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The impact of antidiabetic medications on COVID-19 outcomes in diabetic patients: an overview 2 2 The advent of Coronavirus Disease 2019 (COVID-19), first identified in Wuhan, China, has led to significant mortality and morbidity worldwide, disproportionately affecting individuals with comorbidities such as diabetes mellitus (DM), cardiovascular diseases (CVDs), and obesity. Evidence suggests a strong correlation between DM and heightened risk of severe COVID-19 complications, which is thought to be exacerbated by factors such as hyperglycemia, systemic inflammation, immune dysregulation, and the increased expression of the angiotensin-converting enzyme 2 (ACE2) receptor in pancreatic cells. The interaction of COVID-19 with antidiabetic medications is complex, with varying reports on how these drugs may influence the disease trajectory in diabetic patients. This article seeks to synthesize the current literature on the role of antidiabetic agents in managing COVID-19 in patients with diabetes, elucidating their potential protective or adverse effects and providing a comprehensive overview of the evolving understanding of this critical interface. 363 388 2023/11/24 1402/9/3 2024/05/7 1403/2/18 Malek Zarei Malek Zarei Shahid Beheshti University of Medical Sciences, Tehran, Iran Iran m.zarei@sbmu.ac.ir Navideh Sahebi vaihan Navideh Sahebi vaihan Brigham and Women's Hospital, Boston, Massachusetts, United States United States nsahebivaighan@bwh.harvard.edu Sepideh Shiravand Sepideh Shiravand Shahid Beheshti University of Medical Sciences, Tehran, Iran Iran sepidehshiravand3@gmail.com Sara Mohammadvali-samani Sara Mohammadvali-samani Shahid Beheshti University of Medical Sciences, Tehran, Iran Iran saramvsamani@yahoo.com Mohammad Abbas Sheikholeslami Mohammad Abbas Sheikholeslami Shahid Beheshti University of Medical Sciences, Tehran, Iran Iran mashaikhalagha@gmail.com Zahra Roudbari Zahra Roudbari Shiraz University of Medical Sciences, Shiraz, Iran Iran poro72@gmail.com COVID-19 Diabetic patients Antidiabetic agents COVID-19 outcomes Abdallah D M, Nassar N N, Abd-El-Salam R M. 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The efficacy of Hypericum helianthemoides extraction with phenytoin in diabetic and non-diabetic wound healing: An experimental study in rats 2 2 Introduction: Traditional medicine recommends herbal medicines for metabolic disorders. The present study explores the skin wound healing potential of Hypericum helianthemoides (H. helianthemoides) extract in diabetic and non-diabetic rats. Methods: Following wound induction in diabetic (n=50) (induced by a single dose of streptozotocin) and non-diabetic (n=50) rats, H. helianthemoides extract (5% and 10%) was administered versus standard drug phenytoin (1%) and Osrin to positive and sham control groups. Tropical ointment therapy was applied once a day until the end of the study period (20 days). A Vernier caliper (with a 0.1 mm accuracy) was used to measure the wound length at 1, 3, 7, 11, 15, and 20 days after induction. Furthermore, pathological examination categorized the wound healing process into five categories: poor, mild, moderate, fair, and excellent. Results: On the study’s first day, both diabetic and nondiabetic rats had the same wound area size. After 11 days, the wound area size significantly decreased in groups treated with 5% and 10% H. helianthemoides extract compared to the sham and control groups (P<0.001). Hence, based on the wound pathological evaluation scale, the most frequent phenytoin and H. helianthemoides extract-treated groups were classified as moderate to excellent (P<0.05). Conclusion: H. helianthemoides extract accelerates full-thickness wound healing in diabetic and non-diabetic rats 389 399 2023/11/242024/03/20 1403/1/1 2024/05/72024/10/5 1403/7/14 Soheila Soltanbeigi Soheila Soltanbeigi Department of Physiology, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran Iran ss.soheila@yahoo.com Zeinab Fahimi Zeinab Fahimi Department of Physiology, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran Iran zeinab_fahimi@yahoo.com Maryam Maleki Maryam Maleki Department of Physiology, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran Iran maryammaleki777@yahoo.com Aliashraf Mozafari Aliashraf Mozafari Non-Communicable Diseases Center, Ilam University of Medical Sciences, Ilam, Iran Iran amozafari99@yahoo.com Mohammad Reza Kaffashian Mohammad Reza Kaffashian Department of Physiology, School of Medicine, Ilam University of Medical Sciences, Ilam, Iran Iran kaffashian-mr@medilam.ac.ir Hypericum helianthemoides Wound healing Herbal medicine Streptozotocin Diabetes mellitus Altan A, Aras M H, Damlar İ, Gökçe H, Özcan O, Alpaslan C. 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Cholic acid enhanced hypercholesterol parameters in high cholesterol diet fed Sprague-Dawley rats 2 2 Introduction: Hypercholesterolemia is a condition in which the blood contains elevated levels of low-density lipoprotein (LDL) and non-high-density lipoprotein (HDL). There are varieties of different diets used by different laboratories as a recipe for induction with varying levels of hypercholesterolemia. This study aims to investigate the role of cholic acids in enhancing hypercholesterolemia parameters in Sprague Dawley rats. Methods: Nine Sprague Dawley rats (250 g ± 50 g BW) were used to investigate the most effective diet that is cost-effective for inducing hypercholesterolemia. The rats were randomly divided into 3 groups: normal diet (ND) (n=3), high cholesterol diet (HCD 1), a combination of 2% cholesterol and 0.5% cholic acid (n=3), and high HCD 2, a combination of 2% cholesterol and 30% ghee (n=3). After 4 weeks of feeding, blood samples were collected for lipid profiling, which included total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL). The liver, kidney, and brain were removed for histopathological examination using hematoxylin and eosin (H&E) staining. Results: The lipid profile measurements show significant differences between the HCD 1 group for total cholesterol, LDL cholesterol, non-HDL cholesterol, and total cholesterol/ HDL ratio compared to the normal group. HCD 2 shows no significant changes in lipid profiles compared to the normal group. Conclusion: Cholic acid helps in the absorption of cholesterol and enhances the hypercholesterol parameters in diet-induced SD rats based on lipid profile analysis and histology of the liver and kidney. 