Current pharmaceutical biotechnology最新文献

{"title":"Correlation between Honey Parameters and Wound Healing Properties: The Case of Piedmont (Italy) Samples.","authors":"Simona Martinotti, Gregorio Bonsignore, Mauro Patrone, Elia Ranzato","doi":"10.2174/0113892010328741240828093859","DOIUrl":"10.2174/0113892010328741240828093859","url":null,"abstract":"<p><strong>Introduction: </strong>Honey possesses several positive properties, making it effective in wound healing mechanisms. However, very little information is available on the different honey types for wound healing activity.</p><p><strong>Method: </strong>In the first \"Academy of Sciences\", a public engagement project with high school students, we assessed the properties of thirteen kinds of honey from the Piedmont area (Nord West Italy). In particular, we characterized the color intensity (by Pfund scale), total phenolic content (TPC), total flavonoid content (TFC), H²O² production, and wound closure rate.</p><p><strong>Results: </strong>Then, we tried to verify the presence of a correlation between these parameters, finding a positive correlation between H²O² and wound closure rate.</p><p><strong>Conclusion: </strong>These data pave the way to characterize different types of Italian honey to completely understand its potential.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":"302-311"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revolutionizing Rheumatoid Arthritis Care: AI-infused Herbal Treatments and the Road Ahead.","authors":"Milan Singh Kahlon, Md Moidul Islam, Abhinav Vashishat, Sarjana Raikwar","doi":"10.2174/0113892010305528240506114408","DOIUrl":"10.2174/0113892010305528240506114408","url":null,"abstract":"","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":"316-318"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140956565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibitory Activity of Quercetin, Rutin, and Hyperoside against Xanthine Oxidase: Kinetics, Fluorescence, and Molecular Docking.","authors":"Yali Yu, Yingzhu Xiong, Siman Tong, Yanli Li, Rongcan Cai, Xv Zhang, Feng Gao","doi":"10.2174/0113892010297269240427055003","DOIUrl":"10.2174/0113892010297269240427055003","url":null,"abstract":"<p><strong>Introduction: </strong>Quercetin (Qc), rutin (Ru), and hyperoside (Hyp) are three common polyphenols widely distributed in the plant kingdom.</p><p><strong>Methods: </strong>This study explored the inhibition and mechanisms of Qc, Ru, and Hyp against xanthine oxidase (XOD) by enzyme kinetic analysis, fluorescence analysis, and molecular docking. The inhibitory activities of the three polyphenols on XOD showed the following trend: quercetin > hyperoside > rutin, with IC₅₀ values of 8.327 ± 0.36 μmol/L, 35.215 ± 0.4 μmol/L and 60.811 ± 0.19 μmol/L, respectively. All three polyphenols inhibited xanthine oxidase activity in a mixed-competitive manner. Synchronous fluorescence results demonstrated that three polyphenols binding to XOD were spontaneous and showed static quenching.</p><p><strong>Results: </strong>The binding of the three polyphenols to XOD is mainly driven by hydrogen bonding and van der Waals forces, resulting in the formation of an XOD-XA complex with only one affinity binding site. The binding sites of the three RSFQ phenolic compounds are close to those of tryptophan. Molecular docking showed that all three polyphenols enter the active pocket of XOD and maintain the stability of the complex through hydrogen bonding, hydrophobic interaction, and van der Waals forces.</p><p><strong>Conclusion: </strong>The results provide a theoretical basis for quercetin, rutin, and hyperoside to be used as function factors to prevent hyperuricemia.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":"513-524"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140956433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioactive Compounds from <i>Vicia sativa</i> L. and <i>Vicia monantha</i> Retz. with Unveiling Antiviral Potentials in Newly Green Synthesized CdO Nanoparticles.","authors":"Alyaa Nasr, Ezzat H Elshazly, Dalia F Slima, Mohamed E Elnosary, Ahmed M Sadek, Mona Khamis, Yu Gong, Qian Tian, Gamal A Gouda, Guo-Ping Zhu","doi":"10.2174/0113892010305452240427044346","DOIUrl":"10.2174/0113892010305452240427044346","url":null,"abstract":"<p><strong>Background: </strong>in the current study, a comparative phytochemical analysis was carried out to explore the phenolic and flavonoid contents in the aerial parts of <i>Vicia sativa</i> L and <i>Vicia monantha</i> Retz growing in cultivated, reclaimed, and desert habitats.