Saudi Pharmaceutical Journal最新文献

{"title":"Effects of novel beta-lactam, MC-100093, and ceftriaxone on astrocytic glutamate transporters and neuroinflammatory factors in nucleus accumbens of C57BL/6 mice exposed to escalated doses of morphine","authors":"Youssef Sari ,&nbsp;Ghadeer M.S. Swiss ,&nbsp;Fatin A. Alrashedi ,&nbsp;Kholoud A. Baeshen ,&nbsp;Sultan A. Alshammari ,&nbsp;Shakir D. Alsharari ,&nbsp;Nemat Ali ,&nbsp;Abdullah F. Alasmari ,&nbsp;Ali Alhoshani ,&nbsp;Alaa A. Alameen ,&nbsp;Wayne E. Childers ,&nbsp;Magid Abou-Gharbia ,&nbsp;Fawaz Alasmari","doi":"10.1016/j.jsps.2024.102108","DOIUrl":"10.1016/j.jsps.2024.102108","url":null,"abstract":"<div><p>Chronic exposure to opioids can lead to downregulation of astrocytic glutamate transporter 1 (GLT-1), which regulates the majority of glutamate uptake. Studies from our lab revealed that beta-lactam antibiotic, ceftriaxone, attenuated hydrocodone-induced downregulation of GLT-1 as well as cystine/glutamate antiporter (xCT) expression in central reward brain regions. In this study, we investigated the effects of escalating doses of morphine and tested the efficacy of novel synthetic non-antibiotic drug, MC-100093, and ceftriaxone in attenuating the effects of morphine exposure in the expression of GLT-1, xCT, and neuroinflammatory factors (IL-6 and TGF-β) in the nucleus accumbens (NAc). This study also investigated the effects of morphine and beta-lactams in locomotor activity, spontaneous alternation percentage (SAP) and number of entries in Y maze since opioids have effects in locomotor sensitization. Mice were exposed to moderate dose of morphine (20 mg/kg, i.p.) on days 1, 3, 5, 7, and a higher dose of morphine (150 mg/kg, i.p.) on day 9, and these mice were then behaviorally tested and euthanized on Day 10. Western blot analysis showed that exposure to morphine downregulated GLT-1 and xCT expression in the NAc, and both MC-100093 and ceftriaxone attenuated these effects. In addition, morphine exposure increased IL-6 mRNA and TGF-β mRNA expression, and MC-100093 and ceftriaxone attenuated only the effect on IL-6 mRNA expression in the NAc. Furthermore, morphine exposure induced an increase in distance travelled, and MC-100093 and ceftriaxone attenuated this effect. In addition, morphine exposure decreased the SAP and increased the number of arm entries in Y maze, however, neither MC-100093 nor ceftriaxone showed any attenuating effect. Our findings demonstrated for the first time that MC-100093 and ceftriaxone attenuated morphine-induced downregulation of GLT-1 and xCT expression, and morphine-induced increase in neuroinflammatory factor, IL-6, as well as hyperactivity. These findings revealed the beneficial therapeutic effects of MC-100093 and ceftriaxone against the effects of exposure to escalated doses of morphine.</p></div>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"32 7","pages":"Article 102108"},"PeriodicalIF":4.1,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1319016424001580/pdfft?md5=943b0023f031241d25a09d26fe4b6600&pid=1-s2.0-S1319016424001580-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141131466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of eugenol on cytochrome P450 1A2, 2C9, 2D6, and 3A4 activity in human liver microsomes","authors":"Naif Fahad M. Alharbi,&nbsp;Abdul Ahad,&nbsp;Yousef A. Bin Jardan,&nbsp;Fahad I. Al-Jenoobi","doi":"10.1016/j.jsps.2024.102118","DOIUrl":"https://doi.org/10.1016/j.jsps.2024.102118","url":null,"abstract":"<div><p>This study aimed to provide an understanding of the influence of eugenol on CYP1A2, 2C9, 2D6, and 3A4 in human liver microsomes (HLM). Specific substrate for CYP1A2, 2C9, 2D6, and 3A4 were incubated in HLM with or without eugenol. The formation of their respective metabolites was assessed with HPLC analytical methods. Eugenol at 1, 10 and 100 µM levels inhibited the activity of CYP1A2 and CYP2C9 by 23.38 %, 23.57 %, 39.80 % and 62.82 %, 63.27 %, 67.70 % respectively. While, CYP2D6 and CYP3A4 activity was decreased by 40.70 %, 45.88 %, 62.68 % and 37.41 %, 42.58 % and 67.86 % at 1, 10 and 100 µM eugenol level respectively. The IC₅₀ value of eugenol for CYP2D6 and CYP3A4 was calculated as 11.09 ± 3.49 µM and 13.48 ± 3.86 µM respectively. Potential herb-drug interactions was noted when eugenol is administered simultaneously with medications metabolized by these enzymes, most notably CYP2C9, CYP2D6 and CYP3A4.