Journal of Experimental Pharmacology最新文献

{"title":"Development and Validation of Bioanalytical Method for Efavirenz in Dried Blood Spot Using High Performance Liquid Chromatography-Photodiode Array.","authors":"Dysaprita Nabila Putri, Yahdiana Harahap, Febrina Amelia Saputri","doi":"10.2147/JEP.S515598","DOIUrl":"https://doi.org/10.2147/JEP.S515598","url":null,"abstract":"<p><p>Efavirenz requires adequate serum concentrations (1-4 µg/mL) to ensure therapeutic efficacy and avoid central nervous system toxicity. Due to significant interindividual pharmacokinetic variability, therapeutic drug monitoring (TDM) is often necessary. Reliable bioanalytical methods for quantifying efavirenz in biological matrices are therefore essential. Previous dried blood spot (DBS) methods using High-Performance Liquid Chromatography-Photodiode Array (HPLC-PDA) showed suboptimal performance and lacked compliance with current bioanalytical guidelines. This study aimed to develop and validate an improved HPLC-PDA method for efavirenz quantification in DBS using an internal standard. The optimized sample preparation employed protein precipitation and methanol extraction, followed by chromatographic separation under isocratic conditions with UV detection at 245 nm. The method demonstrated excellent linearity <i>(r²</i> = 0.9995) within 0.1-30 µg/mL, accuracy within ±9.3%, and precision (CV < 4.6%). Recovery ranged from 91.4-95.7%, and no significant carryover or matrix effect was observed. Validation results met the acceptance criteria specified by the US FDA (2018) and EMA (2022) guidelines. The proposed method offers enhanced sensitivity, accuracy, and precision, supporting its suitability for routine TDM of efavirenz to improve treatment safety and effectiveness.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"18 ","pages":"515598"},"PeriodicalIF":0.0,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13035735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147592508","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":"Nutritional and Phytochemical Compositions of <i>Peperomia pellucida</i> (L). Kunth from Bogor, West Java, Indonesia, and Its Hypoglycemic Effects in Normoglycemic Sprague-Dawley Rats Subjected to an Acute Glucose Load.","authors":"Teodhora, Rini Hendriani, Sri Adi Sumiwi, Jutti Levita","doi":"10.2147/JEP.S566863","DOIUrl":"https://doi.org/10.2147/JEP.S566863","url":null,"abstract":"<p><strong>Background: </strong><i>Peperomia pellucida </i>(L). Kunth, a perennial plant belonging to the Piperaceae family, grows mainly in wet tropical environments and has been reported to have various biological activities.</p><p><strong>Purpose: </strong>This study aimed to evaluate the nutritional and phytochemical composition of an ethanol extract of the whole plant <i>Peperomia pellucida</i> (EEPP) collected in Bogor, West Java, Indonesia, and its hypoglycemic effects on normoglycemic rats subjected to an acute glucose load.</p><p><strong>Methods: </strong>Nutritional composition of EEPP was assessed by proximate analysis, and vitamin C and quercetin levels were assessed using HPLC. Total phenols, flavonoids, and sterols were assessed using spectrophotometry, and the phytochemical profiles were assessed using UHPLC-HRMS/MS. The hypoglycemic effects of EEPP at doses of 125, 250, and 500 mg/kg body weight on acute glucose load were evaluated using an oral glucose tolerance test in normoglycemic Sprague-Dawley rats.</p><p><strong>Results: </strong>EEPP contains high ash, carbohydrates, and protein, and low fat, with a total energy of 236.82 ± 1.15 kcal per 100 g extract. EEPP contains negligible levels of vitamin C and quercetin, a TPC of 15.62 mg GAE/100 g, a TFC of 8.00 mg QE/100 g, and total sterols of 2461.5 mg BSE/100 g. At least 50 metabolites, including flavonoids, flavonoid glycosides, alkaloids, sterols, fatty acid esters, chromenes, and coumarins, have been identified. EEPP demonstrated hypoglycemic properties by reducing 14.7-35.8% of blood glucose levels in rats subjected to an acute glucose load, but this was not statistically significant (<i>p</i> > 0.05) compared to the negative control group.</p><p><strong>Conclusion: </strong>Because of its nutritional and phytochemical composition, <i>Peperomia pellucida</i> may have the potential to be developed into a nutraceutical supplement, particularly for maintaining blood glucose levels. However, further studies are needed to confirm this effect.