Muhammad Novrizal Abdi Sahid, Masaki Mogi, Kazutaka Maeyama
Objective: Traditional medicine is often used to relief pain, but its use is frequently not supported by appropriate scientific information. This study aims to investigate the histamine release suppression of Sonchus arvensis (SA) and Curcuma mangga (CM).
Materials and methods: Rat peritoneal mast cells (RPMCs) and Mas-related GPCR-X2(MRGPRX2)-transfected RBL-2H3 cells were activated by 50 μg/ml of compound 48/80. Water suspension of SA or CM (0.1-30 mg/ml) was used to inhibit cell activation by compound 48/80. The level of mast cell activation was determined by measuring histamine release concentration using HPLC-fluorometry.
Results: At a concentration of 10 mg/ml, CM resulted in 22.60±5.86% in a spontaneous histamine release from RPMCs. The net histamine release after compound 48/80 stimulation in RPMC was 67.19±1.31%. CM at 3 mg/ml suppressed histamine release to 8.45±2.53%. In MRGPRX2-transfected RBL-2H3 cells stimulated with compound 48/80, CM at concentrations of 3 and 10 mg/mL suppressed histamine release to 22.85±0.64% and 4.20±1.60%, respectively. SA at 30 mg/ml induced a spontaneous histamine release of 56.76±4.03%, compared to 5.65±2.61% in the control group. The administration of 3 mg/ml of SA to compound 48/80-stimulated RPMCs resulted in a net histamine release of 6.12±0.46%. In MRGPRX2-transfected RBL-2H3 cells activated by compound 48/80, the net release was 35.11±3.10%. SA at 10 mg/ml suppressed histamine release to 4.88±1.42%.
Conclusion: SA and CM water suspension suppressed compound 48/80-induced histamine release.
{"title":"Inhibition of mast cell activation via MRGPRX2 receptor by <i>Curcuma mangga</i> and <i>Sonchus arvensis</i> water suspensions: An <i>in vitro</i> study.","authors":"Muhammad Novrizal Abdi Sahid, Masaki Mogi, Kazutaka Maeyama","doi":"10.22038/ajp.2024.25199","DOIUrl":"10.22038/ajp.2024.25199","url":null,"abstract":"<p><strong>Objective: </strong>Traditional medicine is often used to relief pain, but its use is frequently not supported by appropriate scientific information. This study aims to investigate the histamine release suppression of <i>Sonchus arvensis</i> (SA) and <i>Curcuma mangga</i> (CM).</p><p><strong>Materials and methods: </strong>Rat peritoneal mast cells (RPMCs) and <i>Mas-related GPCR-X2(MRGPRX2)</i>-transfected RBL-2H3 cells were activated by 50 μg/ml of compound 48/80. Water suspension of SA or CM (0.1-30 mg/ml) was used to inhibit cell activation by compound 48/80. The level of mast cell activation was determined by measuring histamine release concentration using HPLC-fluorometry.</p><p><strong>Results: </strong>At a concentration of 10 mg/ml, CM resulted in 22.60±5.86% in a spontaneous histamine release from RPMCs. The net histamine release after compound 48/80 stimulation in RPMC was 67.19±1.31%. CM at 3 mg/ml suppressed histamine release to 8.45±2.53%. In <i>MRGPRX2</i>-transfected RBL-2H3 cells stimulated with compound 48/80, CM at concentrations of 3 and 10 mg/mL suppressed histamine release to 22.85±0.64% and 4.20±1.60%, respectively. SA at 30 mg/ml induced a spontaneous histamine release of 56.76±4.03%, compared to 5.65±2.61% in the control group. The administration of 3 mg/ml of SA to compound 48/80-stimulated RPMCs resulted in a net histamine release of 6.12±0.46%. In <i>MRGPRX2</i>-transfected RBL-2H3 cells activated by compound 48/80, the net release was 35.11±3.10%. SA at 10 mg/ml suppressed histamine release to 4.88±1.42%.</p><p><strong>Conclusion: </strong>SA and CM water suspension suppressed compound 48/80-induced histamine release.</p>","PeriodicalId":8677,"journal":{"name":"Avicenna Journal of Phytomedicine","volume":"15 5","pages":"1376-1384"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12441196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145084806","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}
Objective: This study aimed to evaluate Glasthma, a Persian medicine herbal formulation for its efficacy and safety in managing asthma symptoms and modulating intestinal permeability.
Materials and methods: Forty randomly assigned asthma patients received Glasthma syrup (n=20) or a placebo (n=20) twice daily for 4 weeks. Respiratory symptoms, pulmonary function tests, and 5-hour urine lactulose to mannitol ratio were assessed at baseline and after 4 weeks.
