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Critical Review on Balanites aegyptiaca Delile: Phytoconstituents, Pharmacological Properties and Nanointerventions

Chinese Journal of Integrative Medicine 2024年第7期30卷 653-663页

作者： Surendra Kumar Gautam Rakesh Kumar Paul Devesh M.Sawant Amita Sarwal Kaisar Raza department of pharmacy School of Chemical Sciences and Pharmacy Central University of Rajasthan University Institute of pharmaceutical sciences Panjab University

Balanites aegyptiaca Delile(BA) is an enduring xerophytic woody and spinous flowering tree and is commonly known as desert date or Ingudi(Hingot). It belongs to the family Zygophyllaceae, which is specific to be drought areas of Nigeria, Africa, South Asia and India(Rajasthan). In Ayurveda, this traditional medicinal plant is reported for the management of jaundice, syphilis, yellow fever, metabolic disorders, liver, and spleen problems. The main aim of the review is to compile its medicinal uses and further advancements to showcase the promises inherited in various parts of the plant for the benefit of mankind. As per the literature survey, various researchers have focused on the detailed investigation of BA including the phytopharmacological evidence, chemical constituents, nano-formulations, commercialized products, and clinical trials. Several remarkable scaffolds and isolated compounds like diosgenin, yamogenin, balanitin1/2, balanitin 3, bal4/5, bal6/7, rutin-3-glycosides, 3,7-diglycosides,(3, 12, 14, 16)–(12-hydroxycholest-5-ene-3,16-diyl-bis)-D-glucopyranoside and balanitoside have been identified. Additionally, this traditional plant has been scientifically proven by in vitro and in vivo. Based on the complete review of this plant, most of the compounds have been isolated from the fruit and kernel part. Additionally, based on the literature, a histogram was developed for pharmacological activity in which antidiabetic study was found to be more compared to other pharmacological activity. As a spinous desert dates, this plant needs to be explored more to bring out newer phytochemicals in the management of various diseases.

关键词： Delile desert date phytochemicals nano-phytopharmaceutical pharmacological activities traditional medicine

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Dysregulation of RNA modification systems in clinical populations with neurocognitive disorders

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Neural Regeneration Research 2024年第6期19卷 1256-1261页

作者： Helen M.Knight Merve Demirbugen ?z Adriana PerezGrovas-Saltijeral Division of Cells Organisms and Molecular Genetics School of Life Sciences University of Notingham department of pharmaceutical Toxicology Faculty of Pharmacy Ankara University

The study of modified RNA known as epitranscriptomics has become increasingly relevant in our understanding of disease-modifying mechanisms. Methylation of N6 adenosine(m6A) and C5 cytosine(m5C) bases occur on mRNAs, tRNA, mt-tRNA, and rRNA species as well as non-coding RNAs. With emerging knowledge of RNA binding proteins that act as writer, reader, and eraser effector proteins, comes a new understanding of physiological processes controlled by these systems. Such processes when spatiotemporally disrupted within cellular nanodomains in highly specialized tissues such as the brain, give rise to different forms of disease. In this review, we discuss accumulating evidence that changes in the m6A and m5C methylation systems contribute to neurocognitive disorders. Early studies first identified mutations within FMR1 to cause intellectual disability Fragile X syndromes several years before FMR1 was identified as an m6A RNA reader protein. Subsequently, familial mutations within the m6A writer gene METTL5, m5C writer genes NSUN2, NSUN3, NSUN5, and NSUN6, as well as THOC2 and THOC6 that form a protein complex with the m5C reader protein ALYREF, were recognized to cause intellectual development disorders. Similarly, differences in expression of the m5C writer and reader effector proteins, NSUN6, NSUN7, and ALYREF in brain tissue are indicated in individuals with Alzheimer’s disease, individuals with a high neuropathological load or have suffered traumatic brain injury. Likewise, an abundance of m6A reader and anti-reader proteins are reported to change across brain regions in Lewy bodies diseases, Alzheimer’s disease, and individuals with high cognitive reserve. m6A-modified RNAs are also reported significantly more abundant in dementia with Lewy bodies brain tissue but significantly reduced in Parkinson’s disease tissue, whilst modified RNAs are misplaced within diseased cells, particularly where synapses are located. In parahippocampal brain tissue, m6A modification is enriched in transcripts associated with psychiatri

关键词： 5-methylcytosine methylation Alzheimer’s disease cognitive diseases epitranscriptomics intellectual disability Lewy body diseases N6 adenosine RNA modification

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Bile acid metabolism and signaling in health and disease:molecular mechanisms and therapeutic targets

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2014-2064页

作者： Joshua S.Fleishman Sunil Kumar department of pharmaceutical sciences College of Pharmacy and Health SciencesSt.John’s UniversityQueensNYUSA

