Noor Cahaya, S. A. Kristina, Anna Wahyuni Widayanti, James A Green
Not only antipsychotics but additional interventions such as education for people with schizophrenia are also needed to support optimal therapy. Studies with educational interventions have been conducted and show varied outcomes. The systematic review aimed to summarize and evaluate the effectiveness of studies regarding educational interventions for people with schizophrenia. Two electronic databases (PubMed and Science Direct) were used to find studies with criteria that were educational interventions for people with schizophrenia and focused on outcome measures related to improving knowledge, medication adherence, and other outcomes as an effect of educational interventions, randomized or randomized controlled trial studies, published between 2012 and 2022. The manual search of referenced articles was also applied. A literature search was conducted using the terms ("people with schizophrenia" OR "patients with schizophrenia") AND ("education" OR "knowledge") AND ("medication adherence" OR "medication compliance" OR "medication persistence"). Of the 666 studies, seven were eligible. Some educational interventions are part of a therapy program, while others are full psychoeducational programs that target not only the patient but also the patient's family. There was only one study that used counseling supported by leaflets delivered by a pharmacist. Another intervention used face-to-face interviews and discussions supplemented by modules or booklets, or giving booklets to patients and then following up by phone. Only one of the seven studies was effective in increasing patient knowledge. The rest did not measure knowledge but assessed other parameters, i.e., stigma and insight, symptoms, social functioning, relapse rate, or quality of life as the effect of educational intervention. Three studies showed a significant difference in improvement in medication adherence between the intervention and control groups; two studies were not significant, and the rest were unmeasured. It can be concluded that educational intervention had a positive effect on PwS and their families’ knowledge, improved medication adherence, and other outcomes as an effect of the educational intervention.
{"title":"Effectiveness of Educational Interventions to Improve Knowledge and Medication Adherence for People with Schizophrenia: A Systematic Review","authors":"Noor Cahaya, S. A. Kristina, Anna Wahyuni Widayanti, James A Green","doi":"10.22146/ijp.4768","DOIUrl":"https://doi.org/10.22146/ijp.4768","url":null,"abstract":"Not only antipsychotics but additional interventions such as education for people with schizophrenia are also needed to support optimal therapy. Studies with educational interventions have been conducted and show varied outcomes. The systematic review aimed to summarize and evaluate the effectiveness of studies regarding educational interventions for people with schizophrenia. Two electronic databases (PubMed and Science Direct) were used to find studies with criteria that were educational interventions for people with schizophrenia and focused on outcome measures related to improving knowledge, medication adherence, and other outcomes as an effect of educational interventions, randomized or randomized controlled trial studies, published between 2012 and 2022. The manual search of referenced articles was also applied. A literature search was conducted using the terms (\"people with schizophrenia\" OR \"patients with schizophrenia\") AND (\"education\" OR \"knowledge\") AND (\"medication adherence\" OR \"medication compliance\" OR \"medication persistence\"). Of the 666 studies, seven were eligible. Some educational interventions are part of a therapy program, while others are full psychoeducational programs that target not only the patient but also the patient's family. There was only one study that used counseling supported by leaflets delivered by a pharmacist. Another intervention used face-to-face interviews and discussions supplemented by modules or booklets, or giving booklets to patients and then following up by phone. Only one of the seven studies was effective in increasing patient knowledge. The rest did not measure knowledge but assessed other parameters, i.e., stigma and insight, symptoms, social functioning, relapse rate, or quality of life as the effect of educational intervention. Three studies showed a significant difference in improvement in medication adherence between the intervention and control groups; two studies were not significant, and the rest were unmeasured. It can be concluded that educational intervention had a positive effect on PwS and their families’ knowledge, improved medication adherence, and other outcomes as an effect of the educational intervention.","PeriodicalId":13520,"journal":{"name":"INDONESIAN JOURNAL OF PHARMACY","volume":null,"pages":null},"PeriodicalIF":0.4,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138996205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The development of novel anticancer agents is essential in cancer prevention. One versatile group of compounds, known for their significant bioactivity and several of its derivatives that have been clinically approved, is the group of pyrazolines. This study aimed to synthesize 1-formyl-2-pyrazoline derivatives (pyrazolines 1-2) using chalcone 1-2, hydrazine hydrate, and formic acid via cyclo-condensation. The synthesized compounds were characterized using Fourier Transform Infrared (FTIR), Gas Chromatography-Mass Spectrometry (GC-MS), and Nuclear Magnetic Resonance (1H- and 13C-NMR) spectrometers. Pyrazolines 1-2 were found to be drug-like compounds, satisfying Lipinski’s Rule of Five and possessing favourable absorption, distribution, metabolism, and excretion (ADME) properties, including good gastrointestinal absorption, blood-brain barrier permeability, and no interaction with P-glycoprotein. Furthermore, they were inactive against several toxicity endpoints in a normal body condition, such as immunotoxicity, mutagenicity, and cytotoxicity. In vitro cytotoxic evaluation of the pyrazolines 1-2 against HeLa and MCF7 cancer cell lines demonstrated moderate activity, with IC50 values of 25.01 µM and 82.87 µM, respectively. Pyrazolines 1-2 also showed good selectivity with selectivity index (SI) values of 8.92 and 14.45. The molecular docking study on epidermal growth factor receptor tyrosine kinase (EGFR-TK) (PDB ID: 4HJO) revealed that pyrazolines 1-2 had a binding affinity of -7.9 and -8.0 kcal/mol, respectively. The compounds interacted with Lys721 residue through hydrogen bonds and hydrophobic interactions due to the presence of the pyrazoline ring and the formyl group in their structures. These findings suggest that pyrazolines 1-2 scaffold has the potential to be further studied as a lead compound for anticancer drug candidates.
