Babak Pourgholamali, Fatemeh Yosefbeyk, Masoud Ansar, Arash Zaminy, Shadman Nemati, Sina Ramezani, Hamidreza Bagheri, M. Faghani
Background: Sambucus Ebulus L. (SE) is known as an anti-inflammatory herb in traditional medicine. Nasosinusal polyposis is a common type of chronic nose and paranasal sinus inflammation. It is more common in patients with asthma and aspirin-exacerbated respiratory diseases. Objectives: This study aimed to investigate the apoptotic and anti-inflammatory effects of SE fruit extract on NP. Methods: The extract of SE fruit was prepared and subjected to total phenolic, anthocyanin, and flavonoid content measurement. The antioxidant activity was tested using the DPPH radical scavenging method. Nasal polyp (NP) tissue samples were collected from patients. Different concentrations of the SE extract were exposed to NPT samples for 24 hours. The expression of BAX and BAD proapoptotic markers, IL-5 and GM-CSF levels, and cell apoptosis were evaluated by real-time PCR, ELISA, and TUNEL assay, respectively. Results: The total phenolic and flavonoid contents of the extract were 38.44 (mg GAE/g extract) and 8.62 ± 0.12 (mg QE/g extract), respectively. Moreover, the total anthocyanin content was 0.56 ± 0.01 (mg C3GE/g extract). The IC50 of SE fruit extract in the DPPH radical scavenging assay was 190.78 ± 0.55 µg/mL. Also, BAX and BAD markers and TUNEL-positive cells were observed to increase in NP tissue samples in vitro after treatment with SE fruit extract (P < 0.05). The level of GM-CSF in the treated groups was reduced (P < 0.05). Conclusions: Our results showed that SE fruit extract was a good source of phenolic compounds that can induce anti-inflammatory and anti-apoptotic events in NP tissues, at least partly through increasing the expression of BAD and BAX apoptotic markers and reducing GM-CSF levels. The clinical applicability of SE fruit extract in the treatment of nasal polyps should be investigated in the future.
背景：Sambucus Ebulus L.（SE）在传统医学中被称为消炎草药。鼻窦息肉病是一种常见的慢性鼻和副鼻窦炎。它在哮喘和阿司匹林加重的呼吸道疾病患者中更为常见。研究目的本研究旨在探讨 SE 果实提取物对鼻腔息肉的凋亡和抗炎作用。方法：制备 SE 果实提取物并测定其总酚、花青素和类黄酮含量。采用 DPPH 自由基清除法测试其抗氧化活性。从患者身上采集鼻息肉（NP）组织样本。将不同浓度的 SE 提取物与 NPT 样品接触 24 小时。通过实时 PCR、ELISA 和 TUNEL 检测法分别评估了 BAX 和 BAD 促凋亡标志物的表达、IL-5 和 GM-CSF 水平以及细胞凋亡情况。结果提取物的总酚和类黄酮含量分别为 38.44（毫克 GAE/克提取物）和 8.62 ± 0.12（毫克 QE/克提取物）。此外，花青素总含量为 0.56 ± 0.01（毫克 C3GE/克提取物）。在 DPPH 自由基清除试验中，SE 果实提取物的 IC50 为 190.78 ± 0.55 µg/mL。此外，经 SE 果实提取物处理后，体外观察到 NP 组织样本中的 BAX 和 BAD 标记以及 TUNEL 阳性细胞有所增加（P < 0.05）。治疗组的 GM-CSF 水平降低（P < 0.05）。结论我们的研究结果表明，SE 果实提取物是一种良好的酚类化合物来源，可诱导 NP 组织中的抗炎和抗凋亡事件，至少部分是通过增加 BAD 和 BAX 凋亡标记物的表达以及降低 GM-CSF 水平来实现的。未来应研究 SE 果实提取物在治疗鼻息肉方面的临床适用性。
{"title":"Phytochemical Content, Anti-inflammatory, Anti-apoptotic, and Antioxidant Activities of Dwarf Elder (Sambucus Ebulus) Against Nasal Polyposis","authors":"Babak Pourgholamali, Fatemeh Yosefbeyk, Masoud Ansar, Arash Zaminy, Shadman Nemati, Sina Ramezani, Hamidreza Bagheri, M. Faghani","doi":"10.5812/jjnpp-141803","DOIUrl":"https://doi.org/10.5812/jjnpp-141803","url":null,"abstract":"Background: Sambucus Ebulus L. (SE) is known as an anti-inflammatory herb in traditional medicine. Nasosinusal polyposis is a common type of chronic nose and paranasal sinus inflammation. It is more common in patients with asthma and aspirin-exacerbated respiratory diseases. Objectives: This study aimed to investigate the apoptotic and anti-inflammatory effects of SE fruit extract on NP. Methods: The extract of SE fruit was prepared and subjected to total phenolic, anthocyanin, and flavonoid content measurement. The antioxidant activity was tested using the DPPH radical scavenging method. Nasal polyp (NP) tissue samples were collected from patients. Different concentrations of the SE extract were exposed to NPT samples for 24 hours. The expression of BAX and BAD proapoptotic markers, IL-5 and GM-CSF levels, and cell apoptosis were evaluated by real-time PCR, ELISA, and TUNEL assay, respectively. Results: The total phenolic and flavonoid contents of the extract were 38.44 (mg GAE/g extract) and 8.62 ± 0.12 (mg QE/g extract), respectively. Moreover, the total anthocyanin content was 0.56 ± 0.01 (mg C3GE/g extract). The IC50 of SE fruit extract in the DPPH radical scavenging assay was 190.78 ± 0.55 µg/mL. Also, BAX and BAD markers and TUNEL-positive cells were observed to increase in NP tissue samples in vitro after treatment with SE fruit extract (P < 0.05). The level of GM-CSF in the treated groups was reduced (P < 0.05). Conclusions: Our results showed that SE fruit extract was a good source of phenolic compounds that can induce anti-inflammatory and anti-apoptotic events in NP tissues, at least partly through increasing the expression of BAD and BAX apoptotic markers and reducing GM-CSF levels. The clinical applicability of SE fruit extract in the treatment of nasal polyps should be investigated in the future.","PeriodicalId":17745,"journal":{"name":"Jundishapur Journal of Natural Pharmaceutical Products","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139451426","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}
N. Zaeemzadeh, Marzieh Alavifar, Amal Saki Malehi, Mehrnoosh Zakerkish