Bile acids,once considered mere dietary surfactants,now emerge as critical modulators of macronutrient(lipid,carbohydrate,protein)metabolism and the systemic pro-inflammatory/anti-inflammatory balance.Bile acid metabolism and signaling pathways play a crucial role in protecting against,or if aberrant,inducing cardiometabolic,inflammatory,and neoplastic conditions,strongly influencing health and disease.No curative treatment exists for any bile acid influenced disease,while the most promising and well-developed bile acid therapeutic was recently rejected by the FDA.Here,we provide a bottom-up approach on bile acids,mechanistically explaining their biochemistry,physiology,and pharmacology at canonical and non-canonical receptors.Using this mechanistic model of bile acids,we explain how abnormal bile acid physiology drives disease pathogenesis,emphasizing how ceramide synthesis may serve as a unifying pathogenic feature for cardiometabolic diseases.We provide an in-depth summary on pre-existing bile acid receptor modulators,explain their shortcomings,and propose solutions for how they may be remedied.Lastly,we rationalize novel targets for further translational drug discovery and provide future perspectives.Rather than dismissing bile acid therapeutics due to recent setbacks,we believe that there is immense clinical potential and a high likelihood for the future success of bile acid therapeutics.

关键词： metabolism rejected shortcomings

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Understanding the Novel Approach of Nanoferroptosis for Cancer Therapy

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Nano-Micro Letters 2024年第9期16卷 501-556页

作者： Afsana Sheikh Prashant Kesharwani Waleed H.Almalki Salem Salman Almujri Linxin Dai Zhe‑Sheng Chen Amirhossein Sahebkar Fei Gao department of Pharmaceutics School of Pharmaceutical Education and ResearchJamia HamdardNew Delhi 110062India department of Pharmacology and Toxicology Faculty of PharmacyUmm Al-Qura UniversityMakkahSaudi Arabia department of Pharmacology College of PharmacyKing Khalid University61421 Asir‑AbhaSaudi Arabia State Key Laboratory of Southwestern Chinese Medicine Resources Pharmacy SchoolChengdu University of Traditional Chinese MedicineChengdu 611130People’s Republic of China department of pharmaceutical sciences College of Pharmacy and Health SciencesSt.John’s UniversityNew York 11439USA Biotechnology Research Center Pharmaceutical Technology InstituteMashhad University of Medical SciencesMashhadIran Applied Biomedical Research Center Mashhad University of Medical SciencesMashhadIran

As a new form of regulated cell death,ferroptosis has unraveled the unsolicited theory of intrinsic apoptosis resistance by cancer cells.The molecular mechanism of ferroptosis depends on the induction of oxidative stress through excessive reactive oxygen species accumulation and glutathione depletion to damage the structural integrity of cells.Due to their high loading and structural tunability,nanocarriers can escort the delivery of ferro-therapeutics to the desired site through enhanced permeation or retention effect or by active targeting.This review shed light on the necessity of iron in cancer cell growth and the fascinating features of ferroptosis in regulating the cell cycle and metastasis.Additionally,we discussed the effect of ferroptosis-mediated therapy using nanoplatforms and their chemical basis in overcoming the barriers to cancer therapy.

关键词： Ferroptosis Nanoparticles Ferrotherapy Cancer Genes Nanotechnology Toxicity Reactive oxygen species

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Targeted anti-cancer therapy: Co-delivery of VEGF siRNA and Phenethyl isothiocyanate (PEITC) via cRGD-modified lipid nanoparticles for enhanced anti-angiogenic efficacy

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Asian Journal of pharmaceutical sciences 2024年第2期19卷 170-187页

作者： Bao Li Haoran Niu Xiaoyun Zhao Xiaoyu Huang Yu Ding Ke Dang Tianzhi Yang Yongfeng Chen Jizhuang Ma Xiaohong Liu Keda Zhang Huichao Xie Pingtian Ding School of pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China School of Life Science and Biopharmaceutics Shenyang pharmaceutical University Shenyang 110016 China department of Basic pharmaceutical sciences.School of pharmacy Husson University Bangor ME 04401USA College of pharmacy Shenzhen Technology UniversityShenzhen 518118China

Anti-tumor angiogenesis therapy, targeting the suppression of blood vessel growth in tumors, presents a potent approach in the battle against cancer. Traditional therapies have primarily concentrated on single-target techniques, with a specific emphasis on targeting the vascular endothelial growth factor, but have not reached ideal therapeutic efficacy. In response to this issue, our study introduced a novel nanoparticle system known as CS-siRNA/PEITC&L-cRGD NPs. These chitosan-based nanoparticles have been recognized for their excellent biocompatibility and ability to deliver genes. To enhance their targeted delivery capability, they were combined with a cyclic RGD peptide (cRGD). Targeted co-delivery of gene and chemotherapeutic agents was achieved through the use of a negatively charged lipid shell and cRGD, which possesses high affinity for integrin αvβ3 overexpressed in tumor cells and neovasculature. In this multifaceted approach, co-delivery of VEGF siRNA and phenethyl isothiocyanate (PEITC) was employed to target both tumor vascular endothelial cells and tumor cells simultaneously. The co-delivery of VEGF siRNA and PEITC could achieve precise silencing of VEGF, inhibit the accumulation of HIF-1α under hypoxic conditions, and induce apoptosis in tumor cells. In summary, we have successfully developed a nanoparticle delivery platform that utilizes a dual mechanism of action of anti-tumor angiogenesis and pro-tumor apoptosis, which provides a robust and potent strategy for the delivery of anti-cancer therapeutics.

