Pub Date : 2024-11-22DOI: 10.1016/j.jep.2024.119116
Yetunde Victoria Aladenika , Moses Orimoloye Akinjiyan , Olusola Olalekan Elekofehinti , Isaac Gbadura Adanlawo
Ethnopharmacological relevance
Traditional and medicinal plant treatments for diabetes mellitus (DM) include Bambusa vulgaris (Shrad.), but little is known about the mechanism.
Aim of the study
This study investigated the antioxidant and hepatoprotective effects of B. vulgaris.
Materials and methods
DM was induced by intraperitoneal injection of streptozotocin (60 mg/kg). Thirty (30) male Wistar rats were then divided into six groups: control; diabetic control; metformin (100 mg/kg); 50, 100, and 200 mg/kg of B. vulgaris (BV) treated. Fasting blood glucose and weights of rats were monitored at three-day intervals and sacrifice was done after twenty-one days. The activities of SOD, CAT, and liver marker enzymes were investigated. The expressions of insulin-sensitive (TGR5, GLP-1), pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, ICAM), and antioxidant genes (SOD, CAT) were investigated using RT-PCR. Schrödinger suites and Auto-Dock Vina were used for docking B. vulgaris phytocompounds identified from works of literature with TGR-5. The liver's histology was also assessed.
Results
BV increased antioxidant activities and reduced liver marker activities in the serum. BV downregulated the expressions of genes associated with inflammation and upregulated antioxidant and insulin-sensitive genes relative to diabetic control. BV regenerated the liver architectural tissue degenerated by inflammation due to STZ. B. vulgaris phytocompounds like farobin A (−11.493 kcal/mol), orientin (−12.296 kcal/mol), and rutin (−12.581 kcal/mol) have better binding energy with TGR5 than metformin (−1.961 kcal/mol).
Conclusion
The hepatoprotective and ameliorative effect of B. vulgaris in DM could be due to its ability to boost antioxidant status and insulin secretion and reduce inflammation.
{"title":"Bambusa vulgaris leaf extract inhibits the inflammatory and oxidative pathways in streptozotocin-induced diabetic rats","authors":"Yetunde Victoria Aladenika , Moses Orimoloye Akinjiyan , Olusola Olalekan Elekofehinti , Isaac Gbadura Adanlawo","doi":"10.1016/j.jep.2024.119116","DOIUrl":"10.1016/j.jep.2024.119116","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Traditional and medicinal plant treatments for diabetes mellitus (DM) include <em>Bambusa vulgaris</em> (Shrad.), but little is known about the mechanism.</div></div><div><h3>Aim of the study</h3><div>This study investigated the antioxidant and hepatoprotective effects of <em>B. vulgaris.</em></div></div><div><h3>Materials and methods</h3><div>DM was induced by intraperitoneal injection of streptozotocin (60 mg/kg). Thirty (30) male Wistar rats were then divided into six groups: control; diabetic control; metformin (100 mg/kg); 50, 100, and 200 mg/kg of <em>B. vulgaris</em> (BV) treated. Fasting blood glucose and weights of rats were monitored at three-day intervals and sacrifice was done after twenty-one days. The activities of SOD, CAT, and liver marker enzymes were investigated. The expressions of insulin-sensitive (TGR5, GLP-1), pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, ICAM), and antioxidant genes (SOD, CAT) were investigated using RT-PCR. Schrödinger suites and Auto-Dock Vina were used for docking <em>B. vulgaris</em> phytocompounds identified from works of literature with TGR-5. The liver's histology was also assessed.</div></div><div><h3>Results</h3><div>BV increased antioxidant activities and reduced liver marker activities in the serum. BV downregulated the expressions of genes associated with inflammation and upregulated antioxidant and insulin-sensitive genes relative to diabetic control. BV regenerated the liver architectural tissue degenerated by inflammation due to STZ. <em>B. vulgaris</em> phytocompounds like farobin A (−11.493 kcal/mol), orientin (−12.296 kcal/mol), and rutin (−12.581 kcal/mol) have better binding energy with TGR5 than metformin (−1.961 kcal/mol).</div></div><div><h3>Conclusion</h3><div>The hepatoprotective and ameliorative effect of <em>B. vulgaris</em> in DM could be due to its ability to boost antioxidant status and insulin secretion and reduce inflammation.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"339 ","pages":"Article 119116"},"PeriodicalIF":4.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-22DOI: 10.1016/j.jep.2024.119155
Ji Yeon Hwang , Mi-Yeon Kim , Jae Youl Cho
Ethnopharmacological relevance
Traditional herbal medicine books “Shin Rhong Bon Cho Kyung” and “Hyang Yak Jip Sung Bang” mentioned that Bletilla striata (Thunb.) Rchb.f. (Orchidaceae) was often used as a medicinal plant and is used in oriental medicine to treat wounds, inflammatory symptoms, and ulcers in stomach, lung, and skin. However, systematic studies on its value as a promising anti-inflammatory remedy were not fully elucidated yet.
Aim of the study: The eventual goal of this paper was to explore anti-inflammatory and anti-gastritis effects of Bletilla striata and its inhibitory mechanism with an ethanol extract of this plant (Bs-EE).
Materials and methods
In vitro study includes nitric oxide (NO) inhibitory test by was Griess assay, cell viability check by MTT assay, mRNA level analysis of inflammatory genes by PCR and RT-PCR, and protein level analysis by Western blotting and CESTA. In vivo analysis was done with a mouse gastritis model triggered by HCl/EtOH. Phytochemical finger printing result was observed by GC/MS-MS.
Results
Our in vitro trials showed that Bs-EE dose-dependently reduced NO production in lipopolysaccharide-, Poly(I:C)-, and Pam3CSK-treated RAW264.7 cells without causing cytotoxicity, as shown by an MTT assay. The levels of inflammation-related genes (iNOS, IL-6, IL-1β) showed meaningful reductions in RT-PCR and real-time PCR. The NF-κB activity enhanced in MyD88-overexpressing HEK293T cells was strongly reduced by Bs-EE. Western blotting results indicated that the Bs-EE suppressed the phosphorylation of IκBα, IKKα/β, AKT, p65, p50, Syk, and Src, which produced anti-inflammatory effects. Both Syk and Src were found to be direct targets of Bs-EE. This extract attenuated the inflammatory effect in a murine acute gastritis model induced by HCl/EtOH.