: Diabetes mellitus (DM) is a common chronic disease that can significantly reduce life expectancy due to its complications. Grapes (Vitis vinifera L.) and their byproducts, including grape seeds, have been used worldwide for the treatment of various ailments. This clinical trial investigated the effect of grape seed extract (GSE) on fasting blood sugar (FBS), lipid profile (including total cholesterol, high-density lipoprotein [HDL], low-density lipoprotein [LDL], and triglycerides [TG]), and systolic blood pressure (SBP) and diastolic blood pressure (DBP) in patients with type 2 diabetes mellitus (T2DM). A total of 74 patients with T2DM were divided into two groups, including 38 patients in the treatment (GSE) group receiving 263.2 mg of GSE (standardized to 250 mg proanthocyanidin) twice daily and 36 patients in the placebo (control) group receiving 263.2 mg of the placebo twice daily for 30 days. At the end of the intervention, a statistically significant decrease was observed in SBP (from 125.83 ± 13.39 in the placebo group to 121.94 ± 7.49 in the treatment group, P = 0.002) and FBS (from 144.75 ± 30.82 in the placebo group to 129.87 ± 31.79 in the treatment group, P = 0.001). However, there were no significant changes in total cholesterol, HDL, LDL, TG, and DBP between the two groups. The use of Iranian GSE for a short period might lead to lower FBS and SBP. Therefore, GSE might play a significant role in improving blood pressure and fasting blood glucose levels in patients with T2DM.
{"title":"A 4-week Randomized, Double-Blind, Placebo-Controlled Clinical Trial on the Use of Grape Seed Extract for Reducing Plasma Glucose, Lipid Profile, and Blood Pressure in Patients with Type 2 Diabetes Mellitus","authors":"N. Zaeemzadeh, Marzieh Alavifar, Amal Saki Malehi, Mehrnoosh Zakerkish","doi":"10.5812/jjnpp-142252","DOIUrl":"https://doi.org/10.5812/jjnpp-142252","url":null,"abstract":": Diabetes mellitus (DM) is a common chronic disease that can significantly reduce life expectancy due to its complications. Grapes (Vitis vinifera L.) and their byproducts, including grape seeds, have been used worldwide for the treatment of various ailments. This clinical trial investigated the effect of grape seed extract (GSE) on fasting blood sugar (FBS), lipid profile (including total cholesterol, high-density lipoprotein [HDL], low-density lipoprotein [LDL], and triglycerides [TG]), and systolic blood pressure (SBP) and diastolic blood pressure (DBP) in patients with type 2 diabetes mellitus (T2DM). A total of 74 patients with T2DM were divided into two groups, including 38 patients in the treatment (GSE) group receiving 263.2 mg of GSE (standardized to 250 mg proanthocyanidin) twice daily and 36 patients in the placebo (control) group receiving 263.2 mg of the placebo twice daily for 30 days. At the end of the intervention, a statistically significant decrease was observed in SBP (from 125.83 ± 13.39 in the placebo group to 121.94 ± 7.49 in the treatment group, P = 0.002) and FBS (from 144.75 ± 30.82 in the placebo group to 129.87 ± 31.79 in the treatment group, P = 0.001). However, there were no significant changes in total cholesterol, HDL, LDL, TG, and DBP between the two groups. The use of Iranian GSE for a short period might lead to lower FBS and SBP. Therefore, GSE might play a significant role in improving blood pressure and fasting blood glucose levels in patients with T2DM.","PeriodicalId":17745,"journal":{"name":"Jundishapur Journal of Natural Pharmaceutical Products","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2023-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139140675","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}
Background: Impaired wound healing is one of the complications of diabetes. Carvacrol, a natural substance, shows promising results in diabetic wound healing despite the fact that its therapeutic mechanisms are not fully understood. Objectives: The aim of this study was to investigate the molecular alterations caused by carvacrol intervention in human dermal fibroblasts (HDFs) cultured at a high-glucose condition. Methods: The HDFs were incubated in different glucose concentrations, and cell viability was assessed. In addition, carvacrol cytotoxicity was determined. Then, the HDFs were incubated in 50 mM glucose prior to treatment. After that, the cells were divided into 4 groups: controls, high-glucose (50 mM), carvacrol-treated (9 µM), and high-glucose carvacrol-treated for 24 h. Cell proliferation and migration were examined. Furthermore, superoxide dismutase (SOD) production, collagen deposition, and RNA levels of TGFβ1, ACTA2, and miR-155 were investigated. Results: The in vitro scratch assay revealed that the fibroblast migration, which was reduced at high-glucose concentration, was reversed due to the carvacrol intervention during 12 h and 24 h (P < 0.01 and P < 0.001, respectively). Collagen deposition and SOD synthesis showed an increase in treated cells (P < 0.001). Both TGFβ1 and ACTA2 mRNA expressions were elevated due to the carvacrol treatment, while the miR-155 level decreased (P < 0.001). Conclusions: A high level of glucose impaired the cellular function of human dermal fibroblast. Carvacrol reversed the adverse effects of high-glucose stress and promoted wound healing through greater cell migration, collagen deposition, and levels of TGFb1 and ACTA2 gene expression. It showed inhibitory effects against miR-155, which is known for its negative role in diabetic wound healing.
