Journal of Pharmacy and Pharmacology最新文献

{"title":"Natural product mitigation of ferroptosis in platinum-based chemotherapy toxicity: targeting the underpinning oxidative signaling pathways.","authors":"Ademola C Famurewa, Nupura Manish Prabhune, Sudharshan Prabhu","doi":"10.1093/jpp/rgae132","DOIUrl":"https://doi.org/10.1093/jpp/rgae132","url":null,"abstract":"<p><strong>Objectives: </strong>Platinum-based anticancer chemotherapy (PAC) represents a cornerstone in cancer treatment, retaining its status as the gold standard therapy. However, PAC's efficacy is countered by significant toxicities, such as nephrotoxicity, ototoxicity, and neurotoxicity. Recent studies have linked these toxicities to ferroptosis, characterized by iron accumulation, reactive oxygen species generation, and lipid peroxidation. This review explores the mechanisms underlying PAC-induced toxicities, focusing on the involvement of ferroptosis with three major PAC drugs-cisplatin, carboplatin, and oxaliplatin. Further, we provide a comprehensive analysis of the natural product mitigation of PAC-induced ferroptotic toxicity.</p><p><strong>Key findings: </strong>The mechanistic role of ferroptosis in cisplatin- and oxaliplatin-induced toxicities has been investigated, while studies on carboplatin-induced ferroptotic toxicities are lacking. Natural compounds targeting molecular pathways of ferroptosis have been explored to mitigate PAC-induced ferroptotic toxicity.</p><p><strong>Conclusion: </strong>While ferroptosis in cisplatin- and oxaliplatin-induced toxicities has been investigated, there remains a notable dearth of studies examining its involvement in carboplatin-induced toxicities. Hence, further exploration is warranted to define the role of ferroptosis in carboplatin-induced toxicities, and its further mitigation. Moreover, in-depth mechanistic evaluation is necessary to establish natural products evaluated against PAC-induced ferroptosis, as PAC adjuvants.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142562549","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":"Correction to: Current treatments for oropharyngeal squamous cell carcinoma and the move towards molecular therapy.","authors":"","doi":"10.1093/jpp/rgae139","DOIUrl":"https://doi.org/10.1093/jpp/rgae139","url":null,"abstract":"","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522221","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":"Ganoderma lucidum triterpenoids investigating their role in medicinal applications and genomic protection.","authors":"Sayed Haidar Abbas Raza, Ruimin Zhong, Xiangmei Li, Sameer D Pant, Xing Shen, Mona N BinMowyna, Lin Luo, Hongtao Lei","doi":"10.1093/jpp/rgae133","DOIUrl":"https://doi.org/10.1093/jpp/rgae133","url":null,"abstract":"<p><strong>Objectives: </strong>Ganoderma lucidum (GL) is a white rot fungus widely used for its pharmacological properties and health benefits. GL consists of several biological components, including polysaccharides, sterols, and triterpenoids. Triterpenoids are often found in GL in the form of lanostane-type triterpenoids with quadrilateral carbon structures.</p><p><strong>Key findings: </strong>The study revealed that triterpenoids have diverse biological properties and can be categorized based on their functional groups. Triterpenoids derived from GL have shown potential medicinal applications. They can disrupt the cell cycle by inhibiting β-catenin or protein kinase C activity, leading to anti-cancer, anti-inflammatory, and anti-diabetic effects. They can also reduce the production of inflammatory cytokines, thus mitigating inflammation. Additionally, triterpenoids have been found to enhance the immune system's defenses against various health conditions. They possess antioxidant, antiparasitic, anti-hyperlipidemic, and antimicrobial activities, making them suitable for pharmaceutical applications. Furthermore, triterpenoids are believed to afford radioprotection to DNA, protecting it from radiation damage.