[Pharmacodynamics of Huanglian Jiedu decoction in Alzheimer's disease (AD) model rats and effect on improvement of inflammation microenvironment in brain]

Abstract

To study the pharmacokinetics of active ingredients (alkaloids, iridoids and flavonoids) in Huanglian Jiedu decoction (HLJDD) in Alzheimer's disease (AD) model rats, and investigate its mechanism in treatment of AD. All of rats were divided into normal control group (n=6), shame operation group (n=6) and model group (n=12). Rats in shame operation group received daily subcutaneous injection of D-galactose (D-gal 50 mg·kg⁻¹) for a total of 45 d to induce subacute aging model. Based on the operation of shame operation group, the rats in model group were given with an injection of Aβ₂₅₋₃₅ (4.0 g·L⁻¹)-ibotenic acid (2.0 g·L⁻¹) into the nucleus basalis magnocellularis. Then rats in model group were divided into HLJDD one day administration group (n=6) and HLJDD one week group (n=6). The plasma concentration of alkaloids, iridoid and flavonoids was determined by liquid chromatography tandem mass spectrometry (LC-QQQ-MS) at different time points. The levels of seven inflammatory factors (MIP-2, IL-1β, IL-2, IL-8, IL-10, IL-13, TNF-α) in cerebrospinalfluid (CSF) were measured by Bio-Plex multi-factor detection technology. Iridoids in AD model rats, with high bioavailability, were easily absorbed and eliminated. The plasma concentration of alkaloid was lower, and the AUC (area under the curve) was higher in HLJDD one week group than that in HLJDD one day group. The plasma concentration-time curves of flavonoids showed obvious bimodal phenomena. After the gastric administration of HLJDD, the inflammatory factors in CSF of AD rats demonstrated a callback trend, including IL-1β/IL-10 (P<0.05) with significant difference. The pharmacokinetic behaviors of iridoids, alkaloids and flavonoids (41 compounds) in AD model rats were fundamentally elucidated, and HLJDD can improve the central inflammatory status of AD rats by regulating the levels of inflammatory factors.

Keywords: Alzheimer's disease; Huanglian Jiedu decoction(HLJDD); inflammatory cytokines; pharmacokinetic.