Medicinal Herb Research: Serum Pharmacological Method and Plasma Pharmacological Method

Abstract

INTRODUCTIONPharmacological experiments can be categorized into three types: in vivo, in vitro, and ex vivo. Drug therapeutic effects and adverse/toxic reactions are mainly identified by in vivo tests/trials. Elucidation of pharmacological mechanism usually depends upon analysis of in vitro and/or ex vivo results in addition to in vivo observation. Most natural medicinal herbs contain complex components, and their pharmacokinetics remains unknown. It is difficult to investigate their pharmacological actions and mechanisms in vitro by directly adding herbal powder or crude extracts into an isolated organ or cultured cells or enzymes for multiple reasons: first, direct addition of crude herbal preparations can change important extracellular parameters (e.g. ionic strength, osmotic pressure and pH value etc.); second, the crude preparations contain ingredients that are not absorbed in vivo and therefore not in circulation when taken orally, which may interfere with the ex vivo test system; third, many herbal medications exert their effects through metabolites after undergoing series of biotransformation; and the important step of biotransformation is absent in the ex vivo system. It is therefore more reasonable to use the cell-free portion of a blood specimen, which contains the absorbed medicinal herb components and their metabolites, in pharmacological experiments in vitro.However, there are two major preparations of the cell-free portion of blood specimens: plasma and serum. Plasma is the virtually cell-free supernatant of blood containing anticoagulant after centrifugation. Serum is the undiluted extracellular portion of blood after adequate coagulation is completed. Serum pharmacological method, using serum with herbs as drug source for ex vivo experiments, was proposed by Iwama and his coworkers in 1987.1) To date, several thousand articles based upon this method has been published in various professional journals.1-6) Plasma pharmacological method, i.e. using plasma with herbs as drug source in ex vivo experiments, was proposed by us in early days of the 21st century. 7,8) Recent work by our and other groups has demonstrated the feasibility of plasma pharmacological method in ex vivo studies of medicinal herbs, and the results obtained were partially different from those of serum pharmacological method.9) This review should contribute to our understanding of the principal reasons and facts leading to the uncertainty of serum pharmacological method and summarize the cumulating experimental evidence supporting the feasibility of plasma pharmacological method. DIFFERENCES BETWEEN SERUM AND PLASMASerum differs from plasma in many aspects since blood coagulation involves series of intricate biochemical changes and multiple cellular responses. 10,11) The major differences between serum and plasma are as follows:Activation of Coagulation and Related Systems In plasma coagulation factors, FXII, prekallikrein, FXI, FIX, FX, prothrombin, and FXIII are proenzymes; in cofactors, high molecular weight kininogen, FVIII an...

Effects and mechanisms of total Panax notoginseng saponins on proliferation of vascular smooth muscle cells with plasma pharmacology method

“…An experiment using drug‐containing plasma in vitro is named ‘plasma pharmacological method’. Fingerprint analysis with high‐performance liquid chromatography (HPLC)‐mass spectrometry (MS) showed that drug‐containing serum lost most polar components of TCM, while drug‐containing plasma retained them [2] . Experiments using VSMCs cultured in vitro indicated that drug‐containing plasma could reflect better the role of TCM [3] .…”

“…Fingerprint analysis with high-performance liquid chromatography (HPLC)-mass spectrometry (MS) showed that drugcontaining serum lost most polar components of TCM, while drug-containing plasma retained them. [2] Experiments using VSMCs cultured in vitro indicated that drug-containing plasma could reflect better the role of TCM. [3] So the plasma pharmacological method may minimize the interference of factors activated in coagulation and may be a useful means of research for TCM.…”

Fuzheng Qingjie Granules Inhibit Growth of Hepatoma Cells via Inducing Mitochondria-Mediated Apoptosis and Enhancing Immune Function

“…Biotransformation in the gastrointestinal tract is needed for some herbs to exert their therapeutic action. 35 Therefore it is believed that the application of serum from herb(s)-treated animals, so-called “serum pharmacology,” can more truly simulate the in vivo therapeutic effects. 36 The in vitro results showed that FZQJ could induce the apoptosis of HepG2 cells via mitochondria-dependent apoptotic pathway, which was verified in animal experiments.…”

The effects of BuYang HuanWu Decoction and its effective components on proliferation-related factors and ERK1/2 signal transduction pathway in cultured vascular smooth muscle cells

“…Although serum pharmacological method was a great improvement in pharmacology studies of TCM, its limitations has also been noted (Ge et al, 2010). Serum was the liquid with fibrin and blood cells removed after coagulation.…”