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"18 ","pages":"566863"},"PeriodicalIF":0.0,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13005211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499204","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 Activity of <i>Moringa oleifera</i> Aqueous Leaf Extract on Prediabetic Wistar Male Rats.","authors":"Titing Nurhayati, Vita Murniati Tarawan, Happy Delia, Faisal Faisal, Hanna Goenawan, Setiawan Setiawan","doi":"10.2147/JEP.S490839","DOIUrl":"10.2147/JEP.S490839","url":null,"abstract":"<p><strong>Purpose: </strong>Diabetes mellitus is a chronic metabolic disorder linked to sedentary lifestyles, which reduces insulin sensitivity and increases hyperglycemia risk. Standard treatments include lifestyle changes and medications. Recently, herbal remedies like <i>Moringa oleifera</i> leaves have gained attention due to bioactive compounds-polyphenols and flavonoids-believed to have antihyperglycemic effects. However, research on their impact on prediabetic conditions remains limited. This study aimed to investigate the effect of Moringa leaf extract on blood glucose levels in sedentary male Wistar rats to explore its potential as a natural antihyperglycemic agent.</p><p><strong>Patients and methods: </strong>Thirty sedentary male Wistar rats, representing a lifestyle-induced prediabetic model, were acclimatized for two weeks and randomized into five groups: Control (K), Metformin (M), and three treatment groups receiving <i>Moringa oleifera</i> leaf extract at doses of 200 mg/kgBW (D200), 400 mg/kgBW (D400), and 800 mg/kgBW (D800). The intervention lasted for 12 weeks. Blood glucose levels-including fasting, postprandial, and time-based measurements-were assessed using an Accutrend Plus device. Data were analyzed with the Shapiro-Wilk, Levene, Kruskal-Wallis, and Mann-Whitney tests (<i>p</i> < 0.05).</p><p><strong>Results: </strong><i>Moringa</i> leaf extract demonstrated a dose-dependent reduction in blood glucose levels. In the FBG test, all treatment groups showed significantly lower glucose levels compared to the control (K: 122.8 mg/dL; D200: 85.6 mg/dL; D400: 82.6 mg/dL; D800: 95.4 mg/dL; P=0.015). Similarly, TBG levels were lower in D200 (197.8 mg/dL) and D400 (186.8 mg/dL) compared to K (231 mg/dL; P=0.022). Although the PPBG decreased over time, especially in D200, the differences were not statistically significant (P>0.05).</p><p><strong>Conclusion: </strong>Administration of <i>Moringa</i> leaf powder has been shown to significantly reduce fasting blood glucose levels, but not postprandial or intermittent blood glucose levels.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"17 ","pages":"861-872"},"PeriodicalIF":0.0,"publicationDate":"2025-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12739940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145850148","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":"Repeated Levonorgestrel Administration Impairs Cognitive Function via Glutamatergic Transmission and CaMKII-PKA-BDNF Signaling in the Hippocampus of Female Wistar Rats.","authors":"Halimat Amin Abdulrahim, Noah Adavize Omeiza, Ganiu Jimoh Akorede, Oluwadamilare Iyapo, John Olabode Fatoki, Ben-Azu Benneth, Emmanuel Bukoye Oyewo, Aboyeji Lukuman Oyewole, Abdullateef Isiaka Alagbonsi, Adeniran Sanmi Adekunle","doi":"10.2147/JEP.S559477","DOIUrl":"10.2147/JEP.S559477","url":null,"abstract":"<p><strong>Background: </strong>Levonorgestrel (LNG), a synthetic progestin widely used in emergency contraception, is increasingly taken frequently and often without medical supervision. With rising concerns that repeated exposure to such hormones may adversely affect brain function, this study investigated whether chronic LNG administration impairs cognitive-like behavior and alters key neurochemical pathways in female Wistar rats.</p><p><strong>Methods: </strong>Experimental rats were assigned to three groups receiving normal saline (control) or LNG (4 or 8 µg/kg) every alternate day for 60 days. Cognitive performance was assessed using the Morris water maze (MWM) and novel object recognition (NOR) tests. Hippocampal tissues were subsequently analyzed for glutamatergic markers and downstream signaling molecules involved in learning and memory.