Iranian Journal of Pharmaceutical Research最新文献

{"title":"Cost-Utility Analysis of Erenumab Compared to Topiramate for Preventive Therapy of Migraine in Iran.","authors":"Hosein Mollaee, Sadra Nadimi Parashkouhi, Behzad Fatemi, Meysam Seyedifar, Fatemeh Soleymani","doi":"10.5812/ijpr-146026","DOIUrl":"https://doi.org/10.5812/ijpr-146026","url":null,"abstract":"<p><strong>Background: </strong>Migraine is a prevalent, chronic neurovascular disorder that incurs significant indirect costs due to productivity loss. Preventive therapy is an effective way to alleviate the societal and healthcare burden of migraine. Approximately 14% of both the global and Iranian populations are affected by migraine, which has substantial economic implications.</p><p><strong>Objectives: </strong>To determine the cost-effectiveness of Erenumab compared to Topiramate for migraine treatment in Iran.</p><p><strong>Methods: </strong>A three-state Markov model was used to evaluate the cost-effectiveness of Erenumab. The model considered both direct and indirect costs from a societal perspective. The incremental cost-effectiveness ratio (ICER) was calculated by determining the cost per quality-adjusted life year (QALY) gained. Costs and QALYs were discounted annually at 5.8% and 5%, respectively. Deterministic and probabilistic sensitivity analysis (PSA) were performed to assess the robustness of the model.</p><p><strong>Results: </strong>The average cost for patients using the Erenumab strategy was 16,836 USD over five years, whereas the average cost for the Topiramate strategy was estimated to be 2,660 USD. Additionally, the average QALYs for the Erenumab and Topiramate strategies were 3.64 and 3.46, respectively. The ICER for the Erenumab strategy was 78,923 USD/QALY. This ICER is significantly higher than the fixed Iranian willingness-to-pay (WTP) threshold of 2,456 USD.</p><p><strong>Conclusions: </strong>The study concludes that preventive treatment of migraine with Erenumab, compared to Topiramate, is not cost-effective in Iran based on current prices. Therefore, for Erenumab to be considered cost-effective, a significant price reduction is necessary for its entry into the Iranian pharmaceutical market.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"23 1","pages":"e146026"},"PeriodicalIF":1.8,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antiproliferative and Pro-apoptotic Activities of <i>Tournefortia mutabilis</i> vent. Leaves on the Human Breast Adenocarcinoma Cell Line (MCF-7).","authors":"Zoila Mora-Guzmán, Luis Bernardo Flores-Cotera, Eduardo Pérez-Campos, Rebeca López-Marure, Delia Soto-Castro, Felipe Alonso Masso-Rojas, Araceli Paéz Arenas, Edgar Zenteno, Margarito Martinez-Cruz, Laura Pérez-Campos Mayoral, María Teresa Hernández-Huerta, María Del Socorro Pina-Canseco","doi":"10.5812/ijpr-149405","DOIUrl":"https://doi.org/10.5812/ijpr-149405","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer is the most common cancer among women worldwide, impacting not only the patients but also their families and communities. <i>Tournefortia mutabilis</i> vent. is a plant endemic to Mexico, traditionally used in Zapotec medicine for the treatment of cancer.</p><p><strong>Objectives: </strong>This study aims to evaluate the effects of the chloroformic extract of <i>T. mutabilis</i> vent. leaves on cell proliferation and cell death in MCF-7 cells.</p><p><strong>Methods: </strong>The effect of the extract on MCF-7 cell proliferation was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and crystal violet staining. Apoptosis was evaluated through fluorescein diacetate/propidium iodide staining and caspase-3, -6, and -9 activity assays.</p><p><strong>Results: </strong>The half-maximal inhibitory concentration (IC50) of the <i>T. mutabilis</i> vent. extract on MCF-7 cell proliferation at 48 hours and 72 hours after treatment was 86.4 µg/mL and 2.74 µg/mL, respectively. We observed that the extract and its semi-purified fractions induced cell death through the activation of caspases 3, -6, and -9.</p><p><strong>Conclusions: </strong><i>Tournefortia mutabilis</i> vent. is a potential source of compounds with antiproliferative and pro-apoptotic activities on the MCF-7 cell line, primarily through the intrinsic pathways of apoptosis.