Licorice attenuates cisplatin-induced hepatotoxicity by alleviating endoplasmic reticulum stress and apoptosis
Cisplatin (CP), a widely used antineoplastic drug, could induce hepatotoxicity and is also one of the most common reasons for drug-induced liver injury (DILI). Licorice (Chinese name GanCao, GC) is a commonly used herbal drug in traditional Chinese medicine (TCM) that has been shown to treat liver d...
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Frontiers Media S.A.
2025-03-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1557125/full |
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| author | Jie Li Xiujuan Yang Xiaolong Lian Baojian Li Quhuan Ma Lingling Yang Guangmiao Gao Yi Deng Zhijun Yang |
| author_facet | Jie Li Xiujuan Yang Xiaolong Lian Baojian Li Quhuan Ma Lingling Yang Guangmiao Gao Yi Deng Zhijun Yang |
| author_sort | Jie Li |
| collection | DOAJ |
| description | Cisplatin (CP), a widely used antineoplastic drug, could induce hepatotoxicity and is also one of the most common reasons for drug-induced liver injury (DILI). Licorice (Chinese name GanCao, GC) is a commonly used herbal drug in traditional Chinese medicine (TCM) that has been shown to treat liver diseases and DILI. CP has been documented to induce apoptosis through the promotion of endoplasmic reticulum (ER) stress. However, the exact role of ER stress in the pathogenesis of CP-induced hepatotoxicity remains unclear. A rat DILI model was constructed through intraperitoneal injection of CP, and the anti-DILI effect of GC was detected by liver coefficients, liver function tests, pathological staining, and oxidative stress indices. Additionally, the ER stress and apoptosis indices were investigated by quantitative real-time PCR (qRT-PCR), Western blotting, and immunofluorescence (IF) on CP-induced toxicity in rat liver tissues and LO2 cells. In the model group, liver function indicators significantly elevated, liver lesions more pronounced, and the reactive oxygen species (ROS) level in the liver increased, the expression of ER stress markers, apoptosis factors, and indicators related to the protein kinase RNA-like ER kinase/activating transcription factor 4/C/EBP homologous protein (PERK/ATF4/CHOP) pathway significantly elevated. Treatment of the CP-induced toxicity in the rat model with GC significantly improved liver function, reduced liver lesions, decreased liver ROS. In addition, GC significantly inhibited the expression of ER stress markers, apoptosis factors, and indicators related to PERK/ATF4/CHOP pathway, demonstrating the anti-CP-induced hepatotoxicity effect of GC. In this study, we verified the protective effect of GC in CP-induced hepatotoxicity in rats and clarified its mechanisms related to ER stress and apoptosis. |
| format | Article |
| id | doaj-art-bcfb07cae090423cb8bce39c3be9afad |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-bcfb07cae090423cb8bce39c3be9afad2025-08-20T03:42:41ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-03-011610.3389/fphar.2025.15571251557125Licorice attenuates cisplatin-induced hepatotoxicity by alleviating endoplasmic reticulum stress and apoptosisJie Li0Xiujuan Yang1Xiaolong Lian2Baojian Li3Quhuan Ma4Lingling Yang5Guangmiao Gao6Yi Deng7Zhijun Yang8School of Pharmaceutical Science, Gansu University of Traditional Chinese Medicine, Lanzhou, Gansu, ChinaSchool of Pharmaceutical Science, Gansu University of Traditional Chinese Medicine, Lanzhou, Gansu, ChinaDepartment of pharmacy, Qinghai University Medical College, Xining, ChinaShaanxi University of Chinese Medicine, Xi’an, ChinaSchool of Pharmaceutical Science, Gansu University of Traditional Chinese Medicine, Lanzhou, Gansu, ChinaSchool of Pharmaceutical Science, Gansu University of Traditional Chinese Medicine, Lanzhou, Gansu, ChinaSchool of Pharmaceutical Science, Gansu University of Traditional Chinese Medicine, Lanzhou, Gansu, ChinaSchool of Pharmaceutical Science, Gansu University of Traditional Chinese Medicine, Lanzhou, Gansu, ChinaSchool of Pharmaceutical Science, Gansu University of Traditional Chinese Medicine, Lanzhou, Gansu, ChinaCisplatin (CP), a widely used antineoplastic drug, could induce hepatotoxicity and is also one of the most common reasons for drug-induced liver injury (DILI). Licorice (Chinese name GanCao, GC) is a commonly used herbal drug in traditional Chinese medicine (TCM) that has been shown to treat liver diseases and DILI. CP has been documented to induce apoptosis through the promotion of endoplasmic reticulum (ER) stress. However, the exact role of ER stress in the pathogenesis of CP-induced hepatotoxicity remains unclear. A rat DILI model was constructed through intraperitoneal injection of CP, and the anti-DILI effect of GC was detected by liver coefficients, liver function tests, pathological staining, and oxidative stress indices. Additionally, the ER stress and apoptosis indices were investigated by quantitative real-time PCR (qRT-PCR), Western blotting, and immunofluorescence (IF) on CP-induced toxicity in rat liver tissues and LO2 cells. In the model group, liver function indicators significantly elevated, liver lesions more pronounced, and the reactive oxygen species (ROS) level in the liver increased, the expression of ER stress markers, apoptosis factors, and indicators related to the protein kinase RNA-like ER kinase/activating transcription factor 4/C/EBP homologous protein (PERK/ATF4/CHOP) pathway significantly elevated. Treatment of the CP-induced toxicity in the rat model with GC significantly improved liver function, reduced liver lesions, decreased liver ROS. In addition, GC significantly inhibited the expression of ER stress markers, apoptosis factors, and indicators related to PERK/ATF4/CHOP pathway, demonstrating the anti-CP-induced hepatotoxicity effect of GC. In this study, we verified the protective effect of GC in CP-induced hepatotoxicity in rats and clarified its mechanisms related to ER stress and apoptosis.https://www.frontiersin.org/articles/10.3389/fphar.2025.1557125/fulllicoricehepatotoxicityER stressPERK/ATF4/CHOP pathwayapoptosis |
| spellingShingle | Jie Li Xiujuan Yang Xiaolong Lian Baojian Li Quhuan Ma Lingling Yang Guangmiao Gao Yi Deng Zhijun Yang Licorice attenuates cisplatin-induced hepatotoxicity by alleviating endoplasmic reticulum stress and apoptosis Frontiers in Pharmacology licorice hepatotoxicity ER stress PERK/ATF4/CHOP pathway apoptosis |
| title | Licorice attenuates cisplatin-induced hepatotoxicity by alleviating endoplasmic reticulum stress and apoptosis |
| title_full | Licorice attenuates cisplatin-induced hepatotoxicity by alleviating endoplasmic reticulum stress and apoptosis |
| title_fullStr | Licorice attenuates cisplatin-induced hepatotoxicity by alleviating endoplasmic reticulum stress and apoptosis |
| title_full_unstemmed | Licorice attenuates cisplatin-induced hepatotoxicity by alleviating endoplasmic reticulum stress and apoptosis |
| title_short | Licorice attenuates cisplatin-induced hepatotoxicity by alleviating endoplasmic reticulum stress and apoptosis |
| title_sort | licorice attenuates cisplatin induced hepatotoxicity by alleviating endoplasmic reticulum stress and apoptosis |
| topic | licorice hepatotoxicity ER stress PERK/ATF4/CHOP pathway apoptosis |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1557125/full |
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