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Effects of ethanol extract of Bombax ceiba leaves and its main constituent mangiferin on diabetic nephropathy in mice

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Chinese Journal of Natural Medicines 2017年第8期15卷 597-605页

作者： XU Guang-Kai SUN Chen-Yu QIN Xiao-Ying HAN Yu LI Yi XIE Guo-Yong Qin Min-Jian department of Resources Science of Traditional Chinese Medicines State Key Laboratory of Natural MedicinesChina Phar-maceutical UniversityNanjing 211198China department of pharmacology of Chinese Materia Medica China Pharmaceutical UniversityNanjing 211198China

The present study was designed to explore the mechanism by which ethanol extract of Bombax ceiba leaves(BCE) and its main constituent mangiferin(MGF) affect diabetic nephropathy by combating oxidative stress. Oral administration of BCE and MGF to normal and streptozotocin(STZ)-induced diabetic mice were carried out. Fasting blood glucose, 24-h urinary albumin, serum creatinine, and blood urea nitrogen were tested, histopathology, and immunohistochemical analysis of kidney tissues were performed. Moreover, mesangial cells were treated with BCE and MGF for 48 h with or without 25 mmol·L^(-1) of glucose. Immunofluorescence, Western blot and apoptosis analyses were used to investigate their regulation of oxidative stress and mitochondrial function. BCE and MGF ameliorated biochemical parameters and restored STZ-induced renal injury in the model mice. In vitro study showed that high glucose stimulation increased oxidative stress and cell apoptosis in mesangial cells. BCE and MGF limited mitochondrial membrane potential(Δψm) collapse by inhibiting Nox4, mitochondrially bound hexokinase II dissociation, and subsequent ROS production, which effectively reduced oxidative stress, cleaved caspase-3 expression and cell apoptosis. Our work indicated that BCE and MGF had protective effects on diabetic caused kidney injury and prevented oxidative stress in mesangial cells by regulation of hexokinase II binding and Nox4 oxidase signaling.

关键词： Bombax ceiba Mangiferin Diabetic neprropathy Mitochondrial function Oxidative stress

Long-term potentiation in autonomic ganglia:Potential role in cardiovascular disorders

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World Journal of pharmacology 2016年第2期5卷 51-58页

作者： Karim A Alkadhi department of pharmacological and phar-maceutical sciences College of PharmacyUniversity of Houston

Ganglionic long-term potentiation(gLTP) is an activitydependent,enduring enhancement of ganglionic *** phenomenon may be induced in autonomic ganglia of an organism under certain conditions whererepetitive impulses surge from the central nervous system(CNS) to the *** stress,repetitive epileptic seizure or chronic use of CNS stimulants could induce gL TP,which would result in a long lasting heightening of sympathetic tone to the cardiovascular system causing hypertension and disturbed cardiac rhythm that may lead to sudden cardiac *** conditions are briefly reviewed in this article.

关键词： Electrophysiology Epilepsy Ganglionic longterm potentiation Sudden unexpected death in epilepsy Central nervous system stimulants Sudden cardiac death

Design flaws in randomized, placebo controlled, double blind clinical trials

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World Journal of pharmacology 2012年第1期1卷 4-9页

作者： James David Adams Jr department of pharmacology and phar-maceutical sciences University of Southern California School of Pharmacy Los Angeles CA 90089 United States

The hypothesis in drug clinical trials is that the drug is better than a placebo in patients suffering from a disease. The unstated assumption is that the drug cures the disease or is a powerful treatment for the disease. This is an incorrect assumption. Drugs do not cure or treat diseases. The body heals itself; drugs promote this ability of the body to heal itself. Placebos are assumed to be inactive; however, placebos can also promote the ability of the body to heal itself. Placebos are actually treatments that can stimulate endogenous healing mechanisms. The possible place of placebos in health management is controversial. Clinical trial design should be altered. The hypothesis of clinical trials should be that the drug speeds up or improves the healing of the patient, putting patient healing as the first objective. Placebos should not be used as controls but could be tested as drugs in their own right. The control in clinical trials should be no treatment. Alternatively, new drugs could be compared to existing drugs in clinical trials.

