Research ReportCurcumin, encapsulated in nano-sized PLGA, down-regulates nuclear factor κB (p65) and subarachnoid hemorrhage induced early brain injury in a rat model

- Curcumin, emulsified by PVA, increases its solubility and bio-activity, including anti-inflammatory, antioxidant effect, neuro- and cardioprotective properties.
- Nanocurcumin has a number of pleiotropic effects but devoid of hepatic and renal toxicity.
- Nanocurcumin, in a selected dose, is able to improve neurologic deficit and brain swelling in rats subject to subarachnoid hemorrhage.
- Through the decrease of NF-κB(p65) expression, nanocurcumin is able to attenuate CSF pro-inflammatory cytokines as well as reduce apoptotic related caspases activation.

BackgroundMore and more evidence revealed early brain injury (EBI) may determine the final outcome in aneurismal subarachnoid hemorrhage (SAH) patients. This study is of interest to examine the efficacy of nano-particle curcumin (nanocurcumin), a diarylheptanoid, on a SAH-induced EBI model.MethodsA rodent double hemorrhage model was employed. Nanocurcumin (75/150/300 μg/kg/day) was administered via osmotic mini-pump post-SAH. CSF samples were collected to examine IL-1β, IL-6, IL-8 and TNF-α (rt-PCR). Cerebral cortex was harvested for NF-κB (p50/p65) (western blot), caspases (rt-PCR) measurement.ResultsNanocurcumin significantly reduced the bio-expression of NF-κB (p65), when compared with the SAH groups. The levels of IL-1β and IL-6 were increased in animals subjected to SAH, compared with the healthy controls, but absent in the high dose nanocurcumin+SAH group. Moreover, the levels of TNF-α in the SAH groups were significantly elevated. Treatment with nanocurcumin (300 μg/kg) reduced the level to the healthy control. The cleaved caspase-3 and -9a was significantly reduced in 300 μg/kg nanocurcumin treatment groups (P<0.05).ConclusionTreatment with nanocurcumin exerts its neuroprotective effect through the upward regulation of NF-κB (p65) and also reduced mitochondrion related caspase-9a expression. Besides, nanocurcumin decreased CSF levels of TNF-α and IL-1β, which may contribute to the extrinsic antiapoptotic effect. This study shows promise to support curcuminin, in a nano-particle, could attenuate SAH induced EBI.