400 408 2023/11/242024/03/202023/12/17 1402/9/26 2024/05/72024/10/52024/04/23 1403/2/4 Azmina Hassan Azmina Hassan School of Health Sciences, Health Campus Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia Malaysia nurazminahassan@gmail.com Zuraidah Abdullah Zuraidah Abdullah School of Health Sciences, Health Campus Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia Malaysia zuraidahabdullah@usm.my Niu Jin Tan Niu Jin Tan ZN Abqary Enterprise, 43-1 Jalan DU2/1, Taman Damai Utama, 47180 Puchong, Selangor, Malaysia Malaysia niujinmy@gmail.com Sabreena Safuan Sabreena Safuan School of Health Sciences, Health Campus Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia Malaysia sabreena@usm.my Dietetical recipe Hypercholesterolemia Low-density lipoprotein SD rats Águila M B, Loureiro C C, Pinheiro A d R, Mandarim-de-Lacerda C A. Lipid metabolism in rats fed diets containing different types of lipids. Arquivos Brasileiros de Cardiologia 2002; 78: 32-38. https://doi.org/10.1590/S0066-782X2002000100003##Aminlari L, Shekarforoush S S, Hosseinzadeh S, Nazifi S, Sajedianfard J, Eskandari M H. Effect of probiotics Bacillus coagulans and Lactobacillus plantarum on lipid profile and feces bacteria of rats fed cholesterol-enriched diet. Probiotics Antimicrob Proteins 2019; 11: 1163-1171. https://doi.org/10.1007/s12602-018-9480-1##Antona M E, Ramos C, Stranges A, Monteiro A F, Chaves M M G, Mandalunis P, et al. Fish oil diet effects on alveolar bone loss, in hypercholesterolemic rats. Arch Oral Biol 2020; 109: 104553. https://doi.org/10.1016/j.archoralbio.2019.104553##Ardiana M, Harsoyo P M, Hermawan H O, Sufiyah I M, Firmanda D R, Desita S R, et al. Higher cardiovascular risks and Atherogenic Index of Plasma found in police officers of developing country in Surabaya, East Java, Indonesia. Clin Epidemiol Glob Health 2022; 17: 101132. https://doi.org/10.1016/j.cegh.2022.101132##Basheer S, Malik I R, Awan F R, Sughra K, Roshan S, Khalil A, et al. Histological and microscopic analysis of fats in heart, liver tissue, and blood parameters in experimental mice. Genes 2023; 14: 515. https://doi.org/10.3390/genes14020515##Bentzon J F, Otsuka F, Virmani R, Falk E. Mechanisms of plaque formation and rupture. Circulation research 2014; 114: 1852-1866. https://doi.org/10.1161/CIRCRESAHA.114.302721##Bethesda L. Clinical and research information on drug-induced liver injury [internet]. National Institute of Diabetes and Digestive and Kidney Diseases 2012.##Coelho R P, Feksa D L, Oliveira P M, da Costa Güllich A A, Pilar B C, Piccoli J d C E, et al. Protective effect of the hydroalcoholic extract of Tripodanthus acutifolius in hypercholesterolemic Wistar rats. Biomed Pharmacother 2018; 97: 300-309. https://doi.org/10.1016/j.biopha.2017.10.003##Corso G, Russo A D, Gelzo M. Liver and the defects of cholesterol and bile acids biosynthesis: rare disorders many diagnostic pitfalls. World J Gastroenterol 2017; 23: 5257. https://doi.org/10.3748/wjg.v23.i29.5257##Daneman R, Prat A. The blood-brain barrier. Cold Spring Harbor perspectives in biology 2015; 7: a020412. https://doi.org/10.1101/cshperspect.a020412##Devi S, Singh R. Assessment of lipid lowering effect of Nepeta hindostana herb extract in experimentally induced dyslipidemia. J Nutr Intermed Metab 2017; 9: 17-23. https://doi.org/10.1016/j.jnim.2017.08.002##El-Sayyad H I, El-Shershaby E M, El-Mansi A A, El-Ashry N E. Anti-hypercholesterolemic impacts of barley and date palm fruits on the ovary of Wistar albino rats and their offspring. Reproductive Biology 2018; 18: 236-251. https://doi.org/10.1016/j.repbio.2018.07.003##Gajda A M, Pellizzon M A, Ricci M R, Ulman E A. Diet-induced metabolic syndrome in rodent models. Animal Lab News 2007; 74: 775-793.##Gonzales E, Matarazzo L, Franchi-Abella S, Dabadie A, Cohen J, Habes D, et al. Cholic acid for primary bile acid synthesis defects: a life-saving therapy allowing a favorable outcome in adulthood. Orphanet J Rare Dis 2018; 13: 1-8. https://doi.org/10.1186/s13023-018-0920-5##Hackam D G, Hegele R A. Cholesterol lowering and prevention of stroke: An overview. Stroke 2019; 50: 537-541. https://doi.org/10.1161/STROKEAHA.118.023167##Hassan A, Abdullah Z, Safuan S. Induction of hypercholesterolemia in rodents based on different dietary requirements: a systematic review. Malays J Med Res 2023; 19.##Hofmann A. Bile acid secretion, bile flow and biliary lipid secretion in humans. Hepatology (Baltimore, Md.) 1990; 12: 17S-22S; discussion 22S.##Kazemi T, Hajihosseini M, Moossavi M, Hemmati M, Ziaee M. Cardiovascular risk factors and atherogenic indices in an Iranian population: Birjand East of Iran. Clinical Medicine Insights: Cardiology 2018; 12: 1179546818759286. https://doi.org/10.1177/1179546818759286##Nadig P, Asanaliyar M, Salis K M. Establishment of long-term high-fat diet and low dose streptozotocin-induced experimental type-2 diabetes mellitus model of insulin resistance and evaluation of seed extracts of Syzygium cumini. J Herbmed Pharmacol 2021; 10: 331-338. https://doi.org/10.34172/jhp.2021.38##Pan X. Cholesterol metabolism in chronic kidney disease: physiology, pathologic mechanisms, and treatment. Sphingolipid Metabolism and Metabolic Disease: Springer, 2022: 119-143. https://doi.org/10.1007/978-981-19-0394-6_9##Pandya V, Rao A, Chaudhary K. Lipid abnormalities in kidney disease and management strategies. World J Nephrol 2015; 4: 83. https://doi.org/10.5527/wjn.v4.i1.83##Rodrigues M S, de Paula G C, Duarte M B, de Rezende V L, Possato J C, Farias H R, et al. Nanotechnology as a therapeutic strategy to prevent neuropsychomotor alterations associated with hypercholesterolemia. Colloids and Surfaces B: Biointerfaces 2021; 201: 111608. https://doi.org/10.1016/j.colsurfb.2021.111608##Romain C, Piemontese A, Battista S, Bernini F, Ossoli A, Strazzella A, et al. Anti-atherosclerotic effect of a polyphenol-rich ingredient, Oleactiv®, in a hypercholesterolemia-induced Golden Syrian hamster model. Nutrients 2018; 10: 1511. https://doi.org/10.3390/nu10101511##Suman R K, Ray Mohanty I, Borde M K, Maheshwari U, Deshmukh Y. Development of an experimental model of diabetes co-existing with metabolic syndrome in rats. Adv Pharmacol Sci 2016; 2016: 9463476. https://doi.org/10.1155/2016/9463476##Udomkasemsab A, Prangthip P. High fat diet for induced dyslipidemia and cardiac pathological alterations in Wistar rats compared to Sprague Dawley rats. 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Effect of Thioflavin-T on Adipokine Hormones and Fatty Liver in obese male NMRI mice fed a high-fat diet 2 2 Introduction: The objective of the study was to find out the influence of Thioflavin-T (ThT) on obesity and fatty liver by investigating the adipokine hormones, and insulin serum level of male NMRI mice which were exposed to a high-fat diet (HFD). Methods: 50 adult male NMRI mice were separated into five groups: n=10. The control group was given a standard diet at twelve-week intervals. The sham group was nourished with HFD that lasted for 8 weeks, afterwards, the group received a standard diet and solvent water (0.5ml) by gavage (4 weeks). The experimental groups 1-3 were nourished with HFD (4% cholesterol, 60% fat) eight-week period. Then, the treatment period started in experimental groups by receiving a normal diet in addition to ThT with three doses (5,10 and 15 mg/kg, 0.5ml), via gavage (4 weeks).  Results: HFD contributed to a substantial reduction in serum adiponectin levels and increased leptin serum in the sham group opposite to the control group (P< 0.001). However, the concentration of both adipokine hormones was significantly modified under the treatment of ThT in a dose-dependent manner. Insulin serum increased in the sham group significantly (P< 0.001), meanwhile, a significant decrease was shown in experimental groups 2, and 3 than in the sham group (P<0.01). ThT also reduced HOMA-IR in experimental groups. The introduction of ThT in varying doses led to the induction of polymorphonuclear cells in the liver tissue. Conclusion: Our findings propose that ThT can affect liver function and body weight by modulating the serum levels of adipokine hormones besides decreasing the level of insulin and HOMA-IR in mice fed with HFD. 409 418 2023/11/242024/03/202023/12/172024/01/12 1402/10/22 2024/05/72024/10/52024/04/232024/05/25 1403/3/5 Nafiseh Amani-Ekhtesar Nafiseh Amani-Ekhtesar Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran Iran amaniekhtesar@yahoo.com parichehreh yaghmaei parichehreh yaghmaei Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran Iran yaghmaei_p@yahoo.com azadeh ebrahim habibi azadeh ebrahim habibi Biosensor Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran Iran azadehabibi@yahoo.fr leyla karkhaneh leyla karkhaneh Department of Physiology, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran Iran l_karkhaneh@yahoo.com Adiponectin Leptin Fatty liver Obesity Thioflavin-T Adolph T E, Grander C, Grabherr F, et al. 