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Osteogenic effect of alogliptin in chemical-induced bone loss: a tri-modal in silico, in vitro, and in vivo analysis. 阿格列汀在化学物质诱导的骨质流失中的成骨作用:硅学、体外和体内三模式分析。
IF 2.8 4区 医学
Journal of Pharmacy and Pharmacology Pub Date : 2025-05-02 DOI: 10.1093/jpp/rgae112
Faraha Ahmed, Syed Sufian Ahmad, Mohammad Mumtaz Alam, Mohammad Shaquiquzzaman, Mohammad Altamish, Anuja Krishnan, Divya Vohora, Abul Kalam Najmi, Mohammad Ahmed Khan
{"title":"Osteogenic effect of alogliptin in chemical-induced bone loss: a tri-modal in silico, in vitro, and in vivo analysis.","authors":"Faraha Ahmed, Syed Sufian Ahmad, Mohammad Mumtaz Alam, Mohammad Shaquiquzzaman, Mohammad Altamish, Anuja Krishnan, Divya Vohora, Abul Kalam Najmi, Mohammad Ahmed Khan","doi":"10.1093/jpp/rgae112","DOIUrl":"10.1093/jpp/rgae112","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the effects of Alogliptin in chemical-induced post-menopausal osteoporosis.</p><p><strong>Methodology: </strong>The binding affinity of alogliptin with osteogenic proteins was analysed in silico. The effect of alogliptin on osteogenic proteins and mineralization of osteoblastic cells was evaluated in UMR-106 cells. Further, in vivo anti-osteoporotic activity of alogliptin was evaluated in postmenopausal osteoporosis. Various bone turnover markers were assayed in serum. This followed the analysis of microarchitecture of bone, histology, and immunohistochemistry (IHC) of bone tissue.</p><p><strong>Results: </strong>Docking scores showed that alogliptin has binding affinity for bone alkaline phosphatase (BALP), osteocalcin, and bone morphogenic protein (BMP-2). Alogliptin also enhanced mineralization of osteoblast cells, evidenced with increased ALP, osteocalcin, and BMP-2. Animal studies revealed significant elevation of bone formation markers, bone ALP, osteocalcin and BMP-2, and decreased bone resorption markers, receptor activator of NF-κβ (RANKL), cathepsin K (CTSK), tartrate resistant acid phosphatase (TRAcP5b) in VCD-induced post-menopausal osteoporosis. Micro computed tomography (μCT) analysis and histology of femur bone and lumbar vertebrae demonstrated decrease in trabecular separation and improved bone density. IHC of femur showed reduced DPP4 enzyme.</p><p><strong>Conclusions: </strong>Alogliptin increased mineralization in osteoblast cells. It had beneficial effects also altered bone turnover markers, repaired the trabecular microstructure, improved bone mineral density, and exhibited bone forming capacity targeting DPP-4 enzyme in postmenopausal osteoporosis.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"668-684"},"PeriodicalIF":2.8,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365642","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}
引用次数: 0
Decoding the power of saponins in ferroptosis regulation and disease intervention: a review. 解码皂苷在铁变态反应调节和疾病干预中的作用:综述。
IF 2.8 4区 医学
Journal of Pharmacy and Pharmacology Pub Date : 2025-05-02 DOI: 10.1093/jpp/rgae144
Min Ouyang, Jianhua Wu, Xizhuo Hu, Changfu Liu, Dan Zhou
{"title":"Decoding the power of saponins in ferroptosis regulation and disease intervention: a review.","authors":"Min Ouyang, Jianhua Wu, Xizhuo Hu, Changfu Liu, Dan Zhou","doi":"10.1093/jpp/rgae144","DOIUrl":"10.1093/jpp/rgae144","url":null,"abstract":"<p><strong>Objectives: </strong>This review endeavors to elucidate the complex interplay underlying diseases associated with ferroptosis and to delineate the multifaceted mechanisms by which triterpenoid and steroidal saponins modulate this form of cell death.</p><p><strong>Methods: </strong>A meticulous examination of the literature was undertaken, drawing from an array of databases including Web of Science, PubMed, and Wiley Library, with a focus on the keywords \"ferroptosis,\" \"saponin,\" \"cancer,\" \"inflammation,\" \"natural products,\" and \"signaling pathways.