Results: Glasthma group exhibited significant improvements in clinical and paraclinical scores, including asthma control test (p<0.001), asthma control questionnaire 7 (p<0.007), Forced Expiratory Volume in the First Second (p<0.001), and Maximal Mid-Expiratory Flow 25-75 (p<0.002) compared to the placebo group. Lactulose and mannitol levels significantly decreased in the Glasthma group (p<0.028 and p<0.0000, respectively), with no significant changes in the ratio. No serious adverse effects were observed.
Conclusion: These findings suggest that Glasthma formulation may effectively improve asthma symptoms and regulate the gut-lung axis.
{"title":"Effect of a Persian medicine formula, Glasthma, on lung function and intestinal permeability in Asthma: A triple-blind randomized controlled trial.","authors":"Ali Reza Derakhshan, Majid Mirsadraee, Amirhashem Asnaashari, Roshanak Salari, Majid Khadem-Rezaiyan, Shahin Saeidinejat, Shima Jalali, Shabnam Jalali, Shadi Gaffari","doi":"10.22038/ajp.2025.25579","DOIUrl":"10.22038/ajp.2025.25579","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to evaluate Glasthma, a Persian medicine herbal formulation for its efficacy and safety in managing asthma symptoms and modulating intestinal permeability.</p><p><strong>Materials and methods: </strong>Forty randomly assigned asthma patients received Glasthma syrup (n=20) or a placebo (n=20) twice daily for 4 weeks. Respiratory symptoms, pulmonary function tests, and 5-hour urine lactulose to mannitol ratio were assessed at baseline and after 4 weeks.</p><p><strong>Results: </strong>Glasthma group exhibited significant improvements in clinical and paraclinical scores, including asthma control test (p<0.001), asthma control questionnaire 7 (p<0.007), Forced Expiratory Volume in the First Second (p<0.001), and Maximal Mid-Expiratory Flow 25-75 (p<0.002) compared to the placebo group. Lactulose and mannitol levels significantly decreased in the Glasthma group (p<0.028 and p<0.0000, respectively), with no significant changes in the ratio. No serious adverse effects were observed.</p><p><strong>Conclusion: </strong>These findings suggest that Glasthma formulation may effectively improve asthma symptoms and regulate the gut-lung axis.</p>","PeriodicalId":8677,"journal":{"name":"Avicenna Journal of Phytomedicine","volume":"15 5","pages":"1424-1437"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12441199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085017","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}
Hesamodin Bagheripoor, Mahdieh Mondanizadeh, Mehdi Sadegh
Objective: Carvacrol has anti-inflammatory effects. According to the links between inflammatory processes and seizures, this study was designed to investigate the potential effect of carvacrol in reducing seizure severity and involvement of hippocampal pro- and anti-inflammatory cytokines.
Materials and methods: This research was conducted on 42 adult male Wistar rats. Animals were randomly divided into seven groups (n=6). Seizures were induced by PTZ (Pentylenetetrazol) injection (80 mg/kg). LPS (lippolysaccharide) was injected (400 μg/kg) 4 hr before PTZ. Carvacrol (100 mg/kg) was injected immediately after LPS. All injections were intraperitoneal (i.p.). Experimental groups were as follows: 1. Control (Cnt) 2. Carvacrol (Cav); 3. LPS; 4. PTZ, 5. PTZ+LPS; 6. PTZ+Cav; 7. PTZ+LPS+Cav. Seizures were observed for 30 min after the PTZ injection and the occurrence of behavioral stages of seizures was recorded. Following the behavioral study, hippocampal samples were collected for gene expression evaluation using the Real Time-PCR technique to assess IL (interleukin)-1, IL-6, IL-4 and TNF (tumor necrosis factor)-α gene expression.
Results: The current study showed that receiving LPS exacerbated seizures in the studied groups. Carvacrol reduced the severity of seizures in the LPS-receiving groups. In the gene expression study, receiving LPS increased the expression of cytokines TNF-α and IL-1 in the hippocampal tissue. Carvacrol significantly decreased gene expression of TNF-α and IL-1.No significant changes were detected for IL-6, IL-4 gene expression.
Conclusion: There could be a relationship between carvacrol ability to modulate the proconvulsive effects of LPS and its ability to decrease the gene expression of inflammatory cytokines.