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A high-fat diet has a tissue-specific effect on adiponectin and related enzyme expression. Obesity 2006; 14(12): 2145-2153. https://doi.org/10.1038/oby.2006.251##Bilal M, Nawaz A, Kado T, et al. Fate of adipocyte progenitors during adipogenesis in mice fed a high-fat diet. Mol Metab 2021; 1; 54: 101328. https://doi.org/10.1016/j.molmet.2021.101328##Chen I S, Chang Y Y, Hsu C L, et al. Alleviative effects of deep-seawater drinking water on hepatic lipid accumulation and oxidation induced by a high-fat diet. J Chin Med Assoc 2013;1:76(2): 95-101. https://doi.org/10.1016/j.jcma.2012.10.008##Cui H, López M, Rahmouni K. The cellular and molecular bases of leptin and ghrelin resistance in obesity. Nat Rev Endocrinol 2017a;13(6): 338-351. https://doi.org/10.1038/nrendo.2016.222##Cui J, Pang J, Lin YJ, et al. Adipose-specific deletion of Kif5b exacerbates obesity and insulin resistance in a mouse model of diet-induced obesity. 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Differential changes in the quantity of the hippocampal glial connexins mRNAs during memory consolidation 2 2 Introduction: It is known that glial cells are crucial for memory formation. Glial cells and neurons interconnect via gap junction channels made of connexin (Cx) proteins. Glial connexins were shown to be involved in memory formation. However, the expression profile of different glial connexins was not measured during memory consolidation. Cx43 and Cx30 are expressed in astrocytes, whereas Cx32 is expressed in oligodendrocytes. We quantified the messenger RNA (mRNA) levels of the hippocampal Cx30, Cx32, and Cx43 throughout the consolidation stage of fear or spatial memory. Methods: Male Wistar rats were distributed into eight groups of four each. To assess the spatial or fear memory consolidation, the Morris water maze and passive avoidance task were utilized. At different time intervals (one, three, and twenty-four hours) following the training sessions, rats were sacrificed and the hippocampi were isolated and frozen instantly in liquid nitrogen. A quantitative real-time polymerase chain reaction (PCR) was employed to measure mRNA levels of the target genes. Results: The results revealed that Cx43 and Cx32 downregulated significantly, one or three hours after training in the inhibitory avoidance model. In the Morris water maze, Cx43 expression was upregulated three hours after training. The expression of Cx30 did not exhibit significant alterations in either of the experimental assays. Conclusion: The results indicate the crucial, but differential role of the hippocampal Cx32 and Cx43 during fear or spatial memory consolidation. The exact outcomes of these potential changes need to be clarified. 419 429 2023/11/242024/03/202023/12/172024/01/122023/05/22 1402/3/1 2024/05/72024/10/52024/04/232024/05/252024/05/18 1403/2/29 Siamak Beheshti Siamak Beheshti Department of Plant and Animal Biology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran Iran s.beheshti@sci.ui.ac.ir Nazila Kooravand Bard Pareh Nazila Kooravand Bard Pareh Department of Plant and Animal Biology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran Iran nazila.kooravand93@gmail.com Connexin Glia Gap junction Hippocampus Memory Abel T, Lattal K M. Molecular mechanisms of memory acquisition, consolidation and retrieval. Current Opinion in Neurobiology 2001; 11: 180-187. https://doi.org/10.1016/S0959-4388(00)00194-X##Beheshti S, Aslani N. Local injection of d-lys-3-GHRP-6 in the rat amygdala, dentate gyrus or ventral tegmental area impairs memory consolidation. Neuropeptides 2018; 67: 20-26. https://doi.org/10.1016/j.npep.2017.11.002##Beheshti S, Dehestani H. Differential expression levels of the hippocampal ghrelin and its receptor mRNA during memory consolidation. Behav Brain Res 2021; 408: 113270. https://doi.org/10.1016/j.bbr.2021.113270##Beheshti S, Ghorbanpour Skakakomi A, Ghaedi K, Dehestani H. Frankincense upregulates the hippocampal calcium/calmodulin kinase II-α during development of the rat brain and improves memory performance. Int J Dev Neurosci 2018; 69: 44-48. https://doi.org/10.1016/j.ijdevneu.2018.06.011##Beheshti S, Zeinali R, Esmaeili A. Rapid upregulation of the hippocampal connexins 36 and 45 mRNA levels during memory consolidation. Behav Brain Res 2017; 320: 85-90. https://doi.org/10.1016/j.bbr.2016.11.048##Chaaya N, Battle A R, Johnson L R. An update on contextual fear memory mechanisms: Transition between Amygdala and Hippocampus. 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Melatonin Attenuates Methamphetamine Neurotoxicity through inhibition of NLRP3 and pyroptosis pathway 2 2 Introduction: Methamphetamine (Meth) is a highly addictive psychostimulant and induces neuroinflammatory responses. Melatonin is a neurohormone that has protective effects and reduces inflammation in the central nervous system. Our study focused on the melatonin effect on memory impairment, NLRP3/IL-1β axis, and gasdermin D and caspase-1 expression in the hippocampus of a rat model of Meth use. Methods: Meth and melatonin were administered to the rats for 21 consecutive days. The memory was evaluated using alternation behavior in Y-maze. NLRP3 and IL-1β were assessed by western blotting and ELISA, respectively.  Gasdermin D and caspase-1 expression levels were evaluated using qRT-PCR. Results: The NLRP3 and IL-1β were elevated in the hippocampus following Meth injection. Moreover, Meth increased gasdermin D and caspase-1 expression levels. After 21 days of Meth use, memory impairment was seen in the Y-maze test. Melatonin significantly improved memory and decreased the expression of NLRP3, IL-1β, gasdermin D, and caspase-1 in the hippocampus. Conclusion: Our study revealed that inflammasome formation and pyroptosis pathway are involved in Meth-induced neurotoxicity. Melatonin may be a potential treatment against neurotoxicity and cognitive disorders caused by Meth. 430 439 2023/11/242024/03/202023/12/172024/01/122023/05/222024/02/28 1402/12/9 2024/05/72024/10/52024/04/232024/05/252024/05/182024/05/25 1403/3/5 Seyed Khalil Rashidi Seyed Khalil Rashidi Department of Medical Biotechnology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran Iran m.kh.rashidi@gmail.com Mitra Ansari Dezfouli Mitra Ansari Dezfouli Department of Neurology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran Iran mitraansari84@gmail.com Fariba Khodagholi Fariba Khodagholi Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Iran khodagholi@sbmu.com Mehdi Dadashpour Mehdi Dadashpour Department of Medical Biotechnology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran Iran dadashpourmehdi1400@gmail.com Ali Akbar Shabani Ali Akbar Shabani Department