\"</p><p><strong>Key findings: </strong>Ferroptosis represents a distinctive mode of cell death that holds considerable promise for the development of innovative therapeutic strategies targeting a wide range of diseases, especially cancer and inflammatory disorders. This review reveals the nuanced interactions between saponins and critical signaling pathways, including system Xc--GSH-GPX4, Nrf2, p53, and mTOR. These interactions highlight the dual capacity of saponins to modulate ferroptosis, thereby offering fresh perspectives for therapeutic intervention.</p><p><strong>Conclusions: </strong>The insights garnered from this review significantly advance our comprehension of the dynamic relationship between saponins and ferroptosis. By shedding light on these mechanisms, this work sets the stage for leveraging these insights in the creation of pioneering approaches to disease treatment, marking a significant stride in the evolution of therapeutic modalities.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"593-608"},"PeriodicalIF":2.8,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823545","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}
引用次数: 0
Integrated metabolomics and network pharmacology analysis to reveal the mechanisms of naringin against atherosclerosis. 综合代谢组学和网络药理学分析揭示柚皮苷抗动脉粥样硬化的机制。
IF 2.8 4区 医学
Journal of Pharmacy and Pharmacology Pub Date : 2025-05-02 DOI: 10.1093/jpp/rgae156
Gaoning Zhang, Xiaoyi Yin, Xiao Tang, Kexin Wang, Yifan Liu, Lili Gong, Zhenhua Tian
{"title":"Integrated metabolomics and network pharmacology analysis to reveal the mechanisms of naringin against atherosclerosis.","authors":"Gaoning Zhang, Xiaoyi Yin, Xiao Tang, Kexin Wang, Yifan Liu, Lili Gong, Zhenhua Tian","doi":"10.1093/jpp/rgae156","DOIUrl":"10.1093/jpp/rgae156","url":null,"abstract":"<p><strong>Objectives: </strong>The purpose of this study was to explore the mechanism of naringin in atherosclerotic mice from the perspective of network pharmacology and non-targeted metabolomics.</p><p><strong>Methods: </strong>ApoE-/- mice were induced to establish an atherosclerotic model to explore the pharmacodynamics and potential mechanism of naringin in atherosclerosis (AS). Pathological section and blood lipid levels were used to evaluate the intervention effects. The core targets, metabolites, and related pathways of naringin alleviating atherosclerotic were predicted through network pharmacology and metabolomics analysis. Furthermore, the inflammatory factors and pathway-related protein expression were detected using ELISA and Western blot methods.</p><p><strong>Key findings: </strong>It turned out that compared with the model group, the naringin could reduce the development degree in atherosclerotic mice. The network pharmacology suggested that PI3K-AKT pathway was an important mechanism for naringin to interfere with AS. Serum metabolic data were collected and analyzed, and a total of 27 potential biomarkers were identified, involving vitamin B6 metabolism, arginine metabolism, and retinol metabolism. The experiment verified that naringin inhibited inflammation in AS through the PI3K-AKT/TLR4/NF-κB pathway.</p><p><strong>Conclusions: </strong>This study provides a strategy combining metabolomics and network pharmacology to explore the alleviation of AS by naringin and offers a new idea for its application.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"621-634"},"PeriodicalIF":2.8,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414470","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}
引用次数: 0
Molecular mechanisms of endoplasmic reticulum stress-mediated acute kidney injury in juvenile rats and the protective role of mesencephalic astrocyte-derived neurotrophic factor. 内质网应激介导的幼年大鼠急性肾损伤的分子机制及间脑星形胶质细胞源性神经营养因子的保护作用