{"title":"Study of 1-Formyl-2-Pyrazolines as Anticancer Drug Candidates","authors":"Artania Adnin Tri Suma, T. Wahyuningsih","doi":"10.22146/ijp.7188","DOIUrl":"https://doi.org/10.22146/ijp.7188","url":null,"abstract":"The development of novel anticancer agents is essential in cancer prevention. One versatile group of compounds, known for their significant bioactivity and several of its derivatives that have been clinically approved, is the group of pyrazolines. This study aimed to synthesize 1-formyl-2-pyrazoline derivatives (pyrazolines 1-2) using chalcone 1-2, hydrazine hydrate, and formic acid via cyclo-condensation. The synthesized compounds were characterized using Fourier Transform Infrared (FTIR), Gas Chromatography-Mass Spectrometry (GC-MS), and Nuclear Magnetic Resonance (1H- and 13C-NMR) spectrometers. Pyrazolines 1-2 were found to be drug-like compounds, satisfying Lipinski’s Rule of Five and possessing favourable absorption, distribution, metabolism, and excretion (ADME) properties, including good gastrointestinal absorption, blood-brain barrier permeability, and no interaction with P-glycoprotein. Furthermore, they were inactive against several toxicity endpoints in a normal body condition, such as immunotoxicity, mutagenicity, and cytotoxicity. In vitro cytotoxic evaluation of the pyrazolines 1-2 against HeLa and MCF7 cancer cell lines demonstrated moderate activity, with IC50 values of 25.01 µM and 82.87 µM, respectively. Pyrazolines 1-2 also showed good selectivity with selectivity index (SI) values of 8.92 and 14.45. The molecular docking study on epidermal growth factor receptor tyrosine kinase (EGFR-TK) (PDB ID: 4HJO) revealed that pyrazolines 1-2 had a binding affinity of -7.9 and -8.0 kcal/mol, respectively. The compounds interacted with Lys721 residue through hydrogen bonds and hydrophobic interactions due to the presence of the pyrazoline ring and the formyl group in their structures. These findings suggest that pyrazolines 1-2 scaffold has the potential to be further studied as a lead compound for anticancer drug candidates.","PeriodicalId":13520,"journal":{"name":"INDONESIAN JOURNAL OF PHARMACY","volume":null,"pages":null},"PeriodicalIF":0.4,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138999789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The adverse drug reaction reporting system or pharmacovigilance, as a part of post-marketing surveillance, is the responsibility of every country and national government. Therefore, optimization of knowledge and attitude regarding the system were very essential. This study aimed to examine the relationship between knowledge and attitude regarding pharmacovigilance among pharmacists working in public healthcare services in the rural area. This study was a cross-sectional analytical observational research involving 48 hospital and community pharmacists carried out from July to December 2021 at Bantul Regency, Yogyakarta, Indonesia. Descriptive statistics and frequency distribution analysis were conducted to obtain an overview of knowledge and attitude regarding pharmacovigilance system, while chi-square examined the relationship between them. The results showed that 60.4% of participants had good knowledge, and 52.1% had a positive attitude regarding the system. It was also confirmed that there was a relationship between knowledge and attitude with a p-value of 0.045. Therefore, there was a relationship between knowledge and attitude regarding pharmacovigilance among pharmacists working in rural public healthcare. Based on the results of this study, it was highly recommended for healthcare practitioners, especially pharmacists, to learn and practice pharmacovigilance in their respective practice.
