{"title":"<i>In vitro</i> and <i>in vivo</i> assessment of indomethacin-induced genotoxicity: protection by curcumin.","authors":"Ehsan Zamani, Reza Alipour Klour, Amirreza Gholami Shekarsarayi, Foad Ghazizadeh, Mehdi Evazalipour","doi":"10.4103/RPS.RPS_100_23","DOIUrl":"10.4103/RPS.RPS_100_23","url":null,"abstract":"<p><strong>Background and purpose: </strong>Indomethacin is one of the most widely used non-steroidal anti-inflammatory drugs. This study aimed to investigate the protective effects of curcumin against indomethacin-induced genotoxicity.</p><p><strong>Experimental approach: </strong>For <i>in vitro</i> studies, human peripheral blood lymphocytes were obtained from a healthy volunteer and treated for 24 h as follows: vehicle control, indomethacin at 100 and 200 μΜ, indomethacin (100 μM and 200 μM) plus curcumin (27 μM). For <i>in vivo</i> experiments, mice received a single <i>i.p</i> dose of curcumin (100 mg/kg) and after 30 min genotoxicity induction was carried out by a single <i>i.p</i> injection of indomethacin at 10, 20, and 40 mg/kg. After 24 h, bone marrow cells were obtained from mice femurs. Genotoxicity was evaluated using a micronucleus assay. Oxidative damage was also inspected both <i>in vitro</i> and <i>in vivo</i>.</p><p><strong>Findings/results: </strong><i>In-vitro</i> studies indicated that co-treatment with curcumin caused a significant decrease in the average micronuclei percentage and MDA level, and a significant increase in GSH concentration compared to the groups treated only with indomethacin. <i>In-vivo</i> findings revealed that pretreatment with curcumin induced a significant increase in the average ratio of polychromatic erythrocyte/normochromic erythrocyte, GSH concentration and caused a significant decrease in the average percentage of micronuclei and MDA level, in comparison with the group treated only with indomethacin.</p><p><strong>Conclusion and implications: </strong>Curcumin attenuated indomethacin-induced genotoxicity both <i>in vitro</i> and <i>in vivo</i>. These effects might be partially exerted by decreasing oxidative stress. Further studies are required to elucidate the exact genoprotective mechanism of curcumin against indomethacin.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"19 2","pages":"178-187"},"PeriodicalIF":2.1,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11257203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734846","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}
Giti Sadeghi, Masoud Sadeghi Dinani, Mohammad Rabbani
{"title":"Effects of extracts and manna of <i>Echinops cephalotes</i> on impaired cognitive function induced by scopolamine in mice.","authors":"Giti Sadeghi, Masoud Sadeghi Dinani, Mohammad Rabbani","doi":"10.4103/RPS.RPS_27_23","DOIUrl":"10.4103/RPS.RPS_27_23","url":null,"abstract":"<p><strong>Background and purpose: </strong>Alzheimer's disease (AD) is a neurodegenerative disease specified by chronic and irreversible destruction of neurons. This study aimed to evaluate the effects of different extracts (aqueous, hydroalcoholic, hexane, and ethyl acetate) and manna of <i>Echinops cephalotes</i> (EC) on impaired cognitive function induced by scopolamine in mice. EC is shown to have anti-cholinesterase-butyrylcholinesterase activities.</p><p><strong>Experimental approach: </strong>In this study, aqueous and hydroalcoholic extracts, hexane and ethyl acetate fractions of EC (25, 50, 100 mg/kg, i.p.), and the manna (25, 50, 100 mg/kg, gavage) were administered for 14 days alongside scopolamine (0.7 mg/kg, i.p.). Rivastigmine (reference drug) was administered for 2 weeks i.p. Mice were tested for their memory function using two behavioral models, object recognition test (ORT) and passive avoidance test (PAT).</p><p><strong>Findings/results: </strong>Administration of scopolamine significantly impaired memory function in both behavioral models. In the PAT model, all extracts at 50 and 100 mg/kg significantly reversed the effect of memory destruction caused by scopolamine. At a lower dose of 25 mg/kg, however, none of the extracts were able to significantly change the step-through latency time. In the ORT model, however, administration of all extracts at 50 and 100 mg/kg, significantly increased the recognition index. Only the manna and the aqueous extract at 25 mg/kg were able to reverse scopolamine-induced memory impairment.</p><p><strong>Conclusions and implications: </strong>These results suggest that all forms of EC extracts improve memory impairment induced by scopolamine comparably to rivastigmine. Whether the effects are sustained over a longer period remains to be tested in future work.