Journal of Experimental Pharmacology最新文献

{"title":"Inhibition of Mitochondrial Dynamics by Mitochondrial Division Inhibitor-1 Suppresses Cell Migration and Metastatic Markers in Colorectal Cancer HCT116 Cells.","authors":"Tahir Mehmood, Qandeel Nasir, Iqra Younis, Chatchai Muanprasat","doi":"10.2147/JEP.S510578","DOIUrl":"10.2147/JEP.S510578","url":null,"abstract":"<p><strong>Introduction: </strong>The mitochondria are highly dynamic organelles. The mitochondrial morphology and spatial distribution within the cell is determined by fusion and fission processes of mitochondria. Several studies have used mitochondrial division inhibitor-1 (Mdivi.1) to explore the roles of mitochondrial dynamics in various pathological conditions, including diabetic cardiomyopathy, myocardial infarction, cardiac hypertrophy, Alzheimer's disease, Huntington's disease and cancers.</p><p><strong>Purpose: </strong>The objective of the study was to investigate the role of mitochondrial dynamics in the invasiveness of HCT116 colorectal cancer cells.</p><p><strong>Material and methods: </strong>MTT assay was used to determine the Mdivi.1-induced toxicity in HCT116 cells. Wound healing, cell migration and colony forming assays were adopted to measure the migration and invasion activity of HCT116 cells. Furthermore, flow cytometry was used to determine the Mdivi.1-induced mitochondrial mass quantification, mitochondrial membrane potential and reactive oxygen species generation in HCT116 cells. Additionally, Western Blot analysis was used to determine the expression level of Drp1, p-Drp1, Mnf2, AMPK-α, p-AMPK-α, Cox-2, iNos and MMP9 in HCT116 cells.</p><p><strong>Results: </strong>We found that Mdivi.1 induced toxicity and altered the morphology of HCT116 cells in concentration- and time-dependent manners. Mdivi.1 significantly increased mitochondrial mass and dissipated the mitochondrial membrane potential. Furthermore, Mdivi.1 induced reactive oxygen species (ROS) generation and mitochondrial superoxide production, leading to AMPK activation. Moreover, Mdivi.1 decreased dynamin-related protein-1 (Drp1) and phosphorylated-Drp1 expression and increased mitofusin-2 (Mfn2) expression in a concentration-dependent manner at 48 and 72 h post-treatment. Notably, Mdivi.1 induced inhibition of translocation of Drp1 from the cytosol to the outer mitochondrial membrane. Mdivi.1 significantly suppressed the invasion and migration of HCT116 cells and inhibited the formation of HCT116 cell colonies. In addition, Mdivi.1 significantly decreased the expression of metastatic markers including Cox-2, iNos, and MMP-9 in HCT116 cells.</p><p><strong>Conclusion: </strong>Collectively, this study revealed that Mdivi.1 downregulates Drp1, upregulates Mfn2, and increases mitochondrial mass with attenuated oxidative metabolism, leading to the inhibition of cell invasion and metastasis in colorectal cancer HCT116 cells. Mitochondrial dynamics are regarded as possible drug targets for interrupting colorectal cancer cell migration and metastasis.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"17 ","pages":"143-157"},"PeriodicalIF":0.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phytochemical Analysis, Computational Study, and in vitro Assay of <i>Etlingera elatior</i> Inflorescence Extract Towards Inducible Nitric Oxide Synthase.","authors":"Deshanda Kurniawan Prayoga, Dian Ayu Eka Pitaloka, Diah Lia Aulifa, Arif Budiman, Jutti Levita, Supat Jiranusornkul, Binh Phu Nguyen","doi":"10.2147/JEP.S505658","DOIUrl":"10.2147/JEP.S505658","url":null,"abstract":"<p><strong>Background: </strong>Overproduction of nitric oxide (NO), catalyzed by inducible nitric oxide synthase (iNOS), in the gastric mucosa, contributes to the inflammatory process caused by oxidative stress. Current medications for gastric ulcers, such as proton pump inhibitors and histamine-2 receptor antagonists, have been reported to generate adverse reactions.</p><p><strong>Purpose: </strong>To obtain the phytochemical profile of <i>Etlingera elatior</i> inflorescence extract, computational studies, and in vitro assay of the extract towards iNOS.