Calycosin ameliorates doxorubicin‐induced cardiotoxicity by suppressing oxidative stress and inflammation via the sirtuin 1–NOD‐like receptor protein 3 pathway

Abstract

The limitation of doxorubicin (DOX), which is widely used for the treatment of solid tumors and hematologic malignancies, is a vital problem in clinical application. The most serious of limit factors is cardiotoxicity. Calycosin (CA), an isoflavonoid that is the major active component in Radix astragali, has been reported in many bioactivities including antitumor, anti‐inflammatory, and cardioprotection. The aim of the study was to investigate the effects and mechanisms of CA on DOX‐induced cardiotoxicity in vitro and in vivo. CA increased H9c2 cell viability and reduced apoptosis induced by DOX via Bcl‐2, Bax, and the PI3K‐Akt signaling pathway. Moreover, CA prevented DOX‐induced oxidative stress in cells by decreasing the generation of reactive oxygen species. Similarly, oxidative stress was inhibited by CA through the increased activities of antioxidant enzymes such as glutathione peroxidase, catalase, and superoxide dismutase and decreased the levels of aspartate aminotransferase, lactate dehydrogenase, and malondialdehyde in vivo. Furthermore, the levels of sirtuin 1 (Sirt1)–NOD‐like receptor protein 3 (NLRP3) and related proteins were ameliorated by CA in cells and in mice hearts. When H9c2 cells were treated by Ex527 (Sirt1 inhibitor), the effect of CA on expressions of NLRP3 and thioredoxin‐interacting protein was suppressed. In conclusion, the results suggested that CA might be a cotreatment with DOX to ameliorate cardiotoxicity by Sirt1–NLRP3 pathway.

Calycosin inhibited autophagy and oxidative stress in chronic kidney disease skeletal muscle atrophy by regulating AMPK/SKP2/CARM1 signalling pathway

“…In skeletal muscle, FOXO is key players in controlling LC3, Beclin 1 and p62 49. In our study, Atg7, LC3,50 andFOXO3a protein expression levels were significantly increased in the muscle of 5/6 Nx rats and in TNF-α induced C2C12 cells compared with those in the corresponding control groups. These effects were blocked by treatment with calycosin.…”

Discovery of natural products capable of inducing porcine host defense peptide gene expression using cell-based high throughput screening

“…Calycosin, an isoflavonoid, is found in Astragalus membranaceus, a traditional Chinese medicinal herb. Calycosin has anti-oxidative, anti-inflammatory, and anti-tumorigenic properties [47][48][49]. Similar to isorhapontigenin, calycosin is also a potent activator of SIRT1 [50], suggesting that calycosin may induce porcine HDP expression through SIRT1 activation.…”

Cytokine expressions of spinal cord injury treated by neurotropin and nafamostat mesylate

“…As previously demonstrated, the PI3K-Akt pathway, involved in the repair of SCI, plays an important role in the proliferation, development, differentiation, axon regeneration, myelination, apoptosis, and synaptic plasticity (53)(54)(55). The JAK-STAT, MAPK, and NODlike receptor signaling pathways are usually involved in inflammatory reactions (56)(57)(58). The functions of NTP (neuroprotection and anti-inflammation), and NM (resisting inflammation), in the treatment of SCI have been shown again through pathway analysis.…”