Wuzi Yanzong Pill relieves MPTP-induced motor dysfunction and neuron loss by inhibiting NLRP3 inflammasome-mediated neuroinflammation.

Parkinson disease (PD) is an age-related neurodegenerative disease, which is associated with the loss of dopaminergic neurons (DA neurons) in the substantia nigra pars compacta (SNpc), and neuroinflammation may lead to the occurrence of PD. Wuzi Yanzong Pill (WYP) has demonstrated neuroprotective and anti-inflammatory properties, but its molecular mechanism of action is still unclear. In this study, we used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice and LPS-mediated BV2 microglia to explore WYP intervention, anti-inflammatory effect and molecular mechanism in vivo and in vitro. The results showed that oral administration of WYP in MPTP-induced PD mice for 2 weeks ameliorated abnormal motor dysfunction, attenuated the loss of TH + neurons in SNpc, protected dopaminergic neurons, and inhibited the activation of microglia in MPTP-induced PD mice and LPS-stimulated BV2 cell. Meanwhile, WYP intervention inhibited the expression of IL-6, TNF-α, Pro-IL-1ß, IL-1ß, Pro-IL-18, IL-18 and enhanced the expression of IL-10 in the SNpc of PD mice. Simultaneously, WYP intervention inhibited the expression of NLRP3 inflammasome, accompanied by the decrease of the TLR4/MyD88/NF-κB pathway. However, the exact target and interaction of WYP on NLRP3 inflammasome and TLR4/MyD88/NF-κB pathway still needs to be further investigated.

Protocatechuic acid attenuates ß­secretase activity and okadaic acid­induced autophagy via the Akt/GSK­3ß/MEF2D pathway in PC12 cells.

Okadaic acid (OA) can be used to induce an Alzheimer's disease (AD) model characterized by tau hyperphosphorylation, the formation of neurofibrillary tangles formation and ß­amyloid (Aß) deposition. Previous studies have shown that the upregulation of Beclin­1­dependent autophagy may contribute to the elimination of aggregated Aß. However, the effects of protocatechuic acid (PA) on the levels of Aß42, phosphorylated (p)­tau and ß­secretase in OA­induced cell injury are unclear, and little is known concerning the role of the PA signaling pathway in the regulation of autophagy. The present study aimed to determine whether PA protects cells from OA­induced cytotoxicity via the regulation of Beclin­1­dependent autophagy and its regulatory signaling pathway. PC12 cells were treated with OA with or without PA for 24 h. Enzymatic assays were performed to measure p­tau, Aß42 and ß­secretase activity. Western blotting was performed to detect p­Akt, p­glycogen synthase kinase­3ß (p­GSK­3ß), Akt, GSK­3ß, myocyte enhancer factor 2D (MEF2D) and Beclin­1 protein expression levels. Immunofluorescence and immunocytochemistry were used to measure Beclin­1 expression levels. The results from this study showed that PA could increase cell viability and significantly decrease the levels of Aß42, p­tau, ß­secretase and Beclin­1. PA can also promote the expression of p­Akt and MEF2D while suppressing the expression of p­GSK­3ß. These results indicated that PA protects PC12 cells from OA­induced cytotoxicity, and attenuates autophagy via regulation of the Akt/GSK­3ß/MEF2D pathway, therefore potentially contributing to the neuroprotective effects of PA against OA toxicity. These findings suggested that PA may have potential as a drug candidate in preventative AD therapy.