Anti-inflammatory & anti-allergy agents in medicinal chemistry最新文献

{"title":"Leveraging Underutilized Sri Lankan Fruits in the Fight against Autoimmune Disorders.","authors":"M P Theja Virajini, Mithila Bandara, Prasad Jayasooriya, Kalpa W Samarakoon, Anchala I Kuruppu","doi":"10.2174/0118715230353359241211215415","DOIUrl":"https://doi.org/10.2174/0118715230353359241211215415","url":null,"abstract":"<p><p>The potential of underutilized plant species to improve food security, health, eco-nomic output, and the environment has not been fully realized. Sri Lanka an island on the Indian Ocean is home to numerous plant species with significant medicinal potential, in-cluding many underutilized plants that could help meet the growing demand for food, en-ergy, medicines, and industrial resources. Globally, there are over a thousand known and unknown phytochemicals derived from plants. Although these compounds are primarily produced by plants for self-defence, in vitro and in vivo studies have demonstrated their anti-inflammatory properties. Recent research indicates that several phytochemicals can also protect humans from disease by regulating key inflammatory pathways, such as NF-κB, MAPK, JAK/STAT and Nrf-2, which are involved in autoimmune diseases. Thus, these bioactive compounds are vital for managing autoimmune disorders. This review will ex-plore underutilized fruit crops from Sri Lanka that could be used against inflammation, in-cluding autoimmune diseases.</p>","PeriodicalId":94368,"journal":{"name":"Anti-inflammatory & anti-allergy agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Formulation, Characterization, and Cytotoxic Effect of Indomethacin-Loaded Nanoparticles.","authors":"Kaan Yalçınkaya, Behiye Şenel, Evrim Akyıl","doi":"10.2174/0118715230348349241126053733","DOIUrl":"https://doi.org/10.2174/0118715230348349241126053733","url":null,"abstract":"<p><strong>Background: </strong>Indomethacin (IND), classified as class 2 in the Biopharmaceutical Classification System (BCS), has emerged as an anti-inflammatory agent with low solubility and high permeability. Widely used in the treatment of various diseases, such as rheumatoid arthritis and ankylosing spondylitis, this drug is well-known for its adverse effects, particularly in the stomach, and a short biological half-life, which is around 1.5-2 hours.</p><p><strong>Objective: </strong>The aim of this study was to overcome the challenges of low solubility, short half-life, and serious side effects occurring with the use of IND-loaded formulations of Solid Lipid Nanoparticles (SLNs) and Polymeric Nanoparticles (PNPs).</p><p><strong>Methods: </strong>For PNPs, emulsification/solvent evoporation method was employed, and for SLNs, the hot homogenizaton method was applied. Eudragit® RLPO (RLPO) and Eudragit® RSPO (RSPO) were used as polymers for PNP and Dynasan®116 (DYN) was used as the solid lipid for SLN. Prepared formulations were characterized for Particle Size (PS), Poly-dispersity Index (PDI), Zeta Potential (ZP), Encapsulation Efficiency (%EE), and drug-ex-recipient compatibility using DSC, FT-IR, and 1H NMR; cumulative drug release rates were assessed using HPLC and in vitro cytotoxicities were examined by the MTT assay.</p><p><strong>Results: </strong>Both PNP and SLN formulations' zeta potential, particle size, and PDI results indicated the formulations to have good stability. Encapsulation efficiency values were obtained as desired. Drug-excipient compatibility was proved using DSC, FT-IR, and 1H NMR. In vitro dissolution results have proven both formulations to have longer release than pure indomethacin. In the MTT analysis of indomethacin application for 24 and 48 hours, a linear correlation was observed between drug concentration and cell viability, and it was determined that the PNP formulation exhibited fewer toxic effects among the formulations. This has proven the PNP nanocarrier as safer for normal cells.</p><p><strong>Conclusion: </strong>IND-loaded PNP and SLN formulations have been successfully prepared in this work and they have achieved drug release in the intestine and prolonged the release duration.