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"19 2","pages":"167-177"},"PeriodicalIF":2.1,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11257209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734850","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":"Molecular docking and synthesis of N-alkyl-isatin-3-imino aromatic amine derivatives and their antileishmanial and cytotoxic activities.","authors":"Farshid Hassanzadeh, Seyed Hossein Hejazi, Elham Jafari, Atefeh Mohammadi Fard, Hojjat Sadeghi-Aliabadi","doi":"10.4103/RPS.RPS_244_22","DOIUrl":"10.4103/RPS.RPS_244_22","url":null,"abstract":"<p><strong>Background and purpose: </strong>Isatin derivatives have excited attention due to their biological attractions, especially, anticancer properties. Isatin analogs such as semaxanib and sunitinib were exposed to tyrosine kinase inhibitory properties. N-substituted isatins were reported to show cytotoxic activity. On the other, the extension of impressive and cost-effective agents against leishmaniasis is necessary in third-world countries. The capability of isatin derivatives to create novel anticancer and anti-leishmanial compounds has been identified in medicinal chemistry research. The current study aimed to synthesize N-alkyl-isatin-3-imino aromatic amine compounds and evaluate their biological effects.</p><p><strong>Experimental approach: </strong>Synthesis started with the formation of 2-chloro-N-phenylacetamide derivatives by the reaction of aniline derivatives with chloroacetyl chloride. N-alkylation of isatin was performed in the presence of K2CO3 in N, N-dimethylformamide. Final products were prepared via the condensation of N-alkyl isatin derivatives with aromatic amines. Cell viability was checked out by using the MTT assay against cancer cells. Final compounds were screened for anti-leishmanial activity. The molecules were docked in the active sites of the epidermal growth factor receptor tyrosine kinase to define the possible interactions.</p><p><strong>Findings/results: </strong>Compounds 5c and 4d with IC<sub>50</sub> value of 50 μΜ showed cytotoxic activity on the MCF-7 cell line. Compound 5b presented anti-leishmanial activity against promastigote form after 48 h (IC<sub>50</sub>:59 μΜ) and 72 h (IC<sub>50</sub>: 41 μΜ) incubations. The highest docking score was -7.33 kcal/mol for compound 4d.</p><p><strong>Conclusions and implications: </strong>The nature of substitution in the N1 region of isatin seems to be able to influence the cytotoxic activity. Based on the obtained results of docking and cytotoxic tests, compound 4d seems to be a good compound for further investigations.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"19 2","pages":"238-250"},"PeriodicalIF":2.1,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11257207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734852","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}
Seyedeh Fatemeh Jafari, Maryam Keshavarzi, Amin MalikShah AbdulMajid, Fouad Saleih R Al-Suede, Muhammad Asif, Mohamed B Khadeer Ahamed, Md Shamsuddin Sultan Khan, Loiy Ahmed Elsir Hassan, Aman Shah Abdul Majid, Mohsen Naseri
{"title":"Evaluation of <i>in vitro</i> and <i>in vivo</i> anticancer activities of potassium koetjapate: a solubility improved formulation of koetjapic acid against human colon cancer.","authors":"Seyedeh Fatemeh Jafari, Maryam Keshavarzi, Amin MalikShah AbdulMajid, Fouad Saleih R Al-Suede, Muhammad Asif, Mohamed B Khadeer Ahamed, Md Shamsuddin Sultan Khan, Loiy Ahmed Elsir Hassan, Aman Shah Abdul Majid, Mohsen Naseri","doi":"10.4103/RPS.RPS_247_22","DOIUrl":"10.4103/RPS.RPS_247_22","url":null,"abstract":"<p><strong>Background and purpose: </strong>The previous work on koetjapic acid (KA) isolated from <i>Sandoricum koetjape</i> showed its efficacy towards colorectal cancer however KA has poor water solubility which poses the biggest hindrance to its efficacy. In the present paper, an attempt was made to study the anti-colon cancer efficacy of KA's potassium salt <i>i.e</i>. potassium koetjapate (KKA) applying <i>in vitro</i> and <i>in vivo</i> methods.</p><p><strong>Experimental approach: </strong>KKA was produced by a semi-synthetic method. A human apoptosis proteome profiler array was applied to determine the protein targets responsible for the stimulation of apoptosis. Three doses of KKA were studied in athymic nude mice models to examine the <i>in vivo</i> anti-tumorigenic ability of KKA.</p><p><strong>Findings/results: </strong>The results of this study demonstrated that KKA regulates the activities of various proteins. It downregulates the expression of several antiapoptotic proteins and negative regulators of apoptosis including HSP60, HSP90, Bcl-2, and IGF-1 in HCT 116 cells with consequent upregulation of TRAILR-1 and TRAILR-2, p27, CD40, caspase 3, and caspase 8 proteins. Additionally, KKA showed an <i>in vitro</i> antimetastatic effect against HCT 116 cells. These results are feasibly related to the down-regulation of Notch, Wnt, hypoxia, and MAPK/JNK and MAPK/ERK signalling pathways in HCT 116 cells besides the up-regulation of a transcription factor for cell cycle (pRb-E2F) pathways. In addition, KKA revealed potent inhibition of tumor growth.