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PubMed2025

Mechanisms of Baishao () and Gancao () on major depressive disorder: network pharmacology and o validation.

OBJECTIVE: To elucidate the potential molecular mechanisms of Baishao (Radix Paeoniae Alba) (APR) and Gancao (Radix Glycyrrhizae) (GR) in the treatment of major depressive disorder (MDD). METHODS: Based on the network pharmacology strategy, the therapeutic targets of APR-GR for MDD are predicted, differentially expressed genes from the Integrated Gene Expression database for MDD patients. Topological networks are constructed, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways are enriched, their pharmacological potential molecular mechanisms are discussed, and molecular docking analysis is performed to further motivate compositional and target interactions. Finally, the CUMS mouse model is used for validation. RESULTS: Based on the pharmacological network analysis, 17 candidate genes were identified, including muscarinic acetylcholine receptor M1(CHRM1), muscarinic acetylcholine receptor M2 (CHRM2), β2-adrenergic receptor (ADRB2), adrenergic α1A receptor (ADRA1A) and 5-hydroxytryptamine transfer protein (SLC6A4), etc. which are primarily involved in reactive oxygen species metabolism, neural response, oxidative stress response and other biological processes. Further analysis revealed that these targets are closely related to Ca2+, cyclic adenosine monophosphate, etc., and exhibit optimal binding sites after molecular docking. Finally, in vivo experiments were performed and it was found that APR-GR significantly improved depression-like behavior and hippocampal impairment in mouse models, increasing brain levels of 5-hydroxytryptamine, dopamine and norepinephrine and decreasing serum levels of corticotropin releasing hormone, corticosterone and adreno cortico tropic hormone, while upregulating the expression of CHRM1, CHRM2 and ADRA1A in the hippocampus and downregulating the expression of SLC6A4 and ADRB2. CNCLUSION: This research sheds light on the potential molecular mechanism of APR-GR to improve MDD.

Major Depressive Disorder↗
PubMed2026

Network pharmacological and experimental validation of the mechanism of Chaihu Guizhi Ganjiang decoction regulating T helper cell 17/regulatory T cell balance to improve autoimmune hepatitis.

OBJECTIVE: To elucidate the therapeutic efficacy and mechanism of action of Chaihu Guizhi Ganjiang decoction (, CGGD) in autoimmune hepatitis. METHODS: CGGD components and potential target genes were extracted from previously published databases. The autoimmune hepatitis (AIH)-related regulatory genes were obtained from the DisGeNET database. Intersections were taken, and enrichment analyses were performed on the extracted data. Concanavalin A (ConA)-induced AIH model mice were treated with CGGD via gavage. The results of network pharmacological analysis were experimentally validated. RESULTS: Network pharmacology revealed 228 genes at the intersection of AIH and CGGD. Kyoto Encyclopedia of Genes and Genomes analysis revealed that CGGD primarily regulates the phosphoinositide 3-kinase (PI3K)/ protein kinase B (AKT) signaling pathway and cellular metabolism in AIH. Gene Ontology enrichment analysis revealed that CGGD modulates inflammation through transcription factor-mediated signaling pathways. As predicted, CGGD attenuated ConA-induced AIH in a dose-dependent manner by activating the PI3K/AKT signaling pathway. Histopathological assessment confirmed the protective effects of CGGD against ConA-induced AIH. Further investigation revealed that CGGD regulated the T helper cell 17 (Th17)/regulatory T cell (Treg) balance by modulating the PI3K/Akt/ nuclear factor kappa-B (NF-κB) pathway. CONCLUSIONS: This study demonstrated the therapeutic effect of CGGD on AIH through a combination of network pharmacological prediction and experimental validation. Its mechanism of action involves PI3K/Akt/ NF-κB-mediated regulation of Th17/Treg cells.

Animals↗
PubMed2026

Mechanism of Shaofu Zhuyu decoction in improving diabetic mellitus erectile dysfunction inhibition of ferroptosis based on network pharmacology and experimental validation.

