Neuroprotective effects of Tiaogeng decoction against H 2 O 2 -induced oxidative injury and apoptosis in PC12 cells via Nrf2 and JNK signaling pathways.

Autor: Gao X; Department of Gynecology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. Electronic address: 594572350@qq.com., Li S; Department of Gynecology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. Electronic address: lisncq@163.com., Liu X; Department of Gynecology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. Electronic address: 459124211@qq.com., Cong C; Department of Gynecology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. Electronic address: congchaosunny@163.com., Zhao L; Department of Gynecology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. Electronic address: etzdp@126.com., Liu H; Department of Gynecology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. Electronic address: 903180049@qq.com., Xu L; Department of Gynecology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. Electronic address: doctorsherryxlw@163.com.
Jazyk: angličtina
Zdroj: Journal of ethnopharmacology [J Ethnopharmacol] 2021 Oct 28; Vol. 279, pp. 114379. Date of Electronic Publication: 2021 Jun 30.
DOI: 10.1016/j.jep.2021.114379
Abstrakt: Ethnopharmacological Relevance: Tiaogeng decoction (TGD), a mixture of 10 traditional Chinese herbs, has been used clinically for over 30 years in treating menopause-related symptoms such as cognitive changes, mood disorders, vasomotor symptoms, and sleep disorders. These central nervous system symptoms are closely associated with declined ovarian function, which dramatically increases the risk of neurodegenerative disease. Previous studies revealed that TGD may have anti-oxidative and anti-apoptotic properties, potentially preventing neurodegenerative conditions; however, the underlying pharmacological mechanism remains unclear.
Aim of the Study: This study aimed to examine whether TGD could activate the Nrf2 and C-Jun N-terminal kinase (JNK) signaling pathways to effectively reduce oxidative injury and apoptosis in PC12 cells and elucidate the mechanism by which this medicine may prevent neurodegenerative disease.
Materials and Methods: PC12 cells were exposed to different concentrations of TGD (125, 250, 500 μg/mL) and H 2 O 2 (150 μM). 17β-estradiol (0.05 μg/mL) was used as the positive control. A cell counting kit-8 (CCK-8) and a lactate dehydrogenase (LDH) assay were used to detect cell viability and cytotoxicity, while Hoechst and flow cytometry were performed to evaluate apoptosis levels. Mitochondrial function was assessed by measuring mitochondrial membrane potential (MMP), and superoxide dismutase (SOD), and reactive oxygen species (ROS) levels were used to measure oxidative stress (OS). Western blot analysis was used to identify the levels of Nrf2, phospho-JNK (p-JNK), phospho-mitogen-activated protein kinase kinase 7 (p-MKK7), Kelch-like ECH-associated protein 1 (Keap1), heme oxygenase-1 (HO-1), Caspase3 (Casp3), Caspase9 (Casp9), Bax, and Bcl-2 proteins. Moreover, JNK agonist anisomycin and Nrf2 inhibitor ML385 were used to validate pathways.
Results: TGD pretreatment significantly alleviated H 2 O 2 -induced cytotoxicity, apoptosis, MMP, and OS levels. H 2 O 2 stimulated the activation of Nrf2 and JNK signaling pathways, but TGD increased the extent of Nrf2 antioxidant activation, decreased the activation of JNK, and eventually reversed the H 2 O 2 -induced protein expression of p-MKK7, Keap1, HO-1, Cleaved Caspase3 (CL-Casp3), Cleaved Caspase9 (CL-Casp9), Bax, and Bcl-2.
Conclusions: This study's findings suggest that TGD may attenuate oxidative injury and apoptosis via the Nrf2 and JNK signaling pathways, making it a potential therapeutic candidate for neurodegenerative diseases.
(Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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