IF 2.8 4区 医学
Journal of Pharmacy and Pharmacology Pub Date : 2025-05-02 DOI: 10.1093/jpp/rgae134
Li-Ran Zhu, Wei Cui, Hai-Peng Liu
{"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":"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":" ","pages":"609-620"},"PeriodicalIF":2.8,"publicationDate":"2025-05-02","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}
引用次数: 0
Silencing c-myc gene by siRNA delivered by cationic niosomes in MCF-7 cells. 在 MCF-7 细胞中用阳离子纳米囊递送 siRNA 沉默 c-myc 基因。
IF 2.8 4区 医学
Journal of Pharmacy and Pharmacology Pub Date : 2025-05-02 DOI: 10.1093/jpp/rgae146
Shatha N Abdeljaber, Alaa A Aljabali, Bahaa Altrad, Mohammad A Obeid
{"title":"Silencing c-myc gene by siRNA delivered by cationic niosomes in MCF-7 cells.","authors":"Shatha N Abdeljaber, Alaa A Aljabali, Bahaa Altrad, Mohammad A Obeid","doi":"10.1093/jpp/rgae146","DOIUrl":"10.1093/jpp/rgae146","url":null,"abstract":"<p><strong>Objectives: </strong>Gene therapy has a strong potential to treat different cancer types cancers with high therapeutic outcomes. c-myc is believed to be responsible for more than 15% of all gene regulation and functions as a transcription factor for proteins essential for cell proliferation. This study aimed to develop niosome nanocarriers to knockdown c-myc expression using anti-c-myc short-interfering RNA (siRNA) in MCF-7 cells. Altering the activity of the c-myc proto-oncogene has been identified as an important element in minimizing cancer cell growth because anti-c-myc siRNA degrades c-myc mRNA.</p><p><strong>Methods: </strong>Noisomes were prepared from Tween 85, cholesterol, and didodecyldimethylammonium bromide at 50:40:10 and 40:40:20 molar ratios. Anti-c-myc siRNA was loaded in the prepared niosomes and then applied on MCF-7 cells.</p><p><strong>Key findings: </strong>Niosomes had a total positive charge formed electrostatic interactions with siRNA. Niosomes were spherical with a size range of 70-100 nm. The prepared niosomes were nontoxic to MCF-7 cells, with IC50 values of >250 µg/ml for both formulations. After encapsulation of anti-c-myc siRNA, nioplexes reduced c-myc mRNA expression by more than 50% compared with the untreated cells. Empty niosomes did not affect c-myc mRNA expression levels, indicating that the effect was due to siRNA rather than the particles themselves.</p><p><strong>Conclusions: </strong>This study provides evidence that niosomes can function as suitable carriers for siRNA delivery to knockdown the c-myc oncogene in MCF-7 cells, thus reducing cancer cell growth.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"658-667"},"PeriodicalIF":2.8,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687173","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}
引用次数: 0
Case study: cremophor EL-based liquid formulations as simple substitutes for amorphous solid dispersions in early preclinical in vivo studies. 案例研究:基于 cremophor EL 的液体制剂在早期临床前体内研究中作为无定形固体分散体的简单替代品。
IF 2.8 4区 医学
Journal of Pharmacy and Pharmacology Pub Date : 2025-05-02 DOI: 10.1093/jpp/rgae099
Kalle Sigfridsson, Xiang Zhang, Antonio Llinas
{"title":"Case study: cremophor EL-based liquid formulations as simple substitutes for amorphous solid dispersions in early preclinical in vivo studies.","authors":"Kalle Sigfridsson, Xiang Zhang, Antonio Llinas","doi":"10.1093/jpp/rgae099","DOIUrl":"10.1093/jpp/rgae099","url":null,"abstract":"<p><strong>Objectives: </strong>The objective of the present case study was to increase the exposure of the poorly soluble crystalline compound A.</p><p><strong>Methods: </strong>Mice received 10 mg/kg of crystalline compound A formulated in eight different cosolvent, oil, and cyclodextrin mixtures.