Advances in Pharmacological and Pharmaceutical Sciences最新文献

{"title":"Antiplatelet Effects of a Combination of Sappan Wood (<i>Caesalpinia sappan</i> L.) and Red Ginger (<i>Zingiber officinale var. Rubrum</i>) Extracts in a High-Fat Diet-Induced Rat Model.","authors":"Meidi Utami Puteri, Nur Afifah, Anisa Qisti Mathriul, Farhan Mahmudi Wicaksono, Mellynia Tri Sugiarti, Raihana Izzatinisa, Mitsuyasu Kato, Fadlina Chany Saputri","doi":"10.1155/adpp/5543717","DOIUrl":"10.1155/adpp/5543717","url":null,"abstract":"<p><p><b>Background:</b> Antithrombotic medications, including antiplatelet agents, are standard treatments for patients with hyperlipidemia who have a high risk of developing cardiovascular disease (CVD). The ongoing exploration of new antiplatelet agents with minimal bleeding effects is crucial, including the investigation of potential compounds derived from natural products. This study intended to evaluate the antiplatelet effects of a combined extract of sappan wood (<i>Caesalpinia sappan</i> L.) and red ginger (<i>Zingiber officinale</i> var. <i>Rubrum</i>) in high-fat diet-(HFD)-induced rats. <b>Methods:</b> Eighteen male Wistar rats were grouped into six groups (<i>n</i> = 3): control, negative, positive, and three groups of various combinations of extracts. All groups, excluding the control group, were fed an HFD for 8 weeks. In the eighth week, the control and negative groups were given carboxyl methyl cellulose (CMC) 0.5%, the positive control group was administered aspirin, and the other three groups were administered the combination extract of sappan wood and red ginger at various doses for 2 weeks. Blood samples were collected to assess the levels of hyperlipidemia and platelet hyperactivity markers by enzyme-linked immunosorbent assay (ELISA). The physiological effects of platelet hyperactivity were evaluated using the tail bleeding assay. <b>Results:</b> HFD-induced hypertriglyceridemia and hypercholesterolemia synergistically enhanced platelet hyperactivity after 8 weeks of induction. Interestingly, administration of all doses of the combined extract for 2 weeks significantly decreased the platelet activation markers P-selectin, RANTES, and PCSK9 in a dose-dependent manner compared with the negative control. In addition, the combination of sappan wood and red ginger extract at dose 3 (sappan wood:red ginger: 200:800 mg/200 bw/day) significantly extended the bleeding time of rats (<i>p</i> < 0.05) compared to the negative control. <b>Conclusion:</b> Collectively, our results highlight the antiplatelet effect of a combination of sappan wood and red ginger extract in HFD-fed rats.</p>","PeriodicalId":7369,"journal":{"name":"Advances in Pharmacological and Pharmaceutical Sciences","volume":"2024 ","pages":"5543717"},"PeriodicalIF":2.1,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11679274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ethanolic Extracts of <i>Cissus quadrangularis</i> Linn. (Vitaceae) Attenuate Vincristine-Induced Peripheral Neuropathy in Rats: An Evidence of the Antioxidant, Calcium Inhibitory, and Neuromodulatory Properties.","authors":"Feigni Youyi Marcelle Olga, Mbiantcha Marius, Yousseu Nana William, Tsafack Eric Gonzal, Djuichou Nguemnang Stephanie Flore, Noungoua Mbeugangkeng Chrétien, Atsafack Mboudem Lylie Gisèle, Ateufack Gilbert","doi":"10.1155/adpp/8822369","DOIUrl":"10.1155/adpp/8822369","url":null,"abstract":"<p><p><i>Cissus quadrangularis</i> Linn. (<i>C. quadrangularis</i>, Vitaceae) is a plant reported to treat injured tendons, broken bones, asthma, stomach ache, scurvy, and digestive disorders. The present study evaluated the antihyperalgesic effects of ethanolic extract of <i>C. quadrangularis</i> Linn. Vincristine sulfate (100 μg/kg, i.p.) was administered in rats for 10 days with 2 days break to induce painful peripheral neuropathy. Mechanical hyperalgesia and allodynia tests were performed to assess the threshold of painful neuropathy. Calcium levels in the sciatic nerve, oxidant stress markers, and levels of GABA and 5-HT were also