OBJECTIVE: To explore the medication patterns and mechanisms of action of Shaofu Zhuyu decoction (, SFZYD) in inhibiting ferroptosis through the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1)/glutathione peroxidase 4 (GPX4) pathway to improve diabetes mellitus-induced erectile dysfunction (DMED). METHODS: Firstly, data mining was employed to identify the medication patterns of Traditional Chinese Medicine (TCM) in treating DMED. Secondly, network pharmacology combined with a ferroptosis database was used to predict the targets. Subsequently, cell counting kit-8, 4',6-diamidino-2-phenylindole staining, reverse transcription-polymerase chain reaction (RT-PCR), and reagent kits were utilized to assess the repair effects of SFZYD on corpus cavernosum endothelial cells (CCECs) induced by high glucose (HG). Metabolic indicators, hematoxylin-eosin staining, and Masson staining were performed to observe the restorative effects of SFZYD on erectile function and penile tissue in diabetic rats. Finally, using Nrf2 inhibitors, the expression of related proteins and mRNAs was detected through Western blotting and RT-PCR. Reactive oxygen species levels and mitochondrial membrane potential were detected by flow cytometry. RESULTS: Data mining revealed that the prescription rules for blood stasis-type DMED coincide with the treatment principles of SFZYD. Network pharmacology identified 48 ferroptosis-related targets, primarily heme oxygenase 1 (HMOX1) and GPX4. Kyoto Encyclopedia of Genes and Genomes enrichment analysis associated these targets with the ferroptosis pathway. SFZYD repaired HG-induced CCECs damage and restored HMOX1 and GPX4 mRNA levels. in vivo, SFZYD effectively alleviated erectile dysfunction and repaired blood sinuses and fibrosis in diabetic rats. Following Nrf2 inhibition, the expression of Nrf2, HMOX1, and GPX4 decreased, while SFZYD intervention reversed these effects, improving ferroptosis and oxidative stress indicators. CONCLUSION: This study explored the potential mechanisms and efficacy of the TCM prescription SFZYD in treating DMED through data mining, network pharmacology analysis, cellular experiments, and animal experiments. It verified its effectiveness in repairing HG-induced CCECs damage, improving the pathological state of penile tissue in diabetic rats, and restoring erectile function by regulating the Nrf2/HO-1/GPX4 signaling pathway. This provides new insights and scientific evidence for treating DMED with TCM.

Male↗
PubMed2026

Active components and potential mechanisms of Wuzhuyu decoction in the treatment of ethanol-induced acute gastric mucosal injury: a network pharmacology and experimental verification.

OBJECTIVE: To investigate the underlying mechanisms and active components of Wuzhuyu decoction (, WD) in alleviating ethanol-induced acute gastric mucosal injury (GMI) using an integrated approach of network pharmacology and experimental verification. METHODS: Sprague-Dawley rats were randomly divided into six groups: control (Con), model (Mod), bismuth potassium citrate (BPC), WD at low (WD-L), medium (WD-M), and high (WD-H) doses. Following seven days of continuous intragastric administration of the respective treatments, an ethanol-induced gastric mucosal injury model was established in all groups except the control group by oral gavage of anhydrous ethanol. The gastric mucosal injury index was evaluated, and pathological changes were assessed viahematoxylin and eosin (HE) staining. Levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were measured by enzyme-linked immunosorbent assay (ELISA). The chemical composition was identified by ultra-performance liquid chromatography-tandem mass spectrometry. Active compounds were screened using the Swiss-absorption, distribution, metabolism, and excretion database, and their potential targets were predicted using the Swiss Target Prediction database and bioinformatics annotation database for molecular mechanism. Simultaneously, disease targets related to GMI were retrieved from the online mendelian inheritance in man and GeneCards databases. A protein-protein interaction (PPI) network was constructed, and functional enrichment analyses of gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses were performed using the Metascape database. Key predictions from the network pharmacology analysis were subsequently verified through animal experiments. Protein expression levels of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), Cleaved Caspase-3, and Cleaved Caspase-9 were analyzed by Western blot. Finally, molecular docking was performed using AutoDock Vina to investigate the interactions between the active components and core targets. RESULTS: WD treatment significantly reduced the gastric mucosal injury index and the levels of TNF-α, IL-1β, MDA, while it increased the activities of SOD and GSH-Px. Histopathological examination revealed marked improvement in gastric tissue morphology. A total of 145 compounds were identified in WD. Network pharmacology analysis identified 440 overlapping targets between WD and GMI. GO and KEGG enrichment analyses highlighted the apoptosis signaling pathway as a key mechanism for WD's protective effect against ethanol-induced GMI. Experimental validation demonstrated that WD treatment reduced the apoptosis of gastric mucosal epithelial cells, promoted the expression of Bcl-2, and inhibited the expression of Bax, Cleaved Caspase-3 and Cleaved Caspase-9. Molecular docking results indicated that dehydroevodiamine, rutaecarpine, evodiamine, hexahydrocurcumin, and isorhamnetin are potential active components in WD that contribute to the inhibition of apoptosis. CONCLUSIONS: WD alleviates ethanol-induced acute GMI, at least in part, by inhibiting the apoptosis. The primary active components responsible for this effect are dehydroevodiamine, rutaecarpine, evodiamine, hexahydrocurcumin, and isorhamnetin.