</p>","PeriodicalId":94368,"journal":{"name":"Anti-inflammatory & anti-allergy agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142934173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxicity and anti-inflammatory effects of Eleutherine bulbosa (Miller) Urb, ethanolic extract, in zebrafish (Danio rerio).","authors":"Dionisia P Ferreira, Fabrício H Holanda, Swanny F Borges, Ryan da S Ramos, Victoria Mae T Shinkai, Gisele C De Souza, José Carlos T Carvalho, Raphael S Pimenta, José Luiz M Do Nascimento, Irlon M Ferreira","doi":"10.2174/0118715230352701241130053455","DOIUrl":"https://doi.org/10.2174/0118715230352701241130053455","url":null,"abstract":"<p><strong>Introduction: </strong>Eleutherine bulbosa (Miller) Urb, popularly known as \"marupa-zinho\", is frequently used in traditional medicine for treating various diseases, including hypertension, ulcers, constipation, and intestinal infection. However, there is little scientific knowledge available regarding the pharmacological effects of this species. Thus in vivo and in silico phytochemical studies are required to establish whether this plant has these effects. Further tests were necessary to evaluate the pharmacological activity of the compounds found in this plant, and demonstrate results related to the anti-inflammatory process, which will serve as the basis for future research in this area.</p><p><strong>Methods: </strong>Therefore, our study aimed to determine the acute toxicity levels of the hexanoic fraction of the ethanolic extract of Eleutherine bulbosa (referred to as ExtHF) using adult zebrafish, with the determination of the LD50, behavioral and histopathological evaluations, as well as the anti-inflammatory potential of ExtHF, at different doses, in abdominal edema induced by carrageenan. The acute toxicity study and histopathological analysis in zebrafish showed that ExtHF has a high toxic potential, with an LD50 of 346.74 mg/kg. However, ExtHF showed an anti-inflammatory effect by inhibiting abdominal edema at all doses tested.</p><p><strong>Results: </strong>The inhibition rate of 66.2% and 62.4%, respectively, was observed with the 2.5 mg/kg dose, respectively, indicating that ExtHF is safe in terms of acute toxicity based on behavioral changes, mortality rate, and histopathological examination. Therefore, ExtHF has an acceptable level of safety for acute toxicity, defined by the analysis of behavioral changes, mortality, and histopathology, showing a significant anti-inflammatory effect in zebrafish at all doses, showing that ExtHF was very efficient in preventing the formation of edema, in addition, it was also revealed that ExtHF has a great effect in reversing the edema which is already installed.</p><p><strong>Conclusion: </strong>Molecular docking studies revealed that the eleutherol molecule isolated from E. bulbosa has a dual inhibition profile against cyclooxygenase-1 and 2.</p>","PeriodicalId":94368,"journal":{"name":"Anti-inflammatory & anti-allergy agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142934153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery and Chemical Exploration of Spiro[Benzofuran-3,3'-Pyrroles] Derivatives as Innovative FLT3 Inhibitors for Targeting Acute Myeloid Leukemia.","authors":"Mohammed M Al-Mahadeen, Areej M Jaber, Jalal A Zahra, Belal O Al-Najjar, Mustafa M El-Abadelah, Monther A Khanfar","doi":"10.2174/0118715230343474241009112335","DOIUrl":"https://doi.org/10.2174/0118715230343474241009112335","url":null,"abstract":"<p><strong>Aims: </strong>This study aimed at the synthesis of several spiro[benzofuran-3,3'-pyrroles] derivatives by a three-component reaction conducted by mixing DMAD, N-bridgehead het-erocycles, and benzofuran-2,3-diones in dichloromethane at room temperature for 24 h. Moreover, in vitro evaluation of their cytotoxicity affinities against FMS-like tyrosine kinase 3 was carried out.</p><p><strong>Objectives: </strong>The objective of this study was to use a one-pot, three-component reaction to synthesize a novel set of spiro[benzofuran-3,3'-pyrroles] derivatives.</p><p><strong>Methods: </strong>A novel set of spiro[benzofuran-3,3'-pyrroles] ((11-13)a-e) was synthesized by a one-pot three-component reaction involving dimethyl acetylenedicarboxylate, N-bridgehead heterocycles and benzofuran-2,3-diones in dichloromethane at room temperature for 24 h. The compounds were analyzed using NMR 1H, 13C, 2D-NMR (COSY, HMQC, HMBC), and HRMS. Docking simulations were conducted to elucidate the anticancer activity of synthe-sized compounds on FLT3 protein, with Gilteritinib as a reference for comparison.