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"23 1","pages":"e149405"},"PeriodicalIF":1.8,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Zinc Supplementation in Alleviating Inflammatory Biomarkers in Patients Undergoing Hemodialysis: A Randomized Placebo Controlled, Crossover Trial.","authors":"Shayan Mastoor-Tehrani, Fariba Samadian, Hadi Esmaily, Alireza Kargar, Nasim Markazi, Shideh Anvari, Shadi Ziaie","doi":"10.5812/ijpr-147887","DOIUrl":"https://doi.org/10.5812/ijpr-147887","url":null,"abstract":"<p><strong>Background: </strong>Chronic kidney disease (CKD), which progresses to end-stage renal disease (ESRD) and requires maintenance hemodialysis (MHD), is a global health issue. Inflammation in MHD patients is associated with increased mortality and cardiovascular events. Zinc, essential for immune function and possessing anti-inflammatory properties, is frequently deficient in these patients and could potentially help mitigate inflammation.</p><p><strong>Objectives: </strong>This study aims to assess the impact of zinc supplementation on inflammatory biomarkers, specifically (CRP) and the neutrophil-to-lymphocyte ratio (NLR), in MHD patients.</p><p><strong>Methods: </strong>In a double-blind, randomized controlled crossover trial conducted at Labafinejad Hospital, Tehran, MHD patients with zinc deficiency were initially allocated to either a zinc supplementation group or a placebo group. After 30 days, the groups were crossed over, with patients initially receiving zinc now receiving a placebo and vice versa. The primary outcome was changes in serum zinc levels, while secondary outcomes focused on CRP and NLR levels.</p><p><strong>Results: </strong>Significant changes in serum zinc levels were observed in both groups from baseline to Month 2 (drug-placebo group: Mean change -15.9±10.33 µg/dL, P < 0.05; placebo-drug group: Mean change -14.70 ± 12.58 µg/dL, P < 0.05). A significant initial reduction in CRP levels at Month 1 (P = 0.045) was not sustained at Month 2 (P = 0.812). No statistically significant changes in NLR were noted. Improvements in quality of life, including reductions in muscle pain and skin dryness, were significant in the drug-placebo group (P < 0.05).</p><p><strong>Conclusions: </strong>Zinc supplementation in MHD patients significantly improved serum zinc levels and initially reduced CRP levels, highlighting its potential role in managing inflammation. Although the impact on NLR was not significant, overall patient outcomes and quality of life showed promising improvements.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"23 1","pages":"e147887"},"PeriodicalIF":1.8,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Potential of Crocin and Nobiletin in a Mouse Model of Dry Eye Disease: Modulation of the Inflammatory Response and Protection of the Ocular Surface.","authors":"Ahmad Habibian Sezavar, Seyed Nasser Ostad, Yazdan Hasani Nourian, Hossein Aghamollaei","doi":"10.5812/ijpr-149463","DOIUrl":"https://doi.org/10.5812/ijpr-149463","url":null,"abstract":"<p><strong>Background: </strong>Dry eye disease (DED) is a multifactorial condition characterized by ocular surface inflammation, tear film instability, and corneal epithelial damage. Current treatments often provide temporary relief without addressing the underlying inflammatory mechanisms.</p><p><strong>Objectives: </strong>This study examined the therapeutic potential of crocin and nobiletin, two naturally derived compounds with well-known antioxidant and anti-inflammatory properties, in a mouse model of DED induced by lacrimal gland excision (LGE).</p><p><strong>Methods: </strong>Thirty female Balb/c mice were divided into five groups (n = 6 each): Control (sham surgery), untreated DED, nobiletin-treated DED (32.75 µM), crocin-treated DED (34 µM), and 1% betamethasone-treated DED. Treatments were administered three times daily for 28 days. Ocular tissues were evaluated using Hematoxylin and Eosin (H&E) staining and fluorescein staining. Conjunctival inflammatory cytokines, including interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and tumor necrosis factor-alpha (TNF-α), were measured by enzyme-linked immunosorbent assay (ELISA).</p><p><strong>Results: </strong>Histological analysis showed that the crocin and nobiletin treatment groups exhibited reduced epithelial disruption, keratinization, and inflammatory cell infiltration compared to the untreated DED group. The ELISA assay revealed that both compounds efficiently inhibited the production of the pro-inflammatory cytokines IL-6, TNF-α, and IL-1β, which are key mediators of DED pathogenesis. Fluorescein staining further confirmed the protective impact of crocin and nobiletin on corneal epithelial integrity. Moreover, the anti-inflammatory and epithelial-preserving effects of these compounds were comparable to those of the corticosteroid betamethasone.