Conclusions
These findings suggest that an ethanol extract of Bletilla striata could be developed as a promising natural anti-inflammatory drug or health functional food with NF-κB pathway inhibitory activity.
{"title":"Syk/Src/NF-κB axis is essentially targeted in anti-inflammatory and anti-gastritis effects of Bletilla striata ethanol extract","authors":"Ji Yeon Hwang , Mi-Yeon Kim , Jae Youl Cho","doi":"10.1016/j.jep.2024.119155","DOIUrl":"10.1016/j.jep.2024.119155","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Traditional herbal medicine books “Shin Rhong Bon Cho Kyung” and “Hyang Yak Jip Sung Bang” mentioned that <em>Bletilla striata</em> (Thunb.) Rchb.f. (Orchidaceae) was often used as a medicinal plant and is used in oriental medicine to treat wounds, inflammatory symptoms, and ulcers in stomach, lung, and skin. However, systematic studies on its value as a promising anti-inflammatory remedy were not fully elucidated yet.</div><div><em>Aim of the study</em>: The eventual goal of this paper was to explore anti-inflammatory and anti-gastritis effects of <em>Bletilla striata</em> and its inhibitory mechanism with an ethanol extract of this plant (Bs-EE).</div></div><div><h3>Materials and methods</h3><div><em>In vitro</em> study includes nitric oxide (NO) inhibitory test by was Griess assay, cell viability check by MTT assay, mRNA level analysis of inflammatory genes by PCR and RT-PCR, and protein level analysis by Western blotting and CESTA. In vivo analysis was done with a mouse gastritis model triggered by HCl/EtOH. Phytochemical finger printing result was observed by GC/MS-MS.</div></div><div><h3>Results</h3><div>Our <em>in vitro</em> trials showed that Bs-EE dose-dependently reduced NO production in lipopolysaccharide-, Poly(I:C)-, and Pam3CSK-treated RAW264.7 cells without causing cytotoxicity, as shown by an MTT assay. The levels of inflammation-related genes (iNOS, IL-6, IL-1β) showed meaningful reductions in RT-PCR and real-time PCR. The NF-κB activity enhanced in MyD88-overexpressing HEK293T cells was strongly reduced by Bs-EE. Western blotting results indicated that the Bs-EE suppressed the phosphorylation of IκBα, IKKα/β, AKT, p65, p50, Syk, and Src, which produced anti-inflammatory effects. Both Syk and Src were found to be direct targets of Bs-EE. This extract attenuated the inflammatory effect in a murine acute gastritis model induced by HCl/EtOH.</div></div><div><h3>Conclusions</h3><div>These findings suggest that an ethanol extract of <em>Bletilla striata</em> could be developed as a promising natural anti-inflammatory drug or health functional food with NF-κB pathway inhibitory activity.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"339 ","pages":"Article 119155"},"PeriodicalIF":4.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bergenia ciliata (Haw.) Sternb. (Family Saxifragaceae) remains mentioned as Pashanbheda in Ayurveda and Zakhmehayat in Unani. In North Waziristan, Pakistan, indigenous communities use this plant in ethnodentistry to treat tooth decay and toothaches. However, scientific evidence on its mode of action is still lacking.
Aim of the study
To evaluate the effect of extracts and fractions of B. ciliata flower against oral bacteria and elucidate the possible antibacterial and antibiofilm mechanism.
Materials and methods
Prepared extract of B. ciliata flowers were checked for its antibacterial activity against oral (S. mutans, S. pyogenes, S. oralis) and opportunistic bacteria (Staphylococcus aureus, Citrobacter clonae and Achromobacter insolitus). Preparative TLC-bioautography and silica gel column chromatography was used to isolate bioactive compounds. HRESI-MS and NMR studies were employed for its structural elucidation. Antibacterial and antibiofilm activities of extracts and isolated compounds were studied against S. mutans. Scanning Electron Microscope studies indicated membrane damage. Reactive Oxygen Species (ROS) production, lipid peroxidation and cytoplasmic leakage were also assessed.
Results
The most active ethyl acetate extract (EA) showed potent inhibitory effect against S. mutans (0.390 μg/μl). TLC–bioautography indicated spots F1 & F2 to show inhibition zones. F1 was identified as kaempferol. This is the first report on flowers of B. ciliata against oral infection. The mode of action of F1 can be attributed to its ability to destroy the membrane integrity, reducing and disrupting biofilm. It also produced ROS within the bacterial cell, leading to lipid peroxidation and subsequently causing death of the bacteria.
Conclusion
Kaempferol is the active compound in bioactive spot F1 which showed antibacterial and antibiofilm activity. The antibacterial activity can be linked with the membrane disrupting properties of kaempferol and producing ROS inside S. mutans. Thus, phytochemicals derived from B. ciliata can be used in the development of pharmaceutical dental products.
