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Herbal compounds as promising therapeutic agents in precision medicine strategies for cancer:A systematic review

Journal of Integrative Medicine 2024年第2期22卷 137-162页

作者： Bizhar Ahmed Tayeb Ikhwan Yuda Kusuma Alaa A.M.Osman Renáta Minorics institute of Pharmacodynamics and Biopharmacy Faculty of PharmacyUniversity of Szeged6720 SzegedHungary Institution of Clinical pharmacy Faculty of PharmacyUniversity of Szeged6725 SzegedHungary Department of Clinical pharmacy and pharmacy Practice Faculty of PharmacyUniversity of Gezira20 Wad MadaniSudan pharmacy Study Program Facuity of HealthUniversitas Harapan BangsaPurwokerto 53182Indonesia

Background:The field of personalized medicine has gained increasing attention in cancer care,with the aim of tailoring treatment strategies to individual patients for improved outcomes.Herbal medicine,with its long-standing historical use and extensive bioactive compounds,offers a rich source of potential treatments for various diseases,including cancer.Objective:To provide an overview of the current knowledge and evidence associated with incorporating herbal compounds into precision medicine strategies for cancer diseases.Additionally,to explore the general characteristics of the studies included in the analysis,focusing on their key features and trends.Search strategy:A comprehensive literature search was conducted from multiple online databases,including Pub Med,Scopus,Web of Science,and CINAHL-EBSCO.The search strategy was designed to identify studies related to personalized cancer medicine and herbal interventions.Inclusion criteria:Publications pertaining to cancer research conducted through in vitro,in vivo,and clinical studies,employing natural products were included in this review.Data extraction and analysis:Two review authors independently applied inclusion and inclusion criteria,data extraction,and assessments of methodological quality.The quality assessment and biases of the studies were evaluated based on modified Jadad scales.A detailed quantitative summary of the included studies is presented,providing a comprehensive description of their key features and findings.Results:A total of 121 studies were included in this review for analysis.Some of them were considered as comprehensive experimental investigations both in vitro and in vivo.The majority(n=85)of the studies included in this review were conducted in vitro,with 44 of them specifically investigating the effects of herbal medicine on animal models.Additionally,7 articles with a combined sample size of 31,271 patients,examined the impact of herbal medicine in clinical settings.Conclusion:Personalized medication can optimize the use of herbal m

关键词： Cancer Herbal medicine Personalized medication Active phytochemicals Natural compound

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Phosphorylation-driven aggregative proteins in neurodegenerative diseases:implications and therapeutics

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Neural Regeneration Research 2024年第5期19卷 966-968页

作者： Alba Espargaró Raimon Sabate Department of pharmacy and Pharmaceutical Technology and Physical-Chemistry School of PharmacyUniversity of BarcelonaBarcelonaSpain institute of Nanoscience and Nanotechnology(IN2UB) University of BarcelonaBarcelonaSpain

Protein aggregation is related to a large number of neurodegenerative disorders.Particularly in some cases,aggregation is induced by hyperphosphorylation of a given protein.This is the case of tau,TAR DNA-binding protein 43(TDP-43),amyloid-beta peptides(Aβ)and alpha-synuclein(α-syn),which play a key pathogenic role in Alzheimer’s disease(AD),Parkinson’s disease(PD)and amyotrophic lateral sclerosis,among others(Tenreiro et al.,2014;Chiti and Dobson,2017).In this perspective,we will discuss both the relationship between phosphorylation and amyloid aggregation as well as current and future therapeutic strategies aimed at inhibiting specific kinases involved in the phosphorylation step or inhibiting subsequent protein aggregation.

关键词： tau Aβ Alzheimer

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Nrf2 as a potential target for the treatment of epilepsy

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Neural Regeneration Research 2024年第9期19卷 1865-1866页

作者： Prince Kumar Singh Tawfeeq Shekh-Ahmad institute for Drug Research School of PharmacyFaculty of MedicineThe Hebrew University of JerusalemJerusalemIsrael

Epilepsy is a prevalent chronic brain disorder that is characterized by a persistent predisposition to recurrently generate epileptic seizures and is often associated with cognitive and psychological consequences.Epilepsy affects approximately 65 million individuals,including both males and females of all ages worldwide,and poses a significant burden on patients,their families,and the health system(Vezzani et al.,2019).