</p><p><strong>Key findings: </strong>In all cases, AUC0-24h and maximum blood/plasma concentration (Cmax) were in the range of 6-16 µM × h and <1.4 µm, respectively, with a bioavailability below 18%. When 6% cremophor (CrEL) was added to three selected vehicles, AUC0-24h and Cmax increased ~5-10 times. The obtained pharmacokinetic profile of the most improved formulation using CrEL was possible to superimpose on the one obtained after administration of a CrEL-free amorphous solid dispersion (ASD, HPMC-AS:drug, 80:20) suspension of compound A.</p><p><strong>Conclusions: </strong>It is crucial to find an optimal screen vehicle as early as possible for a poorly water-soluble lead series and then avoid time and resource-consuming vehicle testing of multiple compounds in vivo. An ASD approach is more suited for clinical development when more time and resources are allocated to the project. In this case study, some preclinical formulations were used to maximize exposure but also as preindicators for ASDs later in the development chain.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"645-657"},"PeriodicalIF":2.8,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751972","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}
引用次数: 0
c-MET tyrosine kinase inhibitors reverse multidrug resistance in breast cancer cells by targeting ABCG2 transporter. c-MET酪氨酸激酶抑制剂通过靶向ABCG2转运体逆转乳腺癌细胞的多药耐药。
IF 2.8 4区 医学
Journal of Pharmacy and Pharmacology Pub Date : 2025-05-02 DOI: 10.1093/jpp/rgaf008
Somayeh Nazari, Fatemeh Mosaffa, Alireza Poustforoosh, Luciano Saso, Omidreza Firuzi, Fatemeh Moosavi
{"title":"c-MET tyrosine kinase inhibitors reverse multidrug resistance in breast cancer cells by targeting ABCG2 transporter.","authors":"Somayeh Nazari, Fatemeh Mosaffa, Alireza Poustforoosh, Luciano Saso, Omidreza Firuzi, Fatemeh Moosavi","doi":"10.1093/jpp/rgaf008","DOIUrl":"10.1093/jpp/rgaf008","url":null,"abstract":"<p><strong>Background: </strong>Overcoming multidrug resistance (MDR), which is often caused by the overexpression of ATP binding cassette (ABC) transporters in cancer cells remains a major challenge for cancer treatment. Receptor tyrosine kinase inhibitors have demonstrated potential in reversing MDR. This study aimed to investigate the effects of c-MET RTKIs on the reversal of MDR induced by ABCG2 in breast cancer cells.</p><p><strong>Methods: </strong>MTT assay was employed to assess antiproliferative activity of c-MET inhibitors, including cabozantinib, crizotinib, and PHA665752. The accumulation of the fluorescent probe mitoxantrone was evaluated by flow cytometry. The drug-drug interaction in combination treatments was analyzed using CalcuSyn software.</p><p><strong>Results: </strong>The combination of cabozantinib, crizotinib, and PHA665752 with mitoxantrone resulted in synergistic effects in MDR cells. This was demonstrated by the mean CI values of 0.32 ± 0.07, 0.53 ± 0.05, and 0.59 ± 0.03, respectively. In the same cells, c-MET inhibitors enhanced the accumulation of mitoxantrone, with accumulation ratios ranging from 1.6 to 3.8, while no change was found in parental MCF-7 cells. Computational analysis revealed that the drug-binding region of ABCG2 transporters could be a viable target for these compounds.</p><p><strong>Conclusion: </strong>c-MET inhibitors hold potential as effective agents for reversing MDR in ABCG2-medicated drug-resistant cancer cells.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"685-697"},"PeriodicalIF":2.8,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143575572","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}
引用次数: 0
Niosomes for enhanced oral delivery of pioglitazone: in vitro characterization and in vivo evaluation. 增强吡格列酮口服给药的Niosomes:体外表征和体内评价。
IF 2.8 4区 医学
Journal of Pharmacy and Pharmacology Pub Date : 2025-04-23 DOI: 10.1093/jpp/rgaf015