民族药理学意义：Bergenia ciliata (Haw.) Sternb.（Saxifragaceae 科）在阿育吠陀中被称为 Pashanbheda，在尤那尼中被称为 Zakhmehayat。在巴基斯坦北瓦济里斯坦，土著社区在民族牙科中使用这种植物治疗蛀牙和牙痛。然而，有关其作用模式的科学证据仍然缺乏：研究目的：评估纤毛虫花提取物和馏分对口腔细菌的作用，并阐明可能的抗菌和抗生物膜机制：检查制备的纤毛虫花提取物对口腔细菌（变异性嗜血杆菌、化脓性嗜血杆菌、口腔嗜血杆菌）和机会性细菌（金黄色葡萄球菌、克罗恩柠檬酸杆菌和破产阿奇霉素）的抗菌活性。采用制备型 TLC 生物层析和硅胶柱层析分离生物活性化合物。利用 HRESI-MS 和 NMR 研究对其结构进行了阐明。研究了提取物和分离出的化合物对 S. mutans 的抗菌和抗生物膜活性。扫描电子显微镜研究表明存在膜损伤。此外，还评估了活性氧生成（ROS）、脂质过氧化和细胞质渗漏：结果：活性最强的乙酸乙酯提取物（EA）对突变杆状病毒有很强的抑制作用（0.390 μg/μl）。TLC 生物指纹图谱显示 F1 和 F2 点显示抑制区。F1 被鉴定为山奈酚。这是关于纤毛虫花对口腔感染的首次报道。F1 的作用模式可归因于其破坏膜完整性、减少和破坏生物膜的能力。它还能在细菌细胞内产生 ROS，导致脂质过氧化，进而导致细菌死亡：山奈酚是生物活性斑 F1 中的活性化合物，具有抗菌和抗生物膜活性。山奈酚的抗菌活性可能与山奈酚的膜破坏特性以及在变异单胞菌体内产生 ROS 有关。因此，从纤毛虫中提取的植物化学物质可用于开发药物牙科产品。
{"title":"Antibacterial and antibiofilm activities of extract and bioactive compounds from Bergenia ciliata (Haw.) Sternb. flowers against Streptococcus mutans through cell membrane damage","authors":"Nirza Moktan , Rahul Laxman Gajbhiye , T.V.V.S. Sahithi , Dijendra Nath Roy , Rita Kundu , Anindita Banerjee","doi":"10.1016/j.jep.2024.119144","DOIUrl":"10.1016/j.jep.2024.119144","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Bergenia ciliata</em> (Haw.) Sternb. (Family Saxifragaceae) remains mentioned as Pashanbheda in Ayurveda and Zakhmehayat in Unani. In North Waziristan, Pakistan, indigenous communities use this plant in ethnodentistry to treat tooth decay and toothaches. However, scientific evidence on its mode of action is still lacking.</div></div><div><h3>Aim of the study</h3><div>To evaluate the effect of extracts and fractions of <em>B. ciliata</em> flower against oral bacteria and elucidate the possible antibacterial and antibiofilm mechanism.</div></div><div><h3>Materials and methods</h3><div>Prepared extract of <em>B. ciliata</em> flowers were checked for its antibacterial activity against oral (<em>S. mutans</em>, <em>S. pyogenes</em>, <em>S. oralis</em>) and opportunistic bacteria (<em>Staphylococcus aureus, Citrobacter clonae</em> and <em>Achromobacter insolitus</em>). Preparative TLC-bioautography and silica gel column chromatography was used to isolate bioactive compounds. HRESI-MS and NMR studies were employed for its structural elucidation. Antibacterial and antibiofilm activities of extracts and isolated compounds were studied against <em>S. mutans</em>. Scanning Electron Microscope studies indicated membrane damage. Reactive Oxygen Species (ROS) production, lipid peroxidation and cytoplasmic leakage were also assessed.</div></div><div><h3>Results</h3><div>The most active ethyl acetate extract (EA) showed potent inhibitory effect against <em>S. mutans</em> (0.390 μg/μl). TLC–bioautography indicated spots F1 & F2 to show inhibition zones. F1 was identified as kaempferol. This is the first report on flowers of <em>B. ciliata</em> against oral infection. The mode of action of F1 can be attributed to its ability to destroy the membrane integrity, reducing and disrupting biofilm. It also produced ROS within the bacterial cell, leading to lipid peroxidation and subsequently causing death of the bacteria.</div></div><div><h3>Conclusion</h3><div>Kaempferol is the active compound in bioactive spot F1 which showed antibacterial and antibiofilm activity. The antibacterial activity can be linked with the membrane disrupting properties of kaempferol and producing ROS inside <em>S. mutans</em>. Thus, phytochemicals derived from <em>B. ciliata</em> can be used in the development of pharmaceutical dental products.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"339 ","pages":"Article 119144"},"PeriodicalIF":4.8,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-21DOI: 10.1016/j.jep.2024.119152
Qingping Xiong, Yuhan Zhang, Yisa Cai, Yong Zhu, Yi Jing, Heng Li, Guangzhen Zheng, Jie Chen, Shiyan Wang, Zhimeng Xu, Yadong Yu, Yingying Shi, Hui Yong, Xiangyang Cao
Ethnopharmacological relevance: Buyang Huanwu Decoction (BYHWD), a traditional prescription known for its Supplementing Qi and Promoting Blood Circulation, has demonstrated noteworthy therapeutic roles in regulating macrophage polarization to atherosclerosis (AS). However, its underlying mechanisms remain unknown.
Aim of the study: The purpose of this paper was to decipher mechanism of BYHWD in regulating macrophage polarization to alleviate AS.
Materials and methods: A comprehensive virtual screening strategy, incorporating network pharmacology and batch molecular docking, combined with experimental validation techniques, was employed to systematically elucidate the underlying mechanism of BYHWD regulating macrophage polarization to alleviate AS.
Results: Firstly, based on high-fat diet induced AS model in apolipoprotein E-deficient mice, it was found that BYHWD can significantly regulate macrophage polarization to alleviate AS. Then, the network pharmacological analysis revealed that the core targets of BYHWD regulating macrophage polarization to alleviate AS mainly involved TP53, AKT1 and BCL2. The mitochondrial function and metabolism were the main biological processes. Meanwhile, the main chemical components were identified as 3-O-p-coumaroylquinic acid, D-mandelonitrile, Ellagic acid, Ferulic acid, 5-hydroxy-L-tryptophan zwitterion, Isoliquiritigenin, Senkyunolide-F, Anofinic acid, Trimethylhydroquinone and Senkyunolide-E by batch molecular docking strategy. Further, the in vitro experiments demonstrated that BYHWD not only regulated macrophage polarization and alleviated macrophage foam formation but also modulated mitochondrial function and the expression of TP53, p-AKT, and BCL2 proteins. Finally, multivariate statistical analysis confirmed that the ameliorative effect of BYHWD on AS was closely related to mitochondrial function and macrophage polarization regulated by TP53, AKT1 and BCL2.
Conclusions: BYHWD could activate key targets, including TP53, AKT1, and BCL2, to alleviate mitochondrial dysfunction and regulate macrophage polarization, thereby improving AS. The 10 active compounds of BYHWD, including 5-hydroxy-L-tryptophan zwitterion and Isoliquiritigenin, played an important role in regulating macrophages polarization to alleviate AS.
