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.

The aim of this study was to explore the role of the NOD-like receptor family, pyrin domain containing (NLRP3) inflammasome and autophagy in Astragaloside IV (AS IV)-mediated protection against cisplatin-induced liver and kidney injury in rats. Rats were intraperitoneally administered cisplatin at a dose of 15 mg/kg and orally administered AS IV for 7 days. Histopathological and biochemical analysis were used to assess liver and kidney function. The levels and localization of NLRP3 and autophagy-associated protein were determined by Western blot and immunohistochemistry. Intraperitoneal administration of cisplatin induced acute liver and kidney injury, and activated the NLRP3 inflammasome. Oral administration of AS IV for 7 days protected against the cisplatin-induced injury, and inhibited the expression of NLRP3, as well as the production of pro-inflammatory cytokines. Moreover, cisplatin modulated the conversion of LC3 II and the expression of p62, thereby inhibiting autophagy and the activation of NLRP3. AS IV effectively protected against cisplatin-induced injury by inducing autophagy and limiting the expression of NLRP3. Autophagy-mediated NLRP3 inhibition might play a crucial role in AS IV-mediated protection against cisplatin-induced toxicity. These results provide evidence of a novel therapeutic that may be used to alleviate the toxic effects of platinum-based chemotherapy.

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Xingnaojing (XNJ) injection, derived from traditional Chinese medicine formulation, has a protective effect against stroke, but the underlying mechanism is unclear, which severely limited its clinical application. This research aims to elucidate the role and mechanism of XNJ in reducing cerebral ischemic reperfusion (I/R) injury. Rats received 2 h cerebral ischemia followed by reperfusion of 24 h and were intraperitoneally given 5, 10, or 15 ml/kg XNJ 24 h before ischemia and at the onset of reperfusion, respectively. TTC staining, HE staining, and neurological score were implied to evaluate the effectiveness of XNJ. The protein expressions of PI3K/Akt and eNOS signaling were measured. Experiments were further performed in human brain microvascular endothelial cells (HBMECs) to investigate the protective mechanisms of XNJ. HBMECs were subjected to 3 h oxygen and glucose deprivation following 24 h of reoxygenation (OGD) to mimic cerebral I/R in vitro. PI3K inhibitor LY294002 was added with or without the preconditioning of XNJ. Multiple methods including western blot, immunofluorescence, DAPI staining, JC-1, and flow cytometry were carried out to evaluate the effect of XNJ on HBMECs. XNJ could improve rat cerebral ischemic injury and OGD induced HBMECs apoptosis. In vivo and in vitro researches indicated that the mechanism might be relevant to the activation of PI3K/Akt/eNOS signaling.

Context: XingNaoJing injection (XNJ), extracted from a traditional compound Chinese medicine Angong niuhuang pill, is well known for treating stroke in the clinic, but the specific effects and mechanisms remain unclear. Objective: We investigated the mechanistic basis for the protective effect of XNJ on cerebral ischaemia/ reperfusion (I/R) injury. Materials and methods: Five groups of 10 SD rats underwent 2 h of middle cerebral artery occlusion (MCAO) followed by 24 h reperfusion. XNJ at 10 and 15 mL/kg was intraperitoneally administered 24 h before ischaemia and at the onset of reperfusion respectively. The silent information regulator 1 (SIRT1) inhibitor EX527 was intracerebroventricularly injected 0.5 h before reperfusion. Cerebral infarction size, neurological scores, morphological changes, and expression levels of inflammatory mediators and SIRT1 were measured. Furthermore, human brain microvascular endothelial cells (HBMECs) were subjected to 3 h oxygen and glucose deprivation (OGD) followed by 24 h reoxygenation to mimic cerebral I/R in vitro. EX527 pre-treatment occurred 1 h before OGD. SIRT1 and inflammatory mediator levels were analyzed. Results: Both XNJ doses significantly decreased cerebral infarct area (40.11% vs. 19.66% and 9.87%) and improved neurological scores and morphological changes. Inflammatory mediator levels were remarkably decreased in both model systems after XNJ treatment. XNJ also enhanced SIRT1 expression. Notably, the SIRT1 inhibitor EX527 attenuated the XNJ-mediated decrease in inflammation in vivo and in vitro. Conclusions: XNJ improved cerebral I/R injury through inhibiting the inflammatory response via the SIRT1 pathway, which may be a useful target in treating cerebral I/R injury.