Ginsenoside Rg1 alleviates chronic testicular damage caused by cranial irradiation through the SCF/PI3K/Akt/mTOR pathway in mice

Objective: To investigate whether Ginsenoside Rg1 can mitigate the adverse effects of cranial irradiation on distal reproductive function in mice and to explore the underlying mechanisms. Methods: Forty male C57BL/6J mice were randomly divided to four groups [Control, irradiation (IR), IR ​+ ​Rg1, R...

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Main Authors: Qiuhua Zhou, Yiquan Ou, Xiangsheng Tian, Yujun Ning, Yuwei Mao, Weichao Zhao, Dingxin Long
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:Radiation Medicine and Protection
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Online Access:http://www.sciencedirect.com/science/article/pii/S2666555724001199
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author Qiuhua Zhou
Yiquan Ou
Xiangsheng Tian
Yujun Ning
Yuwei Mao
Weichao Zhao
Dingxin Long
author_facet Qiuhua Zhou
Yiquan Ou
Xiangsheng Tian
Yujun Ning
Yuwei Mao
Weichao Zhao
Dingxin Long
author_sort Qiuhua Zhou
collection DOAJ
description Objective: To investigate whether Ginsenoside Rg1 can mitigate the adverse effects of cranial irradiation on distal reproductive function in mice and to explore the underlying mechanisms. Methods: Forty male C57BL/6J mice were randomly divided to four groups [Control, irradiation (IR), IR ​+ ​Rg1, Rg1), IR ​+ ​Rg1 and Rg1 group treated with intraperitoneal injections of Ginsenoside Rg1 for 30 ​d, followed by single-dose irradiation of 5 ​Gy X-ray irradiation (2 ​Gy/min) for the IR and IR ​+ ​Rg1 group. After three months, testicles, whole brain, and serum samples were collected for analysis. Results: Histological staining, transmission electron microscopy, sperm analysis, and immunofluorescence demonstrated that Ginsenoside Rg1 ameliorated structural and functional damage to the testicles, enhanced sperm count (IR: 20.70 ​± ​1.62 vs. IR ​+ ​Rg1: 33.93 ​± ​2.20, t ​= ​−13.23, P ​< ​0.05), and reduced sperm malformation rates (IR: 46.33 ​± ​2.18 vs. IR ​+ ​Rg1: 39.00 ​± ​1.67, t ​= ​7.33, P ​< ​0.05). Further Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) and Enzyme linked immunosorbent assay (ELISA) assays demonstrated that Rg1 inhibited testicular apoptosis (IR: 3.21 ​± ​0.28 vs. IR ​+ ​Rg1: 1.81 ​± ​0.18, t ​= ​1.40, P ​< ​0.05) and modulated serum testosterone (IR: 4.47 ​± ​0.23 vs. IR ​+ ​Rg1: 6.65 ​± ​0.09, t ​= ​−2.18, P ​< ​0.05), GnRH (IR: 24.37 ​± ​0.92 vs. IR ​+ ​Rg1: 32.98 ​± ​1.33, t ​= ​−8.61, P ​< ​0.05), and FSH levels (IR: 1.41 ​± ​0.11 vs. IR ​+ ​Rg1: 2.69 ​± ​0.21, t ​= ​−1.28, P ​< ​0.05). Additionally, quantitative PCR and Western blot showed that Rg1 downregulated SCF, p-PI3K, p-Akt, and mTOR protein expressions in irradiated mice. Conclusions: Ginsenoside Rg1 potentially alleviate chronic testicular structural and functional damage by inhibiting germ cell apoptosis through the modulation of the HPG axis and the PI3K/Akt/mTOR pathway, suggesting that it is a potential therapeutic agent for reproductive disorders induced by cranial irradiation.