{"title":"Deciphering mechanism of Buyang Huanwu Decoction in regulating macrophage polarization to alleviate atherosclerosis via virtual screening and experimental verification.","authors":"Qingping Xiong, Yuhan Zhang, Yisa Cai, Yong Zhu, Yi Jing, Heng Li, Guangzhen Zheng, Jie Chen, Shiyan Wang, Zhimeng Xu, Yadong Yu, Yingying Shi, Hui Yong, Xiangyang Cao","doi":"10.1016/j.jep.2024.119152","DOIUrl":"https://doi.org/10.1016/j.jep.2024.119152","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Buyang Huanwu Decoction (BYHWD), a traditional prescription known for its Supplementing Qi and Promoting Blood Circulation, has demonstrated noteworthy therapeutic roles in regulating macrophage polarization to atherosclerosis (AS). However, its underlying mechanisms remain unknown.</p><p><strong>Aim of the study: </strong>The purpose of this paper was to decipher mechanism of BYHWD in regulating macrophage polarization to alleviate AS.</p><p><strong>Materials and methods: </strong>A comprehensive virtual screening strategy, incorporating network pharmacology and batch molecular docking, combined with experimental validation techniques, was employed to systematically elucidate the underlying mechanism of BYHWD regulating macrophage polarization to alleviate AS.</p><p><strong>Results: </strong>Firstly, based on high-fat diet induced AS model in apolipoprotein E-deficient mice, it was found that BYHWD can significantly regulate macrophage polarization to alleviate AS. Then, the network pharmacological analysis revealed that the core targets of BYHWD regulating macrophage polarization to alleviate AS mainly involved TP53, AKT1 and BCL2. The mitochondrial function and metabolism were the main biological processes. Meanwhile, the main chemical components were identified as 3-O-p-coumaroylquinic acid, D-mandelonitrile, Ellagic acid, Ferulic acid, 5-hydroxy-L-tryptophan zwitterion, Isoliquiritigenin, Senkyunolide-F, Anofinic acid, Trimethylhydroquinone and Senkyunolide-E by batch molecular docking strategy. Further, the in vitro experiments demonstrated that BYHWD not only regulated macrophage polarization and alleviated macrophage foam formation but also modulated mitochondrial function and the expression of TP53, p-AKT, and BCL2 proteins. Finally, multivariate statistical analysis confirmed that the ameliorative effect of BYHWD on AS was closely related to mitochondrial function and macrophage polarization regulated by TP53, AKT1 and BCL2.</p><p><strong>Conclusions: </strong>BYHWD could activate key targets, including TP53, AKT1, and BCL2, to alleviate mitochondrial dysfunction and regulate macrophage polarization, thereby improving AS. The 10 active compounds of BYHWD, including 5-hydroxy-L-tryptophan zwitterion and Isoliquiritigenin, played an important role in regulating macrophages polarization to alleviate AS.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119152"},"PeriodicalIF":4.8,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ethnopharmacological relevance: Cinnamomum migao H.W. Li, commonly known as migao (MG), is used in the Miao region of China for treating cardiovascular and cerebrovascular diseases, attributed to its detoxifying (Jiedu in Chinese), blood-activating (Huoxue in Chinese), and Qi-promoting (Tongqi in Chinese) effects. However, the therapeutic potential of MG for ischemic stroke (IS) has yet to be explored. Therefore, this study was to explore the protective effect of MG against cerebral ischemia-reperfusion injury caused by IS.
Aim of the study: The aim of this study was to investigate whether ethanol extract of MG (EEMG) attenuates cerebral ischemia-reperfusion injury, and explored the underlying mechanisms.
Materials and methods: Middle cerebral artery occlusion and reperfusion (MCAO/R) was established, and the efficacy of EEMG was evaluated using triphenyltetrazolium chloride (TTC), immunofluorescence, hematoxylin-eosin staining (HE) staining, and real-time quantitative PCR (qRT-PCR). Qualitative analysis of EEMG was analyzed for chemical composition by liquid chromatography-mass spectrometry (LC-MS). The molecular mechanism of EEMG was explored by metabolomics, network pharmacology, immunoblotting, immunofluorescence staining, gene knockdown, and agonist treatment.
Results: The results showed that EEMG can alleviate ischemic injury in MCAO/R-operated rats and neuronal damage of OGD/R-treated SH-SY5Y cells. Specifically, EEHGT inhibited the release of inflammatory factors and reversed serum metabolic profile disorders of MCAO/R rats. Network pharmacology analysis showed that the PI3K-Akt and NF-κB signaling pathways maybe involved in EEMG-mediated neuroprotective effects on ischemic injury and inhibition of inflammatory response. As we expected, EEMG can activate PI3K-AKT and suppress NF-kB signaling pathways both in MCAO/R-operated rats and OGD/R-treated BV2 cells. The results showed that knockdown of TLR4 abolished the EEMG-mediated inhibition on neuroinflammation in OGD/R-treated BV2 cells. After treating BV2 cells with the TLR4 agonist neoseptin 3, EEMG showed a trend toward inhibiting neuroinflammation but with no significant difference. Additionally, EEMG was found to improve liver injury caused by cerebral ischemia-reperfusion and associated with NF-κB signaling pathway in this study.
Conclusions: Collectively, this study demonstrated that EEMG attenuates neuroinflammation in cerebral ischemia-reperfusion injury via regulating TLR4-PI3K-Akt-NF-κB pathways.