of Medical Biotechnology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran Iran aashaebani@yahoo.com Methamphetamine Melatonin NLRP3 Interlukine-1β Working memory Pyroptosis Ares-Santos S, Granado N, Espadas I, Martinez-Murillo R, Moratalla R. Methamphetamine causes degeneration of dopamine cell bodies and terminals of the nigrostriatal pathway evidenced by silver staining. Neuropsychopharmacology 2014; 39: 1066-1080. https://doi.org/10.1038/npp.2013.307##Arioz B I, Tarakcioglu E, Olcum M, Genc S. The role of melatonin on NLRP3 inflammasome activation in diseases. Antioxidants 2021; 10: 1020. https://doi.org/10.3390/antiox10071020##Bernheim A, See R E, Reichel C M. Chronic methamphetamine self-administration disrupts cortical control of cognition. Neuroscience & Biobehavioral Reviews 2016; 69: 36-48. https://doi.org/10.1016/j.neubiorev.2016.07.020##Bulté D, Rigamonti C, Romano A, Mortellaro A. Inflammasomes: mechanisms of action and involvement in human diseases. Cells 2023; 12: 1766. https://doi.org/10.3390/cells12131766##Burgess H J, Revell V L, Molina T A, Eastman C I. Human phase response curves to three days of daily melatonin: 0.5 mg versus 3.0 mg. The Journal of Clinical Endocrinology & Metabolism 2010; 95: 3325-3331. https://doi.org/10.1210/jc.2009-2590##d’Isa R, Comi G, Leocani L. Apparatus design and behavioural testing protocol for the evaluation of spatial working memory in mice through the spontaneous alternation T-maze. Scientific Reports 2021; 11: 21177. https://doi.org/10.1038/s41598-021-00402-7##Danielski L G, Giustina A D, Bonfante S, de Souza Goldim M P, Joaquim L, Metzker K L, et al. NLRP3 activation contributes to acute brain damage leading to memory impairment in sepsis-surviving rats. Molecular Neurobiology 2020; 57: 5247-5262. https://doi.org/10.1007/s12035-020-02089-9##De Crescenzo F, Lennox A, Gibson J, Cordey J, Stockton S, Cowen P, et al. Melatonin as a treatment for mood disorders: a systematic review. Acta Psychiatrica Scandinavica 2017; 136: 549-558. https://doi.org/10.1111/acps.12755##de Zoete M R, Palm N W, Zhu S, Flavell R A. Inflammasomes. Cold Spring Harbor perspectives in biology 2014; 6: a016287. https://doi.org/10.1101/cshperspect.a016287##Degenhardt L, Mathers B, Guarinieri M, Panda S, Phillips B, Strathdee S A, et al. Meth/amphetamine use and associated HIV: Implications for global policy and public health. International Journal of Drug Policy 2010; 21: 347-358. https://doi.org/10.1016/j.drugpo.2009.11.007 ##Dezfouli M A, Zahmatkesh M, Farahmandfar M, Khodagholi F. Melatonin protective effect against amyloid β-induced neurotoxicity mediated by mitochondrial biogenesis; involvement of hippocampal Sirtuin-1 signaling pathway. Physiology & behavior 2019; 204: 65-75. https://doi.org/10.1016/j.physbeh.2019.02.016##Dobšíková K, Michal P, Spálovská D, Kuchař M, Paškanová N, Jurok R, et al. Conformational analysis of amphetamine and methamphetamine: a comprehensive approach by vibrational and chiroptical spectroscopy. Analyst 2023; 148: 1337-1348. https://doi.org/10.1039/D2AN02014A##Gaillard C, Lago T R, Gorka A X, Balderston N L, Fuchs B, Reynolds R C, et al. Effects of methylphenidate on the neural interplay between induced anxiety and working memory. Biological Psychiatry 2021; 89: S88-S89. https://doi.org/10.1016/j.biopsych.2021.02.234##Ge C L, Chen W, Zhang L N, Ai Y H, Zou Y, Peng Q Y. Hippocampus-prefrontal cortex inputs modulate spatial learning and memory in a mouse model of sepsis induced by cecal ligation puncture. CNS Neuroscience & Therapeutics 2023; 29: 390-401. https://doi.org/10.1111/cns.14013##Glasner-edwards S, Mooney L J, Marinelli-casey P, Hillhouse M, Ang A, Rawson R A, et al. Psychopathology in methamphetamine-dependent adults 3 years after treatment. Drug and alcohol review 2010; 29: 12-20. https://doi.org/10.1111/j.1465-3362.2009.00081.x##Golsorkhdan S A, Boroujeni M E, Aliaghaei A, Abdollahifar M A, Ramezanpour A, Nejatbakhsh R, et al. Methamphetamine administration impairs behavior, memory and underlying signaling pathways in the hippocampus. Behavioural Brain Research 2020; 379: 112300. https://doi.org/10.1016/j.bbr.2019.112300##González H, Elgueta D, Montoya A, Pacheco R. Neuroimmune regulation of microglial activity involved in neuroinflammation and neurodegenerative diseases. Journal of neuroimmunology 2014; 274: 1-13. https://doi.org/10.1016/j.jneuroim.2014.07.012##Hadizadeh-Bazaz M, Vaezi G, Hojati V. Curcumin attenuates spatial memory impairment by anti-oxidative, anti-apoptosis, and anti-inflammatory mechanism against methamphetamine neurotoxicity in male Wistar rats: Histological and biochemical changes. Neurotoxicology 2021; 84: 208-217. https://doi.org/10.1016/j.neuro.2021.03.011##Jayanthi S, Daiwile A P, Cadet J L. Neurotoxicity of methamphetamine: Main effects and mechanisms. Experimental neurology 2021; 344: 113795. https://doi.org/10.1016/j.expneurol.2021.113795 ##Jumnongprakhon P, Sivasinprasasn S, Govitrapong P, Tocharus C, Tocharus J. Activation of melatonin receptor (MT1/2) promotes P-gp transporter in methamphetamine-induced toxicity on primary rat brain microvascular endothelial cells. Toxicology in Vitro 2017; 41: 42-48. https://doi.org/10.1016/j.tiv.2017.02.010##Kaushal N, R Matsumoto R. Role of sigma receptors in methamphetamine-induced neurotoxicity. Current neuropharmacology 2011; 9: 54-57. https://doi.org/10.2174/157015911795016930 ##Kilic U, Yilmaz B, Ugur M, Yüksel A, Reiter R J, Hermann D M, et al. Evidence that membrane-bound G protein-coupled melatonin receptors MT1 and MT2 are not involved in the neuroprotective effects of melatonin in focal cerebral ischemia. Journal of pineal research 2012; 52: 228-235. https://doi.org/10.1111/j.1600-079X.2011.00932.x##Kraiwattanapirom N, Komlao P, Harnpramukkul A, Promyo K, Ngampramuan S, Chetsawang B. The neuroprotective role of melatonin against methamphetamine toxicity-induced neurotransmission dysregulation and cognitive deficits in rats. Food and Chemical Toxicology 2021; 157: 112610. https://doi.org/10.1016/j.fct.2021.112610##Kurawa M I, Torkaman-Boutorabi A, Hassanzadeh G, Zah­matkesh M, Vousooghi N, Zarrindast M-R, et al. The Effects of Subchronic Methamphetamine Administration on the NLRP3 Inflammasome, Memory Function, and Hippocampal Morphology. Archive of Neuroscience 2024; 11: 1-13. https://doi.org/10.5812/ans-145644##Lahooti B, Chhibber T, Bagchi S, Varahachalam S P, Jayant R D. Therapeutic role of inflammasome inhibitors in neurodegenerative disorders. Brain, Behavior, and Immunity 2021; 91: 771-783. https://doi.org/10.1016/j.bbi.2020.11.004##Mizoguchi H, Yamada K. Methamphetamine use causes cognitive impairment and altered decision-making. Neurochemistry international 2019; 124: 106-113. https://doi.org/10.1016/j.neuint.2018.12.019##Paknahad S, Akhgari M, Ghadipasha M. An alarming rise in the prevalence of deaths with methamphetamine involved in Tehran, Iran 2011-2018. Forensic Science, Medicine and Pathology 2021; 17: 208-215. https://doi.org/10.1007/s12024-020-00339-9##Panmak P, Nopparat C, Permpoonpattana K, Namyen J, Govitrapong P. Melatonin protects against methamphetamine-induced Alzheimer’s disease-like pathological changes in rat hippocampus. Neurochemistry International 2021; 148: 105121. https://doi.org/10.1016/j.neuint.2021.105121##Parameyong A, Charngkaew K, Govitrapong P, Chetsawang B. Melatonin attenuates methamphetamine-induced