Triphala ameliorates cognitive deficits and anxiety via activation of the Nrf2/HO-1 axis in chronic sleep-deprived mice

Triphala is renowned for its curative attributes and has been utilized for centuries to address diverse health ailments. Moreover, the active component of Triphala, polyphenols, is widely recognized for its excellent pharmacological activities, such as anti-inflammatory properties, and has been utilized as a potential natural remedy. However, the precise mechanism through which Triphala alleviates cognitive dysfunction and anxiety induced by chronic sleep deprivation (SD) remains restricted. The objective of this investigation is to examine and clarify the potential mechanism of action that underlies the therapeutic benefits of Triphala in addressing cognitive dysfunction and anxiety induced by chronic SD. Our results demonstrated that Triphala significantly alleviates chronic SD-induced behavioral abnormalities. Additionally, Triphala was highly effective at preventing histopathological or morphological damage to neurons located in the hippocampus. The therapeutic effects of Triphala in treating cognitive dysfunction and anxiety induced by chronic SD involve the modulation of several biological pathways, including inflammation and immune responses, oxidative stress, cell growth and differentiation, metabolism, and neurotransmitter communication. Moreover, our study illustrated that Triphala increased the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and significantly activated the Nrf2/hemeoxygenase-1 (HO-1) axis. Additionally, the neuroprotective properties of Triphala were found to be counteracted by the Nrf2 inhibitor ML385. Our study represented the first to unveil that Triphala exerts therapeutic benefits in alleviating chronic SD-induced cognitive deficits and anxiety by activation of the Nrf2/HO-1 axis. Triphala emerges as a promising nutraceutical ingredient for mitigating cognitive deficits and anxiety linked to chronic SD.