Linmei Pan

Comparative pharmacokinetics of baicalin in plasma after oral administration of Huang-Lian-Jie-Du-Tang or pure baicalin in MCAO and sham-operated rats.

A sensitive and specific HPLC method was developed to analyze baicalin in rat plasma. The author had compared the pharmacokinetics of baicalin after oral administration of HLJDT decoction or pure baicalin in MCAO and sham-operated rats. All the rats were divided into two groups, MCAO and sham-operated rats. Each group contained two subgroups: HLJDT decoction and pure baicalin subgroup. The HLJDT subgroup oral administration of HLJDT decoction extract 10.00 g/kg according to body weight (containing baicalin 400.00 mg/kg according to body weight), the pure baicalin subgroup received a gavages at a dosage of baicalin 400.00 mg/kg according to body weight too. The pharmacokinetics parameters were analyzed by kinetica. The results indicated that the pharmacokinetics of baicalin in rat plasma was non-linear and there were significant differences between different groups. No matter in MCAO or sham-operated rats, pure baicalin had shown better absorption than HLJDT decoction. Whether administration of pure baicalin or HLJDT decoction, the MCAO rats show better, quicker absorption of baicalin than sham-operated rats. It was good for baicalin to exert pharmacological effects on healed cerebrovascular diseases. The method had been applied successfully to pharmacokinetics of baicalin in rat plasma after oral administration of pure baicalin or HLJDT decoction.

Systematic review of recent advances in pharmacokinetics of four classical Chinese medicines used for the treatment of cerebrovascular disease

Recent studies have focused more on Chinese medicine used for the treatment of cerebrovascular disease. The current review covers researches on the pharmacokinetics of Chinese medicine, providing a convenient reference for researchers to increase efficiency of drug discovery, by compiling and discussing the pharmacokinetics of four classical Chinese medicines for therapy of cerebrovascular disease containing: Panax notoginseng, Salvia miltiorrhiza, Ligusticum Chuanxiong and Gardenia. It also helps to eliminate side effect as far as possible from inappropriate Chinese medicine usage. Current integrative and comprehensive review of Chinese medicine for cerebrovascular disease including 1) the absorption of some constituents is limited such as ginsenosides Rg1 and Rb1. It may be affected by gastric juice, first-pass effect, etc. 2) The interactions between Chinese medicine and prescription can occur. Borneol and carbomer would enhance the absorption of R1 and Rg1 in vivo by increasing adjacent cell transport ability. 3) The distribution of active constituents in brain is important for cerebrovascular disease. BBB protects brain from xenobiotic. Intranasal, intra-tympanic administration is a promising alternative to conventional administration to reach brain for ligustrazine. 4) Renal excretion is the uppermost route of these Chinese medicines. But biliary, fecal and urinary excretion are the other major routes. Theoretical and practical aspects are described with pharmacokinetic examples. In the end, this paper also discusses recent development of bio-analysis of Chinese medicine.

Integrated pharmacokinetics of major bioactive components in MCAO rats after oral administration of Huang-Lian-Jie-Du-Tang.

ETHNOPHARMACOLOGICAL RELEVANCE Huang-Lian-Jie-Du-Tang (HLJDT, or Oren-gedoku-to in Japanese), an important multi-herb remedy in China and other Asia countries, has been used clinically to treat cerebral ischemia for decades. MATERIALS AND METHODS According to the previous studies we have reported, an HPLC method was developed and validated for determination of berberine, palmatine, baicalin, baicalein and geniposide simultaneously in MCAO rat plasma after administration of HLJDT aqueous extract. A classified integral pharmacokinetic method was put forward after having compared the integrated concentration-time profile with that of single component. An AUC based weighting approach was used for integrated principle. RESULTS The results indicated the classified integral pharmacokinetic profile of index components from HLJDT could reveal the pharmacokinetic behavior of original components, and was corresponding to the holistic pharmacological effects of anti-ischemia with HLJDT. CONCLUSIONS This study was aimed to explore an approach that could be applied to integrate the pharmacokinetic behavior of different components derived from HLJDT. The integrated pharmacokinetic results also provided more information for further understanding of the clinical cerebrovascular disease in use of HLJDT.