</p><p><strong>Results: </strong>Chronic LNG exposure (4 and 8 µg/kg) impaired both spatial and non-spatial memory, evidenced by prolonged escape latency and reduced path efficiency in the MWM, along with a decreased discrimination index in the NOR test. Neurochemically, LNG significantly reduced hippocampal levels of glutamate, N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor ligands, protein kinase A (PKA), calcium/calmodulin-dependent kinase II (CaMKII), and brain-derived neurotrophic factor (BDNF), with the 8 µg/kg dose exerting more pronounced effects.</p><p><strong>Conclusion: </strong>Repeated LNG administration leads to notable cognitive deficits, likely mediated by impairments in glutamatergic signaling and downstream molecular pathways essential for synaptic plasticity. These findings underscore potential neurocognitive risks associated with prolonged LNG exposure.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"17 ","pages":"841-859"},"PeriodicalIF":0.0,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12722416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827831","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":"Pyrazoline B Induces Oxidative Stress Mediated Toxicity, Cell Cycle Arrest, and Caspase-Independent Apoptosis in BT-474 Human Breast Cancer Cells.","authors":"Hesti Lina Wiraswati, Pamungkas Bagus Satriyo, Muhammad Hasan Bashari, Eti Nurwening Sholikhah, Tutik Dwi Wahyuningsih, Ilma Fauziah Ma'ruf, Chi-Tai Yeh, Mustofa Mustofa","doi":"10.2147/JEP.S499127","DOIUrl":"10.2147/JEP.S499127","url":null,"abstract":"<p><strong>Introduction: </strong>Luminal subtype B breast cancer represents a clinically challenging subtype, accounting for nearly 40% of all breast cancers. However, clinical outcomes remain suboptimal due to challenges such as poor solubility, resistance, and drug-induced toxicity. In our previous work, a synthesized compound pyrazoline B demonstrated potent toxicity effects towards T47D, 4T1, and Hs578T breast cancer cells, WiDr colorectal cancer cells, and HeLa cervical cancer cells. Building on these findings, we now investigate-for the first time-the therapeutic potential of a lead compound, pyrazoline B, against luminal B breast cancer using the clinically relevant BT-474 model (HER2+/ER+). This study systematically evaluates pyrazoline B's standalone efficacy and preliminary synergistic interactions with paclitaxel, aiming to address current therapeutic gaps in this high-risk subtype.</p><p><strong>Methods: </strong>Comprehensive in vitro analysis included proliferation and cell migration (scratch) assays, flow cytometry (apoptosis and cell cycle), ELISA (EGFR/VEGFR-2), and RT-qPCR, complemented by in silico ADME and molecular docking analyses.</p><p><strong>Results: </strong>Pyrazoline B demonstrated multimodal activity, inducing G0/G1 arrest through Cyclin D1 suppression while reduced EGFR and VEGFR-2 proteins level. The compound triggered caspase-independent cell death via oxidative stress. Additionally, pyrazoline B enhances the inhibitory effect of paclitaxel on the proliferation and migration of cancer cells. ADME predictions revealed that pyrazoline B exhibits more favorable pharmacokinetic properties of than paclitaxel.</p><p><strong>Discussion: </strong>Our findings established pyrazoline B as a first-in-class multi-target agent against BT-474 luminal B breast cancer, uniquely capable of simultaneously disrupting cell cycle progression, growth factor signaling, and redox homeostasis. Pyrazoline B demonstrates strong potential as a monotherapy, and our initial combination screening showed promising boosting effects when used with existing therapies. Future studies should prioritize: mechanistic synergy studies and in vivo validation to assess translational potential.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"17 ","pages":"823-839"},"PeriodicalIF":0.0,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12712847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145804671","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":"In vivo Therapeutic Inhibition of the Tp53-Induced Glycolysis and Apoptosis Regulator (TIGAR) by Intravenous Administration of an Anti-Oncological siRNA-Biopolymer, TI6752 (Tituxistatin), in a Preclinical Xenograft Model of Colorectal Cancer.","authors":"Carolyn K Harrod, Brenda Y Hernandez, Courtney Yates, Robert Harrod","doi":"10.2147/JEP.S546622","DOIUrl":"10.2147/JEP.S546622","url":null,"abstract":"<p><strong>Introduction: </strong>The TP53-induced glycolysis and apoptosis regulator (TIGAR) is upregulated in many cancers and often correlates with poor clinical prognoses and serves as a key determinant of therapy-responsiveness. The TIGAR protein is structurally nearly identical to the phosphatase subunit of the bifunctional, fructose-6-phosphokinase/fructose-2,6-bisphosphatase, which has likely hindered efforts to date to develop small-molecule pharmacological inhibitors of TIGAR.