</p><p><strong>Results: </strong>This study demonstrated the successful design, synthesis, and biological evaluation of spiro[benzofuran-3,3'-pyrroles] derivatives as FLT3 inhibitors for AML treatment. The synthesized compounds demonstrated promising binding affinities and significant inhibitory activity against FLT3 kinase. The inhibitors (11a, 11b, 11c, 12d, and 12e) exhibited excellent selectivity profiles against FLT3. Particularly, compound 12e showed strong binding affinity and potent inhibitory activity (IC50 = 2.5 μM).</p><p><strong>Conclusion: </strong>Fifteen new synthetic spiro[benzofuran-3,3'-pyrroles] were prepared, character-ized, and evaluated for cytotoxicity affinities against FMS-like tyrosine kinase 3. Compound 12e showed strong binding affinity and potent inhibitory activity (IC50 = 2.5 μM), making it a promising candidate for further development as a therapeutic option for AML treatment. These findings lay the groundwork for further optimization and development of spiro[benzo-furan-3,3'-pyrroles] derivatives as potential therapeutics for AML treatment. Further studies are needed to explore their efficacy and safety profiles in preclinical and clinical settings.</p>","PeriodicalId":94368,"journal":{"name":"Anti-inflammatory & anti-allergy agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In-vitro Antioxidant, and In-vivo Analgesics and Anti-inflammatory Activity of Allamanda blanchetii Leaf Extract in Rats.","authors":"Achla Vyas, Revathi Gupta, Rakesh Jatav","doi":"10.2174/0118715230340178241008163943","DOIUrl":"https://doi.org/10.2174/0118715230340178241008163943","url":null,"abstract":"<p><strong>Objective: </strong>This study assessed the In-vitro Antioxidant and In-vivo Analgesics and Anti-inflammatory Activity of Allamanda blanchetii Leaf Extract in Rats.</p><p><strong>Introduction: </strong>Diverse pharmacological applications of plants from the Apocynaceae family are reported in the literature. Allamanda blanchetii; an ornamental species belonging to the Apocynaceae family, is characterized by diverse biological activities, i.e. antioxidant, cyto-toxic, thrombolytic, membrane-stabilizing, antimicrobial, and anti-proliferative effects. This species represents a perennial flora that thrives in tropical and subtropical climates.</p><p><strong>Material and methods: </strong>Ultrasonication-assisted method used for plant extraction. The ex-tracts were subjected to phytochemical screening tests, followed by total phenolic content analysis, using gallic acid as a standard. The antioxidant activity was examined by DPPH scavenging and FRAP assays. The acetic acid-induced writhing test, tail flick, and Hot plate method were used for the determination of analgesic activity. Anti-inflammatory activity by following carrageenan-induced paw edema Results: ABLE treatments show analgesic effectiveness against the acid-induced pain source, tail flick, and hot plate methods at different doses of ABLE 400,200,100 mg/kg results showed respectively- 55.32, 38.67, and 22.85 (% inhibition), 89.47%, 62.57 %, 49.57%, and 100%, 92.40%, 65.33% response after 180 min of drug administration. ABLE 400 and 200 mg/kg exhibit effective results (1.43± 0.005 and 1.50± 0.008) against carra-geenan-induced intoxication.</p><p><strong>Discussion: </strong>The fundamental components of antioxidants that can aid in the reduction of free radicals include phenol, flavonoids, and polyphenols. Applying DPPH and FRAP, ABLE exhibits remarkable antioxidant activity. When it comes to both centrally and periph-erally acting analgesics, ABLE exhibits highly effective activity. Methanolic ABLE had a noticeable impact on paw edema caused by carrageenan. Antioxidants, alkaloids, and gly-cosides were present in methanolic ABLE, which allowed it to efficiently combat inflam-matory mediators and the cause of pain.</p><p><strong>Conclusion: </strong>Ultrasonic assistance is beneficial in isolating active metabolites in plants, with phenolic compounds exhibiting antioxidant activity. ABLE, a plant with 55% squalene, ef-fectively combats inflammatory mediators and pain. Further investigation is needed to iden-tify biomarkers in the plant.