Orientin, a natural product isolated and purified from the herbs of Polygonum orientale Linn., is a candidate therapeutic agent for treatment of vascular inflammatory diseases via inhibition of the HMGB1 signaling pathway, protects vascular barrier integrity by inhibiting hyperpermeability, expression of CAMs, and adhesion and migration of leukocytes, thereby endorsing its usefulness as a therapy for vascular inflammatory diseases, has neuroprotection effect by the intracellular mediation of caspase activity and may alleviate cognitive deficits and oxidative stress in AD mice and can exert antidepressant-like effects on CUMS mice, specifically by improving central oxidative stress, neurotransmission, and neuroplasticity.