{"title":"Carvacrol alleviates the proconvulsive effects of lipopolysaccharide (LPS) and reduces the gene expression of proinflammatory cytokines <i>interleukin-1</i> and <i>tumor necrosis factor-α</i>.","authors":"Hesamodin Bagheripoor, Mahdieh Mondanizadeh, Mehdi Sadegh","doi":"10.22038/ajp.2025.25518","DOIUrl":"10.22038/ajp.2025.25518","url":null,"abstract":"<p><strong>Objective: </strong>Carvacrol has anti-inflammatory effects. According to the links between inflammatory processes and seizures, this study was designed to investigate the potential effect of carvacrol in reducing seizure severity and involvement of hippocampal pro- and anti-inflammatory cytokines.</p><p><strong>Materials and methods: </strong>This research was conducted on 42 adult male Wistar rats. Animals were randomly divided into seven groups (n=6). Seizures were induced by PTZ (Pentylenetetrazol) injection (80 mg/kg). LPS (lippolysaccharide) was injected (400 μg/kg) 4 hr before PTZ. Carvacrol (100 mg/kg) was injected immediately after LPS. All injections were intraperitoneal (i.p.). Experimental groups were as follows: 1. Control (Cnt) 2. Carvacrol (Cav); 3. LPS; 4. PTZ, 5. PTZ+LPS; 6. PTZ+Cav; 7. PTZ+LPS+Cav. Seizures were observed for 30 min after the PTZ injection and the occurrence of behavioral stages of seizures was recorded. Following the behavioral study, hippocampal samples were collected for gene expression evaluation using the Real Time-PCR technique to assess IL (interleukin)-1, IL-6, IL-4 and TNF (tumor necrosis factor)-α gene expression.</p><p><strong>Results: </strong>The current study showed that receiving LPS exacerbated seizures in the studied groups. Carvacrol reduced the severity of seizures in the LPS-receiving groups. In the gene expression study, receiving LPS increased the expression of cytokines TNF-α and IL-1 in the hippocampal tissue. Carvacrol significantly decreased gene expression of TNF-α and IL-1.No significant changes were detected for IL-6, IL-4 gene expression.</p><p><strong>Conclusion: </strong>There could be a relationship between carvacrol ability to modulate the proconvulsive effects of LPS and its ability to decrease the gene expression of inflammatory cytokines.</p>","PeriodicalId":8677,"journal":{"name":"Avicenna Journal of Phytomedicine","volume":"15 5","pages":"1385-1392"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12441194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085019","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}
Objective: This study aims to evaluate the chemical composition antioxidant activity, and diuretic effects of Moroccan Pinus pinaster bark ethanolic extract (PPBE).
Materials and methods: The phytochemical composition of PPBE was assessed using HPLC-DAD. Total polyphenols and flavonoids were quantified using the Folin-Ciocalteu and aluminum trichloride methods, respectively, while mineral content was determined by plasma mass spectrometry. Antioxidant activity was assessed using the reducing power assay, total antioxidant capacity, and anti-DPPH free radical assay. For the diuretic effect, sixteen male Wistar rats were divided into four groups: control (distilled water, 10 ml/kg of BW), furosemide (10 mg/kg of BW), and PPBE (200 and 400 mg/kg of BW) groups. After 15 days, plasma and urine were collected for creatinine, potassium, and sodium analysis, along with urine output measurement. Statistical analysis employed one-way ANOVA followed by Tukey multiple comparison test.
Results: The PPBE displayed high phenolic content and potent antioxidant properties. Besides, the PPBE phenolic screening showed nine phenolic compounds with ferulate glucoside, gallic acid, and catechin as the main compounds. The PPBE demonstrated a richness in essential minerals. Furthermore, at both doses (200 and 400 mg/kg) PPBE led to a notable elevation in urine flow, urinary sodium concentration, and creatinine clearance, without affecting plasma electrolytes. In contrast, furosemide caused a reduction in plasma potassium levels.
Conclusion: PPBE could serve as a bioactive component, antioxidant, or preservative in food formulation. Moreover, it exhibits a diuretic effect without altering plasma composition.
{"title":"Phenolic screening, antioxidant activity and diuretic effect of Moroccan <i>Pinus pinaster</i> Bark extract.","authors":"Widad Tbatou, Abderrazak Aboulghazi, Asmae El Ghouizi, Karima El-Yagoubi, Najoua Soulo, Zineb Benziane Ouaritini, Badiaa Lyoussi","doi":"10.22038/ajp.2024.25198","DOIUrl":"10.22038/ajp.2024.25198","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to evaluate the chemical composition antioxidant activity, and diuretic effects of Moroccan <i>Pinus pinaster</i> bark ethanolic extract (PPBE).</p><p><strong>Materials and methods: </strong>The phytochemical composition of PPBE was assessed using HPLC-DAD. Total polyphenols and flavonoids were quantified using the Folin-Ciocalteu and aluminum trichloride methods, respectively, while mineral content was determined by plasma mass spectrometry. Antioxidant activity was assessed using the reducing power assay, total antioxidant capacity, and anti-DPPH free radical assay. For the diuretic effect, sixteen male Wistar rats were divided into four groups: control (distilled water, 10 ml/kg of BW), furosemide (10 mg/kg of BW), and PPBE (200 and 400 mg/kg of BW) groups. After 15 days, plasma and urine were collected for creatinine, potassium, and sodium analysis, along with urine output measurement. Statistical analysis employed one-way ANOVA followed by Tukey multiple comparison test.</p><p><strong>Results: </strong>The PPBE displayed high phenolic content and potent antioxidant properties. Besides, the PPBE phenolic screening showed nine phenolic compounds with ferulate glucoside, gallic acid, and catechin as the main compounds. The PPBE demonstrated a richness in essential minerals. Furthermore, at both doses (200 and 400 mg/kg) PPBE led to a notable elevation in urine flow, urinary sodium concentration, and creatinine clearance, without affecting plasma electrolytes. In contrast, furosemide caused a reduction in plasma potassium levels.</p><p><strong>Conclusion: </strong>PPBE could serve as a bioactive component, antioxidant, or preservative in food formulation. Moreover, it exhibits a diuretic effect without altering plasma composition.</p>","PeriodicalId":8677,"journal":{"name":"Avicenna Journal of Phytomedicine","volume":"15 5","pages":"1450-1465"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12441190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145084831","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}
Nooshin Ghadiri, Mohammad Rashno, Ali Khodadadi, Ali Asadirad, Mohammad Nemati, Ata A Ghadiri
Objective: Colorectal cancer (CRC) is among the deadliest malignancies, often diagnosed at advanced stages, limiting treatment efficacy and necessitating alternative therapeutic approaches. Scorpion venom has emerged as a promising source of bioactive compounds for cancer therapy. This study investigated the anti-cancer potential of Androctonus crassicauda scorpion venom fractions against CT-26 colon cancer cells.