{"title":"In Vitro Evaluation of Carvacrol's Wound Healing Capacity in Human Dermal Fibroblasts Grown in High-Glucose Stress","authors":"Fatemeh Tabatabaei, Nastaran Asghari Moghaddam, Zeinab Piravar","doi":"10.5812/jjnpp-141691","DOIUrl":"https://doi.org/10.5812/jjnpp-141691","url":null,"abstract":"Background: Impaired wound healing is one of the complications of diabetes. Carvacrol, a natural substance, shows promising results in diabetic wound healing despite the fact that its therapeutic mechanisms are not fully understood. Objectives: The aim of this study was to investigate the molecular alterations caused by carvacrol intervention in human dermal fibroblasts (HDFs) cultured at a high-glucose condition. Methods: The HDFs were incubated in different glucose concentrations, and cell viability was assessed. In addition, carvacrol cytotoxicity was determined. Then, the HDFs were incubated in 50 mM glucose prior to treatment. After that, the cells were divided into 4 groups: controls, high-glucose (50 mM), carvacrol-treated (9 µM), and high-glucose carvacrol-treated for 24 h. Cell proliferation and migration were examined. Furthermore, superoxide dismutase (SOD) production, collagen deposition, and RNA levels of TGFβ1, ACTA2, and miR-155 were investigated. Results: The in vitro scratch assay revealed that the fibroblast migration, which was reduced at high-glucose concentration, was reversed due to the carvacrol intervention during 12 h and 24 h (P < 0.01 and P < 0.001, respectively). Collagen deposition and SOD synthesis showed an increase in treated cells (P < 0.001). Both TGFβ1 and ACTA2 mRNA expressions were elevated due to the carvacrol treatment, while the miR-155 level decreased (P < 0.001). Conclusions: A high level of glucose impaired the cellular function of human dermal fibroblast. Carvacrol reversed the adverse effects of high-glucose stress and promoted wound healing through greater cell migration, collagen deposition, and levels of TGFb1 and ACTA2 gene expression. It showed inhibitory effects against miR-155, which is known for its negative role in diabetic wound healing.","PeriodicalId":17745,"journal":{"name":"Jundishapur Journal of Natural Pharmaceutical Products","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2023-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139153382","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}
P. Gheibi, N. Jabbari, Nazanin Kafi Alghari, Sabina Mah Nesaei, Ramin Farhoudi, Zohre Eftekhari
Background: Low-cost, soluble polyvinyl alcohol (PVA) polymers enhance the efficacy of herbal formulations with established antimicrobial properties. Objectives: This study investigates the healing process of Staphylococcus aureus (S. aureus)-infected wounds using PVA loaded with herbal extracts, including Arnebia euchroma, Allium sativum, and Echinacea purpurea. Methods: minimal bactericidal concentration (MBC) and minimal inhibitory concentration (MIC) assays, Disk Diffusion Method (DDM) tests, and Gas Chromatography-Mass Spectrometry (GC/MS) analyses were conducted on herbal extract samples. Twelve male Wistar rats were divided into G1: Negative control group (healthy mice), G2: Wound model + S. aureus (Positive control), G3: wound model + S. aureus + Povidone-iodine, and G4: Wound model + S. aureus + PVA/formulation. Hematoxylin-eosin and immunofluorescent staining were employed to assess wound healing. Results: The ethanolic herbal extract exhibited potent antibacterial activity against S. aureus, with MIC and MBC values in the 1.87 mg/mL range. The PVA/formulation displayed a zone of inhibition with a diameter of 7 mm against S. aureus. Histopathological investigations indicated that the infected wound treated with Nanofibers extract experienced a significant reduction in inflammation between days 7 and 14. Notably, the increased CD3 expression at this site was remarkable for the healing process. Conclusions: Consequently, this experimental study suggests combining PVA and herbal extracts enhances antibacterial properties and promotes CD3 expression and re-epithelialization effects.
