Shenmai Injection Protects Against Doxorubicin-Induced Cardiotoxicity via Maintaining Mitochondrial Homeostasis

Li, Lin; Li, Jinghao; Wang, Qilong; Zhao, Xin; Yang, Dongli; Niu, Lu; Yang, Yanze; Zheng, Xianxian; Hu, Limin; Li, Yuhong

doi:10.3389/fphar.2020.00815

Cited by 61 publications

(42 citation statements)

References 49 publications

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“…In this study, we investigated the effects of aloin coadministration on the DOX-induced cardiotoxicity using parameters: hemodynamic alterations, oxidative stress, biochemical markers of myocardial damage, and inflammatory mediators. Amifostine (AMF) a chemopreventive agent was used as a standard drug for validation of the DOX-induced cardiotoxicity model [13].…”

Section: Introductionmentioning

confidence: 99%

Aloin alleviates doxorubicin-induced cardiotoxicity in rats by abrogating oxidative stress and pro-inflammatory cytokines

Birari

Wagh

Patil

et al. 2020

Cancer Chemother Pharmacol

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Purpose Aloin, an anthraquinone present in the aloe species, possesses antiangiogenic, chemopreventive and antioxidant properties. It exerts cytotoxicity against breast cancer and ovarian cancer cell lines. These properties of aloin project it as a chemopreventive adjuvant to anticancer chemotherapy. Methods We evaluated the effect of concurrent oral administration of aloin against doxorubicin (DOX)-induced cardiotoxicity in rats. The protective effects of aloin against DOX-induced toxicity were evident as a statistically significant inhibition of a rise in the biochemical markers of myocardial damage including lactate dehydrogenase (LDH), creatinine kinasemyocardial band (CK-MB), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Results Aloin dose dependently inhibited the DOX-induced changes in ECG like increased ST-height and prolonged QT interval. It protected heart against the lipid peroxidation and restored the levels of antioxidative defenses: reduced glutathione, catalase and superoxide dismutase. Aloin prominently reduced the levels of proinflammatory cytokines-TNF-α, IL-1β and IL-6. Notably, the significant protective effects of aloin were evident even at the strikingly lower doses of 1 and 5 mg/kg per day. Conclusion Our results highlight the necessity to further investigate the chemopreventive effects of aloin against other chemotherapeutic agents.

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Section: Introductionmentioning

confidence: 99%

Aloin alleviates doxorubicin-induced cardiotoxicity in rats by abrogating oxidative stress and pro-inflammatory cytokines

Birari

Wagh

Patil

et al. 2020

Cancer Chemother Pharmacol

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“…Shenmai injection (SMI) is a widely used traditional Chinese medicine (TCM) extracted from Panax ginseng and Ophiopogon japonicas [ 1 ]. It has been widely used to treat different disease for its excellent therapeutic effects, such as the shock of qi and yin deficiency [ 2 , 3 ], coronary heart disease [ 4 , 5 ], viral myocarditis [ 6 ], chronic pulmonary heart disease [ 7 ], and neutropenia [ 8 ]. It can also strengthen the immune system of cancer patients to help prevent cancer [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Global metabolomic and lipidomic analysis reveals the potential mechanisms of hemolysis effect of Ophiopogonin D and Ophiopogonin D' in vivo

Jiang²,

Huang

et al. 2021

Chin Med

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Background OPD and OPD' are the two main active components of Ophiopogon japonicas in Shenmai injection (SMI). Being isomers of each other, they are supposed to have similar pharmacological activities, but the actual situation is complicated. The difference of hemolytic behavior between OPD and OPD' in vivo and in vitro was discovered and reported by our group for the first time. In vitro, only OPD' showed hemolysis reaction, while in vivo, both OPD and OPD' caused hemolysis. In vitro, the primary cause of hemolysis has been confirmed to be related to the difference between physical and chemical properties of OPD and OPD'. In vivo, although there is a possible explanation for this phenomenon, the one is that OPD is bio-transformed into OPD' or its analogues in vivo, the other one is that both OPD and OPD' were metabolized into more activated forms for hemolysis. However, the mechanism of hemolysis in vivo is still unclear, especially the existing literature are still difficult to explain why OPD shows the inconsistent hemolysis behavior in vivo and in vitro. Therefore, the study of hemolysis of OPD and OPD' in vivo is of great practical significance in response to the increase of adverse events of SMI. Methods Aiming at the hemolysis in vivo, this manuscript adopted untargeted metabolomics and lipidomics technology to preliminarily explore the changes of plasma metabolites and lipids of OPD- and OPD'-treated rats. Metabolomics and lipidomics analyses were performed on ultra-high performance liquid chromatography (UPLC) system tandem with different mass spectrometers (MS) and different columns respectively. Multivariate statistical approaches such as principal component analysis (PCA) and orthogonal partial least square-discriminant analysis (OPLS-DA) were applied to screen the differential metabolites and lipids. Results Both OPD and OPD' groups experienced hemolysis, Changes in endogenous differential metabolites and differential lipids, enrichment of differential metabolic pathways, and correlation analysis of differential metabolites and lipids all indicated that the causes of hemolysis by OPD and OPD' were closely related to the interference of phospholipid metabolism. Conclusions This study provided a comprehensive description of metabolomics and lipidomics changes between OPD- and OPD'-treated rats, it would add to the knowledge base of the field, which also provided scientific guidance for the subsequent mechanism research. However, the underlying mechanism require further research.

