Ameliorative effects of Danshensu from the functional food Salvia miltiorrhiza against arsenic trioxide-induced cardiac toxicity in vivo and in vitro: Involvement of inhibiting the AKT/IKK/NF-κB signaling pathway
Cardiotoxicity is a serious side effect of arsenic trioxide (ATO) which hinders its clinical use in cancer chemotherapy. Danshensu (DSS) has potential applications in the food and healthcare industry to promote cardiovascular health. The experiment aims to investigate the effects of DSS against ATO-...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Journal of Functional Foods |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1756464622003747 |
| _version_ | 1811300249820463104 |
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| author | Yakun Yang Jiaying Qi Hua Wang Yang Zhao Yongchao Wu Zhonglin Wu Jing Shi Weizhong Qu Li Chu |
| author_facet | Yakun Yang Jiaying Qi Hua Wang Yang Zhao Yongchao Wu Zhonglin Wu Jing Shi Weizhong Qu Li Chu |
| author_sort | Yakun Yang |
| collection | DOAJ |
| description | Cardiotoxicity is a serious side effect of arsenic trioxide (ATO) which hinders its clinical use in cancer chemotherapy. Danshensu (DSS) has potential applications in the food and healthcare industry to promote cardiovascular health. The experiment aims to investigate the effects of DSS against ATO-induced cardiotoxicity and its possible mechanism. Our results demonstrated that DSS improved cardiac dysfunction, alleviated histopathological damage, enhanced antioxidant activity, attenuated cardiomyocyte apoptosis and suppressed inflammation. Further studies showed that DSS prevented ATO-caused activation of NF-κB by inhibiting the phosphorylation of AKT and IKK, degradation of IκBα, and nuclear translocation of NF-κB. In H9c2 cardiomyocytes, DSS significantly increased cell survival rate and inhibited ATO-mediated expression of p-AKT, p-IKKα/β, p-IκBα, and NF-κB. Notably, the efficacy of DSS was synergistically increased by AKT inhibitor GSK690693. To sum up, DSS effectively ameliorated ATO-induced cardiac toxicity in vivo and in vitro, which may be achieved through inhibition of the AKT/IKK/NF-κB pathway. |
| first_indexed | 2024-04-13T06:49:21Z |
| format | Article |
| id | doaj.art-5b2bcb004fe7440489dac0f905a81d7e |
| institution | Directory Open Access Journal |
| issn | 1756-4646 |
| language | English |
| last_indexed | 2024-04-13T06:49:21Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Functional Foods |
| spelling | doaj.art-5b2bcb004fe7440489dac0f905a81d7e2022-12-22T02:57:28ZengElsevierJournal of Functional Foods1756-46462022-12-0199105304Ameliorative effects of Danshensu from the functional food Salvia miltiorrhiza against arsenic trioxide-induced cardiac toxicity in vivo and in vitro: Involvement of inhibiting the AKT/IKK/NF-κB signaling pathwayYakun Yang0Jiaying Qi1Hua Wang2Yang Zhao3Yongchao Wu4Zhonglin Wu5Jing Shi6Weizhong Qu7Li Chu8School of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei, ChinaSchool of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei, ChinaCollege of Integrative Medicine, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei, ChinaThe Fourth Hospital of Hebei Medical University, Shijiazhuang 050200, Hebei, ChinaThe Fourth Hospital of Hebei Medical University, Shijiazhuang 050200, Hebei, ChinaThe Fourth Hospital of Hebei Medical University, Shijiazhuang 050200, Hebei, China; Corresponding authors at: School of Pharmacy, Hebei University of Chinese Medicine, Hebei, China (L. Chu).The Fourth Hospital of Hebei Medical University, Shijiazhuang 050200, Hebei, China; Corresponding authors at: School of Pharmacy, Hebei University of Chinese Medicine, Hebei, China (L. Chu).Faculty of Foundation