determined in the brain and spinal cord after 15 days. Ethanolic extract of <i>C. quadrangularis</i> (180 and 360 mg/kg) and pregabalin (50 mg/kg) were administered for 15 consecutive days. The results revealed that the extract significantly (<i>p</i> < 0.001) inhibited hyperalgesia and allodynia in animals after vincristine administration. The extract decreased total calcium levels in the sciatic nerve, MDA levels while increasing GSH activity, 5-HT level, as well as GABA levels in the brain and spinal cord. The results of this study suggest that the ethanolic extract of <i>C. quadrangularis</i> uses antioxidant capacity, calcium inhibitory action, and neuromodulation of GABA and 5-HT to prevent the development of painful neuropathy after vincristine administration. This demonstrates that <i>C. quadrangularis</i> is a promising molecule for the management of peripheral neuropathic pain induced by anticancer drugs.</p>","PeriodicalId":7369,"journal":{"name":"Advances in Pharmacological and Pharmaceutical Sciences","volume":"2024 ","pages":"8822369"},"PeriodicalIF":2.1,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11658851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification, Synthesis, and Characterization of N-Formyl Mirabegron: A New Degradation Product Formed by Formic Acid Impurity in Pharmaceutical Excipients.","authors":"Bashir Daoud Agha Dit Daoudy, Mohammad Ammar Al-Khayat, Ghassan Abo Chameh, Mohammad Amer Al Mardini","doi":"10.1155/adpp/4971456","DOIUrl":"10.1155/adpp/4971456","url":null,"abstract":"<p><p>This study demonstrated the impact of formic acid (FAc), a common reactive impurity in pharmaceutical excipients, on the stability of mirabegron (MB). The investigation of MB-excipient compatibility tests revealed the formation of a new degradation product, FAc-DP, at 0.2% after 7 days of isothermal stress at 55°C. FAc-DP was synthesized and characterized as N-formyl MB using liquid chromatography-mass spectrometry (LC-MS) and both 1D and 2D nuclear magnetic resonance spectroscopy (NMR).</p>","PeriodicalId":7369,"journal":{"name":"Advances in Pharmacological and Pharmaceutical Sciences","volume":"2024 ","pages":"4971456"},"PeriodicalIF":2.1,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Compliance of Pharmaceutical Manufacturing Companies to Good Manufacturing Practices in Heating, Ventilation, and Air-Conditioning Systems: The Case of Local Ethiopian Firms.","authors":"Desta Tune Tibesso, Tesfaye Gabriel, Tamrat Balcha Balla, Anteneh Belete","doi":"10.1155/adpp/6109415","DOIUrl":"10.1155/adpp/6109415","url":null,"abstract":"<p><p><b>Background:</b> Good manufacturing practice (GMP) is a part of quality management that maintains product quality and manages it according to the criteria of fitness for use. The heating, ventilation, and air-conditioning (HVAC) system comprises the equipment, technology, and procedure that ensure product quality through maintaining heat, ventilation, and coolness of pharmaceutical manufacturing firms. The aim of the study was to evaluate the GMP compliance of HVAC systems and assess the opportunities and challenges of improving these systems in pharmaceutical manufacturing companies in Ethiopia. <b>Methods:</b> The study was conducted in eight local pharmaceutical manufacturing companies in Ethiopia from April 20 to August 30, 2021, by using a concurrent mixed-method approach to evaluate the implementation of GMP in HVAC systems. The pharmaceutical firms were directly observed by using a structured and standard observational checklist that was adopted from the WHO minimum GMP requirements. In order to understand the challenges and opportunities, face-to-face interviews with key informants using a purposive sampling technique were conducted. <b>Results:</b> The study findings revealed that the local pharmaceutical companies applied for 67.1% of the GMP requirements of the HVAC systems. The GMP implementation status in the basic quality features of HVAC systems of local pharmaceutical companies was 75% on premises, 70.67% in HVAC system design and maintenance practices, 56.25% in product protection, 61.25% in environmental protection, and 75% in cross-contamination prevention. The primary obstacles to implementing GMP in the HVAC systems were a shortage of skilled professionals, HVAC system spare parts, and foreign currency besides poor practice of HVAC system calibration. <b>Conclusion:</b> The study revealed that the local pharmaceutical manufacturing companies did not adhere to GMP standards in HVAC systems.