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PubMed2026

Network pharmacology insights into the mechanistic basis of Taohe Chengqi Decoction in the treatment of constipation.

Constipation is a common gastrointestinal disorder associated with impaired motility, inflammation, and altered neuro-intestinal regulation. Taohe Chengqi Decoction, a classical prescription from Shang Han Lun, has been widely applied in the treatment of constipation, yet its pharmacological mechanisms remain insufficiently understood. We integrated systems pharmacology and network analysis to elucidate the therapeutic mechanisms of Taohe Chengqi Decoction against constipation. Active compounds and their putative targets were retrieved from traditional Chinese medicine systems pharmacology and PubChem, while constipation-related genes were collected from GeneCards and OMIM. Shared targets were identified and subsequently analyzed using STRING to construct a protein-protein interaction network. Hub proteins were ranked by degree centrality. A drug-disease-target network was built to map the interactions between Taohe Chengqi Decoction and constipation. Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses were performed to uncover functional modules and signaling pathways. A total of 188 common targets were identified. Protein-protein interaction network analysis highlighted AKT1, interleukin-6 (IL6), IL1B, and JUN as hub proteins, suggesting central roles in regulating inflammation, apoptosis, and signal transduction. Additional nodes with high connectivity, such as caspase-3, PTGS2, signal transducer and activator of transcription 3, hypoxia-inducible factor-1α, estrogen receptor 1, and epidermal growth factor receptor, were implicated in apoptosis, oxidative stress, and transcriptional regulation. The drug-disease-target network revealed a dense and highly interconnected structure, reflecting the multicomponent, multi-target nature of Taohe Chengqi Decoction. Kyoto encyclopedia of genes and genomes enrichment indicated significant involvement of the advanced glycation end-product binding to their receptor signaling pathway, along with IL-17, TNF, and HIF-1 pathways, underscoring the contribution of inflammatory and oxidative stress-related processes. This study, based on computational pharmacology analysis, predicts that Taohe Chengqi Decoction may exert therapeutic effects on constipation through an integrated regulation involving multiple components, targets, and pathways. The potential mechanisms are likely associated with the modulation of inflammatory responses, apoptosis, and oxidative stress, with the advanced glycation end-product binding to their receptor signaling pathway possibly acting as a key mediator. These findings provide theoretical insights and future directions for elucidating the molecular mechanisms underlying the therapeutic effects of Taohe Chengqi Decoction against constipation.

Drugs, Chinese Herbal↗
PubMed2025

Network pharmacology approach to unveiling the mechanism of berberine in the amelioration of morphine tolerance.

OBJECTIVE: To investigate the mechanism underlying the effect of the Huanglian decoction (, HLD) on morphine tolerance (MT), using network pharmacology, and to verify these mechanisms in vitro and in vivo. METHODS: Available biological data on each drug in the HLD were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. The target proteins of MT were retrieved from the GeneCards, PharmGkb, Therapeutic Target Database, DrugBank, and Online Mendelian Inheritance in Man databases. Information regarding MT and the drug targets was compared to obtain overlapping elements. This information was imported into the Search Tool for the Retrieval of Interacting Genes/Proteins platform to obtain a protein-protein interaction network diagram. Then, a "component-target" network diagram was constructed using screened drug components and target information, viaCytoscape (Institute for Systems Biology, Seattle, WA, USA). The database for annotation, visualization, and integrated discovery was used for Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathways analyses. Pathway information predicted by network pharmacology was verified using animal studies and cell experiments. RESULTS: Network pharmacology analysis identified 22 active compounds of HLD and revealed that HLD partially ameliorated MT by modulating inflammatory, apoptosis, and nuclear factor kappa B (NF-κB) signaling pathways. Berberine (BBR), one of the main components of HLD, inhibited the development of MT in mice. BBR reduced cell viability while increasing B-cell lymphoma 2 (Bcl-2) protein expression and decreasing CD86, NF-κB, Bax, and Caspase-3 protein expression in brain vascular 2 (BV2) mcroglia cells treated with morphine. Additionally, BBR contributed to a reduction in pro-inflammatory cytokine release and apoptotic cell number. CONCLUSIONS: BBR, a key component of HLD, effectively suppressed microglial activation and neuro-inflammation by regulating the NF-κB and apoptosis signaling pathways, thereby delaying MT. This study offers a novel approach to enhance the clinical analgesic efficacy of morphine.