</p><p><strong>Summary: </strong>This review focuses on the types of triterpenoids isolated from GL, their synthesis pathways, and their chemical structures. Additionally, it highlights the pharmacological characteristics of triterpenoids derived from GL, emphasizing their significant role in various therapeutic applications and health benefits for both humans and animals.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502627","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":"Brazilian red propolis synergistically with imipenem modulates immunological parameters and the bactericidal activity of human monocytes against methicillin-resistant Staphylococcus aureus (MRSA).","authors":"Nicolas Ripari, Mariana da Silva Honorio, Arthur Alves Sartori, Larissa Ragozo Cardoso de Oliveira, Jairo Kenupp Bastos, José Maurício Sforcin","doi":"10.1093/jpp/rgae135","DOIUrl":"https://doi.org/10.1093/jpp/rgae135","url":null,"abstract":"<p><strong>Objectives: </strong>Propolis is a bee product found all over the globe and has a well-known antibacterial activity. Previous findings of our group revealed that the combination of Brazilian red propolis (BRP) with a lower concentration of imipenem (IPM) exerted a bactericidal action against methicillin-resistant Staphylococcus aureus (MRSA) in vitro. Here, we aimed at investigating the effects of BRP in combination or not with IPM on human monocytes to assess a possible immunomodulatory action.</p><p><strong>Methods: </strong>Monocyte metabolic activity was analysed by MTT assay, cytokine production (TNF-α, IL-1β, IL-6, IL-8, and IL-10) by ELISA, and the expression of cell markers (TLR-2, TLR-4, HLA-DR, and CD80) by flow cytometry. The bactericidal activity of monocytes over MRSA was determined by colony-forming units' count.</p><p><strong>Key findings: </strong>BRP alone or in combination with IPM exerted no cytotoxic effects on monocytes. BRP downregulated TLR-2 expression and inhibited TNF-α, IL-1β, and IL-6 production, while BRP + IPM stimulated these parameters. BPR alone or in combination increased the bactericidal activity similarly to LPS-activated monocytes.</p><p><strong>Conclusions: </strong>Data indicated the potential of BRP as an anti-inflammatory agent increasing the bactericidal activity of monocytes against MRSA. The combination of BRP + IPM exhibited a stimulatory profile that may be potentially useful in treating patients with MRSA infection.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502626","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":"Stachys byzantina K. Koch (Lamiaceae) as a potential ingredient for delaying skin ageing and treating hyperpigmentation disorders in pharmaceutical products.","authors":"Victor Campana Leite, José Alisson da Silva Lima, Jéssica Pereira Silva, Pedro Henrique Santos de Freitas, Luciana Poty Manso Dos Santos, Ana Paula Guarnieri, Maria Clara Machado Resende Guedes, Gilson Costa Macedo, Natália Prado da Silva, Guilherme Diniz Tavares, Elita Scio, Mara Rubia Costa Couri, Jair Adriano Kopke de Aguiar, Nícolas de Castro Campos Pinto","doi":"10.1093/jpp/rgae138","DOIUrl":"https://doi.org/10.1093/jpp/rgae138","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to investigate whether the plant species Stachys byzantina produces bioactives with the potential to delay the skin ageing process and treat hyperpigmentation conditions.</p><p><strong>Methods: </strong>The antioxidant action was assessed by 2,2-diphenyl-1-picrylhydrazylradical scavenging, Griess reaction, oxygen radical absorption capacity, and β-carotene bleaching assays. Inhibitory activities for tyrosinase, hyaluronidase, and elastase enzymes were tested. The antiglycation activity, the sun protection factor (SPF), and the toxicity to skin cells by MTT (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) assay were also evaluated.</p><p><strong>Key findings: </strong>The ethanolic extract of S. byzantina aerial parts and all fractions obtained by solvent partition inhibited the tyrosinase enzyme at different levels. The dichloromethane fraction (DF) demonstrated the highest inhibition (IC50 = 63.5 ± 10.9 µg/ml). DF also inhibited the hyaluronidase enzyme with IC50 = 369 ± 11.64 μg/ml and elastase by 40% at 500 μg/ml. This fraction showed prominent antioxidant and antiglycation activities, high SPF, and no cytotoxicity at concentrations lower than 50 μg/ml. The phenolic and flavonoid contents were 116.30 ± 6.7 (mgTAE/g) and 66.38 ± 13.5 (mgQE/g), respectively. Chlorogenic acid (23.54 ± 2.46 mg/g) and verbascoside (203.97 ± 19.8 mg/g) were identified and quantified.