Miao Zhang

Bio: Miao Zhang is an academic researcher from Peking University. The author has contributed to research in topics: Physiologically based pharmacokinetic modelling & Pharmacokinetics. The author has an hindex of 8, co-authored 15 publications receiving 371 citations. Previous affiliations of Miao Zhang include China Pharmaceutical University & Peking Union Medical College.

Interpretation the Hepatotoxicity Based on Pharmacokinetics Investigated Through Oral Administrated Different Extraction Parts of Polygonum multiflorum on Rats.

Abstract: The liver injury induced by Polygonum multiflorum (PM) used for clinical treatment has recently received widespread attention. This study aimed to determine the hepatotoxicity of PM through pharmacokinetics studies. The extract of PM was separated to isolate the anthraquinone fraction, the tannin and polysaccharide fraction, the hydroxystilbene fraction, and the combined anthraquinone fraction. A rapid LC-MS/MS method was developed and validated to simultaneously analyze 2,3,5,4'-tetrahydroxystilbene-2-O-β-glucoside (TSG), emodin-8-O-β-D-glucopyranoside (EDG), and emodin in rat plasma, and was applied to the pharmacokinetics (PK) studies. The hepatotoxicity of different extracted parts of PM was evaluated through the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBil), direct bilirubin (DBil), and indirect bilirubin (IBil) in rat serum. The results showed that liver injury occurred in all the treated groups and that the hepatotoxicity performance of the total extract was different from other groups. The pharmacokinetic studies showed that the Cmax, Tmax, AUC, t1/2, and MRT of the major compounds of different extracted parts were significantly different in rat plasma at same dosage. Emodin-O-hex-sulfate, tetrahydroxystilbene-O-(galloyl)-hex, emodin (original and generated through EDG deglycosylation), and other free anthraquinones might be responsible for the hepatotoxicity of PM in vivo. PM extracts produced inhibitory effects on drug metabolic enzymes, include CYP3A4, CYP2C19, CYP2E1, UGT1A1, etc. And these effects may be related to its hepatotoxicity and pharmacokinetic behavior different. This information on hepatotoxicity and the pharmacokinetic comparison may be useful to understand the toxicological effects of PM.

Types, principle, and characteristics of tandem high-resolution mass spectrometry and its applications

Abstract: Tandem high-resolution mass spectrometry (THRMS) is an analytical technique that has arisen in recent years and is now widely used in pharmaceutical research and development (RD for example, for the identification of constituents in herbs and formulae, pharmacokinetics, omics, and drug degradation), food safety, environmental contamination and other research fields. Time of Flight (TOF) and Orbitrap are the most widely used mass analysers in THRMS, and the technical specifications vary among the different types of THRMS and even among the different manufacturers for a given type of analyser. In this article, we review the principle and functional characteristics of different types or models for THRMS and provide a brief description of its applications in the medical research, food safety, and environmental protection fields.

A New Perspective on Liver Injury by Traditional Chinese Herbs Such As Polygonum multiflorum: The Geographical Area of Harvest As an Important Contributory Factor.

Abstract: Herbal medicine has been widely used in the treatment of various diseases; however, the adverse reactions cannot be ignored. Most previous studies have ignored the relationship between the factors of geographical areas/batches and toxicity. This study used Polygonum multiflorum (PM) as an example to analyze the relationship between the geographical areas/batches and toxicity and speculated on the hepatotoxicity-inducing components in PM based on high content screening, UHPLC-Q-TOF/MS and Progenesis QI software analysis. The results of the study show that the toxicity of PM was obviously different among the different geographical areas, and the most toxic PM was from the Sichuan province. To obtain more accurate results and to reduce the false-positive rate, two methods were used to evaluate the speculative results. It was noteworthy that emodin was not the main hepatocyte toxicity constituent of PM. The analysis methods suggested that PM toxicity may be associated with tetrahydroxystilbene-O-(galloyl)-hex and emodin-O-hex-sulphate. The toxicity of these two components requires further study.

Challenges and emergent solutions for LC-MS/MS based untargeted metabolomics in diseases.

Abstract: In the past decade, advances in liquid chromatography-mass spectrometry (LC-MS) have revolutionized untargeted metabolomics analyses. By mining metabolomes more deeply, researchers are now primed to uncover key metabolites and their associations with diseases. The employment of untargeted metabolomics has led to new biomarker discoveries and a better mechanistic understanding of diseases with applications in precision medicine. However, many major pertinent challenges remain. First, compound identification has been poor, and left an overwhelming number of unidentified peaks. Second, partial, incomplete metabolomes persist due to factors such as limitations in mass spectrometry data acquisition speeds, wide-range of metabolites concentrations, and cellular/tissue/temporal-specific expression changes that confound our understanding of metabolite perturbations. Third, to contextualize metabolites in pathways and biology is difficult because many metabolites partake in multiple pathways, have yet to be described species specificity, or possess unannotated or more-complex functions that are not easily characterized through metabolomics analyses. From a translational perspective, information related to novel metabolite biomarkers, metabolic pathways, and drug targets might be sparser than they should be. Thankfully, significant progress has been made and novel solutions are emerging, achieved through sustained academic and industrial community efforts in terms of hardware, computational, and experimental approaches. Given the rapidly growing utility of metabolomics, this review will offer new perspectives, increase awareness of the major challenges in LC-MS metabolomics that will significantly benefit the metabolomics community and also the broader the biomedical community metabolomics aspire to serve.