</p>","PeriodicalId":7369,"journal":{"name":"Advances in Pharmacological and Pharmaceutical Sciences","volume":"2024 ","pages":"6109415"},"PeriodicalIF":2.1,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Update on the Potential of <i>Punica granatum</i> L. Traditional Uses and Pharmacological Uses: A Review.","authors":"Abdulrahman Mahmoud Dogara, Harmand A Hama, Dogan Ozdemir","doi":"10.1155/adpp/6523809","DOIUrl":"10.1155/adpp/6523809","url":null,"abstract":"<p><p>Since the dawn of civilization, humans have turned to plants as a reliable source of safe and efficient treatment for a wide variety of medical conditions. The medicinal value of <i>Punica granatum</i> has been recognized for some time. Inflammation, diabetes, parasitic infections, cancer, and many other diseases have all been treated with its components. This review provides a comprehensive overview of the current biological data (those from 2018 to 2023 are included in the preclinical studies while articles of clinical studies have no limit due to their scarcity) and explores the potential applications of <i>P. granatum</i> as a novel platform for treating various disease conditions. Electronic searches for scholarly articles were performed using Elsevier, Springer, Google Scholar, Taylor & Francis, PubMed, and Scopus. Research the following terms: \"<i>Punica granatum</i>,\" \"chemical composition,\" \"antioxidant,\" \"antibacterial,\" \"anti-diabetic,\" \"anticancer,\" and other relevant terms. It has been scientifically proven that the fruit peel exhibits antioxidant, anti-inflammatory, antimicrobial, antiparasitic, antidiabetic, hepatoprotective, nerve-recovery, antihypertensive, anti-asthma, wound healing, and anticancer activities. Based on both preclinical and clinical experimentation on <i>P. granatum</i>, there is considerable evidence that supports the use of <i>P. granatum</i> extract as therapeutic agent for different ailments. The review paved the ground to precursor evidence of <i>P. granatum</i> extract benefits with its antioxidant, anti-inflammatory, antimicrobial, and antidiabetic properties. Furthermore, clinical trials stand out as a substrate supporting these effects with the enhancements of ailments including post menstrual, menstrual pain, semen quality, knee joint arthritis, and cardiovascular-related diseases. Nonetheless, more controlled large-scale clinical trials are needed for all the conditions to determine the effectiveness and risk benefit profile of <i>P. granatum</i> extract for these diseases.</p>","PeriodicalId":7369,"journal":{"name":"Advances in Pharmacological and Pharmaceutical Sciences","volume":"2024 ","pages":"6523809"},"PeriodicalIF":2.1,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11625089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytotoxic Effect of <i>Trypanosoma cruzi</i> Calcineurin B Against Melanoma and Adenocarcinoma Cells In Vitro.","authors":"Mayela Serrano-Rodríguez, Jorge E Araya, Mauro Cortez, Patricio R Orrego","doi":"10.1155/adpp/5394494","DOIUrl":"10.1155/adpp/5394494","url":null,"abstract":"<p><p>Chagas disease caused by the obligate intracellular flagellate protozoan <i>Trypanozoma cruzi</i> infects about 6 million people. From the 1930s to the present, the antitumor capacity of <i>T. cruzi</i> has been studied; however, the identification of the responsible molecules for this effect remains undiscovered. Calcineurin, a calcium/calmodulin-dependent serine/threonine phosphatase, is a heterodimer consisting of a catalytic subunit (CaNA) and a regulatory subunit (CaNB). It has been described that <i>T. cruzi</i> CaN is involved in the cell invasion and proliferation of the parasite. Recently, extracellular human CaNB has been demonstrated to be capable of inhibiting tumor growth cells, conferring an antitumor effect; however, the extracellular role of <i>T. cruzi</i> CaNB (<i>Tc</i>CaNB) is still unknown. The objective of this work was to investigate the antitumor potential of <i>Tc</i>CaNB by interacting with membrane proteins and evaluating its effects on the viability, proliferation, and morphology of tumor cells in vitro. Additionally, the possible mechanism of action of <i>Tc</i>CaNB was explored. Murine melanoma (B16-F10), human cervical adenocarcinoma (HeLa), and African green monkey kidney epithelial (Vero) cell lines were employed for in vitro assays. Far Western blot and immunofluorescence were performed to assess the interaction of <i>Tc</i>CaNB with membrane proteins, and the effect of <i>Tc</i>CaNB on cell viability and proliferation was evaluated using the MTS assay and the CyQUANT NF assay, respectively. The effect of the caspase inhibitor Z-VAD-FMK on <i>Tc</i>CaNB-stimulated tumor cells was investigated to determine if <i>Tc</i>CaNB-induced cell death was associated with apoptosis. To assess cell cycle progression, <i>Tc</i>CaNB-treated cells were analyzed by flow cytometry. In this study, the results showed an interaction of <i>Tc</i>CaNB with cell membrane proteins in B16-F10 and HeLa tumor lines, indicating that <i>Tc</i>CaNB is capable of decreasing viability and proliferation of B16-F10 and HeLa cells, with no significant effect observed in Vero cells. Furthermore, morphological changes were observed in tumor cells treated with TcCaNB. DNA fragmentations and inhibition of caspases with Z-VAD-FMK partially counteracted the cytotoxic effects of <i>Tc</i>CaNB on tumor cells, suggesting that <i>Tc</i>CaNB-induced cell death might be associated with apoptosis. Additionally, <i>Tc</i>CaNB caused S phase cell cycle arrest in HeLa cells, with an increase in the sub-G1 population indicative of apoptosis, while no significant effects were observed in Vero cells.</p>","PeriodicalId":7369,"journal":{"name":"Advances in Pharmacological and Pharmaceutical Sciences","volume":"2024 ","pages":"5394494"},"PeriodicalIF":2.1,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11620811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The β₃-Adrenergic Receptor: Structure, Physiopathology of Disease, and Emerging Therapeutic Potential.","authors":"Julius T Dongdem, Axandrah E Etornam, Solomon Beletaa, Issah Alidu, Hassan Kotey, Cletus A Wezena","doi":"10.1155/2024/2005589","DOIUrl":"10.1155/2024/2005589","url":null,"abstract":"<p><p>The discovery and characterization of the signal cascades of the β-adrenergic receptors have made it possible to effectively target the receptors for drug development. β-Adrenergic receptors are a class A rhodopsin type of G protein-coupled receptors (GPCRs) that are stimulated mainly by catecholamines and therefore mediate diverse effects of the parasympathetic nervous system in eliciting \"fight or flight\" type responses. They are detectable in several human tissues where they control a plethora of physiological processes and therefore contribute to the pathogenesis of several disease conditions. Given the relevance of the β-adrenergic receptor as a molecular target for many pathological conditions, this comprehensive review aims at providing an in-depth exploration of the recent advancements in β₃-adrenergic receptor research. More importantly, we delve into the prospects of the β₃-adrenergic receptor as a therapeutic target across a variety of clinical domains.