</p></div>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"32 7","pages":"Article 102118"},"PeriodicalIF":4.1,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1319016424001683/pdfft?md5=618e179146b39dd3b052fb58e8edc5d8&pid=1-s2.0-S1319016424001683-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141097396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Formulation, development and evaluation of hyaluronic acid-conjugated liposomal nanoparticles loaded with regorafenib and curcumin and their in vitro evaluation on colorectal cancer cell lines","authors":"Sewar G. Shnaikat ,&nbsp;Ashok K. Shakya ,&nbsp;Sanaa K. Bardaweel","doi":"10.1016/j.jsps.2024.102099","DOIUrl":"https://doi.org/10.1016/j.jsps.2024.102099","url":null,"abstract":"<div><p>Colorectal cancer is one of the major causes of global cancer, with chemotherapy and radiation therapy being effective but limited due to low specificity. Regorafenib, a multikinase inhibitor, provides hope to patients with metastatic colorectal cancer and was approved by the FDA in 2012. However, due to resistance issues and adverse events, its efficacy is compromised, necessitating further refinement. Meanwhile, curcumin, a compound of turmeric, exhibits anticancer effects through antioxidant and anti-inflammatory actions, induction of the apoptosis, arrest of cell cycle, inhibition of angiogenesis, and modulation of signaling pathways. Unfortunately, its clinical utility is limited by its poor bioavailability, pointing towards innovative drug delivery strategies for enhanced efficacy in colorectal cancer treatment.</p><p>Hyaluronic acid (HA)-decorated liposomes (LIPO) have been developed to target colorectal cells through an overexpressed CD44 receptor, increasing antitumor and antimetastasis efficacy. This study investigates the possibility of loading curcumin (CUR) or regorafenib (REGO) into a liposomal formulation for passive and HA-actively targeted treatment, evaluating its critical quality attributes (CQA) (size, zeta potential, polydispersity index) and cytotoxic activity in the HT29 colorectal cancer cell line. The average particle size of the plain liposomes and those decorated with HA was 144.00 ± 0.78 nm and 140.77 ± 1.64 nm, respectively. In contrast, curcumin-loaded plain liposomes and HA-decorated liposomes had 140 ± 2.46 nm and 164.53 ± 15.13 nm, respectively. The prepared liposomes had a spherical shape with a narrow size distribution and an acceptable zeta potential of less than −30 mV. The encapsulation efficiency was 99.2 % ± 0.3 and 99.9 ± 0.2 % for HA-decorated and bare regorafenib loaded. The % EE was 98.9 ± 0.2 % and 97.5 ± 0.2 % for bare liposomal nanoparticles loaded with curcumin and coated with curcumin. The IC₅₀ of free REGO, CUR, REGO-LIPO, CUR-LIPO, REGO-LIPO-HA and CUR-LIPO-HA were 20.17 ± 0.78, 64.4 ± 0.33, 224.8 ± 0.06, 49.66 ± 0.22, 73.66 ± 0.6, and 27.86 ± 0.49 µM, respectively. The MTT assay in HT29 cells showed significant cytotoxic activity of the HA-decorated liposomal formulation compared to the base uncoated formulation, indicating that hyaluronic acid-targeted liposomes loaded with regorafenib or curcumin could be a promising targeted formulation against colorectal cancer cells.</p></div>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"32 7","pages":"Article 102099"},"PeriodicalIF":4.1,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S131901642400149X/pdfft?md5=5cd50216e308c94951791310c3d15aab&pid=1-s2.0-S131901642400149X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141072574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of KDM2B epigenetic factor in regulating calcium signaling in prostate cancer cells","authors":"Evangelia Pantazaka ,&nbsp;Saad Alkahtani ,&nbsp;Saud Alarifi ,&nbsp;Abdullah A. Alkahtane ,&nbsp;Christos Stournaras ,&nbsp;Galatea Kallergi","doi":"10.1016/j.jsps.2024.102109","DOIUrl":"https://doi.org/10.1016/j.jsps.2024.102109","url":null,"abstract":"<div><p>KDM2B, a histone lysine demethylase, is expressed in a plethora of cancers. Earlier studies from our group, have showcased that overexpression of KDM2B in the human prostate cancer cell line DU-145 is associated with cell adhesion, actin reorganization, and improved cancer cell migration. In