{"title":"Knowledge and Attitude among Community Pharmacists regarding Pharmacovigilance – A Cross Sectional Survey","authors":"MT Ghozali, Intan Waskita Murni","doi":"10.22146/ijp.5814","DOIUrl":"https://doi.org/10.22146/ijp.5814","url":null,"abstract":"The adverse drug reaction reporting system or pharmacovigilance, as a part of post-marketing surveillance, is the responsibility of every country and national government. Therefore, optimization of knowledge and attitude regarding the system were very essential. This study aimed to examine the relationship between knowledge and attitude regarding pharmacovigilance among pharmacists working in public healthcare services in the rural area. This study was a cross-sectional analytical observational research involving 48 hospital and community pharmacists carried out from July to December 2021 at Bantul Regency, Yogyakarta, Indonesia. Descriptive statistics and frequency distribution analysis were conducted to obtain an overview of knowledge and attitude regarding pharmacovigilance system, while chi-square examined the relationship between them. The results showed that 60.4% of participants had good knowledge, and 52.1% had a positive attitude regarding the system. It was also confirmed that there was a relationship between knowledge and attitude with a p-value of 0.045. Therefore, there was a relationship between knowledge and attitude regarding pharmacovigilance among pharmacists working in rural public healthcare. Based on the results of this study, it was highly recommended for healthcare practitioners, especially pharmacists, to learn and practice pharmacovigilance in their respective practice.","PeriodicalId":13520,"journal":{"name":"INDONESIAN JOURNAL OF PHARMACY","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135547103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ni Made Dwi Sandhiutami, Rila Nurefrialia Nisa, Bantari Wisynu Kusuma Wardhani
Nephrotoxicity is the most common side effect of gentamicin, an aminoglycoside antibiotic group. It was mediated by oxidative stress mechanisms. Abelmoschus manihot L. leaves (AML) have antioxidant activity flavonoids. This study aims to determine the nephroprotective effect of AML in gentamicin-induced nephrotoxicity using mice models. It conducted an experimental design study in a pharmacology laboratory using mice models. It was conducted experimentally in 7 groups. There are normal, solvent, negative control, and four test groups (given an ethanolic extract of AML at doses of 50, 100, 200, and 400 mg/kgBW) which were administered orally for 7 days. Gentamicin 112 mg/kgBW was induced intraperitoneally on the 8th day. All mice were anesthetized on the 11th day to collect blood serum and renal organs for further examination. The data were analyzed using SPSS version 26 for One Way ANOVA test and followed by Duncan's post-hoc analysis test. The difference is considered significant if the p-value <0.05. Gentamicin successfully induced renal damage based on increasing creatinine and blood urea nitrogen (BUN) levels. This was by histopathology analysis which showed renal necrosis in the negative control group. Ethanolic extract of AML prevents nephrotoxicity due to gentamicin in a dose-dependent manner in creatinine level but not in BUN and histopathology. However, taken together all results showed that ethanol extract of AML has a nephroprotective effect in gentamicin-induced nephrotoxicity.
Keywords: Abelmoschus manihot L., gentamicin, nephroprotection, renal histopathology
{"title":"Nephroprotective effect of ethanol extract Abelmoschus manihot l. Leaves in gentamicin-induced mice","authors":"Ni Made Dwi Sandhiutami, Rila Nurefrialia Nisa, Bantari Wisynu Kusuma Wardhani","doi":"10.22146/ijp.8563","DOIUrl":"https://doi.org/10.22146/ijp.8563","url":null,"abstract":"Nephrotoxicity is the most common side effect of gentamicin, an aminoglycoside antibiotic group. It was mediated by oxidative stress mechanisms. Abelmoschus manihot L. leaves (AML) have antioxidant activity flavonoids. This study aims to determine the nephroprotective effect of AML in gentamicin-induced nephrotoxicity using mice models. It conducted an experimental design study in a pharmacology laboratory using mice models. It was conducted experimentally in 7 groups. There are normal, solvent, negative control, and four test groups (given an ethanolic extract of AML at doses of 50, 100, 200, and 400 mg/kgBW) which were administered orally for 7 days. Gentamicin 112 mg/kgBW was induced intraperitoneally on the 8th day. All mice were anesthetized on the 11th day to collect blood serum and renal organs for further examination. The data were analyzed using SPSS version 26 for One Way ANOVA test and followed by Duncan's post-hoc analysis test. The difference is considered significant if the p-value <0.05. Gentamicin successfully induced renal damage based on increasing creatinine and blood urea nitrogen (BUN) levels. This was by histopathology analysis which showed renal necrosis in the negative control group. Ethanolic extract of AML prevents nephrotoxicity due to gentamicin in a dose-dependent manner in creatinine level but not in BUN and histopathology. However, taken together all results showed that ethanol extract of AML has a nephroprotective effect in gentamicin-induced nephrotoxicity.
