Journal of Experimental Pharmacology最新文献

{"title":"Prevention of Hepatalin-Dependent Insulin Resistance Induced by a High Sucrose Diet Using a Synergistic Combination of S-Adenosyl Methionine, Vitamin E and Vitamin C (SAMEC) in Virgin and Pregnant Sprague Dawley Rats.","authors":"Nicole E J Lovat, Kawshik Chowdhury, Dallas J Legare, W Wayne Lautt","doi":"10.2147/JEP.S508879","DOIUrl":"10.2147/JEP.S508879","url":null,"abstract":"<p><strong>Introduction: </strong>Storage of nutrient energy from a meal is partitioned in the body approximately equally by insulin (with its known actions on the liver and adipose tissue) and hepatalin (released from the liver with its glycogenic action selectively in skeletal muscle, heart, and kidneys). During healthy pregnancy, there is a late stage mixed insulin resistance involving both insulin and hepatalin. In pregnant rats on a high sucrose diet, hepatalin-dependent insulin resistance (HDIR) develops with unaffected direct insulin action. Compensatory hyperinsulinemia maintains blood glucose level with resultant hypertriglyceridemia and adiposity. Previously, in male Sprague Dawley sucrose-supplemented rats, aged for one year, HDIR and the associated cardiometabolic consequences were prevented by using a targeted synergistic antioxidant cocktail composed of S-Adenosyl-Methionine, vitamin E and vitamin C (SAMEC). The current study tested the hypothesis that SAMEC would confer protection against sucrose-induced HDIR in virgin and pregnant rats.</p><p><strong>Methods: </strong>Post-prandial insulin sensitivity was quantified using the rapid insulin sensitivity test (RIST). Sucrose supplementation (35% sucrose in water) was used to induce HDIR in female rats. Eight weeks of normal or SAMEC diet with or without sucrose supplementation was used as an intervention to determine the extent of protection against HDIR by SAMEC in virgin and pregnant rats.</p><p><strong>Results and discussion: </strong>SAMEC administered with the sucrose diet prevented the development of HDIR resulting in normal plasma glucose, insulin, and triglyceride concentrations in both virgin and pregnant groups, and attenuated sucrose-induced fat mass gain in virgin rats. The direct insulin action was unimpaired.</p><p><strong>Conclusion: </strong>SAMEC preserves hepatalin-dependent glucose uptake in virgin and pregnant rats on sucrose supplementation, thus can be used as a preventative in obesity and gestational diabetes.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"17 ","pages":"193-205"},"PeriodicalIF":0.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12087585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101944","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":"Influence of the Solvent and the Harvesting Site on the Content of Phenolic Compounds and the in Vitro Antidiabetic Potential of Leafy Stems and Roots of <i>Phyllanthus amarus Schum. and Thonn</i>.","authors":"Abdoul Aziz Zanté, Daouda Zoungo, Yacouba Sanou, Pawendé Kabré, Relwendé Justin Ouédraogo, Lazare Belemnaba, Lassina Ouattara, Paulin Ouoba, Georges Anicet Ouédraogo","doi":"10.2147/JEP.S516770","DOIUrl":"https://doi.org/10.2147/JEP.S516770","url":null,"abstract":"<p><strong>Purpose: </strong>The objective was to verify the impact of the solvent and the harvesting site on the content of phenolic compounds as well as the in vitro antidiabetic activity of leafy stems and roots of <i>Phyllanthus amarus</i>.</p><p><strong>Methods: </strong>The polyphenols and total flavonoids were measured on the crude extracts, obtained after maceration for 48 hours with acetone-water 50:50 (v/v), and ethanol-water 70:30 (v/v) . These extracts were evaluated for their antioxidant properties by DPPH, ABTS, and iron reduction (FRAP) tests. Finally, the α-amylase inhibitory activity of the crude extracts was determined by the method using DNS.</p><p><strong>Results: </strong>The results show that acetone-water favors polyphenol extraction, with a maximum content of 32.62 ± 0.85 mg EAG/100 mg DE in leafy stems from Banfora (LSBaAw). In contrast, ethanol-water extracted more flavonoids, with 4.59 ± 0.02 mg EQ/100 mg DE in roots from Bobo (RBoEw). For antioxidant activity, the ethanol-water extract of Bobo leafy stems (LSBoEw) showed the highest ABTS free radical scavenging activity (81.34 ± 1.07 µg/mL). In comparison, the ethanol-water extract of Banfora roots (RBaEw) showed the best DPPH free radical scavenging activity (55.71 ± 2.48 µg/mL). On the other hand, the acetone-water extract of Banfora leafy stems (LSBaAw) showed the highest iron reduction activity (15,445.81 ± 835.75 µmol EAA/100 mg DE). Finally, the highest α-amylase inhibitory activity was observed with ethanol-water extracts from roots (RBaEw: 98.45 ± 0.38%; RBoEw: 96.56±0.31%).</p><p><strong>Conclusion: </strong>These results underline the importance of the choice of solvent, organ, and harvesting site in optimizing the use of <i>Phyllanthus amarus</i>. Further studies involving other solvents and environmental conditions will enable us to refine these observations and optimize the pharmacological potential of this plant.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"17 ","pages":"181-192"},"PeriodicalIF":0.