Drugs, Chinese Herbal↗
PubMed2026

Elucidating the Mechanism of Xiaoqinglong Decoction in Chronic Urticaria Treatment: An Integrated Approach of Network Pharmacology, Bioinformatics Analysis, Molecular Docking, and Molecular Dynamics Simulations.

INTRODUCTION: Xiaoqinglong Decoction (XQLD) is a traditional Chinese medicinal formula commonly used to treat chronic urticaria (CU). However, its underlying therapeutic mechanisms remain incompletely characterized. This study employed an integrated approach combining network pharmacology, bioinformatics, molecular docking, and molecular dynamics simulations to identify the active components, potential targets, and related signaling pathways involved in XQLD's therapeutic action against CU, thereby providing a mechanistic foundation for its clinical application. METHODS: The active components of XQLD and their corresponding targets were identified using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. CU-related targets were retrieved from the OMIM and GeneCards databases. Subsequently, core components and targets were determined via protein-protein interaction (PPI) network analysis and component-target-pathway network construction. Topological analyses were performed using Cytoscape software to prioritize core nodes within these networks. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted via the DAVID database to identify enriched biological processes and signaling pathways. Molecular docking was performed to evaluate binding interactions between key components and core targets, while molecular dynamics (MD) simulations were employed to assess the stability of the component-target complexes with the lowest binding energy. Finally, CU-related targets of XQLD were validated using datasets from the Gene Expression Omnibus (GEO) database. RESULTS: A total of 135 active components and 249 potential targets of XQLD were identified, alongside 1,711 CU-related targets. Core components, such as quercetin, kaempferol, beta-sitosterol, naringenin, stigmasterol, and luteolin, exhibited high degree values in the constructed networks. The core targets identified included AKT1, TNF, IL6, TP53, PTGS2, CASP3, BCL2, ESR1, PPARG, and MAPK3. GO and KEGG pathway enrichment analyses revealed the PI3K-Akt signaling pathway as a central regulatory mechanism. Molecular docking studies demonstrated strong binding affinities between active components and core targets, with the stigmasterol-AKT1 complex exhibiting the lowest binding energy (-11.4 kcal/mol) and high stability in MD simulations. Validation using GEO datasets identified 12 core genes shared between CU-related targets and XQLD-associated targets, including PTGS2 and IL6, which were also prioritized as core targets in the network pharmacology analyses. DISCUSSION: This study comprehensively integrates multidisciplinary approaches to clarify the potential molecular mechanisms of XQLD in treating CU, highlighting its multitarget and multipathway synergistic effects. Molecular docking and dynamics simulations confirm the stable interaction between stigmasterol and the core target AKT1. Additionally, GEO dataset analysis verifies the pathogenic relevance of targets such as PTGS2 and IL6, significantly enhancing the credibility of our findings. These results provide a modern scientific basis for the traditional therapeutic effects of XQLD on CU and have important implications for developing multitarget treatments for this condition. However, this study mainly relies on database mining and computational simulations. Further in vitro and in vivo experimental validations are needed to confirm the predicted component-target-pathway interactions. CONCLUSION: This study identifies the active components, potential targets, and pathways through which XQLD exerts therapeutic effects on CU. These findings provide a theoretical foundation for further mechanistic studies and support their clinical application in the treatment of CU.