 Keywords: Abelmoschus manihot L., gentamicin, nephroprotection, renal histopathology","PeriodicalId":13520,"journal":{"name":"INDONESIAN JOURNAL OF PHARMACY","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135902728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cancer is a disease that is a global problem with a high prevalence and mortality rate. Indonesia has biodiversity with enormous potential as a source of medicinal ingredients. Phaleria macrocarpa (Scheff) Boerl) It is known to contain active metabolites, potentially an anticancer. Some endophytes are reported to be able to produce secondary metabolites similar to their parent plants. This study aimed to obtain endophytic fungi from P. macrocarpa capable of producing compounds with anticancer potential. Endophytes producing anticancer compounds were explored by screening endophytic fungi producing secondary metabolites from parts of the plant P. macrocarpa collected in the Yogyakarta area. The anticancer bioassay (MTT assay) was performed in vitro using cancer cells T47D, MCF7, HeLa, and normal Vero cells. Potential extracts were traced for their mechanism of cell cycle modulation and apoptosis using Flowcytometry. First, fungal identification was carried out on fungi producing potential cytotoxic extracts. Then the compound content was analyzed using LC-HRMS. The results from the six extracts obtained from fruit, leaf, and stem parts showed that the endophytic extract from the leaves (code PC-L2) had the best cytotoxicity compared to other endophytes and showed the best result on MCF-7 cells with an IC50 value of 110.66 µg/mL. The producing PC-L2 extract fungi are closely associated with Clonostachys wenpingii strain DUCC5606. This extract induced apoptosis but not through the mechanism of cell cycle modulation.
{"title":"Cytotoxicity Screening of Endophytic Fungi from Phaleria macrocarpa (Scheff) Boerl) Collected in Yogyakarta District","authors":"Puji Astuti, Ikra Agustina, Caterina Siskadewi Lay, Triana Hertiani","doi":"10.22146/ijp.7415","DOIUrl":"https://doi.org/10.22146/ijp.7415","url":null,"abstract":"Cancer is a disease that is a global problem with a high prevalence and mortality rate. Indonesia has biodiversity with enormous potential as a source of medicinal ingredients. Phaleria macrocarpa (Scheff) Boerl) It is known to contain active metabolites, potentially an anticancer. Some endophytes are reported to be able to produce secondary metabolites similar to their parent plants. This study aimed to obtain endophytic fungi from P. macrocarpa capable of producing compounds with anticancer potential. Endophytes producing anticancer compounds were explored by screening endophytic fungi producing secondary metabolites from parts of the plant P. macrocarpa collected in the Yogyakarta area. The anticancer bioassay (MTT assay) was performed in vitro using cancer cells T47D, MCF7, HeLa, and normal Vero cells. Potential extracts were traced for their mechanism of cell cycle modulation and apoptosis using Flowcytometry. First, fungal identification was carried out on fungi producing potential cytotoxic extracts. Then the compound content was analyzed using LC-HRMS. The results from the six extracts obtained from fruit, leaf, and stem parts showed that the endophytic extract from the leaves (code PC-L2) had the best cytotoxicity compared to other endophytes and showed the best result on MCF-7 cells with an IC50 value of 110.66 µg/mL. The producing PC-L2 extract fungi are closely associated with Clonostachys wenpingii strain DUCC5606. This extract induced apoptosis but not through the mechanism of cell cycle modulation.","PeriodicalId":13520,"journal":{"name":"INDONESIAN JOURNAL OF PHARMACY","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135721927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wenny Putri Nilamsari, Indri Yuliani Hamdani, Budi Suprapti, Mochammad Yusuf Assegaf, Mohammad Yogiarto, None Suharjono
In Indonesia warfarin remains the most widely oral anticoagulation prescribed. However, the time in therapeutic range remain low in Indonesia and also in some countries in throughout the world. This study aimed to analyse the challenges of optimal warfarin control from the perspectives of healthcare professionals, patients, health system, and to propose strategies to address these challenges. This research consists of two stages. The first stage was a prospective observational study aiming to analyse the challenges and the second stage of the research was focus group discussion to propose strategies to overcome the challenges. The result of this study showed that the average of TTR was 49.4 ± 32.1, where only 37.5% patients had TTR ≥ 65%. The average dosing consistency obtained was 62.33 ± 32.42%. With regard to INR monitoring interval, almost all patient who had supraterapeutic INR had their INR monitoring interval set to 1 month after the dose adjustment. There were also identified that only 43.8% patients classified as adherent and only 39.5 % patients had good knowledge of warfarin, indicating that the level of medication adherence and knowledge was not optimal. In this study, 14.6% of patients received other drugs that potentially interacted with warfarin that cause fluctuate INR. In conclusion, this study's results showed that there were multiple challenges for optimal warfarin control including barrier for dosing consistency, INR monitoring, patients’ adherence and knowledge, as well as drug interactions. However, there will be still room for improvement. The proposed strategy that likely will achieve optimal benefit was a holistic approach that combine multifaceted strategies to address each barrier.
