Huanglian Jiedu decoction ameliorates Alzheimer's disease by regulating calcium homeostasis via mitochondria-associated endoplasmic reticulum membranes.

OBJECTIVES: Huanglian Jiedu decoction (HLJDD), a classic traditional Chinese medicine formula, is investigated for its protective effects against Alzheimer's disease (AD). This study explored its mechanism in an AD cell model, focusing on calcium ion (Ca²⁺) homeostasis regulation via mitochondria-associated endoplasmic reticulum membranes (MAMs). MATERIALS AND METHODS: Mouse hippocampal HT22 cells were induced with 10 μmol·L⁻¹ Aβ₁₋₄₂ to establish the AD model, then divided into blank, model, and 15% HLJDD-containing serum intervention groups. Fluorescent dyes, qRT-PCR, western blotting, laser scanning confocal microscopy, and Annexin V-FITC/PI staining were used to detect intracellular reactive oxygen species (ROS), mitochondrial membrane potential, VDAC1/GRP75/IP3R (mRNA/protein levels), MAMs formation, intracellular Ca²⁺, and cell apoptosis, respectively. RESULTS: Aβ₁₋₄₂ reduced HT22 viability in a concentration-dependent manner, while HLJDD significantly improved viability. Compared to the model group, HLJDD evidently decreased ROS levels (P<0.001), elevated mitochondrial membrane potential (P<0.001), up-regulated GRP75 (mRNA/protein, P<0.05), down-regulated VDAC1/IP3R (mRNA/protein, P<0.05 or P<0.001), reduced MAMs (via lower ER-mitochondria co-localization, P<0.05), alleviated Ca²⁺ overload (P<0.001), and lowered apoptosis. CONCLUSION: HLJDD exerts protective anti-AD effects likely by reducing MAMs formation to alleviate intracellular Ca²⁺ overload, thereby lessening cell damage and apoptosis.