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

Juthamart Maneenet,Yaowared Chulikhit,Supawadee Daodee,Pakakrong Kwankhao,Orawan Monthakantirat,Supaporn Pitiporn,Suresh Awale,Chantana Boonyarat,Yutthana Chotritthirong

doi:10.3390/ph14070659

Abstract

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.

Highlights

Major depressive disorder (MDD) is a common and serious illness presenting a significant socioeconomic burden [1,2]
We demonstrated that Kleeb Bua Daeng (KBD) formula improved unpredictable chronic mild stress (UCMS)-induced cognitive dysfunction by a reduction in serum CORT level and brain oxidative damage [21]
We found that neither imipramine nor KBD formula altered the locomotor activity of UCMS mice indicating that the KBD formula can ameliorate the anhedonia and hopeless behavior caused by UCMS

Summary

Introduction

Major depressive disorder (MDD) is a common and serious illness presenting a significant socioeconomic burden [1,2]. Depression is a neuropsychiatric syndrome characterized by psychological, behavioral, and physiological symptoms, such as sadness, depressed mood, anhedonia, hopelessness, and suicidal tendencies [3]. Pharmaceuticals 2021, 14, 659 recognized as being complex, incorporating interactions between genetics, multiple biological systems, and environmental factors. The brain-derived neurotrophic factor (BDNF) is a neurotrophin related to neuronal growth differentiation and survival that is associated with mood disorders [5,6]. A reduction in BDNF serum levels has been seen in patients diagnosed with MDD, which implies a role for BDNF in the pathology of depression

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