Pharmacovigilance Practice and Risk Control of Traditional Chinese Medicine Drugs in China

Abstract: ETHNOPHARMACOLOGICAL RELEVANCE Traditional Chinese Medicine (TCM), including Traditional Chinese Medicine drugs (TCM drugs), has been playing a very important role in health protection and disease control for thousands of years in China. Relying on natural products, mainly of herbal origin, used either as raw materials for decoction, as prepared herbal medicines or as formulated traditional medicines, TCM is still widely accepted by Chinese people, especially for chronic diseases treatment. This extensive use warrants safety measures and so TCM drug safety monitoring and risk management are becoming increasingly important tasks for the Chinese State Food and Drug Administration (SFDA). METHODS The Adverse Drug Reaction (ADR) monitoring system in China was established both for western and TCM drugs in 1989 as a voluntary reporting system with a National Center collecting and compiling reports. Serious or multi-case reports on individual TCM drug or formulated products are detailed in the Chinese ADR Information Bulletin to inform the public and Drug Administrative authorities for risk management. RESULTS About 10-15% of the ADR reports received by the National Center are related to TCM drugs and mainly pertaining to the formulated products. In certain cases, the suspension of a particular TCM preparation is decided by SFDA China. CONCLUSION The model of safety monitoring and risk management of TCM drugs is still under exploration. Indeed, the characteristics and risk factors associated with these drugs require both proper understanding and control of the risk by strengthening standardization of clinical applications, basic science research, quality control in manufacturing, exploration of the actives monitoring methodology and enhancement of international communication and cooperation.

Flavonoids as Therapeutic Agents in Alzheimer’s and Parkinson’s Diseases: A Systematic Review of Preclinical Evidences

Abstract: Alzheimer’s and Parkinson’s diseases are considered the most common neurodegenerative disorders, representing a major focus of neuroscience research to understanding the cellular alterations and pathophysiological mechanisms involved. Several natural products, including flavonoids, are considered able to cross the blood-brain barrier and are known for their central nervous system-related activity. Therefore, studies are being conducted with these chemical constituents to analyze their activities in slowing down the progression of neurodegenerative diseases. The present systematic review summarizes the pharmacological effects of flavonoids in animal models for Alzheimer’s and Parkinson’s diseases. A PRISMA model for systematic review was utilized for this search. The research was conducted in the following databases: PubMed, Web of Science, BIREME, and Science Direct. Based on the inclusion criteria, 31 articles were selected and discussed in this review. The studies listed revealed that the main targets of action for Alzheimer’s disease therapy were reduction of reactive oxygen species and amyloid beta-protein production, while for Parkinson’s disease reduction of the cellular oxidative potential and the activation of mechanisms of neuronal death. Results showed that a variety of flavonoids is being studied and can be promising for the development of new drugs to treat neurodegenerative diseases. Moreover, it was possible to verify that there is a lack of translational research and clinical evidence of these promising compounds.

Radix Bupleuri: A Review of Traditional Uses, Botany, Phytochemistry, Pharmacology, and Toxicology.

Abstract: Radix Bupleuri (Chaihu) has been used as a traditional medicine for more than 2000 years in China, Japan, Korea, and other Asian countries Phytochemical studies demonstrated that this plant contains essential oils, triterpenoid saponins, polyacetylenes, flavonoids, lignans, fatty acids, and sterols Crude extracts and pure compounds isolated from Radix Bupleuri exhibited various biological activities, such as anti-inflammatory, anticancer, antipyretic, antimicrobial, antiviral, hepatoprotective, neuroprotective, and immunomodulatory effects However, Radix Bupleuri could also lead to hepatotoxicity, particularly in high doses and with long-term use Pharmacokinetic studies have demonstrated that the major bioactive compounds (saikosaponins a, b2, c, and d) were absorbed rapidly in rats after oral administration of the extract of Radix Bupleuri This review aims to comprehensively summarize the traditional uses, botany, phytochemistry, pharmacology, toxicology, and pharmacokinetics of Radix Bupleuri reported to date with an emphasis on its biological properties and mechanisms of action