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. 2019 Dec 14;24(24):4587.
doi: 10.3390/molecules24244587.

Kleeb Bua Daeng, a Thai Traditional Herbal Formula, Ameliorated Unpredictable Chronic Mild Stress-Induced Cognitive Impairment in ICR Mice

Juthamart Maneenet  1   2 , Supawadee Daodee  2 , Orawan Monthakantirat  2 , Chantana Boonyarat  2 , Charinya Khamphukdee  2 , Pakakrong Kwankhao  3 , Supaporn Pitiporn  3 , Suresh Awale  4 , Yaowared Chulikhit  2 , Anake Kijjoa  5
Affiliations

Kleeb Bua Daeng, a Thai Traditional Herbal Formula, Ameliorated Unpredictable Chronic Mild Stress-Induced Cognitive Impairment in ICR Mice

Juthamart Maneenet et al. Molecules. .

Abstract

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.

Keywords: Centella asiatica; Nelumbo nucifera; Piper nigrum; herbal formula; learning and memory behaviors; oxidative stress; unpredictable chronic mild stress.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The effect of Kleeb Bua Daeng (KBD) and vitamin E on the unpredictable chronic mild stress (UCMS)-induced cognitive impairment in the Y-maze test (A) and the novel object recognition test (NORT) (B). Each column represents the mean ± S.E.M. (n = 8–10). # p < 0.05, ## p < 0.001 vs. the vehicle-treated non-stress group. * p < 0.05, ** p < 0.001 vs. the vehicle-treated UCMS group. ¤ p < 0.05 compared between doses of KBD.
Figure 2
Figure 2
Effects of KBD and vitamin E on the UCMS-induced elevation in serum corticosterone (CORT) level. Each column represents the mean ± S.E.M (n = 3). ## p < 0.001 vs. the vehicle-treated non-stress group. * p < 0.05, ** p < 0.001 vs. the vehicle-treated UCMS group.
Figure 3
Figure 3
Effect of KBD and vitamin E on the UCMS-induced lipid peroxidation in mice frontal cortex and hippocampus. The lipid peroxidation in brain homogenate was determined using malondialdehyde (MDA) as a standard, and was expressed as nmol MDA/mg protein. Each data column represents the mean ± S.E.M. (n = 3–5). ## p < 0.001 vs. the vehicle-treated non-stress group. ** p < 0.001 vs. the vehicle-treated UCMS group.
Figure 4
Figure 4
The effect of KBD and vitamin E on the activities of the brain antioxidant enzymes in the UCMS mice (A: CAT activity, B: SOD activity). Each data column represents the mean ± S.E.M (n = 3–5). #p < 0.05 and ##p < 0.001 vs. the vehicle-treated non-stress group. * p < 0.05 and ** p < 0.001 vs. the vehicle-treated UCMS group. ¤¤ p < 0.001 compared between doses of KBD.
Figure 5
Figure 5
Structure of piperine (1), madecassoside (2), asiaticoside (3), quercetin (4), kaempferol (5), kaempferol-3-glucoside (6), rutin (7), luteolin-7-O-glucoside (8) and ferulic acid (9).
Figure 6
Figure 6
A schematic presentation of the experimental protocols. Mice were divided into a non-stress group and the chronic mild stress (UCMS) group at week 0. The UCMS group was exposed to various unpredictable, stressful stimuli from week 0 to week 6. The UCMS group was divided into four groups which were daily administered with (i) vehicle, (ii) vitamin E (100 mg/kg, p.o.), (iii) KBD (100 mg/kg, p.o), and (iv) KBD (500 mg/kg, p.o) for 3 weeks after day 21. Y-maze test and NORT were conducted at week 5 to week 6. Twenty-four hours after the behavioral test, the animals were decapitated to collect the blood and brain for neurochemical assessment.
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