</p><p><strong>Methods: </strong>High-performance liquid chromatography (HPLC) was used to detect Vicia methanolic extracts' individual phenolic and flavonoid constituents. The first-time synthesis of cadmium oxide nanoparticles (CdO NPs) using the aqueous extract of <i>V. monantha</i> has been developed using a green approach. Also, the cytotoxicity of <i>V. monantha</i> extract and CdO NPs was examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for unveiling them as anti-HAV and anti-AdV.</p><p><strong>Results: </strong>Our results indicated that in the case of desert habitat, the contents of total phenolics (76.37 mg/g) and total flavonoids (65.23 mg/g) of <i>V. monantha</i> were higher than those of V. sativa (67.35 mg/g and 47.34 mg/g, respectively) and the contents of these secondary metabolites were even increased in <i>V. monantha</i> collected from reclaimed land (phenolics: 119.77 mg/g, flavonoids: 88.61 mg/g). Also, <i>V. monantha</i> surpassed V. sativa in the contents of some individual HPLC constituents, and hence, <i>V. monantha</i> was used to synthesize the green CdO NPs and subsequent antiviral tests. The average size of CdO NPs was determined to be 24.28 nm, and the transmission electron microscopy (TEM) images of CdO NPs clearly showed their spherical form and varying particle sizes, with different diameters in the range of 19-29 nm. MTT assay was positive to the exposure of CdO NPs in the normal cell line, proposing that CdO NPs can reduce cell viability. <i>V. monantha</i> extract showed promising antiviral activity against Hepatitis A virus (HAV) and Adenovirus (AdV) with SI of 16.40 and 10.54. On the other hand, CdO NPs had poor antiviral activity against HAV with an SI of 4.74 and moderate antiviral activity against AdV with an SI of 10.54.</p><p><strong>Conclusion: </strong><i>V. monantha</i> is now considered a new, valuable natural resource for phenolics and flavonoids, especially when grown in reclaimed soil. The green CdO NPs based on <i>V. monantha</i> extract showed a promising antiviral effect against HAV and AdV.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":"497-512"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140956467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Self-emulsifying Drug Delivery Systems: Concept to Applications, Regulatory Issues, Recent Patents, Current Challenges and Future Directions.","authors":"Rajib Lochan Maharana, Suryakanta Swain, Santosh Kumar Mahapatra, Bikash Ranjan Jena","doi":"10.2174/0113892010296223240612050639","DOIUrl":"10.2174/0113892010296223240612050639","url":null,"abstract":"<p><p>Self-emulsifying drug delivery systems (SEDDS) can increase the solubility and bioavailability of poorly soluble drugs. The inability of 35% to 40% of new pharmaceuticals to dissolve in water presents a serious challenge for the pharmaceutical industry. As a result, there must be dosage proportionality, considerable intra- and inter-subject variability, poor solubility, and limited lung bioavailability. As a result, it is critical that drugs intended for oral administration be highly soluble. This can be improved through a variety of means, including salt generation and the facilitation of solid and complicated dispersion. Surfactants, co-surfactants, and cosolvents may occasionally be found in SEDDS or isotropic blends. Lipophilic drugs, whose absorption is limited by their dissolution rate, have been used to demonstrate the effectiveness of various formulations and techniques. These particles can form microemulsions and suitable oilin- water emulsions with minimal agitation and dilution by the water phase as they pass through the gastrointestinal tract. This study summarises the numerous advances, biopharmaceutical components, variations, production techniques, characterisation approaches, limitations, and opportunities for SEDDS. With this context in mind, this review compiles a current account of biopharmaceutical advancements, such as the application of quality by design (QbD) methodologies to optimise drug formulations in different excipients with controllable ratios, the presence of regulatory roadblocks to progress, and the future consequences of SEDDS, encompassing composition, evaluation, diverse dosage forms, and innovative techniques for in-vitro converting liquid SEDDS to solid forms.