AG
- Published
- 2021-07-09
- Volume
- 14
- Issue
- 7
- Pages
- 659
- ISSN
- 1424-8247 (ISSN-L)
- PMC
- PMC8308724
- OpenAlex
- W3177815552
- Cited by
- 10
- References
- 68
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 5 · 2022: 3
- FWCI
- 2.53
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Pharmaceuticals (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plant Extracts Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Medicinal Plants and Bioactive Compounds
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
- Keywords
- traditional herbal formula, major depressive disorder, chronic unpredictable mild stress, antidepressant effects, anhedonia, neurogenesis, brain-derived neurotrophic factor, CREB, HPA axis dysregulation, glucocorticoid receptor, SGK1, FKBP5, inflammatory cytokines, monoamine oxidase inhibition, Centella asiatica, black pepper, Nelumbo nucifera, Thai herbal medicine
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