Abstract
Catalpol is an iridoid glycoside with rich content, rich nutrition, and numerous biological activities in Rehmanniae Radix contained in classic antidepressant prescriptions in Chinese clinical medicine. Catalpol has been confirmed previously its exact antidepressant-like effect involved heme oxygenase (HO)-1, but its antidepressant molecular targets and mechanism are still unclear. Here, catalpol's antidepressant-like molecular target was diagnosed and confirmed by ZnPP intervention [the antagonist of HO-1, (10 μg/rat), intracerebroventricular] for the first time, and its molecule mechanism network was determined through HO-1 related pathway and molecules in the hippocampus. Results showed that ZnPP significantly abolished catalpol’s (10 mg/kg) reversal on depressive-like behaviors of chronic unpredictable mild stress rats, abolished catalpol’s up-regulation on the phosphorylation level of extracellular regulated protein kinases (ERK)1/2 and brain-derived neurotrophic factor (BDNF)’s receptor tropomyosin-related kinase B (TrkB), the nuclear expression level of nuclear factor E 2-related factor 2 (Nrf2), the levels of anti-oxidant factors (such as HO-1, SOD, GPX, GST, GSH) and BDNF, and abolished catalpol’s down-regulation on the levels of peroxide and neuroinflammation factors [cyclooxygenase-2 (COX-2), induced nitrogen monoxide synthase (iNOS), nitric oxide (NO)]. Thus, HO-1 could serve as an important potential molecular target for catalpol's antidepressant-like process, and the antidepressant-like mechanism of catalpol could at least involve the activation of HO-1 triggering the up-regulation of the ERK1/2/Nrf2/HO-1 pathway-related factors to enhance the anti-oxidant defense, triggering the down-regulation of the COX-2/iNOS/NO pathway-related factors to inhibit neuroinflammation, and triggering the up-regulation of the BDNF/TrkB pathway to enhance neurotrophy.
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Data Availability
The datasets used and/or analyzed during the current study are available from the first author on reasonable request.
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This work was supported by the foundation of the National Natural Science Foundation of China (81773928), Zhong**g High-level Talent Special Fund of Henan University of Chinese Medicine (00104311-2021-1-43), and the Funding Scheme for Young Key Teachers of Colleges and Universities in Henan Province (2014GGJS-072).
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XW conducted the animal experiment, completed western blot, performed the testing of the kits, and developed the manuscript. CL conducted the animal experiment and performed the testing of the kits. JW designed the experiments, developed the manuscript, and acquired funding. YG, LS, and RC participated in the animal experiment. MG performed the testing of the kits. All authors read and approved the final manuscript.
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The experimental protocol was duly approved by the Experimental Animal Ethics Committee of the Henan University of Chinese Medicine in 27th February 2017.
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Wu, X., Liu, C., Wang, J. et al. Catalpol Exerts Antidepressant-Like Effects by Enhancing Anti-oxidation and Neurotrophy and Inhibiting Neuroinflammation via Activation of HO-1. Neurochem Res 47, 2975–2991 (2022). https://doi.org/10.1007/s11064-022-03641-w
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DOI: https://doi.org/10.1007/s11064-022-03641-w