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“…Shenmai injection (SMI) is a widely used traditional Chinese medicine (TCM) extracted from Panax ginseng and Ophiopogon japonicas [1]. It has been widely used to treat different disease for its excellent therapeutic effects, such as shock of qi and yin de ciency [2,3], coronary heart disease [4,5], viral myocarditis [6], chronic pulmonary heart disease [7], and neutropenia [8]. It can also boost the immune system of cancer patients to help prevent cancer [9,10].…”

Section: Introductionmentioning

confidence: 99%

Global Metabolomic and Lipidomic Analysis Reveals the Potential Mechanisms of Hemolysis Effect of Ophiopogonin D and Ophiopogonin D’ in vivo

Jiang²,

Huang

et al. 2020

Preprint

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Background OPD and OPD’ are the two main active monomers of Ophiopogon japonicus in Shenmai injection, being isomers of each other with the same chemical formula and similar chemical structure. According to common sense, they are supposed to have similar pharmacological activities, but the actual situation is exactly the opposite. The difference of distinct hemolytic behavior between OPD and OPD’ in vivo and in vitro was discovered and reported by our group for the first time. In the hemolysis experiment in vitro, only OPD’ showed hemolysis reaction, while in vivo, both OPD and OPD’ revealed hemolysis reaction. The primary cause of hemolysis in vitro has been confirmed to be related to the difference between physical and chemical properties of OPD and OPD’, but the mechanism of hemolysis in vivo is still unclear, especially the existing research are still difficult to explain why OPD shows the inconsistent hemolysis behavior in vivo and in vitro. However, the detection of hemolysis of OPD and OPD’ in vivo is of great practical significance in response to the increase of adverse events of Shenmai injection. Methods Aiming at the phenomenon of hemolysis in vivo, this paper adopted untargeted metabolomics and lipidomics technology to preliminarily explore the changes of plasma metabolites and lipids of OPD and OPD’ in vivo during the occurrence of hemolysis. Metabolomics and lipidomics analysis was performed on ultra-high performance liquid chromatography (UPLC) system tandem with different mass spectrometer and different columns respectively. Multivariate statistical approaches such as principal component analysis (PCA) and orthogonal partial least square-discriminant analysis (OPLS-DA) were applied to screen the differential metabolites and lipids. Results Both OPD and OPD’ groups experienced hemolysis, Changes in endogenous differential metabolites and differential lipids, enrichment of differential metabolic pathways, and correlation analysis of differential metabolites and lipids all indicated that the causes of hemolysis by OPD and OPD’ were closely related to the interference of phospholipid metabolism. Conclusions This study provided a comprehensive description of metabolomics and lipidomic changes between OPD and OPD’ treated rats, which also provided scientific guidance for the subsequent mechanism research, and the underlying mechanism require further research.

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Shenmai Injection Protects Against Doxorubicin-Induced Cardiotoxicity via Maintaining Mitochondrial Homeostasis

Cited by 61 publications

References 49 publications

Aloin alleviates doxorubicin-induced cardiotoxicity in rats by abrogating oxidative stress and pro-inflammatory cytokines

Aloin alleviates doxorubicin-induced cardiotoxicity in rats by abrogating oxidative stress and pro-inflammatory cytokines

Global metabolomic and lipidomic analysis reveals the potential mechanisms of hemolysis effect of Ophiopogonin D and Ophiopogonin D' in vivo

Global Metabolomic and Lipidomic Analysis Reveals the Potential Mechanisms of Hemolysis Effect of Ophiopogonin D and Ophiopogonin D’ in vivo

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