</p><p><strong>Conclusions: </strong>Overall, these findings suggest that crocin and nobiletin have therapeutic potential for DED management by modulating inflammatory responses and enhancing ocular surface healing. These naturally derived compounds offer promising avenues for the development of safer and more effective treatments for this challenging condition. However, further investigations, including clinical trials, are essential to elucidate the underlying mechanisms of action and optimize therapeutic approaches.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"23 1","pages":"e149463"},"PeriodicalIF":1.8,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibitory Effects of <i>Marrubium vulgare</i> L. Extract on the Female Hormones Based on Bioautography-HPTLC-MS.","authors":"Sahar Hassannejad, Abdulghany O I Sarmamy, Fateme Mirzajani","doi":"10.5812/ijpr-148259","DOIUrl":"https://doi.org/10.5812/ijpr-148259","url":null,"abstract":"<p><strong>Background: </strong>Hormonal imbalances related to women's health, physical activity, and fluctuations are prevalent metabolic disorders in several nations and have significantly impacted women's health for an extended period. The application of individual or combined botanical extracts in traditional, alternative, and complementary medicine is employed to manage and alleviate these issues.</p><p><strong>Objectives: </strong>The objective of this study is to examine the suppressive properties of horehound (<i>Marrubium vulgare</i> L.) on pivotal hormones associated with feminine disorders.</p><p><strong>Methods: </strong>The horehound plant was exposed to ultrasonic radiation while five different solvents (methanol, ethyl acetate, n-hexane, acetone, and water) were used to extract its components. The individuals were isolated using high-performance thin-layer chromatography (HPTLC). The most powerful compounds were analyzed using a direct antioxidant assay (DPPH test) and a hormone inhibitory assay (Oestrogen, Progesterone, Estradiol, and Testosterone) on the HPTLC plate. The compounds that had a significant effect were then identified using LC-ESI/MSMS.</p><p><strong>Results: </strong>The antioxidant properties of the extracts and hormone inhibitors were evaluated, and the substances were separated from the HPTLC plate and analyzed using mass spectrometry. The results showed strong antioxidant capabilities, with an IC50 range of 8.24 - 12.42 µg/mL. Moreover, the plant extract showed beneficial effects on hormones associated with female health issues.</p><p><strong>Conclusions: </strong>The extract was subjected to chemical and molecular analysis using the HPTLC technique, followed by LC-ESI/MSMS. The study revealed the presence of vulgarole, marrubiin, and marrubenol chemicals.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"23 1","pages":"e148259"},"PeriodicalIF":1.8,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Preliminary Study to Evaluate the Immune Response to a Booster Dose of the Adult Tetanus-Diphtheria Vaccine (Td) Available in Iran.","authors":"Sepideh Noorian, Negar Mottaghi-Dastjerdi, Mohammad Soltany-Rezaee-Rad, Hamed Montazeri, Masoumeh Baghaei, Mohammad-Javad Niazi","doi":"10.5812/ijpr-146572","DOIUrl":"https://doi.org/10.5812/ijpr-146572","url":null,"abstract":"<p><strong>Background: </strong>Despite the availability of tetanus-diphtheria (TD) vaccines in Iran, the seroconversion rate of these products as a booster dose is unknown.</p><p><strong>Objectives: </strong>This study evaluates the seroconversion rate of the Iranian Td vaccine in adults who have not been vaccinated in the past decade.</p><p><strong>Methods: </strong>In this study, 20 adult volunteers aged 18 to 60 who had not received the Td vaccine in the past decade received a booster dose of the Iranian Td vaccine. Twenty-eight days after vaccination, the seroconversion rate was evaluated using the ELISA method. Vaccine adverse events were monitored at three time points after vaccination.</p><p><strong>Results: </strong>Seroconversion rates with the Iranian Td vaccine boosters were 75% and 90%, respectively, based on a 4-fold increase in anti-tetanus toxoid antibody titers and a 2- and 4-fold combination. Significant associations were found between the demographic data, specifically female gender and age 43 years and older, with seroconversion rates. Injection-site pain was the most common adverse reaction, with a frequency of 35%. No adverse events were reported between one week and one month after vaccination.</p><p><strong>Conclusions: </strong>Results showed that a booster dose of the Iranian Td vaccine produced a protective titer (> 0.1 IU/mL) and a long-term protective titer (> 1.0 IU/mL) in 100% of participants. The seroconversion rate of the Iranian Td vaccine was comparable to other common tetanus vaccines, including Tenivac^®, Adacel^®, Infanrix^®, Tetavax^®, and Vacteta^®. The proportion of suitable candidates for plasma donation, based on minimum (2 IU/mL) and maximum (10 IU/mL) anti-tetanus toxoid antibody titers, was 100% and 45%, respectively.