Materials and methods: A. crassicauda venom fractions were isolated using gel filtration chromatography. Murine peritoneal macrophages, harvested from BALB/c mice, were polarized towards the M2 phenotype and characterized by flow cytometry. Real-time PCR and ELISA quantified M1 and M2 macrophage-associated gene and cytokine expression. The impact of venom fractions on CT-26 cell proliferation and migration was assessed via MTT and wound-healing assays. Phagocytic activity was evaluated using a yeast phagocytosis assay.
Results: The F2 venom fraction significantly upregulated pro-inflammatory gene and cytokine expression, and downregulated anti-inflammatory gene and cytokine expression in M2 macrophages. Furthermore, the F2 fraction significantly inhibited CT-26 cell proliferation and migration. Critically, it also enhanced the phagocytic capacity of M2 macrophages.
Conclusion: Our results suggest that the F2 fraction of A. crassicauda scorpion venom reprograms tumor-associated M2 macrophages towards an anti-tumor M1 phenotype. These findings suggest the potential of the F2 fraction of A. crassicauda scorpion venom as a novel therapeutic strategy for the treatment of colon cancer. However, to confirm this potential, further in vivo studies need to be carried out.
{"title":"F2 peptide fraction of <i>Androctonus crassicauda</i> scorpion venom: Inducing M2 to M1 macrophage polarization and inhibiting colon carcinoma cell proliferation and migration.","authors":"Nooshin Ghadiri, Mohammad Rashno, Ali Khodadadi, Ali Asadirad, Mohammad Nemati, Ata A Ghadiri","doi":"10.22038/ajp.2025.25721","DOIUrl":"10.22038/ajp.2025.25721","url":null,"abstract":"<p><strong>Objective: </strong>Colorectal cancer (CRC) is among the deadliest malignancies, often diagnosed at advanced stages, limiting treatment efficacy and necessitating alternative therapeutic approaches. Scorpion venom has emerged as a promising source of bioactive compounds for cancer therapy. This study investigated the anti-cancer potential of <i>Androctonus crassicauda</i> scorpion venom fractions against CT-26 colon cancer cells.</p><p><strong>Materials and methods: </strong><i>A. crassicauda</i> venom fractions were isolated using gel filtration chromatography. Murine peritoneal macrophages, harvested from BALB/c mice, were polarized towards the M2 phenotype and characterized by flow cytometry. Real-time PCR and ELISA quantified M1 and M2 macrophage-associated gene and cytokine expression. The impact of venom fractions on CT-26 cell proliferation and migration was assessed via MTT and wound-healing assays. Phagocytic activity was evaluated using a yeast phagocytosis assay.</p><p><strong>Results: </strong>The F2 venom fraction significantly upregulated pro-inflammatory gene and cytokine expression, and downregulated anti-inflammatory gene and cytokine expression in M2 macrophages. Furthermore, the F2 fraction significantly inhibited CT-26 cell proliferation and migration. Critically, it also enhanced the phagocytic capacity of M2 macrophages.</p><p><strong>Conclusion: </strong>Our results suggest that the F2 fraction of <i>A. crassicauda</i> scorpion venom reprograms tumor-associated M2 macrophages towards an anti-tumor M1 phenotype. These findings suggest the potential of the F2 fraction of <i>A. crassicauda</i> scorpion venom as a novel therapeutic strategy for the treatment of colon cancer. However, to confirm this potential, further <i>in vivo</i> studies need to be carried out.</p>","PeriodicalId":8677,"journal":{"name":"Avicenna Journal of Phytomedicine","volume":"15 5","pages":"1502-1518"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12441195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085071","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}
Saeed Khazayel, Mohammad Hossein Faraji, Mohsen Akbaribazm, Mozafar Khazaei, Elham Niromand, Mohammad Rasool Khazaei
Objective: Triple-negative breast cancer (TNBC) presents significant therapeutic challenges. This study investigates the combination effects of Trifolium pratense L. (red clover) and doxorubicin (DOX) on the Wnt/β-catenin signaling pathway, epithelial-mesenchymal transition (EMT) and apoptosis in 4T1 tumor-bearing BALB/c mice.