Berberine↗
PubMed2026

Validation of the Mechanism of Action of Jiedu Shengji Oil in the Treatment of Radiation Dermatitis based on Network Pharmacology and In vivo Experiments.

BACKGROUND: Radiation Dermatitis (RD) is a common complication of radiation therapy, with approximately 90% of patients experiencing moderate to severe radiation dermatitis injury after radiotherapy. Jiedu Shengji oil (JDSJY) is a commonly used herbal topical preparation in our hospital, with remarkable clinical efficacy in treating radiation dermatitis. However, the mechanism of JDSJY in treating RD is unclear. AIMS: The aim of the study is to explore JDSJY's mechanism of action in treating RD through methods, such as network pharmacology and in vivo experiments. METHODS: The active components and disease targets of JDSJY were screened and intersected via network pharmacology for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The pharmacodynamics of JDSJY was evaluated by establishing a rat model of RD. RESULTS: Network pharmacology showed that the pathway network of JDSJY action involved 64 targets and 6 pathways and might act by targeting key targets, such as C-reactive protein (CRP) and regulating the MAPK signalling pathway. In addition, in vivo experiments showed that JDSJY reduced skin inflammation and inhibited apoptosis, significantly ameliorated mitochondrial damage in keratinocytes, and reduced the levels of antioxidant-related indicators. CONCLUSION: Comprehensive network pharmacology and in vivo experiments revealed that JDSJY's therapeutic efficacy in RD is mediated by ameliorating oxidative stress and maintaining mitochondrial homeostasis in keratinocytes.

Animals↗
PubMed2004

Learning of medical pharmacology via innovation: a personal experience at McMaster and in Asia.

Pharmacology, a discrete preclinical discipline of the traditional medical curriculum, identifies itself distinctly different from the other preclinical or clinical subjects in knowledge base as well as learning/teaching instructions. It exists in series with other pre-clinical courses (e.g., anatomy, biochemistry and physiology), and in parallel with other paraclinical courses such as pathology, microbiology and community medicine. Such arrangement makes learning of pharmacology rather difficult and deficient with regard to its therapeutic relevance and clinical application. In recent years, medical curricula based on clinical cases have emerged as a platform in which pharmacology is one integrated component in a holistic approach to medical education. In this problem-based learning (PBL) model, students learn, with teachers' facilitation, in a student-centered environment, based on self-directed, clinically relevant and case-oriented approach, usually in a small-group tutorial format. In PBL, pharmacology is learned in concert with other subject issues relevant to the case-problem in question, such as anatomy, physiology, pathology, microbiology, population health, behavior science, etc. Students learn via problem-evoked curiosity and motivation, in an environment which encourages free inquiries and intensive discussions in a cooperative rather than competitive atmosphere. Teachers facilitate students' learning objectives rather than deliver pre-packed knowledge and dictate what they think students should learn. A change towards PBL curriculum appears to be beneficial in better preparing the medical students as life-long learners capable of coping with changes in knowledge and skills associated with the progressive and dynamic social/economic transformation in the Asia-Pacific regions. Evidence is presented that this is indeed happening.

Asia↗
PubMed1981

History of clinical pharmacy and clinical pharmacology.