</p>","PeriodicalId":94368,"journal":{"name":"Anti-inflammatory & anti-allergy agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142840726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genistein Enhances the Beneficial Effects of Exercise on Antioxidant and Anti-Inflammatory Balance and Cardiomyopathy in Ovariectomized Diabetic Rats.","authors":"Mohammad Mohammadi, Amir Mohammad Salehi, Samaneh Mohassel Azadi, Maryam Khajvand-Abedini, Farzaneh Nazari-Serenjeh, Parisa Habibi","doi":"10.2174/0118715230305886240916105248","DOIUrl":"https://doi.org/10.2174/0118715230305886240916105248","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Aims: &lt;/strong&gt;This study aimed to investigate the effects of genistein, swimming exercise, and their co-treatment on heart oxidative stress, inflammation, and cardiomyopathy in ovariectomized diabetic rats.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;It is well-established that diabetes is a major risk factor for cardiovascular disease in both young and postmenopausal women. Genistein is a natural phytoestrogen that has estrogenic effects. Studies have shown that genistein has a positive impact on menopause, cardiovascular dis-ease, and diabetes in women. However, the impact of genistein treatment alone and in combination with exercise training on the management of cardiac disease in diabetic women after ovarian hor-mone deprivation has not been fully explored.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;The objective of this study was to evaluate the effect of genistein alone or in combination with exercise training on the cardiac expression of oxidative/inflammation biomarkers (MDA, OSI, TOS, TNF- α, and NF-κB) and miRNA-133, IGF-1, and Bcl-2 in the diabetic ovariectomized rats.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A group of Wistar rats were randomly divided into seven groups, with eight rats in each group. The groups were named control, sham, ovariectomized group (OVX), OVX +diabetes (OD), OD+ genistein (1 mg/kg, eight weeks; daily SC), OD+exercise (eight weeks), and OD+ genistein+exercise (eight weeks). The rats were given a high-fat diet and low-dose streptozotocin injection to induce diabetes. After eight weeks, the rats were anesthetized, and their hearts were removed. The study assessed the effects of treatment by measuring the expression of miRNA-133 using Real-time Polymerase Chain Reaction (PCR) and the protein levels of Bcl-2, Bax, and IGF-1 using Western blotting. The study also evaluated the levels of inflammation and oxidative stress markers using ELISA. Pathological changes were also assessed using periodic acid Schiff and he-matoxylin & eosin.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;After ovariectomy, the levels of cardiac miRNA-133, IGF-1, and Bcl-2 expression were down-regulated, and the levels of MDA, OSI, TOS, TNF-α, and NF-κB were increased, with a reduced total antioxidant capacity. Diabetes had an additive effect on these factors. Genistein was found to have a positive impact on oxidative and inflammation levels, and it also increased the expression of miRNA-133, Bcl-2, and IGF-1 in rats with OD. Furthermore, the combination of genistein and exercise had a positive effect on miRNA-133, Bcl-2, and IGF-1 expression in the heart, leading to a decrease in Bax levels. The combined intervention showed a noticeable improve-ment in oxidative and inflammation conditions. Histological examination revealed some abnormal-ities in cardiac tissue, which were found to be improved with genistein and/or exercise treatments.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Genistein or/and exercise as a natural replacement therapy could improve diabetic-induced cardiac com","PeriodicalId":94368,"journal":{"name":"Anti-inflammatory & anti-allergy agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Comprehensive Review on Insect Repellent Agents: Medicinal Plants and Synthetic Compounds.","authors":"Deepak Kumar Yadav, Sunny Rathee, Versha Sharma, Umesh K Patil","doi":"10.2174/0118715230322355240903072704","DOIUrl":"https://doi.org/10.2174/0118715230322355240903072704","url":null,"abstract":"<p><p>Plant-based repellents have been used for generations as personal protection against mosquitoes. Ethnobotanical studies provide valuable knowledge for developing natural prod-ucts. Commercial repellents with plant-based