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":"341-364"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design of Optimized Solid Lipid Nanoparticles of Montelukast Sodium and Assessment of Oral Bioavailability in Experimental Model.","authors":"Pankaj Dangre, Paresh Wankhede, Kailas Moravkar, Mohan Kalaskar, Atish Mundada, Shailesh Chalikwar","doi":"10.2174/0113892010300965240612054349","DOIUrl":"10.2174/0113892010300965240612054349","url":null,"abstract":"<p><strong>Introduction: </strong>The objective of the reported work was to develop Montelukast sodium (MS) solid lipid nanoparticles (MS-SLNs) to ameliorate its oral bio-absorption. Herein, the highpressure homogenization (HPH) principle was utilized for the fabrication of MS-SLNs.</p><p><strong>Method: </strong>The study encompasses a 2³ full factorial statistical design approach where mean particle size (Y₁) and percent entrapment efficiency (Y₂) were screened as dependent variables while, the concentration of lipid (X₁), surfactant (X₂), and co-surfactant (X₃) were screened as independent variables. The investigation of MS-SLNs by DSC and XRD studies unveiled the molecular dispersion of MS into the SLNs while TEM study showed the smooth surface of developed MSSLNs. The optimized MS-SLNs exhibited mean particle size (MPS) = 115.5 ± 1.27 nm, polydispersity index (PDI) = 0.256 ± 0.04, zeta potential (ζ) = -21.9 ± 0.32 mV and entrapment efficiency (EE) = 90.97 ± 1.12 %. The <i>In vivo</i> pharmacokinetic study performed in Albino Wistar rats revealed 2.87-fold increments in oral bioavailability.</p><p><strong>Results: </strong>The accelerated stability studies of optimized formulation showed good physical and chemical stability. The shelf life estimated for the developed MS-SLN was found to be 22.38 months.</p><p><strong>Conclusion: </strong>At the outset, the developed MS-SLNs formulation showed a significant increment in oral bioavailability and also exhibited excellent stability in exaggerated storage conditions.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":"576-590"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141450021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardioprotective Potential of <i>Moringa Oleifera</i> Leaf Extract Loaded Niosomes Nanoparticles - Against Doxorubicin Toxicity In Rats.","authors":"Ebtesam A Mohamad, Samya Mahmoud Ahmed, Marwa A Masoud, Fatma Adel Mohamed, Haitham S Mohammed","doi":"10.2174/0113892010303097240605105013","DOIUrl":"10.2174/0113892010303097240605105013","url":null,"abstract":"<p><strong>Introduction: </strong>Doxorubicin (DOX) is one of the most potent anticancer drugs that has ubiquitous usage in oncology; however, its marked adverse effects, such as cardiotoxicity, are still a major clinical issue. Plant extracts have shown cardioprotective effects and reduced the risk of cardiovascular diseases.</p><p><strong>Method: </strong>The current study is intended to explore the cardioprotective effect of ethanolic <i>Moringa Oleifera</i> extracts (MOE) leaves loaded into niosomes (MOE-NIO) against DOXinduced cardiotoxicity in rats. MOE niosomes nanoparticles (NIO-NPs) were prepared and characterized by TEM. Seventy male Wistar rats were randomly divided into seven groups: control, NIO, DOX, DOX+MOE, DOX+MOE-NIO, MOE+DOX, and MOE-NIO+DOX. DOX (4 mg/kg, IP) was injected once per week for 4 weeks with daily administration of MOE or MOENIO (250 mg/kg, PO) for 4 weeks; in the sixth and seventh groups, MOE or MOE-NIO (250 mg/kg, PO) was administered one week before DOX injection. Various parameters were assessed in serum and cardiac tissue. Pre and co-treatment with MOE-NIO have mitigated the cardiotoxicity induced by DOX as indicated by serum aspartate aminotransferase (AST), creatine kinase - MB(CK-MB) and lactate dehydrogenase (LDH), cardiac Troponin 1(cTn1) and lipid profile. MOE-NIO also alleviated lipid peroxidation (MDA), nitrosative status (NO), and inflammatory markers levels; myeloperoxidase (MPO) and tumor necrosis factor-alpha (TNF-α) obtained in DOX-treated animals. Additionally, ameliorated effects have been recorded in glutathione content and superoxide dismutase activity. MOE-NIO effectively neutralized the DOXupregulated nuclear factor kappa B (NF-kB) and p38 mitogen-activated protein kinases (p38 MAPK), and DOX-downregulated nuclear factor-erythroid 2-related factor 2 (Nrf2) expressions in the heart.