Molecular Docking Simulation↗
PubMed1997

Aging and pharmacology.

Research on aging and pharmacology in humans has been termed geriatric clinical pharmacology, which is an established subdiscipline within the broad field of clinical pharmacology. This article reviews information relevant to clinical cancer research and the care of older patients with cancer. Accordingly, the current state of knowledge on drug utilization, pharmacokinetics, pharmacodynamics, adverse drug events, drug interactions, polypharmacy, adherence to treatment, and clinical research considerations are reviewed. Although a review of the literature on aging and cancer chemotherapy is not included in this particular presentation, information is very sparse. Thus, there is significant potential for valuable contributions from clinical research through partnerships between geriatric clinical pharmacologists and medical oncologists.

Aged↗
PubMed1987

Clinical pharmacology and therapeutics education for senior medical students.

In many medical schools instruction of students in clinical pharmacology remains informal and may be inadequate. To determine the short-term efficacy of a mandatory senior medical year course in clinical pharmacology, we compared examination scores of senior students in the College of Medicine, University of Iowa, either prior to or following the Clinical Pharmacology and Therapeutics Lecture Series. A significantly higher (P less than .001) mean score was demonstrated by students taking the examination following the course (75 +/- 4% correct) versus those taking the examination prior to the course (55 +/- 4% correct). To determine student acceptance, postcourse questionnaires were completed. Students surveyed immediately postcourse and alumni surveyed up to four years after graduation highly recommended the course and favored retaining it as a mandatory part of the fourth-year curriculum. This study confirms the efficacy and acceptance of senior medical courses in therapeutics and suggests an effective role for clinical pharmacologists in their design and execution.

Curriculum↗
PubMed1998

Urine drug screening results from volunteers in phase I clinical pharmacology studies: are we being misled?

The general intent of phase I clinical pharmacology studies is to demonstrate the safety and tolerability of investigational new drugs in healthy human volunteers. There is emerging evidence that people who volunteer for these studies are not always truthful with investigators during the screening process. All healthy volunteers who participate in studies at the SmithKline Beecham Clinical Pharmacology Unit in Philadelphia, Pennsylvania, are required to submit to urine drug testing. During 11 months of 1996, a total of 1,469 urine samples were collected and tested for eight different drugs or classes of drugs of abuse. The urine samples collected during the first five months of 1996 were all analyzed using EMIT (Syva Corporation) and interpreted according to the guidelines established by the National Institutes of Drug Abuse (NIDA). Of 534 samples, 12 (2.2%) were reported as positive. During the last 6 months of 1996, a new methodology using a fluorescence polarization immunoassay (FPIA) was used. This assay had lower limits of quantification than EMIT, and more stringent interpretation guidelines than those of the NIDA were used. Of 935 samples analyzed by FPIA, 89 (9.5%) were positive. Of the 89 positive test results, 59 were below the cut-offs specified by the NIDA guidelines and would have been reported as negative. Interpretation of urine drug screen results according to the NIDA guidelines is not acceptable for clinical pharmacology investigations.

Clinical Trials, Phase I as Topic↗
PubMed1988

Bioavailability assessment and pharmacologic response: impact of first-pass loss when both drug and metabolites are active.

Many drugs with low oral bioavailability due to substantial first-pass hepatic loss form pharmacologically active metabolites. In such cases, the pharmacologic activity after oral administration is greater than anticipated from bioavailability data, based on chemical assay of drug alone. This paper explores the use and meaning of pharmacologic data to assess bioavailability under these circumstances. Two steady-state concepts are introduced: a metabolite-to-drug intravenous delivery rate potency ratio and an effective bioavailability, defined as the ratio of intravenous-to-oral delivery rates of drug required to produce the same response. Using a combined pharmacokinetic-pharmacodynamic model, the impact of various factors on the effective bioavailability and on its estimation, using the intravenous-to-oral dose ratio required to produce the same area under the response time curve after acute administration, are explored. It is proposed that attention be centered more on comparison of rates of administration, or doses, that produce equal responses than on bioavailability per se.