The purpose of the Symposium on Clinical Pharmacy and Clinical Pharmacology is to describe the present and future functional roles of clinical pharmacists and clinical pharmacologists in drug research, professional education, and patient care. Clinical pharmacy is a relatively new professional discipline, being only about 15 years old. This new breed of pharmacists is patient rather than drug product oriented. The discipline arose out of dissatisfaction with old practice norms and the pressing need for a health professional with a comprehensive knowledge of the therapeutic use of drugs. The clinical pharmacy movement began at the University of Michigan in the early 1960s, but much of the pioneering work was done by David Burkholder, Paul Parker, and Charles Walton at the University of Kentucky in the latter part of the 1960s. Clinical pharmacology is a professional discipline that combines basic pharmacology and clinical medicine. Its development began in the early 1950s, primarily as a result of the efforts of Harry Gold. It has had a slower growth than clinical pharmacy but it has made many important contributions to our knowledge of human pharmacology and the rational use of drugs.

Drug Information Services↗
PubMed1988

Academic-industrial cooperative graduate program in clinical pharmacology.

Because a new level of sophistication among clinical investigators is necessary for the testing of new agents in human subjects, a close integration of basic science, clinical medicine, and pharmaceutical medicine is required. Experts from the Departments of Pharmacology and Medicine at Temple University School of Medicine and Smith Kline and French Laboratories have combined to form a joint training program in clinical pharmacology. This structured graduate program for physicians couples didactic courses with a defined program of independent research, leading to a Master of Science degree in pharmacology. The development of new technologies and the transfer of them from the "bench to the bedside" demands that the clinician have special competence in clinical pharmacology. This unique joint academic-industrial program sets the goals ensuring that this objective is met.

Clinical Trials as Topic↗
PubMed1993

Pediatric pharmacology: the path clears for a noble mission.

Unlabeled use of drugs in children occurs frequently and contributes to the therapeutic orphan dilemma. This situation can no longer be condoned; few acceptable reasons still exist for not evaluating potentially effective drug therapy in children. An apparent lack of research funds is not one of these reasons; only allocation of these funds to pediatric pharmacology is found wanting. Availability of clinical pharmacology programs, pediatric pharmacology manpower, sensitive analytical techniques, and acceptable ethical approaches to pediatric research reveal that drug evaluation is feasible in children. Studies readily include the required therapeutic indication for drug use in pediatrics. Efforts of academia, government and industry are now converging to show that the path for the noble mission of pediatric pharmacology--rational use of FDA approved drugs for children--is now clear for action.

Child, Preschool↗
PubMed1995

Experience-based teaching of therapeutics and clinical pharmacology of antiepileptic drugs. Sudden unexplained death in epilepsy: do antiepileptic drugs have a role?

The contents of this paper have been written to be used in a teaching program specifically designed for medical postgraduate education of resident physicians and fellows in training interested in the clinical pharmacology of antiepileptic drugs and their role in the treatment of epilepsy and/or in the prevention of sudden unexpected death associated with this disease. With some modifications, such as a specific lecture to provide an overview of the numerous concepts presented in the text, the article could be used when teaching fourth-year medical students. The format of the paper is a combination of didactic review and eight case reports in a self-learning format. A quiz for self-assessment is included at the end of the article (see Appendix). This material was covered in part in the 1992 Board Review Course for Clinical Pharmacology sponsored by the American College of Clinical Pharmacology. The format or setting of instruction for this material could include small learning groups composed of 10 to 15 students. When used in combination with other topics prepared in similar formats, this could become a take home course for those preparing to take the Boards in Clinical Pharmacology. Each instructor could select specific publications from the reference list for assigned readings depending upon the material emphasized by the instructor. The questions included at the end of the text could be used as either a closed or an open book quiz to assess student learning.

Adolescent↗
PubMed2003

Hemoperfused isolated porcine slaughterhouse kidneys as a valid model for pharmacological studies.