Aya R Elbasuony, Abdelaziz E Abdelaziz, Eman A Mazyed, Gamal M El Maghraby
{"title":"Niosomes for enhanced oral delivery of pioglitazone: in vitro characterization and in vivo evaluation.","authors":"Aya R Elbasuony, Abdelaziz E Abdelaziz, Eman A Mazyed, Gamal M El Maghraby","doi":"10.1093/jpp/rgaf015","DOIUrl":"https://doi.org/10.1093/jpp/rgaf015","url":null,"abstract":"<p><strong>Objectives: </strong>The aim was to investigate oleic acid and nigella oil modified niosomes as novel carriers for enhanced pioglitazone (PGZ) oral delivery.</p><p><strong>Methods: </strong>PGZ was encapsulated into niosomes of cholesterol, tween 80, and span 60 before (F1) and after incorporation of nigella oil (F2) or oleic acid (F3) as membrane fluidizers. Niosomes were characterized for morphology, size, zeta potential, PGZ entrapment, and release. Hypoglycemic effect was also assessed.</p><p><strong>Key findings: </strong>Vesicles were spherical recording size values of 286.4, 111.3, and 137.5 nm for F1, F2, and F3 niosomes, respectively. The zeta potential predicted good stability of niosomes. The lipophilic nature of PGZ resulted in more than 99% entrapment into niosomes. PGZ niosomes significantly boosted rate and extent of hypoglycemic activity compared with the unprocessed PGZ. This is clear from the Tmax, which was 3.6, 1.5, 0.87, and 0.62 h for control, F1, F2, and F3, respectively. This was associated with increase in the area above hypoglycemia curve, which was 655.8, 1613.6, 1617.2, and 1764.9 mg h/dl for the same formulations, respectively.</p><p><strong>Conclusion: </strong>Vesicular structure is responsible for enhanced oral bioavailability and drug release is not the limiting factor. Fluidizing material showed potential contribution in enhanced efficacy but requires future verification.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144027600","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}
引用次数: 0
Updated progression of honokiol in lung cancer treatment. 厚朴酚在肺癌治疗中的最新进展。
IF 2.8 4区 医学
Journal of Pharmacy and Pharmacology Pub Date : 2025-04-04 DOI: 10.1093/jpp/rgaf007
Ziwei Gao, Yuping Yang, Na Huang, Wei Zhao
{"title":"Updated progression of honokiol in lung cancer treatment.","authors":"Ziwei Gao, Yuping Yang, Na Huang, Wei Zhao","doi":"10.1093/jpp/rgaf007","DOIUrl":"https://doi.org/10.1093/jpp/rgaf007","url":null,"abstract":"<p><strong>Objectives: </strong>Despite significant advancements in innovative therapy, lung cancer continues to have an unexpectedly low 5-year survival rate. This necessitates the urgent development of novel and effective therapies. One such potential therapy is Honokiol (HNK, C18H18O2), a biphenolic natural compound isolated from the leaves and bark of Magnolia plant species. The objective of this review is to examine the various studies supporting the anti-lung cancer effects of HNK and its potential use in the treatment of lung cancer.</p><p><strong>Key findings: </strong>Emerging research has shown that HNK possesses a range of pharmacological characteristics that make it a promising agent in the fight against lung cancer. Specifically, HNK has been found to regulate various molecular targets, including the activation of pro-apoptotic factors and the suppression of anti-apoptotic proteins and different transcription factors. It also downregulates various enzymes, chemokines, cell surface adhesion molecules, and cell cycle proteins. Additionally, HNK inhibits the activity of protein tyrosine kinases and serine/threonine kinases. These effects contribute to its ability to efficiently prevent the progression of lung cancer, either solely or in combination with other therapeutic strategies. Furthermore, several nanotechnologies have been employed to modify HNK for the treatment of lung cancer, enhancing its potential efficacy.