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Phytochemicals as inhibitors of tumor necrosis factor alpha and neuroinflammatory responses in neurodegenerative diseases

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Neural Regeneration Research 2022年第8期17卷 1675-1684页

作者： Fatemeh Zahedipour Seyede Atefe Hosseini Neil C.Henney George E.Barreto Amirhossein Sahebkar Department of Medical Biotechnology School of MedicineMashhad University of Medical SciencesMashhadIran Student Research Committee Faculty of MedicineMashhad University of Medical SciencesMashhadIran Pharmacy&Biomolecular Sciences Liverpool John Moores UniversityLiverpoolUK Department of Biological sciences University of LimerickLimerickIreland Health Research Institute University of LimerickLimerickIreland Applied Biomedical Research Center Mashhad University of Medical SciencesMashhadIran Biotechnology Research Center Pharmaceutical Technology InstituteMashhad University of Medical SciencesMashhadIran Polish Mother’s Memorial Hospital Research Institute(PMMHRI) LodzPoland School of pharmacy Mashhad University of Medical SciencesMashhadIran

Inflammatory processes and proinflammatory cytokines have a key role in the cellular processes of neurodegenerative diseases and are linked to the pathogenesis of functional and mental health disorders.Tumor necrosis factor alpha has been reported to play a major role in the central nervous system in Alzheimer’s disease,Parkinson’s disease and amyotrophic lateral sclerosis and many other neurodegenerative diseases.Therefore,a potent proinflammatory/proapoptotic tumor necrosis factor alpha could be a strong candidate for targeted therapy.Plant derivatives have now become promising candidates as therapeutic agents because of their antioxidant and chemical characteristics,and anti-inflammatory features.Recently,phytochemicals including flavonoids,terpenoids,alkaloids,and lignans have generated interest as tumor necrosis factor alpha inhibitor candidates for a number of diseases involving inflammation within the nervous system.In this review,we discuss how phytochemicals as tumor necrosis factor alpha inhibitors are a therapeutic strategy targeting neurodegeneration.

关键词： brain central nervous system cytokine herbal medicine inflammation neurodegenerative diseases phytochemicals tumor necrosis factor-alpha

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Antidiabetic effect of combination of fractionated-extracts of Andrographis paniculata and Centella asiatica: In vitro study

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Asian Pacific Journal of Tropical Biomedicine 2018年第11期8卷 527-532页

作者： LOM.Fitrawan R.Ariastuti RR.TjANDrawinata AE.Nugroho S.Pramono Master Program of Pharmaceutical sciences of Faculty of pharmacy Universitas Gadjah Mada Faculty of pharmacy Universitas Halu Oleo Dexa Laboratories of biomolecular sciences Department of Pharmacology and Clinical pharmacy Faculty of Pharmacy Universitas Gadjah Mada Department of Pharmaceutical Biology Faculty of Pharmacy Universitas Gadjah Mada

Objective: To examine the effect of combination of Andrographis paniculata herb fraction(AHF) and Centella asiatica herb fraction(CHF) on PPAR γ and GLUT4 mRNA expression in 3 T3-L1 adipocyte, and its effect on insulin-stimulated glucose uptake. Methods: 3 T3 L1 adipocyte cells were used to investigate gene expression of PPARy reverse transcription-polymerase chain reaction method. The γ and GLUT4 protein b adipocyte cells were differentiated by using insulin, dexamethasone and 3-isobutyl-1-methylxanthine from 3 T3-L1 cells. Pioglitazone, AHF, CHF and the combination of both herbs were evaluated on glucose uptake activity, PPAR γ and GLUT4 mRNA expressions in 3 T3-L1 adipocyte. Results: The results showed that combination of AHF at 30 μg/mL and CHF at 10 μg/mL could enhance insulin-stimulated glucose uptake. The combination also increased PPAR γ and GLUT4 mR NA expressions significantly in comparison to those of negative control(DMSO). These effects were equal in comparison to those of pioglitazone(0.02 μM) and its single extracts Conclusions: The combination of AHF and CHF can increase glucose uptake and insulin sensitivity through up-regulation of PPAR γ and GLUT4 mRNA expressions in 3 T3-L1 adipocyte.