{"title":"Challenges in Achieving Optimal Warfarin Anticoagulation Control: A Comprehensive Exploration and Proposed Holistic Approaches","authors":"Wenny Putri Nilamsari, Indri Yuliani Hamdani, Budi Suprapti, Mochammad Yusuf Assegaf, Mohammad Yogiarto, None Suharjono","doi":"10.22146/ijp.8169","DOIUrl":"https://doi.org/10.22146/ijp.8169","url":null,"abstract":"In Indonesia warfarin remains the most widely oral anticoagulation prescribed. However, the time in therapeutic range remain low in Indonesia and also in some countries in throughout the world. This study aimed to analyse the challenges of optimal warfarin control from the perspectives of healthcare professionals, patients, health system, and to propose strategies to address these challenges. This research consists of two stages. The first stage was a prospective observational study aiming to analyse the challenges and the second stage of the research was focus group discussion to propose strategies to overcome the challenges. The result of this study showed that the average of TTR was 49.4 ± 32.1, where only 37.5% patients had TTR ≥ 65%. The average dosing consistency obtained was 62.33 ± 32.42%. With regard to INR monitoring interval, almost all patient who had supraterapeutic INR had their INR monitoring interval set to 1 month after the dose adjustment. There were also identified that only 43.8% patients classified as adherent and only 39.5 % patients had good knowledge of warfarin, indicating that the level of medication adherence and knowledge was not optimal. In this study, 14.6% of patients received other drugs that potentially interacted with warfarin that cause fluctuate INR. In conclusion, this study's results showed that there were multiple challenges for optimal warfarin control including barrier for dosing consistency, INR monitoring, patients’ adherence and knowledge, as well as drug interactions. However, there will be still room for improvement. The proposed strategy that likely will achieve optimal benefit was a holistic approach that combine multifaceted strategies to address each barrier.","PeriodicalId":13520,"journal":{"name":"INDONESIAN JOURNAL OF PHARMACY","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136378843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Belal M Ali, Hanan S El-Abhar, Dalaal M Abdallah, Ghada Mohamed, Marwa Sharaky, Samia A. Shouman, Marwa Kamel
Androgen receptor (AR) and its splicing variant 7 (ARv7) play vital roles in the pathobiology of breast cancer (BC) but their role in the estrogen receptor-positive (ER+) type is controversial. Hence, we studied the influence of the blockers of AR (Enzalutamide) and ARv7 (EPI-001) on tumorigenesis processes using T47D, an ER+ BC cell line. Several techniques were employed: Sulphorhodamine assay (SRB), Flow cytometry, Immunostaining, Scratch wound healing assay, Enzyme Linked Immunosorbent assay (ELISA), and Western blot. Mechanistically, the drugs successfully arrested the cell cycle at S-phase and downregulated the protein expression of cyclins A, E, & C. Additionally, they inhibited the cell proliferation stimulator nuclear factor kappa B (NF-ĸB), whereas only EPI-001 reduced the cell regulatory marker c-Myc. They also opposed the endothelial-to-mesenchymal transition (EMT) process, by boosting the epithelial marker E-cadherin and reducing the protein expression of the mesenchymal marker fibronectin. Their anti-metastatic potential was evidenced by the hindrance of cell migration using the wound healing assay and further confirmed by the downregulation of metalloproteinase (MMP) 2 and 9 protein expression, and protein content of Rho kinase (ROCK)1 and 2. Besides, by downregulating the protein expression of vascular endothelial growth factor (VEGF) the drugs point to their anti-angiogenic aptitude. In conclusion, this in-vitro study highlights the importance of targeting AR/ARv7 using Enzalutamide and EPI-001 in decreasing proliferation cell markers, EMT, and metastasis in ER+ BC cells, findings that may have great impact in the treatment of ER+ BC.
