Pub Date : 2025-02-10DOI: 10.1016/j.jep.2025.119474
Yiliu Chen , Ran Su , Yunguang Hu , Jiali Luo , Chu Yi , Yinbin Zhu , Qing Feng , Xianxin Yan , Min Ma , Weifeng Feng
Ethnopharmacological relevance
Li-Chong-Xiao-Zhen granules (LCXZG) has the effect of " activate blood and resolve stasis," " soften hardness and dissipate binds " properties, and was widely used in the clinic for decades to treat uterine fibroids and ovarian cancer (OC), which is called "zheng jia" in traditional Chinese medicine.
Aim of the study
The aim of this study is to identify the active components of LCXZG and elucidate the mechanism of LCXZG in ovarian cancer by combining network pharmacology, metabolomics and proteomics.
Material and methods
The absorbed compounds in serum of LCXZG was identified by liquid chromatography-mass spectrometry. Network pharmacology was used to predict the active components and target genes of LCXZG. The therapy mechanism of LCXZG on OC were determined by establishing a nude mouse xenograft tumor model and using combined metabolomics and proteomics analysis.
Results
A total of 218 absorbed compounds in serum of LCXZG were identified by UPLC-MS. Network pharmacology results showed that lipid and atherosclerosis, chemical carcinoma-receptor activation and PI3K-AKT signaling were potential target pathways of LCXZG in the treatment of OC. Further metabolomics and proteomics studies demonstrated that LCXZG altered glycerophospholipid metabolism in ovarian cancer.
Conclusions
This study demonstrated that most of the active Compound of LCXZG are Paeoniflorin, Turanose, Amygdalin and Benzoylpaeoniflorin, which may exert their anti-tumor effects by regulating glycerophospholipid metabolism in ovarian cancer.
{"title":"The active components and potential mechanisms of Li-Chong-Xiao-Zhen granules in the treatment of ovarian cancer: An integrated metabolomics, proteomics, network pharmacology and experimental validation","authors":"Yiliu Chen , Ran Su , Yunguang Hu , Jiali Luo , Chu Yi , Yinbin Zhu , Qing Feng , Xianxin Yan , Min Ma , Weifeng Feng","doi":"10.1016/j.jep.2025.119474","DOIUrl":"10.1016/j.jep.2025.119474","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Li-Chong-Xiao-Zhen granules (LCXZG) has the effect of \" activate blood and resolve stasis,\" \" soften hardness and dissipate binds \" properties, and was widely used in the clinic for decades to treat uterine fibroids and ovarian cancer (OC), which is called \"zheng jia\" in traditional Chinese medicine.</div></div><div><h3>Aim of the study</h3><div>The aim of this study is to identify the active components of LCXZG and elucidate the mechanism of LCXZG in ovarian cancer by combining network pharmacology, metabolomics and proteomics.</div></div><div><h3>Material and methods</h3><div>The absorbed compounds in serum of LCXZG was identified by liquid chromatography-mass spectrometry. Network pharmacology was used to predict the active components and target genes of LCXZG. The therapy mechanism of LCXZG on OC were determined by establishing a nude mouse xenograft tumor model and using combined metabolomics and proteomics analysis.</div></div><div><h3>Results</h3><div>A total of 218 absorbed compounds in serum of LCXZG were identified by UPLC-MS. Network pharmacology results showed that lipid and atherosclerosis, chemical carcinoma-receptor activation and PI3K-AKT signaling were potential target pathways of LCXZG in the treatment of OC. Further metabolomics and proteomics studies demonstrated that LCXZG altered glycerophospholipid metabolism in ovarian cancer.</div></div><div><h3>Conclusions</h3><div>This study demonstrated that most of the active Compound of LCXZG are Paeoniflorin, Turanose, Amygdalin and Benzoylpaeoniflorin, which may exert their anti-tumor effects by regulating glycerophospholipid metabolism in ovarian cancer.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"343 ","pages":"Article 119474"},"PeriodicalIF":4.8,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-10DOI: 10.1016/j.jep.2025.119482
Soibam Thoithoisana Devi, Vimi Kshetrimayum, Rameshwari Heisnam, Sai Jyothi Akula, Pullapanthula Radhakrishnanand, Pulok K Mukherjee, Kshetrimayum Birla Singh, Nanaocha Sharma