关键词： Andrographis paniculata Centella asiatica GLUT4 PPAR γ 3T3-L1

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Riding the rails-different modes for RNA complex transport in axons

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Neural Regeneration Research 2022年第12期17卷 2664-2665页

作者： Ofri Abraham Mike Fainzilber Departments of biomolecular sciences and Molecular Neuroscience Weizmann Institute of ScienceRehovotIsrael

Neurons are highly polarized cells with axons that innervate distant targets.The distance of subcellular compartments from the nucleus requires sophisticated transport mechanisms and local action of vital processes for proper function and rapid responses to local stimuli(Terenzio et al.,2017).This is partially achieved by transport of mRNAs to subcellular locations and regulation of local translation for axonal growth,branching,synaptic plasticity,and regeneration,among other needs.Axonally synthesized proteins support neuronal survival,and axonal development,maintenance,and growth(Rishal and Fainzilber,2014;Dalla Costa et al.,2021).Thus,understanding the mechanisms that promote RNA transport to subcellular locations in neurons will contribute to the development of novel strategies to enhance axon regeneration and survival.

关键词： branching polarized plasticity

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Not only myelination: the immune-inflammatory functions of oligodendrocytes

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Neural Regeneration Research 2022年第12期17卷 2661-2663页

作者： Marta Boccazzi Stefano Raffaele Marta Fumagalli Department of Pharmacological and biomolecular sciences Universitàdegli Studi di MilanoMilanItaly

Oligodendrocytes(OLs)are highly specialized cells of the central nervous system(CNS).Their primary and most investigated role is to form myelin,a multilamellar fatty membrane that enwraps axons ensuring their insulation and the saltatory conduction of nerve impulses.The formation of myelin is a complex process during which the OL precursor cells(OPCs,also known as NG2-glia)become mature OLs through a highly regulated program of differentiation.In addition,OPCs persist in the adult grey and white matter parenchyma,representing approximately 6%of the total number of CNS cells.Beyond their role in myelin generation and turn-over,it is now clear that OPCs have the capability to control tissue homeostasis and to sense and react to inflammation which characterizes many neurological diseases.

关键词： myelin cytes homeostasis

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Axonal tuning by GABA_(A) receptor unveils novel tricks from an old dog

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Neural Regeneration Research 2023年第3期18卷 533-534页

作者： Veronica Bonalume Valerio Magnaghi Department of Pharmacological and biomolecular sciences Universitàdegli Studi di MilanoMilanItaly

In the last years,axonal conductance of action potential trains became a novel subject of study,changing the view of axons,from a static cable-like compartment to a more complex and dynamic system(Debanne et al.,2011).Axonal computation,indeed,is canonically constituted by the action of voltage-gated ion channels,such as the classic Na+and K+channels,but recent studies demonstrated that it can be modulated by the action of other ion channel pumps,and metabolic factors(Byczkowicz et al.,2019;Zang and Marder.

关键词： tuning action classic

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Extended synaptotagmins, peroxisome-endoplasmic reticulum contact and cholesterol transport

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Science China(Life sciences) 2019年第9期62卷 1266-1269页

作者： Hongyuan Yang School of Biotechnology and biomolecular sciences the University of New South Wales

Cholesterol is an essential component of mammalian cell membranes where it regulates membrane permeability,fluidity,fusion and cell signaling pathways (Chang et al.,2006).Cholesterol must be sorted precisely and transported efficiently for the proper functioning of membranes,as each cellular organelle has its distinct cholesterol concentration.The need to understand the molecular mechanisms governing cellular cholesterol transport and distribution is further highlighted by the link between abnormal subcellular distribution of cholesterol and a range of human diseases such as cancer (Zhuang et al.,2005),coronary heart disease (Zhang et al.,2008),steatohepatitis (Marí et al.,2006),neurodegenerative diseases including Alzheimer’s disease and Niemann Pick C (NP-C) disease (Vance et al.,2005),and early-onset obesity and insulin resistance (Liu et al.,2017).