雄激素受体(AR)及其剪接变体7 (ARv7)在乳腺癌(BC)的病理生物学中起着重要作用，但它们在雌激素受体阳性(ER+)型中的作用尚存争议。因此，我们利用ER+ BC细胞系T47D研究了AR阻断剂(Enzalutamide)和ARv7阻断剂(EPI-001)对肿瘤发生过程的影响。采用了几种技术:硫罗丹明试验(SRB)、流式细胞术、免疫染色、划伤愈合试验、酶联免疫吸附试验(ELISA)和Western blot。从机制上讲，这些药物成功地阻止了细胞周期在s期，并下调了细胞周期蛋白A、E和amp的蛋白表达;C.此外，它们抑制细胞增殖刺激因子核因子κ B (NF-ĸB)，而只有EPI-001降低细胞调节标志物c-Myc。他们还通过提高上皮标记物e -钙粘蛋白和降低间充质标记物纤维连接蛋白的表达来反对内皮到间充质转化(EMT)过程。通过伤口愈合实验证明了它们的抗转移潜力，并通过下调金属蛋白酶(MMP) 2和9蛋白表达以及Rho激酶(ROCK)1和2蛋白含量进一步证实了它们的抗转移潜力。此外，通过下调血管内皮生长因子(VEGF)的蛋白表达，表明药物具有抗血管生成的能力。总之，这项体外研究强调了使用Enzalutamide和EPI-001靶向AR/ARv7在降低ER+ BC细胞增殖细胞标志物、EMT和转移中的重要性，这些发现可能对ER+ BC的治疗有很大影响。
{"title":"The Enzalutamide and EPI-001 modulate cell proliferation and metastasis markers in T47D by targeting AR/ARV7","authors":"Belal M Ali, Hanan S El-Abhar, Dalaal M Abdallah, Ghada Mohamed, Marwa Sharaky, Samia A. Shouman, Marwa Kamel","doi":"10.22146/ijp.7416","DOIUrl":"https://doi.org/10.22146/ijp.7416","url":null,"abstract":"Androgen receptor (AR) and its splicing variant 7 (ARv7) play vital roles in the pathobiology of breast cancer (BC) but their role in the estrogen receptor-positive (ER+) type is controversial. Hence, we studied the influence of the blockers of AR (Enzalutamide) and ARv7 (EPI-001) on tumorigenesis processes using T47D, an ER+ BC cell line. Several techniques were employed: Sulphorhodamine assay (SRB), Flow cytometry, Immunostaining, Scratch wound healing assay, Enzyme Linked Immunosorbent assay (ELISA), and Western blot. Mechanistically, the drugs successfully arrested the cell cycle at S-phase and downregulated the protein expression of cyclins A, E, & C. Additionally, they inhibited the cell proliferation stimulator nuclear factor kappa B (NF-ĸB), whereas only EPI-001 reduced the cell regulatory marker c-Myc. They also opposed the endothelial-to-mesenchymal transition (EMT) process, by boosting the epithelial marker E-cadherin and reducing the protein expression of the mesenchymal marker fibronectin. Their anti-metastatic potential was evidenced by the hindrance of cell migration using the wound healing assay and further confirmed by the downregulation of metalloproteinase (MMP) 2 and 9 protein expression, and protein content of Rho kinase (ROCK)1 and 2. Besides, by downregulating the protein expression of vascular endothelial growth factor (VEGF) the drugs point to their anti-angiogenic aptitude. In conclusion, this in-vitro study highlights the importance of targeting AR/ARv7 using Enzalutamide and EPI-001 in decreasing proliferation cell markers, EMT, and metastasis in ER+ BC cells, findings that may have great impact in the treatment of ER+ BC.","PeriodicalId":13520,"journal":{"name":"INDONESIAN JOURNAL OF PHARMACY","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135109426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
None Agus Saputra, None Ietje Wientarsih, None Mohamad Rafi, None Lina Noviyanti Sutardi, None Silmi Mariya
L. amara is a medicinal plant used as an aphrodisiac. Several studies show it has a compound with biological activities such as inhibition of cell proliferation, one of the mechanisms leading to anticancer activities. This study aimed to profile the metabolites and predict activity against two breast cancer receptors (ERα (3ERT) and HER2 (3PPO)) with an in silico approach. Metabolite profiling of water and 80% ethanol extract was analyzed by UHPLC-Q-Orbitrap-HRMS. Also, we performed a radical scavenging activity by 1,1-diphenyl-2-picrylhydrazyl (DPPH). Putative identification of metabolite in L. amara showed the 46 metabolites (4 unknown) were identified and predominantly as quinoline alkaloids. Some of the compounds from glycosides and phenol groups were also identified. From the antioxidant capacity test results, the 80% ethanol extract had a higher radical scavenging capacity than the aqueous extract. Based on the molecular docking results, the highest affinity for the ERα receptor was found in the tested compound tetrahydropapaveroline and exceeded the native 4-OHT ligand. For the HER2 receptor, graveolinine has the highest affinity but is still below the native lapatinib ligand. Ligand interactions with the amino acids Leu 387 and Glu 419 on the active site of the ERα receptor and Phe1004 on the HER2 receptor are thought to play an important role in increasing the energy affinity. Overall, all compounds showed higher affinity for HER2 receptors than ERα. Alkaloids demonstrated anticancer activity. Further research should be conducted to determine the in vitro activity of these compounds on breast cancer cells.