{"title":"Electrospun PVA Nanofibers Loaded with Antimicrobial Herbal Extracts for Healing the Infectious Wound","authors":"P. Gheibi, N. Jabbari, Nazanin Kafi Alghari, Sabina Mah Nesaei, Ramin Farhoudi, Zohre Eftekhari","doi":"10.5812/jjnpp-137995","DOIUrl":"https://doi.org/10.5812/jjnpp-137995","url":null,"abstract":"Background: Low-cost, soluble polyvinyl alcohol (PVA) polymers enhance the efficacy of herbal formulations with established antimicrobial properties. Objectives: This study investigates the healing process of Staphylococcus aureus (S. aureus)-infected wounds using PVA loaded with herbal extracts, including Arnebia euchroma, Allium sativum, and Echinacea purpurea. Methods: minimal bactericidal concentration (MBC) and minimal inhibitory concentration (MIC) assays, Disk Diffusion Method (DDM) tests, and Gas Chromatography-Mass Spectrometry (GC/MS) analyses were conducted on herbal extract samples. Twelve male Wistar rats were divided into G1: Negative control group (healthy mice), G2: Wound model + S. aureus (Positive control), G3: wound model + S. aureus + Povidone-iodine, and G4: Wound model + S. aureus + PVA/formulation. Hematoxylin-eosin and immunofluorescent staining were employed to assess wound healing. Results: The ethanolic herbal extract exhibited potent antibacterial activity against S. aureus, with MIC and MBC values in the 1.87 mg/mL range. The PVA/formulation displayed a zone of inhibition with a diameter of 7 mm against S. aureus. Histopathological investigations indicated that the infected wound treated with Nanofibers extract experienced a significant reduction in inflammation between days 7 and 14. Notably, the increased CD3 expression at this site was remarkable for the healing process. Conclusions: Consequently, this experimental study suggests combining PVA and herbal extracts enhances antibacterial properties and promotes CD3 expression and re-epithelialization effects.","PeriodicalId":17745,"journal":{"name":"Jundishapur Journal of Natural Pharmaceutical Products","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139206510","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}
F. Dehbashi, L. Zeidooni, Esrafil Mansouri, Elaheh Mohammadi, M. Khodayar
Background: Nowadays, the use of over-the-counter drugs such as acetaminophen (APAP) may cause severe liver injury, which can occur not only in high doses but also in therapeutic doses due to nutritional deficiency, alcoholism, or using cytochrome p450 inducers. Objectives: In this study, the protective effect of epicatechin (EPC) was evaluated against APAP-induced hepatotoxicity to find an effective and inexpensive therapy. Methods: The animals were divided into preventive and therapeutic groups. In the preventive study, the animals received EPC (25, 50, and 100 mg/kg/day) for five days, and the last dose was administered 1 hour before APAP (400 mg/kg). In the therapeutic groups, the animals received EPC just before and 2 hours after the APAP injection. All the animals were killed, and blood and liver samples were taken for further analysis. The liver pathology, enzymes, and oxidant, antioxidant, inflammatory, and anti-inflammatory factors were evaluated. Results: EPC significantly decreased the serum activity level of the liver biomarkers ALT and AST in the APAP-treated mice. Furthermore, the hepatic levels of thiobarbituric acid-reactive substances were noticeably lowered, and the levels of total thiol and catalase activity increased significantly with EPC. Histopathological results were strongly consistent with those of the biochemical estimations. The most effective dose was observed at EPC 100 mg/kg, and the therapeutic groups showed better results than the preventive groups. Conclusions: EPC attenuated the liver toxicity in the mice by suppressing oxidative stress and can be considered a preventive and therapeutic agent for inhibiting and resolving the liver damage induced by APAP.
{"title":"Preventive and Therapeutic Effects of Epicatechin on Acetaminophen-Induced Liver Injury in Mice","authors":"F. Dehbashi, L. Zeidooni, Esrafil Mansouri, Elaheh Mohammadi, M. Khodayar","doi":"10.5812/jjnpp-137505","DOIUrl":"https://doi.org/10.5812/jjnpp-137505","url":null,"abstract":"Background: Nowadays, the use of over-the-counter drugs such as acetaminophen (APAP) may cause severe liver injury, which can occur not only in high doses but also in therapeutic doses due to nutritional deficiency, alcoholism, or using cytochrome p450 inducers. Objectives: In this study, the protective effect of epicatechin (EPC) was evaluated against APAP-induced hepatotoxicity to find an effective and inexpensive therapy. Methods: The animals were divided into preventive and therapeutic groups. In the preventive study, the animals received EPC (25, 50, and 100 mg/kg/day) for five days, and the last dose was administered 1 hour before APAP (400 mg/kg). In the therapeutic groups, the animals received EPC just before and 2 hours after the APAP injection. All the animals were killed, and blood and liver samples were taken for further analysis. The liver pathology, enzymes, and oxidant, antioxidant, inflammatory, and anti-inflammatory factors were evaluated. Results: EPC significantly decreased the serum activity level of the liver biomarkers ALT and AST in the APAP-treated mice. Furthermore, the hepatic levels of thiobarbituric acid-reactive substances were noticeably lowered, and the levels of total thiol and catalase activity increased significantly with EPC. Histopathological results were strongly consistent with those of the biochemical estimations. The most effective dose was observed at EPC 100 mg/kg, and the therapeutic groups showed better results than the preventive groups. Conclusions: EPC attenuated the liver toxicity in the mice by suppressing oxidative stress and can be considered a preventive and therapeutic agent for inhibiting and resolving the liver damage induced by APAP.","PeriodicalId":17745,"journal":{"name":"Jundishapur Journal of Natural Pharmaceutical Products","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139215912","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}