</p><p><strong>Conclusions: </strong>Stachys byzantina is a potential source of cosmetic and therapeutic ingredients to reduce hyperpigmentation and the impacts caused by free radicals, advanced glycation end products, and sun radiation in skin ageing.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502629","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":"Alleviating vascular calcification with Bushen Huoxue formula in rats with chronic kidney disease by inhibiting the PTEN/PI3K/AKT signaling pathway through exosomal microRNA-32.","authors":"Xingyun Guo, Shiwei Liu, Xiaoyi Wu, Ronglu Yang, Qiuyue Ren, Yanyan Zhou, Kaifeng Shi, Lisha Yuan, Ning Zhang, Shiyi Liu","doi":"10.1093/jpp/rgae120","DOIUrl":"https://doi.org/10.1093/jpp/rgae120","url":null,"abstract":"<p><strong>Background: </strong>Vascular calcification (VC) significantly raises cardiovascular mortality in chronic kidney disease (CKD) patients. VC is characterized by the phenotypic transformation of vascular smooth muscle cells (VSMCs) to osteoblast-like cells, mediated by exosomes derived from calcified VSMCs and the exosomal microRNAs (miRNA) which may trigger some signals to recipient VSMCs. Bushen Huoxue (BSHX) formula has demonstrated its clinical efficacy in CKD and its protective role in CKD-VC rats has also been observed. However, little is known about its underlying mechanism.</p><p><strong>Methods: </strong>To establish a VC model, aortic VSMCs from rats were induced to osteogenic differentiation by high-level phosphate (HP) in vitro. The expression of exosome and calcification makers were analyzed by western blot, including CD9, CD63, α-SMA, BMP-2, and Runx2, respectively. Differential expression of exosomal miRNAs in normal and HP-induced VSMCs were identified by using whole miRNA microarray technology. GO and KEGG analyses were performed to determine the significant enrichment of functions and signaling pathways in the target genes. In vivo, the CKD-VC rat model was established by administering adenine gavage combined with a high phosphorus diet. The rats were divided into normal control, model, low-dose BSHX, medium-dose BSHX, high-dose BSHX groups, and sevelamer groups. The blood biochemical parameters were measured. Renal histopathology and aortic calcification were observed. Western blot detected the levels of the calcification markers. Quantitative real-time PCR (qPCR) assay detected exosomal microRNA-32 (miR-32) mRNA expression in the aorta, the most differentially expressed exosomal miRNA previously identified. Phosphatase and tensin homolog located on chromosome ten (PTEN)/phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT) signaling pathway components were also tested by western blot.</p><p><strong>Results: </strong>Exosomal miRNA-32 and PI3K/AKT signaling pathways were highly differentially expressed between normal and HP-induced VSMCs. In vivo, BSHX improved blood biochemical parameters, renal histopathology, and aortic calcification in CKD-VC rats. BSHX increased the expression level of α-SMA and decreased the level of BMP-2 and Runx2. BSHX also lowered the expression level of exosomal miR-32 mRNA, enhanced PTEN expression, therefore, reduced p-PI3K and p-AKT levels in the aorta.</p><p><strong>Conclusion: </strong>BSHX alleviated VC in CKD rats by downregulating exosomal miR-32 expression in the aorta, thereby promoting PTEN expression and inhibiting the PI3K/AKT signaling pathway.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502625","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":"Molecular mechanisms of endoplasmic reticulum stress-mediated acute kidney injury in juvenile rats and the protective role of mesencephalic astrocyte-derived neurotrophic factor.","authors":"Li-Ran Zhu, Wei Cui, Hai-Peng Liu","doi":"10.1093/jpp/rgae134","DOIUrl":"https://doi.org/10.1093/jpp/rgae134","url":null,"abstract":"<p><strong>Objectives: </strong>This study examined the role of endoplasmic reticulum stress in pediatric acute kidney injury and the therapeutic effect of midbrain astrocyte-derived neurotrophic factor.