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The multi-component pharmacokinetic study of Chinese herbal extracts elaborates the in vivo processes,including absorption,distribution,metabolism,and excretion,of multiple bioactive components,which is of significance in revealing pharmacodynamic material basis of Chinese herbal medicine. In recent years,with the innovation in ideas,and development of techniques and methods on traditional Chinese medicine( TCM) research,the pharmacokinetic studies of Chinese herbal extracts were extensively performed,and notable progress has been made. This paper reviewed the advancement of multi-component pharmacokinetics of Chinese herbal extracts in recent five years from analysis technology of biological sample,the pharmacokinetic characteristics of Chinese herbal medicine with complex system,and the impacts of processing and pathological state on pharmacokinetics of Chinese herbal extracts,aiming to provide a reference for quality control,product development and rational medication of Chinese herbal extracts.
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Humans , China , Drugs, Chinese Herbal , Medicine, Chinese Traditional , Quality ControlABSTRACT
Traditional Chinese medicine(TCM) injections boast a definite efficacy and have been widely used in clinic. However, the problems in medication safety have been attracted increasing attention. Pharmacokinetics is of significance to guiding TCM injection administration regimen design and improving safety and effectiveness in clinical use. In recent years, with the improvement of ideas, technology and methods of TCM studies, the pharmacokinetic studies of TCM injections have been broadly performed, with a notable progress. This paper reviewed the advance in pharmacokinetics studies of TCM injections in recent ten years, which mainly focused on pre-clinical concentration-time course, distribution, metabolism and excretion in vivo based on analysis techniques, pharmacokinetic interactions of constitutes, impact of pathological state, pharmacokinetic interactions between TCM injection and chemical drugs, and clinical pharmacokinetics studies of TCM injections, in the expectation of providing reference for studies on quality control, product development and rational clinical use of TCM injections.
Subject(s)
Drugs, Chinese Herbal , Injections , Medicine, Chinese Traditional , Quality ControlABSTRACT
Total glucosides of peony (TGP), containing the effective components of paeoniflorin (Pae), albiflorin (Alb) and so on, are effective parts of Radix Paeoniae Alba. And it possesses extensive pharmacological actions, one of which is hepatoprotective effect. In recent years, abundant of pharmacokinetics and pharmacodynamics research of TGP in hepatoprotective effects have been performed. However, the relative medicine of TGP in hepatoprotective effect has not been developed for clinical application. In order to provide reference for the development and rational clinical application of TGP, the research progresses of pharmacokinetics and pharmacodynamics of TGP in hepatoprotective effect were summarized in this paper. Pharmacokinetics research has clarified the process of absorption, distribution, metabolism and excretion of TGP in vivo, and liver injury disease can significantly influence its metabolic processes. Pharmacodynamics studies suggested that TGP can protect against acute liver injury, non-alcoholic fatty liver diseases (NAFLD), chronic liver fibrosis and liver cancer. However, the action mechanism and in vivo process about hepatoprotective effects of TGP have not been clearly revealed. How liver injury influences the metabolism of TGP and its integrated regulation through multiple targets need to be further studied. The combined pharmacokinetics and pharmacodynamics studies should be performed in favour of medicine development and clinical application of TGP in hepatoprotective effects.
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Chinese medicinal formulae are the important means of clinical treatment in traditional Chinese medicine. It is urgent to use modern advanced scientific and technological means to reveal the complicated mechanism of Chinese medicinal formulae because they have the function characteristics of multiple components, multiple targets and integrated regulation. The systematic and comprehensive research model of proteomic is in line with the function characteristics of Chinese medicinal formulae, and proteomic has been widely used in the study of pharmacological mechanism of Chinese medicinal formulae. The recent applications of proteomic in pharmacological study of Chinese medicinal formulae in anti-cardiovascular and cerebrovascular diseases, anti-liver disease, antidiabetic, anticancer, anti-rheumatoid arthritis and other diseases were reviewed in this paper, and then the future development direction of proteomic in pharmacological study of Chinese medicinal formulae was put forward. This review is to provide the ideas and method for proteomic research on function mechanism of Chinese medicinal formulae.