Materials and methods: Female BALB/c mice were divided into six (n=10) groups: control, DOX (5 mg/kg), and three treatment groups receiving 100, 200, or 400 mg/kg T. pratense extract alongside DOX, and a single dose of 400 mg/kg T. pratense. Tumor size was measured using Vernier calipers, and survival rates were analyzed through Kaplan-Meier curves. Tumors were removed to analyze histological examinations and gene expression of Ccnd, Myc, Cdh1, Snai1, Sfrp2, Wif1, Kremen1, and ARHGAP17. Immunohistochemical staining was performed to evaluate p53, Ki-67, β-catenin, Cdh1, and vimentin expression.
Results: Co-treatment of T. pratense (400 mg/kg) with DOX (5 mg/kg) synergistically reduced cell proliferation and increased apoptosis by increasing p53 and decreasing Ki-67 expression in a dose-dependent manner. This co-treatment effectively inhibited the Wnt/β-catenin pathway by upregulating antagonists (Wif1 and Sfrp2), modulating β-catenin accumulation, and reversing EMT through increased E-cadherin expression and decreased vimentin (protein level) and Snai1 (gene expression) levels.
Conclusion: T. pratense extract shows potential as an adjuvant therapy against TNBC by targeting the Wnt/β-catenin pathway and reversing EMT while enhancing DOX efficacy. Further research is warranted to explore additional anticancer mechanisms of T. pratense extract.
{"title":"Synergistic inhibitory effects of <i>Trifolium pratense</i> L. extract and doxorubicin on 4T1 tumor-bearing mice are mediated via targeting the Wnt/β-catenin pathway and reversal of epithelial-mesenchymal transition.","authors":"Saeed Khazayel, Mohammad Hossein Faraji, Mohsen Akbaribazm, Mozafar Khazaei, Elham Niromand, Mohammad Rasool Khazaei","doi":"10.22038/ajp.2025.25940","DOIUrl":"10.22038/ajp.2025.25940","url":null,"abstract":"<p><strong>Objective: </strong>Triple-negative breast cancer (TNBC) presents significant therapeutic challenges. This study investigates the combination effects of Trifolium pratense L. (red clover) and doxorubicin (DOX) on the Wnt/β-catenin signaling pathway, epithelial-mesenchymal transition (EMT) and apoptosis in 4T1 tumor-bearing BALB/c mice.</p><p><strong>Materials and methods: </strong>Female BALB/c mice were divided into six (n=10) groups: control, DOX (5 mg/kg), and three treatment groups receiving 100, 200, or 400 mg/kg <i>T. pratense</i> extract alongside DOX, and a single dose of 400 mg/kg <i>T. pratense</i>. Tumor size was measured using Vernier calipers, and survival rates were analyzed through Kaplan-Meier curves. Tumors were removed to analyze histological examinations and gene expression of <i>Ccnd</i>, <i>Myc</i>, <i>Cdh1</i>, <i>Snai1</i>, <i>Sfrp2</i>, <i>Wif1</i>, <i>Kremen1</i>, and <i>ARHGAP17</i>. Immunohistochemical staining was performed to evaluate p53, Ki-67, β-catenin, Cdh1, and vimentin expression.</p><p><strong>Results: </strong>Co-treatment of <i>T. pratense</i> (400 mg/kg) with DOX (5 mg/kg) synergistically reduced cell proliferation and increased apoptosis by increasing p53 and decreasing Ki-67 expression in a dose-dependent manner. This co-treatment effectively inhibited the Wnt/β-catenin pathway by upregulating antagonists (<i>Wif1</i> and <i>Sfrp2</i>), modulating β-catenin accumulation, and reversing EMT through increased E-cadherin expression and decreased vimentin (protein level) and <i>Snai1</i> (gene expression) levels.</p><p><strong>Conclusion: </strong><i>T. pratense</i> extract shows potential as an adjuvant therapy against TNBC by targeting the Wnt/β-catenin pathway and reversing EMT while enhancing DOX efficacy. Further research is warranted to explore additional anticancer mechanisms of <i>T. pratense</i> extract.</p>","PeriodicalId":8677,"journal":{"name":"Avicenna Journal of Phytomedicine","volume":"15 5","pages":"1546-1561"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12441188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145084882","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}
Masoud Ojarudi, Ali Golchin, Hamid Reza Karamdel, Mohammad Valilo, Parviz Ranjbarvan
Objective: Hepatic cells face oxidative stress-induced damage, but plant antioxidants may offer protection. This study aimed to assess Elaeagnus angustifolia L. fruit extract's potential in shielding rat livers from CCl4 damage.