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"23 1","pages":"e146572"},"PeriodicalIF":1.8,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selection and Characterization of a DNA Aptamer Recognizing High Mobility Group Box 1 Protein (HMGB1) and Enhancing Its Pro-inflammatory Activity.","authors":"Hanchao Li, Wengang Sun, Yanhua Huang, Qian Li, Hong Tian, Zhiming Hao, Yongwei Huo","doi":"10.5812/ijpr-147246","DOIUrl":"https://doi.org/10.5812/ijpr-147246","url":null,"abstract":"<p><strong>Background: </strong>High mobility group box 1 (HMGB1) plays an essential role in various pathological conditions, including inflammation, fibrosis, autoimmune diseases, and carcinogenesis. The quantification of HMGB1 in body fluids holds promise for clinical applications.</p><p><strong>Objectives: </strong>This study aimed to isolate high-affinity single-stranded DNA (ssDNA) aptamers that target HMGB1.</p><p><strong>Methods: </strong>In this study, ssDNA aptamers were selected using Systematic Evolution of Ligands by Exponential Enrichment (SELEX). The affinity and specificity of the aptamers were evaluated through South-Western blot analysis, enzyme-linked aptamer sorbent assay (ELASA), and aptamer-based histochemistry staining. The impact of the aptamers on the biological activity of HMGB1 was tested in the human acute monocytic leukemia cell line, THP-1.</p><p><strong>Results: </strong>An aptamer (H-ap25, dissociation constant = 8.20 ± 0.53 nmol/L) with high affinity for the HMGB1 B box was generated. Further experiments verified that H-ap25 can be used to detect HMGB1 in South-Western blot analysis, ELASA, and aptamer-based histochemistry staining. Moreover, H-ap25 significantly augmented HMGB1-induced expression of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, Toll-like receptor 9 (TLR9), and activation of NF-κB in THP-1 cells.</p><p><strong>Conclusions: </strong>Our results demonstrated that H-ap25 can be used both as an enhancer of HMGB1 and as a probe in research.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"23 1","pages":"e147246"},"PeriodicalIF":1.8,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishment of an HPLC Fingerprint and Cluster Analysis for Miao Ethnic Medicine <i>Osbeckia opipara</i>.","authors":"Qiang Su, Ting Su, Yun Lu, Min Wu, Song Huang, Shouneng Chen, Jiang Liang, Zhenxiang An","doi":"10.5812/ijpr-146396","DOIUrl":"https://doi.org/10.5812/ijpr-146396","url":null,"abstract":"<p><p><i>Osbeckia opipara</i>, a traditional Miao medicine, is commonly used by the renowned national-level Chinese Traditional Medicine practitioner Zhengshi Wu for the treatment of diarrhea due to its strong antioxidative, anti-inflammatory, and antidiarrheal effects. This study aimed to establish a high-performance liquid chromatography (HPLC) fingerprint for <i>O. opipara</i> to provide new evidence and technical means for the scientific evaluation and effective quality control of <i>O. opipara</i>. The procedure involved isolation with a Nano ChromCore C18 column (250 mm × 4.6 mm, 5 μm), using a gradient elution of 0.1% formic acid in water and 0.1% formic acid in acetonitrile as the mobile phase, with a flow rate of 1.0 mL/min, a column temperature of 30°C, an injection volume of 10 μL, and detection at a wavelength of 254 nm. Under these chromatographic conditions, fingerprint analysis was conducted on 11 batches of <i>O. opipara</i> collected from different origins. The National Pharmacopoeia Committee developed the 'Chromatographic Fingerprint Similarity Evaluation System' (2004A version) for automated comparison, similarity computation, and analysis of chromatographic data. The results revealed 13 common peaks across the 11 batches of <i>O. opipara</i> samples, with a similarity to the automatically generated reference spectrum exceeding 0.9. SPSS 26.0 software was used to conduct cluster analysis on the peak areas of the 13 common peaks. The observations indicated that the reference spectrum generated from the 11 batches could serve as the standard fingerprint profile for <i>O. opipara</i>, providing sufficient characteristic information extraction.