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To establish a rapid and accurate method for the determination of 34 chemical hypotensors which were illegally added into the blood pressure lowering class Chinese patent medicines (CPM) and the blood pressure regulating class health foods. The UPLC-MS/MS method was adopted. The samples were extracted with methanol by ultrasonic processing and separated on a Waters Acquity BEH-C18 (100 mm × 2.1 mm, 1.7 μm) column with 0.1% formic acid methanol (A) and 0.1% formic acid water solution (B) as the mobile phase by gradient elution (0-5 min, 32% A; 5-8 min, 32%-50% A; 8-12 min, 50% A; 12-14 min, 50%-60% A; 14-16 min, 60%-80% A; 16-18 min, 80% A; 18-19 min, 80%-90% A; 19-20 min, 90%-100% A; 20-21 min, 100% A; and 21-22 min, 100%-32% A) at a flow rate of 0.2 mL/min, and the column temperature was 40℃. A positive-ion (ESI+) source and a MRM mode were used to separate and quantitatively determine the chemical hypotensors. The obtained molecular ions, fragment ions, and retention time for MRM channels were used to identify the 34 kinds of drugs by comparison with those of reference substances. The obtained peak areas were used to determine the accurate content of chemical hypotensors in the blood pressure lowering class CPM and the blood pressure regulating class health foods. A good resolution of 34 kinds of chemical drugs, including clonidine, captopril, yohimban-16-carboxylicacid, L-tyrosine, hydrochlorothiazide, furosemide, indapamide, minoxidil, hydralazine, atenolol, lisinopril, dibazole, metoprolol, bisoprolol, prazosin, terazosin, propranolol, enalapril, quinapril, benazepril, dilthiazem, doxazosin, nicardipine, nifedipine, amlodipine, nimodipine, felodipine, nitrendipine nisoldipine, valsartan, telmisartan, candesartan cilexetil, rbesartan, and olmesartan medoxomil was obtained under this UPLC and MS/MS condition. The limits of qualitative and quantitative were in the range of 0.1-0.5 and 0.3-1.5 ng/g. The standard addition recoveries were in the range of 81.4%-118.9%. The method is simple, accurate, and with high sensitivity, which can be used for the determination of illegally added chemical hypotensors in CPM and health foods.
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OBJECTIVE: Chemotherapy is the primary treatment in addition to surgery and radiotherapy in cancer therapy, and drug resistance of tumor cells remains a major obstacle to successful cancer chemotherapy. In present study, we aim to develop a novel drug delivery system, ie, doxorubicin (DOX) conjugated poly (amido amine) (PAMAM) dendrimers was further decorated by hyaluronic acid (HA) (DOX-PAMAM-HA) to circumvent drug resistance in cancer cells. METHODS: Nuclear magnetic resonance (NMR) was performed to confirm the synthesis of the DOX-PAMAM-HA, its average size was analyzed by a dynamic light-scattering detector, and its morphological examination was performed by transmission electron microscope (TEM). To study the ability of DOXPAMAM-HA in overcome multi-drug resistance, the multi-drug resistant breast cancer cells (MCF-7/ADR cells) was used as model cell, and the confocal microscopy was utilized to observe the drug intracellular distribution, moreover, the hematoxylin-eosin staining (HE) studies were employed to evaluate the tissue staining and toxicity. RESULTS: The drug delivery system DOX-PAMAM-HA was successfully synthesized, which is spherical particles with a average particle size of 323 nm. The uptake in MCF-7/ADR cells for DOXPAMAM-HA is higher than that of DOX solution, and DOX-PAMAM-HA maybe distribute mainly in the lysosome of the cells, which could increase the accumulation of DOX in its action target (nucleus). In contrast, DOX solution was mainly diffused in the cytoplasm of the tumor cells. Furthermore, less toxicity in heart and spleen induced by DOX-PAMAM-HA in comparing to that of DOX solution after intravenous administration for 3 weeks. CONCLUSION: DOX-PAMAM-HA is a prospect future nanodrug delivery system in overcoming drug-resistance of tumor cells.