</p><p><strong>Purpose: </strong>The objective of this study was to investigate the efficacy of a siRNA-<i>tigar</i>-biopolymer, TI6752 (Tituxistatin), to therapeutically inhibit tumorigenesis in an in vivo xenograft model of colorectal cancer.</p><p><strong>Materials and methods: </strong>The overexpression of TIGAR within K-Ras+ tumor cells and the infiltration of PECAM-1+ endothelial progenitors in primary colorectal carcinoma clinical samples were detected by immunoconfocal microscopy. Immunodeficient NIH III-nude mice were subcutaneously engrafted with HCT116 colon cancer cells and then treated with three doses of TI6752 (1 mg/kg bw) or a Vehicle control, administered intravenously at weekly intervals. The animals were humanely sacrificed and HCT116 cells within the tumor tissues were visualized using an Anti-human Ki67 primary antibody. The accumulation of biotin-labeled TI6752 within preexisting HCT116 tumor tissues, compared to other secondary organs (heart, liver, kidneys), was visualized using an AlexaFluor488-conjugated Anti-Biotin primary antibody.</p><p><strong>Results: </strong>We have shown that TIGAR is highly expressed in K-Ras+ colorectal carcinoma clinical samples and correlates with robust angiogenesis. Using a preclinical HCT116 xenograft model of colorectal carcinoma, we have demonstrated that therapeutic IV-administration of a pegylated siRNA-biopolymer, TI6752, inhibited tumor growth and reduced the infiltration of PECAM-1+ endothelial progenitors into xenograft tumor tissues without causing any adverse secondary effects.</p><p><strong>Conclusion: </strong>This study has demonstrated that IV-delivery of a pegylated siRNA-biopolymer, TI6752, targeted against <i>tigar</i> mRNA transcripts, effectively inhibited tumor growth and angiogenesis in an HCT116 xenograft model of colorectal carcinoma. TI6752 could represent a effective therapeutic approach to target TIGAR's pro-oncogenic functions in human cancers.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"17 ","pages":"805-822"},"PeriodicalIF":0.0,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12595972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145482247","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":"<i>Colocasia Esculenta</i> as a Potential Plant-Based Medicine: A Review on Its Bioactive Constituents and Pharmacological Activities.","authors":"Reza Pertiwi, Gofarana Wilar, Sri Adi Sumiwi, Jutti Levita","doi":"10.2147/JEP.S550113","DOIUrl":"10.2147/JEP.S550113","url":null,"abstract":"<p><p><i>Colocasia esculenta</i> (L.) Scott, commonly known as taro, is a tuberous plant widely cultivated and utilized as a food source and traditional medicine in various cultures worldwide. Its ethnopharmacological significance, particularly in Asia, Africa, and the Pacific Islands, has increased scientific interest in exploring its therapeutic potential. This review provides a comprehensive overview of the diverse characteristics of <i>C. esculenta</i>, emphasizing its bioactive constituents and reported pharmacological activities. To gather relevant information, articles were retrieved from the PubMed database using the keyword \"Colocasia esculenta\", with filters applied to full-text articles published between 2015 and 2024. Inclusion criteria comprised studies reporting pharmacological, toxicological, or phytochemical findings, while unrelated agricultural studies were excluded. The evidence suggests that <i>C. esculenta</i> exhibits multiple pharmacological activities across various experimental models. In vitro studies have shown this plant has anticancer, antibacterial, anti-inflammatory, antiproliferative, anti-oxidant, and antidiabetic properties. Animal models have demonstrated their anticancer, antidiarrheal, anti-obesity, hepatoprotective, antidiabetic, diuretic, antihyperlipidemic, anti-inflammatory, neuroprotective, and anticonvulsant properties. Flavonoids, phenolic compounds, and alkaloids contribute to the therapeutic effects of <i>C. esculenta</i>. Limited human investigations, including studies using the proximity extension assay (PEA) protocol, suggest potential translational applications, although clinical evidence remains scarce. In conclusion, <i>C. esculenta</i> demonstrates promising pharmacological activities supported by preclinical evidence, yet significant research gaps persist, particularly regarding varietal differences, standardized dosages, safety profiles, and rigorous clinical validation. Future studies should focus on comparative phytochemical analyses, toxicological evaluations, and well-designed clinical trials to establish its efficacy and safety as a plant-based therapeutic agent.