addition, we have previously examined changes of cytosolic Ca²⁺, regulated by the pore-forming proteins ORAI and the Ca²⁺ sensing stromal interaction molecules (STIM), via store-operated Ca²⁺ entry (SOCE) in wild-type DU-145. This study sought to evaluate the impact of KDM2B overexpression on the expression of key molecules (<em>SGK1</em>, <em>Nhe1</em>, <em>Orai1, Stim1</em>) and SOCE. Furthermore, this is the first study to evaluate KDM2B expression in circulating tumor cells (CTCs) from patients with prostate cancer. mRNA levels for <em>SGK1</em>, <em>Nhe1</em>, <em>Orai1, and Stim1</em> were quantified by RT-PCR. Calcium signals were measured in KDM2B-overexpressing DU-145 cells, loaded with Fura-2. Blood samples from 22 prostate cancer cases were scrutinized for KDM2B expression using immunofluorescence staining and the VyCAP system. KDM2B overexpression in DU-145 cells increased <em>Orai1</em>, <em>Stim1,</em> and <em>Nhe1</em> mRNA levels and significantly decreased Ca²⁺ release. KDM2B expression was examined in 22 prostate cancer patients. CTCs were identified in 45 % of these patients. 80 % of the cytokeratin (CK)-positive patients and 63 % of the total examined CTCs exhibited the (CK + KDM2B + CD45−) phenotype. To conclude, this study is the first to report increased expression of KDM2B in CTCs from patients with prostate cancer, bridging <em>in vitro</em> and preclinical assessments on the potentially crucial role of KDM2B on migration, invasiveness, and ultimately metastasis in prostate cancer.</p></div>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"32 7","pages":"Article 102109"},"PeriodicalIF":4.1,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1319016424001592/pdfft?md5=143b6a5fb60498a4d6a07d4589d7ab0e&pid=1-s2.0-S1319016424001592-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141072669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Baeckea frutescens L. Promotes wound healing by upregulating expression of TGF-β, IL-1 β, VEGF and MMP-2","authors":"Ihsan Safwan Kamarazaman ,&nbsp;Ling Sui Kiong ,&nbsp;Mohd Kamal Nik Hasan ,&nbsp;Norlia Basherudin ,&nbsp;Nur Aini Mohd Kasim ,&nbsp;Aida Azlina Ali ,&nbsp;Salfarina Ramli ,&nbsp;Sandra Maniam ,&nbsp;Richard Johari James ,&nbsp;Pornchai Rojsitthisak ,&nbsp;Hasseri Halim","doi":"10.1016/j.jsps.2024.102110","DOIUrl":"10.1016/j.jsps.2024.102110","url":null,"abstract":"<div><p><em>Baeckea frutescens</em> L. has been traditionally used for treating snakebites and is known to possess antifebrile and hemostatic properties. These properties are closely related to wound healing. This study aimed to evaluate the wound healing properties of <em>B. frutescens</em> leaves extract (BFLE) in vitro and in vivo. The in vitro study focused on proliferation, migration, and expression of TGF-β, IL-1β, VEGF, and MMP-2 genes and proteins. The in vivo study included excisional wound healing, histology, and tensile strength studies. The ethanolic extract of <em>B. frutescens</em> (BFLE) was tested for its effects on proliferation and migration using keratinocytes (HaCaT) and fibroblasts (BJ) cells. Gene and protein expression related to wound healing were analyzed using real-time PCR and Western blot assays. The wound healing properties of BFLE were evaluated in vivo using Wistar albino rats, focusing on excisional wound healing, histology, and tensile strength studies. The BFLE displayed significant proliferative and migratory effects on keratinocytes and fibroblasts cells, while upregulating the expression of TGF-β, IL-1β, VEGF, and MMP-2 genes and proteins. BFLE also exhibited significant wound healing effects on Wistar albino rats’ excisional wounds and improved the overall tensile strength. The results suggest that BFLE has strong wound healing properties, as demonstrated by its ability to increase keratinocytes and fibroblasts proliferation and migration, upregulate genes and proteins involved in the wound healing process, and improve wound healing rates and tensile strength. The findings of this study provide important insights into the potential use of <em>B. frutescens</em> as a natural wound healing agent.