</p><p><strong>Conclusion and implications: </strong>In sum, the findings indicate that KKA can be a promising candidate as a chemotherapeutic agent against colorectal cancer.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"19 2","pages":"203-216"},"PeriodicalIF":2.1,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11257210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734851","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":"Determination of the anticancer activity of standardized extract of <i>Centella asiatica</i> (ECa 233) on cell growth and metastatic behavior in oral cancer cells.","authors":"Suwisit Manmuan, Sukannika Tubtimsri, Nattaya Chaothanaphat, Nipatha Issaro, Mayuree H Tantisira, Ponwit Manmuan","doi":"10.4103/RPS.RPS_81_23","DOIUrl":"10.4103/RPS.RPS_81_23","url":null,"abstract":"<p><strong>Background and purpose: </strong>The anticancer drugs used for oral cancer treatment present many disadvantages, such as low solubility, low permeability, and poor bioavailability. However, the anticancer activity of ECa 233 has not been widely studied. Therefore, the anticancer activity of ECa 233 was investigated in this study.</p><p><strong>Experimental approach: </strong>MTT assay was carried out to determine cell viability. Characterizations of cell apoptosis were monitored using DAPI and FDA staining and Hoechst 33258 and AO staining. Confirmation of the apoptosis-induced KON cells was done using annexin V-FITC staining, and ROS generation was determined by DCFDA staining. Cell death and the cell cycle arrest activity of ECa 233 were demonstrated by a flow cytometer. The anti-migration and anti-invasion properties of ECa 233 were examined. The anti-proliferative of ECa 233 was investigated. Cellular uptake of ECa 233 was measured by TEER values. The pharmacokinetics of ECa 233 were estimated using the pkCSM web server.</p><p><strong>Findings/results: </strong>ECa 233 decreased the KON cell viability. Morphological analysis showed the KON cells' loss of cell stability and structure, disorganized nucleus and cytoplasm, and induced cell death. ECa 233 acted as a cell cycle arrest in the G0/G1 phase and reduced the migration and invasion ability in KON cells. TEER values significantly increased in KON cells, which decreased cell colony and multicellular spheroid formations. The pharmacokinetic profiles of the main components are of interest for future usage.</p><p><strong>Conclusion and implication: </strong>ECa 233 can be used as an alternative therapy as well as a medicinal plant selected for sensitizing oral cancer cells to chemotherapy.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"19 2","pages":"121-147"},"PeriodicalIF":2.1,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11257205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734849","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 effect of redox bacteria on the programmed cell death-1 cancer immunotherapy.","authors":"Majid Nejati, Masoud Soheili, Mahmoud Salami, Mostafa Khedri","doi":"10.4103/RPS.RPS_28_23","DOIUrl":"10.4103/RPS.RPS_28_23","url":null,"abstract":"<p><strong>Background and purpose: </strong>Extracellular electron transferring (EET) or redox bacteria employ a shuttle of flavins to transfer electrons to the oxygen in the intestinal mucosa. Although clinical studies suggest that the gut microbiome modulates the efficiency of immune checkpoint therapy in patients with cancer, the modulation mechanisms have not been well-characterized yet.</p><p><strong>Experimental approach: </strong>In the present study, the oral gavage administration of <i>Shewanella oneidensis</i> MR-1 as a prototypic EET bacteria was assayed in a mouse model of lung cancer to determine the effect of EET bacterium on the efficacy of the programmed cell death protein 1 (PD1)-immune checkpoint therapy.</p><p><strong>Findings/results: </strong>It was indicated that <i>in vitro</i> EET from <i>S. oneidensis</i> was mediated by riboflavins that were supplied through extrinsic sources. Co-administration of <i>S. oneidensis</i> and anti-PD 1 antibodies represent better tumor remission compared to the single-administration of each one; however, no statistically significant change was observed in the tumor volume.</p><p><strong>Conclusion and implications: </strong>More detailed studies are needed to definitively confirm the therapeutic effects of electrogenic bacteria in patients with cancer. Given the findings of the present study, increasing flavin compounds or EET bacteria in the intestine may provide novel strategies for modulating cancer immunotherapy.