</p><p><strong>Methods: </strong>Two-week-old Sprague-Dawley rats were divided into: Sham, ischemia-reperfusion injury-induced acute kidney injury (AKI), mesencephalic astrocyte-derived neurotrophic factor (MANF)-treated, tauroursodeoxycholic acid (TUDCA)-treated. Analyses were conducted 24 h post-treatment. Serum creatinine, cystatin C, Albumin, MANF levels were measured, cytokine concentrations in serum and renal tissues were determined using a Luminex assay. Histopathology was assessed via light and electron microscopy. Western blotting and RT-qPCR analyzed markers for oxidative stress, apoptosis, endoplasmic reticulum (ER) stress, and autophagy. HK-2 cells underwent hypoxia/reoxygenation (H/R) to simulate AKI and were treated with MANF or TUDCA.</p><p><strong>Results: </strong>AKI rats had increased serum creatinine, cystatin C, and inflammatory cytokines, along with significant renal damage, and showed loose and swollen ER structures, reduced cell proliferation, and elevated levels of IRE1, PERK, ATF6, CHOP, LC3-II/I, KIM-1, TLR4, JNK, and NF-κB. MANF treatment reduced these biomarkers and protein levels, improved ER structure and cell proliferation, alleviated oxidative stress, apoptosis, ER stress, and inhibited JNK/TLR4/NF-κB signaling. In HK-2 cells, MANF reduced ER stress and inflammation post-H/R exposure.</p><p><strong>Conclusions: </strong>MANF treatment alleviates ER stress, oxidative stress, apoptosis, and inflammation in pediatric AKI, improving renal function and morphology.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502628","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":"DST regulates cisplatin resistance in colorectal cancer via PI3K/Akt pathway.","authors":"Jianwei Yu, Xueqiong Deng, Xueqin Lin, Li Xie, Sisi Guo, Xiaoliang Lin, Dong Lin","doi":"10.1093/jpp/rgae104","DOIUrl":"https://doi.org/10.1093/jpp/rgae104","url":null,"abstract":"<p><strong>Objectives: </strong>Dystonin (DST), a potential tumor suppressor gene, plays a crucial role in regulating cancer cell proliferation and resistance to chemotherapy. However, DST's specific role in colorectal cancer (CRC) has not been thoroughly investigated, and this study aims to elucidate its molecular role in modulating cisplatin (DDP) resistance in CRC.</p><p><strong>Methods: </strong>DST expression was analyzed in CRC tumors, DDP-resistant CRC tissues, paracancer tissues, and normal tissues. Lentiviral overexpression and shRNA knockdown were conducted in advanced CRC and DDP-resistant cell lines to assess cell viability, apoptosis, invasion, migration, proliferation, and angiogenesis. Xenograft mouse models studied DST's impact on CRC tumor growth and DDP resistance in vivo.</p><p><strong>Results: </strong>DST expression was significantly reduced in CRC tumor and DDP-resistant CRC tissues compared to paracancer and normal tissues (P < .001). Upregulating DST inhibited CRC and DDP-resistant cell viability, proliferation, invasion, and migration while promoting apoptosis. DST overexpression also reduced angiogenesis and attenuated DDP-induced cytotoxicity in CRC cells. Mechanistically, DST upregulation suppressed DDP resistance in CRC cells via the PI3K/Akt signaling pathway. DST upregulation reduced CRC tumor growth and mitigated DDP resistance, in vivo.</p><p><strong>Conclusion: </strong>DST plays a crucial role in limiting CRC progression and overcoming DDP resistance, suggesting potential for targeted CRC therapies.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468354","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":"Improvement of primary Sjögren's syndrome salivary gland function by Xinfeng capsule and its effect on EGR1-STAT3 signaling pathway.","authors":"Ling Zhu, Beijia Wang, Pingping Li, Gangli Cheng, Su Bu, Sijie Bian, Xiaoting Qiu, Jian Liu, Xingxing Huo","doi":"10.1093/jpp/rgae121","DOIUrl":"https://doi.org/10.1093/jpp/rgae121","url":null,"abstract":"<p><strong>Objectives: </strong>The study was aimed to investigate the effects of Xinfeng capsule (XFC) on tissue morphology, and gland function of the salivary gland (SG) in a primary Sjögren's syndrome (pSS) mouse model.