</p></div>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"32 7","pages":"Article 102110"},"PeriodicalIF":4.1,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1319016424001609/pdfft?md5=88480f22fd6337881fb89861635bed31&pid=1-s2.0-S1319016424001609-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141041404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"α-Glucosidase, butyrylcholinesterase and acetylcholinesterase inhibitory activities of phenolic compounds from Carthamus tinctorius L. flowers: In silico and in vitro studies","authors":"Jawaher A.M. Alotaibi ,&nbsp;Alaa Sirwi ,&nbsp;Ali M. El-Halawany ,&nbsp;Ahmed Esmat ,&nbsp;Gamal A. Mohamed ,&nbsp;Sabrin R.M. Ibrahim ,&nbsp;Abdulrahim A. Alzain ,&nbsp;Taher F. Halawa ,&nbsp;Martin Safo ,&nbsp;Hossam M. Abdallah","doi":"10.1016/j.jsps.2024.102106","DOIUrl":"10.1016/j.jsps.2024.102106","url":null,"abstract":"<div><p>Chemical investigation of <em>Carthamus tinctorius</em> L. flowers resulted in isolation of seven metabolites that were identified as; <em>p</em>-Hydroxybenzoic acid (<strong>1</strong>), <em>trans</em> hydroxy cinnamic acid (<strong>2</strong>), kaempferol-6-C-glucoside (<strong>3</strong>), astragalin (<strong>4</strong>), cartormin (<strong>5</strong>), kaempferol-3-<em>O</em>-rutinoside (<strong>6</strong>), and kaempferol–3-<em>O</em>-sophoroside (<strong>7</strong>). Virtual screening of the isolated compounds against human intestinal α-glucosidase, acetylcholinesterase, and butyrylcholinesterase was carried out. Additionally, the antioxidant activity of the bioactive compounds was assessed. Compounds <strong>1</strong> and <strong>5</strong> exhibited moderate binding affinities to acetylcholinesterase (binding energy −5.33 and −4.18 kcal/mol, respectively), compared to donepezil (-83.33kcal/mol). Compounds <strong>1</strong>–<strong>7</strong> demonstrated weak affinity to butyrylcholinesterase. Compounds <strong>2</strong> and <strong>4</strong> displayed moderate binding affinity to human intestinal α-glucosidase,compared to Acarbose (reference compound), meanwhile compound <strong>2</strong> exhibited lower affinity. Molecular dynamic studies revealed that compound <strong>4</strong> formed a stable complex with the binding site throughout a 100 ns simulation period. The <em>in-vitro</em> results were consistent with the virtual experimental results, as compounds <strong>1</strong> and <strong>5</strong> showed mild inhibitory effects on acetylcholinesterase (IC₅₀s 150.6 and 168.7 µM, respectively). Compound <strong>4</strong> exhibited moderate α-glucosidase inhibition with an IC₅₀ of 93.71 µM. The bioactive compounds also demonstrated notable antioxidant activity in ABTS [2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)], ORAC (oxygen radical-absorbance capacity), and metal chelation assays, suggesting their potential in improving dementia in Alzheimer’s disease (AD) and mitigating hyperglycemia.</p></div>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"32 7","pages":"Article 102106"},"PeriodicalIF":4.1,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1319016424001567/pdfft?md5=062c78b6f27f8d19f5d4515b04cfe4c8&pid=1-s2.0-S1319016424001567-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141037640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Formulation and evaluation of Fluconazole Nanosuspensions: In vitro characterization and transcorneal permeability studies","authors":"Basmah N. Aldosari,&nbsp;Mohamed Abbas Ibrahim,&nbsp;Yara Alqahtani,&nbsp;Amal El Sayeh F. Abou El Ela","doi":"10.1016/j.jsps.2024.102104","DOIUrl":"10.1016/j.jsps.2024.102104","url":null,"abstract":"<div><p>The aim in this study was to develop and evaluate a nanofluconazole (FLZ) formulation with increased solubility and permeation rate using nanosuspensions. The FLZ nanosuspensions were stabilized using a variety of stabilizing agents and surfactants in various concentrations. The FLZ nanosuspension was characterized in vitro using particle size, zeta potential, X-ray powder diffraction (XRPD), and solubility. In addition, the ex vivo ocular permeation of FLZ through a goat cornea was analyzed. The results showed that the particle size of all nanosuspension formulations was in the nanometer range from 174.5 ± 1.9 to 720.2 ± 4.77 nm; that of the untreated drug was 18.34 μm. The zeta potential values were acceptable, which indicated suitable stability for formulations. The solubility of the nanosuspensions was up to 5.7-fold higher compared with that of the untreated drug. The results of the ex vivo ocular diffusion of the FLZ nanosuspensions showed the percentage of FLZ penetrating via the goat cornea increased after using Kollicoat to stabilize the nanosuspension formulation. Consequently, when using a nanosuspension formulation of Kollicoat, the antifungal activity of the drug strengthens.