</p><p><strong>Results: </strong>It is concluded that pre and co-treatment with MOE-NIO could protect the heart against DOX-induced cardiotoxicity by suppressing numerous pathways including oxidative stress, inflammation, and apoptosis and by the elevation of tissue antioxidant status.</p><p><strong>Conclusion: </strong>Thus, it may be reasonable to suggest that pre and co-treatment with MOE-NIO can provide a potential cardioprotective effect when doxorubicin is used in the management of carcinoma.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":"289-301"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141450020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Study on Enhanced Skin Permeation Efficiency of Phenylephrine via Novel Lipid Vesicles: A Promising Approach in Preventing Chemotherapy-induced Alopecia Management.","authors":"Ravi Shankar, Manish Kumar, Prabhat Kumar Upadhyay","doi":"10.2174/0113892010336809240815050316","DOIUrl":"10.2174/0113892010336809240815050316","url":null,"abstract":"<p><strong>Background: </strong>Chemotherapy-induced alopecia (CIA) significantly impacts patients' emotional and psychological well-being and treatment regimen. Phenylephrine, a topical vasoconstrictor, can potentially reduce hair loss by limiting chemotherapy drug delivery to hair follicles. However, effective delivery of Phenylephrine through the skin remains challenging. This study investigates lipid vesicles as delivery vehicles to enhance Phenylephrine's skin permeation and sustained release due to their biocompatibility and encapsulation capabilities.</p><p><strong>Objective: </strong>This study aimed to formulate and compare different lipid vesicles of Phenylephrine HCl for enhanced permeation through the skin for deep dermal delivery with sustained release of the drug so as to achieve local vasoconstriction.</p><p><strong>Methods: </strong>Phenylephrine-loaded ethosomes, invasomes, and transfersomes were prepared and characterized for particle size (PS), polydispersity index (PDI), and entrapment efficiency (EE %). These lipid vesicles were incorporated into hydrogels to facilitate sustained drug release to deep dermal layers where they could target local vasculature and cause vasoconstriction. The prepared vesicular gels were evaluated for various permeation parameters.</p><p><strong>Results: </strong>The entrapment efficiencies of the developed vesicles ranged from 49.51 ± 3.25% to 69.09 ± 2.32%, with vesicle sizes ranging from 162.5 ± 5.21 nm to 321.32 ± 3.75 nm. Statistical analysis revealed significantly higher flux values (Jss, μg/cm² h) of 0.6251, 0.6314, and 0.4075 for invasomal gel, ethosomal gel, and transfersomal gel, respectively, compared to plain gel (0.1254) (p < 0.005). The enhancement factors were 4.9848, 5.0350, and 3.2496 for invasomal gel, ethosomal gel, and transfersomal gel, respectively, indicating superior permeation abilities of ethosomal and invasomal formulations.</p><p><strong>Conclusion: </strong>The results demonstrate that ethosomal and invasomal formulations were efficient in delivering the drug to deep dermal layers of skin in a sustained manner. These findings suggest that these Lipidic vesicles would be able to target the local vasoconstrictor to vasculature, causing reduced hair loss by limiting chemotherapy drug delivery to hair follicles and managing chemotherapy-induced alopecia.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":"465-475"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GC-MS/MS Analysis and Wound Repair Potential of <i>Urtica dioica</i> Essential Oil: <i>In silico</i> Modeling and In vivo Study in Rats.","authors":"Ahlem Ben Chira, Yassine Kadmi, Riadh Badraoui, Kaïss Aouadi, Fahad Alhawday, Mariem Boudaya, Kamel Jamoussi, Choumous Kallel, Abdelfattah El Feki, Adel Kadri, Mongi Saoudi","doi":"10.2174/0113892010304346240619061848","DOIUrl":"10.2174/0113892010304346240619061848","url":null,"abstract":"<p><strong>Background: </strong>The study aimed to assess the antioxidant and wound healing properties of <i>Urtica dioica</i> essential oil (UDEO) through a comprehensive evaluation involving <i>in silico, in vitro</i>, and <i>in vivo</i> analyses. The phytochemistry of UDEO was also investigated to identify trace compounds crucial.