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

Zhu, Hua; Qian, Zhong‐Ji; Li, Huan; Li-wei, Guo; Pan, Linmei; Zhang, Qichun; Tang, Yuping

doi:10.1016/j.jep.2012.02.014

Cited by 30 publications

(26 citation statements)

References 19 publications

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“…Both hydrolyzation by enterobacteria and subsequently glucuronidation reactions of flavonoids occurred in vivo (Lai et al, 2003). This was caused by the joint action of intestinal absorption and hepatic metabolism together, which was in consistent with the published paper (Zhu et al, 2012). After the biotransformation of intestinal bacteria and liver microsomes, the chemical complexity of HLJDD was simplified radically.…”

Section: Discussionsupporting

confidence: 76%

Metabolic fate analysis of Huang–Lian–Jie–Du Decoction in rat urine and feces by LC–IT-MS combining with LC–FT-ICR-MS: a feasible strategy for the metabolism study of Chinese medical formula

et al. 2015

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1. Huang-Lian-Jie-Du Decoction (HLJDD) is widely used for the treatment of hypertension, diabetes, inflammation and neural system diseases in clinic. In the present study, the comprehensive metabolic profile of HLJDD was demonstrated reliably and rapidly followed by the metabolic pathway analysis of six typical pure compounds (four alkaloids, one flavonoid and one iridoid) in HLJDD using LC-IT-MS combined with high resolution LC-FT-ICR-MS. 2. Totally, 85 compounds, including 32 prototype components and 53 biotransformed metabolites were detected and characterized in the urine and feces after oral administration of HLJDD and six pure compounds to rats, respectively. Among them, 17 prototypes were identified definitely with standard references. 3. Hydroxylation, demethylation and glucuronidation reactions of alkaloids, as well as glucuronidation and sulfonation reactions of iridoids and flavonoids, were observed as the major metabolic pathways of HLJDD. Flavonoids, iridoids and their metabolites were mainly excreted from urine. However, amount of alkaloids were detected in feces. 4. In general, the distinctive metabolic process of three kinds of representative components in HLJDD was clarified. The in vivo metabolic network of HLJDD was demonstrated. Meanwhile, the investigation of representative pure compounds in metabolic study provided a valuable strategy to elucidate the full-scale metabolic fate of HLJDD. This might be helpful to understand the in vivo mechanism of Traditional Chinese medicine (TCM).

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Section: Discussionsupporting

confidence: 76%

Metabolic fate analysis of Huang–Lian–Jie–Du Decoction in rat urine and feces by LC–IT-MS combining with LC–FT-ICR-MS: a feasible strategy for the metabolism study of Chinese medical formula

et al. 2015

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“…Modern pharmacological works displayed that HLJDD possesses widely effects, including the treatment of inflammation [16, 17], gastrointestinal disorders [18], diabetes [17], vasodilation [19], acute liver injury [20], Alzheimer disease [21, 22], hypertension [23], multiple myeloma [24] and other cardiovascular diseases [25, 26]. Until now, some research had reported the content determinations of the main bioactive components contained in HLJDD, in order to understand and elucidate its pharmacological effects and the relevant mechanisms [27, 28].…”

Section: Introductionmentioning

confidence: 99%

Reno-protective effect and mechanism study of Huang Lian Jie Du Decoction on lupus nephritis MRL/lpr mice

Nie

Deng

Xiang

et al. 2016

BMC Complement Altern Med

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BackgroundHuang Lian Jie Du Decoction (HLJDD), a very famous traditional Chinese medicinal prescription, has been used for heat dissipation and detoxification in China. This study was aimed to evaluate the reno-protective effects of HLJDD against lupus nephritis (LN) in vivo in MRL/lpr mice.MethodsAnimals were administered orally every day for eight consecutive weeks except the mice of normal group and model group. Organ indexes, serum interleukin-6 (IL-6), interleukin-10 (IL-10), interferon-gamma (IFN-γ) and the anti-double stranded DNA (anti-dsDNA) antibody were tested, respectively. Creatinine (Cr), blood urea nitrogen (BUN) and urine protein were measured for renal function evaluation. The expression of phosphorylated signal transducer and activator of transcription 3 (p-STAT 3) in kidney tissue was observed by western blot (WB) and immunohistochemical (IHC) method. Meanwhile, histopathological changes in the renal were studied by hematoxylin-eosin (H&E) staining.ResultsThe mice of HLJDD-treated group exhibited a significant reduced mortality (p < 0.05), serum anti-dsDNA level (p < 0.05) and renal immune complex deposition (p < 0.05), compared with the untreated MRL/lpr mice. In addition, HLJDD treatment remarkably reduced the levels of BUN, Cr, proteinuria (p < 0.01) and the levels of inflammatory cytokines such as IL-6, IL-10 and IFN-γ (p < 0.01). Moreover, HLJDD significantly suppressed the phosphorylations of STAT 3 (p < 0.05) and the renal pathological changes.ConclusionsThe study implied that HLJDD may be a potential agent for the therapy of LN, and the down-regulated p-STAT 3 expression suggesting that it may be one of the LN therapy targets for HLJDD.