</p><p><strong>Methods: </strong>Fresh <i>E. elatior</i> inflorescence petals collected from West Java, Indonesia, were extracted using ethanol, and their nutritional composition, anthocyanin content, and levels of vitamin C, C3G, and quercetin in the extract were determined. Drug-likeness and ADMET properties were predicted, and the binding affinity and stability of the phytoconstituents towards iNOS were studied using molecular docking and molecular dynamic simulation, and in vitro assay of the extract towards human iNOS.</p><p><strong>Results: </strong>The extract contains protein 21.81%, fat 0.99%, carbohydrate 38.27%, water 24.56%, and ash 14.37%. The total anthocyanin and vitamin C levels were 47.535 mg/100 g and 985.250 mg/100 g, respectively. The levels of C3G and quercetin were 0.0007% w/w, 0.004% w/w, and 0.0005% w/w, respectively. Drug-likeness and ADMET properties of the constituents showed that most followed Lipinski Rules of Five (Ro5), with few violations. All phytoconstituents occupied the catalytic site by binding to Glu377, and Trp372, similar to <i>S-</i>ethylisothiourea (SEITU) and quinazoline, the iNOS inhibitors. Among these, the flavylium cation of cyanidin, demethoxycurcumin, C3G, cyanidin, and quercetin showed the best binding affinities. Root mean square deviation (RMSD), root mean square fluctuation (RMSF), solvent-accessible surface area (SASA), and radius of gyration (Rg) graphs confirmed the stability of the complexes. <i>E. elatior</i> inflorescence extract inhibited human iNOS with an IC50 value of 24.718 µg/mL.</p><p><strong>Conclusion: </strong><i>Etlingera elatior</i> inflorescence may inhibit iNOS activity due to its anthocyanin and flavonoid content. The flavylium cation of cyanidin, demethoxycurcumin, C3G, cyanidin, and quercetin play leading roles in the interaction with iNOS.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"17 ","pages":"123-141"},"PeriodicalIF":0.0,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11899951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antiproliferative Activity and Apoptotic Mechanisms of β-Sitosterol and Its Derivatives as Anti-Breast Cancer Agents: In Silico and In Vitro.","authors":"Mutakin Mutakin, Lauren Pangestu, Nafisa Nurfatia Hidayat, Fajar Fauzi Abdullah, Yuni Elsa Hadisaputri","doi":"10.2147/JEP.S496986","DOIUrl":"10.2147/JEP.S496986","url":null,"abstract":"<p><strong>Introduction: </strong>Breast cancer has become the most frequently diagnosed cancer worldwide. Beta-sitosterol and its derivatives have been explored for its anticancer properties. Therefore, this study aims to analyze the testing procedure carried out on MCF7 and MDA-MB-231 breast cancer cells, as well as MCF 10A non-cancerous breast epithelial cells.</p><p><strong>Methods: </strong>The compounds tested included β-sitosterol and its derivatives: 3β-galactose sitosterol, sitostenone, 3β-glucose sitosterol, poriferasta-5, 22E, 25-trien-3β-ol, and 22-dehydrocholesterol. Cytotoxicity assay was conducted using the PrestoBlue™ Cell Viability Reagent on MCF-7, MDA-MB-231, and MCF 10A cells. The compounds with the highest and lowest cytotoxicity were further analyzed for their mechanisms of action through cell morphology assessments and molecular docking studies. mRNA expression levels were also evaluated to confirm the findings.</p><p><strong>Results: </strong>The results showed that 3β-glucose sitosterol exhibited the most promising cytotoxic activity with IC₅₀ values against MCF7, MDA-MB-231 breast cancer cells, and MCF 10A non-cancerous cells of 265 µg/mL, 393.862 µg/mL, and 806.833 µg/mL, respectively. Molecular docking simulations showed that the compound is bound to estrogen receptor beta and caspase-3, suggesting a potential mechanism of action as evidenced by the best binding energy of -6.94 kcal/mol and inhibition constant values of 8.16 μM. Furthermore, gene expression analysis confirmed the induction of apoptosis through the upregulation of <i>caspase-9</i> and <i>caspase-3 mRNA expression</i>.</p><p><strong>Conclusion: </strong>Based on the results, β-sitosterol and its derivatives, particularly 3β-glucose sitosterol, show as the most promising potential adjuvant therapy for hormone-positive breast cancer.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"17 ","pages":"107-121"},"PeriodicalIF":0.