</p><p><strong>Methods: </strong>An animal model of pSS was established by inducing SG protein in C57BL/6 mice. SG tissues were collected for tissue sequencing and subsequent experiments to detect the expression of cholinergic receptor muscarinic 3(M3R), early growth response factor 1 (EGR1) and target genes in the SG before and after XFC intervention, with in vitro validation.</p><p><strong>Results: </strong>Downstream targets of the EGR1 gene were predicted and analyzed using data analysis. EGR1 showed high expression and was selected for subsequent experiments. Administration of XFC significantly increased saliva production (P < 0.001) and reduced the extent of lymphatic infiltration observed in SG. Furthermore, the expression of EGR1 was increased in the model group with statistical significance in contrast with the control group but decreased after administration of XFC (P < 0.05). Data analysis predicted the downstream target of EGR1 as signal transducer and activator of transcription 3 (STAT3), which was validated in SG tissues of mice (P < .05).</p><p><strong>Conclusions: </strong>XFC demonstrated a significant improvement in the salivary secretion function of the SG in pSS mice. EGR1 can serve as a biomarker and therapeutic target for pSS.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468355","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":"Pyrazolone-nicotinic acid derivative (4Z)-4-(2-hydroxybenzylidine)-5-methyl-2-(pyridine-3-ylcarbonyl)-2, 4-dihydro-3H-pyrazole-3-one (IIc) as multitarget inhibitor of neurodegeneration and behavioural impairment in Dementia.","authors":"Madiha Kanwal, Sadia Sarwar, Humaira Nadeem, Suad A Alghamdi, Abir Abdullah Alamro, Sumra Malik, Saima Maqsood, Amani A Alghamdi, Muhammad Junaid Tariq, Imran Malik, Arif Ullah Khan, Aleena Muskan","doi":"10.1093/jpp/rgae075","DOIUrl":"https://doi.org/10.1093/jpp/rgae075","url":null,"abstract":"<p><strong>Objective: </strong>The study was aimed at the synthesis and pharmacological investigation of (4Z)-4-(2-hydroxybenzylidine)-5-methyl-2-(pyridine-3-ylcarbonyl)-2, 4-dihydro-3H-pyrazole-3-one (IIc) in mice model of scopolamine-induced neurodegeneration and cognition impairment.</p><p><strong>Methods: </strong>The behavioural studies included Y-Maze Test, Water Morris Test, and Novel Object Recognition Test in Albino mice (20-25 g). Scopalamine was used as an inducing agent. The acetylcholinesterase (AChE) inhibitory assay was used to assess the role of the test compounds in vitro. The Crystal Violet Staining (Nissl staining) was used to assess the neuroprotective and antiapoptotic effect through quantifying the number of neurons and viability. The expression of the anti-inflammatory enzyme cyclooxygenase-2 (COX-2), cytokine tumour necrotic factor (TNF-α), key transcription factor producing pro-inflammatory signals nuclear factor kappa B (P-NFkB), and apoptosis marker p-JNK was validated through enzyme-linked immunosorbent assay (ELISA) and immunohistochemical (IHC) analysis. The tested compound reverted cognitive and behavioural impairment through inhibiting scopolamine-induced inflammation and oxidative stress.</p><p><strong>Key findings: </strong>We found that the compound IIc improved the short-term memory and learning behaviour of the experimental animals. Further investigation into molecular mechanisms showed that this effect was the manifestation of immunomodulatory, antioxidant, and consequently, of downsizing of inflammatory cytokines. These results were further validated through docking analysis.</p><p><strong>Conclusion: </strong>Finally, we conclude that the pyrazolone-nicotinic acid derivative IIc reversed the scopolamine-induced cognitive and behavioural deficits, attributed to acetylcholinesterase inhibition, neuronal recovery, antioxidant potential, and through downregulating the neuroinflammatory mediators p-NF-kB, cytokine TNF-α, and anti-inflammatory enzyme COX-2.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468357","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}