Natural product Erianin: mitigating FOLFOX toxicity and enhancing against colorectal cancer
IntroductionColorectal cancer (CRC) is a prevalent malignant tumor of the digestive tract. The FOLFOX regimen (oxaliplatin + calcium folinate + 5-fluorouracil) serves as the primary treatment for advanced CRC clinically, yet its application is significantly limited by substantial toxic side effects....
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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Chemistry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fchem.2025.1650197/full |
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| author | Fuqin Yang Zeqiao Li Haishan Zhang Mingxiao Zhang Zhenwei He Xiaoqin Zheng Yingru Zhu Pei Long Ruirui Ding Zhengbin Lin Lijuan Deng Lijuan Deng |
| author_facet | Fuqin Yang Zeqiao Li Haishan Zhang Mingxiao Zhang Zhenwei He Xiaoqin Zheng Yingru Zhu Pei Long Ruirui Ding Zhengbin Lin Lijuan Deng Lijuan Deng |
| author_sort | Fuqin Yang |
| collection | DOAJ |
| description | IntroductionColorectal cancer (CRC) is a prevalent malignant tumor of the digestive tract. The FOLFOX regimen (oxaliplatin + calcium folinate + 5-fluorouracil) serves as the primary treatment for advanced CRC clinically, yet its application is significantly limited by substantial toxic side effects. Erianin, a natural compound from Chinese medicine Dendrobium chrysotoxum Lindl, demonstrates significant potential in both tumor growth inhibition and chemotherapy toxicity reduction. This study aims to investigate the potential of Erianin in reducing the toxicity of the FOLFOX regimen while enhancing its antitumor efficacy.MethodsThis study integrated network toxicology and molecular docking to predict the potential targets of Erianin in alleviating FOLFOX-induced side effects. Using an orthotopic MC38 CRC transplantation model, we conducted a comprehensive evaluation of the effects of Erianin in mitigating FOLFOX-induced changes in body weight changes, hematological parameters, and histopathology of major organs (heart, liver, spleen, kidneys, and intestines). IHC analysis elucidated alterations in intestinal barrier proteins, AKT1/mTOR pathway, and tumor proliferation and apoptosis biomarkers. Tumor progression was dynamically monitored by in vivo imaging.ResultsThe results showed that Erianin improved weight loss, pathological changes in organs, and reduction in peripheral blood cell counts (WBC, RBC, HGB, PLT, HCT) caused by FOLFOX in mice. Erianin reversed the inhibition of intestinal tight junction proteins (e.g. ZO-1, Occludin, Claudin-5) and AKT1/mTOR pathway caused by FOLFOX. In addition, the tumor size was significantly reduced in the combination group, and the expression of the apoptosis marker Cleaved Caspase-3 was up-regulated, and the proliferation markers Ki67/PCNA were down-regulated.DiscussionErianin can enhance the anti-CRC effect of FOLFOX, and mitigates FOLFOX-induced toxicity by activating the AKT1/mTOR pathway. |
| format | Article |
| id | doaj-art-c5f63eeccc344ced96dca26db31b69ab |
| institution | Kabale University |
| issn | 2296-2646 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Chemistry |
| spelling | doaj-art-c5f63eeccc344ced96dca26db31b69ab2025-08-22T09:35:51ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462025-08-011310.3389/fchem.2025.16501971650197Natural product Erianin: mitigating FOLFOX toxicity and enhancing against colorectal cancerFuqin Yang0Zeqiao Li1Haishan Zhang2Mingxiao Zhang3Zhenwei He4Xiaoqin Zheng5Yingru Zhu6Pei Long7Ruirui Ding8Zhengbin Lin9Lijuan Deng10Lijuan Deng11Guangzhou Key Laboratory of Formula-Pattern Research Center, School of Traditional Chinese Medicine, The Fifth Affiliated Hospital of Jinan University (Heyuan Shenhe People’s Hospital), Jinan University, Guangzhou, ChinaState Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, College of Pharmacy, Jinan University, Guangzhou, ChinaState Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, College of Pharmacy, Jinan University, Guangzhou, ChinaState Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, College of Pharmacy, Jinan University, Guangzhou, ChinaGuangzhou Key Laboratory of Formula-Pattern Research Center, School of Traditional Chinese Medicine, The Fifth Affiliated Hospital of Jinan University (Heyuan Shenhe People’s Hospital), Jinan University, Guangzhou, ChinaState Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, College