</p>","PeriodicalId":7369,"journal":{"name":"Advances in Pharmacological and Pharmaceutical Sciences","volume":"2024 ","pages":"2005589"},"PeriodicalIF":2.1,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11620816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibacterial and Antioxidant Activities, Toxicity, and Physicochemical Properties of <i>Crassocephalum montuosum</i> (S Moore) Milne-Redh and <i>Crassocephalum picridifolium</i> (DC) S Moore.","authors":"Bashige Chiribagula Valentin, Bakari Amuri Salvius, Lumbu Simbi Jean Baptiste","doi":"10.1155/adpp/9954073","DOIUrl":"10.1155/adpp/9954073","url":null,"abstract":"<p><p>In traditional Congolese medicine, the plants <i>Crassocephalum montuosum</i> (CrasMon) and <i>Crassocephalum picridifolium</i> (CrasPic) are used to treat bacterial gastroenteritis. In the present study, the antibacterial and antioxidant activities as well as the acute and subacute toxicity of organic extracts from the whole plant of the two investigated taxa were evaluated. Physicochemical parameters were also determined, and total phenolics, flavonoids, and tannins were investigated and assayed. The antibacterial and antioxidant activities of the plant extracts were evaluated using disc diffusion, tube macrodilution, and DPPH tests. Conversely, traditional solution reactions, gravimetric tests, and spectrophotometric tests were used to generate physicochemical profiles, identify secondary metabolite groups, and perform microdilution and DPPH tests to evaluate the antibacterial and antioxidant activities, respectively. OECD tests were adapted to assess the acute and subacute toxicity. All the extracts showed antibacterial activity against <i>E. coli</i> and <i>S. typhi</i> strains with the diameter zone of inhibition (DZI) ranging from 12 to 23 mm and the minimum inhibitory concentration (MIC): 15.625-125 μg·mL^-1. The methanolic extract of CrasPic showed the most pronounced activity with a DZI of 21-23 mm and MIC of 15.625-62.5 μg·mL^-1. All extracts showed high antioxidant activity with IC₅₀ (half maximal inhibitory concentration) ranging from 11.6 to 21.8 μg·mL^-1, with the methanolic extract of CrasMon showing the most pronounced activity. Both plants contain a variety of phytochemicals including coumarins, quinones, flavonoids, phenols, saponins, tannins, and terpenoids. The methanolic extract of CrasPic exhibits the highest content of total phenolics (300 mg·GAE·g^-1), flavonoids (56 mg·QE·g^-1), and tannins (155 mg·GAE·g^-1). These extracts have a median lethal dose (LD₅₀) > 5000 mg·kg^-1 and no signs of toxicity at 200 mg·kg^-1 after 30 days of oral administration to <i>Cavia porcellus</i>. The total ash content was determined to be 14.2% and 15.8% (on a dry weight basis), with the ash insoluble in hydrochloric acid exhibiting a range of 4.04%-5.03%. CrasMon and CrasPic have been demonstrated to exhibit a good antibacterial and antioxidant activities, at least in part, due to the presence of phenolic compounds. These activities may provide a rationale for their use in traditional Congolese medicine against gastroenteritis.</p>","PeriodicalId":7369,"journal":{"name":"Advances in Pharmacological and Pharmaceutical Sciences","volume":"2024 ","pages":"9954073"},"PeriodicalIF":2.1,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11620814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Octanoic Acid and Decanoic Acid Inhibit Tunicamycin-Induced ER Stress in Rat Aortic Smooth Muscle Cells.","authors":"Wanida Sukketsiri, Varomyalin Tipmanee, Panlekha Rungruang, Mayo Higashihara, Tomoko Sumi, Tatsuya Moriyama, Nobuhiro Zaima","doi":"10.1155/adpp/9076988","DOIUrl":"10.1155/adpp/9076988","url":null,"abstract":"<p><p>ER stress is a crucial factor in the progression of vascular cell diseases. Notably, octanoic acid (OA; C8:0) and decanoic acid (DA; C10:0), prominent components of medium-chain fatty acids (MCFAs), may provide potential health benefits. However, their effects on vascular smooth muscle cells (VSMCs) remain unknown. Given the link between ER stress and vascular cell pathological conditions, the primary goal of this research is to investigate the protective effects of OA and DA against ER stress induction in rat aortic smooth muscle cells (RASMCs). To achieve this objective, RASMCs were pretreated with OA and DA at concentrations of 250 and 500 μM for 24 h. Subsequently, the cells were exposed to 1 μg/mL of tunicamycin, an ER stress inducer, for an additional 24 