Pretreatment with Berberine and Yohimbine Protects Against LPS-Induced Myocardial Dysfunction Via Inhibition of Cardiac I-κBα Phosphorylation and Apoptosis in Mice

Abstract

Myocardial dysfunction is a common complication in sepsis and significantly contributes to the mortality of patients with septic shock. Our previous study demonstrated that pretreatment with berberine (Ber) protected against the lethality induced by LPS, which was enhanced by yohimbine, an [alpha]2-adrenergic receptor antagonist, and Ber combined with yohimbine also improved survival in mice subjected to cecal ligation and puncture. However, no studies have examined whether Ber and yohimbine reduce LPS-induced myocardial dysfunction. Here, we report that pretreatment with Ber, Ber combined with yohimbine, or yohimbine significantly reduced LPS-induced cardiac dysfunction in mice. LPS-provoked cardiac apoptosis, I-[kappa]B[alpha] phosphorylation, IL-1[beta], TNF-[alpha], and NO production were attenuated by pretreatment with Ber and/or yohimbine, whereas cardiac Toll-like receptor 4 mRNA expression, malondialdehyde content, and superoxide dismutase activity were not affected. These data demonstrate for the first time that pretreatment with Ber and/or yohimbine prevents LPS-induced myocardial dysfunction in mice through inhibiting myocardial apoptosis, cardiac I-[kappa]B[alpha] phosphorylation, and TNF-[alpha], IL-1[beta], and NO production, suggesting that activation of [alpha]2-adrenergic receptor in vivo may be responsible at least in part for LPS-induced cardiac dysfunction, and Ber in combination with yohimbine may be a potential agent for preventing cardiac dysfunction during sepsis.

Berberine Inhibits Doxorubicin-Triggered Cardiomyocyte Apoptosis via Attenuating Mitochondrial Dysfunction and Increasing Bcl-2 Expression

“…However, there is no investigation concerning the effect of Ber on DOX-triggered cardiomyocyte apoptosis. Our previous study has showed that Ber attenuates myocardial apoptosis and cardiac dysfunction in endotoxemic mice [17]. Thus, we hypothesized Ber could inhibit DOX-induced cardiomyocyte apoptosis.…”

“…In separate experiments, rats were treated as described above, but a single dose of Ber (60 mg/kg) was used. Then, the cardiac function was assessed at 84 h after DOX administration with VisualSonics R Vevo770™ High-Resolution In Vivo Imagine System ((VisualSonics Inc., Toronto, Ontario, Canada) as described previously [17]. After echocardiographic assessment, the rats were immediately anesthetized with pentobarbital sodium (50 mg/kg, intraperitoneally) and morphine hydrochloride (50 mg/kg, subcutaneously), the adequacy of the anesthesia was monitored by disappearance of the corneal reflex, loss of the pedal reflex and failure to respond to a skin incision.…”

Berberine protects against lipopolysaccharide-induced intestinal injury in mice via alpha 2 adrenoceptor-independent mechanisms

“…In the present study, we demonstrate that Y does not enhance the protective effects of Ber against intestinal damage that is caused by treatment with LPS. It has been reported that pretreatment with Y once a day for 3 days prevents LPS-induced myocardial dysfunction in mice [24] . Thus, the enhanced protection of Ber against endotoxemia by Y may be related to the improvement of LPS-induced myocardial dysfunction in mice that are pretreated with Y.…”

Rhynchophylline prevents cardiac dysfunction and improves survival in lipopolysaccharide-challenged mice via suppressing macrophage I-κBα phosphorylation

“…Furthermore, both Rhy and yohimbine belong to the indole alkaloid, and have similar chemical structure [11]. Our recent study showed that pretreatment with yohimbine prevented myocardial dysfunction in mice challenged with lipopolysaccharide (LPS), which has been implicated as one of the major causes of Gram-negative bacteria-induced sepsis [12]. Based on these findings, we hypothesize that Rhy has a protective effect on LPS-induced cardiac dysfunction.…”