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"19 2","pages":"228-237"},"PeriodicalIF":2.1,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11257211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734878","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 protective effect of Thai rice bran on N-acetyl-ρ-aminophen-induced hepatotoxicity in mice.","authors":"Pitchaporn Wanyo, Charinya So-In","doi":"10.4103/RPS.RPS_210_23","DOIUrl":"10.4103/RPS.RPS_210_23","url":null,"abstract":"<p><strong>Background and purpose: </strong>N-acetyl-ρ-aminophen (APAP) is a widely used medication with analgesic and antipyretic characteristics. High paracetamol doses can damage the liver. Thai-pigmented rice may treat numerous liver disorders due to its antioxidant, anti-inflammatory, and glutathione-restoring capabilities. This study aimed to evaluate the phenolic components in three Thai rice bran extracts and their antioxidant and hepatoprotective activities in an animal model.</p><p><strong>Experimental approach: </strong>Fifty male mice were randomly assigned to the control and APAP studies. Each study was divided into 5 groups (n = 5) treated with distilled water, Hom Mali, Hang-Ngok, and Hom Nil (HN) rice compared with N-acetylcysteine with/without 60 mg/kg/day of APAP orally once a day for two weeks. Blood and liver sampling were collected for analysis.</p><p><strong>Findings/results: </strong>HN rice bran exhibited higher contents of total phenolic, total flavonoid, total anthocyanin, ferric-reducing antioxidant, and 1,1-diphenyl-2-picrylhydrazyl radical scavenging activities than Hom Mali and Hang-Ngok. Anthocyanin was merely detected in HN. Following APAP administration, mice exhibited significant increases in hepatic enzymes including alanine aminotransferase (ALT) and aspartate aminotransferase (AST), pro-inflammatory cytokines (tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6)), and malondialdehyde (MDA), but lower levels of antioxidant enzymes and glutathione profiles. Amongst the three cultivars, HN rice was the only compound that decreased MDA, ALT, AST, TNF-α, and IL-6 while increasing antioxidant enzyme activity such as superoxide dismutase, catalase, and glutathione peroxidase that was very close to that of N-acetylcysteine groups.</p><p><strong>Conclusion and implications: </strong>Given the hepatoprotective and antioxidant properties, HN has the potential to be used as a health supplement.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"19 2","pages":"188-202"},"PeriodicalIF":2.1,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11257212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734879","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":"Carbon nanotubes induce cytotoxicity and apoptosis through increasing protein levels of Bax and ROS in mouse skin fibroblasts.","authors":"Zahra Nazeri, Vahid Zarezade, Mostafa Jamalan, Maryam Cheraghzadeh, Shirin Azizidoost, Alireza Kheirollah","doi":"10.4103/RPS.RPS_157_22","DOIUrl":"10.4103/RPS.RPS_157_22","url":null,"abstract":"<p><strong>Background and purpose: </strong>Carbon nanotubes (CNTs) are a significant discovery in nanotechnology, with widespread applications in modern technology. However, there are concerns about their potential toxicity, particularly in skin cells. This study aimed to investigate the mechanisms by which CNTs induced cytotoxicity and apoptosis in mouse skin fibroblasts.</p><p><strong>Experimental approach: </strong>The mice skin fibroblasts were isolated and exposed to two types of CNTs at various concentrations and then analyzed for changes in viability, reactive oxygen species (ROS) production, the levels of Bcl-2-associated X protein (Bax), and lactate production.</p><p><strong>Findings/results: </strong>The results demonstrated that CNTs reduced cell viability and increased ROS production in a dose-dependent manner. Additionally, the current study found that CNTs increased the protein levels of Bax, a pro-apoptotic protein, in mouse skin fibroblasts. Furthermore, it was observed a significant decrease in lactate production in cells exposed to CNTs.</p><p><strong>Conclusion and implications: </strong>The findings concluded that CNTs have the potential to be toxic substances for skin fibroblasts, which serve as the body's first line of defense. This is evidenced by their ability to increase the production of ROS and the protein levels of Bax, as well as reduce lactic acid levels. As lactic acid has been reported to have beneficial effects on skin collagen production, further studies are needed to fully understand the impact of carbon nanotube exposure on human skin health.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"19 2","pages":"148-156"},"PeriodicalIF":2.1,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11257208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734848","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}
Dedy Hermansyah, Desiree Anggia Paramita, Adi Muradi Muhar, Nur Dina Amalina
