Journal of Experimental Pharmacology最新文献

{"title":"Anti-Tyrosinase and Radical Scavenging Activities of Selected Cassipourea Plants and Isolated 7-Methoxygeranin A: Traditional Use as Skin Lighteners.","authors":"Nomakhosi Mpofana, Michael Paulse, Masande Yalo, Ncoza Cordelia Dlova, Ahmed Hussein, Adedayo Ayodeji Lanrewaju, Halimat Yusuf Lukman, Jamiu Olaseni Aribisala, Fanie Rautenbach, Jeanine L Marnewick, Saheed Sabiu","doi":"10.2147/JEP.S504759","DOIUrl":"https://doi.org/10.2147/JEP.S504759","url":null,"abstract":"<p><strong>Background: </strong>In rural areas of KwaZulu-Natal and Eastern Cape Provinces, South Africa, women have traditionally used bark extracts from <i>Cassipourea flanaganii, C. malosana</i>, and <i>C. gummiflua</i> for skin lightening and sun protection. This study investigates the anti-tyrosinase and antioxidant activities of methanolic bark extracts from these species, aiming to validate their traditional use and identify potential lead compounds for the treatment of skin hyperpigmentation.</p><p><strong>Methods: </strong>Anti-tyrosinase activity was evaluated using half-maximal inhibitory concentration (IC₅₀) values, and antioxidant capacity was measured through FRAP, DPPH, and TEAC assays. Polyphenol and flavanol contents were quantified using Folin-Ciocalteu method. Potential lead compounds were identified through molecular docking, pharmacokinetic analysis, and molecular dynamics (MD) simulations. Statistical analyses, including ANOVA and post-hoc tests, compared extract activities.</p><p><strong>Results: </strong><i>C. flanaganii</i> exhibited the most potent anti-tyrosinase activity (IC₅₀: 37.10 µg/mL), though statistical differences among species were non-significant. <i>C. gummiflua</i> showed the highest polyphenol (143.68 mg GAE/g) and flavanol (14.67 mg QE/g) content, correlating with superior antioxidant activity (FRAP: 526.07 µmol AAE/g; DPPH: 390.26 µmol TE/g; TEAC: 596.98 µmol TE/g). The isolated compound 7-methoxygeranin A demonstrated lower anti-tyrosinase activity (IC₅₀: 45.16 µg/mL) compared to <i>C. flanaganii</i> extract, suggesting the presence of more potent metabolites. Molecular docking and MD simulations identified emodin 6,8-dimethyl ether as a thermodynamically stable lead compound (binding free energy: -39.88 kcal/mol), interacting with key catalytic residues over 150 ns. The compound demonstrated prolonged residence at the active site of tyrosinase, indicating strong-binding stability.</p><p><strong>Conclusion: </strong>While <i>C. flanaganii</i> demonstrated the strongest anti-tyrosinase activity, C. gummiflua showed the highest antioxidant potential. Emodin 6,8-dimethyl ether emerged as a promising candidate for skin-lightening applications, warranting further in vitro and in vivo validation. These findings support the traditional use of <i>Cassipourea</i> species and highlight their potential for developing natural skin health products. Further studies are needed to explore the pharmacokinetics, safety, and efficacy of these compounds in clinical settings.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"17 ","pages":"287-306"},"PeriodicalIF":0.0,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12136075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225676","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":"Biocompatibility and Effectiveness of Amphotericin B-Loaded Metal-Organic Structures (AmB-ZIF-8) as Dermal Drug Transporters in Experimental Cutaneous Leishmaniasis.","authors":"Heider Carreño, Jorge Osorio, Enrique Mejía-Ospino, Patricia Escobar","doi":"10.2147/JEP.S511808","DOIUrl":"10.2147/JEP.S511808","url":null,"abstract":"<p><strong>Purpose: </strong>Information on metal-organic frameworks (MOFs) as topical drug delivery systems (DDS) for antileishmanial drugs is limited. This study outlines our strategies for developing MOF-drug conjugate as a topical treatment for cutaneous leishmaniasis (CL) in mice infected with <i>Leishmania (L). amazonensis</i>.</p><p><strong>Methods: </strong>We selected conjugates from two commercial MOFs (ZIF-8 and Fe-BTC) and seven antileishmanial compounds. Amphotericin B (AmB) and zeolitic imidazolate framework-8 (AmB@ZIF-8) were chosen and prepared at an AmB: ZIF-8 ratio of 1.5:1.0 using the impregnation method. Conjugates were characterised using dynamic light scattering, UV-Vis, FTIR, and SEM. Hydrogels were prepared and evaluated for toxicity and efficacy in CL-BALB/c mice.</p><p><strong>Results: </strong>AmB@ZIF-8 exhibited a 59.6% loading capacity, 6.67% encapsulation efficiency, and 2% in vitro drug release (IVR). The particle size of AmB@ZIF-8 was smaller and more polydisperse than ZIF-8 (1370 nm vs 2537 nm). The conjugation of AmB to ZIF-8 was demonstrated. AmB@ZIF-8 exhibited similar antileishmanial activity to AmB against promastigotes. Topical 0.5% AmB@ZIF-8 and 0.5% AmB hydrogels, administered for 30 days, were unable to decrease lesion sizes or parasite loads. Initially, there was stabilisation of the lesion size; however, the lesions subsequently increased considerably during the 30-day follow-up period. The MOF-hydrogel treatment was non-irritating.