Nasrin Nasrin Hajiabadi, Saeid Abbasi Maleki, Zahra Mousavi, P. Najafizadeh
Background: Research shows that α-Pinene interacts with the opioidergic system. Objectives: This study aims to examine the toxicity and the effects of α-Pinene on morphine tolerance and dependence in mice. Methods: Guidelines No. 423 and No. 407 were used to investigate acute and sub-chronic toxicity, respectively. For sub-chronic toxicity analysis, the animals were sacrificed on day 28, and blood and tissue samples were collected. After inducing morphine tolerance or dependence, in both phases, animals received i.p. vehicle, diazepam (5 mg/kg), and α-Pinene (3.125, 6.25, and 12.5 mg/kg). Withdrawal signs were recorded for 30 minutes. Results: Only the acute dose of α-Pinene showed mortality in animals, but mild lesions were seen in the brain, liver, and kidneys in the mice receiving its subchronic dose. Moreover, ALT, AST, ALP, and TG levels increased (P < 0.05) in female mice. Besides, 6.25 and 12.5 mg/kg (P < 0.001) of α-Pinene and only its high dose (12.5 mg/kg) (P < 0.001) reduced the number of jumps in the tolerance and dependence phases, respectively. Diarrhea (P < 0.001), writhing (P < 0.001), rearing, and climbing (P < 0.05 and P < 0.001, respectively) behaviors decreased in the tolerance phase, and grooming, climbing, and teeth chattering declined in the dependence phase (P < 0.001). Conclusions: The LD50 of α-Pinene was lower than 2000 mg/kg, but its subchronic dose caused mild tissue toxicities and biochemical changes. Moreover, α-Pinene decreased morphine tolerance and dependence and possibly was useful for the treatment of opioid dependence after complimentary trials.
{"title":"Assessment of Toxicity and Biological Effects of α-Pinene on Morphine Tolerance and Dependence in Mice","authors":"Nasrin Nasrin Hajiabadi, Saeid Abbasi Maleki, Zahra Mousavi, P. Najafizadeh","doi":"10.5812/jjnpp-141534","DOIUrl":"https://doi.org/10.5812/jjnpp-141534","url":null,"abstract":"Background: Research shows that α-Pinene interacts with the opioidergic system. Objectives: This study aims to examine the toxicity and the effects of α-Pinene on morphine tolerance and dependence in mice. Methods: Guidelines No. 423 and No. 407 were used to investigate acute and sub-chronic toxicity, respectively. For sub-chronic toxicity analysis, the animals were sacrificed on day 28, and blood and tissue samples were collected. After inducing morphine tolerance or dependence, in both phases, animals received i.p. vehicle, diazepam (5 mg/kg), and α-Pinene (3.125, 6.25, and 12.5 mg/kg). Withdrawal signs were recorded for 30 minutes. Results: Only the acute dose of α-Pinene showed mortality in animals, but mild lesions were seen in the brain, liver, and kidneys in the mice receiving its subchronic dose. Moreover, ALT, AST, ALP, and TG levels increased (P < 0.05) in female mice. Besides, 6.25 and 12.5 mg/kg (P < 0.001) of α-Pinene and only its high dose (12.5 mg/kg) (P < 0.001) reduced the number of jumps in the tolerance and dependence phases, respectively. Diarrhea (P < 0.001), writhing (P < 0.001), rearing, and climbing (P < 0.05 and P < 0.001, respectively) behaviors decreased in the tolerance phase, and grooming, climbing, and teeth chattering declined in the dependence phase (P < 0.001). Conclusions: The LD50 of α-Pinene was lower than 2000 mg/kg, but its subchronic dose caused mild tissue toxicities and biochemical changes. Moreover, α-Pinene decreased morphine tolerance and dependence and possibly was useful for the treatment of opioid dependence after complimentary trials.","PeriodicalId":17745,"journal":{"name":"Jundishapur Journal of Natural Pharmaceutical Products","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139230005","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}
Background: Breast cancer is the second leading cause of death in women. The advent of machine learning (ML) has opened up a world of possibilities for the discovery and formulation of drugs. It is an exciting development that could revolutionize the pharmaceutical industry. By leveraging ML algorithms, researchers can now identify disease-related targets with greater accuracy. Additionally, ML techniques can be used to predict the toxicity and pharmacokinetics of potential drug candidates. Objectives: The main purpose of ML techniques, such as feature selection (FS) and classification, is to develop a learning model based on datasets. Methods: This paper proposed a hybrid intelligent approach using a Binary Grey Wolf Optimization Algorithm and a Self-Organizing Fuzzy Logic Classifier (BGWO-SOF) for breast cancer diagnosis. The proposed FS approach can not only reduce the complexity of feature space but can also avoid overfitting and improve the learning process. The performance of this proposed approach was evaluated on the 10-fold cross-validation technique and the Wisconsin Diagnostic Breast Cancer dataset. Although the performance of breast cancer detection is highly dependent on classification accuracy, most good classification methods have an essential flaw in that they simply seek to maximize the accuracy of classification while ignoring the costs of misclassification among various categories. This is even more important in classification problems when the initial set of features is large. With such a large number of features, it is of special interest to search for a dependency between an optimal number of selected features and the accuracy of the classification model. Results: In experiments, standard performance evaluation metrics, including accuracy, F-measure, precision, sensitivity, and specificity, were performed. The evaluation results demonstrated that the BGWO-SOF approach achieves 99.70% accuracy and 99.66% F-measure, which outperforms other state-of-the-art methods. Conclusions: During the comparison of the results, it was observed that the proposed approach gives better or more competitive results than other state-of-the-art methods. By leveraging the power of ML algorithms and artificial intelligence (AI) and the findings of the current study, we can optimize the selection of natural pharmaceutical products for the treatment of breast cancer and maximize their efficacy.