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatoprotective Effects of Cilnidipine in Cholestatic Liver Disease: Role of FXR and NRF2 Signalling.","authors":"Thamer Abdulla Mohammed, Munaf H Zalzala","doi":"10.2147/JEP.S504511","DOIUrl":"10.2147/JEP.S504511","url":null,"abstract":"<p><strong>Background: </strong>Bile acid (BA) is a type of cholesterol derivative that has long been established for its crucial role in the breakdown and absorption of fat from food. Cholestasis occurs when the liver fails to transfer BAs to the intestines. Chronic cholestatic diseases can lead to liver cirrhosis.</p><p><strong>Objective: </strong>Ursodeoxycholic acid (UDCA) treatment is ineffective for certain cholestatic diseases like benign recurrent intrahepatic cholestasis (BRIC), despite increasing the hydrophilic bile acid pool. Moreover, studies indicate that UDCA and other bile acids affect liver cell functions, such as biotransformation through CYP enzymes. In hepatitis B virus transgenic mice, a UDCA-rich diet promoted hepatocyte proliferation and tumor growth. Hepatologists advise against using UDCA in patients with severe obstructive cholangiopathies. Given the foregoing, new medications are required to treat these illnesses.</p><p><strong>Methods: </strong>Twenty-four male Wistar albino rats were separated into three groups (8 rats for each group): negative control group I, positive control group II (ANIT-induced cholestasis), and treatment group III (Cil and ANIT). The mRNA and protein expression levels of FXR, small heterodimer partner (SHP), bile salt export pump (BSEP), nuclear factor erythroid 2-related factor 2 (NRF2), hepatocyte nuclear factor 1α (HNF1α), sirtuin 1 (SIRT1), NADPH dehydrogenase-quinone-1 (NQO-1), and heme oxygenase-1 (HO-1) were assessed post euthanasia. Additionally, other tissue oxidative stress markers were measured.</p><p><strong>Results: </strong>Cil significantly increased the mRNA expression levels of FXR, SHP, BSEP, HNF1α, and NRF2 and the protein expression levels of FXR, BSEP, SIRT1, NQO-1, and HO-1 in the treatment group compared with those in the positive control group. Additionally, Cil decreased the oxidative stress level compared with that in the ANIT-treated group.</p><p><strong>Conclusion: </strong>The results suggest that Cil effectively treats cholestasis by affecting the FXR signaling system and the NRF2 pathway.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"17 ","pages":"93-105"},"PeriodicalIF":0.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-Inflammatory Activities of Some Plants of Genus <i>Alpinia</i>: Insights from In Vitro, In Vivo, and Human Studies.","authors":"Kiki Mulkiya Yuliawati, Raden Maya Febriyanti, Sri Adi Sumiwi, Jutti Levita","doi":"10.2147/JEP.S499115","DOIUrl":"https://doi.org/10.2147/JEP.S499115","url":null,"abstract":"<p><p>This narrative review intends to provide thorough information on the anti-inflammatory activities of <i>Alpinia</i> plants, the largest genus of the family Zingiberaceae. The articles were searched on the PubMed database using 'Alpinia AND anti-inflammatory activity' as the keywords, filtered to articles published from 2020 to 2024 and free full-text. Of the approximately 248 members of the genus <i>Alpinia</i> plants, the most commonly studied for their anti-inflammatory activities are <i>A. galanga</i>, <i>A. officinarum</i>, <i>A. zerumbet</i>, and <i>A. oxyphylla</i>. Only <i>A. galanga</i>, <i>A. officinarum</i>, and <i>A. zerumbet</i> have been studied in humans. Studies in animal models revealed that the plants contributed as exogenous antioxidants, reduced proinflammatory cytokines, inhibited proinflammatory enzymes, improved gastric acid and gastrointestinal motility, and promoted ulcer healing. The terpenoids, flavonoids (such as kaempferol, quercetin, and galangin), and diarylheptanoids obtained from the rhizomes of these plants may crucially play important roles in their anti-inflammatory activities. These plants did not show toxicity toward numerous normal cell lines (RAW 264.7, IEC-6, HepG2, MT-4, NIH-3T3, Vero cells, human peripheral blood mononuclear cells, and HaCaT) but were toxic to cancer cell lines (HT29). In humans, <i>A. galanga</i> was studied for its effects as psychostimulants improving mental health, improving sperm motility, and erectile dysfunction. Similarly, <i>A. officinarum</i> could improve sperm morphology and idiopathic infertility, whereas <i>A. zerumbet</i> worked as a cardio-myorelaxant in patients with cardiovascular diseases.