ingredients are popular, but insufficient studies follow Pesticide Evaluation Scheme WHO guidelines. Further standardized studies are needed to evaluate repellent compounds and develop high-repellency and safe products. Essential Oils (EOs) from aromatic plants have gained popularity as low-risk insecticides due to their low toxicity and short environmental persistence. These plant-derived EOs, produced through steam distillation, have repellent, insecticidal, and growth-reducing effects on various insects. They control phytophagous insects, bite flies, and home and garden insects. US registration is the main hurdle for new EOs. This review explores the use of essential oils from plants as a natural repellent, focusing on their effectiveness and synergistic effects. Essential oils are vol-atile mixtures of hydrocarbons with diverse functional groups, and their effectiveness is linked to monoterpenes and sesquiterpenes. Synergistic effects can improve their effectiveness, and the use of other natural products, like vanillin, can increase protection time. Cymbopogon spp., Ocimum spp., and Eucalyptus spp. are among the most promising plant families.</p>","PeriodicalId":94368,"journal":{"name":"Anti-inflammatory & anti-allergy agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142485100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Review on Phytochemical Constituents Used as Current Treatment Strategies for Neurodegenerative Disease.","authors":"Krishna Jee, Rishabh Gaur, Jai Prakash Kadian, Meenu, Muhammad Murtaza, Sanjay Kumar Verma, Bharati Malik, Shilpa","doi":"10.2174/0118715230310192240925165925","DOIUrl":"https://doi.org/10.2174/0118715230310192240925165925","url":null,"abstract":"<p><p>In today's time, a diversity of neurodegenerative diseases that widely affect the CNS causing insufficiency in particular brain processes such as memory, mobility, and cognition due to the moderate loss of CNS neurons. This review emphasizes different phytochemical constituents used widely for the prevention or treatment of various neurodegenerative diseases such as Alzheimer's disease (AD) and Parkin-son's disease (PD). Berberin (BBR), which is an isoquinoline class of alkaloid and isolated from the plant Hydrastis condenses and Berberis aaristata, has both acetylcholine esterase (AChE) inhibiting properties as well as monoamine oxidase (MAO) inhibiting properties involved in the betterment of AD by decreasing the production of reactive oxygen species (ROS). Like BBR, Physostigmine, isolated from the Physostigma venenosum / Calabar bean and belongs to the family Leguminosae, and Morphine, isolated from the plant Papaver somniferum / Opium poppy or Breadseed poppy, also has a significant impact on the management and treatment of AD and PD by reducing both neuroinflammation and pro-inflammatory cytokines production. Morphine bineurodegenerative diseases with μ-opioid receptor (MOR) in CNS elevate GABA levels in the synaptic cleft of the brain and reduces the neurotoxicity via stimulation of MOR. It has been discovered that physostigmine improves cognitive function in AD patients and reduces α-synu-clein expression in PD neural cell lines. Isorhyncophylline (IRN) is a Chinese herbal medicine isolated from the plant Uncaria rhyncophylla which provides neuroprotective efficiency against neurotoxicity that occurs by amyloid β (the main component of amyloid plaques) found in the brain of people with AD.</p>","PeriodicalId":94368,"journal":{"name":"Anti-inflammatory & anti-allergy agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142485101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dry-feed Added Quercetin Mitigates Cyclophosphamide-induced Oxidative Stress, Inflammation and Gonadal Fibrosis in Adult Male Rats.","authors":"Anthony T Olofinnade, Oladotun B Ajifolawe, Olakunle J Onaolapo, Adejoke Y Onaolapo","doi":"10.2174/0118715230316410240821105658","DOIUrl":"https://doi.org/10.2174/0118715230316410240821105658","url":null,"abstract":"<p><strong>Background: </strong>Cyclophosphamide (CYP), a widely used cancer chemotherapeutic agent has been linked with male gonadotoxicity, resulting in infertility. The notion that potent antioxidants could be beneficial in mitigating CYP-induced gonadotoxicity necessitated this research. Therefore, we examined the effects of feed-added quercetin on CYP-induced gon-adotoxicity in male rats.