背景：乳腺癌是女性的第二大死因。机器学习（ML）的出现为药物的发现和配制开辟了一个充满可能性的世界。这是一个令人兴奋的发展，可能会彻底改变制药行业。通过利用 ML 算法，研究人员现在可以更准确地识别与疾病相关的靶点。此外，ML 技术还可用于预测潜在候选药物的毒性和药代动力学。目标：特征选择 (FS) 和分类等 ML 技术的主要目的是基于数据集开发学习模型。方法：本文提出了一种使用二元灰狼优化算法和自组织模糊逻辑分类器（BGWO-SOF）的混合智能方法，用于乳腺癌诊断。所提出的 FS 方法不仅能降低特征空间的复杂度，还能避免过拟合并改进学习过程。在 10 倍交叉验证技术和威斯康星乳腺癌诊断数据集上评估了该方法的性能。虽然乳腺癌检测的性能高度依赖于分类的准确性，但大多数好的分类方法都有一个本质的缺陷，那就是只追求分类准确性的最大化，而忽略了不同类别之间误分类的代价。当初始特征集很大时，这一点在分类问题中就更加重要。面对如此大量的特征，寻找所选特征的最佳数量与分类模型准确性之间的关系就显得尤为重要。实验结果在实验中，执行了标准的性能评估指标，包括准确率、F-measure、精确度、灵敏度和特异性。评估结果表明，BGWO-SOF 方法达到了 99.70% 的准确率和 99.66% 的 F-measure，优于其他最先进的方法。结论在结果对比过程中，我们发现所提出的方法比其他最先进的方法提供了更好或更有竞争力的结果。通过利用 ML 算法和人工智能（AI）的力量以及当前研究的结果，我们可以优化治疗乳腺癌的天然药物产品的选择，并最大限度地提高其疗效。
{"title":"A Hybrid Intelligent Approach to Breast Cancer Diagnosis and Treatment Using Grey Wolf Optimization Algorithm","authors":"Mohammad Jafar Dehghan, A. Azizi","doi":"10.5812/jjnpp-142058","DOIUrl":"https://doi.org/10.5812/jjnpp-142058","url":null,"abstract":"Background: Breast cancer is the second leading cause of death in women. The advent of machine learning (ML) has opened up a world of possibilities for the discovery and formulation of drugs. It is an exciting development that could revolutionize the pharmaceutical industry. By leveraging ML algorithms, researchers can now identify disease-related targets with greater accuracy. Additionally, ML techniques can be used to predict the toxicity and pharmacokinetics of potential drug candidates. Objectives: The main purpose of ML techniques, such as feature selection (FS) and classification, is to develop a learning model based on datasets. Methods: This paper proposed a hybrid intelligent approach using a Binary Grey Wolf Optimization Algorithm and a Self-Organizing Fuzzy Logic Classifier (BGWO-SOF) for breast cancer diagnosis. The proposed FS approach can not only reduce the complexity of feature space but can also avoid overfitting and improve the learning process. The performance of this proposed approach was evaluated on the 10-fold cross-validation technique and the Wisconsin Diagnostic Breast Cancer dataset. Although the performance of breast cancer detection is highly dependent on classification accuracy, most good classification methods have an essential flaw in that they simply seek to maximize the accuracy of classification while ignoring the costs of misclassification among various categories. This is even more important in classification problems when the initial set of features is large. With such a large number of features, it is of special interest to search for a dependency between an optimal number of selected features and the accuracy of the classification model. Results: In experiments, standard performance evaluation metrics, including accuracy, F-measure, precision, sensitivity, and specificity, were performed. The evaluation results demonstrated that the BGWO-SOF approach achieves 99.70% accuracy and 99.66% F-measure, which outperforms other state-of-the-art methods. Conclusions: During the comparison of the results, it was observed that the proposed approach gives better or more competitive results than other state-of-the-art methods. By leveraging the power of ML algorithms and artificial intelligence (AI) and the findings of the current study, we can optimize the selection of natural pharmaceutical products for the treatment of breast cancer and maximize their efficacy.","PeriodicalId":17745,"journal":{"name":"Jundishapur Journal of Natural Pharmaceutical Products","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139229688","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}
Ainolsyakira Mohd Rodhi, Pei Gee Yap, Olusegun Abayomi Olalere, Chee Yuen Gan
Context: α-Glucosidase (AG) inhibitory peptides represent a promising new class of therapeutic agents for the treatment of diabetes. However, there is a need to further understand the mechanisms and properties of these peptides. Evidence Acquisition: In this comprehensive review, AG inhibitory peptides were categorized into three groups based on their length: short, medium, and long peptides. Data from the BioPEP-UWM database and recent publications were gathered to conduct a structure-activity relationship analysis for these peptides, focusing on identifying their reactive residues and AG binding sites. Results: Through extensive examination, five substrate analogs (Trp376, Asp404, Ile441, Met519, and Phe649) and two catalytic residues (Asp518 and Asp616) were identified as the preferred inhibitory sites on AG. Furthermore, amino acid preferences and their positionings at different terminals on peptides, including the ultimate (N1 and C1), penultimate (N2 and C2), and antepenultimate (N3 and C3), were explored. Our findings revealed that these peptides were predominantly hydrophobic and tended to contain hydrophobic amino acids with hydrophobic alkyl/aryl side chains (such as lysine, glutamine, proline, and/or arginine). To gain further insights into peptide-AG interactions, docking analysis was performed, which highlighted the significance of hydrophobic bonds as the primary mode of interaction. Conclusions: By pooling all the findings, this review provided essential and practical information for the design and discovery of peptide-based anti-diabetic agents.
