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Tanshinone IIA ameliorates energy metabolism dysfunction of pulmonary fibrosis using 13C metabolic flux analysis

Journal of Pharmaceutical Analysis 2024年第2期14卷 244-258页

作者： Baixi Shan Haoyan Zhou Congying Guo Xiaolu Liu Mingyu Wu Rao Zhai Jun Chen State Key laboratory of Natural Medicines China Pharmaceutical UniversityNanjing210009China Department of pharmacognosy School of Traditional Chinese PharmacyChina Pharmaceutical UniversityNanjing210009China

Evidence indicates that metabolic reprogramming characterized by the changes in cellular metabolic patterns contributes to the pathogenesis of pulmonary fibrosis (PF). It is considered as a promising therapeutic target anti-PF. The well-documented against PF properties of Tanshinone IIA (Tan IIA) have been primarily attributed to its antioxidant and anti-inflammatory potency. Emerging evidence suggests that Tan IIA may target energy metabolism pathways, including glycolysis and tricarboxylic acid (TCA) cycle. However, the detailed and advanced mechanisms underlying the anti-PF activities remain obscure. In this study, we applied [U-13C]-glucose metabolic flux analysis (MFA) to examine metabolism flux disruption and modulation nodes of Tan IIA in PF. We identified that Tan IIA inhibited the glycolysis and TCA flux, thereby suppressing the production of transforming growth factor-β1 (TGF-β1)-dependent extracellular matrix and the differentiation and proliferation of myofibroblasts in vitro. We further revealed that Tan IIA inhibited the expression of key metabolic enzyme hexokinase 2 (HK2) by inhibiting phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/hypoxia-inducible factor 1α (HIF-1α) pathway activities, which decreased the accumulation of abnormal metabolites. Notably, we demonstrated that Tan IIA inhibited ATP citrate lyase (ACLY) activity, which reduced the collagen synthesis pathway caused by cytosol citrate consumption. Further, these results were validated in a mouse model of bleomycin-induced PF. This study was novel in exploring the mechanism of the occurrence and development of Tan IIA in treating PF using 13C-MFA technology. It provided a novel understanding of the mechanism of Tan IIA against PF from the perspective of metabolic reprogramming.

关键词： Pulmonary fibrosis Tanshinone IIA 13C-metabolic flux analysis Metabolic reprogramming

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Flavonoid chemical composition and antidiabetic potential of Brachychiton acerifolius leaves extract

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Asian Pacific Journal of Tropical Biomedicine 2017年第5期7卷 389-396页

作者： Aisha Hussein Abou Zeid Mohamed Ali Farag Manal Abdel Aziz Hamed Zeinab Abdel Aziz Kandil Radwa Hassan El-Akad Hanaa Mohamed El-Rafie pharmacognosy Department National Research Centre pharmacognosy Department College of PharmacyCairo University therapeutic chemistry Department National Research Centre

Objective:To evaluate Brachychiton acerifolius leaf extracts as antidiabetic potential agent and to identify the main active constituents using bioactivity guided ***:In vitro antioxidant activity was evaluated for *** different extracts using DPPH assay and vitamin C as *** activity was then determined using STZ-induced rats treated daily with ethyl acetate and 70% ethanol leaf extracts for4 weeks at a dose of 200 g/kg body weight against gliclazide reference *** glucose,a-amylase,lipid profile,liver function enzymes and oxidative stress markers were assessed along with histopathological study for liver and pancreatic *** and structural elucidation of active compounds were made using Diaion and Sephadex followed by spectral ***:The results indicated that ethyl acetate and ethanol leaf extracts exhibited the strongest antioxidant activity compared to that of vitamin C(IC500.05,0.03 and 12 mg/m L,respectively).Both extracts showed potent anti-hyperglycemic activity evidenced by a significant decrease in serum glucose levels by 82.5% and 80.9% and a-amylase by45.2% and 53.6%,as compared with gliclazide 68% and 59.4%,*** of ethanol extract resulted in the isolation of 9 flavonoids including apigenin-7-O-arhamnosyl(1/2)-b-D-glucuronide,apigenin-7-O-b-D-glucuronide,apigenin-7-O-b-Dglucoside and ***:This study highlights the potential use of *** leaf extract enriched in flavones for the treatment of diabetes that would warrant further clinical trials investigation.