关键词： epilepsy Nrf2

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Tetramic acid-motif natural products from a marine fungus Tolypocladium cylindrosporum FB06 and their anti-Parkinson activities

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Marine Life Science & Technology 2024年第1期6卷 84-92页

作者： Yuna Jung Chaesun Kwon Taeyeon Kim Jin Woo Lee Min-Kyoo Shin Sang Hee Shim Natural Products Research institute College of PharmacySeoul National UniversitySeoul 08826Republic of Korea College of pharmacy and Research institute of Pharmaceutical Sciences Seoul National UniversitySeoul 08826Republic of Korea College of pharmacy Duksung Women’s UniversitySeoul 01369Republic of Korea

Tetramic acid-containing natural products are attracting significantly increasing attention from biologists and chemists due to their intriguing structures and biological activities.In the present study,two new tetramic acid alkaloids tolypyridone I(1)and tolypyridone J(2),together with five known ones(3–7),were isolated from cultures of a marine fungus Tolypocladium cylindrosporum FB06 isolate obtained from a marine sediment in Beaufort sea of North Alaska.Their structures were elucidated using 1D,2D NMR,and HRESIMS.Their configurations were established on the basis of 1H coupling constants,ROESY correlations and DP4 calculations.Compound 2 was isolated as mixtures of rotational isomers with C-3 to C-7 axis between 4-hydroxy-2-pyridone and 1-ethyl-3,5-dimethylcyclohexane,hindering rotation.In our unbiased screening to discover neuroprotective compounds in an in vitro Parkinson’s disease(PD)model,SH-SY5Y dopaminergic cells were treated with isolated compounds followed by treatment with 1-methyl-4-phenylpyridinium(MPP^(+)),a parkinsonian neurotoxin.Among tested compounds,F-14329(7)significantly protected cells from MPP^(+)-induced cytotoxicity.MPP^(+)-mediated cell death is known to be related to the regulation of Bcl-2 family proteins,specifically the down-regulation of anti-apoptotic Bcl-2 and the up-regulation of pro-apoptotic Bax levels.Treatment with 2 mmol/L of MPP^(+)for 24 h significantly reduced Bcl-2 levels compared to control treated with vehicle.However,treatment with F-14329(7)attenuated such reduction.This study demonstrates that tetramic acid-motif compounds could be potential lead compounds for treating PD.

关键词： Tolypocladium cylindrosporum Tetramic acid Tolypyridone Parkinson’s disease

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SIRT2 as a potential new therapeutic target for Alzheimer's disease

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Neural Regeneration Research 2024年第1期19卷 124-131页

作者： Noemi Sola-Sevilla Elena Puerta Department of Pharmacology and Toxicology Faculty of PharmacyUniversity of NavarraNavarra Institute for Health Research(IdiSNA)PamplonaSpain

Alzheimer's disease is the most common cause of dementia globally with an increasing incidence over the years,bringing a heavy burden to individuals and society due to the lack of an effective treatment.In this context,sirtuin 2,the sirtuin with the highest expression in the brain,has emerged as a potential therapeutic target for neurodegenerative diseases.This review summarizes and discusses the complex roles of sirtuin 2 in different molecular mechanisms involved in Alzheimer's disease such as amyloid and tau pathology,microtubule stability,neuroinflammation,myelin formation,autophagy,and oxidative stress.The role of sirtuin 2 in all these processes highlights its potential implication in the etiology and development of Alzheimer's disease.However,its presence in different cell types and its enormous variety of substrates leads to apparently contra dictory conclusions when it comes to understanding its specific functions.Further studies in sirtuin 2 research with selective sirtuin2 modulators targeting specific sirtuin 2 substrates are necessary to clarify its specific functions under different conditions and to validate it as a novel pharmacological target.This will contribute to the development of new treatment strategies,not only for Alzheimer's disease but also for other neurodegenerative diseases.

关键词： Alzheimer's disease amyloid autophagy memory neurodegenerative diseases neuroinflammation sirtuin 2 tau

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Sustained release of vascular endothelial growth factor A and basic fibroblast growth factor from nanofiber membranes reduces oxygen/glucose deprivation-induced injury to neurovascular units

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Neural Regeneration Research 2024年第4期19卷 887-894页

作者： Yifang Wu Jun Sun Qi Lin Dapeng Wang Jian Hai Department of Neurosurgery Tongji HospitalSchool of MedicineTongji University Department of pharmacy Institute of Medical SciencesShanghai Jiao Tong University School of Medicine