{"title":"Exploring α-Glucosidase Inhibitory Peptides: Structure-Activity Relationship Analysis and Perspectives for Designing Potential Anti-Diabetic Agents","authors":"Ainolsyakira Mohd Rodhi, Pei Gee Yap, Olusegun Abayomi Olalere, Chee Yuen Gan","doi":"10.5812/jjnpp-139988","DOIUrl":"https://doi.org/10.5812/jjnpp-139988","url":null,"abstract":"Context: α-Glucosidase (AG) inhibitory peptides represent a promising new class of therapeutic agents for the treatment of diabetes. However, there is a need to further understand the mechanisms and properties of these peptides. Evidence Acquisition: In this comprehensive review, AG inhibitory peptides were categorized into three groups based on their length: short, medium, and long peptides. Data from the BioPEP-UWM database and recent publications were gathered to conduct a structure-activity relationship analysis for these peptides, focusing on identifying their reactive residues and AG binding sites. Results: Through extensive examination, five substrate analogs (Trp376, Asp404, Ile441, Met519, and Phe649) and two catalytic residues (Asp518 and Asp616) were identified as the preferred inhibitory sites on AG. Furthermore, amino acid preferences and their positionings at different terminals on peptides, including the ultimate (N1 and C1), penultimate (N2 and C2), and antepenultimate (N3 and C3), were explored. Our findings revealed that these peptides were predominantly hydrophobic and tended to contain hydrophobic amino acids with hydrophobic alkyl/aryl side chains (such as lysine, glutamine, proline, and/or arginine). To gain further insights into peptide-AG interactions, docking analysis was performed, which highlighted the significance of hydrophobic bonds as the primary mode of interaction. Conclusions: By pooling all the findings, this review provided essential and practical information for the design and discovery of peptide-based anti-diabetic agents.","PeriodicalId":17745,"journal":{"name":"Jundishapur Journal of Natural Pharmaceutical Products","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136351444","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}
Arezoo Moini Jazani, Sahar Shafiei, Hosna Khazaei, Mohammad Hashemnia, Sajad Fakhri, Mohammad Hosein Farzaei
Background: Herbal medicines can be used as a possible therapeutic agent in inflammatory diseases. Objectives: This study aimed to determine the effect of Artemisia vulgaris (AV) hydro-alcoholic extract on oxidative stress and inflammatory damage in an experimental rat model of colitis. Methods: Thirty male Sprague-Dawley rats were randomly divided into 6 groups: Control, colitis, sulfasalazine, AV50, AV100, and AV200. The animals of the AV groups were treated with the hydro-alcoholic extract of A. vulgaris via gavage for 72 h. Body weight was measured at the beginning and end of the experiment. In the end, serum levels of malondialdehyde (MDA) as a lipid peroxidation marker, antioxidants such as glutathione (GSH), superoxide dismutase (SOD) activity, serum tumor necrosis factor-α (TNF-α), and nitric oxide (NO) levels as inflammatory biomarkers were measured. Macroscopic and microscopic damage in the rat's colon was also examined in histological studies. Results: The A. vulgaris extract treatment dose-dependently improved colonic injury (P < 0.001 to P < 0.05) and body weight (P < 0.001) in colitis rats. Moreover, it enhanced SOD activity and GSH levels (P < 0.001) and reduced serum MDA, TNF-α, and NO levels (P < 0.001 to P < 0.01) in the rats with colitis. Conclusions: Treatment with A. vulgaris could mitigate ulcerative colitis (UC) symptoms, which is probably attributed to its antioxidant and anti-inflammatory properties.
