gms | German Medical Science

Objective: Plumbagin, a naphthoquinone, is derived from the roots of the medical plant Plumbago, and has long been used in traditional medicine in ayurveda. This vitamine K3 analogue has shown anti-cancer and anti-inflammatory effect in oncological research. Additionally, it protected cells against oxidative stress-induced death in-vitro and reduced infarction volume in a stroke animal model pretreated with plumbagin via nuclear-factor-E2-related-factor 2 (Nrf2) activation. The aim of this study is to evaluate the effect of plumbagin treatment in different dosages after experimental SAH in rats. We suggest, the underlying mechanism is via E3 ubiquitin ligase seven-in-absentia-2 (SIAH-2) signaling.

Method: SAH was induced by using the perforation rat model, and plumbagin in three different dosages (0.3mg/kg, 1mg/kg, 3mg/kg) was administered intraperitoneal one hour after SAH-induction. After 24 hours, neurological outcome was assessed using modified-Garcia-test, the animals were euthanized, and brain water content was evaluated. Additionally for molecular analysis, Westernblot, PCR and immunohistochemistry have been used.

Results: The SAH animals treated with the higher dosage (3mg/kg) plumbagin demonstrated significantly improved neurological outcome, while the low and medium dose treated animals showed no difference compared to the vehicle group. An increased steady-state level of cerebral SIAH-2 was detected in the plumbagin treated group, same as after vitamin K3 application. In contrast, sham operated animal presented decreased expression of SIAH-2. So far no systemic adverse effects have been observed.

Conclusions: Our data show, that plumbagin has neuroprotective effect in terms of improving neurological outcome and brain edema after SAH in rats. Therefore, plumbagin is a promising phytochemical compound with potential for future clinical translation. The pathophysiological mechanism is currently under investigation.