关键词： membrane permeability coronary heart disease cellular organelle

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Determinants of survival outcomes among esophageal cancer patients at a national referral hospital in Kenya

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Chronic Diseases and Translational Medicine 2023年第1期9卷 20-28页

作者： Amsalu Degu Peter N.Karimi Sylvia A.Opanga David G.Nyamu Department of Pharmaceutics and pharmacy Practice School of Pharmacy and Health SciencesUnited States International University–AfricaNairobiKenya Department of pharmacy Faculty of Health SciencesUniversity of NairobiNairobiKenya

Introduction:The overall 5-year survival rate for esophageal cancer patients in low-and middle-income countries was reported to be low,despite the availability of advanced treatments.Thus,this study aimed to assess determinants of survival outcomes among esophageal cancer patients in Kenya.Methods:A retrospective cohort study was employed among 299 adult esophageal cancer patients.The data were collected using a data abstraction tool consisting of patients’clinical characteristics and survival outcome measuring parameters.Statistical Package for the Social sciences(SPSS)statistical software(version 20.0,IBM.USA)was used to analyze the data.The Kaplan–Meier and Cox regression analyses were used to determine the survival outcome and determinants of mortality,respectively.Results:The mortality rate was 43.1%,and 11.1%of patients demonstrated distant metastases in the follow-up period.Despite treatment,20.1%had progressed disease,and 13.0%did not respond to treatment.Radiotherapy(AHR:3.3,95%CI:1.4−7.8,p=0.007),chemotherapy(AHR:3.9,95%CI:1.2−6.1,p=0.020),and chemoradiation(AHR:5.6,95%CI:1.6−10.2,p=0.006)were the significant determinants of survival in advanced stage(III and and IV)patients.Conclusions:There was a high mortality rate,disease progression,and nonresponse of esophageal cancer patients.Hence,it is essential to improve the survival of patients through early detection and timely initiation of the available treatment options.

关键词： determinants esophageal cancer mortality survival outcomes

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Cytotoxicity and Apoptosis Assay of Novel Cyclomyrsinol Diterpenes Against Breast Cancer Cell Lines

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World Journal of Traditional Chinese Medicine 2022年第2期8卷 273-277页

作者： Faezeh Rabbani Zeinab Yazdiniapour Mustafa Ghanadian Behzad Zolfaghari Melika Maleki Fatemeh Shafiee pharmacy Student’s Research Committee School of PharmacyIsfahan University of Medical Sciences Department of Pharmacognosy School of Pharmacy and Pharmaceutical SciencesIsfahan University of Medical Sciences Department of Pharmaceutical Biotechnology School of Pharmacy and Pharmaceutical SciencesIsfahan University of Medical SciencesIsfahanIran

Background:Cyclomyrsinane diterpenes especially those extracted from various Euphorbia species have shown interesting biological properties in recent years.Because of the high prevalence of breast cancer and the challenges ahead in its treatment,the use of these compounds as potential anti cancer agents seem reasonable.Objectives:The aim of the present study was to evaluate the cytotoxic effects of some myrsinane type diterpenoids extracted from Euphorbia sogdiana Popov and determine their induced cell death mechanism.Methods:MTT assay was used to determine the cytotoxicity of six various myrsinane compounds on MCF 7 and 4 T1 breast cancer cell lines.Human umbilical vein endothelial cells were used as the normal cell line too.The apoptotic effects of the structure with the most cytotoxic effects were determined using flow cytometry assay in IC50 concentration for 24 h of incubation.Results:Compound(6)showed the most cytotoxic effects with IC50 of about 8±4 and 24±4μg/mL for MCF 7 and 4 T1 cell lines,respectively.Furthermore,the cells treated with 5 and 10μg/mL of compound(6)for 24 h,showed 37 and 55%of apoptotic cells.Conclusions:These surveyed compounds have the potential to be considered as useful anti-breast cancer agents due to the great cytotoxicity and apoptotic effects against these cancer cells and the fact that there was no significant cytotoxicity on normal cells.