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"17 ","pages":"51-91"},"PeriodicalIF":0.0,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11775820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two Novel Compounds Isolated from the Marine Fungal Symbiont of <i>Aspergillus unguis</i> Induce Apoptosis and Cell Cycle Arrest in Breast Cancer Cells: In vitro Study.","authors":"Muhammad Hasan Bashari, Mochamad Untung Kurnia Agung, Eko Fuji Ariyanto, Laode Muhammad Ramadhan Al Muqarrabun, Syefira Salsabila, Agus Chahyadi, Andi Rifki Rosandy, Ervi Afifah, Merry Afni, Harold Eka Atmaja, Tenny Putri, Fitria Utami, Beginer Subhan, Syafrizayanti, Yosie Andriani, Elfahmi","doi":"10.2147/JEP.S494777","DOIUrl":"10.2147/JEP.S494777","url":null,"abstract":"<p><strong>Purpose: </strong>A promising feature of marine sponges is the potential anticancer efficacy of their secondary metabolites. The objective of this study was to explore the anticancer activities of compounds from the fungal symbiont of <i>Aaptos suberitoides</i> on breast cancer cells.</p><p><strong>Methods: </strong>In the present research, <i>Aspergillus unguis</i>, an endophytic fungal strain derived from the marine sponge <i>A. suberitoides</i> was successfully isolated and characterized. Subsequently, ethyl acetate extraction and isolation of chemical constituents produced was performed. The structures of the isolated compounds were identified using several spectroscopic methods, ie, UV, NMR, and mass spectrometry. Thereafter, MDA-MB-231, MCF-7 breast cancer cells and HaCat cells were treated with the isolated compounds. Not only viability, apoptosis, and cell cycle analyses were conducted, but also the mRNA expression of <i>MCL1, BCL2L1, AKT1</i> and <i>CDK2</i> were evaluated.</p><p><strong>Results: </strong>The extract showed cytotoxic activity in breast cancer cells. Two novel compounds were successfully isolated and identified, ie, Unguisol A (15.1 mg) and Unguisol B (97.9 mg). Both compounds share the same basic skeleton and comprise an aromatic ring which is attached to a sulphur-containing, seven-membered ring via an oxygen atom. This marked the first-time isolation of Unguisol A and Unguisol B from <i>A. unguis</i>, highlighting their novelty. Both compounds induced early apoptosis (p < 0.01) and cell cycle arrest at the S phase (p < 0.05) in MDA-MB-231 cells, but not in HaCat cells. Both compounds suppressed <i>BCL2L1</i> and <i>AKT1</i> mRNA expression (p < 0.01).</p><p><strong>Conclusion: </strong>Two novel compounds were isolated from <i>A. unguis</i>. Unguisol A and Unguisol B induced apoptosis in MDA-MB-231 breast cancer cells via <i>BCL2L1</i> mRNA downregulation, while both compounds induced cell cycle arrest at the S phase through <i>AKT1</i> mRNA downregulation.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"17 ","pages":"37-50"},"PeriodicalIF":0.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11766706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oyster Mushroom (<i>Pleurotus ostreatus</i>) Ethanolic Extract Inhibits Pparg Expression While Maintaining the Methylation of the <i>Pparg</i> Promoter During 3T3-L1 Adipocyte Differentiation.","authors":"Eko Fuji Ariyanto, Anastasya Kania Farahana, Gabriella Sachiko Jannesha Sudirman, Erlina Widiarsih, Nurul Qomarilla, Nurul Setia Rahayu, Tenny Putri Wikayani, Henhen Heryaman, Dwi Wahyudha Wira, Rima Destya Triatin, Muhammad Hasan Bashari, Yunisa Pamela, Yuni Susanti Pratiwi, Mohammad Ghozali","doi":"10.2147/JEP.S494116","DOIUrl":"10.2147/JEP.S494116","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to provide new insights into the potential of oyster mushroom (<i>Pleurotus ostreatus</i>) ethanolic extract in preventing obesity through the inhibition of <i>Pparg</i> expression and modulation of methylation level on <i>Pparg</i> promoter during 3T3-L1 adipocyte differentiation.