</p></div>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"32 7","pages":"Article 102104"},"PeriodicalIF":4.1,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1319016424001543/pdfft?md5=c9ff351479b5cbdc78dae3f83fd589b6&pid=1-s2.0-S1319016424001543-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141041944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diuretic effects of Hecogenin and Hecogenin acetate via aldosterone synthase inhibition","authors":"Abdulmohsin J. Alamoudi ,&nbsp;Maria Nazeer ,&nbsp;Nabi Shah ,&nbsp;Saif Ullah ,&nbsp;Meshal Alshamrani ,&nbsp;Waleed Y. Rizg ,&nbsp;Osama M. Ashour ,&nbsp;Ashraf B. Abdel-naim ,&nbsp;Abdul Jabbar Shah","doi":"10.1016/j.jsps.2024.102105","DOIUrl":"10.1016/j.jsps.2024.102105","url":null,"abstract":"<div><p>Hecogenin (HEC) is a steroidal saponin found in many plant species and serves as a precursor for steroidal drugs. The diuretic effects of HEC and its derivative<u>,</u> hecogenin acetate (HA), remain largely unexplored. The present study aimed to explore the potential diuretic effects of HEC and HA compared to furosemide (FUR) and spironolactone (SPIR). Additionally, the study aimed to explore the underlying mechanism particularly focusing on aldosterone synthase gene expression. Fifty-four Sprague-Dawley rats were allocated into nine groups (Group 1–9). Group 1 (control) received the vehicle, Groups 2 received FUR 10 mg/kg, Group 3, 4, and 5 were given HEC, while Groups 6, 7 and 8 received HA i.p at doses of 5, 10, and 25 mg/kg, respectively. Group 9 received SPIR i.p at the dose of 25 mg/kg. Urine volume, diuretic index and diuretic activity were monitored at 1, 2, 3, 4, 5, 6, and 24 h post-administration. Treatment was given daily for seven days. After that, rats were sacrificed and blood was collected for serum electrolytes determination. Adrenal glands were dissected out for gene expression studies. The results revealed that HEC and HA at the administered doses significantly and dose-dependently increased urine and electrolyte excretion. These results were primarily observed at 25 mg/kg of each compound. Gene expression studies demonstrated a dose-dependent reduction in aldosterone synthase gene expression, suggesting aldosterone synthesis inhibition as a potential mechanism for their diuretic activity. Notably, HA exhibited more pronounced diuretic effects surpassing those of HEC. This enhanced diuretic activity of HA can be attributed to its stronger impact on aldosterone synthase inhibition. These findings offer valuable insights into the diuretic effects of both HEC and HA along with their underlying molecular mechanisms.</p></div>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"32 7","pages":"Article 102105"},"PeriodicalIF":4.1,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1319016424001555/pdfft?md5=54b54ed24bc9fc78548136d1aea7f2c0&pid=1-s2.0-S1319016424001555-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141027647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antifibrotic effect of the P2X7 receptor antagonist A740003 against acute myocardial infarction-induced fibrotic remodelling","authors":"Noura Almusallam ,&nbsp;Asma Alonazi ,&nbsp;Anfal Bin Dayel ,&nbsp;Abdullah Almubarak ,&nbsp;Rizwan Ali ,&nbsp;Wajd Althakfi ,&nbsp;Rehab Ali ,&nbsp;Nouf Alrasheed","doi":"10.1016/j.jsps.2024.102102","DOIUrl":"10.1016/j.jsps.2024.102102","url":null,"abstract":"<div><p>Post-acute myocardial infarction (AMI) fibrosis is a pathophysiologic process characterised by activation of the profibrotic mediator, transforming growth factor-β (TGF-β). AMI is associated with a substantial increase in the levels of extracellular adenosine triphosphate (eATP), which acts on the purinergic P2X7-receptor (P2X7-R) and triggers an inflammatory response that contributes to myocardial fibrotic remodelling. P2X7-R has been implicated in several cardiovascular diseases; however, its role in the regulation of cardiac fibrosis remains unclear. Therefore, the current study aimed to