disturbances in mitochondrial dynamics and degeneration in neuroblastoma SH-SY 5 Y cells. Journal of pineal research 2013; 55: 313-323. https://doi.org/10.1111/jpi.12078##Pohlentz M S, Müller P, Cases-Cunillera S, Opitz T, Surges R, Hamed M, et al. Characterisation of NLRP3 pathway-related neuroinflammation in temporal lobe epilepsy. Plos one 2022; 17: e0271995. https://doi.org/10.1371/journal.pone.0271995##Polvat T, Prasertporn T, Na Nakorn P, Pannengpetch S, Suwanjang W, Panmanee J, et al. Proteomic analysis reveals the neurotoxic effects of chronic methamphetamine self-administration-induced cognitive impairments and the role of melatonin-enhanced restorative process during methamphetamine withdrawal. Journal of Proteome Research 2023. https://doi.org/10.1021/acs.jproteome.3c00502##Rashidi S K, Kalirad A, Rafie S, Behzad E, Dezfouli M A. The role of microRNAs in neurobiology and pathophysiology of the hippocampus. Frontiers in Molecular Neuroscience 2023; 16. https://doi.org/10.3389/fnmol.2023.1226413##Roy S, Ansari M A, Choudhary K, Singh S. NLRP3 inflammasome in depression: A review. International Immunopharmacology 2023; 117: 109916. https://doi.org/10.1016/j.intimp.2023.109916##Ruan Q T, Yazdani N, Blum B C, Beierle J A, Lin W, Coelho M A, et al. A mutation in Hnrnph1 that decreases methamphetamine-induced reinforcement, reward, and dopamine release and increases synaptosomal hnRNP H and mitochondrial proteins. Journal of Neuroscience 2020; 40: 107-130. https://doi.org/10.1523/JNEUROSCI.1808-19.2019##Rui T, Wang H, Li Q, Cheng Y, Gao Y, Fang X, et al. Deletion of ferritin H in neurons counteracts the protective effect of melatonin against traumatic brain injury-induced ferroptosis. Journal of pineal research 2021; 70: e12704. https://doi.org/10.1111/jpi.12704##Sabrini S, Russell B, Wang G, Lin J, Kirk I, Curley L. Methamphetamine induces neuronal death: Evidence from rodent studies. Neurotoxicology 2020; 77: 20-28. https://doi.org/10.1016/j.neuro.2019.12.006##Shi J, Gao W, Shao F. 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Evaluation of ulcer healing activity of Mahonia napaulensis in Swiss albino mice 2 2 Introduction: The indigenous population of Nagaland has traditionally utilized the bark of Mahonia napaulensis as a remedy for gastrointestinal ailments; however, its therapeutic effectiveness has not been scientifically verified. The objective of the current investigation is to assess the efficacy of the methanolic bark extract of M. napaulensis in promoting the healing of peptic ulcers. Methods: The study involved the induction of ulcers in Swiss albino mice via the oral administration of a single dose of 80% ethanol (1 ml/100g body weight). The effect of the methanolic bark extract of the plant on ethanol-induced peptic ulcer was studied using repeated dosing of 200 mg/kg body weight for ten and fourteen days, respectively. The standard drug utilized in the study was Ranitidine (30 mg/kg body weight). The assessment of ulcer healing activity was conducted through the evaluation of various parameters, including the ulcer index, healing percentage, gross macroscopic lesions, as well as histopathological and ultrastructural observations. The concentrations of malondialdehyde (MDA), glutathione (GSH), protein, and sialic acid were quantified.  Results: The results indicate that the oral consumption of methanolic bark extract of M. napaulensis has pro-healing efficacy on ulcerated mice. Thus, this justifies the use of the plant as a healing agent among the rural population. Conclusion: The results indicate that the oral consumption of methanolic bark extract of M. napaulensis has pro-healing efficacy on ulcerated mice. Thus, this justifies the use of the plant as a healing agent among the rural population. 440 452 2023/11/242024/03/202023/12/172024/01/122023/05/222024/02/282023/07/24 1402/5/2 2024/05/72024/10/52024/04/232024/05/252024/05/182024/05/252024/05/25 1403/3/5 Sanchayeeta Roy Sanchayeeta Roy North-Eastern Hill University, 793022, Shillong,Meghalaya, India India sancuroy@gmail.com Deepjyoti Dev Deepjyoti Dev North-Eastern Hill University, 793022, Shillong,Meghalaya, India India deepjyotidev1510@gmail.com Bishnupada Roy Bishnupada Roy North-Eastern Hill University, 793022, Shillong,Meghalaya, India India broy@nehu.ac.in Mahonia napaulensis Methanolic extract Acute toxicity Sialic acid Peptic ulcer Ahmad A A, Kasim K F, Ma’Radzi A H, Gopinath S C. Peptic ulcer: Current prospects of diagnostic and nano biotechnological trends on pathogenicity. Process Biochemistry 2019; 85: 51-59. https://doi.org/10.1016/j.procbio.2019.06.024##Ahmed O, Nedi T, Yimer E M. Evaluation of anti-gastric ulcer activity of aqueous and 80% methanol leaf extracts of Urtica simensis in rats. Metabolism Open 2022, 14: 100172. https://doi.org/10.1016/j.metop.2022.100172 ##Bajpai D, Vankar P S. Antifungal textile dyeing with Mahonia napaulensis DC leaves extract based on its antifungal activity. Fibers and Polym 2007; 8: 487-494. https://doi.org/10.1007/BF02875870##Bonamin F, Moraes T M, Dos Santos R C, Kushima H, Faria F M, Silva M A, et al. The effect of a minor constituent of essential oil from Citrus aurantium: the role of β-myrcene in preventing peptic ulcer disease. Chemico-biological interactions 2014; 212: 11-19. https://doi.org/10.1016/j.cbi.2014.01.009##Bradford M M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248-254. https://doi.org/10.1016/0003-2697(76)90527-3##Buege J A, Aust S D. Microsomal lipid peroxidation. 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Biomarkers 2019; 24(3): 286-294. https://doi.org/10.1080/1354750X.2018.1556340##Fahmy N M, Al-Sayed E, Michel H E, El-Shazly M, Singab A N B. Gastroprotective effects of Erythrina Speciosa (Fabaceae) leaves cultivated in egypt against ethanol-induced gastric ulcer in rats. J Ethnopharmacol 2020; 248-112297. https://doi.org/10.1016/j.jep.2019.112297##Fu Y, Wu HQ, Cui H L, Li Y Y, Li C Z. Gastroprotective and anti-ulcer effects of oxymatrine against several gastric ulcer models in rats: Possible roles of antioxidant, anti-inflammatory, and pro survival mechanisms. Phytother Res 2018; 32(10): 2047-2058. https://doi.org/10.1002/ptr.6148##Guzmán-Gómez O, García-Rodríguez R V, Quevedo-Corona L. et al. Amelioration of ethanol-induced gastric ulcers in rats pretreated with phycobiliproteins of arthrospira (Spirulina) maxima. Nutrients 2018; 10(6): 763. https://doi.org/10.3390/nu10060763##Halabi M F, Shakir R M, Bardi D A, et al. Gastroprotective activity of ethyl-4-[(3,5-di-tert-butyl-2-hydroxybenzylidene) amino] benzoate against ethanol-induced gastric mucosal ulcer in rats. PLoS One 2014; 9(5): e95908. https://doi.org/10.1371/journal.pone.0095908##Hayat M A. Principles and techniques of electron microscopy. Biological application, 4th ed. Cambridge: Cambridge University Press, 2000, p. 543.