Materials and methods: 30 Male Wistar rats were randomly divided into five groups: normal control (received distilled water), E. angustifolia hydroalcoholic extract control, CCl4 control, E. angustifolia extract pretreatment (600 mg/kg), and silymarin pretreatment (100 mg/kg). After 14 days of oral administration of extracts, CCl4 was injected intraperitoneally. The samples were collected 48 hr later. Histological and biochemical analyses were then carried out.
Results: CCl4 injection caused significant (p<0.001) changes in liver serum enzymes, lipid profile, bilirubin, total protein, serum albumin, antioxidant enzymes, malondialdehyde, Inflammatory cytokines, and liver tissue morphology. E.angustifolia extract pre-treatment significantly (p<0.05) returned changes to the normal state.
Conclusion: This study's findings revealed that E. angustifolia extract pretreatment could reduce liver injury caused by CCl4 in rats.
{"title":"Protective effects of <i>Elaeagnus angustifolia</i> L. fruit extract on CCl<sub>4</sub>-induced oxidative stress and inflammation in rats liver.","authors":"Masoud Ojarudi, Ali Golchin, Hamid Reza Karamdel, Mohammad Valilo, Parviz Ranjbarvan","doi":"10.22038/ajp.2025.25915","DOIUrl":"10.22038/ajp.2025.25915","url":null,"abstract":"<p><strong>Objective: </strong>Hepatic cells face oxidative stress-induced damage, but plant antioxidants may offer protection. This study aimed to assess <i>Elaeagnus angustifolia</i> L. fruit extract's potential in shielding rat livers from CCl<sub>4</sub> damage.</p><p><strong>Materials and methods: </strong>30 Male Wistar rats were randomly divided into five groups: normal control (received distilled water), <i>E. angustifolia</i> hydroalcoholic extract control, CCl<sub>4</sub> control, <i>E. angustifolia</i> extract pretreatment (600 mg/kg), and silymarin pretreatment (100 mg/kg). After 14 days of oral administration of extracts, CCl<sub>4</sub> was injected intraperitoneally. The samples were collected 48 hr later. Histological and biochemical analyses were then carried out.</p><p><strong>Results: </strong>CCl<sub>4</sub> injection caused significant (p<0.001) changes in liver serum enzymes, lipid profile, bilirubin, total protein, serum albumin, antioxidant enzymes, malondialdehyde, Inflammatory cytokines, and liver tissue morphology. <i>E</i> <i>.</i> <i>angustifolia</i> extract pre-treatment significantly (p<0.05) returned changes to the normal state.</p><p><strong>Conclusion: </strong>This study's findings revealed that <i>E. angustifolia</i> extract pretreatment could reduce liver injury caused by CCl<sub>4</sub> in rats.</p>","PeriodicalId":8677,"journal":{"name":"Avicenna Journal of Phytomedicine","volume":"15 5","pages":"1519-1530"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12441200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145084911","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}
Objective: Considering the burden of non-cardiac chest pain (NCCP) on emergency departments and the difficulties related to the treatment of the disorder, the present study aims to investigate the effect of Asvard capsule (containing Myrtus communis and Rosa damascena) compared to routine treatment (omeprazole) in a double-blind randomized controlled clinical trial.
Materials and methods: This study was carried out for 8 weeks including 6 weeks of therapeutic intervention and 2 weeks of follow-up. The participants were assigned to a control group that received omeprazole capsule 20 mg/day and three intervention groups A) Asvard capsule 1200 mg/day )2 cap 300 mg/BID), B) Asvard capsule 1600 mg/day (2 cap 400 mg/BID), and C) Asvard capsule 2000 mg/day (2 cap 500 mg/BID). The therapeutic efficiency for NCCP was assessed in 4 phases (days 0, 21, 42, and 56) using a standardized questionnaire of frequency scale for the symptoms of gastroesophageal reflux disease (FSSG).
Results: The average value of NCCP was reduced after the intervention compared to the study's baseline in all groups (Pv <0.001). However, two weeks after treatment (follow-up), participants recorded higher scores of NCCP in the omeprazole 20 mg group, the average of NCCP for the intervention groups remained constant or increased slightly.
Conclusion: Our findings present that although omeprazole 20 mg decreased chest pain score, it has less lasting effect compared to the herbal medicine used in this study. It seems that Asvard can be effective for the treatment of NCCP related to gastroesophageal reflux disease (GERD), however, a long-term study.