{"title":"LC-HRMS Metabolite Profiling of Lunasia amara Stem Bark and In Silico Study in Breast Cancer Receptors","authors":"None Agus Saputra, None Ietje Wientarsih, None Mohamad Rafi, None Lina Noviyanti Sutardi, None Silmi Mariya","doi":"10.22146/ijp.6938","DOIUrl":"https://doi.org/10.22146/ijp.6938","url":null,"abstract":"L. amara is a medicinal plant used as an aphrodisiac. Several studies show it has a compound with biological activities such as inhibition of cell proliferation, one of the mechanisms leading to anticancer activities. This study aimed to profile the metabolites and predict activity against two breast cancer receptors (ERα (3ERT) and HER2 (3PPO)) with an in silico approach. Metabolite profiling of water and 80% ethanol extract was analyzed by UHPLC-Q-Orbitrap-HRMS. Also, we performed a radical scavenging activity by 1,1-diphenyl-2-picrylhydrazyl (DPPH). Putative identification of metabolite in L. amara showed the 46 metabolites (4 unknown) were identified and predominantly as quinoline alkaloids. Some of the compounds from glycosides and phenol groups were also identified. From the antioxidant capacity test results, the 80% ethanol extract had a higher radical scavenging capacity than the aqueous extract. Based on the molecular docking results, the highest affinity for the ERα receptor was found in the tested compound tetrahydropapaveroline and exceeded the native 4-OHT ligand. For the HER2 receptor, graveolinine has the highest affinity but is still below the native lapatinib ligand. Ligand interactions with the amino acids Leu 387 and Glu 419 on the active site of the ERα receptor and Phe1004 on the HER2 receptor are thought to play an important role in increasing the energy affinity. Overall, all compounds showed higher affinity for HER2 receptors than ERα. Alkaloids demonstrated anticancer activity. Further research should be conducted to determine the in vitro activity of these compounds on breast cancer cells.","PeriodicalId":13520,"journal":{"name":"INDONESIAN JOURNAL OF PHARMACY","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134973090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
An increasing percentage of people have or are at risk to develop the non-alcoholic fatty liver disease (NAFLD) worldwide. Fibrosis has also been identified as the most important predictor of prognosis in patients with NAFLD. Ciplukan (Physalis angulata Linn.) was reported to have antifibrotic potency in CCl4-induced liver fibrotic rats. This study was conducted to evaluate the antifibrotic effect of ciplukan extract through repairing the liver function, anti-inflammatory, and lowering cholesterol. The liver fibrosis model using 20% margarine was injected subcutaneously 8 times with a frequency of twice a week for 4 weeks in 35 male and 35 female Wistar strains which were divided into 7 groups. Furthermore, the rats were given Ciplukan extract (CPL) orally starting the 6th week of treatment with 2 different doses, namely 13.5 mg (CPL-1) and 27 mg (CPL-2) every day for 4 weeks. The histopathological changes of liver fibrosis was analyzed using Haematoxylin Eosin (HE) staining. Determination of serum IL-6 and TGF-β1 levels was carried out by the ELISA method. ALT and cholesterol levels were tested using a diagnostic kit. Single and multiple doses of ciplukan extract with or without standard therapy (Vitamin E) can reduce fibrotic scores up to 1.30±0.95 (p=0.001), TGF-β1 levels up to 24.20±2.02 ng/mL (p = 0.000), IL-6 levels up to 1.68±0.52 pg/mL (p=0.156), ALT levels up to 104.57±2.02 U/mL (p=0.001), and cholesterol levels up to 81, 07±2.02 mg/dL (p=0.000). Ciplukan herb ethanol extract was proven to have liver antifibrotic activity, which means it has potential as a liver fibrotic drug. The liver antifibrotic effect of Ciplukan herb was shown by a histopathological decrease in liver fibrosis scores accompanied by a decrease in TGF-β1, IL-6, ALT, and cholesterol levels.
Keywords: Physalis angulata Linn (Ciplukan), liver fibrosis, NAFLD, ALT, Cholesterol, IL-6
{"title":"Ciplukan (Physalis Angulata Linn.) Extract Compounds Potential on High-Fat Diet Induced Nonalcoholic Fatty Liver Disease (NAFLD) for Liver Anti-Fibrotic Drug Development","authors":"Enny Rohmawaty, Sumartini Dewi, Aziiz Mardanarian Rosdianto, Hermin Aminah Usman, Ade Zuhrotun, Rini Hendriani, Yoga Windhu Wardhana, Savira Ekawardhani, Hesti Lina Wiraswati, Andri Reza Rahmadi, Nenny Agustanti, M. Begawan Bestari","doi":"10.22146/ijp.6259","DOIUrl":"https://doi.org/10.22146/ijp.6259","url":null,"abstract":"An increasing percentage of people have or are at risk to develop the non-alcoholic fatty liver disease (NAFLD) worldwide. Fibrosis has also been identified as the most important predictor of prognosis in patients with NAFLD. Ciplukan (Physalis angulata Linn.) was reported to have antifibrotic potency in CCl4-induced liver fibrotic rats. This study was conducted to evaluate the antifibrotic effect of ciplukan extract through repairing the liver function, anti-inflammatory, and lowering cholesterol. The liver fibrosis model using 20% margarine was injected subcutaneously 8 times with a frequency of twice a week for 4 weeks in 35 male and 35 female Wistar strains which were divided into 7 groups. Furthermore, the rats were given Ciplukan extract (CPL) orally starting the 6th week of treatment with 2 different doses, namely 13.5 mg (CPL-1) and 27 mg (CPL-2) every day for 4 weeks. The histopathological changes of liver fibrosis was analyzed using Haematoxylin Eosin (HE) staining. Determination of serum IL-6 and TGF-β1 levels was carried out by the ELISA method. ALT and cholesterol levels were tested using a diagnostic kit. Single and multiple doses of ciplukan extract with or without standard therapy (Vitamin E) can reduce fibrotic scores up to 1.30±0.95 (p=0.001), TGF-β1 levels up to 24.20±2.02 ng/mL (p = 0.000), IL-6 levels up to 1.68±0.52 pg/mL (p=0.156), ALT levels up to 104.57±2.02 U/mL (p=0.001), and cholesterol levels up to 81, 07±2.02 mg/dL (p=0.000). Ciplukan herb ethanol extract was proven to have liver antifibrotic activity, which means it has potential as a liver fibrotic drug. The liver antifibrotic effect of Ciplukan herb was shown by a histopathological decrease in liver fibrosis scores accompanied by a decrease in TGF-β1, IL-6, ALT, and cholesterol levels.