</p><p><strong>Conclusion: </strong>There were very low EE% and AmB IVR. AmB@ZIF-8 and AmB hydrogels were found to be safe but ineffective against CL-infected mice. Several factors may explain these negative results, including the large size of the commercial ZIF-8, the aggregation of AmB in solution, the excess AmB used for impregnation, and the conditions of the IVR assay. We suggest continuing to use ZIF-8 as a DDS due to its sensitivity to acidic pH levels; however, we recommend reducing the particle size and lowering the drug-to-ZIF-8 ratio. Other alternatives are discussed in the present paper. We also advocate investigating alternative antileishmanial drugs as cargo, such as miltefosine or pentamidine.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"17 ","pages":"269-286"},"PeriodicalIF":0.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12133161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216036","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":"Small Interfering RNA (siRNA) in Dyslipidemia: A Systematic Review on Safety and Efficacy of siRNA.","authors":"Sai Santhosha Mrudula Alla, Dhruv Jayeshkumar Shah, Shourya Meyur, Pahel Agarwal, Deekshitha Alla, Sai Lokesh Moraboina, Gayatri Vijay Ghadvaje, Ruth Getaneh Bayeh, Aparna Malireddi, Tess Shajan, Bodipudi Vineetha, Thalvayapati Sai Prudhvi, Patrick Biziyaremye","doi":"10.2147/JEP.S521579","DOIUrl":"10.2147/JEP.S521579","url":null,"abstract":"<p><strong>Introduction: </strong>RNA interference (RNAi) therapy represents an evolving advancement in the management of dyslipidemia. One prominent form of RNAi therapy is small interfering RNA (siRNA), which has emerged as a promising therapeutic strategy. This study aims to critically analyze the efficacy and safety of siRNA in the treatment of dyslipidemia.</p><p><strong>Methods: </strong>PubMed, Scopus, and Web of Science servers were used to conduct a systematic search in compliance with the PRISMA guidelines.</p><p><strong>Results: </strong>A total of 20 studies with 6651 participants were included in the analysis. The drugs used in the studies were. Inclisiran led to a notable 44.09% reduction in LDL and 37.5% in apolipoprotein levels among individuals with hypercholesterolemia. In hyperlipoproteinemia(a), therapies like Lepodisiran and Olpasiran achieved a 75.69% drop in apolipoproteins and 16.25% in LDL. For hypertriglyceridemia, agents such as ARO-APOC3 and Plozasiran showed over 50% reductions in both VLDL and triglycerides. In mixed hyperlipidemia and chylomicronemia, Plozasiran significantly reduced triglycerides by up to 79% and apolipoproteins by 87.5%. The 5 most common adverse effects reported were nasopharyngitis, diabetes mellitus (including new-onset diabetes mellitus and worsening diabetes mellitus), injection site adverse effects, back pain, and hypertension.</p><p><strong>Conclusion: </strong>In conclusion, the benefits of siRNA therapy in dyslipidemia management appear to outweigh its potential drawbacks, demonstrating promising efficacy and safety profiles. However, further research is necessary to fully understand its long-term effects and optimize its therapeutic potential.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"17 ","pages":"249-267"},"PeriodicalIF":0.0,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12126973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199346","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 Alters Vimentin Expression and Migration Capability of Triple-Negative Breast Cancer Cells.","authors":"Astrid Feinisa Khairani, Widad Aghnia Shalannandia, Muhammad Hasan Bashari, Nur Atik","doi":"10.2147/JEP.S512099","DOIUrl":"10.2147/JEP.S512099","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to explore the effect of Aaptamine, an alkaloid derived from marine sponges, on the vimentin expression in both mRNA and protein levels and the migration capacity of breast cancer cells.</p><p><strong>Methods: </strong>The triple-negative breast cancer cell line MDA-MB-231 was used for in vitro experiments. Low-cytotoxicity concentrations of Aaptamine (12.5 to 50 μM) were given to MDA-MB-231 cells. The vimentin mRNA and protein expression were evaluated using RT-qPCR and immunofluorescence, respectively, 72 h after Aaptamine treatment. The migration scratch assay was conducted for 48 hours.</p><p><strong>Results: </strong>Aaptamine treatment in three different doses did not affect the expression of vimentin at the mRNA level while significantly lowering vimentin protein expression at the concentration of 12.5 µM. In addition, Aaptamine significantly inhibited breast cancer cell migration in a dose-dependent manner.</p><p><strong>Conclusion: </strong>Aaptamine inhibits vimentin protein expression and demonstrates anti-migration activity in the sub-cytotoxic dose.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"17 ","pages":"239-247"},"PeriodicalIF":0.