</p><p><strong>Methods: </strong>This in vitro quantitative experimental study was conducted by treating the 3T3-L1 cell line differentiated using 0.5 mM methyl-isobutyl-xanthine, 1 μM dexamethasone, and 10 μg/mL insulin-containing medium with oyster mushroom ethanolic extract. The extract was obtained from 80 g of dried oyster mushroom powder extracted three times with 800 mL of ethanol, filtered, evaporated, and reconstituted in dimethyl sulfoxide (DMSO) to final concentrations of 0, 25, 50, and 100 µg/mL, with DMSO limited to 0.5% in all solutions. <i>Pparg</i> mRNA expression was quantified by qRT-PCR analysis and <i>Pparg</i> promoter methylation levels were measured quantitatively by pyrosequencing of bisulfite-treated DNA samples.</p><p><strong>Results: </strong>The addition of 25 µg/mL oyster mushroom ethanolic extract significantly suppressed <i>Pparg</i> mRNA expression with no significant change in the <i>Pparg</i> promoter methylation levels.</p><p><strong>Conclusion: </strong>Oyster mushroom ethanolic extract inhibited <i>Pparg</i> mRNA expression without altering <i>Pparg</i> promoter methylation, suggesting reduced adipocyte differentiation. This study emphasizes the potential of oyster mushroom in the prevention or treatment of obesity by inhibiting adipocyte differentiation.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"17 ","pages":"27-36"},"PeriodicalIF":0.0,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11745172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Suppression of Signal Transducer and Activator of Transcription-3 in A549 human Lung Carcinoma Cells Induced by Marine Sponge <i>Callyspongia aerizusa</i>.","authors":"Yuni Elsa Hadisaputri, Annida Adha Nurhaniefah, Mutakin Mutakin, Rini Hendriani, Andri Rezano, Iyan Sopyan, Yusnaini Yusnaini, Yonathan Asikin, Rizky Abdulah","doi":"10.2147/JEP.S494158","DOIUrl":"10.2147/JEP.S494158","url":null,"abstract":"<p><strong>Introduction: </strong>Lung cancer is recognized as a highly lethal disease, demanding swift and accurate solutions. Previous analysis showed the cytotoxic impact of <i>Callyspongia aerizusa (C. aerizusa)</i> extract containing ergost-22-en-3-one and ergost-7-en3-ol against A549 lung cancer cells, with an IC₅₀ value of 9.38 μg/mL. However, the extract did not have cytotoxicity towards Het-1A esophagus epithelial cells. Several reviews also validated the upregulation of pro-apoptotic molecules and the inhibition of anti-apoptotic molecules linked to the caspase-dependent signaling pathway.</p><p><strong>Purpose: </strong>The objective of this research was to extend the understanding of the effects of <i>C. aerizusa</i> extract on A549 lung carcinoma, examining its influence on various signaling pathways, malignancy, migration, and invasion.</p><p><strong>Materials and methods: </strong>PCR was used to measure <i>mRNA</i> expression, targeting <i>PTEN, Akt, mTOR, STAT-3, IL-6, VEGF</i>, and <i>HIF1α</i>. Additionally, Western Blot analysis was adopted to assess PTEN, p-Akt, Akt, p-mTOR, and p-STAT-3 protein expressions. Wound healing and invasion assays were performed to measure the migration and invasion capabilities of A549 cells post-treatment with <i>C. aerizusa</i> extract.</p><p><strong>Results: </strong>The <i>mRNA</i> expression analysis showed an increase in <i>Akt</i> and <i>m-TOR</i> but a decrease in <i>PTEN</i> and <i>STAT-3</i> after 24 hours of treatment with <i>C. aerizusa</i> extract. At the protein level, there was a downregulation of p-Akt, Akt, p-mTOR, and p-STAT-3, while PTEN increased during 24-hour treatment. Wound healing and invasion assay results showed a weakened ability of A549 cells after a 24-hour treatment with <i>C. aerizusa</i> extract. Moreover, <i>IL-6</i> and <i>HIF-1α mRNA</i> expression levels decreased during 24 hours, while <i>VEGF</i> mRNA had a slight decrease compared to untreated cells.</p><p><strong>Conclusion: </strong>In conclusion, the ergosteroids present in marine sponge <i>C. aerizusa</i> extract signified a remarkable reduction in malignancy, migration, and invasion capabilities in A549 lung carcinoma cells. These results suggested their promising candidacy for future anti-angiogenesis in anticancer therapy.