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spelling doaj-art-48e7b81473e2490d8741e6e54b8e26872025-02-12T05:32:54ZengElsevierRadiation Medicine and Protection2666-55572025-02-01611121Ginsenoside Rg1 alleviates chronic testicular damage caused by cranial irradiation through the SCF/PI3K/Akt/mTOR pathway in miceQiuhua Zhou0Yiquan Ou1Xiangsheng Tian2Yujun Ning3Yuwei Mao4Weichao Zhao5Dingxin Long6School of Public Health, Hengyang Medical School, University of South China, Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, Hengyang 421001, ChinaSchool of Public Health, Hengyang Medical School, University of South China, Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, Hengyang 421001, China; Department of nutrition, The First People's Hospital of Chenzhou, Chenzhou 423000, ChinaSchool of Public Health, Hengyang Medical School, University of South China, Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, Hengyang 421001, ChinaSchool of Public Health, Hengyang Medical School, University of South China, Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, Hengyang 421001, ChinaSchool of Public Health, Hengyang Medical School, University of South China, Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, Hengyang 421001, ChinaSchool of Public Health, Hengyang Medical School, University of South China, Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, Hengyang 421001, China; Corresponding author.School of Public Health, Hengyang Medical School, University of South China, Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, Hengyang 421001, China; Corresponding author.Objective: To investigate whether Ginsenoside Rg1 can mitigate the adverse effects of cranial irradiation on distal reproductive function in mice and to explore the underlying mechanisms. Methods: Forty male C57BL/6J mice were randomly divided to four groups [Control, irradiation (IR), IR ​+ ​Rg1, Rg1), IR ​+ ​Rg1 and Rg1 group treated with intraperitoneal injections of Ginsenoside Rg1 for 30 ​d, followed by single-dose irradiation of 5 ​Gy X-ray irradiation (2 ​Gy/min) for the IR and IR ​+ ​Rg1 group. After three months, testicles, whole brain, and serum samples were collected for analysis. Results: Histological staining, transmission electron microscopy, sperm analysis, and immunofluorescence demonstrated that Ginsenoside Rg1 ameliorated structural and functional damage to the testicles, enhanced sperm count (IR: 20.70 ​± ​1.62 vs. IR ​+ ​Rg1: 33.93 ​± ​2.20, t ​= ​−13.23, P ​< ​0.05), and reduced sperm malformation rates (IR: 46.33 ​± ​2.18 vs. IR ​+ ​Rg1: 39.00 ​± ​1.67, t ​= ​7.33, P ​< ​0.05). Further Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) and Enzyme linked immunosorbent assay (ELISA) assays demonstrated that Rg1 inhibited testicular apoptosis (IR: 3.21 ​± ​0.28 vs. IR ​+ ​Rg1: 1.81 ​± ​0.18, t ​= ​1.40, P ​< ​0.05) and modulated serum testosterone (IR: 4.47 ​± ​0.23 vs. IR ​+ ​Rg1: 6.65 ​± ​0.09, t ​= ​−2.18, P ​< ​0.05), GnRH (IR: 24.37 ​± ​0.92 vs. IR ​+ ​Rg1: 32.98 ​± ​1.33, t ​= ​−8.61, P ​< ​0.05), and FSH levels (IR: 1.41 ​± ​0.11 vs. IR ​+ ​Rg1: 2.69 ​± ​0.21, t ​= ​−1.28, P ​< ​0.05). Additionally, quantitative PCR and Western blot showed that Rg1 downregulated SCF, p-PI3K, p-Akt, and mTOR protein expressions in irradiated mice. Conclusions: Ginsenoside Rg1 potentially alleviate chronic testicular structural and functional damage by inhibiting germ cell apoptosis through the modulation of the HPG axis and the PI3K/Akt/mTOR pathway, suggesting that it is a potential therapeutic agent for reproductive disorders induced by cranial irradiation.http://www.sciencedirect.com/science/article/pii/S2666555724001199Cranial irradiationAbscopal effectsGinsenoside Rg1Testicular apoptosisHPG axisSCF/PI3K/AKT/mTOR signaling
spellingShingle Qiuhua Zhou
Yiquan Ou
Xiangsheng Tian
Yujun Ning
Yuwei Mao
Weichao Zhao
Dingxin Long
Ginsenoside Rg1 alleviates chronic testicular damage caused by cranial irradiation through the SCF/PI3K/Akt/mTOR pathway in mice
Radiation Medicine and Protection
Cranial irradiation
Abscopal effects
Ginsenoside Rg1
Testicular apoptosis
HPG axis
SCF/PI3K/AKT/mTOR signaling
title Ginsenoside Rg1 alleviates chronic testicular damage caused by cranial irradiation through the SCF/PI3K/Akt/mTOR pathway in mice
title_full Ginsenoside Rg1 alleviates chronic testicular damage caused by cranial irradiation through the SCF/PI3K/Akt/mTOR pathway in mice
title_fullStr Ginsenoside Rg1 alleviates chronic testicular damage caused by cranial irradiation through the SCF/PI3K/Akt/mTOR pathway in mice
title_full_unstemmed Ginsenoside Rg1 alleviates chronic testicular damage caused by cranial irradiation through the SCF/PI3K/Akt/mTOR pathway in mice
title_short Ginsenoside Rg1 alleviates chronic testicular damage caused by cranial irradiation through the SCF/PI3K/Akt/mTOR pathway in mice
title_sort ginsenoside rg1 alleviates chronic testicular damage caused by cranial irradiation through the scf pi3k akt mtor pathway in mice
topic Cranial irradiation
Abscopal effects
Ginsenoside Rg1
Testicular apoptosis
HPG axis
SCF/PI3K/AKT/mTOR signaling
url http://www.sciencedirect.com/science/article/pii/S2666555724001199
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