Study on Integrated Pharmacokinetics of Gardenia Acid and Geniposide: Time-Antioxidant Efficacy after Oral Administration of Huanglian–Zhizi Couplet Medicine from Huang–Lian–Jie–Du–Tang in MCAO Rats

Abstract

Huanglian-Zhizi couplet medicine comes from classical prescription Huang-Lian-Jie-Du-Tang (HLJDT), which has been proven by previous researches to be an effective compound for cerebral ischemia. This paper explores the integrated pharmacokinetics of gardenia acid and geniposide-time-antioxidant efficacy after the oral administration of Huanglian-Zhizi couplet medicine from HLJDT in rats with middle cerebral artery occlusion (MCAO). To investigate the differences in pharmacokinetics and antioxidant effect of Huanglian-Zhizi and HLJDT in MCAO rats, which have been scarcely reported, an oral dose, 24 crud drug g/kg, of Huanglian-Zhizi and 40 crud drug/kg of HLJDT were administered in two groups of normal rats and two groups of Sprague-Dawley (SD) MCAO rats, respectively. At different time points, concentrations of gardenia acid and geniposide were determined by high performance liquid chromatography (HPLC), and levels of superoxide dismutase (SOD) were calculated by ELIASA. Pharmacokinetic parameters including AUC, MRT, t1/2, T max , C max were estimated by statistical moment analysis using a data analysis system (DAS) 2.0. An AUC based on weighting approach was used for integrating gardenia acid and geniposide. Finally, the concentration-time efficacy profiles were obtained. The integrated pharmacokinetics profiles of index components could reveal the pharmacokinetics behavior of Huanglian-Zhizi and HLJDT, corresponding to the antioxidant efficacy.

Neuroprotective effects of geniposide on Alzheimer’s disease pathology

“…The authors found that geniposide inhibited palmitate-induced ER stress, reducing hepatic lipid accumulation through the secretion of apolipoprotein B and associated triglycerides and cholesterol in human HepG2 hepatocytes . Oral administration of geniposide was also reduced in middle cerebral artery occlusion rat model (Pan et al, 2014).…”

Huang-Lian Jie-Du decoction: a review on phytochemical, pharmacological and pharmacokinetic investigations

“…In addition, there were a handful of PK investigations of couplet medicines from HLJDD. Pan et al explored the differences in PK and antioxidant effect of RC-FG couplet medicine and HLJDD in MCAO rats, which have been scarcely reported [170]. In MCAO group, the C max of RC-FG and HLJDD were 1.188 ± 0.162 mg/L and 1.44 ± 50.295 mg/L, respectively.…”

Discovery and Current Status of Evaluation System of Bioavailability and Related Pharmaceutical Technologies for Traditional Chinese Medicines—Flos Lonicerae Japonicae—Fructus Forsythiae Herb Couples as an Example

“…F.H.Chen (Sanqi). Pan et al , 2014 [ 68 ], and Zhu et al , 2012 [ 69 ], showed the integrated PK of baicalin, baicalein, geniposide, palmatine, and berberine, the main effective ingredients in Huang-Lian-Jie-Du-Tang in middle cerebral artery occlusion (MCAO) rats, and found that the correlation with the anti-ischemia index (Interleukin 6 (IL-6), tumor necrosis factor (TNF-α), superoxide dismutase (SOD), glutamic acid (Glu), and MDA) in the serum was good, which would provide comprehension better understanding of cerebrovascular disease as Huang-Lian-Jie-Du-Tang is used in clinical practice. Xie et al , 2010 [ 70 ], reported the holistic PK of Schisandrin, schisantherin A, deoxyschisandrin, and γ-schisandrin, the four main lignin components in Schisandra , and found that the integral AUC and CYP3A activities correlated well with hepatic injury biomarkers (ALT and aspartate aminotransferase (AST)) in serum.…”