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"17 ","pages":"15-25"},"PeriodicalIF":0.0,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11734514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of Probiotic Supplements and Topical Applications in the Treatment of Acne: A Scoping Review of Current Results.","authors":"Ida Ayu Manik Partha Sutema, Irma Rahayu Latarissa, I Gusti Ayu Rai Widowati, Cynthia Retna Sartika, Ni Wayan Eka Ciptasari, Keri Lestari","doi":"10.2147/JEP.S498769","DOIUrl":"10.2147/JEP.S498769","url":null,"abstract":"<p><p>Acne vulgaris is a prevalent dermatological condition characterized by comedones, papules, and pustules, with significant physical and psychological implications. Conventional treatments for this condition, including antibiotics and retinoids, face challenges, such as side effects and antibiotic resistance, necessitating alternative treatments. Recent studies show the potential of probiotics to modulate skin microbiome and alleviate acne symptoms. Therefore, this study aimed to consolidate evidence from randomized controlled trials (RCTs) and clinical investigations, evaluating the efficacy of probiotics in acne management. A comprehensive literature search was conducted across PubMed, Scopus, and Cochrane databases using several keywords, such as \"probiotic\", \"microbiome\", and \"acne vulgaris\". Inclusion criteria are RCTs and clinical studies from 2009 to 2024 examining probiotics for acne treatment. Studies were selected, screened, and analyzed based on population, intervention, design, and results. Descriptive statistics were used to summarize study characteristics. Fifteen studies including 811 participants met the inclusion criteria. The studies tested various oral and topical probiotics, including <i>Lactobacillus, Bifidobacterium, Bacillus</i>, and <i>Enterococcus</i> strains, over treatment periods ranging from 4 to 12 weeks. The results showed that probiotics, reduced acne lesions, improved skin barrier function, and decreased inflammatory markers. Both oral and topical probiotics showed potential in balancing skin microbiome and reducing acne severity. Some studies reported outcomes comparable to conventional acne treatments, such as antibiotics and benzoyl peroxide. However, there is variability in individual responses to different probiotic strains, and potential side effects, though rare, have been reported in some cases. Probiotics presented a natural, effective alternative to conventional acne treatment. However, future studies are needed to determine optimal treatment protocols.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"17 ","pages":"1-14"},"PeriodicalIF":0.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11727500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"6-Gingerol, a Bioactive Compound of <i>Zingiber officinale</i>, Ameliorates High-Fat High-Fructose Diet-Induced Non-Alcoholic Related Fatty Liver Disease in Rats.","authors":"Shirly Gunawan, Vivian Soetikno, Erni Hernawati Purwaningsih, Frans Ferdinal, Puspita Eka Wuyung, Dwi Ramadhani","doi":"10.2147/JEP.S492971","DOIUrl":"10.2147/JEP.S492971","url":null,"abstract":"<p><strong>Purpose: </strong>Endoplasmic reticulum (ER) stress has a prominent role in the pathogenesis of high-fat diet-induced non-alcohol related fatty liver disease (NAFLD). The aim of this study is to investigate the effects of 6-G on the reduction of ER stress-induced NAFLD in metabolic syndrome (MetS) rats.</p><p><strong>Methods: </strong>Twenty-five male Sprague-Dawley rats were fed with a high-fat high-fructose (HFHF) diet for 16 weeks. The rats were treated orally with 6-G (50,100, and 200 mg/kgBW) once daily for eight weeks. At Week 16, all animals were sacrificed, and serum and liver tissue were harvested for biochemical and structural analysis.</p><p><strong>Results: </strong>NAFLD liver rats were shown to have elevated protein expression of GRP78, and ER-associated apoptotic protein, such as IRE1, TRAF2, p-JNK, and p-NF-κB, which were considerably reduced by the 6-G at three doses treatment. Furthermore, a significant increase in liver apoptosis and non-alcoholic steatohepatitis (NAS) score were observed in the NAFLD rat liver and which were also attenuated by the 6-G treatment at three doses. 6-G treatment also reduced ALT, AST, and ALP serum levels.</p><p><strong>Conclusion: </strong>Considering all the findings, it is suggested that the 6-G treatment could be a potential candidate therapy in treating ER stress-induced NAFLD in rats.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"16 ","pages":"455-466"},"PeriodicalIF":0.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11662909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}