</p><p><strong>Summary: </strong>In summary, Honokiol (HNK) is a biphenolic natural compound with significant anti-lung cancer properties. Its pharmacological characteristics, including the regulation of various molecular targets and the inhibition of key enzymes and kinases, make it a promising agent for the treatment of lung cancer. Emerging research supports its ability to prevent the progression of lung cancer, either alone or in combination with other therapies. Additionally, nanotechnologies have been used to modify HNK, potentially enhancing its efficacy in the treatment of lung cancer. This review highlights the various studies documenting the anti-lung cancer effects of HNK, underscoring its potential as a novel and effective therapy for this deadly disease.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143784415","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}
引用次数: 0
Natural product Pulsatilla saponin D sensitizes BRCA-proficient ovarian cancers to PARP inhibitors through inhibiting homologous recombination repair. 天然产物白头翁皂苷D通过抑制同源重组修复使brca精通的卵巢癌对PARP抑制剂敏感。
IF 2.8 4区 医学
Journal of Pharmacy and Pharmacology Pub Date : 2025-04-03 DOI: 10.1093/jpp/rgaf006
Shengbin Lin, Binghe Sun, Yin Zhu, Yi Huang, Yu Qin, Nan Yao, Yongzhu Liu, Guo Chen
{"title":"Natural product Pulsatilla saponin D sensitizes BRCA-proficient ovarian cancers to PARP inhibitors through inhibiting homologous recombination repair.","authors":"Shengbin Lin, Binghe Sun, Yin Zhu, Yi Huang, Yu Qin, Nan Yao, Yongzhu Liu, Guo Chen","doi":"10.1093/jpp/rgaf006","DOIUrl":"10.1093/jpp/rgaf006","url":null,"abstract":"<p><strong>Background: </strong>As a strategy in the development of effective cancer therapeutics, synthetic lethality has been used in clinical practice. Poly adenosine diphosphate (ADP)-ribose polymerase inhibitors are the first approved drug utilized synthetic lethality and achieved promising therapeutic efficacy in cancer cells with BRCA1/2 mutation. Nonetheless, most cancer patients with wild-type BRCA1/2 gene are not qualified for PARPi therapy. To induce BRCAness phenotype in cancer cells with normal BRCA1/2 status, we identified Pulsatilla Saponin D (SB365), which efficiently inhibited recruitment of BRCA1 at DNA double-strand breaks, leading to homologous recombination repair deficiency.</p><p><strong>Methods: </strong>We utilized the HR repair reporter system. The reporter cells were treated with a natural compounds library to identify the agent that significantly decreased HR activity. Then, we detected the expression of HR related proteins using immunofluorescence and western blot. Colony formation and CCK8 was used to detect the inhibitory effect of Pulsatilla Saponin D on cell proliferation. Apoptosis was measured using Annexin V/PI staining. Comet assay kits were used to carry out the comet assay. Ovarian cancer xenograft model, immunohistochemical staining and Hematoxylin-Eosin staining was used to detect the antitumor efficacy and toxicity of Pulsatilla Saponin D.</p><p><strong>Key findings: </strong>Pulsatilla Saponin D greatly increased PARPi-induced DNA DSBs, growth inhibition and apoptosis in ovarian cancer cells. Combined administration of PARPi and Pulsatilla Saponin D induced synergistic anti-tumor effects in ovarian cancer cells and xenograft mouse model without obvious toxicity.</p><p><strong>Conclusions: </strong>In summary, our study found Pulsatilla Saponin D is a novel HR repair inhibitor and would optimize clinical application of PARP inhibitors on cancer patients with WT BRCA1/2.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"511-523"},"PeriodicalIF":2.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557048","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}
引用次数: 0
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