<p><strong>Ethnopharmalogical relevance: </strong>Terminalia chebula, known for its extensive use in traditional medicinal practices among indigenous cultures, is recognised for its effectiveness in treating various oral disorders. Healers in India and China utilize the ripe fruits of T. chebula to prevent and manage conditions such as dental cavities, gingivitis, bleeding gums and stomatitis. The fruits have also been traditionally used in Ayurvedic and Siddha medicines for treatment of various diseases including anticancer properties. It is also an important component of Tibetan traditional medicine used for the treatment of cancer. Studies have demonstrated the efficacy of T. chebula against lung and colon carcinoma.</p><p><strong>Aim of the study: </strong>Despite its historical significance in oral health, the potential of T. chebula against oral cancer has not been explored, warranting further investigation into its bioactive properties. This study aims to explore the therapeutic potential of the hydroalcoholic extract of Terminalia chebula fruits and its fractions against oral squamous cell carcinoma (OSCC) using SCC9 cells focusing on their cytotoxicity, anti-proliferative effect and the synergistic action of its ethyl-acetate fraction with cisplatin (CP). Additionally it seeks to identify the bioactive phytoconstituents phytoconstituents in EAF were identified using LC-ESI-QTOF-MS.</p><p><strong>Materials and methods: </strong>Antioxidant activity of TYH and its fraction were assessed using DPPH and ABTS assays. Total phenolic (TPC) and total flavonoid content (TFC) were quantified via Folin-ciocalteau and alluminium chloride assays respectively. Cytotoxic and antiproliferative effects were assessed using MTT assay, clonogenic assay and cell migration assay. Apoptosis in EAF treated SCC9 cells was analysed by using DAPI, Giemsa staining and flow cytometry using Annexin V-FITC/PI apoptosis detection kit. Intracellular reactive oxygen species (ROS) was assessed using H<sub>2</sub>DCFDA, western blotting examined expression of apoptosis related proteins in SCC9 cells. Combinational effect of EAF with cisplatin (CP) was also assessed and phytochemical constituents of EAF were analysed using LC-ESI-QTOF-MS.</p><p><strong>Results: </strong>The ethyl acetate fraction (EAF) showed the highest antioxidant activity (IC50 value of 8.16 ± 0.59μg/mL and 4.99 ± 0.82μg/mL in DPPH and ABTS assays respectively) which reciprocated with a high TPC and TFC (528.46 ± 2.59 mgGAE/g and 49.10± 1.61 mgQE/g dry weight of the extract respectively) content. EAF significantly reduced cell viability with an IC<sub>50</sub> value of 86.73 ± 0.55 μg/mL, resulted in dose dependent cell death, and prevented the proliferation and migration in SCC9 cells. Further Annexin V-PI based flow cytometric analysis and caspase-3/7 enzyme activity assay confirmed the apoptotic effect of EAF in SCC9 cells. Intrinsic pathway of apoptosis post treatment with EAF was confirmed by wester
{"title":"Investigating the Impact of Terminalia chebula, an underutilized functional fruit, on oral squamous cell carcinoma: Exploring Cell Death Mechanisms.","authors":"Soibam Thoithoisana Devi, Vimi Kshetrimayum, Rameshwari Heisnam, Sai Jyothi Akula, Pullapanthula Radhakrishnanand, Pulok K Mukherjee, Kshetrimayum Birla Singh, Nanaocha Sharma","doi":"10.1016/j.jep.2025.119482","DOIUrl":"https://doi.org/10.1016/j.jep.2025.119482","url":null,"abstract":"<p><strong>Ethnopharmalogical relevance: </strong>Terminalia chebula, known for its extensive use in traditional medicinal practices among indigenous cultures, is recognised for its effectiveness in treating various oral disorders. Healers in India and China utilize the ripe fruits of T. chebula to prevent and manage conditions such as dental cavities, gingivitis, bleeding gums and stomatitis. The fruits have also been traditionally used in Ayurvedic and Siddha medicines for treatment of various diseases including anticancer properties. It is also an important component of Tibetan traditional medicine used for the treatment of cancer. Studies have demonstrated the efficacy of T. chebula against lung and colon carcinoma.