{"title":"<i>Curcuma longa</i> extract inhibits migration by reducing MMP-9 and Rac-1 expression in highly metastatic breast cancer cells.","authors":"Dedy Hermansyah, Desiree Anggia Paramita, Adi Muradi Muhar, Nur Dina Amalina","doi":"10.4103/RPS.RPS_46_23","DOIUrl":"10.4103/RPS.RPS_46_23","url":null,"abstract":"<p><strong>Background and purpose: </strong>Highly metastatic breast cancer is a population of cancer cells that has metastasized to other organs in the body leading to apoptosis resistance. It was reported that MDAMB-231 cells contain lower levels of reactive oxygen species associated with metastatic capability. <i>Curcuma longa</i> (CL) possesses cytotoxic effects in several cancer cells including metastatic breast cancer cells. This study aimed to investigate the effect of CL-inhibited cell migration in highly metastatic breast cancer MDAMB-231 cells.</p><p><strong>Experimental approach: </strong>CL was extracted under maceration with methanol. The cytotoxic effect on single and combination treatment of CL was assessed through the MTT assay. Migration analysis was evaluated using scratch wound healing assay, MMP-9 expression by gelatine zymography, Rac-1, and MMP-9 gene expression using Real-Time Quantitative Reverse transcription polymerase chain reaction (qRT-PCR). The apoptosis induction was analyzed through Bax gene expression and Bcl-2 protein expression.</p><p><strong>Findings/results: </strong>We found that CL inhibits the growth of MDAMB-231 cells, induces Bax gene expression, and suppresses Bcl-2 expression in a dose-dependent manner. Moreover, cancer cell migration was suppressed by the presence of CL. qRT-PCR and gelatine zymography assay showed that CL downregulates Rac-1 and MMP-9 gene expression.</p><p><strong>Conclusion and implications: </strong>CL could inhibit the growth and migration of highly metastatic breast cancer cells by reducing the Rac-1 gene expression and regulating apoptosis protein expression.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"19 2","pages":"157-166"},"PeriodicalIF":2.1,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11257204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141736324","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}
Ghaidafeh Akbari, Mohammad Reza Abasi, Maral Gharaghani, Sadegh Nouripoor, Nasrin Shakerinasab, Mahdokht Azizi, Marjan Salahi, Farzaneh Karimi, Mahdieh Eftekhari, Damoun Razmjoue, Amir Hossein Doustimotlagh
{"title":"Antioxidant and hepatoprotective activities of <i>Juniperus excelsa M. Bieb</i> against bile duct ligation-induced cholestasis.","authors":"Ghaidafeh Akbari, Mohammad Reza Abasi, Maral Gharaghani, Sadegh Nouripoor, Nasrin Shakerinasab, Mahdokht Azizi, Marjan Salahi, Farzaneh Karimi, Mahdieh Eftekhari, Damoun Razmjoue, Amir Hossein Doustimotlagh","doi":"10.4103/RPS.RPS_52_23","DOIUrl":"10.4103/RPS.RPS_52_23","url":null,"abstract":"<p><strong>Background and purpose: </strong>Cholestasis is caused by a malfunction of the biliary liver system. Oxidative stress plays an essential role in the progression of cholestasis. This study aimed to investigate the antioxidant and hepatoprotective effects of ethanolic extract of <i>Juniperus excelsa M. Bieb</i> (JE) fruits on hepatic impairment induced by bile duct ligation (BDL) in rats.</p><p><strong>Experimental approach: </strong>Forty male Wistar rats were randomly divided into 4 groups; sham control + vehicle (SC), BDL + vehicle (BDL), BDL + JE extract (BDL + JE), and SC + extract (SC + JE). One day after surgery, the animals were treated with vehicle or ethanolic extract of JE (500 mg/kg/day) for 7 days. Finally, the blood was taken for biochemical and oxidative stress analysis. Furthermore, the liver tissue of rats was removed for histological examination.</p><p><strong>Findings/results: </strong>Treatment with the extract of JE decreased the ALP level, whereas it enhanced total protein content compared to the BDL group. Also, JE increased the activity of SOD and GPx, as well as FRAP content compared to the BDL group; while it did not significantly affect the levels of MDA and inflammation markers. However, JE could not improve BDL-induced histopathological alterations in hepatic tissue.</p><p><strong>Conclusion and implication: </strong>This study demonstrated that JE may be useful as an adjuvant therapy by attenuating ALP activity, increasing serum total protein and FRAP content, as well as improving the antioxidant enzymes activity of SOD and GPx. However, further research is warranted to explore the other underlying mechanisms of action.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"19 2","pages":"217-227"},"PeriodicalIF":2.1,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11257206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734847","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}