Nutritional neuroscience · 2025
Phytoconstituents of Indian mustard honey impart antidepressant activity in reserpine-induced depressed condition through activation of TrkB/CREB/BDNF pathway in hippocampus.
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Saini Saakshi, Kumar Viney, Chauhan Samrat, Saini Rajat, Biswas Partho, Pathak Tiyasa, Gurjeet Singh Thakur, Saini Surendra Kumar, Ghosh Kaushik, Kumar Prabhat, Roy Partha
Аннотация
OBJECTIVE: Depression is a global health issue, with traditional antidepressants raising safety concerns. Indian mustard honey (MH) offers a potential alternative due to its health benefits, though its antidepressant effects remain unexplored. This study investigates the neuroprotective and antidepressant effects of MH in HT-22 cells in vitro and in Wistar rats in vivo.
METHODS: Chemical constituents of MH were identified using liquid chromatography-mass spectrometry (LC-MS). Effects of MH on phosphorylated tyrosine kinase receptor B (p-TrkB), brain-derived neurotropic factor (BDNF) and phosphorylated cyclic AMP-dependent response element-binding protein (p-CREB) were assessed in reserpine-treated HT-22 cells and rat models. Antidepressant effects in rats were evaluated using forced swim, tail suspension and locomotor activity tests, along with hippocampal histopathology and molecular analyses.
RESULTS: MH profiling identified key polyphenols with antioxidant properties. In HT-22 cells, MH showed neuroprotection at 60 mg/mL (p < 0.001), and upregulated p-TrkB, BDNF, and p-CREB (p < 0.001) against reserpine-induced oxidative stress. In rats, compared to fluoxetine, MH at 1 g/kg BW increased locomotor activity by ∼2.3 fold and reduced immobility by ∼50% and 25% in the tail suspension and forced swim tests (p < 0.001), respectively, showing comparable/ better antidepressant effects. It also preserved hippocampal architecture and upregulated p-TrkB, BDNF, and p-CREB (p < 0.001) levels compared to reserpine-treated rats.
DISCUSSIONS: MH demonstrated antioxidant, neuroprotective and antidepressant activities in in vitro and in vivo models, suggesting therapeutic potential. However, further studies on additional pathways, including β-catenin/Wnt, MAPK/ERK, along with pharmacokinetics, are essential before recommending MH as an antidepressant agent.
METHODS: Chemical constituents of MH were identified using liquid chromatography-mass spectrometry (LC-MS). Effects of MH on phosphorylated tyrosine kinase receptor B (p-TrkB), brain-derived neurotropic factor (BDNF) and phosphorylated cyclic AMP-dependent response element-binding protein (p-CREB) were assessed in reserpine-treated HT-22 cells and rat models. Antidepressant effects in rats were evaluated using forced swim, tail suspension and locomotor activity tests, along with hippocampal histopathology and molecular analyses.
RESULTS: MH profiling identified key polyphenols with antioxidant properties. In HT-22 cells, MH showed neuroprotection at 60 mg/mL (p < 0.001), and upregulated p-TrkB, BDNF, and p-CREB (p < 0.001) against reserpine-induced oxidative stress. In rats, compared to fluoxetine, MH at 1 g/kg BW increased locomotor activity by ∼2.3 fold and reduced immobility by ∼50% and 25% in the tail suspension and forced swim tests (p < 0.001), respectively, showing comparable/ better antidepressant effects. It also preserved hippocampal architecture and upregulated p-TrkB, BDNF, and p-CREB (p < 0.001) levels compared to reserpine-treated rats.
DISCUSSIONS: MH demonstrated antioxidant, neuroprotective and antidepressant activities in in vitro and in vivo models, suggesting therapeutic potential. However, further studies on additional pathways, including β-catenin/Wnt, MAPK/ERK, along with pharmacokinetics, are essential before recommending MH as an antidepressant agent.