Pretreatment or treatment with anti-apoptotic, anti-inflammatory, or anti-oxidative approaches could be critical for attenuated the severity of
myocardial ischemia/reperfusion (I/R) injury.
Naringin, a natural
flavonoid, plays important roles in
inflammation-related diseases. Immature dry fruits of Citrus wilsonii Tanaka (Xiang Yuan) are rich in
naringin that can be used as
traditional Chinese medicine to treat
inflammation-related symptoms. However, its roles in cardioprotective role remain unclear. This study aimed to isolate
naringin from Citrus wilsonii Tanaka fruit and tested their cardioprotective effect. The dry fruits of Citrus wilsonii Tanaka were extracted with boiling water and then supernatants were freeze-dried to yield aqueous extract (ZQAE). The extract was chemoprofiled using UPLC-MS/MS to stand for major constituents, and then subjected to different chromatographic separation steps, and
naringin was isolated in a high yield. The cardioprotective effects of the aqueous extract of ZQAE and
naringin were investigated in a myocardial I/R rat model and to elucidate the mechanism underlying its cardioprotective effect. Our results indicated that 5-day ZQAE and
naringin pretreatments both promoted histopathological changes and reduced myocardial
enzymes (cTnl, CK-MB, CK and LDH) induced by I/R. Moreover, the 50 mg/kg and 100 mg/kg ZQAE dose pretreatments presented a significantly decreased
infarct size as well as myocardial
enzyme levels but also inhibited myocardial apoptosis (cleaved-caspase3
protein expression), the inflammatory response (IL-23, IL-6, and TNF-α) and oxidative stress (MDA and SOD). The cardioprotective effect of 5 mg/kg dose of
naringin pretreatment is comparable with that of 5 mg/kg drug ditiazem pretreatment. Additionally,
naringin pretreatment exhibited striking decreases in the apoptosis index and downregulation of the
protein expression levels of cleaved-Caspase3, Bcl2 and Bax. Meanwhile,
naringin downregulated
HMGB1 expression and upregulated
SIRT1 expression in the myocardium. These findings suggest that short-term pretreatments with ZQAE and
naringin both protect against myocardial I/R injury by suppressing myocardial apoptosis, the inflammatory response, and oxidative stress. The cardioprotective effect of
naringin involves
SIRT1 activation and may interact with
HMGB1 and inhibit the release of
HMGB1.