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150691","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":"Antidiabetic Effect of Hydro-Ethanolic Leaf Extract of <i>Sclerocarya Birrea</i> (A. Rich.) Hochst in Wistar Rats.","authors":"Abdul Gafar Victoir Coulidiaty, Estelle Noëla Hoho Youl, Téné Marceline Yaméogo, Farouk Adedeji Oladoja, Tolulope Anuoluwapo Odejobi, Raogo Ouedraogo, Olufunsho Awodele","doi":"10.2147/JEP.S523697","DOIUrl":"10.2147/JEP.S523697","url":null,"abstract":"<p><strong>Introduction: </strong>Diabetes mellitus, characterized by chronic hyperglycaemia, remains a major global health burden. Limitations of conventional therapies have led to growing interest in medicinal plants like <i>Sclerocarya birrea</i> (A. Rich.) Hochst. widely used in African ethnomedicine. Though prior research has focused more on the stem bark, studies on the leaves, considered more sustainable and traditionally relevant, are still lacking in vivo data. This study assessed the antidiabetic potential of a hydroethanolic leaf extract of <i>Sclerocarya birrea</i> in Wistar rats.</p><p><strong>Methods: </strong>The extract was tested at 25-200 mg/kg in an oral glucose tolerance test (OGTT), and at 100-400 mg/kg in normoglycemic and high fructose-fed, streptozotocin (STZ)-induced type 2 diabetic rats over 21 and 28 days, respectively. Fasting blood glucose, insulin, glycated haemoglobin (HbA1c), glucose transporter type 4 (GLUT4), haematological and biochemical parameters, and histopathological changes in key organs were evaluated.</p><p><strong>Results: </strong>In the OGTT, the extract significantly reduced postprandial blood glucose at 100 and 200 mg/kg starting from 60 minutes post-glucose load (p < 0.05). In normoglycemic rats, repeated administration over 21 days led to a dose-dependent and statistically significant reduction in fasting blood glucose beginning on day 14 and sustained through day 21 (p < 0.01). In diabetic rats, fasting blood glucose levels were significantly reduced from day 7 onward, with 400 mg/kg producing effects comparable to glibenclamide by day 28 (p < 0.01). Insulin, GLUT4, and HbA1c levels were not significantly altered (p > 0.05). Haematological and biochemical parameters remained within normal ranges, and histopathological examination showed preservation of pancreatic and renal tissues in treated groups.</p><p><strong>Conclusion: </strong><i>Sclerocarya birrea</i> leaf extract significantly lowers blood glucose in both normoglycemic and diabetic rats without adverse effects, supporting its potential as a safe plant-based option for diabetes management. Further research is warranted to clarify its mechanisms and long-term impact.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"17 ","pages":"223-237"},"PeriodicalIF":0.0,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12094824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119832","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 Effects of the Ethanol Extract of <i>Allium Ascalonicum</i> L. in High-Fat-High-Fructose-Induced Insulin Resistance Swiss-Webster Male Mice.","authors":"Rani Yulifah Elkanawati, Sri Adi Sumiwi, Jutti Levita","doi":"10.2147/JEP.S513301","DOIUrl":"10.2147/JEP.S513301","url":null,"abstract":"<p><strong>Background: </strong>Insulin resistance (IR) is a condition where the body cannot respond properly to insulin, leading to elevated blood glucose and the development of type 2 diabetes mellitus (T2DM). The first-line anti-T2DM drug is metformin, however, it has shown adverse effects, challenging the search for alternative natural drugs. Plant flavonoids stimulate cellular glucose uptake, decrease hyperglycemia, and regulate key signaling pathways in glucose metabolism. Brebes shallots (<i>Allium ascalonicum</i> L.) are known to contain flavonoids and thus may have the potential to inhibit IR.</p><p><strong>Purpose: </strong>To evaluate the effects of the ethanol extract of Brebes shallots in improving IR conditions.</p><p><strong>Methods: </strong>Brebes shallots were collected from West Java, Indonesia. 500 g of the shallots were oven-dried and extracted using 70% ethanol for 3×24 h, the solvent was evaporated to a thick consistency, and the extract was abbreviated as EAA. The effects of EAA were studied in high-fat-high-fructose (HFHF)-induced Swiss-Webster male mice by performing the insulin tolerance test (ITT) and oral glucose tolerance test (OGTT), and the liver and pancreas index. The nutritional composition and quercetin levels in the extract were also determined.</p><p><strong>Results: </strong>The extraction process yielded a 28.1% EAA. EAA reduces % weight gain, blood glucose levels in OGTT, and liver and pancreas index. EAA significantly improved insulin tolerance in the HFHF-induced mice (<i>p <</i> 0.05). Proximate analysis resulted in 3.92% ash, 0.12% fat, 13.45% protein, and 60.69% carbohydrate, while quercetin was at 0.0065%.</p><p><strong>Conclusion: </strong><i>Allium ascalonicum</i> L. extract may improve IR conditions as confirmed by its ability to increase the ITT value and reduce blood glucose levels. However, further studies are needed to confirm its role in alleviating metabolic disorders.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"17 ","pages":"207-221"},"PeriodicalIF":0.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12091064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110877","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":"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}