 Keywords: Physalis angulata Linn (Ciplukan), liver fibrosis, NAFLD, ALT, Cholesterol, IL-6","PeriodicalId":13520,"journal":{"name":"INDONESIAN JOURNAL OF PHARMACY","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136027142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wadah Osman, Mohamed A. Maaz, Amna Ali, None Eltayeb Fadul, None Ahmed H. Arbab, None Mosab Yahya Al-Nour, None Ahmed Ashour, None Asmaa E. Sherif, None Hamada S. Abulkhair, Sabrin R.M Ibrahim, None Kholoud F. Ghazawi, None Gamal A. Mohamed, None Mona S. Mohamed
Antioxidants and acetylcholinesterase inhibitors play a key role in the prevention and management of degenerative disorders including Alzheimer’s disease in particular. Identifying new anticholinesterases from natural sources may contribute to combating this class of diseases. The present study aimed to evaluate the potential anti-Alzheimer’s activity of Geigeria alata (DC), a plant used in Sudanese folkloric medicine. Accordingly, the whole DC plant extract including twenty phytoconstituents of phenolic, flavonoid, and tannin types was evaluated in vitro as antioxidants and acetylcholinesterase inhibitors. As well, their pharmacokinetics, drug likeliness, and toxicity profiles were assessed. Additionally, the virtual binding of the plant’s phytoconstituents with the cholinesterase target was investigated by docking against two AChE X-ray crystallographic structures. The best effective DPPH radical scavenging activity was demonstrated by both ethyl acetate and n-butanol fractions with percentages of inhibition of 91 ± 0.02% and 90 ± 0.02% (IC50 22 ± 0.01 and 66 ± 0.02 µg/mL), respectively. The ethyl acetate fraction showed statistically significant, and the highest AChE inhibitory activity (78% inhibition, IC50 0.246 ± 0.02 mg/mL). Furthermore, the ethyl acetate fraction exhibited the highest total phenolic, flavonoid, and tannin values. Among identified compounds, quercetin and hispidulin showed promising in silico anti-AChE activity and hence merit further studies for the isolation and characterization of these active constituents.
{"title":"Geigeria alata- a potential source for anti-Alzheimer’s constituents: In vitro and computational investigations","authors":"Wadah Osman, Mohamed A. Maaz, Amna Ali, None Eltayeb Fadul, None Ahmed H. Arbab, None Mosab Yahya Al-Nour, None Ahmed Ashour, None Asmaa E. Sherif, None Hamada S. Abulkhair, Sabrin R.M Ibrahim, None Kholoud F. Ghazawi, None Gamal A. Mohamed, None Mona S. Mohamed","doi":"10.22146/ijp.7967","DOIUrl":"https://doi.org/10.22146/ijp.7967","url":null,"abstract":"Antioxidants and acetylcholinesterase inhibitors play a key role in the prevention and management of degenerative disorders including Alzheimer’s disease in particular. Identifying new anticholinesterases from natural sources may contribute to combating this class of diseases. The present study aimed to evaluate the potential anti-Alzheimer’s activity of Geigeria alata (DC), a plant used in Sudanese folkloric medicine. Accordingly, the whole DC plant extract including twenty phytoconstituents of phenolic, flavonoid, and tannin types was evaluated in vitro as antioxidants and acetylcholinesterase inhibitors. As well, their pharmacokinetics, drug likeliness, and toxicity profiles were assessed. Additionally, the virtual binding of the plant’s phytoconstituents with the cholinesterase target was investigated by docking against two AChE X-ray crystallographic structures. The best effective DPPH radical scavenging activity was demonstrated by both ethyl acetate and n-butanol fractions with percentages of inhibition of 91 ± 0.02% and 90 ± 0.02% (IC50 22 ± 0.01 and 66 ± 0.02 µg/mL), respectively. The ethyl acetate fraction showed statistically significant, and the highest AChE inhibitory activity (78% inhibition, IC50 0.246 ± 0.02 mg/mL). Furthermore, the ethyl acetate fraction exhibited the highest total phenolic, flavonoid, and tannin values. Among identified compounds, quercetin and hispidulin showed promising in silico anti-AChE activity and hence merit further studies for the isolation and characterization of these active constituents.
","PeriodicalId":13520,"journal":{"name":"INDONESIAN JOURNAL OF PHARMACY","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136027339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：