{"title":"Effect of Artemisia vulgaris Hydro-Alcoholic Extract on Oxidative Stress and Inflammatory Damages in a Rat Model of Experimental Colitis","authors":"Arezoo Moini Jazani, Sahar Shafiei, Hosna Khazaei, Mohammad Hashemnia, Sajad Fakhri, Mohammad Hosein Farzaei","doi":"10.5812/jjnpp-139442","DOIUrl":"https://doi.org/10.5812/jjnpp-139442","url":null,"abstract":"Background: Herbal medicines can be used as a possible therapeutic agent in inflammatory diseases. Objectives: This study aimed to determine the effect of Artemisia vulgaris (AV) hydro-alcoholic extract on oxidative stress and inflammatory damage in an experimental rat model of colitis. Methods: Thirty male Sprague-Dawley rats were randomly divided into 6 groups: Control, colitis, sulfasalazine, AV50, AV100, and AV200. The animals of the AV groups were treated with the hydro-alcoholic extract of A. vulgaris via gavage for 72 h. Body weight was measured at the beginning and end of the experiment. In the end, serum levels of malondialdehyde (MDA) as a lipid peroxidation marker, antioxidants such as glutathione (GSH), superoxide dismutase (SOD) activity, serum tumor necrosis factor-α (TNF-α), and nitric oxide (NO) levels as inflammatory biomarkers were measured. Macroscopic and microscopic damage in the rat's colon was also examined in histological studies. Results: The A. vulgaris extract treatment dose-dependently improved colonic injury (P < 0.001 to P < 0.05) and body weight (P < 0.001) in colitis rats. Moreover, it enhanced SOD activity and GSH levels (P < 0.001) and reduced serum MDA, TNF-α, and NO levels (P < 0.001 to P < 0.01) in the rats with colitis. Conclusions: Treatment with A. vulgaris could mitigate ulcerative colitis (UC) symptoms, which is probably attributed to its antioxidant and anti-inflammatory properties.","PeriodicalId":17745,"journal":{"name":"Jundishapur Journal of Natural Pharmaceutical Products","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135041833","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}
Background: Chemotherapy, the primary treatment for acute lymphoblastic leukemia (ALL), often yields inadequate responses. Epigallocatechin gallate (EGCG) has been shown to significantly affect tumor cells through various mechanisms, including cell cycle arrest, apoptosis, and autophagy. Objectives: The objective of this study is to explore the impact of EGCG on autophagy, apoptosis, and the interplay between them in NALM-6, a pre-B-ALL cell line. Methods: NALM-6 cells were subjected to various concentrations of EGCG for 24 and 48 hours. Additionally, NH4Cl 10 mM was used as an autophagy inhibitor to examine this mechanism. The EGCG effect on cell viability and apoptosis was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), trypan blue exclusion assay, and flow cytometry. Moreover, western blot analysis and real-time PCR were performed to investigate autophagy. Results: Our findings demonstrated that EGCG significantly affected cell proliferation and viability. It reduced cell viability by 55.24 ± 8.43% (P < 0.0001) while inducing apoptosis by 51.04 ± 1.88% (P = 0.006). Furthermore, in the presence of NH4Cl, EGCG led to a 3.92 ± 1.76-fold increase in LC3 protein level (P = 0.001). It also resulted in an approximately 1.34 ± 0.34-fold enhancement in DRAM1 mRNA expression levels (P = 0.013), while reducing of LC3B by 33.3 ± 30.5% (P = 0.008), P62/SQSTM1 by 46.5 ± 28.26% (P < 0.001), and Atg2B by 45.5 ± 16.25% (P < 0.001). However, the inhibition of autophagy did not alter the apoptosis rate in either untreated or EGCG-treated cells. Conclusions: Overall, our findings suggest that EGCG can trigger apoptosis and autophagy in the NALM-6 cell line. However, blockage of autophagy does not appear to impact apoptosis in this cell line.
{"title":"Autophagy and Apoptosis Cross-Talk in Response to Epigallocatechin Gallate in NALM-6 Cell Line","authors":"Faezeh Gharehchahi, Farahnaz Zare, Gholamreza Rafiei Dehbidi, Zahra Yousefi, Somayeh Pourpirali, Gholamhossein Tamaddon","doi":"10.5812/jjnpp-138054","DOIUrl":"https://doi.org/10.5812/jjnpp-138054","url":null,"abstract":"Background: Chemotherapy, the primary treatment for acute lymphoblastic leukemia (ALL), often yields inadequate responses. Epigallocatechin gallate (EGCG) has been shown to significantly affect tumor cells through various mechanisms, including cell cycle arrest, apoptosis, and autophagy. Objectives: The objective of this study is to explore the impact of EGCG on autophagy, apoptosis, and the interplay between them in NALM-6, a pre-B-ALL cell line. Methods: NALM-6 cells were subjected to various concentrations of EGCG for 24 and 48 hours. Additionally, NH4Cl 10 mM was used as an autophagy inhibitor to examine this mechanism. The EGCG effect on cell viability and apoptosis was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), trypan blue exclusion assay, and flow cytometry. Moreover, western blot analysis and real-time PCR were performed to investigate autophagy. Results: Our findings demonstrated that EGCG significantly affected cell proliferation and viability. It reduced cell viability by 55.24 ± 8.43% (P < 0.0001) while inducing apoptosis by 51.04 ± 1.88% (P = 0.006). Furthermore, in the presence of NH4Cl, EGCG led to a 3.92 ± 1.76-fold increase in LC3 protein level (P = 0.001). It also resulted in an approximately 1.34 ± 0.34-fold enhancement in DRAM1 mRNA expression levels (P = 0.013), while reducing of LC3B by 33.3 ± 30.5% (P = 0.008), P62/SQSTM1 by 46.5 ± 28.26% (P < 0.001), and Atg2B by 45.5 ± 16.25% (P < 0.001). However, the inhibition of autophagy did not alter the apoptosis rate in either untreated or EGCG-treated cells. Conclusions: Overall, our findings suggest that EGCG can trigger apoptosis and autophagy in the NALM-6 cell line. However, blockage of autophagy does not appear to impact apoptosis in this cell line.","PeriodicalId":17745,"journal":{"name":"Jundishapur Journal of Natural Pharmaceutical Products","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135141647","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}
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