Biological Availability↗
PubMed2002

A variable structure, less resource intensive modification of problem-based learning for pharmacology instruction to health science students.

A less resource intensive but more structured modification of problem-based learning was developed to teach pharmacology to pharmacy students in classes of 90 students. The method utilizes an active learning tool developed from cognitive science and cognitive learning theory. This case-based approach was developed to address the need to teach problem-solving skills to relatively large classes while conserving faculty and other resources. The method involves students working through cases in small groups according to a prescribed format. Groups are chosen at random to present the case to the whole class followed by open but structured discussion. Students bring recommended texts to class and groups are asked to answer questions relating to the material in the case, or to determine how the way their approach to the case would differ if patient parameters or medications in the case were altered utilizing the required texts. Each class begins with a short 1-min quiz on the fact-based material to be discussed that day and ends with a wrap-up of critical issues or principles learned. Continual probing of "what" and "why" characterizes each class meeting. Examinations are predominately open book and follow the same format as the in class cases. Learning outcomes for each general topic are provided at the beginning of the semester. Although the method does require students to learn pharmacology "facts", it places the facts within the context of application to practice. Rather than memorizing lists of side effects, for example, the format requires utilizing the side effects list and information about them to appropriately counsel the patient on how to deal with each and/or to suggest modifications in the therapy. Since implementing this method in an endocrine pharmacology course, student performance on problem-solving examinations has improved. Additionally, student evaluation of the method is extremely positive.

Adult↗
PubMed2002

Teaching rational prescribing: a new clinical pharmacology curriculum for medical schools.

In most U.S. and Canadian medical schools, pharmacology is taught during the preclinical year 2 of the 4-year-long curriculum. This is despite the fact that medical school graduates and residency directors have identified teaching rational therapeutics as a priority. Hence, we have developed a core curriculum in clinical pharmacology for 4th-year medical students that builds on the core principles of rational therapeutics described by Nierenberg 10 years ago (Nierenberg, DW. Clin Pharmacol Ther 1990; 48:606-610). Here we report on our 3-year experience teaching this course, which addresses the following teaching objectives: to teach medical students on how to (1) critically evaluate medications; (2) obtain a complete medication history including herbal and over-the-counter medications; (3) apply pharmacokinetic principles to clinical practice; (4) recognize and report adverse drug events and interactions; (5) optimize pain management; (6) recognize and treat substance abuse and poisoning; and (7) prescribe rationally regardless of prescribing environment. Student assessment was in the form of multiple-choice and formative oral examinations, which were validated against the clinical part of the U.S. medical licensing examination. The course significantly increased the student rating of clinical pharmacology teaching measured by a national survey of U.S. medical school graduates. We conclude that this course may be useful for teaching rational prescribing to medical students. With the guidance and educational material provided by this article, a successful implementation of such a course should be possible in most medical schools.

Curriculum↗
PubMed2006

A meta-analysis of ECG data from healthy male volunteers: diurnal and intra-subject variability, and implications for planning ECG assessments and statistical analysis in clinical pharmacology studies.