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"17 ","pages":"755-803"},"PeriodicalIF":0.0,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12584820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145452038","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":"A Narrative Review of the Biological Activities of <i>Anredera cordifolia</i> (Ten). Steenis for Its Potential as a Natural Feed Additive for Livestock: Bridging Phytochemical Profile and in silico, in vitro, and in vivo Studies.","authors":"Ken Ratu Gharizah Alhuur, Diky Ramdani, Indah Suasani Wahyuni, Yaya Rukayadi, Jutti Levita","doi":"10.2147/JEP.S555718","DOIUrl":"10.2147/JEP.S555718","url":null,"abstract":"<p><p>Antibiotic growth promoters (AGPs) are commonly used as feed additives to enhance livestock productivity; however, their side effects, such as antimicrobial resistance in both animal and human bacterial pathogens, have arisen, thus leading to the discovery of safer alternatives. Plants added to the basal diet have been explored for their effectiveness in animal nutrition and health, particularly to replace AGPs. <i>Anredera cordifolia</i> (Ten). Steenis, which contains numerous secondary metabolites, is believed to contribute significantly to its biological activities. This review aims to identify the potential of <i>A. cordifolia</i> to be utilized as a natural feed additive for livestock and poultry, through exploration of its in silico, in vitro, and in vivo studies, as well as its application as a feed additive in various animal species. The Scopus and PubMed databases were used to initially search for articles published between 2015 and 2025, written in English. The resulting articles were further screened for their eligibility. The main biological properties of this plant studied in rodents were wound healing, anti-inflammatory, antioxidant, and antimicrobial, which, related to its application to goats, poultry, rabbits, and guinea pigs, confirmed antiprotozoal and anthelmintic properties, a reduction of methane production, and a decrease of cholesterol in egg yolk. The plant extract has no acute toxic effects or mortality in guinea pigs. Secondary metabolites contained in the leaves, such as flavonoids, have shown antioxidant and antimicrobial properties, while tannins can reduce methane and ammonia production in ruminants. Therefore, <i>A. cordifolia</i> leaves have the potential to be used as a feed additive, replacing AGP, to increase livestock productivity, with more benefits and fewer side effects.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"17 ","pages":"743-753"},"PeriodicalIF":0.0,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12577591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145431886","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":"Effects of <i>Catha edulis</i> Extract on Atorvastatin-Induced Myotoxicity in Rats: Biochemical and Histopathological Evidence.","authors":"Abdulatef Mohammed Mohammed Abbas, Safia Abdulatef Abdulruhman Alrezami, Butheina Abdulwalli Al-Amrani","doi":"10.2147/JEP.S555519","DOIUrl":"10.2147/JEP.S555519","url":null,"abstract":"<p><strong>Background: </strong>Rhabdomyolysis (RML) is a complex disorder caused by muscle cell injury and the subsequent release of intracellular components into circulation. Statins are widely used and generally well tolerated; however, some patients report muscle weakness, particularly in the lower extremities. The concomitant use of statins with other substances, including herbal products such as khat (<i>Catha edulis</i>), may increase the risk of adverse events. Khat chewing is known to cause multiple health problems and has been associated with musculoskeletal weakness.</p><p><strong>Aim: </strong>This study aimed to evaluate the effects of khat extract on atorvastatin-induced rhabdomyolysis in rats.