Novel pharmacokinetic studies of the Chinese formula Huang-Lian-Jie-Du-Tang in MCAO rats

Our previous studies showed that after oral administration of an Huang-Lian-Jie-Du-Tang (HLJDT) decoction, there is a higher concentration of the pure components, berberine, baicalin and gardenoside in the plasma of Middle cerebral artery occlusion (MCAO) rats than in sham-operated rats, The aim of the present study was to determine whether these components could be reliably measured in MCAO rat tissues. First, the plasma concentration-time profiles of berberine, palmatine, baicalin, baicalein and gardenoside were characterised in MCAO rats after oral administration of the aqueous extract of HLJDT. Subsequently, liver, lung and kidney tissues were obtained from sudden death MCAO rats in the absorption phase (0.25 h), the distribution phase (1.0 h) and the elimination phase (8.0 h) after administration of the HLJDT aqueous extract. An HPLC method was developed and validated for the determination of the distribution characteristics of berberine, palmatine, baicalin, baicalein and gardenoside simultaneously from the above-mentioned rat tissues. The results indicated that berberine, palmatine, baicalin and baicalein distributed rapidly and accumulated at high levels in the lung, while gardenoside distributed widely in the lung and the kidney. To the best of our knowledge, this is the first report to describe the distribution of the active ingredients derived from HLJDT in MCAO rat tissues. The tissue distribution results provide a biopharmaceutical basis for the design of the clinic application of HLJDT in cerebrovascular disease.

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

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.

Distribution of α-asarone in brain following three different routes of administration in rats.

The goal of the present paper is to compare the distributions of α-asarone administered to rats through three different routes: oral, intravenous and intranasal. The concentrations of α-asarone in seven distinct brain regions, the olfactory bulb, cerebellum, hypothalamus, frontal cortex, striatum, hippocampus and medulla/pons as well as in plasma and cerebrospinal fluid (CSF), were determined by HPLC. The quantities of α-asarone accumulated in liver were measured to determine whether α-asarone could generate hepatotoxicity when administered via the three different routes. The results indicated that α-asarone could be absorbed via two different routes into the brain, after intranasal administration of dry powders. In the systemic route, α-asarone immediately entered the brain through the blood-brain barrier (BBB) after uptake into the circulatory system. In the olfactory bulb route, α-asarone traveled from the olfactory epithelium in the nasal cavity straight into brain tissue via the olfactory bulb. Furthermore, intranasal administration of α-asarone as a dry powder can ensure quick absorption and avoid excessive concentrations in the blood and liver, while achieving concentrations in the brain comparable to those attained by intravenous and oral administration routes.

The traditional Chinese medicine Huang-Lian-Jie-Du- Tang inhibits hypoxia-induced neuronal apoptosis

Huang-Lian-Jie-Du-Tang (HLJDT) has been used clinically for cerebral ischemia therapeutics. Here, we aimed to demonstrate whether and how HLJDT regulates neuronal apoptosis under hypoxia/ischemia. Apoptosis analysis was performed in vitro in PC12 cells with flow cytometry and in vivo in MCAO rats using TUNEL staining. The levels of caspase 9, caspase 3, Bcl-2, Bax and HIF-1α were demonstrated with western blotting. HLJDT remarkably inhibited apoptosis of neurons, both in vitro and in vivo. Caspase 9, caspase 3m Bcl-2, Bax and HIF-1α play important roles in anti-apoptotic effect of HLJDT on neuronal apoptosis hypoxia and ischemia induced.

