Pharmacodynamics of Huanglian Jiedu decoction in Alzheimer's disease (AD) model rats and effect on improvement of inflammation microenvironment in brain.
10.19540/j.cnki.cjcmm.2018.0092
- Author:
Xin-Ru GU
1
;
Si-Yue FANG
2
;
Wei REN
3
;
Hong-Jie WANG
1
;
Jian YANG
1
;
Nan SI
1
;
Bao-Lin BIAN
1
;
Hai-Yu ZHAO
1
Author Information
1. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
2. Dongzhimen Hospital, Beijing University of Traditional Chinese Medicine, Beijing 100190, China.
3. Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
- Publication Type:Journal Article
- Keywords:
Alzheimer's disease;
Huanglian Jiedu decoction(HLJDD);
inflammatory cytokines;
pharmacokinetic
- From:
China Journal of Chinese Materia Medica
2018;43(14):3006-3011
- CountryChina
- Language:Chinese
-
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 (=6), shame operation group (=6) and model group (=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 (=6) and HLJDD one week group (=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 (<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.