Education, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei, China; Corresponding authors at: School of Pharmacy, Hebei University of Chinese Medicine, Hebei, China (L. Chu).School of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei, China; Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei, China; Corresponding authors at: School of Pharmacy, Hebei University of Chinese Medicine, Hebei, China (L. Chu).Cardiotoxicity is a serious side effect of arsenic trioxide (ATO) which hinders its clinical use in cancer chemotherapy. Danshensu (DSS) has potential applications in the food and healthcare industry to promote cardiovascular health. The experiment aims to investigate the effects of DSS against ATO-induced cardiotoxicity and its possible mechanism. Our results demonstrated that DSS improved cardiac dysfunction, alleviated histopathological damage, enhanced antioxidant activity, attenuated cardiomyocyte apoptosis and suppressed inflammation. Further studies showed that DSS prevented ATO-caused activation of NF-κB by inhibiting the phosphorylation of AKT and IKK, degradation of IκBα, and nuclear translocation of NF-κB. In H9c2 cardiomyocytes, DSS significantly increased cell survival rate and inhibited ATO-mediated expression of p-AKT, p-IKKα/β, p-IκBα, and NF-κB. Notably, the efficacy of DSS was synergistically increased by AKT inhibitor GSK690693. To sum up, DSS effectively ameliorated ATO-induced cardiac toxicity in vivo and in vitro, which may be achieved through inhibition of the AKT/IKK/NF-κB pathway.http://www.sciencedirect.com/science/article/pii/S1756464622003747DanshensuArsenic trioxideCardiotoxicityOxidative stressAKT/IKK/NF-κB pathwayApoptosis |
| spellingShingle | Yakun Yang Jiaying Qi Hua Wang Yang Zhao Yongchao Wu Zhonglin Wu Jing Shi Weizhong Qu Li Chu Ameliorative effects of Danshensu from the functional food Salvia miltiorrhiza against arsenic trioxide-induced cardiac toxicity in vivo and in vitro: Involvement of inhibiting the AKT/IKK/NF-κB signaling pathway Journal of Functional Foods Danshensu Arsenic trioxide Cardiotoxicity Oxidative stress AKT/IKK/NF-κB pathway Apoptosis |
| title | Ameliorative effects of Danshensu from the functional food Salvia miltiorrhiza against arsenic trioxide-induced cardiac toxicity in vivo and in vitro: Involvement of inhibiting the AKT/IKK/NF-κB signaling pathway |
| title_full | Ameliorative effects of Danshensu from the functional food Salvia miltiorrhiza against arsenic trioxide-induced cardiac toxicity in vivo and in vitro: Involvement of inhibiting the AKT/IKK/NF-κB signaling pathway |
| title_fullStr | Ameliorative effects of Danshensu from the functional food Salvia miltiorrhiza against arsenic trioxide-induced cardiac toxicity in vivo and in vitro: Involvement of inhibiting the AKT/IKK/NF-κB signaling pathway |
| title_full_unstemmed | Ameliorative effects of Danshensu from the functional food Salvia miltiorrhiza against arsenic trioxide-induced cardiac toxicity in vivo and in vitro: Involvement of inhibiting the AKT/IKK/NF-κB signaling pathway |
| title_short | Ameliorative effects of Danshensu from the functional food Salvia miltiorrhiza against arsenic trioxide-induced cardiac toxicity in vivo and in vitro: Involvement of inhibiting the AKT/IKK/NF-κB signaling pathway |
| title_sort | ameliorative effects of danshensu from the functional food salvia miltiorrhiza against arsenic trioxide induced cardiac toxicity in vivo and in vitro involvement of inhibiting the akt ikk nf κb signaling pathway |
| topic | Danshensu Arsenic trioxide Cardiotoxicity Oxidative stress AKT/IKK/NF-κB pathway Apoptosis |
| url | http://www.sciencedirect.com/science/article/pii/S1756464622003747 |
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