Exploratory Pharmacokinetics of Geniposide in Rat Model of Cerebral Ischemia Orally Administered with or without Baicalin and/or Berberine

Huang-Lian-Jie-Du-Tang (HLJDT), a classical Chinese prescription, has been clinically employed to treat cerebral ischemia for thousands of years. Geniposide is the major active ingredient in HLJDT. The aim is to investigate the comparative evaluations on pharmacokinetics of geniposide in MCAO rats in pure geniposide, geniposide : berberine, and geniposide : berberine : baicalin. Obviously, the proportions of geniposide : berberine, geniposide : baicalin, and geniposide : berberine : baicalin were determined according to HLJDT. In our study, the cerebral ischemia model was reproduced by suture method in rats. The MCAO rats were randomly assigned to four therapy groups and orally administered with different prescription proportions of pure geniposide, geniposide : berberine, geniposide : baicalin, and geniposide : berberine : baicalin, respectively. The concentrations of geniposide in rat serum were determined using HPLC, and main pharmacokinetic parameters were investigated. The results indicated that the pharmacokinetics of geniposide in rat serum was nonlinear and there were significant differences between different groups. Berberine might hardly affect the absorption of geniposide, and baicalin could increase the absorption ability of geniposide. Meanwhile, berberine could decrease the absorption increase of baicalin on geniposide.

Explore the effects of Huang-Lian-Jie-Du-Tang on Alzheimer’s disease by UPLC-QTOF/MS-based plasma metabolomics study

Graphical abstract Figure. No caption available. HighlightsThe underlying mechanism of HLJDT was explored by valid UPLC–MS‐based metabolomics.Memory amelioration and reduced neuroinflammation were observed in HLJDT group mice.Callback of lipid metabolic disorder indicates the effects of HLJDT on APP/PS1 mice. ABSTRACT Alzheimers disease (AD) is a progressive neurodegenerative disease with neither definitive pathogenesis nor effective treatment method so far. Huang‐Lian‐Jie‐Du‐Tang (HLJDT) is a classic formula of traditional Chinese medicine (TCM) proven to have ameliorative effects on learning and memory deficits of dementia. Morris water maze (MWM) test and pathology analysis have demonstrated that HLJDT could ameliorate learning and memory deficits in AD mouse model, which may act via its anti‐neuroinflammation properties. According to our previous studies, an UPLC‐QTOF/MS‐based metabolomics approach was performed to explore the potential mechanisms of HLJDT on preventing AD. As a result, a total of 23 potential metabolites (VIP >1, |Pcorr| >0.58, CUFjk excludes 0, P < 0.05) contributing to AD progress were identified. The metabolic pathway analysis with MetPA revealed that glycerophospholipid metabolism, sphingolipid metabolism, arachidonic acid metabolism, linoleic acid metabolism and tryptophan metabolism were disturbed in mouse model of AD. After HLJDT treatment, 14 metabolites were restored back to the control‐like levels.

Microfiltration process by inorganic membranes for clarification of TongBi liquor.

Membrane separation is an alternative separation technology to the conventional method of filtration. Hence, it has attracted use in the purification and concentration of Chinese Herbal Medicine Extracts (CHMEs). The purpose of this work was to study the process of microfiltration of Tongbi liquor (TBL), a popular Chinese herbal drink, using ceramic membranes. Zirconium oxide and aluminum oxide membranes with pore mean sizes of 0.2 μm and 0.05 μm, respectively, are used for comparisons in terms of flux, transmittance of the ingredients, physical-chemical parameters, removal of macromolecular materials and fouling resistance. The results show that 0.2 μm zirconium oxide membrane is more suitable. The stable permeate flux reaches 135 L·h−1·m−2, the cumulative transmittance of the indicator is 65.53%. Macromolecular materials, such as starch, protein, tannin, pectin and total solids were largely eliminated in retentate after filtration using 0.2 μm ZrO2 ceramic membrane, resulting in clearer TBL. Moreover, this work also reveals that continuous ultrasound could strengthen membrane process that the permeate flux increases significantly. This work demonstrates that the purification of CHME with ceramic membranes is possible and yielded excellent results.