关键词： Anti-angiogenesis Tumor apoptosis Nanoparticles VEGF siRNA Hypoxia inducible factor(HIF)-1 protein Phenethyl isothi ocyanate(PEITC)

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Progress in experimental models to investigate the in vivo and in vitro antidiabetic activity of drugs

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Animal Models and Experimental Medicine 2024年第3期7卷 297-309页

作者： Yasodha Krishna Janapati Sunil Junapudi School of pharmacy&Health sciences United States International University-AFRICA(USIU-A)NairobiKenya department of pharmaceutical Chemistry Geethanjali College of PharmacyKeesaraIndia

Diabetes mellitus is one of the world's most prevalent and complex metabolic disorders,and it is a rapidly growing global public health issue.It is characterized by hyperglycemia,a condition involving a high blood glucose level brought on by deficiencies in insulin secretion,decreased activity of insulin,or both.Prolonged effects of diabetes include cardiovascular problems,retinopathy,neuropathy,nephropathy,and vascular alterations in both macro-and micro-blood vessels.In vivo and in vitro models have always been important for investigating and characterizing disease pathogenesis,identifying targets,and reviewing novel treatment options and medications.Fully understanding these models is crucial for the researchers so this review summarizes the different experimental in vivo and in vitro model options used to study diabetes and its consequences.The most popular in vivo studies involves the small animal models,such as rodent models,chemically induced diabetogens like streptozotocin and alloxan,and the possibility of deleting or overexpressing a specific gene by knockout and transgenic technologies on these animals.Other models include virally induced models,diet/nutrition induced diabetic animals,surgically induced models or pancreatectomy models,and non-obese models.Large animals or non-rodent models like porcine(pig),canine(dog),nonhuman primate,and Zebrafish models are also outlined.The in vitro models discussed are murine and human beta-cell lines and pancreatic islets,human stem cells,and organoid cultures.The other enzymatic in vitro tests to assess diabetes include assay of amylase inhibition and inhibition ofα-glucosidase activity.

关键词： animal models diabetes mellitus typeⅠ diabetes mellitus typeⅡ in vitro and in vivo models

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Krüppel-like factor 2(KLF2),a potential target for neuroregeneration

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Neural Regeneration Research 2024年第11期19卷 2327-2328页

作者： Surajit Hansda Prateeksha Prateeksha Hiranmoy Das department of pharmaceutical sciences Jerry H.Hodge School of PharmacyTexas Tech University Health Sciences CenterAmarilloTXUSA

Neurological disorders and injuries lead to the impairment or depletion of neurons in terms of quantity,structure,or function,resulting in the loss of cognitive,emotional,and physical abilities in human beings.This,in turn,accompanies the shortfall of valuable human resources and economic potential,causing a detriment to society.Addressing these challenges,therefore,becomes imperative not only from a humanitarian perspective but also as a means of preserving human capital and bolstering economic prosperity.

关键词： companies injuries potential

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mIgM-mediated splenic marginal zone B cells targeting of folic acid for immunological evasion

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Acta Pharmaceutica Sinica B 2024年第2期14卷 808-820页

作者： Huan Wang Zhuxuan Jiang Zhiwei Guo Gan Luo Tianhao Ding Changyou Zhan department of Pharmacology School of Basic Medical Sciences&Department of PharmacyShanghai Pudong HospitalFudan UniversityShanghai 200032China department of pharmaceutical sciences School of PharmacyNaval Medical UniversityShanghai 200433China Shanghai Engineering Research Center for Synthetic Immunology Fudan UniversityShanghai 200032China

Folic acid is a fully oxidized synthetic folate with high bioavailability and stability which has been extensively prescribed to prevent congenital disabilities.Here we revealed the immunosuppressive effect of folic acid by targeting splenic marginal zone B(MZB)cells.Folic acid demonstrates avid binding with the Fc domain of immunoglobulin M(IgM),targeting IgM positive MZB cells in vivo to destabilize IgM-B cell receptor(BCR)complex and block immune responses.The induced anergy of MZB cells by folic acid provides an immunological escaping window for antigens.Covalent conjugation of folic acid with therapeutic proteins and antibodies induces immunological evasion to mitigate the production of anti-drug antibodies,which is a major obstacle to the long-term treatment of biologics by reducing curative effects and/or causing adverse reactions.Folic acid acts as a safe and effective immunosuppressant via IgM-mediated MZB cells targeting to boost the clinical outcomes of biologics by inhibiting the production of anti-drug antibodies,and also holds the potential to treat other indications that adverse immune responses need to be transiently shut off.