{"title":"Ethanol extracts of Cinnamomum migao H.W. Li attenuates neuroinflammation in cerebral ischemia-reperfusion injury via regulating TLR4-PI3K-Akt-NF-κB pathways.","authors":"Wenze Wu, Libin Xu, Danyang Mu, Dequan Wang, Shaowen Tan, Linge Liu, Yubo Li, Huifang Chai, Yue Hou","doi":"10.1016/j.jep.2024.119150","DOIUrl":"https://doi.org/10.1016/j.jep.2024.119150","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Cinnamomum migao H.W. Li, commonly known as migao (MG), is used in the Miao region of China for treating cardiovascular and cerebrovascular diseases, attributed to its detoxifying (Jiedu in Chinese), blood-activating (Huoxue in Chinese), and Qi-promoting (Tongqi in Chinese) effects. However, the therapeutic potential of MG for ischemic stroke (IS) has yet to be explored. Therefore, this study was to explore the protective effect of MG against cerebral ischemia-reperfusion injury caused by IS.</p><p><strong>Aim of the study: </strong>The aim of this study was to investigate whether ethanol extract of MG (EEMG) attenuates cerebral ischemia-reperfusion injury, and explored the underlying mechanisms.</p><p><strong>Materials and methods: </strong>Middle cerebral artery occlusion and reperfusion (MCAO/R) was established, and the efficacy of EEMG was evaluated using triphenyltetrazolium chloride (TTC), immunofluorescence, hematoxylin-eosin staining (HE) staining, and real-time quantitative PCR (qRT-PCR). Qualitative analysis of EEMG was analyzed for chemical composition by liquid chromatography-mass spectrometry (LC-MS). The molecular mechanism of EEMG was explored by metabolomics, network pharmacology, immunoblotting, immunofluorescence staining, gene knockdown, and agonist treatment.</p><p><strong>Results: </strong>The results showed that EEMG can alleviate ischemic injury in MCAO/R-operated rats and neuronal damage of OGD/R-treated SH-SY5Y cells. Specifically, EEHGT inhibited the release of inflammatory factors and reversed serum metabolic profile disorders of MCAO/R rats. Network pharmacology analysis showed that the PI3K-Akt and NF-κB signaling pathways maybe involved in EEMG-mediated neuroprotective effects on ischemic injury and inhibition of inflammatory response. As we expected, EEMG can activate PI3K-AKT and suppress NF-kB signaling pathways both in MCAO/R-operated rats and OGD/R-treated BV2 cells. The results showed that knockdown of TLR4 abolished the EEMG-mediated inhibition on neuroinflammation in OGD/R-treated BV2 cells. After treating BV2 cells with the TLR4 agonist neoseptin 3, EEMG showed a trend toward inhibiting neuroinflammation but with no significant difference. Additionally, EEMG was found to improve liver injury caused by cerebral ischemia-reperfusion and associated with NF-κB signaling pathway in this study.</p><p><strong>Conclusions: </strong>Collectively, this study demonstrated that EEMG attenuates neuroinflammation in cerebral ischemia-reperfusion injury via regulating TLR4-PI3K-Akt-NF-κB pathways.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119150"},"PeriodicalIF":4.8,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-21DOI: 10.1016/j.jep.2024.119145
Jialei Song , Wuling Liu , Xiao Xiao , Jingrui Song , Chunlin Wang , Babu Gajendran , Xuenai Wei , Changfu Yang , Yunzhi Chen , Yiying Yang , Lei Huang , Junrong Song , Yaacov Ben-David , Yanmei Li
<div><h3>Ethnopharmacological relevance</h3><div>The theory of traditional Chinese medicine (TCM) views leukemia as an imbalance between cell growth and death mainly caused by blood stasis. Medicinal plants <em>Aglaia</em> Lour. (family Meliaceae) are traditionally used as folk medicine in China. It possesses the effects of removing blood stasis and swelling for treatment of cancer. Rocaglamide (RocA) is the main active phytochemical component of the genus <em>Aglaia</em> Lour. Possessing highly anti-leukemia properties. However, the molecular mechanisms by which RocA exerts its anti-growth effect on erythroleukemia cells are largely unknown.</div></div><div><h3>Aim of the study</h3><div>This study aimed to explore the underlying mechanism and glucose metabolism regulation effects of RocA responsible for its anti-erythroleukemia activity.</div></div><div><h3>Materials and methods</h3><div>Human erythroleukemic cells were tested for glucose metabolism and treated with glucose deprivation and RocA. MTT assay, cell cycle and apoptosis were used to elucidate growth inhibition. Glucose uptake, glucose consumption and lactate production were evaluated for identification of glucose metabolism. Luciferase assay and ChIP were used to examine the transcriptional activity of c-MYC on the conserved E-boxes binding of the <em>TXNIP</em> (<em>thioredoxin-interacting protein</em>) and <em>HK2</em> (<em>hexokinase 2</em>) <em>genes</em>. siRNA, shRNA and exogenous transfection were employed to elucidate the effects of TXNIP and HK2 on glucose metabolism.</div></div><div><h3>Results</h3><div>We find that glucose deprivation results in growth inhibition, cell cycle arrest and extensive apoptosis in erythroleukemic cells accompanied by downregulation of c-MYC and HK2, responsible for glucose metabolism. The similar results emerged in RocA treated erythroleukemic cells in presence of glucose. RocA is shown to decrease glucose uptake, glucose consumption and lactate production. Mechanistically, RocA dramatically increases TXNIP expression through interference with c-MYC binding to the promoter of the <em>TXNIP</em> gene. RocA also represses c-MYC transcriptional recognition of conserved E-boxes in the <em>HK2</em> first intron, resulting in HK2 loss. These results implicate c-MYC as an important regulator of TXNIP and HK2 after RocA treatment. TXNIP overexpression or knockdown of HK2 suppresses the proliferation of erythroleukemic cells. Ectopic TXNIP expression restricts glucose uptake and HK2 suppression decreases glucose utilization. Further, our data suggests that loss of HK2 weakens the RocA-driven inhibition effects. We propose repression of c-MYC or the binding by RocA upregulates TXNIP and downregulates HK2, possibly contributes to growth inhibition in human erythroleukemic cells.</div></div><div><h3>Conclusions</h3><div>This study uncovers molecular mechanism of RocA against leukemic cells proliferation, linking the anti-erythroleukemia properties of RocA to