Upregulation of vascular endothelial growth factor A/basic fibroblast growth factor(VEGFA/b FGF)expression in the penumbra of cerebral ischemia can increase vascular volume,reduce lesion volume,and enhance neural cell proliferation and differentiation,thereby exerting neuroprotective effects.However,the beneficial effects of endogenous VEGFA/b FGF are limited as their expression is only transiently increased.In this study,we generated multilayered nanofiber membranes loaded with VEGFA/b FGF using layer-by-layer self-assembly and electrospinning techniques.We found that a membrane containing 10 layers had an ideal ultrastructure and could efficiently and stably release growth factors for more than 1 month.This 10-layered nanofiber membrane promoted brain microvascular endothelial cell tube formation and proliferation,inhibited neuronal apoptosis,upregulated the expression of tight junction proteins,and improved the viability of various cellular components of neurovascular units under conditions of oxygen/glucose deprivation.Furthermore,this nanofiber membrane decreased the expression of Janus kinase-2/signal transducer and activator of transcription-3(JAK2/STAT3),Bax/Bcl-2,and cleaved caspase-3.Therefore,this nanofiber membrane exhibits a neuroprotective effect on oxygen/glucose-deprived neurovascular units by inhibiting the JAK2/STAT3 pathway.

关键词： brain ischemia brain microvascular endothelial cell nanofiber membrane neurovascular unit

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New phenylbutenoids and terpene glycosides from Ginkgo biloba leaves

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Chinese Journal of Natural Medicines 2024年第2期22卷 161-170页

作者： SUN Zeshi LIN Shan WU Zhi-Li DONG Hong-Yuan XU Xi-Ke LI Hui-Liang WANG Jinxin School of pharmacy Second Military Medical UniversityShanghai 200433China State Key Laboratory of New Drug and Pharmaceutical Process Shanghai Institute of Pharmaceutical IndustryChina State Institute of Pharmaceutical IndustryShanghai 201203China

Our continued works on the chemical constituents of Ginkgo biloba(G.biloba)leaves has led to the isolation of two novel phenylbutenoids(1,2),along with five previously unidentified terpene glycosides(3−7).Among them,compounds 1 and 2 represent unique(Z)-phenylbutenoids,3−6 are megastigmane glycosides,and 7 is identified as a rare bilobanone glycoside(Fig.1).This study marks the first reported isolation of phenylbutenoid and bilobanone glycoside from G.biloba.The chemical structures of these compounds were elucidated through extensive spectroscopic analysis,including HR-ESI-MS and various 1D and 2D NMR experiments.Furthermore,the absolute configurations of these molecules were determined using Mosher’s method,ECD experiments,and Cu-KαX-ray crystallographic analyses.

关键词： Ginkgo biloba Phenylbutenoid Megastigmane glycoside Bilobanone glycoside

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Glucose-mediated mitochondrial reprogramming by cholesterol export at TM4SF5-enriched mitochondria-lysosome contact sites

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Cancer Communications 2024年第1期44卷 47-75页

作者： Ji Eon Kim So-Young Park Chulhwan Kwak Yoonji Lee Dae-Geun Song Jae Woo Jung Haesong Lee Eun-Ae Shin Yangie Pinanga Kyung-hee Pyo Eun Hae Lee Wonsik Kim Soyeon Kim Chang-Duck Jun Jeanho Yun Sun Choi Hyun-Woo Rhee Kwang-Hyeon Liu Jung Weon Lee Department of pharmacy College of PharmacySeoul National UniversitySeoulRepublic of Korea Research institute of Pharmaceutical Sciences College of PharmacySeoul National UniversitySeoulRepublic of Korea BK21 FOUR Community-Based Intelligent Novel Drug Discovery Education Unit College of Pharmacy and Research Institute of Pharmaceutical SciencesKyungpook National UniversityDaeguRepublic of Korea Department of Chemistry Seoul National UniversitySeoulRepublic of Korea College of pharmacy Chung-Ang UniversitySeoulRepublic of Korea Natural Product Informatics Research Center Korea Institute of Science and Technology(KIST)Gangneung-siGangwon-doRepublic of Korea School of Life Sciences Gwangju Institute of Science and Technology(GIST)GwangjuRepublic of Korea Department of Biochemistry College of MedicineDong-A UniversityBusanRepublic of Korea Global AI Drug Discovery Center College of Pharmacy and Graduate School of Pharmaceutical SciencesEwha Womans UniversitySeoulRepublic of Korea Interdisciplinary Program in Genetic Engineering Seoul National UniversitySeoulRepublic of Korea

