Bee Venom Activates the Nrf2/HO-1 and TrkB/CREB/BDNF Pathways in Neuronal Cell Responses against Oxidative Stress Induced by Aβ1–42

Nguyen, Cong Duc; Yoo, Jaehee; Hwang, Sun-Young; Cho, Sung-Young; Kim, Myeonghun; Jang, Hyemin; No, Kyoung Ok; Shin, Jeong Cheol; Kim, Jae-Hong; Lee, Gihyun

doi:10.3390/ijms23031193

Open AccessArticle

Bee Venom Activates the Nrf2/HO-1 and TrkB/CREB/BDNF Pathways in Neuronal Cell Responses against Oxidative Stress Induced by Aβ_1–42

by

Cong Duc Nguyen

^1,†,

Jaehee Yoo

^2,3,†,

Sun-Young Hwang

¹,

Sung-Young Cho

¹,

Myeonghun Kim

¹,

Hyemin Jang

¹,

Kyoung Ok No

¹,

Jeong Cheol Shin

^2,4,

Jae-Hong Kim

^2,3,* and

Gihyun Lee

^1,*

¹

College of Korean Medicine, Dongshin University, 67 Dongshindae-gil, Naju 58245, Korea

²

Department of Acupuncture and Moxibustion Medicine, Dongshin University, 67 Dongshindae-gil, Naju 58245, Korea

³

Dongshin University Gwangju Korean Medicine Hospital, 141 Wolsan-ro Nam-gu, Gwangju 61619, Korea

⁴

Dongshin University Mokpo Korean Medicine Hospital, 313 Baengnyeon-daero, Mokpo 58665, Korea

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Int. J. Mol. Sci. 2022, 23(3), 1193; https://doi.org/10.3390/ijms23031193

Submission received: 15 December 2021 / Revised: 16 January 2022 / Accepted: 18 January 2022 / Published: 21 January 2022

(This article belongs to the Special Issue The Role of Natural Products in the Treatment of Neuronal Disease)

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Abstract

Honeybee venom has recently been considered an anti-neurodegenerative agent, primarily due to its anti-inflammatory effects. The natural accumulation of amyloid-beta (Aβ) in the brain is reported to be the natural cause of aging neural ability downfall, and oxidative stress is the main route by which Aβ ignites its neural toxicity. Anti-neural oxidative stress is considered an effective approach for neurodegenerative therapy. To date, it is unclear how bee venom ameliorates neuronal cells in oxidative stress induced by Aβ. Here, we evaluated the neuroprotective effect of bee venom on Aβ-induced neural oxidative stress in both HT22 cells and an animal model. Our results indicate that bee venom protected HT22 cells against apoptosis induced by Aβ_1–42. This protective effect was explained by the increased nuclear translocation of nuclear factor erythroid 2-like 2 (Nrf2), consequently upregulating the production of heme oxygenase-1 (HO-1), a critical cellular instinct antioxidant enzyme that neutralizes excessive oxidative stress. Furthermore, bee venom treatment activated the tropomyosin-related kinase receptor B (TrkB)/cAMP response element-binding (CREB)/brain-derived neurotrophic factor (BDNF), which is closely related to the promotion of cellular antioxidant defense and neuronal functions. A mouse model with cognitive deficits induced by Aβ_1–42 intracerebroventricular (ICV) injections was also used. Bee venom enhanced animal cognitive ability and enhanced neural cell genesis in the hippocampal dentate gyrus region in a dose-dependent manner. Further analysis of animal brain tissue and serum confirmed that bee venom reduced oxidative stress, cholinergic system activity, and intercellular neurotrophic factor regulation, which were all adversely affected by Aβ_1–42. Our study demonstrates that bee venom exerts antioxidant and neuroprotective actions against neural oxidative stress caused by Aβ_1–42, thereby promoting its use as a therapeutic agent for neurodegenerative disorders.

Keywords: bee venom; BDNF; amyloid-beta; Nrf2; neurodegeneration

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MDPI and ACS Style

Nguyen, C.D.; Yoo, J.; Hwang, S.-Y.; Cho, S.-Y.; Kim, M.; Jang, H.; No, K.O.; Shin, J.C.; Kim, J.-H.; Lee, G. Bee Venom Activates the Nrf2/HO-1 and TrkB/CREB/BDNF Pathways in Neuronal Cell Responses against Oxidative Stress Induced by Aβ_1–42. Int. J. Mol. Sci. 2022, 23, 1193. https://doi.org/10.3390/ijms23031193

AMA Style

Nguyen CD, Yoo J, Hwang S-Y, Cho S-Y, Kim M, Jang H, No KO, Shin JC, Kim J-H, Lee G. Bee Venom Activates the Nrf2/HO-1 and TrkB/CREB/BDNF Pathways in Neuronal Cell Responses against Oxidative Stress Induced by Aβ_1–42. International Journal of Molecular Sciences. 2022; 23(3):1193. https://doi.org/10.3390/ijms23031193

Chicago/Turabian Style

Nguyen, Cong Duc, Jaehee Yoo, Sun-Young Hwang, Sung-Young Cho, Myeonghun Kim, Hyemin Jang, Kyoung Ok No, Jeong Cheol Shin, Jae-Hong Kim, and Gihyun Lee. 2022. "Bee Venom Activates the Nrf2/HO-1 and TrkB/CREB/BDNF Pathways in Neuronal Cell Responses against Oxidative Stress Induced by Aβ_1–42" International Journal of Molecular Sciences 23, no. 3: 1193. https://doi.org/10.3390/ijms23031193

APA Style

Nguyen, C. D., Yoo, J., Hwang, S.-Y., Cho, S.-Y., Kim, M., Jang, H., No, K. O., Shin, J. C., Kim, J.-H., & Lee, G. (2022). Bee Venom Activates the Nrf2/HO-1 and TrkB/CREB/BDNF Pathways in Neuronal Cell Responses against Oxidative Stress Induced by Aβ_1–42. International Journal of Molecular Sciences, 23(3), 1193. https://doi.org/10.3390/ijms23031193

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Bee Venom Activates the Nrf2/HO-1 and TrkB/CREB/BDNF Pathways in Neuronal Cell Responses against Oxidative Stress Induced by Aβ_1–42

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