##He J M, Mu Q. The medicinal uses of the genus Mahonia in traditional Chinese medicine: An ethnopharmacological, phytochemical and pharmacological review. J Ethnopharmacol 2015; 175: 668-683. https://doi.org/10.1016/j.jep.2015.09.013##Jain P. Secondary metabolites for antiulcer activity. Nat Prod Res 2016; 30(6): 640-656. https://doi.org/10.1080/14786419.2015.1036269##Kadasah S, Al Eid A S, Alawad S S, Al Shahrani A S, Alruwaihi A S, Elfaki I, et al. Gastro protecting influence of to piramate in ethanol produced gastric ulcers in rats. Toxicol Rep 2021; 8: 1031-1039. https://doi.org/10.1016/j.toxrep.2021.05.004##Kavitt R T, Lipowska A M, Anyane-Yeboa A, Gralnek I M. Diagnosis and treatment of peptic ulcer disease. Am J Med 2019; 132(4): 447-456. https://doi.org/10.1016/j.amjmed.2018.12.009##Khoder G, Al-Menhali A A, Al-Yassir F, Karam S M. Potential role of probiotics in the management of gastric ulcer. Exp Ther Med 2016; 12(1): 3-17. https://doi.org/10.3892/etm.2016.3293##Kulkarni S K. “Handbook of experimental pharmacology,” 3rd Edition, Vallabh Prakashan, Delhi, 2005.##Li W S, Lin S C, Chu C H, Chang Y K, Zhang X. Lin C C, et al. The gastroprotective effect of naringenin against ethanol-induced gastric ulcers in mice through inhibiting oxidative and inflammatory responses. Int J Mol Sc 2021; 22(21): 11985. https://doi.org/10.3390/ijms222111985##Matzner M J, Windwer C, Sobel A E. The role of protein in the prevention of experimental gastric ulcers. 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Increased inflammation in the lungs of asthmatic pregnant mice was associated with elevated leptin levels 2 2 Introduction: Many studies have shown that asthma is characterized by inflammation of the airway and infiltration of eosinophil cells (EOSCs). It has also shown that during pregnancy, the level of leptin, as a regulator of immune responses, increases with the progression of the pregnancy process. In this study, the effect of asthma on inflammatory factors was evaluated in the lung and uterine tissues of asthmatic pregnant or non-pregnant mice. Methods: In this experimental study, 40 female Balb/c mice (8 weeks old) were classified into 4 groups, and asthma by ovalbumin (OVA) at a concentration of 20 μg/100μl was induced. Lung and uterus tissues were histopathologically evaluated for the presence of inflammation. The level of leptin hormone in blood serum was investigated using an indirect enzyme-linked immunosorbent assay (ELISA). Also, Interleukin-8 (IL-8), forkhead box protein 3 (Foxp3), eosinophil chemotactic protein (eotaxin), and mucin 5AC (Muc5ac) gene expression were measured in respiratory and uterine cells by Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) assay (P<0.05, P<0.01 and P<0.001).  Results: Morphological assessment of inflammation in lung tissue showed a significant increase in asthmatic groups compared to healthy groups. Hormone measurement revealed a significant rise in leptin levels in pregnant groups compared to non-pregnant groups. Also, the expression level of IL-8, Foxp3, eotaxin, and Muc5ac genes increased in pregnancy compared to negative control. Conclusion: In asthma, inflammation rate increases at the cellular and molecular levels, and the leptin increment might have an influence on the inflammation. 453 464 2023/11/242024/03/202023/12/172024/01/122023/05/222024/02/282023/07/242023/12/11 1402/9/20 2024/05/72024/10/52024/04/232024/05/252024/05/182024/05/252024/05/252024/05/7 1403/2/18 Gisou Barid Oliaei Gisou Barid Oliaei Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran Iran gisoubarid@gmail.com Leila Mirzaeian Leila Mirzaeian Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran Iran Lmirzaey64@gmail.com Seyedeh Maryam Hosseinikhah Seyedeh Maryam Hosseinikhah Nanotechnology Research Center, Pharmaceutical Technology Institute, MashhadUniversity Medical Sciences, Mashhad, Iran Iran mhosseinikhah@yahoo.com Mahdiyeh Sarabadani Mahdiyeh Sarabadani Nanotechnology Research Center, Pharmaceutical Technology Institute, MashhadUniversity Medical Sciences, Mashhad, Iran Iran flower201415@gmail.com Parichehreh Yaghmaei Parichehreh Yaghmaei Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran Iran yaghmaei_p@srbiau.ac.ir Shahryar Farahmand Giglou Shahryar Farahmand Giglou Center for Comprehensive Genetic Services, Shahid Beheshti University of Medical Sciences, Tehran, Iran Iran sfarahmand.fg@gmail.com Paul Mozdziak Paul Mozdziak Physiology Graduate Program, North Carolina State University, Raleigh, NC, USA USA pemozdzi@ncsu.edu Ehsan Ehsani Ehsan Ehsani Department of Biology, Roudehen Branch, Islamic Azad University, Roudehen, Iran Iran ehsan.ehsani@iau.ac.ir Seyed Shamsadin Athari Seyed Shamsadin Athari Department of Immunology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran Iran ss.athari@zums.ac.ir Asthma Pregnancy Eosinophils cell Leptin Inflammatory factors. 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Histone methyltransferase G9a inhibitor (UNC0631) reinforces mitochondrial function and upregulates UCP1 in brown adipocytes and screening of epigenetic libraries 2 2 Introduction: Obesity leads to massive death worldwide by initiating numerous illnesses like Nonalcoholic Steatohepatitis (NASH), liver disease, and cardiovascular diseases. Developing new therapeutics against obesity is an emergency need. Targeting mitochondrial uncoupling protein 1 (UCP1) will provide new therapeutic strategies for drug discovery research against obesity and obesity-related disorders.  Methods: We screened UCP1 up-regulators from epigenetic drug libraries by using a previously developed Ucp1-A-GFP cellular GFP screening platform, ATP production, and mitochondrial DNA quantification.  Results: We discovered that the histone methyltransferase G9a inhibitor UNC0631 has a considerable effect on the expression of UCP1 in adipocytes when used in vitro. Here, we discovered that UNC0631 is crucial for controlling mitochondrial activity and anti-obesity. The UNC0631-treated fat cells have higher UCP1 expression at the cellular level. Taken together, in our studies, we have established an efficient in vitro cell experiment system to study the metabolic regulation of UCP1. Enhanced mitochondrial DNA, ATP synthesis, and cell survival showed that UNC0631 had a benign impact on the HEK293T cell line. As a result, UNC0631 reveals a promising therapeutic option for the treatment of diseases associated with obesity and metabolic disorders. Conclusion: In this study, we make a list of potent drug candidates from epigenetic drug libraries that can upregulate mitochondrial UCP1 gene expression and promote thermogenesis. UNC0631 improves mitochondrial function and would be an effective drug candidate to treat metabolic diseases and obesity-related diseases. Further investigation will require both the human and animal models to reveal new insight into the mechanism against obesity, metabolic diseases, or mitochondrial dysfunction-related diseases. Supplementary Files 465 475 2023/11/242024/03/202023/12/172024/01/122023/05/222024/02/282023/07/242023/12/112022/08/12 1401/5/21 2024/05/72024/10/52024/04/232024/05/252024/05/182024/05/252024/05/252024/05/72024/05/25 1403/3/5 Md Reyad-ul Ferdous Md Reyad-ul Ferdous Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, PR China china rockyreyad@yahoo.com Mengjiao Yang Mengjiao Yang Department of Endocrinology and Metabolism, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China China Md. Shofiul Azam Md. Shofiul Azam Department of Chemical and Food Engineering, Dhaka University of Engineering & Technology, Gazipur, Bangladesh Bangladesh shofiul@duet.ac.bd Yongfeng Song Yongfeng Song Department of Endocrinology and Metabolism, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, China china Haiqing Zhang Haiqing Zhang Department of Endocrinology and Metabolism, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China china Vijay panday Vijay panday Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, PR China China vjpandey@sz.tsinghua.edu.cn Obesity UCP1 Histone methyltransferase Mitochondrial function Epigenetic drug libraries Metabolic disorders Abe Y, Fujiwara Y, Takahashi H, Matsumura Y, Sawada T, Jiang S, et al. 