{"title":"Rocaglamide reprograms glucose metabolism in erythroleukemic cells via c-MYC transcriptional regulation of TXNIP and HK2","authors":"Jialei Song , Wuling Liu , Xiao Xiao , Jingrui Song , Chunlin Wang , Babu Gajendran , Xuenai Wei , Changfu Yang , Yunzhi Chen , Yiying Yang , Lei Huang , Junrong Song , Yaacov Ben-David , Yanmei Li","doi":"10.1016/j.jep.2024.119145","DOIUrl":"10.1016/j.jep.2024.119145","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>The theory of traditional Chinese medicine (TCM) views leukemia as an imbalance between cell growth and death mainly caused by blood stasis. Medicinal plants <em>Aglaia</em> Lour. (family Meliaceae) are traditionally used as folk medicine in China. It possesses the effects of removing blood stasis and swelling for treatment of cancer. Rocaglamide (RocA) is the main active phytochemical component of the genus <em>Aglaia</em> Lour. Possessing highly anti-leukemia properties. However, the molecular mechanisms by which RocA exerts its anti-growth effect on erythroleukemia cells are largely unknown.</div></div><div><h3>Aim of the study</h3><div>This study aimed to explore the underlying mechanism and glucose metabolism regulation effects of RocA responsible for its anti-erythroleukemia activity.</div></div><div><h3>Materials and methods</h3><div>Human erythroleukemic cells were tested for glucose metabolism and treated with glucose deprivation and RocA. MTT assay, cell cycle and apoptosis were used to elucidate growth inhibition. Glucose uptake, glucose consumption and lactate production were evaluated for identification of glucose metabolism. Luciferase assay and ChIP were used to examine the transcriptional activity of c-MYC on the conserved E-boxes binding of the <em>TXNIP</em> (<em>thioredoxin-interacting protein</em>) and <em>HK2</em> (<em>hexokinase 2</em>) <em>genes</em>. siRNA, shRNA and exogenous transfection were employed to elucidate the effects of TXNIP and HK2 on glucose metabolism.</div></div><div><h3>Results</h3><div>We find that glucose deprivation results in growth inhibition, cell cycle arrest and extensive apoptosis in erythroleukemic cells accompanied by downregulation of c-MYC and HK2, responsible for glucose metabolism. The similar results emerged in RocA treated erythroleukemic cells in presence of glucose. RocA is shown to decrease glucose uptake, glucose consumption and lactate production. Mechanistically, RocA dramatically increases TXNIP expression through interference with c-MYC binding to the promoter of the <em>TXNIP</em> gene. RocA also represses c-MYC transcriptional recognition of conserved E-boxes in the <em>HK2</em> first intron, resulting in HK2 loss. These results implicate c-MYC as an important regulator of TXNIP and HK2 after RocA treatment. TXNIP overexpression or knockdown of HK2 suppresses the proliferation of erythroleukemic cells. Ectopic TXNIP expression restricts glucose uptake and HK2 suppression decreases glucose utilization. Further, our data suggests that loss of HK2 weakens the RocA-driven inhibition effects. We propose repression of c-MYC or the binding by RocA upregulates TXNIP and downregulates HK2, possibly contributes to growth inhibition in human erythroleukemic cells.</div></div><div><h3>Conclusions</h3><div>This study uncovers molecular mechanism of RocA against leukemic cells proliferation, linking the anti-erythroleukemia properties of RocA to","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"339 ","pages":"Article 119145"},"PeriodicalIF":4.8,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-21DOI: 10.1016/j.jep.2024.119146
Dan Cheng, Sheng Sheng, Jing Hu, Shanshan Cai, Yan Liu, Ruixi Gan, Zhenpeng Zhu, Lan Ge, Weidong Chen, Xiaoyu Cheng
<p><strong>Ethnopharmacological significance: </strong>The therapeutic efficacy of Ershen Zhenwu Decoction (ESZWD)-a famous formulation from Xin'an for patients with chronic heart failure heart-kidney Yang deficiency (CHF-HKYD)-is well established. Still, the underlying molecular mechanism is not clear.</p><p><strong>Aim of the study: </strong>This study investigated mechanisms by which ESZWD suppresses cardiac pathology, including myocardial fibrosis, in CHF-HKYD model rats and Ang II-stimulated cardiac fibroblasts (CFs).</p><p><strong>Materials and methods: </strong>The components in ESZWD were analyzed by ultra-high-performance liquid chromatography coupled with Quadrupole Time-Of-Flight mass spectrometry (UHPLC-Q-TOF-MS). CHF-HKYD model was established in the male Sprague-Dawley rats through bilateral thyroidectomy and intraperitoneal administration of 0.02% doxorubicin (DOX), twice weekly for 3 weeks. Subsequently, the CHF-HKYD model rats were randomly categorized into the Model, ESZWD-L (3.96 g/kg/d ESZWD), ESZWD-M (7.92 g/kg/d ESZWD), ESZWD-H (15.84 g/kg/d ESZWD), and Sac/Val (68 mg/kg/d sacubitril/valsartan) groups and treated daily for 4 weeks. As a control, the sham surgery group (Sham) was used. Primary cardiac fibroblasts (CFs) were categorized into Control, Model, ESZWD, and Sac/Val groups. Then, the CFs were stimulated with Ang-II. The ESZWD and Sac/Val groups were incubated with different concentrations of drug-containing sera and their effects on CF viability were assessed via the CCK-8 assay. The ESZWD and Sac/Val groups received drug-containing serum concentrations determined by CCK-8 assay results. The cardioprotective effects of ESZWD were determined using echocardiography, Hematoxylin & Eosin (H&E) staining, Masson staining, and Sirius red staining, and the Enzyme Linked Immunosorbent Assay (ELISA). ESZWD's effects on the Ras Homolog Gene Family Member A (RhoA) / Rho-Associated Coiled-Coil Kinases (ROCKs) signaling pathway and myocardial fibrosis were assessed by Western blotting and Quantitative Real-Time PCR (qRT-PCR) analyses. Immunofluorescence was used to observe fibrotic markers in CFs.</p><p><strong>Results: </strong>ESZWD treatment improved cardiac function in the CHF-HKYD rats by significantly reducing myocardial fibrosis and ventricular remodeling. ESZWD treatment increased the rats' body temperature (T<sub>b</sub>) and 24-hour urine volume, left ventricular ejection fraction (LVEF) and LV fractional shortening (LVFS), and decreased LV internal systolic diameter (LVIDs), LV internal diastolic diameter (LVIDd), and heart weight/ body weight (HW/BW) compared to the Model group. In comparison to the model rats, ESZWD treatment decreased serum levels of B-type natriuretic peptide precursor (NT-proBNP), tumor necrosis factor-alpha (TNF-α), interleukin-11 (IL-11), and IL-17A. ESZWD treatment significantly down-regulated the protein and mRNA expression levels of collagen I A1, α-SMA, RhoA, ROCK1, and ROCK2 in the heart tis
{"title":"Ershen Zhenwu Decoction Suppresses Myocardial Fibrosis of Chronic Heart Failure with Heart-Kidney Yang Deficiency by Down-Regulating the Ras Homolog Gene Family Member A/Rho-Associated Coiled-Coil Kinases Signaling Pathway.","authors":"Dan Cheng, Sheng Sheng, Jing Hu, Shanshan Cai, Yan Liu, Ruixi Gan, Zhenpeng Zhu, Lan Ge, Weidong Chen, Xiaoyu Cheng","doi":"10.1016/j.jep.2024.119146","DOIUrl":"https://doi.org/10.1016/j.jep.2024.119146","url":null,"abstract":"<p><strong>Ethnopharmacological significance: </strong>The therapeutic efficacy of Ershen Zhenwu Decoction (ESZWD)-a famous formulation from Xin'an for patients with chronic heart failure heart-kidney Yang deficiency (CHF-HKYD)-is well established. Still, the underlying molecular mechanism is not clear.</p><p><strong>Aim of the study: </strong>This study investigated mechanisms by which ESZWD suppresses cardiac pathology, including myocardial fibrosis, in CHF-HKYD model rats and Ang II-stimulated cardiac fibroblasts (CFs).