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12066366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020027","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":"Andrographolide Reduces Cytokine Release and Cyclooxygenase-2 Expression by Inhibiting the JNK and NF-κB Pathways in Glioblastoma Cells Exposed to Cadmium.","authors":"Thitima Kasemsuk, Pornpun Vivithanaporn, Pichsinee Woonfak, Phisit Khemawoot","doi":"10.2147/JEP.S506062","DOIUrl":"10.2147/JEP.S506062","url":null,"abstract":"<p><strong>Background: </strong>Neuroinflammation is associated with brain cancer and several neurodegenerative diseases. At nontoxic concentrations, the environmental pollutant cadmium is known to increase the secretion of pro-inflammatory cytokines, including interleukin (IL)-6, IL-8, and chemokine (C-C motif) ligand 2 (CCL2) by activating the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) pathways. Andrographolide, a diterpenoid lactone, exhibits anti-inflammatory and antioxidant activity in vitro and in vivo. Hence, in this study, we aimed to determine the effects of andrographolide on cadmium-induced inflammation and the underlying mechanisms in U-87 MG glioblastoma cells.</p><p><strong>Methods: </strong>U-87 MG cells, obtained from American Type Culture Collection (ATCC), are adherent cells derived from malignant gliomas and express the astrocyte cell marker glial fibrillary acidic protein. Cell viability was measured using the methyl thiazolyl tetrazolium (MTT) assay. Human IL-6, IL-8, and CCL2 levels were measured using enzyme-linked immunosorbent assays (ELISAs). Cyclooxygenase-2 (COX-2) and the proteins involved in the MAPK and NF-κB pathways were detected via Western blotting.</p><p><strong>Results: </strong>Treating cells with andrographolide or cadmium alone or in combination did not alter cell viability. Andrographolide decreased cadmium-induced IL-6, IL-8, and CCL2 release and downregulated cadmium-induced COX-2 expression. Andrographolide also reduced the levels of cadmium-induced phospho-Jun N-terminal kinase (JNK) and phospho-p65.</p><p><strong>Conclusion: </strong>In this study, andrographolide exerted an anti-inflammatory effect on cadmium-induced inflammation by inhibiting the JNK and NF-κB pathways. These findings have implications for the development of therapies for cadmium poisoning since the efficacy of current therapeutic approaches is limited.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"17 ","pages":"169-179"},"PeriodicalIF":0.0,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795596","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":"Aaptamine Inhibits Lipid Accumulation and <i>Pparg</i> and <i>Slc2a4</i> Expression While Maintaining the Methylation of the <i>Pparg</i> Promoter During 3T3-L1 Adipocyte Differentiation.","authors":"Eko Fuji Ariyanto, Ibnu Wijaya, Zaky Alif Pradian, Agung Putri Mayasari Bhaskara, Mohammad Parezal Lastialno, Putri Halleyana Adrikni Rahman, Muhammad Hasan Bashari, Nandina Oktavia, Muhammad Iman Pratama Putra, Yuni Susanti Pratiwi, Henhen Heryaman, Diah Dhianawaty","doi":"10.2147/JEP.S511866","DOIUrl":"10.2147/JEP.S511866","url":null,"abstract":"<p><strong>Purpose: </strong>Excessive adipogenesis plays a role in the development of obesity and related metabolic disorders. Aaptamine is an alkaloid compound that has been proven to have various effects, however, no studies have yet investigated its effects on adipogenesis. This study aims to examine whether aaptamine inhibits lipid accumulation and <i>Pparg</i> and <i>Slc2a4</i>, two important genes in adipogenesis, mRNA expression, and increases the methylation of the <i>Pparg</i> promoter. This study strengthens the insights regarding these genes regulation, with future research potentially expanding to other adipogenic regulators for a broader perspective.</p><p><strong>Methods: </strong>The effects of aaptamine (0 µM, 25 µM and 50 µM) were investigated in 3T3-L1 preadipocytes. The adipocytes were differentiated using a medium containing 3-isobutyl-1-methylxanthine, dexamethasone, and insulin. Cell viability was evaluated by the MTT assay, gene expression was analyzed by RT-qPCR, and lipid accumulation was determined using Oil Red O staining. Pyrosequencing was performed to measure the methylation of the <i>Pparg</i> promoter region.</p><p><strong>Results: </strong>Aaptamine treatment significantly dose-dependently decreased lipid accumulation and inhibited <i>Pparg</i> and <i>Slc2a4</i> mRNA expression. However, there were no significant differences in the methylation level of the <i>Pparg</i> promoter.</p><p><strong>Conclusion: </strong>Aaptamine inhibits lipid accumulation and <i>Pparg</i> and <i>Slc2a4</i> mRNA expression while maintaining the methylation level of the <i>Pparg</i> promoter during 3T3-L1 adipocyte differentiation.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"17 ","pages":"159-168"},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11932118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700652","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":"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}