关键词： STZ-induced diabetes Diaion fractionation Flavonoid glucuronides Brachychiton acerifolius

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Cysteine proteases as therapeutic targets:does selectivity matter? A systematic review of calpain and cathepsin inhibitors

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Acta Pharmaceutica Sinica B 2015年第6期5卷 506-519页

作者： Marton Siklos Manel Ben Aissa Gregory R.J.Thatcher Department of Medicinal chemistry and pharmacognosy University of Illinois College of Pharmacy

Cysteine proteases continue to provide validated targets for treatment of human *** neurodegenerative disorders,multiple cysteine proteases provide targets for enzyme inhibitors,notably caspases,calpains,and *** reactive,active-site cysteine provides specificity for many inhibitor designs over other families of proteases,such as aspartate and serine;however,a)inhibitor strategies often use covalent enzyme modification,and b)obtaining selectivity within families of cysteine proteases and their isozymes is *** review provides a general update on strategies for cysteine protease inhibitor design and a focus on cathepsin B and calpain 1 as drug targets for neurodegenerative disorders;the latter focus providing an interesting query for the contemporary assumptions that irreversible,covalent protein modification and low selectivity are anathema to therapeutic safety and efficacy.

关键词： Cysteine protease Calpain Cathepsin Enzyme inhibitors Neurodegeneration Alzheimer’s disease

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TRADITIONAL HERBAL MEDICINES IN LITHUANIA

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World Journal of Traditional Chinese Medicine 2015年第4期1卷 79-80页

作者： V.Povilaityte-Petri Department of therapeutic chemistry and pharmacognosy University of Mons

Lithuania is an Eastern European country with 60 miles of sandy coastline to the open Baltic *** country can be divided into 4 ethnographic regions with specific nature scenery,soil,traditions and linguistic *** experienced many political changes through the centuries leading finally to regained independence and EU membership in ***,climatic conditions,

关键词： TRADITIONAL HERBAL MEDICINES IN LITHUANIA

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Herbal Medicines for Acute Kidney Injury: Evidence, Gaps and Frontiers

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World Journal of Traditional Chinese Medicine 2015年第3期1卷 47-66页

作者： Valérian Bunel Fan Qu Pierre Duez Qi-he Xu laboratory of Experimental Nephrology Faculty of MedicineUniversité Libre de Bruxelles(ULB) laboratory of pharmacognosy Bromatology and Human NutritionFaculty of PharmacyULB Women’s Hospital School of MedicineZhejiang University Department of therapeutic chemistry and pharmacognosy Université de Mons(UMONS) Centre for Integrative Chinese Medicine and Department of Renal Medicine King’s College London

Acute kidney injury(AKI) is a major health threat worldwide. The literature on herbal intervention in AKI was searched from English and Chinese databases and reports were critically analyzed in terms of preventing AKI, promoting repair and regeneration, enhancing extrarenal clearance of uremic toxins, and preventing progression to chronic kidney disease(CKD). Altogether, 16 herbal formulae and a few extracts derived from individual herbs were reported to prevent or mitigate AKI in animal models induced by renal ischemia/reperfusion, cisplastin,gentamicin, glycerol, adenine, sepsis or physical exhaustion. Four formulae and six individual herbs were reported to accelerate recovery and/or to prevent CKD in established AKI animal models. Intrarectal herbal medicines, with or without simultaneous oral administration, were reported in six clinical trials and in an animal model to increase extrarenal clearance of uremic toxins. Additional 13 clinical trials reported oral or intravenous herbal interventions in AKI of different etiologies. Despite recurring problems, notably poor compliance with good practice guidelines for clinical trials and for authentication, naming and quality control of herbal materials, accumulating experimental data on the preventive effects of herbal medicines in AKI look encouraging and urge for better, definitive trials to guide clinical practice. Herbal enemas promoting extrarenal clearance of uremic toxins seem cost-effective, but better clinical evidence is certainly needed before any affirmative recommendation be made for AKI patients without access to dialysis. New frontiers, however, lie in those herbal remedies that promote repair/regeneration and prevent chronicity after AKI. Recent experimental data suggest that this may be possible.