Mammalian models of isolated perfused kidneys provide an important tool to study pharmacological, toxicological, and physiological properties of drugs, hormones, and vasoactive substances. As organs from small laboratory animals are difficult to compare to human conditions, porcine and bovine kidneys permit better approaches to simulate human conditions. We developed an alternative model for pharmacological studies using isolated hemoperfused porcine kidneys from slaughterhouse animals to reduce laboratory animal experiments. Controlled pharmacological studies were established using furosemide (2 mg/100 g organweight) as a model drug. Kidneys were hemoperfused after a preservation period of 4.6 +/- 1.7 h. In comparison to the control period, furosemide application led to significant changes in renal parameters with urine flow: 4.2/1.7 mL/min*100 g (furosemide/control), urine-sodium: 108/77.5 mmol/L, sodium excretion: 0.47/0.14 mmol/min*100 g; all differences significant, p < 0.01. The parameters stabilized to normal values as found in the control period within a period of 80 min. A second group of laboratory-harvested kidneys was examined for differences and revealed limitations of the slaughterhouse organs in parameters such as oxygen consumption. In summary, the present study demonstrates the valid use of hemoperfused slaughterhouse kidneys as a pharmacological model of renal function within the limits of the use of slaughterhouse organs, and indicates that future studies using this alternative approach could reduce animal experiments.

Animals↗
PubMed1999

[Responsibilities of clinical pharmacology in the early phase of drug development].

The path of a new drug from the idea to the product may be divided into 2 phases, namely drug discovery and drug development. Due to the scientific progress new and simple methods could be developed to determine the biological efficacy of a large number of compounds. During the first part of drug development necessary requirements for the first use in man are met by performing preclinical pharmacological, toxicological and pharmacokinetic investigations in the animal and in in-vitro testing. After a first clinical-pharmacological profile of the new substance has been established during phase I on the basis of which a decision for the continuation of the clinical trial is made, the aim of phases II and III is now to answer the important questions of the therapeutic efficacy and tolerability in a large number of patients with the target indication. Due to the continuously increasing time and costs of drug development, drug development should be streamlined combining preclinical and early clinical phases as an exploratory stage and later clinical development as a confirmatory stage. The development and appropriate use of surrogates and models may be helpful to determine drug actions in human and to assist in dose selection as the main requirement for a successful large clinical trial in the confirmatory stage. Identifying the genes responsible for the huge variations in how different patients respond to a drug, in terms of both the product's effectiveness and its side effects, and genotyping patients before including in large clinical trials may prevent selecting the wrong patient population and avoid expensive repetition of these studies. Taking responsibility as the link between research and development gives clinical pharmacology a major opportunity to assume a pivotal role in drug development. To reach this goal, clinical pharmacology must be fully integrated in the whole process of drug development from the candidate selection until the approval.

Animals↗
PubMed2002

Teaching pharmacology within a multidisciplinary organ system-based medical curriculum.

We have described how the pharmacology of agents that act on the central nervous system (CNS) and endocrine system were incorporated into a case-based, multidisciplinary, integrated sophomore medical curriculum at Southern Illinois University School of Medicine (SIUSM). Faculty members from the Departments of Pharmacology, Pathology, Internal Medicine, Psychiatry, and Neurology were major participants in the CNS block, and faculty with primary expertise in radiology, epidemiology, and immunology also participated. Integrated sessions involving the entire class were organized around brief patient cases, which were given to the students in advance of the session. During the sessions, each patient case was presented by a physician or pathologist who briefly described symptoms, history, physical findings, differential diagnosis, and the classification of the subtypes of the particular class of disorder. The pathophysiology of the disease was discussed, and the pharmacology of agents to be considered for therapy was presented in the context of the Pharmacology Mental Algorithm, a systematic and rational approach to drug therapy. The session was completed by a clinician who added further clinically relevant information, which was followed by a question-and-answer period involving all faculty participants. The CNS block was presented over a 1-month period and included standardized patients and real patients who consistently exhibited specific disease findings, and these patient-oriented sessions were followed with small group tutorial sessions. Single discipline large-group sessions were also used to present material that is introductory or unique to a particular discipline. Student knowledge was assessed, using integrated evaluations based on case vignettes with multiple-choice questions provided by each discipline. The goal of the examination was to evaluate knowledge base in the discipline areas and its application to clinical problem-solving. A practical evaluation of each student's patient examination skills in CNS was also performed by clinicians. Feedback from the students on the organ system activities was obtained using a questionnaire. Development of these sessions required leadership and a considerable amount of time to organize, improve, and update sessions. The integrated approach largely eliminated the use of conflicting terminology and redundancy of material common with separate presentations on the same subject by different disciplines. The multidisciplinary, case-based sessions were perceived to be instructive, valuable learning experiences, based on formal and informal student and faculty feedback.

