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Rhubarb granule promotes diethylnitrosamine-induced liver tumorigenesis by activating the oxidative branch of pentose phosphate pathway via G6PD in rats
Huang, Hongwu1; Liu, Zhenzhen1; Qi, Xiaoru1; Gao, Nailong3; Chang, Jianguo3; Yang, Miaomiao4,5; Na, Sha1; Liu, Yanyan1; Song, Rui1; Li, Lu1,2; Chen, Guangliang2; Zhou, Hui1
2021-12-05
Source PublicationJOURNAL OF ETHNOPHARMACOLOGY
ISSN0378-8741
Corresponding AuthorLi, Lu(deerlyee@hotmail.com) ; Chen, Guangliang(1453345650@qq.com) ; Zhou, Hui(729431741@qq.com)
AbstractEthnopharmacological relevance: Rhubarb is a natural herbal medicine widely used clinically with numerous pharmacological activities including anti-cancer. Specifically, several studies reported that free anthraquinones from Rhubarb suppressed the proliferation of hepatoma cells. Nonetheless, recent studies revealed that Rhubarb caused hepatotoxicity in vivo, confirming its "two-way" effect on the liver. Therefore, the efficacy and safety of Rhubarb in the in vivo treatment of liver cancer should be further elucidated. Aim of the study: This study investigated the presence of hepatoprotection or hepatotoxicity of Rhubarb in diethylnitrosamine (DEN)-induced hepatocarcinogenesis. Material and methods: A total of 112 male Sprague-Dawley rats weighing 190-250 g were enrolled. The rats were induced hepatocarcinogenesis using diethylnitrosamine (0.002 g/rat) until 17 weeks. Starting at week 11, Rhubarb granules (4 g/kg and 8 g/kg) were intragastrically administered daily for 7 weeks. All rats were euthanized at week 20 and the livers were analyzed via non-targeted metabolomics analysis. We established hepatic glucose 6 phosphate (6PG) levels and glucose 6 phosphate dehydrogenase (G6PD) activities to assess the pentose phosphate pathway (PPP). And the liver injuries of rats were analyzed via histological changes, hepatic function, as well as hepatic protein levels of alpha-fetoprotein (AFP), pyruvate kinase isozyme type M2 (PKM2), and proliferating cell nuclear antigen (PCNA). Furthermore, polydatin (0.1 g/kg/d) as a specific inhibitor of G6PD was used to treat rats. Notably, their histological changes, hepatic function, hepatic 6PG levels, hepatic G6PD activities, PCNA levels, and PKM2 levels were recorded. Results: Non-targeted metabolomics revealed that Rhubarb regulated the PPP in the liver of Rhubarb-DEN-treated rats. Besides, Rhubarb activated the oxidative branch of the PPP by activating G6PD (a rate-limiting enzyme in the oxidative PPP) in the liver of Rhubarb-DEN-treated rats. Meanwhile, Rhubarb promoted DEN-induced hepatocarcinogenesis. Moreover, polydatin attenuated the promoting effect of Rhubarb on DEN-induced hepatocarcinogenesis. Conclusions: Rhubarb promoted DEN-induced hepatocarcinogenesis by activating the PPP, indicating that the efficacy and safety of Rhubarb in the treatment of liver cancer deserve to be deliberated.
KeywordRhubarb Hepatocarcinogenesis Diethylnitrosamine The pentose phosphate pathway Glucose 6 phosphate dehydrogenase
DOI10.1016/j.jep.2021.114479
WOS KeywordHEPATOCELLULAR-CARCINOMA ; 6-PHOSPHOGLUCONATE DEHYDROGENASE ; APOPTOSIS ; GLUCOSE-6-PHOSPHATE-DEHYDROGENASE ; EMODIN ; EXPRESSION ; EXTRACT ; GROWTH ; HEPATOTOXICITY ; PROLIFERATION
Indexed BySCI
Language英语
Funding ProjectNational Natural Science Foundation of China[81703826] ; Anhui Province Natural Science Foundation of China[1808085MH301]
Funding OrganizationNational Natural Science Foundation of China ; Anhui Province Natural Science Foundation of China
WOS Research AreaPlant Sciences ; Pharmacology & Pharmacy ; Integrative & Complementary Medicine
WOS SubjectPlant Sciences ; Chemistry, Medicinal ; Integrative & Complementary Medicine ; Pharmacology & Pharmacy
WOS IDWOS:000704786400002
PublisherELSEVIER IRELAND LTD
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Document Type期刊论文
Identifierhttp://ir.hfcas.ac.cn:8080/handle/334002/125524
Collection中国科学院合肥物质科学研究院
Corresponding AuthorLi, Lu; Chen, Guangliang; Zhou, Hui
Affiliation1.Anhui Univ Tradit Chinese Med, Sch Integrated Chinese & Western Med, Dept Biochem & Mol Biol, 1 Qianjiang Rd, Hefei, Anhui, Peoples R China
2.Anhui Acad Chinese Med, Inst Integrated Chinese & Western Med, Hefei, Anhui, Peoples R China
3.Univ Sci & Technol China, Dept Precis Machinery & Precis Instrumentat, Hefei, Peoples R China
4.Chinese Acad Sci, Ctr Med Phys & Technol, Hefei Inst Phys Sci, Hefei, Peoples R China
5.Anhui Med Univ, Clin Pathol Ctr, Affiliated Hosp 4, Hefei, Anhui, Peoples R China
Recommended Citation
GB/T 7714
Huang, Hongwu,Liu, Zhenzhen,Qi, Xiaoru,et al. Rhubarb granule promotes diethylnitrosamine-induced liver tumorigenesis by activating the oxidative branch of pentose phosphate pathway via G6PD in rats[J]. JOURNAL OF ETHNOPHARMACOLOGY,2021,281.
APA Huang, Hongwu.,Liu, Zhenzhen.,Qi, Xiaoru.,Gao, Nailong.,Chang, Jianguo.,...&Zhou, Hui.(2021).Rhubarb granule promotes diethylnitrosamine-induced liver tumorigenesis by activating the oxidative branch of pentose phosphate pathway via G6PD in rats.JOURNAL OF ETHNOPHARMACOLOGY,281.
MLA Huang, Hongwu,et al."Rhubarb granule promotes diethylnitrosamine-induced liver tumorigenesis by activating the oxidative branch of pentose phosphate pathway via G6PD in rats".JOURNAL OF ETHNOPHARMACOLOGY 281(2021).
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