OBJECTIVE: To evaluate the innate variability in key electrocardiography (ECG) parameters from clinical pharmacology studies. METHODS: Meta-analysis of ECG data from seven clinical pharmacology studies in healthy male volunteers using model building and stepwise multiple regression analyses. RESULTS: Data from 115 male subjects provided over 2,000 observations for all key ECG parameters from baseline (Day-1) and placebo treatment periods (Day 1). Only heart rate and uncorrected QT showed clear and marked changes over the day. QTcB had greater variability compared to QTcF. 1.4% of QTcB and 0.7% QTcF observations were >430 ms and 0.1% of QTcB and 0% of QTcF observations were >450 ms. We estimated that 8.9% of subjects would have at least one out of eight post-observation QTc value in the range 430-450 ms [assuming QTc mean 385 ms, standard deviation (SD) 20 ms] due to intrinsic variability alone. Time-matched within-subjects observations demonstrated that the SD between measurements taken 1 h apart was less than seen with a longer interval, but there was little increase in variability beyond 1 h. The probability of observing an increase in QTc of 30-60 ms in a subject was estimated as 3.0% and 21.8% for one and eight post-dose observations, respectively. The greater the number of observations used to define baseline the narrower the spread; for QTcF the SD of the baseline value was 17.1 ms for a single assessment, 13.3 ms for the mean of three assessments, and 13.2 ms for the mean of all Day-1 assessments. CONCLUSIONS: The spontaneous variability in QTc measurements must be taken into account when designing studies and interpreting analyses of ECG data. The categorical analysis of QTc change of 30-60 ms is unlikely to be of any additional value to analyses of central tendency. For standard early clinical pharmacology studies, QTcF should be chosen as the primary correction method, while the mean of three measures taken in the afternoon and evening of Day-1 and pre-dose Day 1 should provide a reliable and representative baseline assessment.

Adolescent↗
PubMed2007

Fate of the abstracts presented at three Spanish clinical pharmacology congresses and reasons for unpublished research.

OBJECTIVES: To assess the publication rate of abstracts at 5 years after their presentation at three consecutive clinical pharmacology congresses and to examine the reasons relating to the lack of publication. METHODS: Oral and poster presentations from the congresses of the Spanish Society of Clinical Pharmacology (SSCP) in 1994, 1996, and 1998 were reviewed. Authors were contacted to determine the fate of their presented studies and the reasons for not publishing them. Publications of abstracts with unknown fate were searched the in PubMed database. Determinants of publication were examined by Cox regression. RESULTS: In all, 248 abstracts were analysed. The cumulative publication rate at 5 years was 26%, and the median time for publication was 18 months (range: 2-60). The European Journal of Clinical Pharmacology was the English language medical journal where most abstracts were published. The median impact factor of the articles published was 1.96 (range: 0.29-8.32). The author survey identified a lack of time (38.2%) and a lack of interest (33.3%) as the main reasons for failure to publish. The only predictor of an abstract's publication was to be affiliated with a university department (hazard ratio: 1.98, 95% confidence interval: 1.20-3.27). CONCLUSIONS: Only one-quarter of the abstracts presented at SSCP congresses were subsequently published. A lack of time and interest were the main reasons given for not submitting these presentations for publication. Authors, scientific societies and editorial boards should enhance publications as full papers in peer-reviewed journals of the abstracts presented at meetings.

Abstracting and Indexing↗
PubMed1998

Overview of recent topics in clinical pharmacology of anticancer agents.

The rationale for studying the clinical pharmacology of antineoplastic agents is that the information obtained will result in enhanced drug development and enhanced or improved clinical use. A great deal of effort has been expended in studying the pharmacokinetics and pharmacodynamics of investigational and noninvestigational antineoplastic agents. More recently, a deeper appreciation has developed regarding the importance of the metabolism of antineoplastic agents and the potential role of metabolites in their activity or toxicity, as well as the potential for drug-drug interactions. Investigators studying the clinical pharmacology of antineoplastic agents face an increasingly challenging task as new agents continue to be developed. Some of these challenges arise from the enhanced potency of new agents, resulting in increased difficulty in measuring such agents in biological matrices. Furthermore, as agents have been developed to affect specific biological targets, the necessity of assessing pharmacodynamics at the biochemical or molecular level has become increasingly important. In addition, development of agents with cytostatic, as opposed to cytotoxic, properties poses a further challenge to assessment of pharmacologic effect. In addressing these challenges, a great deal of effort has been expended to develop increasingly sensitive analytical chemical techniques, in evaluating alternative biological matrices, such as saliva, in which to monitor drug concentrations in a less invasive fashion, and in developing limited sampling strategies to assess both the pharmacokinetics and pharmacodynamics of antineoplastic agents. Similarly, a great deal of effort has been expended in providing suitable means for assessing the numerous novel targets for which antineoplastic agents are being developed. These include the assessment of cell cycle kinetics and specific oncoproteins, definition of cell damage such as cleavable complexes, and formation of drug-macromolecular adducts in suitable target cells. Additional effort is being expended to explore nontraditional means of drug delivery. In this regard, the increasing importance of orally administered agents reflects a fundamental change in the approach to antineoplastic drug delivery. Finally, the increased computational power made available by faster personal computers has facilitated a number of innovative modeling techniques involving population modeling, modeling of combination chemotherapy, and assessment of drug-drug interactions.