关键词： Randomized clinical trials Placebo effect Drug effcacy Healing

Hormone-based pharmacotherapy for metabolic dysfunction-associated fatty liver disease

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Medical Review 2024年第2期4卷 158-168页

作者： Zara Siu Wa Chui Yaqian Xue Aimin Xu State Key Laboratory of pharmaceutical Biotechnology The University of Hong KongHong Kong SARChina department of Medicine The University of Hong KongHong Kong SARChina School of Biomedical sciences The University of Hong KongHong Kong SARChina State Key Laboratory of pharmaceutical Biotechnology The University of Hong Kong999077Hong Kong SARChina department of Medicine The University of Hong Kong999077Hong Kong SARChina department of pharmacology and pharmacy The University of Hong Kong999077Hong Kong SARChina

Metabolic dysfunction-associated fatty liver disease(MAFLD)has reached epidemic proportions globally in parallel to the rising prevalence of *** its significant burden,there is no approved pharmacotherapy specifically tailored for this *** potential drug candidates for MAFLD have encountered setbacks in clinical trials,due to safety concerns or/and insufficient therapeutic ***,several investigational drugs that mimic the actions of endogenous metabolic hormones,including thyroid hormone receptorβ(THRβ)agonists,fibroblast growth factor 21(FGF21)analogues,and glucagon-like peptide-1 receptor agonists(GLP-1RAs),showed promising therapeutic efficacy and excellent safety *** them,resmetirom,a liver-targeted THRβ-selective agonist,has met the primary outcomes in alleviation of metabolic dysfunction-associated steatohepatitis(MASH),the advanced form of MAFLD,and liver fibrosis in phase-3 clinical *** hormone-based pharmacotherapies not only exhibit varied degrees of therapeutic efficacy in mitigating hepatic steatosis,inflammation and fibrosis,but also improve metabolic ***more,these three hormonal agonists/analogues act in a complementary manner to exert their pharmacological effects,suggesting their combined therapies may yield synergistic therapeutic *** in-depth studies on the intricate interplay among these metabolic hormones are imperative for the development of more efficacious combination therapies,enabling precision management of MAFLD and its associated comorbidities.

关键词： metabolic hormones metabolic dysfunctionassociated steatohepatitis(MASH) liver fibrosis biopharmaceutical development clinical trials

Valproic acid as a micro RNA modulator to promote neurite outgrowth

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Neural Regeneration Research 2016年第10期11卷 1564-1565页

作者： Hirotaka Oikawa Judy C.G.Sng Neuroepigenetics Laboratory Singapore Institute for Clinical Sciences Agency for Science and Technology (A*STAR) department of pharmacology Yong Loo Lin School of Medicine National University of Singapore

Valproic acid （VPA） has been a first-choice drug for clinical treatment of epilepsy and manic disorder. For decades, its phar- macological action was believed to act on inhibition of gam- ma-aminobutyric acid （GABA） transaminase, in turn, increas- ing GABA in inhibitory synapses. However, in recent years, VPA has been investigated on other therapeutic actions. Those investigations demonstrate that VPA shows neuroprotective ef- fects by promoting neurogenesis, neuronal differentiation, and neuroregeneration （Foti et al., 2013）.

关键词： VPA RNA Valproic acid as a micro RNA modulator to promote neurite outgrowth acid

Effects and mechanisms of Cryptotanshinone on rats with adjuvant arthritis

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Chinese Medical Journal 2011年第24期124卷 4293-4298页

作者： ZHENG Fu-lin CHANG Yan JIA Xiao-yi HUANG Min WEI Wei department of phar-macology Medical College Anhui Universityof Science and Technology Huainan Anhui 232001 China Institute of Clinical pharmacology Anhui Medical UniversityHefei Anhui 230032 China School of pharmaceutical sciences Sun Yat-sen UniversityGuangzhou Guangdong 510006 China

Background Cryptotanshinone （CT） is the major active constituent of Salvia miltiorrhiza Bunge. The present study was carried out to investigate the effects of CT on rats with adjuvant arthritis （AA）. Methods AA was induced by the metatarsal footpad injection with complete Freund＇s adjuvant in male Sprague-Dawley rats. The secondary inflammatory reaction was evaluated by hind paw swelling and the polyarthritis index. Activity of interleukin-1 （IL-1） was detected by the concanavalin A-induced thymocytes proliferation assay. The lymphocytes proliferation and IL-2 production were assayed by 3-（4,5-2dimethylthiazal-2yl）2,5-diphenyltetrazoliumbromide （MTT） and activated mouse splenocytes proliferation, respectively. Results Intragastric administration of CT （50 and 100 mg/kg） significantly decreased secondary inflammatory reactions and increased the spleen and thymus index. There was a marked immunologic and inflammatory response in the AA model, which was accompanied by the decrease of thymocyte proliferation and IL-2 production as well as the increase of IL-1 production. CT apparently enhanced thymocyte proliferation and decreased IL-1 production in AA rats. Conclusion These results indicate that CT may exert its anti-inflammatory and immunoregulatory effects through inhibiting lymphocyte proliferation and production of pro-inflammatory mediators.