determine the effect of the P2X7-R antagonist, A740003, on post-AMI fibrosis, via the profibrotic TGF-β1/Smad signalling pathway, and elucidate whether its effect is mediated via the modulation of GSK-3β. AMI was induced by surgical ligation of the left anterior descending coronary artery, Thereafter, animals were divided into groups: sham control, MI-untreated, MI-vehicle, and MI-A740003 (50 mg/kg/day) and treated for seven days accordingly. The heart weight/body weight ratio of untreated-ligated rats significantly increased by 15.1 %, creatine kinase‐MB (CK‐MB) significantly increased by 40 %, troponin‐I levels significantly increased by 25.4 %, and lactate dehydrogenase significantly increased by 47.2 %, indicating myocardial damage confirmed by morphological changes and massive cardiac fibrosis. The protein expression of cardiac fibronectin, TGF-β1, and p-Smad2 were also upregulated by 143 %, 40 %, and 8 %, respectively, indicating cardiac fibrosis. The treatment of ligated rats with A740003 led to improvement in all the above-mentioned parameters. Overall, A740003 exhibits potential cardio-protective effects on post-AMI fibrotic remodelling in the animal model of AMI through P2X7-R blockade, possibly by downregulating the profibrotic TGF-β1/Smad signalling pathway and restoring GSK-3β phosphorylation. Altogether, treatment with A740003 could serve as a new cardioprotective strategy to attenuate post-AMI fibrotic remodelling.</p></div>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"32 7","pages":"Article 102102"},"PeriodicalIF":4.1,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S131901642400152X/pdfft?md5=2d71383d60b023c6db4f155fd103c4b1&pid=1-s2.0-S131901642400152X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141041676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of diosmin in preventing doxorubicin-induced cardiac oxidative stress, inflammation, and hypertrophy: A mechanistic approach","authors":"Abdullah F. AlAsmari ,&nbsp;Mohammed M. Al-Shehri ,&nbsp;Nasser Algarini ,&nbsp;Nada A. Alasmari ,&nbsp;Alabid Alhazmi ,&nbsp;Mohammed AlSwayyed ,&nbsp;Metab Alharbi ,&nbsp;Fawaz Alasmari ,&nbsp;Nemat Ali","doi":"10.1016/j.jsps.2024.102103","DOIUrl":"https://doi.org/10.1016/j.jsps.2024.102103","url":null,"abstract":"<div><p>Chemotherapeutic drugs, such as doxorubicin (Dox), are commonly used to treat a variety of malignancies. However, Dox-induced cardiotoxicity limits the drug’s clinical applications. Hence, this study intended to investigate whether diosmin could prevent or limit Dox-induced cardiotoxicity in an animal setting. Thirty-two rats were separated into four distinct groups of controls, those treated with Dox (20 mg/kg, intraperitoneal, i.p.), those treated with diosmin 100 mg plus Dox, and those treated with diosmin 200 mg plus Dox. At the end of the experiment, rats were anesthetized and sacrificed and their blood and hearts were collected. Cardiac toxicity markers were analyzed in the blood, and the heart tissue was analyzed by the biochemical assays MDA, GSH, and CAT, western blot analysis (NF-kB, IL-6, TLR-4, TNF-α, iNOS, and COX-2), and gene expression analysis (β-MHC, BNP). Formalin-fixed tissue was used for histopathological studies. We demonstrated that a Dox insult resulted in increased oxidative stress, inflammation, and hypertrophy as shown by increased MDA levels and reduced GSH content and CAT activity. Furthermore, Dox treatment induced cardiac hypertrophy and damage, as evidenced by the biochemical analysis, ELISA, western blot analysis, and gene expression analysis. However, co-administration of diosmin at both doses, 100 mg and 200 mg, mitigated these alterations. Data derived from the current research revealed that the cardioprotective effect of diosmin was likely due to its ability to mitigate oxidative stress and inflammation. However, further study is required to investigate the protective effects of diosmin against Dox-induced cardiotoxicity.</p></div>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"32 6","pages":"Article 102103"},"PeriodicalIF":4.1,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1319016424001531/pdfft?md5=97e135b42dae2b3b1373655940c7cb83&pid=1-s2.0-S1319016424001531-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140952261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}