关键词： Apoptosis breast cancer cyclomyrsinol diterpenoids cytotoxicity Euphorbia sogdiana Popov

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Small interfering RNAs based therapies for intracerebral hemorrhage: challenges and progress in drug delivery systems

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Neural Regeneration Research 2022年第8期17卷 1717-1725页

作者： Daniyah A.Almarghalani Sai H.S.Boddu Mohammad Ali Akhila Kondaka Devin Ta Rayyan A.Shah Zahoor A.Shah Department of Pharmacology and Experimental Therapeutics College of Pharmacy and Pharmaceutical SciencesUniversity of ToledoToledoOHUSA Department of Medicinal and Biological Chemistry College of Pharmacy and Pharmaceutical SciencesUniversity of ToledoToledoOHUSA Department of Pharmaceutical sciences College of Pharmacy and Health SciencesAjman UniversityAjmanUnited Arab Emirates

Intracerebral hemorrhage(ICH)is a subtype of stroke associated with higher rates of mortality.Currently,no effective drug treatment is available for ICH.The molecular pathways following ICH are complicated and diverse.Nucleic acid therapeutics such as gene knockdown by small interfering RNAs(siRNAs)have been developed in recent years to modulate ICH’s destructive pathways and mitigate its outcomes.However,siRNAs delivery to the central nervous system is challenging and faces many roadblocks.Existing barriers to systemic delivery of siRNA limit the use of naked siRNA;therefore,siRNA-vectors developed to protect and deliver these therapies into the specific-target areas of the brain,or cell types seem quite promising.Efficient delivery of siRNA via nanoparticles emerged as a viable and effective alternative therapeutic tool for central nervous system-related diseases.This review discusses the obstacles to siRNA delivery,including the advantages and disadvantages of viral and nonviral vectors.Additionally,we provide a comprehensive overview of recent progress in nanotherapeutics areas,primarily focusing on the delivery system of siRNA for ICH treatment.

关键词： intracerebral hemorrhage lipid-based nanoparticle nanoparticles nanotechnology nonviral vectors peptide-mediated nanoparticle polymer-based nanoparticle siRNA therapeutics siRNA-barriers viral vectors

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Use of stimulatory responsive soft nanoparticles for intracellular drug delivery

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Nano Research 2023年第5期16卷 6974-6990页

作者： Krystal A Hughes Bishal Misra Maryam Maghareh Sharan Bobbala Department of Pharmaceutical sciences West Virginia University School of PharmacyMorgantownWV 26505USA Department of Clinical pharmacy West Virginia University School of PharmacyMorgantownWV 26505USA

Drug delivery has made tremendous advances in the last decade.Targeted therapies are increasingly common,with intracellular delivery highly impactful and sought after.Intracellular drug delivery systems have limitations due to imprecise and non-targeted release profiles.One way this can be addressed is through using stimuli-responsive soft nanoparticles,which contain materials with an organic backbone such as lipids and polymers.The choice of biomaterial is essential for soft nanoparticles to be responsive to internal or external stimuli.The nanoparticle must retain its integrity and payload in non-targeted physiological conditions while responding to particular intracellular environments where payload release is desired.Multiple internal and external factors could stimulate the intracellular release of drugs from nanoparticles.Internal stimuli include pH,oxidation,enzymes,while external stimuli include ultrasound,light,electricity,magnetic fields.Stimulatory responsive soft nanoparticulate systems specifically utilized to modulate intracellular delivery of drugs are explored in this review.

关键词： nanoparticles biomaterials stimuli-responsive targeted delivery intracellular drug delivery

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