Tiao Geng decoction for treating menopausal syndrome exhibits anti-aging effects likely via suppressing ASK1/MKK7/JNK mediated apoptosis in ovariectomized rats. (28th October 2020)

• Record Type: Journal Article
• Authors: Li, Shengnan; Cong, Chao; Liu, Yang; Liu, Xiaofei; Kluwe, Lan; Shan, Xin; Liu, Huicong; Gao, Min; Zhao, Li; Gao, Xianwei; Xu, Lianwei
• Is Part Of: Journal of ethnopharmacology. Volume 261(2020)
• Publication Date: 2020-10-28
• Subjects: TG-Decoction -- Menopausal syndrome -- Chinese herbs -- Hypothalamic neuron -- ASK1/MKK7/JNK; AP-1 Activating protein 1 -- ASK1 Apoptosis signal-regulating kinase 1 -- p-ASK1 Phospho-Apoptosis signal-regulating kinase 1 -- Bcl-2 B-cell lymphoma 2 -- Casp3 caspase-3 -- ERK Extracellular signal-regulated kinase -- ER Estrogen Receptor -- Ev Estradiol valerate -- JNK c-Jun N-terminal kinase -- p-JNK Phospho-c-Jun N-terminal kinase -- MAPK Mitogen-activated protein kinase -- MAP2K Mitogen-activated protein kinase kinase -- MAP3K Mitogen-activated protein kinase kinase kinase -- MKK7 Mitogen-activated protein kinase kinase 7 -- p-MKK7 Phospho-Mitogen-activated protein kinase kinase 7 -- ROS Reactive oxygen species -- TEM Transmission electron microscopy -- TNF Tumor necrosis factor; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2020.113061
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: TG-decoction (Tiao Geng decoction) is the extract of a Chinese herb mixture that has been used for treating menopausal symptoms for over 30 years. We have previously reported anti-aging and anti-oxidative effects of the TG-decoction on hypothalamic neurons in ovariectomized (OVX) rats. Aim of the study: The present study further investigates the effects of TG-decoction on the prevention of aging-related ultrastructural changes in menopausal hypothalamic neurons and the likely molecular mechanism. Materials and methods: A total of 120 four-month-old female SPF Sprague Dawley rats were divided into six groups. Five groups were ovariectomized (OVX) and one group served as a sham control. Three OVX groups received TG-decoction at three different doses. The remaining two OVX groups served as positive and negative controls by receiving estradiol valerate and saline solution. The sham group received saline. After one month, aging-related ultrastructural alterations in hypothalamic neurons were evaluated using transmission electron microscopy. Nissl staining was used to assess the pathomorphological changes of the hypothalamic neurons. Cell apoptosis was evaluated by TUNEL. Expression of Bcl-2 family genes was studied using qRT-PCR. Expression of the apoptosis-related proteins ASK1, MKK7, JNK, c-Jun, Bax, Casp3 and Bcl-2 was studied using western blotting. Results: Ovariectomy of female rats led to visible damage and aging-like alterations in the mitochondria and endoplasmic reticulum as well as large deposits of lipofuscin in hypothalamic tissue. TG-decoction treatment prevented this visible damage and lipofuscin deposition, increased the number of nerve cells and normally-shaped Nissl bodies, and reduced the number of TUNEL-positive cells. Expression of Bcl-2 gene was increased, while Bax gene reduced. Expression of the proteins ASK1, MKK7, JNK, c-Jun, Bax and Casp3 was reduced, while that of Bcl-2 was increased. Conclusion: TG-decoction reduces aging-related ultrastructural changes in hypothalamic neurons, likely by suppressing ASK1/MKK7/JNK-mediated apoptosis in neuronal mitochondria or nuclei. Graphical abstract: ASK1/MKK7/JNK pathway may play a role in the mechanisms of TG-decoction. Image 1