</p><p><strong>Materials and methods: </strong>The components in ESZWD were analyzed by ultra-high-performance liquid chromatography coupled with Quadrupole Time-Of-Flight mass spectrometry (UHPLC-Q-TOF-MS). CHF-HKYD model was established in the male Sprague-Dawley rats through bilateral thyroidectomy and intraperitoneal administration of 0.02% doxorubicin (DOX), twice weekly for 3 weeks. Subsequently, the CHF-HKYD model rats were randomly categorized into the Model, ESZWD-L (3.96 g/kg/d ESZWD), ESZWD-M (7.92 g/kg/d ESZWD), ESZWD-H (15.84 g/kg/d ESZWD), and Sac/Val (68 mg/kg/d sacubitril/valsartan) groups and treated daily for 4 weeks. As a control, the sham surgery group (Sham) was used. Primary cardiac fibroblasts (CFs) were categorized into Control, Model, ESZWD, and Sac/Val groups. Then, the CFs were stimulated with Ang-II. The ESZWD and Sac/Val groups were incubated with different concentrations of drug-containing sera and their effects on CF viability were assessed via the CCK-8 assay. The ESZWD and Sac/Val groups received drug-containing serum concentrations determined by CCK-8 assay results. The cardioprotective effects of ESZWD were determined using echocardiography, Hematoxylin & Eosin (H&E) staining, Masson staining, and Sirius red staining, and the Enzyme Linked Immunosorbent Assay (ELISA). ESZWD's effects on the Ras Homolog Gene Family Member A (RhoA) / Rho-Associated Coiled-Coil Kinases (ROCKs) signaling pathway and myocardial fibrosis were assessed by Western blotting and Quantitative Real-Time PCR (qRT-PCR) analyses. Immunofluorescence was used to observe fibrotic markers in CFs.</p><p><strong>Results: </strong>ESZWD treatment improved cardiac function in the CHF-HKYD rats by significantly reducing myocardial fibrosis and ventricular remodeling. ESZWD treatment increased the rats' body temperature (T<sub>b</sub>) and 24-hour urine volume, left ventricular ejection fraction (LVEF) and LV fractional shortening (LVFS), and decreased LV internal systolic diameter (LVIDs), LV internal diastolic diameter (LVIDd), and heart weight/ body weight (HW/BW) compared to the Model group. In comparison to the model rats, ESZWD treatment decreased serum levels of B-type natriuretic peptide precursor (NT-proBNP), tumor necrosis factor-alpha (TNF-α), interleukin-11 (IL-11), and IL-17A. ESZWD treatment significantly down-regulated the protein and mRNA expression levels of collagen I A1, α-SMA, RhoA, ROCK1, and ROCK2 in the heart tis","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119146"},"PeriodicalIF":4.8,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-21DOI: 10.1016/j.jep.2024.119132
Tahereh Maleki, Marco Leonti, Maja Dal Cero, Ali Sonboli, Caroline S Weckerle
Ethnopharmacological relevance: Community displacement and cultural integration influence the use of plants for medicine. This study enhances our understanding of how communities adapt their medical practices in response to environmental changes.
Aim of the study: We investigate how Kurds in SE Iran (Balochi Kurds), displaced between the 16th and 18th centuries from their homeland in NW Iran, retained and adapted their medicinal knowledge.
Materials and methods: Fieldwork was conducted over 12 months across 8 Kurdish municipalities in NW Iran and 3 in SE Iran, using standard ethnobotanical methods. Totally 121 people were interviewed; data were analysed at the level of use reports (UR), classifying therapeutic uses according to ICPC. Comparisons between NW and SE Iran are based on plant genera available in both regions.
Results: Medicinal knowledge is maintained by various practitioners, including herbalists, midwives, bonesetters, ritual healers, knowledgeable laypersons, and herb collectors/sellers in both regions. We documented 278 plant species (177 in NW Iran and 142 in SE Iran) and 4722 UR. SE Iran shows a greater variety of preparation methods, such as vaporization and suppositories. Gastrointestinal diseases are the most significant, followed by musculoskeletal issues in SE Iran, and skin and respiratory diseases at both locations. Commonly used plants in NW Iran include Urtica dioica (75 UR) for female genitourinary infections and Quercus spp. (50 UR) for gastric ulcers. In SE Iran, Haplophyllum canaliculatum (83 UR) is widely used. Pistacia atlantica resin is widely used in both areas. The comparison reveals continuation of uses (e.g., Mentha longifolia), plant substitutions (e.g., Thymus vs. Zataria), new uses (e.g., Capparis spinosa), and the loss of certain plant uses (e.g., Eryngium, Euphorbia) among the Balochi Kurds.
Conclusion: The greater medicinal plant diversity in NW Iran reflects its richer biodiversity. In SE Iran, the higher diversity in preparation methods and therapeutic uses is likely due to its less developed healthcare system and more traditional lifestyle. The loss of their native language has not negatively impacted the traditional knowledge of the Balochi Kurds.
{"title":"Kurdish ethnomedicine in the context of historic migration.","authors":"Tahereh Maleki, Marco Leonti, Maja Dal Cero, Ali Sonboli, Caroline S Weckerle","doi":"10.1016/j.jep.2024.119132","DOIUrl":"https://doi.org/10.1016/j.jep.2024.119132","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Community displacement and cultural integration influence the use of plants for medicine. This study enhances our understanding of how communities adapt their medical practices in response to environmental changes.</p><p><strong>Aim of the study: </strong>We investigate how Kurds in SE Iran (Balochi Kurds), displaced between the 16th and 18th centuries from their homeland in NW Iran, retained and adapted their medicinal knowledge.</p><p><strong>Materials and methods: </strong>Fieldwork was conducted over 12 months across 8 Kurdish municipalities in NW Iran and 3 in SE Iran, using standard ethnobotanical methods. Totally 121 people were interviewed; data were analysed at the level of use reports (UR), classifying therapeutic uses according to ICPC. Comparisons between NW and SE Iran are based on plant genera available in both regions.</p><p><strong>Results: </strong>Medicinal knowledge is maintained by various practitioners, including herbalists, midwives, bonesetters, ritual healers, knowledgeable laypersons, and herb collectors/sellers in both regions. We documented 278 plant species (177 in NW Iran and 142 in SE Iran) and 4722 UR. SE Iran shows a greater variety of preparation methods, such as vaporization and suppositories. Gastrointestinal diseases are the most significant, followed by musculoskeletal issues in SE Iran, and skin and respiratory diseases at both locations. Commonly used plants in NW Iran include Urtica dioica (75 UR) for female genitourinary infections and Quercus spp. (50 UR) for gastric ulcers. In SE Iran, Haplophyllum canaliculatum (83 UR) is widely used. Pistacia atlantica resin is widely used in both areas. The comparison reveals continuation of uses (e.g., Mentha longifolia), plant substitutions (e.g., Thymus vs. Zataria), new uses (e.g., Capparis spinosa), and the loss of certain plant uses (e.g., Eryngium, Euphorbia) among the Balochi Kurds.</p><p><strong>Conclusion: </strong>The greater medicinal plant diversity in NW Iran reflects its richer biodiversity. In SE Iran, the higher diversity in preparation methods and therapeutic uses is likely due to its less developed healthcare system and more traditional lifestyle. The loss of their native language has not negatively impacted the traditional knowledge of the Balochi Kurds.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119132"},"PeriodicalIF":4.8,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ethnopharmacological relevance: Zuojin formula (ZJF) is a well-known herbal medicine in Pharmacopoeia of China, which is widely used for gastritis. Modified Zuojin formula (MZJF) was adapted based on traditional Chinese medicine (TCM) theories concerning gastric atrophy and dysplasia, along with extensive clinical experience, has been clinically employed to treat chronic atrophic gastritis (CAG). However, the underlying mechanisms by which MZJF intervenes in CAG remain to be fully elucidated.