Background:Transmembrane 4 L six family member 5(TM4SF5)translocates subcellularly and functions metabolically,although it is unclear how intracellu-lar TM4SF5 translocation is linked to metabolic contexts.It is thus of interests to understand how the traffic dynamics of TM4SF5 to subcellular endosomal membranes are correlated to regulatory roles of metabolisms.Methods:Here,we explored the metabolic significance of TM4SF5 localization at mitochondria-lysosome contact sites(MLCSs),using in vitro cells and in vivo animal systems,via approaches by immunofluorescence,proximity labelling based proteomics analysis,organelle reconstitution etc.Results:Upon extracellular glucose repletion following depletion,TM4SF5 became enriched at MLCSs via an interaction between mitochondrial FK506-binding protein 8(FKBP8)and lysosomal TM4SF5.Proximity labeling showed molecular clustering of phospho-dynamic-related protein I(DRP1)and certain mitophagy receptors at TM4SF5-enriched MLCSs,leading to mitochondrial fis-sion and autophagy.TM4SF5 bound NPC intracellular cholesterol transporter 1(NPC1)and free cholesterol,and mediated export of lysosomal cholesterol to mitochondria,leading to impaired oxidative phosphorylation but intact tri-carboxylic acid(TCA)cycle andβ-oxidation.In mouse models,hepatocyte Tm4sf5 promoted mitophagy and cholesterol transport to mitochondria,both with positive relations to liver malignancy.Conclusions:Our findings suggested that TM4SF5-enriched MLCSs regu-late glucose catabolism by facilitating cholesterol export for mitochondrial reprogramming,presumably while hepatocellular carcinogenesis,recapitulating aspects for hepatocellular carcinoma metabolism with mitochondrial repro-gramming to support biomolecule synthesis in addition to glycolytic energetics.

关键词： cholesterol fluorescent imaging glucose catabolism hepatocellular carcinogenesis mem-brane contact sites mitochondria function mitophagy oxidative phosphorylation protein-protein interaction tetraspanin

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Comprehensive reutilization of herbal waste:Coproduction of magnolol,honokiol,and β-amyrin from Magnolia officinalis residue

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Green Energy & Environment 2024年第2期9卷 403-412页

作者： Lukun Xiao Anyi Zhao Jie Qiu An Liu Sha Chen Jinzhu Jiang Jun Zhang Cong Guo Jipeng Di Jintang Cheng Chang Chen Kangxin Hou Aiping Zhang Yan Liu Caixia Wang institute of Chinese Materia Medica China Academy of Chinese Medical SciencesBeijing100700China School of pharmacy Shanxi Medical UniversityTaiyuan030001China

Herbal extraction residues(HERs)cause serious environmental pollution and resource waste.In this study,a novel green route was designed for the comprehensive reutilization of all components in HERs,taking Magnolia officinalis residues(MOR)as an example.The reluctant structure of MOR was first destroyed by alkali pretreatment to release the functional ingredients(magnolol and honokiol)originally remaining in MOR and to make MOR more accessible for hydrolysis.A metal–organic frame material MIL-101(Cr)with a maximum absorption capacity of 255.64 mg g^(-1)was synthesized to absorb the released honokiol and magnolol from the pretreated MOR solutions,and 40 g L^(-1)reducing sugars were obtained with 81.8%enzymatic hydrolysis rate at 10%MOR solid loading.Finally,382 mg L-1β-amyrin was produced from MOR hydrolysates by an engineered yeast strain.In total,1 kg honokiol,8 kg magnolol,and 7.64 kg β-amyrin could produce from 1 ton MOR by this cleaner process with a total economic output of 170,700 RMB.

关键词： Magnolia officinalis residues(MOR) Comprehensive utilization Metal-organic frame material Biosynthesis

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1,12-cyclic apelin-12 ameliorates Ang II and Apelin-13-induced cardiac hypertrophy by reducing mitochondrial oxidative damage

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Chinese Medical Journal 2024年第6期137卷 749-751页

作者： Xueqian Ouyang Wei Chen Guolong Peng Huimei Liu Sisi Fan Qin Li Liwen Wang Linxi Chen Lanfang Li The institute of pharmacy and Pharmacology Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug ResearchUniversity of South ChinaHengyangHunan 421001China

To the Editor:Pathological cardiac hypertrophy is commonly stimulated by stress or induced by cardiovascular diseases,such as hypertension and myocardial infarction.A sustained pathological hypertrophic response can lead to declines in diastolic and systolic functions and eventually develop heart failure.Angiotensin II(Ang II)can mediate cardiac hypertrophy through the angiotensin II type 1 receptor(AT1R).^([1])

关键词： hypertrophy cardiac Ang

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