</p><p><strong>Methods: </strong>Various injection methods of the multimode inlet (MMI) in chromatography were investigated to attain lower instrumental detection limits. Subsequently, <i>in silico</i> studies were employed to delve deeper into the potential biological activities of the identified compounds. Standard antioxidative tests, encompassing ABTS^•+ and TAC, were performed. <i>In vivo</i> tests centered on wound healing were implemented using rat models. The rats were randomly allocated to four groups: saline solution, vaseline vehicle, cytol centella, and 5% UDEO ointment. Wound healing progress was evaluated through a chromatic study.</p><p><strong>Results: </strong>Gas chromatography combined with triple quadrupole mass spectrometry (GC-MS/MS) analysis revealed the presence of 97 thermolabile compounds in UDEO. Subsequent <i>in silico</i> studies unveiled the potential of identified compounds to inhibit COX-2, TNF-α, and IL-6, suggesting a possible enhancement of anti-inflammatory responses and healing processes. <i>In vitro</i> tests elucidated the notable antioxidant capacity of UDEO, a finding reinforced by wound healing data, revealing a substantial closure rate of 89% following the topical application of UDEO. Notably, fibrinogen and C-reactive protein (CRP) levels were significantly reduced, indicating minimized oxidative stress damage compared to control. Additionally, UDEO exhibited an increase in antioxidant enzyme activities compared to control.</p><p><strong>Conclusion: </strong>The study concludes that UDEO possesses significant antioxidant and wound-healing properties, supported by its rich phytochemical composition. The findings suggest its potential application in therapeutic interventions for oxidative stress and inflammatory conditions.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":"591-607"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Neem Limonoid Nimbolide Modulates Key Components of the DNA Damage Response Signalling in Cellular and Animal Models of Oral Squamous Cell Carcinoma.","authors":"Soundararajan Arvindh, Manashi Priyadarshini, Abdul Basit Baba, Veeran Veeravarmal, Rajakishore Mishra, Rupesh Dash, Siddavaram Nagini","doi":"10.2174/0113892010291998240321074920","DOIUrl":"10.2174/0113892010291998240321074920","url":null,"abstract":"<p><strong>Background: </strong>Deregulated DNA damage response (DDR) network is implicated in cancer progression and therapy resistance.</p><p><strong>Objective: </strong>The present study was designed to investigate whether nimbolide, an anticancer neem limonoid, targets key components of the DDR signalling pathway in cellular and animal models of oral squamous cell carcinoma (OSCC).</p><p><strong>Methods: </strong>OSCC cells (SCC-4 and SCC-9), 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinoma model, chemoresistant OSCC patient-derived xenograft (PDX) model established in athymic nude mice, and tissue sections from patients with oral premalignant/malignant disease were used for the study. Key molecules that orchestrate the DDR, including the MRN complex, ATM, DNA-PKcs, H2AX, and p53, were analysed by qRTPCR, immunoblotting, immunofluorescence, and immunohistochemistry. Cell proliferation and apoptosis indices were evaluated.</p><p><strong>Results: </strong>Nimbolide significantly reduced 8-oxodG levels, expression of MRN, ATM^S1891, and γ- H2AX, with an increase in p-p53^S15 in OSCC cells as well as in the HBP model. Nimbolide potentiated the effect of KU-55933 in ATM inhibition. In the PDX model, nimbolide suppressed tumor formation, stimulated DDR and apoptosis, inhibited cell proliferation, and enhanced sensitivity to cisplatin. Analysis of p-ATM expression revealed a significant increase during the sequential progression of hamster and human OSCC.</p><p><strong>Conclusion: </strong>This study provides compelling evidence that nimbolide functions as a DDR inhibitor in cellular and hamster OSCC models and as a DDR activator in the PDX model primarily by targeting ATM. Small molecules like nimbolide that modulate DDR are of immense benefit in cancer therapy. The study has also unveiled p-ATM as a promising biomarker of tumour progression in human OSCCs.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":"428-442"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140335069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}