关键词： cryptotanshinone adjuvant arthritis lymphocyte proliferation cytokine

Harnessing pharmacological knowledge for personalized medicine and pharmacotyping: Challenges and lessons learned

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World Journal of pharmacology 2014年第4期3卷 110-119页

作者： Ioannis S Vizirianakis Laboratory of pharmacology Department of Pharmaceutical Sciences School of Health Sciences Aristotle University of Thessaloniki GR-54124 Thessaloniki Greece

The contribution of the genetic make-up to an individual’s capacity has long been recognized in modern pharmacology as a crucial factor leading to therapy ineffciency and toxicity, negatively impacting the economic burden of healthcare and restricting the monitoring of diseases. In practical terms, and in order for drug prescription to be improved toward meeting the personalized medicine concept in drug delivery, the maximum clinical outcome for most, if not all, patients must be achieved, i.e. , pharmacotyping. Such a direction although promising and of high expectation from the society, it is however hardly to be afforded for healthcare worldwide. To overcome any existed hurdles, this means that practical clinical utility of personalized medicine decisions have to be documented and validated in the clinical setting. The latter implies for drug delivery the effcient implementation of previously gained in vivo pharmacology experience with pharmacogenomics knowledge. As an approach to work faster and in a more productive way, the elaboration of advanced physiologically based phar-macokinetics models is discussed. And in better clarifying this topic, the example of tamoxifen is thoroughly presented. Overall, pharmacotyping represents a major challenge in modern therapeutics for which pharmacologists need to work in successfully fulflling this task.

关键词： pharmacology pharmacogenomics Personalized medicine pharmacokinetics pharmacodynamics pharmacotyping Translational medicine Drug delivery Education Curricula

Nanotechnology-based therapeutics: new hope for ischemic cerebral stroke intervention

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Journal of Translational Neuroscience 2020年第1期5卷 8-17页

作者： Sihan Wang Qiming Gao Fuyao Xiao Yuming Zhao department of pharmacology School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China

Ischemic cerebral stroke is a leading cause of death and disability *** present,thrombolytics,such as recombinant tissue-type plasminogen activator,are the only effective treatment for acute ***,usage of thrombolytics has a strict therapeutic window and cannot be applied to a number of *** the promising effects of some neuroprotectants in preclinical studies,they failed in clinical trials as a result of poor pharmacokinetic properties,particularly with regard to solubility and permeability across the blood-brain barrier(BBB).Approaches for delivering these drugs by nanotechnologies may overcome these pharmacokinetic deficits and enhance their neuroprotective ***,issues such as potential side effects and biosafety properties currently limit clinical application of these *** this article,we reviewed recent progress of nanotechnology-based interventions for stroke treatment,and in particular,summarized novel materials applied to synthesize nanocarriers,encapsulation with neuroprotectants,and factors impacting nanodrug bioactivities to provide a theoretical basis for the development of anti-stroke drugs.

关键词： ischemic cerebral stroke blood-brain barrier(BBB) nanoparticles drug delivery neuroprotection

Statin use and the risk of colorectal cancer: A population-based case-control study

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World Journal of Gastroenterology 2011年第47期17卷 5197-5202页

作者： Meng-Hsuan Cheng Hui-Fen Chiu Shu-Chen Ho Shang-Shyue Tsai Trong-Neng Wu Chun-Yuh Yang Division of Pulmonary and Critical Medicine Department of Internal Medicine Kaohsiung Medical University Hospital Graduate Institute of Medicine Kaohsiung Medical University department of Internal Medicine PingTung HospitalDepartment of Health Executive Yuan Institute of pharmacology College of Medicine Kaohsiung Medical University Institute of Occupational Safety and Health College of Health Sciences Kaohsiung Medical University department of Healthcare Administration I-Shou University department of Public Health China Medical University Division of Environmental Health and Occupational Medicine National Health Research Institute Faculty of Public Health College of Health Sciences Kaohsiung Medical University

AIM: To investigate whether the use of statins is associated with colorectal cancer risk. METHODS: We conducted a population-based case-control study in Taiwan. Data were retrospectively collected from the Taiwan National Health Insurance Research Database. Cases consisted of all patients who were aged 50 years and older and had a first-time diagnosis of colorectal cancer between the period 2005 and 2008. The controls were matched to cases by age, sex, and index date. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multiple logistic regression. RESULTS: We examined 1156 colorectal cancer cases and 4624 controls. The unadjusted ORs for any statin prescription was 1.10 (95% CI = 0.94-1.30) and the adjusted OR was 1.09 (95% CI = 0.91-1.30). When statin use was categorized by cumulative dose, the adjusted ORs were 0.99 (95% CI = 0.78-1.27) for the group with cumulative statin use below 105 defined daily doses (DDDs); 1.07 (95% CI = 0.78-1.49) for the group with cumulative statin use between 106 and 298.66 DDDs; and 1.30 (95% CI = 0.96-1.75) for the group with cumulative statin use of 298.66 DDDs or more compared with nonusers. CONCLUSION: This study does not provide support for a protective effect of statins against colorectal cancer.

关键词： Case-control study Colorectal cancer phar-macoepidemiology Statins