Adolescent↗
PubMed1999

The past, present and future of clinical pharmacology.

Four decades of clinical pharmacological research (1960-2000) have emphasized different aspects of the discipline from controlled clinical trial and drug metabolism during the early 1960s to molecular pharmacogenetics and pharmacoeconomy during the late 1990s. Clinical pharmacology is not only a research discipline, but also a clinical specialty in its own right with functions in health care that focus on the rational use of drugs by physicians and patients. Clinical pharmacology should bridge the gap between product specialists and prescribers by emphasizing both pharmacological and medical aspects of drug treatment. A recent review of the development of the discipline in Europe shows satisfactory progress in several countries, but active recruitment of young physicians to the discipline is necessary to avoid a shortage of clinical pharmacologists in the future.

Europe↗
PubMed1994

Wither, whether and whither pharmacology.

There has been considerable discussion over the last couple of years about the nature of pharmacology as a discipline and the training programmes for pharmacologists. Recently the British Pharmacological Society devoted a whole symposium to this important issue. In the UK in particular, pressure from government has nearly doubled the number of undergraduate students entering the university sector over the last five years, which has put considerable pressure on the teaching of essential practical courses for this experimental discipline. Similar pressures face the teaching of pharmacology in other countries and the situation, discussed here by Clive Page, Morley Sutter and Michael Walker, clearly has implications for academic pharmacology and the pharmaceutical industry. It is intended that the following article will stimulate both dialogue and positive action towards redressing this important problem.

Animals↗
PubMed2006

A brief history of British Pharmacological Society meetings.

The British Pharmacological Society (BPS) is currently celebrating its 75th anniversary. It is therefore a young society compared with some other biomedical societies and particularly when compared with the origins of the oldest learned societies. In this article, I briefly review the origins of learned societies and examine the rise of pharmacology in the UK, as reflected in the scientific meetings of the BPS. The rapid growth of British pharmacology and clinical pharmacology in the 1970s and 1980s and changes in the way that scientific literature is published have resulted in the BPS having to adapt quickly in the way that its meetings are run. However, evidence suggests that the Society will continue to move strongly and confidently towards its 100th birthday.

Congresses as Topic↗
PubMed1996

Survey of clinical pharmacology training in the United States and Canada.

A survey of 139 medical schools in the United States and Canada was conducted in 1993-1994 to determine where active training programs in clinical pharmacology were located. A secondary survey of clinical pharmacology program directors followed in 1994-1995. Thirty-nine active programs were identified where 113 fellows (84 physicians and 29 nonphysicians) were enrolled. Sixty-eight percent of current physician fellows were trained in internal medicine before they entered their clinical pharmacology program. Forty-four percent of trainees were reported to be U.S. citizens. Fewer than 20 fellows complete training each year. The reported content of training programs was 12% didactic, 72% research, 12% clinical service, and 9% supervised teaching. Funding sources for trainees varied considerably. Nearly 50% of trainees were supported all or in part by funds from the National Institutes of Health (NIH), and approximately 40% relied on international sources of support. No correlation between salary and funding source or fellow degree was found. Nearly two-thirds of recent program graduates obtained employment in an academic setting, whereas 15% entered the pharmaceutical industry. These data indicate that subspecialty training in clinical pharmacology is available at 39 medical schools in the United States and Canada. Current fellowship training is primarily research based and nearly equally supported by NIH and international sources.

Canada↗
PubMed2002

Fuzzy pharmacology: theory and applications.

