Essential oil of Acorus tatarinowii Schott inhibits neuroinflammation by suppressing NLRP3 inflammasome activation in 3 x Tg-AD transgenic mice

Background: Shi chang pu (Acorus tatarinowii Schott) is a herbal used in the treatment of Alzheimer's disease (AD) in China. The essential oil of Shi chang pu (SCP-oil) is the main active component. However, its effects on the neuroinflammation of AD have not been well studied. Purpose: Neuroinflammation mediated by the NLRP3 inflammasome plays a crucial role in AD. This study was designed to evaluate the effect of SCP-oil on cognitive impairment of App(Swe)/PSEN1(M146)V/MAPT(P301L) triple transgenic (3 x Tg-AD) mice model and investigate the mechanism underlying its anti-inflammation effects. Methods: Thirty-two 3 x Tg-AD mice at 12 months and 8 wild-type B6 mice were used for this experiment. The 3 x Tg-AD mice were administered with SCP-oil or donepezil hydrochloride for 8 weeks. Morris water maze test and step-down test were used to evaluate the cognitive ability of mice. The pathological changes, neuroinflammation, and the NLRP3 inflammasome related-protein of AD mice were detected by histomorphological examination, TUNEL staining, immunofluorescence, immunohistochemistry, qRT-PCR, Elisa, and western blot assays. Results: SCP-oil treatment attenuated cognitive dysfunction of 3 x Tg-AD mice. Moreover, SCP-oil also ameliorated characteristics pathological of AD, such as pathological changes damage, deposition of A beta, phosphorylation of Tau, and neuronal loss. Additionally, SCP-oil treatment alleviated the neuroinflammation and inhibited phosphorylation of IKK beta, NF-kappa B, and NLRP3 inflammasome related-protein NLRP3, ASC, Caspase-1, cleavedCaspase-1, and GSDMD-N in the hippocampus of 3 x Tg-AD mice. Conclusion: Overall, SCP-oil contributed to neuroprotection in 3 x Tg-AD mice by reduced activation of NLRP3 inflammasome by inhibiting the NF-kappa B signaling pathway.