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<p><b>OBJECTIVE</b>To investigate the roles of phosphatidylinositol 3 kinase regulatory subunit alpha (PIK3R1）gene in the development of hepatocellular carcinoma （HCC）.</p><p><b>METHODS</b>Surgical specimens of liver cancer and corresponding pericancerous liver tissue were collected from 20 patients with hepatocellular carcinoma. Expression of p85α, encoded by PIK3R1, in HCC tissue specimens was detected by Western blotting and immunohistochemistry. HCC HepG2 cells were transfected with PIK3R1 siRNA or PIK3R1-cDNA. The expression of PIK3R1 in transfected HepG2 cells or control cells were detected by real-time PCR. Cell proliferation was evaluated by MTT, colony formation assays and flow cytometry respectively. The expression of PI3K/AKT pathway-related proteins were detected by Western blotting.</p><p><b>RESULTS</b>The expression of p85α in liver tissue was higher than that in pericancerous tissues (1.27±0.58 vs 0.99±0.47，t=-3.25，P<0.05）. The expression of PIK3R1 was decreased by 0.19±0.03 fold in PIK3R1siRNA-transfected HepG2 cells(t=46.77，P<0.05)，and increased by 32.36±3.33 fold in PIK3R1 cDNA -transfected cells（t=-16.31， P<0.05）. MTT result showed that PIK3R1 siRNA inhibited growth of HepG2 cells （0.611±0.072 vs 0.807±0.059，t=3.65，P<0.05），while PIK3R1 cDNA increased the cell growth（0.937±0.060 vs 0.693±0.065，t=-4.78，P<0.05）. PIK3R1 siRNA transfected cells presented lower colony-forming efficiency than control group（3.8%±0.84% vs 15.0%±2.3%，t=7.92，P<0.05），while PIK3R1 cDNA transfected cells had higher colony-forming efficiency than control group (23.6%±3.4% vs 12.0%±1.5%，t=-5.40，P<0.05）. PIK3R1 siRNA reduced the ratio of S phase cells（13.9%±0.015% vs 32.9%±0.07%，t=45.97，P<0.01, while PIK3R1 cDNA increased S phase cells（56.33%±0.024% vs 31.94%±0.042%，t=-8.73，P<0.01）. PIK3R1 increased the level of p-AKT and decreased p53 level. CONCLUSION：p85α is highly expressed in HCC，and PIK3R1 gene may promote proliferation of HepG2 cells by activating PI3K/AKT pathway.</p>
Subject(s)
Humans , Carcinoma, Hepatocellular , Genetics , Cell Proliferation , Gene Expression Regulation, Neoplastic , Hep G2 Cells , Liver Neoplasms , Genetics , Phosphatidylinositol 3-Kinases , Genetics , Proteins , RNA, Small Interfering , TransfectionABSTRACT
In this study, we prepared various matrices of hydrogel patches and studied their cross-linking mechanism by observing their rheological properties, which could provide theoretical basis and deep technical support for further industrial development of hydrogel patch. Rheology method was used to do the amplitude scanning and single-frequency scanning for various hydrogel matrix, under the condition of oscillation mode of the rheometer. Then the linear viscoelastic region, composite modulus value, as well as changes in slope with time of the composite modulus and phase angle of various hydrogel matrix were analyzed in detail. The results showed that the stability of matrix was mainly determined by hydrogel frame; only in acidic environment, the cross-linking reaction between cross-linker and hydrogel frame can occur; elasticity of matrix can be decreased by organic acid and the effect level was related to the ratio of the number of carboxyl and hydroxyl (-COO(-)/-OH) in adjusters: if the ratio was not equal, the higher -COO(-)/-OH in adjusters would be the less elasticity of matrix decreased; the cross-linking speed of matrix was determined by adjuster, the cross-linking speed of matrix contain different adjusters was ranged in following order: matrix containing tartaric acid > matrix containing lactic acid > matrix containing malic acid > matrix containing citric acid; the cross-linking speed of matrix was not uniform in the whole cross-linking process.
Subject(s)
Citric Acid , Chemistry , Cross-Linking Reagents , Chemistry , Hydrogels , Chemistry , Lactic Acid , Chemistry , Malates , Chemistry , Rheology , Tartrates , Chemistry , ViscosityABSTRACT
Active tumor targeting drug delivery system( ATTDDS) can selectively combine with and react to the target tissue at the cellular or sub-cellular level, making it possible for drugs to be distributed in a controlled manner and released in a slow and continuous manner, subsequently resulting in enhanced anti-cancer drugs effects and reduced adverse effects on normal tissues. Although there are many problems need to be solved in research on ATTDDS, and there is still a long way to go before it can be used clinically, its roles in overcoming adverse effects of cancer treatment and improving the therapeutic effect are valuable. Generally, ATTDDS is an ideal anti-tumor drug dosage and has a promising prospect. This paper introduces the effects and characteristics of various types of ATTDDS as well as their problems and countermeasures, hoping to provide research ideas and methods for the anti-tumor targeted drug delivery.