Fuzzy pharmacology is a term coined to represent the application of fuzzy logic and fuzzy set theory to pharmacological problems. Fuzzy logic is the science of reasoning, thinking and inference that recognizes and uses the real world phenomenon that everything is a matter of degree. It is an extension of binary logic that is able to deal with complex systems because it does not require crisp definitions and distinctions for the system components. In pharmacology, fuzzy modeling has been used for the mechanical control of drug delivery in surgical settings, and work has begun evaluating its use in other pharmacokinetic and pharmacodynamic applications. Fuzzy pharmacology is an emerging field that, based on these initial explorations, warrants further investigation.

Animals↗
PubMed1987

A study of training in clinical pharmacology of the elderly.

Training of physicians in geriatrics is essential to improving health care for the elderly. Considering the frequent use, cost, and side effects of drugs in the elderly, knowledge in clinical pharmacology is an important component of that training. The present study surveyed 68 geriatric medicine, 27 geropsychiatry, and 46 clinical pharmacology fellowship programs in the United States for the clinical geropharmacology content of their programs. In geriatric medicine, 73% of the programs had formal didactic material, 58% had formal training in this area during clinical experiences, and 43% formally interacted with clinical pharmacology faculty or fellows. In geropsychiatry these numbers were 79%, 67%, and 31%, respectively. In clinical pharmacology, 34% of the programs had formal didactic content, 9% had clinical experience on a specific geriatrics unit, and 14% had clinical experiences in a long-term care facility. Although some training in clinical geropharmacology exists in fellowship training programs, clearly there is much room for expansion and improvement in this important area of health care of the elderly.

Fellowships and Scholarships↗
PubMed2001

Continuing Medical Education in Clinical Pharmacology and Therapeutics: report of a questionnaire survey.

AIMS: To seek the views of medically qualified members of the Clinical Section of the British Pharmacological Society (BPS) on their perceived needs for Continuing Medical Education (CME); on how and by whom these needs should be addressed; and on how the outcome of any educational intervention might best be assessed. METHODS: A structured questionnaire. RESULTS: Of 233 recipients, 140 (60%) responded, but only 123 of these fulfilled the criteria for analysis. A large majority of respondents were clinicians, most of whom devoted at least 25% of their working week to their NHS commitment. There was widespread reliance on textbooks and journals as sources of CME, supplemented by discussions with specialist peers at national and international meetings. Many felt that fulfilling even this agenda was stretching their commitment to the limit, and their greatest need was for protected time in which to learn. There was a desire among 49% of all respondents for the BPS Clinical Section to take some responsibilty for addressing the future needs of its members, and 75% took the view that academic departments should contribute to the development and updating of materials. There was no clear agreement about what these should comprise, but around half of all respondents favoured web-based, journal-based or computer-assisted educational material offering self-assessment opportunities; and CME symposia or workshops at BPS meetings. Almost half (46%) felt that assessment of CME should be integrated with a well-organized appraisal system and the use of portfolios. Six out of 10 respondents were already, or were about to be, regularly appraised at their place of work. CONCLUSIONS: The questionnaire survey revealed a broad canvas of views and little evidence of consensus except for a general plea for more time in which to learn. The aim of the Clinical Section should be to facilitate and help its members to organize their learning, in a way that is consistent with national trends in Continuing Professional Development. The Clinical Section should co-ordinate the setting up of an electronic library of appropriate published material, compiled by academic and industrial sources, that would guide members seeking up-to-date knowledge of Clinical Pharmacology and Therapeutics. The British Journal of Clinical Pharmacology (BJCP) should commission review articles on recent developments where no suitable published material exists. Academic departments should also be invited to identify or develop self-assessment material that members could use to reinforce their learning, and demonstrate their knowledge to relevant professional bodies. The Clinical Section should organize Symposia and Workshops at which contentious issues in Clinical Pharmacology and Therapeutics can be discussed and resolved.

Education, Medical, Continuing↗