Aim of the study: The aim of this study was to evaluate the effects of MZJF intervention in CAG and explore its potential mechanisms.
Methods: Four induction factors were used to establish a CAG rat model. HE and AB-PAS staining was utilized to assess the effects of MZJF in the intervention of CAG. The stomach weight index and gastric acid pH was used to assess the overall state of stomach. ELISA was used to assess the gastric mucosal inflammatory response. Using transmission electron microscopy to observe chief cells and parietal cells, we evaluate the improvement of ultrastructure by MZJF. Through network pharmacology analysis, the possible regulatory mechanism of MZJF in CAG was preliminarily explored. Binding interactions between MZJF components and predicted targets were explored using molecular docking. Subsequently, quantitative real-time PCR (qRT-PCR), Western blot, biochemical analysis and TUNEL staining were applied to validate the effect of MZJF on predicted pathways.
Results: MZJF treatment ameliorated gastric mucosal pathology, inflammation, cellular ultrastructural damage and PG levels, halted the exacerbation of CAG in rats, along with a reduction in stomach weight index and gastric acid pH. A total of 79 compounds in MZJF targeting 203 CAG-related molecules were identified through network pharmacology. Enrichment analysis of the core targets was focused on the hypoxia inducible factor-1α (HIF-1α) signaling pathway. Molecular docking results identified HIF-1α as stable binding targets for MZJF primary components. Subsequently, PCR, WB, and biochemical results showed that MZJF suppressed the gene and protein expression levels of HIF-1α and its downstream molecules including glycolytic enzymes and transporters, modulated glucose, pyruvic acid and lactate levels in gastric mucosal tissue. Moreover, MZJF induced apoptosis of gastric epithelial cells, as evidenced by the upregulation of cleaved caspase-3, Bax, Bax/Bcl-2 and TUNEL positive cells ratio.
Conclusions: MZJF suppressed the HIF-1α-mediated glycolytic pathway, and promoted cell apoptosis, thereby halting the malignant transformation of CAG. The study provides a valuable reference point for applying TCM in preventing and treating CAG.
{"title":"Integrative pharmacological analysis of modified Zuojin formula: inhibiting the HIF-1α-mediated glycolytic pathway in chronic atrophic gastritis.","authors":"Shan Liu, Tai Zhang, Lihui Fang, Lanshuo Hu, Xiaolan Yin, Xudong Tang","doi":"10.1016/j.jep.2024.119136","DOIUrl":"https://doi.org/10.1016/j.jep.2024.119136","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Zuojin formula (ZJF) is a well-known herbal medicine in Pharmacopoeia of China, which is widely used for gastritis. Modified Zuojin formula (MZJF) was adapted based on traditional Chinese medicine (TCM) theories concerning gastric atrophy and dysplasia, along with extensive clinical experience, has been clinically employed to treat chronic atrophic gastritis (CAG). However, the underlying mechanisms by which MZJF intervenes in CAG remain to be fully elucidated.</p><p><strong>Aim of the study: </strong>The aim of this study was to evaluate the effects of MZJF intervention in CAG and explore its potential mechanisms.</p><p><strong>Methods: </strong>Four induction factors were used to establish a CAG rat model. HE and AB-PAS staining was utilized to assess the effects of MZJF in the intervention of CAG. The stomach weight index and gastric acid pH was used to assess the overall state of stomach. ELISA was used to assess the gastric mucosal inflammatory response. Using transmission electron microscopy to observe chief cells and parietal cells, we evaluate the improvement of ultrastructure by MZJF. Through network pharmacology analysis, the possible regulatory mechanism of MZJF in CAG was preliminarily explored. Binding interactions between MZJF components and predicted targets were explored using molecular docking. Subsequently, quantitative real-time PCR (qRT-PCR), Western blot, biochemical analysis and TUNEL staining were applied to validate the effect of MZJF on predicted pathways.</p><p><strong>Results: </strong>MZJF treatment ameliorated gastric mucosal pathology, inflammation, cellular ultrastructural damage and PG levels, halted the exacerbation of CAG in rats, along with a reduction in stomach weight index and gastric acid pH. A total of 79 compounds in MZJF targeting 203 CAG-related molecules were identified through network pharmacology. Enrichment analysis of the core targets was focused on the hypoxia inducible factor-1α (HIF-1α) signaling pathway. Molecular docking results identified HIF-1α as stable binding targets for MZJF primary components. Subsequently, PCR, WB, and biochemical results showed that MZJF suppressed the gene and protein expression levels of HIF-1α and its downstream molecules including glycolytic enzymes and transporters, modulated glucose, pyruvic acid and lactate levels in gastric mucosal tissue. Moreover, MZJF induced apoptosis of gastric epithelial cells, as evidenced by the upregulation of cleaved caspase-3, Bax, Bax/Bcl-2 and TUNEL positive cells ratio.</p><p><strong>Conclusions: </strong>MZJF suppressed the HIF-1α-mediated glycolytic pathway, and promoted cell apoptosis, thereby halting the malignant transformation of CAG. The study provides a valuable reference point for applying TCM in preventing and treating CAG.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119136"},"PeriodicalIF":4.8,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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