</p><p><strong>Methods: </strong>Male postpubertal rats were randomly assigned into six groups of 10 rats each. The normal control (fed standard rodent diet) and two groups fed quercetin-supplemented diet at 100 and 200 mg/kg of feed received normal saline intraperitoneally at 2 ml/kg daily. A fourth group which served as the CYP control (fed standard rodent diet) and the last two groups fed quercetin at 100 and 200 mg/kg of feed were administered CYP at 150 mg/kg/day. Rats were administered normal saline or CYP intraperitoneally on days 1 and 2, while standard diet or feed-added quercetin was administered daily for 21 days. On day 22, half of the animals were either sacrificed or paired with age-matched females for fertility assessment. Estimation of testosterone levels, antioxidant, anti-inflammatory markers, and histomorphological exami-nation of the testis and epididymis was also assessed.</p><p><strong>Results: </strong>The administration of CYP was associated with weight loss, decreased food intake, decreased antioxidant capacity, increased gonadosomatic index, increased lipid peroxidation, sub-fertility, and histological evidence of gonadal injury. However, administration of querce-tin reversed CYP-induced changes.</p><p><strong>Conclusion: </strong>The result of this study suggests that dietary quercetin supplementation has the ability to mitigate CYP induced gonadotoxicity and mitigate subfertility in male rats. How-ever, further studies are required to assess its possible use in humans.</p>","PeriodicalId":94368,"journal":{"name":"Anti-inflammatory & anti-allergy agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142335924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Docking, Pharmacophore Modeling, and ADMET Prediction of Novel Heterocyclic Leads as Glucokinase Activators.","authors":"Anuradha Mehra, Amit Mittal, Shivangi Singh","doi":"10.2174/0118715230325278240821053346","DOIUrl":"https://doi.org/10.2174/0118715230325278240821053346","url":null,"abstract":"<p><strong>Background: </strong>A pivotal impetus has driven the development of numerous small molecules aiming to improve therapeutic strategies for type 2 diabetes. Glucokinase (GK) activation has been offered a new realm of therapeutic antidiabetic activity with novel heter-ocyclic derivatives. In the context of antidiabetic drug design, GK is an interesting and newly validated target. A key enzyme needed for blood glucose homeostasis is Glucokinase, which is dysfunctional in individuals with type 2 diabetes. Heterocyclic derivatives are utilized in this innovative approach to activate GK enzymes as medicinal agents that will significantly improve type 2 diabetes management.</p><p><strong>Objective: </strong>To address type 2 diabetes, as well as minimize unwanted side effects, this research endeavor aimed to develop activators of glucokinase.</p><p><strong>Methods: </strong>A rigorous scrutiny was conducted of the Maybridge online repository, which houses a formidable collection of 53,000 lead compounds. A collection of 125 compounds that contain the thiazolidinedione core was selected from this extensive collection. The struc-tures were generated using ChemDraw 2D, stabilized conformation with ChemBioDraw Ul-tra, and docked using Auto Dock Vina 1.5.6 in this methodology. In addition, log P was pre-dicted online using the Swiss ADME algorithm. The PKCSM software was used to predict the toxicity of the leading compounds.</p><p><strong>Results: </strong>The highest binding affinity was found for AS72 and AS108 to GK receptors. GI absorption and excretion of these compounds were efficient due to Lipinski's Rule of Five compliance. When compared with the standard drugs Dorzagliatin (GKA) and MRK (co-crys-tallized ligand), these substances demonstrated a notable lack of AMES toxicity, skin sensiti-zation, and hepatotoxicity.</p><p><strong>Conclusion: </strong>In recent studies, lead molecules that possess enhanced pharmacokinetic profiles, increased binding affinity, and lower toxicity were developed to act as glucokinase activators.</p>","PeriodicalId":94368,"journal":{"name":"Anti-inflammatory & anti-allergy agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142335936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}