关键词： Acute renal failure renoprotective traditional Chinese medicine herbal medicinal products traditional medicine

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Preliminary Study on Counterfeiting of Artemether and Artesunate Marketed in Lubumbashi

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Pharmacology & Pharmacy 2016年第5期7卷 185-192页

作者： Pierrot Mwamba Tshilumba Elie Rongorongo Kagoha Valentin Bashige Chiribagula Glauber Mbayo Kalubandika Vianney Ntabaza Ndage Trésor Sumbu Nzuzi Evodie Numbi Wa Ilunga Pierre Duez Jean Baptiste Kalonji Ndoumba laboratory of Galenic Pharmacy and Drug Analysis University of Lubumbashi Lubumbashi Democratic Republic of Congo laboratory of therapeutic chemistry and pharmacognosy University of Mons Mons Belgium laboratory of pharmacognosy University of Lubumbashi Lubumbashi Democratic Republic of Congo

Pharmaceutical counterfeiting is a health scourge responsible for several cases of morbidity and mortality. Counterfeit medicines cause therapeutic failure, emergence of resistance in the treatment of infections. This study was conducted in order to identify counterfeit and authentic medicines in circulation in Lubumbashi. The study included artemether and artesunate for oral administration. A careful visual inspection of medicine, investigation of authenticity of pharmaceutical products from manufacturers and pharmaceutical regulatory authorities and determination of content were used as study parameters. 52 samples: 37 artemether and 15 of artésunate were collected. 7 samples (13%) have proven to be counterfeit. Artemether was the most counterfeit (71%) and 29% for artesunate. 6 (12%) samples were substandard according to the international pharmacopoeia in terms of content of active ingredient. Sixty-seven percent of non-compliance concerned counterfeit medicines. The proportion of non-compliance is highest among counterfeit medicines (71.43% vs 2.22%;p = 0.000004). It is obvious that strengthening the capacity of the drug regulatory authority of the DRC reduces the influx of counterfeit drug and substandard.

关键词： Counterfeit Medicines Antimalarial Lubumbashi DR Congo

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Biological activity and toxicity of the Chinese herb Magnolia officinalis Rehder & E. Wilson(Houpo) and its constituents

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2017年第3期18卷 194-214页

作者： Melanie POIVRE Pierre DUEZ (Unit of therapeutic chemistry and pharmacognosy Faculty of Medicine and Pharmacy Research Institute for Health Sciences and Technology University of Mons-UMONS Mons Belgium

Traditional Chinese herbal drugs have been used for thousands of years in Chinese pharmacopoeia. The bark of Magnolia officinalis Rehder ＆ E. Wilson, known under the pinyin name ＂Houpo＂, has been traditionally used in Chinese and Japanese medicines for the treatment of anxiety, asthma, depression, gastrointestinal disorders, headache, and more. Moreover, Magnolia bark extract is a major constituent of currently marketed dietary supplements and cosmetic products. Much pharmacological activity has been reported for this herb and its major compounds notably antioxidant, anti-inflammatory, antibiotic and antispasmodic effects. However, the mechanisms underlying this have not been elucidated and only a very few clinical trials have been published. In vitro and in vivo toxicity studies have also been published and indicate some intriguing features. The present review aims to summarize the literature on M. officinalis bark composition, utilisation, pharmacology, and safety.

关键词： Magnolia bark Houpo Chinese herb Traditional Chinese medicine

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Essential tremor:A three-dimensional neurosphere in vitro model to assess the neurotoxicity of harmane

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Journal of Traditional Chinese Medical Sciences 2023年第1期10卷 19-34页

作者： Rania Aro Amandine Nachtergael Laurence Ris Mario Manto Pierre Duez Unit of therapeutic chemistry and pharmacognosy University of Mons(UMONS)Mons 7000Belgium Department of Neuroscience Research Institute for BiosciencesUniversity of MonsMons 7000Belgium Department of Neurology CHU-CharleroiCharleroi 6000Belgium

