Liujunzi decoction attenuates cisplatin-induced anorexia in rats via inhibiting PERK/eIF2α/ATF4/CHOP pathway and GDF15/GFRAL expression

Background and aim: Liujunzi Decoction (LJZD), also called Rikkunshito, is a traditional formula that has proven effective in clinical treatment against chemotherapy-induced anorexia (CIA). Previous study indicated the importance of GDF15/GFRAL axis in the pathogenesis of CIA, and suggested the pote...

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Main Authors: Yongzhao Dai, Wanting Hu, Jinyuan Han, Yaozhong Zhao, Xipei Wu, Xiuxiu Liao, Ke Nie
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2024-06-01
Series:Journal of Holistic Integrative Pharmacy
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Online Access:http://www.sciencedirect.com/science/article/pii/S2707368824000293
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author Yongzhao Dai
Wanting Hu
Jinyuan Han
Yaozhong Zhao
Xipei Wu
Xiuxiu Liao
Ke Nie
author_facet Yongzhao Dai
Wanting Hu
Jinyuan Han
Yaozhong Zhao
Xipei Wu
Xiuxiu Liao
Ke Nie
author_sort Yongzhao Dai
collection DOAJ
description Background and aim: Liujunzi Decoction (LJZD), also called Rikkunshito, is a traditional formula that has proven effective in clinical treatment against chemotherapy-induced anorexia (CIA). Previous study indicated the importance of GDF15/GFRAL axis in the pathogenesis of CIA, and suggested the potential connection between endoplasmic reticulum stress and GDF15 expression. However, further exploration is required to determine whether the mechanism of LJZD against CIA is related to the PERK/eIF2α/ATF4/CHOP signaling and GDF15/GFRAL expression. Methods: The CIA model of rats was established via intraperitoneal injection of cisplatin, and the rats were given LJZD orally for 72 ​h. Food intake and body weight were recorded daily. The expression of GDF15/GFRAL and ER stress factors, as well as the histological injuries were investigated. Results: LJZD led to a significant increase in food intake in rats and a decrease in serum GDF15 levels at 24 ​h and 72 ​h after cisplatin injection. This effect may be associated with the inhibition of Gdf15 transcription and the amelioration of pathological injuries or endoplasmic reticulum stress in the liver and ileum. Moreover, LJZD suppressed the cisplatin-induced activation of the hepatic and ileal PERK/eIF2α/ATF4/CHOP pathway, resulting in the alleviation of central GDF15/GFRAL expression. Conclusion: LJZD effectively improves cisplatin-induced anorexia in a rat model, which might be attributed to its inhibition of the PERK/eIF2α/ATF4/CHOP pathway and GDF15/GFRAL expression activated by cisplatin.
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spelling doaj-art-d992fe3b15694474a309691d6094f37a2024-11-12T05:21:48ZengKeAi Communications Co., Ltd.Journal of Holistic Integrative Pharmacy2707-36882024-06-0152113120Liujunzi decoction attenuates cisplatin-induced anorexia in rats via inhibiting PERK/eIF2α/ATF4/CHOP pathway and GDF15/GFRAL expressionYongzhao Dai0Wanting Hu1Jinyuan Han2Yaozhong Zhao3Xipei Wu4Xiuxiu Liao5Ke Nie6School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou, 510006, ChinaSchool of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou, 510006, ChinaSchool of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou, 510006, ChinaSchool of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou, 510006, ChinaSchool of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou, 510006, ChinaSchool of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou, 510006, ChinaCorresponding author. School of Chinese Materia Medica, Guangdong Pharmaceutical University, 280 Waihuandong Road, Guangzhou Higher Education Mega Center, Guangzhou, 510006, China.; School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou, 510006, ChinaBackground and aim: Liujunzi Decoction (LJZD), also called Rikkunshito, is a traditional formula that has proven effective in clinical treatment against chemotherapy-induced anorexia (CIA). Previous study indicated the importance of GDF15/GFRAL axis in the pathogenesis of CIA, and suggested the potential connection between endoplasmic reticulum stress and GDF15 expression. However, further exploration is required to determine whether the mechanism of LJZD against CIA is related to the PERK/eIF2α/ATF4/CHOP signaling and GDF15/GFRAL expression. Methods: The CIA model of rats was established via intraperitoneal injection of cisplatin, and the rats were given LJZD orally for 72 ​h. Food intake and body weight were recorded daily. The expression of GDF15/GFRAL and ER stress factors, as well as the histological injuries were investigated. Results: LJZD led to a significant increase in food intake in rats and a decrease in serum GDF15 levels at 24 ​h and 72 ​h after cisplatin injection. This effect may be associated with the inhibition of Gdf15 transcription and the amelioration of pathological injuries or endoplasmic reticulum stress in the liver and ileum. Moreover, LJZD suppressed the cisplatin-induced activation of the hepatic and ileal PERK/eIF2α/ATF4/CHOP pathway, resulting in the alleviation of central GDF15/GFRAL expression. Conclusion: LJZD effectively improves cisplatin-induced anorexia in a rat model, which might be attributed to its inhibition of the PERK/eIF2α/ATF4/CHOP pathway and GDF15/GFRAL expression activated by cisplatin.http://www.sciencedirect.com/science/article/pii/S2707368824000293Liujunzi decoctionChemotherapy-induced anorexiaGDF15/GFRAL axisEndoplasmic reticulum stressRat
spellingShingle Yongzhao Dai
Wanting Hu
Jinyuan Han
Yaozhong Zhao
Xipei Wu
Xiuxiu Liao
Ke Nie
Liujunzi decoction attenuates cisplatin-induced anorexia in rats via inhibiting PERK/eIF2α/ATF4/CHOP pathway and GDF15/GFRAL expression
Journal of Holistic Integrative Pharmacy
Liujunzi decoction
Chemotherapy-induced anorexia
GDF15/GFRAL axis
Endoplasmic reticulum stress
Rat
title Liujunzi decoction attenuates cisplatin-induced anorexia in rats via inhibiting PERK/eIF2α/ATF4/CHOP pathway and GDF15/GFRAL expression
title_full Liujunzi decoction attenuates cisplatin-induced anorexia in rats via inhibiting PERK/eIF2α/ATF4/CHOP pathway and GDF15/GFRAL expression
title_fullStr Liujunzi decoction attenuates cisplatin-induced anorexia in rats via inhibiting PERK/eIF2α/ATF4/CHOP pathway and GDF15/GFRAL expression
title_full_unstemmed Liujunzi decoction attenuates cisplatin-induced anorexia in rats via inhibiting PERK/eIF2α/ATF4/CHOP pathway and GDF15/GFRAL expression
title_short Liujunzi decoction attenuates cisplatin-induced anorexia in rats via inhibiting PERK/eIF2α/ATF4/CHOP pathway and GDF15/GFRAL expression
title_sort liujunzi decoction attenuates cisplatin induced anorexia in rats via inhibiting perk eif2α atf4 chop pathway and gdf15 gfral expression
topic Liujunzi decoction
Chemotherapy-induced anorexia
GDF15/GFRAL axis
Endoplasmic reticulum stress
Rat
url http://www.sciencedirect.com/science/article/pii/S2707368824000293
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