h. Apoptosis was assessed using DAPI staining, while DCFH₂-DA probe was used to measure ROS levels. Furthermore, the gene expression of ER stress markers, such as <i>CHOP</i>, <i>GRP78</i>, <i>ATF4</i>, and <i>eIF2α</i>, as well as contractile markers like <i>αSMA</i> and <i>MYH11</i>, was assessed using real-time reverse transcription polymerase chain reaction. Moreover, the <i>α</i>SMA protein level was measured using immunocytochemistry techniques. The study revealed that OA and DA significantly mitigated cell death caused by tunicamycin, decreased ROS production, and inhibited the gene expression of ER stress markers (<i>CHOP</i>, <i>GRP78</i>, and <i>eIF2α</i>). Notably, OA and DA also inhibited the expression of contractile genes (<i>α-SMA</i> and <i>MYH11</i>) and reduced the number of <i>α</i>-SMA-positive cells in tunicamycin-treated RASMCs. These findings indicate that OA and DA offer protection against ER stress-stimulated cell death and ROS generation in VSMCs, thereby supporting their potential therapeutic applications for safeguarding these cells.</p>","PeriodicalId":7369,"journal":{"name":"Advances in Pharmacological and Pharmaceutical Sciences","volume":"2024 ","pages":"9076988"},"PeriodicalIF":2.1,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11614520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Combination of Sorafenib and PGV-1 Inhibits the Proliferation of Hepatocellular Carcinoma Through c-Myc Suppression in an Additive Manner: In Vitro Studies.","authors":"Dhania Novitasari, Ikuko Nakamae, Noriko Yoneda-Kato, Jun-Ya Kato, Yoshitaka Hippo, Yusuke Suenaga, Dyaningtyas Dewi Pamungkas Putri, Edy Meiyanto, Muthi' Ikawati","doi":"10.1155/adpp/4297953","DOIUrl":"10.1155/adpp/4297953","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is one of the most aggressive types of liver cancer, and it is frequently associated with upregulated c-Myc expression. Sorafenib (Sor) is commonly used to treat HCC, but many patients experienced mild to severe side effects due to prolonged Sor treatment during therapy. It has been known that Pentagamavunone-1 (PGV-1) exhibits a remarkable antiproliferative effect on several cancer cells, yet limited studies have reported its cellular activities in HCC. The current study aims to evaluate the anticancer effects of Sor in combination with PGV-1 on the progression of HCC proliferation. c-Myc expressing cells, JHH-7 and Huh-7, were used for this study, then Sor and PGV-1 were tested for their effect on the cellular physiology phenomena including cytotoxicity combination assay and colony formation assay, cell cycle profile and reactive oxygen species (ROS) level by flow cytometry, senescence induction by beta-galactosidase (SA-<i>β</i>-gal) assay, and migration inhibition by wound healing assay. The c-Myc expression was evaluated through Western blot. PGV-1 was more effective than Sor at inhibiting cell growth, and it showed greater selectivity for HCC over fibroblast cells. The combination of Sor with PGV-1 exhibited synergistic-additive cytotoxicity with an irreversible effect in HCC cell lines. The combination induced senescence similarly with Sor alone in JHH-7 cells, while PGV-1 enhanced the cellular senescence when combined with Sor in Huh-7 cells. Furthermore, the combination increased ROS level in the same way as PGV-1 did in HCC. The combination with PGV-1 acted better than Sor alone to inhibit JHH-7 cell migration. In addition, the combination treatment led to the suppression of c-Myc, particularly in JHH-7 cells. Taken together, combining Sor with PGV-1 promotes better efficacy than Sor alone to inhibit HCC cell proliferation, and further evaluation of the efficacy and safety of adding PGV-1 to Sor in HCC therapy is worthwhile as a potential combination treatment option.</p>","PeriodicalId":7369,"journal":{"name":"Advances in Pharmacological and Pharmaceutical Sciences","volume":"2024 ","pages":"4297953"},"PeriodicalIF":2.1,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11614502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}