</p><p><strong>Aim of the study: </strong>Despite its historical significance in oral health, the potential of T. chebula against oral cancer has not been explored, warranting further investigation into its bioactive properties. This study aims to explore the therapeutic potential of the hydroalcoholic extract of Terminalia chebula fruits and its fractions against oral squamous cell carcinoma (OSCC) using SCC9 cells focusing on their cytotoxicity, anti-proliferative effect and the synergistic action of its ethyl-acetate fraction with cisplatin (CP). Additionally it seeks to identify the bioactive phytoconstituents phytoconstituents in EAF were identified using LC-ESI-QTOF-MS.</p><p><strong>Materials and methods: </strong>Antioxidant activity of TYH and its fraction were assessed using DPPH and ABTS assays. Total phenolic (TPC) and total flavonoid content (TFC) were quantified via Folin-ciocalteau and alluminium chloride assays respectively. Cytotoxic and antiproliferative effects were assessed using MTT assay, clonogenic assay and cell migration assay. Apoptosis in EAF treated SCC9 cells was analysed by using DAPI, Giemsa staining and flow cytometry using Annexin V-FITC/PI apoptosis detection kit. Intracellular reactive oxygen species (ROS) was assessed using H<sub>2</sub>DCFDA, western blotting examined expression of apoptosis related proteins in SCC9 cells. Combinational effect of EAF with cisplatin (CP) was also assessed and phytochemical constituents of EAF were analysed using LC-ESI-QTOF-MS.</p><p><strong>Results: </strong>The ethyl acetate fraction (EAF) showed the highest antioxidant activity (IC50 value of 8.16 ± 0.59μg/mL and 4.99 ± 0.82μg/mL in DPPH and ABTS assays respectively) which reciprocated with a high TPC and TFC (528.46 ± 2.59 mgGAE/g and 49.10± 1.61 mgQE/g dry weight of the extract respectively) content. EAF significantly reduced cell viability with an IC<sub>50</sub> value of 86.73 ± 0.55 μg/mL, resulted in dose dependent cell death, and prevented the proliferation and migration in SCC9 cells. Further Annexin V-PI based flow cytometric analysis and caspase-3/7 enzyme activity assay confirmed the apoptotic effect of EAF in SCC9 cells. Intrinsic pathway of apoptosis post treatment with EAF was confirmed by wester","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119482"},"PeriodicalIF":4.8,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408219","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 : 2025-02-10DOI: 10.1016/j.jep.2025.119476
Yan-Ao Wang , Xu Guo , Meng-Qi Zhang , Shu-Tao Sun , Qi-Dong Ren , Mu-Xuan Wang , Li-Na Wang , Mohamed A. Farag , Jin-Yue Sun , Chao Liu , Ying-Ying Chen
Ethnopharmacological relevance
As a traditional Chinese medicine, Morus alba L. root bark (MAR) has diuretic and detumescent effects, which is used in prescriptions like Niaoduqing granules for hyperuricemia treatment. However, the anti-hyperuricemic and nephroprotective activities, underlying mechanism and material basis of MAR have not been reported.
Aim of the study
This research aimed to explore the anti-hyperuricemic and nephroprotective activity and mechanism of MAR, along with the pursuit of potential xanthine oxidase (XOD) inhibitors within MAR.
Materials and methods
XOD inhibitory assay and hyperuricemic mice model were employed to screen and estimate the active fraction of MAR. Then, active compositions were isolated and elucidated by diverse separation and spectroscopic techniques. The enzyme inhibition mechanism of the active compositions was investigated by enzyme kinetic and molecular docking.
Results
The ethyl acetate fraction (MAR-EA) showed the strongest inhibitory activity against XOD. In hyperuricemic mice, MAR-EA decreased serum uric acid levels by suppressing XOD activity and modulating renal uric acid transporters (URAT1, GLUT9, ABCG2). Moreover, it alleviated hyperuricemia-induced kidney damage, which may be related to inhibiting the production of inflammatory factors. Noticeably, the combination of MAR-EA with allopurinol showed a synergistic effect. Meanwhile, a Diels-Alder adduct, albanol A (1) was isolated from MAR-EA with excellent XOD inhibition activity (IC50 = 0.116 mg/mL), which was categorized as a mixed-type XOD inhibitor. The molecular docking outcomes demonstrated that albanol A (1) exhibited a desirable interaction with XOD.
Conclusion
This research supports MAR and albanol A as anti-hyperuricemic drug candidates, laying a foundation for further exploration.