</p><p><strong>Methods: </strong>Methanolic extraction of khat leaves was performed, and phytochemical analysis confirmed the presence of alkaloids, tannins, flavonoids, and other bioactive compounds. Twenty-four healthy rats were randomly divided into four groups: control, khat extract (500 mg/kg), atorvastatin (40 mg/kg), and khat extract plus atorvastatin. Treatments were administered orally for 28 days. On day 28, blood samples were collected for biochemical assays of myoglobin, creatine kinase (CK-MM), lactate dehydrogenase (LDH, LDH5), alkaline phosphatase (ALP), troponin fast skeletal (fsTnI), creatinine, albumin, and total protein. Histopathological analysis of skeletal muscle and kidney tissues was also conducted. Data were analyzed using the Kruskal-Wallis, expression by median(IQR), CI(95%) with significance set at p < 0.05.</p><p><strong>Results: </strong>The khat-atorvastatin group showed significant weight reduction and marked increases in biochemical markers compared with controls. The khat-only and atorvastatin-only groups also demonstrated elevated biomarkers but at lower levels. Histopathology confirmed severe muscle necrosis and kidney tubular injury in the khat-atorvastatin group, while mild myopathy was evident in the khat-only and atorvastatin-only groups.</p><p><strong>Conclusion: </strong>Khat extract contributes to biochemical and histopathological changes indicative of muscle injury. When combined with atorvastatin, these effects are exacerbated, leading to pronounced myopathy and kidney damage. These findings suggest that khat use may potentiate statin-induced rhabdomyolysis and increase the risk of musculoskeletal and renal complications.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"17 ","pages":"721-741"},"PeriodicalIF":0.0,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12577584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145431819","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":"<i>Artemisia annua</i> Extract Ameliorates Atopic Dermatitis: Evidence from 3D Epidermal Model and Complementary in vitro Assays.","authors":"Yuanyuan Tian, Lei Jiao, Yiran Li, Yi Tian, Yuanyuan Chen, Haidong Jia, Lin Ma","doi":"10.2147/JEP.S550568","DOIUrl":"10.2147/JEP.S550568","url":null,"abstract":"<p><strong>Background: </strong>Atopic dermatitis (AD) is a chronic and recurrent inflammatory skin disease. The disruption of the epidermal barrier and the inflammatory response are the key factors for the occurrence and development of this disease. <i>Artemisia annua</i> extract (AAE), a widely used traditional Chinese medicine, exhibits anti-inflammatory properties that may benefit AD management.</p><p><strong>Objective: </strong>To evaluate the ability of AAE to inhibit inflammation and promote skin barrier repair in an AD-like three-dimensional (3D) epidermal equivalent model.</p><p><strong>Methods: </strong>Keratinocytes were treated with three AAE concentrations (0.1%, 0.3%, and 1%) to assess their cytotoxic effects using Cell Counting Kit-8. Methyl-β-cyclodextrin and interleukin (IL)-4, IL-13, and IL-25 were used to induce the AD-like model. The expression of skin structural proteins, inflammatory factors, and histopathological manifestations were compared among AAE-treated AD models, an untreated AD model, and normal control models.</p><p><strong>Results: </strong>Expression of the skin barrier proteins filaggrin (<i>p</i> < 0.0001, 95% CI: 0.7006 to 0.8265), loricrin (<i>p</i> < 0.0001, 95% CI: 0.2028 to 0.3031), and desmoglein-1 (<i>p</i> < 0.05, 95% CI: 0.0298 to 0.4227) was remarkably restored, whereas that of HAS3 (<i>p</i> < 0.05, 95% CI: 1.169 to 7.207), NELL2 (<i>p</i> < 0.0001, 95% CI: 5.787 to 6.978), TSLP (<i>p</i> < 0.01, 95% CI: 1.657 to 7.513), and IL-1α (<i>p</i> < 0.001, 95% CI: 19.33 to 63.35), IL-6 (<i>p</i> < 0.01, 95% CI: 2.474 to 13.78), and IL-8 (<i>p</i> < 0.0001, 95% CI: 36.55 to 55.63) was reduced significantly in 1% AAE concentration. AAE may exert its effects by inhibiting the over-activation of the MAPK pathway in an AD-like 3D epidermal model.</p><p><strong>Conclusion: </strong>1% AAE inhibits inflammation and promotes skin barrier function in an AD-like 3D epidermal equivalent model. AAE which mainly includes Arteannuin B, Chlorogenic Acid, Chrysoplenol D, Scopolin, and Vitexicarpin is identified as the putative targets for AD therapy.</p>","PeriodicalId":15846,"journal":{"name":"Journal of Experimental Pharmacology","volume":"17 ","pages":"707-720"},"PeriodicalIF":0.0,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12535716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336995","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}