关键词： Membrane-bound IgM Anti-drugantibodies Bcell anergy Folic acid Marginal zoneBcells Bcell receptor Biologics Targeting

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Targeting brain tumors with innovative nanocarriers:bridging the gap through the blood-brain barrier

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Oncology Research 2024年第5期32卷 877-897页

作者： KARAN WADHWA PAYAL CHAUHAN SHOBHIT KUMAR RAKESH PAHWA RAVINDER VERMA RAJAT GOYAL GOVIND SINGH ARCHANA SHARMA NEHA RAO DEEPAK KAUSHIK department of pharmaceutical sciences Maharshi Dayanand UniversityRohtak124001India department of pharmaceutical Technology Meerut Institute of Engineering and Technology(MIET)NH-58Delhi-Roorkee HighwayMeerut250005India Institute of pharmaceutical sciences Kurukshetra UniversityKurukshetra136119India department of pharmaceutical sciences Chaudhary Bansi Lal UniversityBhiwani127021India MM College of pharmacy Maharishi Markandeshwar(Deemed to be University)Mullana-AmbalaHaryana133207India Delhi pharmaceutical sciences.and Research University(DIPSAR) Delhi Pharmaceutical Sciences and Research UniversityNew Delhi110017India

Background:Glioblastoma multiforme(GBM)is recognized as the most lethal and most highly invasive tumor.The high likelihood of treatment failure arises fromthe presence of the blood-brain barrier(BBB)and stemcells around GBM,which avert the entry of chemotherapeutic drugs into the tumormass.Objective:Recently,several researchers have designed novel nanocarrier systems like liposomes,dendrimers,metallic nanoparticles,nanodiamonds,and nanorobot approaches,allowing drugs to infiltrate the BBB more efficiently,opening up innovative avenues to prevail over therapy problems and radiation therapy.Methods:Relevant literature for this manuscript has been collected from a comprehensive and systematic search of databases,for example,PubMed,Science Direct,Google Scholar,and others,using specific keyword combinations,including“glioblastoma,”“brain tumor,”“nanocarriers,”and several others.Conclusion:This review also provides deep insights into recent advancements in nanocarrier-based formulations and technologies for GBM management.Elucidation of various scientific advances in conjunction with encouraging findings concerning the future perspectives and challenges of nanocarriers for effective brain tumor management has also been discussed.

关键词： Glioblastoma Brain tumor Blood-brain barrier Liposomes Metallic nanoparticles Nanocarriers

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Medicinal Effects, Phytochemistry,Pharmacology of Euphorbia prostrata and Promising MolecularMechanisms

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Chinese Journal of Integrative Medicine 2024年第2期30卷 181-192页

作者： Nirmala Kumari Yadav Rakesh Yadav department of pharmacy Banasthali VidyapithBanasthali(304022)RajasthanIndia department of pharmaceutical sciences Indira Gandhi UniversityMeerpurRewari(122502)HaryanaIndia National Forensic sciences.University Tripura CampusAgartala(799001)TripuraIndia

Euphorbiaceae is a large family of dicotyledonous angiosperms with diverse genera including Euphorbia prostrata(E.prostrata).Current research has provided scientific evidence for traditional uses of E.prostrata against diverse pathological conditions such as anti-hemorrhoidal,anti-inflammatory,analgesic,wound healing,antioxidant,antibacterial,leishmanicidal,antitumor activity,and so on.The phytochemical screening has revealed the presence of glycosides,phytosterols,flavonoids,polyphenols,tannins,and anthraquinones with chemical structures elucidation of their respective compounds.The uniqueness of such multifactorial compounds present in this species endorses it as the potent therapeutic or prophylactic choice for several fatal diseases.Although ethnomedical applications served as a significant citation for pharmacology,the molecular mechanism has not been reviewed yet.The present paper provides a comprehensive review of research outcomes,pharmacology,toxicology,and molecular signaling of phytochemicals of E.prostrata species as a reference for relevant researchers.The study of bioactive compounds in crude extracts and fractions,the demonstration of primary mechanisms of pharmacology,along with the addition of toxicity,and clinical trials,should be conceded in depth.This review underlines the E.prostrata species that can be a promising phytomedicine since we are committed to excavating more intensely into their pharmacological role.

关键词： Euphorbia prostrata Euphorbiaceae phytochemicals ethnomedical applications toxicology molecularmechanism

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