Objectives: To use a novel in vitro model of three-dimensional(3D) neurosphere cultures to assess neurotoxic or neuroprotective effects with harmane as a model ***: A reproducible model of 3D spheroids was developed from embryonic mouse cortical neurons,using molded agarose micro-wells;this method seems particularly practical as it is customizable and widely available and does not require specific cell treatments or assay components different from 2D cultures, allowing for the easy transposition of routine protocols. To assess the neurotoxic effects of harmane, a resazurin assay was performed to measure cell viability, and a highly sensitive fluorometric method, based on the oxidation of dichlorodihydrofluorescein, was applied to measure eventually induced reactive oxygen species(ROS) after exposure to harmane at increasing concentrations of 50 100,and 250 μ***: Hydrogel microwells facilitated the assembly of spheroids containing neurons and glial cells into a complex 3D structure and prevented the agglomeration of spheroids. Exposure to harmane induced cytotoxicity in 3D neural spheroids, which was correlated with harmane concentrations, with a 27%reduction in viability at 250 μm. Harmane that did not induce significant levels of oxidative stress was detected for all tested ***: This 3D neurosphere model mimics a neuronal microenvironment, allowing a fine study of neurodegenerative disorders and the effects of chemicals on the brain. This model opens novel opportunities, not only from a pathogenetic point of view but also from a therapeutic perspective.

关键词： 3D spheroid Toxicity Neurotoxicity Harmane Essential tremor

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Traditional Chinese medicine enables the development of small-molecule inhibitors of HSP47,future therapeutic implication in venous thromboembolism

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Chinese Journal of Natural Medicines 2023年第9期21卷 641-642页

作者： LI Yuan YAO Li Department of Medicinal chemistry and Natural Medicine chemistry Department of PharmacognosyCollege of PharmacyHarbin Medical UniversityHarbin 150081China

Venous thromboembolism(VTE)is a typical cardiovascular disease,which is phenotypically characterized by painful leg swelling,chest pain,shortness of breath,and even death[1].VTE renders a high morbidity and mortality as it is the main cause of death of hospitalized *** treatment of VTE mostly adopts immediate anticoagulation agents via a risk assessment of ***,traditional Chinese medicine(TCM)has unique medicinal priority on reducing swelling,stopping bleeding and promoting blood circulation,which therefore can eliminate the obstruction of patient’s channels so as to exert analgesic and anti-inflammatory bioactivities[2].However,well-controlled and-designed clinical trials of the selected TCM formulae are widely performed to support the clinical application of traditional Chinese medicine for the prevention of VTE in a real world.

关键词： prevention swelling enable

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Osthole attenuates pulmonary arterial hypertension by the regulation of sphingosine 1-phosphate in rats

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Chinese Journal of Natural Medicines 2020年第4期18卷 308-320页

作者： YAO Li YANG Yu-Xia CAO Hui REN Huan-Huan NIU Zheng SHI Ling Department of Medicinal chemistry and Natural Medicine chemistry Department of PharmacognosyCollege of PharmacyHarbin Medical UniversityHarbin 150081China State-Province Key laboratory of Biomedicine-Pharmaceutics of China Harbin Medical UniversityHarbin 150081China Department of Pharmacology College of PharmacyHarbin Medical UniversityHarbin 150081China

Osthole is observed to have the capacity to treat pulmonary arterial hypertension(PAH) in rats, but molecular mechanism is still unknown. The present study aims to discover therapeutic targets and explore therapeutic mechanism of osthole against PAH from metabolic perspective. A rat model with PAH was successfully established with MCT, following osthole administration, then untargeted metabolomics assay was performed using UPLC-Q-TOF-MS to identify differential metabolites and associated metabolic pathways, at last mechanism investigation was done by qRT-PCR, Western blot and ELISA. Differential metabolites characterized in rats with PAH were mostly assigned to sphingolipid metabolism, synthesis of unsaturated fatty acids, glycolysis, nucleotide metabolism, steroid hormone biosynthesis. Furthermore, osthole reversed high level of S1 P by modulating metabolic enzyme Sphk1 in rats with PAH. In addition, osthole inhibited the expression of Sphk1 by downregulating microRNA-21, phosphorylation of Akt, phosphorylation of mTOR in vivo and in vitro. These results demonstrated that metabolomics is a promising approach to discover potential drug target for PAH treatment. Importantly, our findings further elucidated therapeutic mechanism of osthole, a natural product, having a role of metabolic regulator to potentially treat PAH by targeting inhibition of Sphk1/S1 P via microRNA-21-PI3 K/Akt/mTOR signal pathway. Altogether, this discovery paves a critical foundation for enabling osthole to be a candidate compound to treat PAH.

关键词： Pulmonary arterial hypertension Osthole Metabolomics Sphk1/S1P MicroRNA-21-PI3K/Akt/mTOR therapeutic mechanism

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