Triptolide Improves Cognitive Dysfunction in Rats with Vascular Dementia by Activating the SIRT1/PGC-1α Signaling Pathway.

Tripterygium Wilfordii Hook F has been exploited as a treatment for several diseases due to its neuroprotective, anti-tumor, and anti-inflammatory effects. Triptolide is one of its key bioactive compounds. Currently, the role of triptolide in cognitive dysfunction remains unclear. Here, the role of triptolide on cognitive dysfunction was investigated using chronic cerebral hypoperfusion-induced vascular dementia (VD) rat model. SD rats were administrated with Triptolide (5 μg/kg) for 6 weeks after undergoing permanent bilateral common carotid artery occlusion. The results show that triptolide treatment conferred neuroprotective effects in VD rats. Intraperitoneal injection of triptolide attenuated oxidative stress, learning and memory deficits, and neuronal apoptosis in the hippocampi. Moreover, triptolide enhanced the expression of SIRT1, PGC-1α, ZO-1, Claudin-5, and decreased the serum levels of NSE and S100B significantly. It also improved CCH-induced learning and memory deficits, and this is attributed to its capacity to promote SIRT1/PGC-1α signaling, confer antioxidant effects, and inhibit neuronal apoptosis. These findings indicate that triptolide may be an effective therapeutic agent for vascular cognitive dysfunction.