{"title":"Comparison the effect of Asvard capsule and omeprazole in treatment and recurrence of non-cardiac chest pain related to gastroesophageal reflux disease in adults: A controlled double blind clinical trial.","authors":"Saeed Sepehrikia, Nasser Behnampour, Ayesheh Enayati, Alireza Norouzi, Fatemeh Kolangi","doi":"10.22038/ajp.2025.25580","DOIUrl":"10.22038/ajp.2025.25580","url":null,"abstract":"<p><strong>Objective: </strong>Considering the burden of non-cardiac chest pain (NCCP) on emergency departments and the difficulties related to the treatment of the disorder, the present study aims to investigate the effect of Asvard capsule (containing <i>Myrtus communis</i> and <i>Rosa damascena</i>) compared to routine treatment (omeprazole) in a double-blind randomized controlled clinical trial.</p><p><strong>Materials and methods: </strong>This study was carried out for 8 weeks including 6 weeks of therapeutic intervention and 2 weeks of follow-up. The participants were assigned to a control group that received omeprazole capsule 20 mg/day and three intervention groups A) Asvard capsule 1200 mg/day )2 cap 300 mg/BID), B) Asvard capsule 1600 mg/day (2 cap 400 mg/BID), and C) Asvard capsule 2000 mg/day (2 cap 500 mg/BID). The therapeutic efficiency for NCCP was assessed in 4 phases (days 0, 21, 42, and 56) using a standardized questionnaire of frequency scale for the symptoms of gastroesophageal reflux disease (FSSG).</p><p><strong>Results: </strong>The average value of NCCP was reduced after the intervention compared to the study's baseline in all groups (Pv <0.001). However, two weeks after treatment (follow-up), participants recorded higher scores of NCCP in the omeprazole 20 mg group, the average of NCCP for the intervention groups remained constant or increased slightly.</p><p><strong>Conclusion: </strong>Our findings present that although omeprazole 20 mg decreased chest pain score, it has less lasting effect compared to the herbal medicine used in this study. It seems that Asvard can be effective for the treatment of NCCP related to gastroesophageal reflux disease (GERD), however, a long-term study.</p>","PeriodicalId":8677,"journal":{"name":"Avicenna Journal of Phytomedicine","volume":"15 5","pages":"1438-1449"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12441189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085063","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}
Objective: Patients undergoing treatment with antineoplastic drugs face numerous challenges. This study investigates the effects of thymoquinone (Tq) in NMRI mice treated with cyclophosphamide (Cph), aiming to enhance patients' optimism for the future by redirecting their focus towards achieving a normal life and restoring fertility after treatment.
Materials and methods: Female NMRI mice were divided into five groups: Control, Sham, Cph-treated (CPH), and two groups treated with Tq alongside Cph (TQ5 and TQ10). All mice were sacrificed to aspirate their oocytes for further analysis. The development of embryos up to the blastocyst stage was assessed using in vitro fertilization (IVF) with mature oocytes.
Results: The Tq treatment groups exhibited a dose-dependent decrease in oocyte degeneration compared to the CPH group. A dose-dependent reduction in the rate of metaphase I maturation arrest was also observed in the TQ groups compared to CPH. Tq significantly increased the number of two-cell and four-cell embryos at 24- and 48-hrs post-fertilization compared to the CPH group. Additionally, Tq treatment resulted in significant dose-dependent increases in catalase levels, while malondialdehyde and nitric oxide levels were significantly lower in the TQ groups compared to the CPH groups. Tq-treated groups also demonstrated significant dose-dependent increases in the expression levels of BMP15 and GDF9 compared to the CPH group.
Conclusion: In this study, Tq mitigated oocyte factors expression (GDF9 and BMP15) and oxidative damage in ovarian tissues following CPH-induced oocyte degeneration in mice.