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The Effect of Different Polar Solvents on the Extraction of Bioactive Compounds in Ferula assafoetida and Subsequent Cytotoxic Effects 2 2 Introduction: The cytotoxic effects of Ferula assafoetida extract intensely depend on high-quality extraction. The type of solvent used is a critical parameter for efficient extraction in the maceration method. In the present study, the phytochemical and cytotoxic effects of different Ferula assafoetida extracts were compared. Methods: The Ferula assafoetida gum was extracted using different polar solvents: hydroethanol (70% v/v), dimethyl sulfoxide (DMSO), and water. The phytochemical properties of the extracts were evaluated, focusing on their herbal content of phenols and flavonoids. The antioxidant activity of the extracts was also compared by assessing their radical scavenging capacity (by DPPH assay) and reducing activity (using the FRAP assay). Finally, the cytotox effects of the extracts were evaluated using the MTT assay on MCF-7 and MDA-MB-231 breast cancer cell lines for the first time. Results: The phytochemical properties of hydroethanolic extract of Ferula assafoetida (HEFA) were significantly (P< 0.0001) higher than those of the DMSO (DEFA) and water extracts (WEFA). The reducing power, radical scavenging activity, and cytotoxic effects of HEFA were also significantly (P< 0.05) higher than those of DEFA and WEFA. The cytotoxicity of the extracts was dose- and incubation time-dependent. HEFA exhibited the highest cell cytotoxicity at 72 hours, with IC50 values of 69.97± 9.45 µg/mL on the MCF-7 cell line and 60.22± 2.37 µg/mL on the MDA-MB-231 cell line. Conclusion: Hydroethanol was the best solvent for extracting phenolic compounds and flavonoids. The cytotoxic effects of HEFA were also the highest, probably due to the high ability of hydroethanol in the extraction of hydrophilic and lipophilic phenols. 476 485 2023/11/242024/03/202023/12/172024/01/122023/05/222024/02/282023/07/242023/12/112022/08/122023/09/25 1402/7/3 2024/05/72024/10/52024/04/232024/05/252024/05/182024/05/252024/05/252024/05/72024/05/252024/04/23 1403/2/4 Alireza Moulazadeh Alireza Moulazadeh Department of Medical Nanotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran Iran javaneh.fums@gmail.com Razieh Ranjbar Razieh Ranjbar Noncommunicable Disease Research Center, Fasa University of Medical Sciences, Fasa, Iran Iran ranjbarrazie@gmail.com Seyyed Amin Kouhpayeh Seyyed Amin Kouhpayeh Noncommunicable Disease Research Center, Fasa University of Medical Sciences, Fasa, Iran Iran kouhpayeha@gmail.com Abdolmajid ghasemian Abdolmajid ghasemian Noncommunicable Disease Research Center, Fasa University of Medical Sciences, Fasa, Iran Iran majidghasemian86@gmail.com Maryam maghbool Maryam maghbool Noncommunicable Disease Research Center, Fasa University of Medical Sciences, Fasa, Iran Iran maghbol.maryam@yahoo.com Sohrab Najafipour Sohrab Najafipour Noncommunicable Disease Research Center, Fasa University of Medical Sciences, Fasa, Iran Iran resimmuno@gmail.com Solvent Bioactive compounds Oxidative stress Cytotoxicity Ferula assafoetida Bagheri S, Javidmehr D, Ghaffari M, Ghoderti-Shatori E. Chemical compositions and antiproliferative effect of essential oil of asafoetida on MCF7 human breast cancer cell line and female wistar rats. Cancer Transl Med 2020; 6(2): 34-39. ##Bagheri S M, Abdian-Asl A, Moghadam M T, Yadegari M, Mirjalili A, Zare-Mohazabieh F, et al. Antitumor effect of Ferula assa foetida oleo gum resin against breast cancer induced by 4T1 cells in BALB/c mice. J Ayurveda Integr Med 2017; 8(3): 152-158. https://doi.org/10.1016/j.jaim.2017.02.013##Baharum Z, Akim A M, Taufiq-Yap YH, Hamid R A, Kasran R. In vitro antioxidant and antiproliferative activities of methanolic plant part extracts of Theobroma cacao. Molecules 2014; 19(11): 18317-18331. https://doi.org/10.3390/molecules191118317##Chen Z, Bertin R, Froldi G. EC50 estimation of antioxidant activity in DPPH assay using several statistical programs. Food chemistry 2013; 138(1): 414-420. https://doi.org/10.1016/j.foodchem.2012.11.001##Dent M, Dragović-Uzelac V, Penić M, Bosiljkov T, Levaj B. The effect of extraction solvents, temperature and time on the composition and mass fraction of polyphenols in Dalmatian wild sage (Salvia officinalis L.) extracts. Food Technol Biotechnol 2013; 51(1): 84-91. https://hrcak.srce.hr/99751##Esmaeili S, Hajimehdipoor H, Ramezani A, Mosaddegh M. The cytotoxic effects of Ferula persica var. persica and Ferula hezarlalehzarica against HepG2, A549, HT29, MCF7 and MDBK cell lines. Iran J Pharm Sci 2012; 8(2): 115-119. https://doi.org/10.22037/ijps.v8.40972##Iranshahi M, Kalategi F, Rezaee R, Shahverdi A R, Ito C, Furukawa H, et al. Cancer chemopreventive activity of terpenoid coumarins from Ferula species. Planta Medica 2008; 74(02): 147-150. https://doi.org/ 10.1055/s-2008-1034293##Jelic MD, Mandic AD, Maricic SM, Srdjenovic BU. Oxidative stress and its role in cancer. J Cancer Res Ther 2021; 17(1): 22-28. https://doi.org/10.4103/jcrt.JCRT_862_16##Keyghobadi N, Bagheri V, Rahnamaii M S, Sarab G A. Evaluation of hydroalcoholic extract effects of Ferula assa-foetida on expression change of EMT and CD44-related genes in gastric cancer stem cell. Gene Reports 2022; 1(27): 101535. https://doi.org/10.1016/j.genrep.2022.101535##Koffi E, Sea T, Dodehe Y, Soro S. Effect of solvent type on extraction of polyphenols from twenty three Ivorian plants. J Anim Plant Sci 2010; 5(3): 550-558. https://www.cabidigitallibrary.org/doi/full/10.5555/20103274240##Lakey-Beitia J, Burillo A M, La Penna G, Hegde M L, Rao K S. Polyphenols as potential metal chelation compounds against Alzheimer’s disease. J Alzheimers Dis 2021; 82(s1): 335-337. https://doi.org/10.3233/jad-200185##Latifi E, Mohammadpour A, Nourani H. Antidiabetic and antihyperlipidemic effects of ethanolic Ferula assa-foetida oleo-gum-resin extract in streptozotocin-induced diabetic wistar rats. Biomed Pharmacother 2019; 110: 197-202. https://doi.org/10.1016/j.biopha.2018.10.152##Makoolati Z, Bahrami H, Zamanzadeh Z, Mahaldashtian M, Moulazadeh A, Ebrahimi L. Efficacy of Ficus carica leaf extract on morphological and molecular behavior of mice germ stem cells. Anim Reprod 2022; 19(2): e20220036. https://doi.org/10.1590/1984-3143-AR2022-0036##Maleki S J, Crespo J F, Cabanillas B. Anti-inflammatory effects of flavonoids. Food Chem 2019; 299: 125124. https://doi.org/10.1016/j.foodchem.2019.125124##Mallikarjuna G U, Dhanalakshmi S, Raisuddin S, Ramesha Rao A. Chemomodulatory influence of Ferula asafoetida on mammary epithelial differentiation, hepatic drug metabolizing enzymes, antioxidant profiles and N-methyl-N-nitrosourea-induced mammary carcinogenesis in rats. Breast Cancer Res Treat 2003; 81: 1-10. https://doi.org/10.1023/A:1025448620558##Mosaddegh M, Esmaeil, S, Hamzelomoghadam M. In vitro cytotoxic assay of giant Fennel fractions. 