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"23 1","pages":"e146396"},"PeriodicalIF":1.8,"publicationDate":"2024-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Protective Effects of <i>Pistacia Atlantica</i> Gum in a Rat Model of Aluminum Chloride-Induced Alzheimer's Disease via Affecting BDNF and NF-kB.","authors":"Mohammad Mehdi Gravandi, Seyede Zahra Hosseini, Seyede Darya Alavi, Tayebeh Noori, Antoni Sureda, Roshanak Amirian, Mohammad Hosein Farzaei, Samira Shirooie","doi":"10.5812/ijpr-142203","DOIUrl":"10.5812/ijpr-142203","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a neurodegenerative condition characterized by progressive cognitive deterioration, including deficits in memory and other cognitive functions. Oxidative stress and free radical damage play significant roles in its pathogenesis. This study aimed to investigate the potential anti-inflammatory and neuroprotective effects of <i>Pistacia atlantica</i> gum (administered at doses of 50 and 100 mg/kg for 14 days) in a rat model of AD induced by aluminum chloride (AlCl₃). Behavioral changes were assessed using open field, passive avoidance, and elevated plus maze tests. Additionally, nitrite levels, nuclear factor-kappa B (NF-κB), brain-derived neurotrophic factor (BDNF), and immunostaining were evaluated. Administration of <i>P. atlantica</i> gum significantly increased step-through latency in the passive avoidance test (P < 0.01 and P < 0.001), enhanced mobility in the open field test (P < 0.01 and P < 0.001), and reduced anxiety-like behaviors in the elevated plus maze (P < 0.001) compared to the AlCl₃ group. Treatment with the gum partially normalized the elevated levels of NF-κB and the decreased levels of BDNF caused by AlCl₃ exposure. Our findings suggest that <i>P. atlantica</i> gum administration may alleviate oxidative stress, neuroinflammation, and cognitive impairment in AD rats.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"23 1","pages":"e142203"},"PeriodicalIF":1.8,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11246649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141618024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insulin and TLR4 Inhibitor Improve Motor Impairments in a Rat Model of Parkinson's Disease.","authors":"Fatemeh Hemmati, Neda Valian, Abolhassan Ahmadiani, Zahurin Mohamed, Raymond Azman Ali, Norlinah Mohamed Ibrahim, Seyed Farshad Hosseini Shirazi","doi":"10.5812/ijpr-144200","DOIUrl":"https://doi.org/10.5812/ijpr-144200","url":null,"abstract":"<p><strong>Background: </strong>Insulin resistance is an important pathological hallmark of Parkinson's disease (PD). Proinflammatory cytokines during neuroinflammation decrease insulin sensitivity by suppressing insulin signaling elements. Toll-like receptor 4 (TLR4), the main receptor involved in neuroinflammation, is also associated with the pathogenesis of PD.</p><p><strong>Objectives: </strong>The present study evaluated the effect of insulin, an insulin receptor antagonist, and a TLR4 inhibitor on behavioral deficits and insulin resistance induced by 6-hydroxydopamine (6-OHDA).</p><p><strong>Methods: </strong>Male Wistar rats were divided into nine groups: (1) sham (normal saline [NS] in the medial forebrain bundle [MFB]); (2) 6-OHDA (20 µg in the MFB); (3) 6-OHDA + NS; (4) 6-OHDA + dimethyl sulfoxide (DMSO); (5) 6-OHDA + insulin (2.5 IU/day, intracerebroventricular ([ICV]); (6) 6-OHDA + insulin (5 IU/day, intranasal [IN]); (7) 6-OHDA + insulin receptor antagonist (S961; 6.5 nM/kg, ICV); (8) 6-OHDA + TLR4 inhibitor (TAK242; 0.01 µg/rat, ICV); (9) 6-OHDA + insulin + TLR4 inhibitor. All treatments were administered for seven consecutive days. Motor performance was evaluated using apomorphine-induced rotation and cylinder tests. Gene expression and protein levels of α-synuclein, TLR4, insulin receptor substrate (IRS) 1, IRS2, and glycogen synthase kinase 3β (GSK3β) were measured by real-time PCR and western blotting, respectively, in the striatum.</p><p><strong>Results: </strong>Insulin, alone and with TAK242, improved motor deficits induced by 6-OHDA. Administration of the insulin receptor antagonist had no effect on motor deficits. The increased expression of α-synuclein and TLR4 following 6-OHDA was attenuated by insulin and TAK242. GSK3β levels, both mRNA and protein, were significantly increased by 6-OHDA and attenuated with insulin and TAK242.</p><p><strong>Conclusions: </strong>The findings suggest that 6-OHDA induces neurodegeneration via activation of TLR4 and GSK3β, indicating insulin resistance, and that insulin can improve these impairments. Moreover, TLR4 inhibition prevents insulin signaling dysfunction and improves behavioral and molecular impairments, highlighting the critical role of TLR4 in the development of insulin resistance in PD pathology.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"23 1","pages":"e144200"},"PeriodicalIF":1.8,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}