Abstract
Cisplatin is a widely used chemotherapeutic agent for the treatment of various cancers. However, the clinical use of cisplatin is limited by its cardiotoxic side effects. The primary mechanisms implicated in this cardiotoxicity include mitochondrial dysfunction, oxidative stress, inflammation, and apoptotic. Numerous natural compounds (NCs) have been introduced as promising protective factors against cisplatin-mediated cardiac damage. The current review summarized the potential of various NCs as cardioprotective agents at the molecular levels. These compounds exhibited potent antioxidant and anti-inflammatory effects by interaction with the PI3K/AKT, AMPK, Nrf2, NF-κB, and NLRP3/caspase-1/GSDMD pathways. Generally, the modulation of these signaling pathways by NCs represents a promising strategy for improving the therapeutic index of cisplatin by reducing its cardiac side effects.
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Data availability
No datasets were generated or analysed during the current study.
Abbreviations
- ACC:
-
Acetyl-CoA carboxylase
- ALA:
-
Alpha-lipoic acid
- AMPK:
-
AMP-activated protein kinase
- Apaf-1:
-
Apoptosis-protease activating factor 1
- APO:
-
Apocynin
- ARE:
-
Antioxidant response element
- BACH1:
-
BTB and CNC homology 1
- BAX:
-
Bcl-2-associated X protein
- Bcl-2:
-
B-cell lymphoma-2
- Bzip:
-
Basic leucine zipper
- CAT:
-
Catalase
- COX-2:
-
Cyclooxygenase-2
- CNC:
-
Cap ‘n’ collar
- CUR:
-
Curcumin
- CYN:
-
Cyaniding
- DUBs:
-
Deubiquitinases
- E1:
-
Ubiquitin-activating enzymes
- E2:
-
Ubiquitin-conjugating enzymes
- E3:
-
Ubiquitin ligases
- ELA:
-
Ellagic acid
- ER:
-
Endoplasmic reticulum
- ETC:
-
Electron transport chain
- GCL:
-
Glutamate cysteine ligase
- GPx:
-
Glutathione peroxidase
- GSDMD:
-
Gasdermin D
- GSH:
-
Glutathione
- GSK-3β:
-
Glycogen synthase kinase-3 beta
- GSTs:
-
Glutathione S-transferases
- HES:
-
Hesperidin
- HO-1:
-
Heme oxygenase-1
- ICA:
-
Icariin
- IKK:
-
IκB kinase
- IκB-α:
-
NF-κB inhibitor-alpha
- ILs:
-
Interleukins
- Inos:
-
Inducible nitric oxide synthase
- I/R:
-
Ischemia/reperfusion
- IRF3:
-
Interferon regulatory factor 3
- Keap1:
-
Kelch-like ECH-associated protein 1
- KPF:
-
Kaempferol
- LUT:
-
Luteolin
- LYC:
-
Lycopene
- Maf:
-
Small musculoaponeurotic fibrosarcoma oncogene
- MAL:
-
Maltol
- MCP-1:
-
Monocyte chemotactic protein-1
- MDA:
-
Malondialdehyde
- MOR:
-
Morphine
- NAR:
-
Naringin
- NCs:
-
Natural compounds
- NEK7:
-
NIMA-related kinase 7
- NF-Κb:
-
Nuclear factor-kappa B
- NLRP3:
-
NOD-like receptor family pyrin domain-containing 3
- NQO-1:
-
NAD(P)H quinone oxidoreductase-1
- Nrf2:
-
Nuclear factor erythroid 2-related factors
- p38 MAPK:
-
P38 mitogen-activated protein kinase
- PI3Ks:
-
Phosphoinositide 3-kinases
- PIP2:
-
Phosphatidylinositol (4,5)-bisphosphate
- PIP3:
-
Phosphatidylinositol (3,4,5)-trisphosphate
- QUE:
-
Quercetin
- ROS:
-
Reactive oxygen species
- RSV:
-
Resveratrol
- RUT:
-
Rutin trihydrate
- SA:
-
Sinapic acid
- SalB:
-
Salvianolic acid B
- SAPs:
-
Saponins
- SOD:
-
Superoxide dismutase
- STING:
-
Stimulator of interferon genes
- SYL:
-
Silymarin
- TBK1:
-
TANK-binding kinase 1
- TG:
-
Tangeretin
- TNF-α:
-
Tumor necrosis factor alpha
- TQ:
-
Thymoquinone
- TSC2:
-
Tuberous sclerosis complex 2
- WOG:
-
Wogonin
- ZN:
-
Zingerone
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Acknowledgements
Authors are grateful to the Kermanshah University of Medical Sciences, Health Technology Institute, Medical Biology Research Center, Kermanshah, Iran for financial support.
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This work was supported by the Kermanshah University of Medical Sciences Office of Vice Chancellor for Research, Kermanshah, Iran (Grant numbers: IR.KUMS.REC.1403.021).
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F.Y. conceived and designed the research. M.H., P.M., and M.M. conducted screening. M.H., P.M., and M.M. extracted data. F.Y. and D.SH. wrote the manuscript. All authors read and approved the manuscript. The authors confirm that no paper mill and artificial intelligence was used.
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Hesari, M., Mohammadi, P., Moradi, M. et al. Molecular mechanisms involved in therapeutic effects of natural compounds against cisplatin-induced cardiotoxicity: a review. Naunyn-Schmiedeberg's Arch Pharmacol (2024). https://doi.org/10.1007/s00210-024-03207-3
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DOI: https://doi.org/10.1007/s00210-024-03207-3