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Ferulic acid mitigates H2 O2 -induced oxidative stress by hindering the activity of reactive oxygen species and programmed cell death in rat PC12 cells 2 2 Introduction: Oxidative stress (OS) is related to the onset and development of different disorders including neurodegenerative diseases. Attenuation of OS may be an appropriate way to combat such a situation. Ferulic acid (FA) as a natural antioxidant compound has been shown to have potent free radical scavenging activity. Hence, the present study aimed to investigate the effects of FA to inhibit the intrinsic apoptosis pathway evoked by H2O2 in rat pheochromocytoma (PC12) cells. Methods: PC12 cells were treated with various concentrations of FA at different times. Then, H2O2 (300 µM for 2h) was added. Afterward, cell viability was assessed by MTT assay followed by determining the levels of total antioxidant power (TAP), and malondialdehyde (MDA) level. The protein expressions of Caspase-3, Bax, and Bcl-2 were also measured by western blotting.   Results: Current results indicate that after 72 hours, FA significantly protected PC12 cells against H2O2-induced damage by reducing the generation of MDA levels as well as increasing TAP. H2O2-induced caspase-3 overexpression and the increase of the Bax/BCL-2 protein ratio were also diminished by FA treatment. Conclusion: Taken together, FA may be considered a protective agent to prevent or postpone the progression of oxidative neurodegenerative diseases through its anti-oxidant and anti-apoptotic effects. 486 493 2023/11/242024/03/202023/12/172024/01/122023/05/222024/02/282023/07/242023/12/112022/08/122023/09/252023/08/22 1402/5/31 2024/05/72024/10/52024/04/232024/05/252024/05/182024/05/252024/05/252024/05/72024/05/252024/04/232024/05/28 1403/3/8 Mehrnaz Mehrabani Mehrnaz Mehrabani Physiology Research Centre, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran Iran mehrnaz.mehrabani@yahoo.com Mitra mehrabani Mitra mehrabani Herbal and Traditional Medicines Research Centre, Kerman University of Medical Sciences, Kerman, Iran Iran mmehrabani@hotmail.com Arian Amirkhosravi Arian Amirkhosravi Pharmaceutical Sciences and Cosmetic Products Research Centre, Kerman University of Medical Sciences, Kerman, Iran Iran arianamirkhosravi@yahoo.com Azadeh Aminzadeh Azadeh Aminzadeh Department of Pharmacology and Toxicology, School of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran Iran azadehaminzadeh@yahoo.com Neda Tekiyeh Maroof Neda Tekiyeh Maroof Razi Drug Research Centre and Department of Pharmacology, Iran University of Medical Sciences, Tehran, Iran Iran neda.maroof@gmail.com Atiqah Ab Aziz Atiqah Ab Aziz Tissue Engineering Group, Department of Orthopedic Surgery, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia Malaysia eyqa@um.edu.my Tunku Kamarul Tunku Kamarul Tissue Engineering Group, (NOCERAL), Department of Orthopedic Surgery, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia. Malaysia tkzrea@um.edu.my Alimohammad sharifi Alimohammad sharifi Razi Drug Research Centre and Department of Pharmacology, Iran University of Medical Sciences, Tehran, Iran Malaysia sharifalim@gmail.com Apoptosis Ferulic acid H2O2 oxidative stress PC12 cells Adams J M, Cory S. The BCL-2 arbiters of apoptosis and their growing role as cancer targets. Cell Death & Differentiation 2018; 25: 27-36. https://doi.org/10.1038/cdd.2017.161##Amirkhosravi A, Heidari M R, Karami-Mohajeri S, Torshabi M, Mandegary A, Mehrabani M. Losartan enhances the suppressive effect of pirfenidone on the bleomycin-induced epithelial-mesenchymal transition and oxidative stress in A549 cell line. Iranian Journal of Basic Medical Sciences 2023; 26: 972.##Ao G-Z, Chu X-J, Ji Y-Y, Wang J-W. Antioxidant properties and PC12 cell protective effects of a novel curcumin analogue (2 E, 6 E)-2, 6-bis (3, 5-dimethoxybenzylidene) cyclohexanone (MCH). 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Corrigendum to “The evaluation of synergistic effects of combination therapy with sulfasalazine and angiotensin-converting enzyme inhibitor in the treatment of experimental colitis in mice” [Physiol Pharmacol 28 (2024) 169-179] 2 2 Aims: Intestinal colitis or ulcerative colitis is an inflammatory bowel disease that causes long-term inflammation and ulcers in the gastrointestinal tract. It has been suggested that mucosal expression of angiotensin II (AT-II) is increased in colitis. Here, we examined the potential therapeutic effects of combination therapy regarding Enalapril, as an Angiotensin-converting enzyme inhibitor, with sulfasalazine (SSZ) in a murine colitis model. Methods: Male C57BL/6 mice divided to five groups: control group (distilled water), dextran sulphate sodium (DSS) (colitis group) (1 % DSS), SSZ (positive control group) with 100 mg/ kg/day, Enalapril alone group with 4 mg/kg/day, Enalapril (4 mg/kg/day) + SSZ (100 mg/kg/day). Results: There was a significant reduction in disease activity index among the group of mice receiving the combination of Enalapril and SSZ compared to the colitis group. Enalapril and SSZ treatment was associated with a lower reduction in colon length, decreased colon weight, spleen weight and spleen-to-body weight in mice with colitis. Following DSS administration, Enalapril and SSZ also significantly decreased MDA levels as an oxidant marker, and increased total thiol, SOD, and CAT levels, as anti-oxidants. In addition, mucosal damage, crypt loss, pathological changes, and inflammation score decreased after treatment with Enalapril and SSZ in comparison with colitis group. The combination of Enalapril and SSZ reduced colon collagen content and caused fibrosis to decrease in comparison with colitis group.  Conclusion: The results of this study indicated that Enalapril alone and in combination with SSZ decreased inflammation and clinical symptoms of colitis induced by DSS.   494 495 2023/11/242024/03/202023/12/172024/01/122023/05/222024/02/282023/07/242023/12/112022/08/122023/09/252023/08/222023/02/5 1401/11/16 2024/05/72024/10/52024/04/232024/05/252024/05/182024/05/252024/05/252024/05/72024/05/252024/04/232024/05/282025/01/25 1403/11/6 Asma Mostafapour Asma Mostafapour Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran Iran MostafapourA1@mums.ac.ir Fereshteh Asgharzadeh Fereshteh Asgharzadeh Department of Medical Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Iran Asgharzadehyf@mums.ac.ir Seyedeh Elnaz Nazari Seyedeh Elnaz Nazari Department of Medical Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Iran nazarie4003@mums.ac.ir Moein Eskandari Moein Eskandari Department of Medical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Iran EskandariM982@mums.ac.ir Niloufar Naghibzadeh Niloufar Naghibzadeh Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Iran Naghibzadehn951@mums.ac.ir Javad baharara Javad baharara Department of Biology & Research Center for Animal Development Applied Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran Iran Bahararaj@gmail.com Amir Avan Amir Avan Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Iran avana@mums.ac.ir Seyed Mahdi Hassanian Seyed Mahdi Hassanian Department of Medical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Iran HASANIANMEHRM@MUMS.AC.IR Majid Khazaei Majid Khazaei Department of Medical Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Iran khazaeimaj@gmail.com Colitis Angiotensin-converting enzyme inhibitor Enalapril inflammation Alican I, Şener G, Yüksel M, Gedik N, Ercan F, Jahovic N. 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