{"title":"Thymoquinone alleviates the adverse effects of cyclophosphamide on oogenesis and in vitro fertilization (IVF) in NMRI mice.","authors":"Sima Etebari, Vajihe Rouki, Mohsen Asouri, Mehrab Nasirikenari, Seyed Elyas Meshkani, Mohammad Reza Momtaz, Sakineh Amoueian, Yahya Babaki, Fateme Hajati, Ali Asghar Ahmadi","doi":"10.22038/ajp.2025.25734","DOIUrl":"10.22038/ajp.2025.25734","url":null,"abstract":"<p><strong>Objective: </strong>Patients undergoing treatment with antineoplastic drugs face numerous challenges. This study investigates the effects of thymoquinone (Tq) in NMRI mice treated with cyclophosphamide (Cph), aiming to enhance patients' optimism for the future by redirecting their focus towards achieving a normal life and restoring fertility after treatment.</p><p><strong>Materials and methods: </strong>Female NMRI mice were divided into five groups: Control, Sham, Cph-treated (CPH), and two groups treated with Tq alongside Cph (TQ5 and TQ10). All mice were sacrificed to aspirate their oocytes for further analysis. The development of embryos up to the blastocyst stage was assessed using in vitro fertilization (IVF) with mature oocytes.</p><p><strong>Results: </strong>The Tq treatment groups exhibited a dose-dependent decrease in oocyte degeneration compared to the CPH group. A dose-dependent reduction in the rate of metaphase I maturation arrest was also observed in the TQ groups compared to CPH. Tq significantly increased the number of two-cell and four-cell embryos at 24- and 48-hrs post-fertilization compared to the CPH group. Additionally, Tq treatment resulted in significant dose-dependent increases in catalase levels, while malondialdehyde and nitric oxide levels were significantly lower in the TQ groups compared to the CPH groups. Tq-treated groups also demonstrated significant dose-dependent increases in the expression levels of <i>BMP15</i> and <i>GDF9</i> compared to the CPH group.</p><p><strong>Conclusion: </strong>In this study, Tq mitigated oocyte factors expression (<i>GDF9</i> and <i>BMP15</i>) and oxidative damage in ovarian tissues following CPH-induced oocyte degeneration in mice.</p>","PeriodicalId":8677,"journal":{"name":"Avicenna Journal of Phytomedicine","volume":"15 5","pages":"1477-1488"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12441191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145084942","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}
Objective: This research aimed to explore the cytotoxic, apoptotic, and antioxidant effects of selenium nanoparticles (Se-NPs) produced by Cordia myxa (C. myxa) aqueous extract via a green reduction method.
Materials and methods: To synthesize Se-NPs, Na2SeO3 and C. myxa plant extract were used and their anticancer and antioxidant effects were investigated. After the synthesis of Se-NPs, their physicochemical properties were investigated by various techniques such as UV-Vis, XRD, TEM, FESEM/PSA, EDX, FT-IR, and DLS/Zeta. Next, the lethality of Se-NPs on cancerous Huh-7 and normal L929 cells was investigated. Then, using Annexin V/PI and DAPI kits, the number of apoptotic cells in terms of the obtained percentage and the amount of ROS production was determined by flow cytometry. The influence of Se-NPs on the expression of genes associated with apoptosis has been examined.
Results: The XRD pattern and FESEM/TEM images confirmed the successful production of Se-NPs with an amorphous nature and size average of 11.9 nm. Flow cytometry analyses revealed a significant increase in ROS levels after 24 h of treatment with Se-NPs, demonstrating a concentration-dependent effect.
Conclusion: The findings indicate that Se-NPs exhibit anticancer activity against Huh-7 cells, as evidenced by the upregulation of Bax, p53, and Caspase3 gene expression. Therefore, it can be asserted that Se-NPs have the potential to eliminate cancer cells, while simultaneously providing a protective effect on normal cells.
{"title":"Green synthesis of selenium nanoparticles using <i>Cordia myxa</i> extract and assessment of their cytotoxic and antioxidant properties.","authors":"Leili Hosseinpour, Javad Baharara, Majid Darroudi, Zahra Sabouri, Aryam Haji Ghasem Kashani, Saeed Zaker Bostanabad","doi":"10.22038/ajp.2025.25954","DOIUrl":"10.22038/ajp.2025.25954","url":null,"abstract":"<p><strong>Objective: </strong>This research aimed to explore the cytotoxic, apoptotic, and antioxidant effects of selenium nanoparticles (Se-NPs) produced by <i>Cordia myxa</i> (<i>C. myxa</i>) aqueous extract via a green reduction method.</p><p><strong>Materials and methods: </strong>To synthesize Se-NPs, Na<sub>2</sub>SeO<sub>3</sub> and <i>C. myxa</i> plant extract were used and their anticancer and antioxidant effects were investigated. After the synthesis of Se-NPs, their physicochemical properties were investigated by various techniques such as UV-Vis, XRD, TEM, FESEM/PSA, EDX, FT-IR, and DLS/Zeta. Next, the lethality of Se-NPs on cancerous Huh-7 and normal L929 cells was investigated. Then, using Annexin V/PI and DAPI kits, the number of apoptotic cells in terms of the obtained percentage and the amount of ROS production was determined by flow cytometry. The influence of Se-NPs on the expression of genes associated with apoptosis has been examined.</p><p><strong>Results: </strong>The XRD pattern and FESEM/TEM images confirmed the successful production of Se-NPs with an amorphous nature and size average of 11.9 nm. Flow cytometry analyses revealed a significant increase in ROS levels after 24 h of treatment with Se-NPs, demonstrating a concentration-dependent effect.</p><p><strong>Conclusion: </strong>The findings indicate that Se-NPs exhibit anticancer activity against Huh-7 cells, as evidenced by the upregulation of <i>Bax, p53, and Caspase3 gene</i> expression. Therefore, it can be asserted that Se-NPs have the potential to eliminate cancer cells, while simultaneously providing a protective effect on normal cells.</p>","PeriodicalId":8677,"journal":{"name":"Avicenna Journal of Phytomedicine","volume":"15 5","pages":"1531-1545"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12441193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085136","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}