of Pharmacy, Jinan University, Guangzhou, ChinaGuangzhou Key Laboratory of Formula-Pattern Research Center, School of Traditional Chinese Medicine, The Fifth Affiliated Hospital of Jinan University (Heyuan Shenhe People’s Hospital), Jinan University, Guangzhou, ChinaGuangzhou Key Laboratory of Formula-Pattern Research Center, School of Traditional Chinese Medicine, The Fifth Affiliated Hospital of Jinan University (Heyuan Shenhe People’s Hospital), Jinan University, Guangzhou, ChinaXinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Changxing Branch, Shanghai, ChinaGuangzhou Key Laboratory of Formula-Pattern Research Center, School of Traditional Chinese Medicine, The Fifth Affiliated Hospital of Jinan University (Heyuan Shenhe People’s Hospital), Jinan University, Guangzhou, ChinaGuangzhou Key Laboratory of Formula-Pattern Research Center, School of Traditional Chinese Medicine, The Fifth Affiliated Hospital of Jinan University (Heyuan Shenhe People’s Hospital), Jinan University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization, Jinan University, Guangzhou, ChinaIntroductionColorectal cancer (CRC) is a prevalent malignant tumor of the digestive tract. The FOLFOX regimen (oxaliplatin + calcium folinate + 5-fluorouracil) serves as the primary treatment for advanced CRC clinically, yet its application is significantly limited by substantial toxic side effects. Erianin, a natural compound from Chinese medicine Dendrobium chrysotoxum Lindl, demonstrates significant potential in both tumor growth inhibition and chemotherapy toxicity reduction. This study aims to investigate the potential of Erianin in reducing the toxicity of the FOLFOX regimen while enhancing its antitumor efficacy.MethodsThis study integrated network toxicology and molecular docking to predict the potential targets of Erianin in alleviating FOLFOX-induced side effects. Using an orthotopic MC38 CRC transplantation model, we conducted a comprehensive evaluation of the effects of Erianin in mitigating FOLFOX-induced changes in body weight changes, hematological parameters, and histopathology of major organs (heart, liver, spleen, kidneys, and intestines). IHC analysis elucidated alterations in intestinal barrier proteins, AKT1/mTOR pathway, and tumor proliferation and apoptosis biomarkers. Tumor progression was dynamically monitored by in vivo imaging.ResultsThe results showed that Erianin improved weight loss, pathological changes in organs, and reduction in peripheral blood cell counts (WBC, RBC, HGB, PLT, HCT) caused by FOLFOX in mice. Erianin reversed the inhibition of intestinal tight junction proteins (e.g. ZO-1, Occludin, Claudin-5) and AKT1/mTOR pathway caused by FOLFOX. In addition, the tumor size was significantly reduced in the combination group, and the expression of the apoptosis marker Cleaved Caspase-3 was up-regulated, and the proliferation markers Ki67/PCNA were down-regulated.DiscussionErianin can enhance the anti-CRC effect of FOLFOX, and mitigates FOLFOX-induced toxicity by activating the AKT1/mTOR pathway.https://www.frontiersin.org/articles/10.3389/fchem.2025.1650197/fullErianinFOLFOX regimencolorectal cancertoxicity reductionefficacy enhancement |
| spellingShingle | Fuqin Yang Zeqiao Li Haishan Zhang Mingxiao Zhang Zhenwei He Xiaoqin Zheng Yingru Zhu Pei Long Ruirui Ding Zhengbin Lin Lijuan Deng Lijuan Deng Natural product Erianin: mitigating FOLFOX toxicity and enhancing against colorectal cancer Frontiers in Chemistry Erianin FOLFOX regimen colorectal cancer toxicity reduction efficacy enhancement |
| title | Natural product Erianin: mitigating FOLFOX toxicity and enhancing against colorectal cancer |
| title_full | Natural product Erianin: mitigating FOLFOX toxicity and enhancing against colorectal cancer |
| title_fullStr | Natural product Erianin: mitigating FOLFOX toxicity and enhancing against colorectal cancer |
| title_full_unstemmed | Natural product Erianin: mitigating FOLFOX toxicity and enhancing against colorectal cancer |
| title_short | Natural product Erianin: mitigating FOLFOX toxicity and enhancing against colorectal cancer |
| title_sort | natural product erianin mitigating folfox toxicity and enhancing against colorectal cancer |
| topic | Erianin FOLFOX regimen colorectal cancer toxicity reduction efficacy enhancement |
| url | https://www.frontiersin.org/articles/10.3389/fchem.2025.1650197/full |
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