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Background: The aggregation of tau hyperphosphorylation (p-tau) into neurofibrillary tangles (NFT) is a hallmark in the histopathology of Alzheimer's disease (AD). Our previous experiments found that β-asarone could prevent injury of PC12 cells induced by A 1–42, but could it fight cell damage of p-tau induced by okadaic acid (OA) is poorly understood. Objectives: The emphasis of this study lies in β-asarone's therapeutical effect on p-tau inhibition stimulated by OA. Materials and Methods: 175 nmol OA was used to establish AD cells. Cell viability rate and cell toxicity were evaluated by the CCK-8 kit and LDH kit, respectively. The p-tau, Aβ42, β-secretase, and protein phosphatase 2A (PP2A) were examined by ELISA. Proteins closely related to the pathogenesis of AD are involved p-tau, Beclin-1, p-Akt, and p-mTOR were analyzed by western-blotting and immunofluorescence detection. Results: The results revealed that β-asarone enhanced cell viability induced by OA in a dose-dependent manner. Moreover, compared to the OA model, p-tau, Aβ42, β-secretase, and Beclin-1 were reduced, while PP2A, p-Akt, and p-mTOR increased after treatment with β-asarone. Conclusion: All data suggested that β-asarone decreased p-tau, Aβ42, and β-secretase levels, and activated PP2A levels by inhibiting Beclin-1-dependent autophagy in OA model cells, involving Akt/mTOR/Beclin-1 pathway. [ABSTRACT FROM AUTHOR]

Background: β-amyloid (Aβ) deposition and tau protein abnormality are the major pathogenesis of Alzheimer's disease (AD). Autophagy is contributed to eliminating the misfolded proteins or organelles and alleviated cellular injury. Our pre-experimental findings showed that bornyl acetate (BA), the main component of the volatile oil of Amomum villosum, has a neuroprotective effect in okadaic acid (OA)–induced PC12 cells. However, the protective mechanism of autophagy that BA relieves OA-induced cellular injury is still unclear. Objectives: The purpose of our experiment was to elucidate the mechanism of treatment of AD. Materials and Methods: To explore how BA has therapeutic effects on AD, a model of OA-induced PC12 cells was established. The OA modelling induction and BA treatment in cells were evaluated by LDH and CCK-8 methods; ELISA assay was used to detect the tau hyperphosphorylation (p-tau), Aβ42 and β-secretase levels; The expression of p-Akt and p-mTOR were detected by western blot analysis; and immunohistochemical, immunofluorescence methods and western blot analysis were used to detect Beclin-1 expression. Autophagosomes in each group were observed by transmission electron microscopy (TEM). 175 nM OA for 48 hr was applied to OA modelling induction. Results: Compared to the control group, the OA-induced AD model cells displayed higher levels of p-tau, Aβ42 and β-secretase (P < 0.01), suggesting that the AD model was successfully established. Compared to the OA model group alone, p-tau, Aβ42 and β-secretase levels and autophagy promoter Beclin-1 expression decreased significantly in the BA group (P < 0.05), whereas p-Akt and p-mTOR increased (P < 0.01). Conclusion: BA exhibited a neuroprotection effect against OA-induced cellular injury in the AD model by suppressing the Beclin-1-dependent autophagy pathway, indicating that BA might be an appealing potential strategy to treat AD. [ABSTRACT FROM AUTHOR]

Piperine, the major pharmacological ingredient of pepper, can delay the procession of neuropharmacological effects, but its effects and mechanisms on Parkinson's disease dementia (PDD) mice is still unclear, we investigated whether piperine could help treating PDD mice. Here, PDD mice were randomly divided into eight groups (n = 12/group): a normal control group, a PDD model group, a madopar group, an autophagy inhibitor group, an autophagy activator group, and groups receiving low, medium or high doses of piperine respectively. The normal control and PDD model mice were injected with saline. Treatments were administered to the mice once per day continuously for 30 days. The behavioral tests were assessed. Dopamine (DA), Monoamine Oxidase-B (MAO-B), DOPA decarboxylase (DDC), β-secretase, acetylcholinesterase (AChE), amyloid β42 (Aβ42), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were detected. α-synuclein (α-syn), tyrosine hydroxylase (TH), HSP90, Beclin-1, LC3B, p62 mRNA levels and miRNA-99a-5p expression were determined. Neuronal histology was observed. The behavior of PDD mice improved significantly after peperine treatment compared with the PDD model mice. In addition, our results also showed that peperine treatment increased DA, TH, DDC and p62 levels, decreased MAOB, β-secretase, AChE, Aβ42, TNF-α, IL-6, Beclin-1 and LC3B levels, and down-regulated α-syn, HSP90, Beclin-1, LC3B mRNA levels and miR-99a-5p expression. These findings suggest that piperine may reduce the expression of mmu-miR-99a-5p and autophagy-related factors (HSP90, Beclin-1, LC3B and p62) to alleviate the neurological impairment of PDD mice, which is shown to slow down the process of DA metabolism and Aβ production and resist neuroinflammation. [ABSTRACT FROM AUTHOR]