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“…7,39,40) Though these methods are sensitive and specific, because of the complexity of pharmacokinetic studies on Chinese medicine compounds, the disadvantages of these methods have been revealed. Firstly, cleanup and pre-concentration steps consisting of liquid-liquid extraction followed by solid-phase extraction procedures are required, rendering high sample volume and very difficult to screen large numbers of samples in a timely way.…”

Section: Discussionmentioning

confidence: 99%

“…2) Numerous recent studies have described several pharmacological characteristics of HJT, including antioxidant, [3][4][5] anti-inflammatory, 6,7) and neuroprotective activities. 8,9) Geniposide, an iridoid glycoside, is the major medical component of the Fructus Gardeniae 10) ( Fig.…”

Section: Pharmacokinetics Of Geniposide By Monoclonal Antibody-based mentioning

confidence: 99%

Pharmacokinetics of Geniposide by Monoclonal Antibody-Based icELISA in Mice after Oral Administration of Huanglian-Jiedu-Tang

Sun

et al. 2014

Biological & Pharmaceutical Bulletin

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Geniposide, Geniposide, the main active component in extracts of Gardenia jasminoides ELLIS., is one of the main components of Huanglian-Jiedu-Tang (HJT). This study aimed to validate an indirect competitive enzyme-linked immunosorbent assay (icELISA) based on monoclonal antibodies (mAb) against geniposide (anti-geniposide mAb), which was developed by our lab, and apply the assay to study the pharmacokinetics of geniposide in HJT in mice. Blood samples were drawn from mice at predetermined time points after oral administration of HJT in three dosages. A linear correlation was obtained for geniposide concentrations in the range from 1.17 to 37.50 µg/mL. The intra-day and inter-day precision values of the icELISA method were well within the recommended range (≤10%). The recovery rates ranged from 99.74 to 102.40%. Stability studies showed that geniposide sample solutions were intact for 12 h. The T max and mean residence time (MRT) of geniposide of the three groups were consistent with previous data. The results suggest that a reliable and effective method was established and could be applied to the study of the pharmacokinetics of geniposide in HJT.Key words geniposide; monoclonal antibody; pharmacokinetics; indirect competitive enzyme-linked immunosorbent assay; Huanglian-Jiedu-Tang; mouse Hanglian-Jiedu-Tang (HJT) is a famous traditional Chinese medicine (TCM) compound first described during the Tang Dynasty (Wai-Tai-Mi-Yao). HJT is composed of 4 Chinese herbs: Rhizoma Coptidis (Coptis chinensis FRANCH.), Radix Scutellariae (Scutellaria baicalensis GEORGI.), Cortex phellodendri (Phellodendron amurense RUPRECHT.) and Fructus Gardeniae (Gardenia jasminoides ELLIS.).1) In modern medicine, HJT is used to treat cardiovascular and cerebrovascular diseases, such as cerebral ischemia.2) Numerous recent studies have described several pharmacological characteristics of HJT, including antioxidant, [3][4][5] anti-inflammatory, 6,7) and neuroprotective activities. 8,9) Geniposide, an iridoid glycoside, is the major medical component of the Fructus Gardeniae 10) (Fig. 1). Geniposide can cross the blood-brain barrier, [11][12][13] which makes it a promising therapeutics for brain diseases. Geniposide can inhibit damage due to ischemia and limit memory impairment through its antioxidant 14) and antiinflammatory 15,16) activities. Therefore, geniposide is also one of the main components of HJT.Despite of the efficacy in indications has been proved by clinic; there are still adverse effect reports of geniposide. 17)Therefore, the effective measures for trace detecting are needed in the pharmacology studies of geniposide.Monoclonal antibodies (mAb) are immunoglobulins with high specificity and biological activity, 18) which have been extensively applied in prevention, diagnosis and treatment of diseases, detection of residues of pesticides and chloramphenicol in food samples, 19) and veterinary medicine development. The indirect competitive ELISA (icELISA), an immunological assay based on mAb, was reported to provide a valuable t...

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

Cited by 30 publications

References 19 publications

Metabolic fate analysis of Huang–Lian–Jie–Du Decoction in rat urine and feces by LC–IT-MS combining with LC–FT-ICR-MS: a feasible strategy for the metabolism study of Chinese medical formula

Metabolic fate analysis of Huang–Lian–Jie–Du Decoction in rat urine and feces by LC–IT-MS combining with LC–FT-ICR-MS: a feasible strategy for the metabolism study of Chinese medical formula

Reno-protective effect and mechanism study of Huang Lian Jie Du Decoction on lupus nephritis MRL/lpr mice

Pharmacokinetics of Geniposide by Monoclonal Antibody-Based icELISA in Mice after Oral Administration of Huanglian-Jiedu-Tang

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