Antineoplastic Agents↗
PubMed2019

Network pharmacology exploration reveals the bioactive compounds and molecular mechanisms of Li-Ru-Kang against hyperplasia of mammary gland.

Li-Ru-Kang (LRK) has been commonly used in the treatment of hyperplasia of mammary gland (HMG) as a cipher prescription and achieved obvious therapeutic effects. However, the bioactive compounds and underlying pharmacological mechanisms remain unclear. This study aims to decipher the bioactive compounds and potential action mechanisms of LRK in the treatment of HMG using an integrated pharmacology approach. The ingredients of LRK and the corresponding drug targets were retrieved through drug target databases and were used to construct the "compound-target-disease" network and function-pathway network. Ultimately, 89 compounds and 2150 drug targets were collected. Gene ontology enrichment analysis revealed that mammary gland alveolus development and mammary gland lobule development were the key biological processes and were regulated simultaneously by three direct targets, including androgen receptor (AR), estrogen receptor (ER) and cyclin-D1. Moreover, 14 compounds of LRK were directly involved in the regulation of the three aforementioned targets. KEGG pathway enrichment analysis found that five signaling pathways and seven direct targets were closely related with HMG treatment by LRK. The results of animal experiments showed that LRK significantly improved the histopathological status of HMG in rats. Additionally, LRK markedly regulated the protein expressions of AR, cyclin-D1, MMP2, MMP3 and MMP9. But interestingly, the effect of LRK on ER was not obvious. This study demonstrated that LRK exerted its therapeutic efficacy based on multi-components, multi-targets and multi-pathways. This research confirms the advantages of network pharmacology analyses and the necessity for experimental verification.

Animals↗
PubMed1988

Developmental pharmacology and toxicology: principles of study design and problems of methodology.

Pharmacologic investigations in the fetus, neonate and child are difficult for the various reasons outlined above, ranging from ethical constraints to difficulties with microanalytic techniques. Attempts to circumvent these difficulties through animal studies, retrospective analyses, and prospective surveys have provided only partial answers. These studies have often helped to guide subsequent similar studies in humans. Results of developmental pharmacologic studies applied to the human must be conducted in humans. The alternatives to randomized, controlled trials presented above may help with these studies, but these innovative study designs must be applied carefully to avoid biasing the results. Although difficult, definitive studies in developmental pharmacology are possible with investigators willing to work within the ethical constraints outlined above, to sensitively consider the needs of perinatal and pediatric patients, and to adhere to the strictest standards of study design.

Animals↗
PubMed1994

The history of pharmacology in Canada.

Pharmacology training in Canada was initiated at McGill University in Montréal in 1824, and there are now 17 pharmacology departments in Canada offering graduate training to more than 500 students. In this article, Gerald Marks reviews the growth of pharmacology in Canada since the early 19th century in both academic establishments and in the pharmaceutical industry.

Canada↗
PubMed1994

Quality education for undergraduates in pharmacology: a Canadian experiment.

Quality education in pharmacology requires the active participation of the student. This article by P.K. Rangachari describes a novel honours programme in biology and pharmacology at McMaster University, Hamilton, Ontario. The pharmacology courses are taught in a problem-based, self-directed and small-group format where students are encouraged to be responsible for seeking and critically assessing knowledge, communicating it effectively and gauging their own progress. These skills are reinforced by placing students in work terms in industry, government and university laboratories. This new programme has received high ratings from students, Faculty and employers.

Canada↗