{"title":"Evaluation of anti-hyperuricemic and nephroprotective activities and discovery of new XOD inhibitors of Morus alba L. root bark","authors":"Yan-Ao Wang , Xu Guo , Meng-Qi Zhang , Shu-Tao Sun , Qi-Dong Ren , Mu-Xuan Wang , Li-Na Wang , Mohamed A. Farag , Jin-Yue Sun , Chao Liu , Ying-Ying Chen","doi":"10.1016/j.jep.2025.119476","DOIUrl":"10.1016/j.jep.2025.119476","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>As a traditional Chinese medicine, <em>Morus alba</em> L. root bark (MAR) has diuretic and detumescent effects, which is used in prescriptions like Niaoduqing granules for hyperuricemia treatment. However, the anti-hyperuricemic and nephroprotective activities, underlying mechanism and material basis of MAR have not been reported.</div></div><div><h3>Aim of the study</h3><div>This research aimed to explore the anti-hyperuricemic and nephroprotective activity and mechanism of MAR, along with the pursuit of potential xanthine oxidase (XOD) inhibitors within MAR.</div></div><div><h3>Materials and methods</h3><div>XOD inhibitory assay and hyperuricemic mice model were employed to screen and estimate the active fraction of MAR. Then, active compositions were isolated and elucidated by diverse separation and spectroscopic techniques. The enzyme inhibition mechanism of the active compositions was investigated by enzyme kinetic and molecular docking.</div></div><div><h3>Results</h3><div>The ethyl acetate fraction (MAR-EA) showed the strongest inhibitory activity against XOD. In hyperuricemic mice, MAR-EA decreased serum uric acid levels by suppressing XOD activity and modulating renal uric acid transporters (URAT1, GLUT9, ABCG2). Moreover, it alleviated hyperuricemia-induced kidney damage, which may be related to inhibiting the production of inflammatory factors. Noticeably, the combination of MAR-EA with allopurinol showed a synergistic effect. Meanwhile, a Diels-Alder adduct, albanol A (<strong>1</strong>) was isolated from MAR-EA with excellent XOD inhibition activity (IC<sub>50</sub> = 0.116 mg/mL), which was categorized as a mixed-type XOD inhibitor. The molecular docking outcomes demonstrated that albanol A (<strong>1</strong>) exhibited a desirable interaction with XOD.</div></div><div><h3>Conclusion</h3><div>This research supports MAR and albanol A as anti-hyperuricemic drug candidates, laying a foundation for further exploration.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"343 ","pages":"Article 119476"},"PeriodicalIF":4.8,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407704","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 : 2025-02-09DOI: 10.1016/j.jep.2025.119450
Guangzhen Zheng , Xiangyang Cao , Yi Jing , Ling Wang , Ruixue Yan , Yan Ji , Yuhan Zhang , Heng Li , Yunpeng Wang , Yingying Shi , Yadong Yu , Qingping Xiong
Ethnopharmacological relevance
Danggui Buxue Decoction (DBD), a traditional Chinese medicinal formula, has historically been used for cardiovascular health, including managing atherosclerotic plaques (ASP). However, its precise mechanisms remain elusive.
Aim of the study
The purpose of this study was to use a novel integrative bioinformatics analysis and experimental validation approach to provide a molecular basis for ASP's stabilization by DBD.
Materials and methods
A mice model of ApoE-deficient atherosclerosis fed with a high-fat diet was employed to evaluate the efficacy of DBD in stabilizing ASP. The potential mechanism underlying the stabilization effect of DBD on ASP was systematically investigated using an integrated approach combining network pharmacology, molecular docking, and molecular dynamics simulation. Additionally, an ox-LDL-induced macrophage foam cell model and multivariate statistical analysis were utilized to validate the pharmacodynamic material basis and target of DBD in stabilizing ASP.
Results
Firstly, it was found that DBD can significantly alleviate ASP, which was manifested as a significant reduction in the atherosclerosis index, ratio of area for plaque to lumen, and vulnerability index. Afterwards, network pharmacology investigation identified quercetin and kaempferol as the primary active compounds in DBD anti-ASP. Key core targets mainly involved TP53, AKT1, IL-6 and TNF. The main action pathways included lipid and atherosclerosis, PI3K-Akt signaling, and other pathways. Subsequently, molecular docking and molecular dynamics simulation results confirmed the strong stability of the main active compounds with the key target. Finally, the cell validation experiment in vitro revealed that both quercetin and kaempferol could significantly inhibit RAW264.7 macrophage foaming formation induced by ox-LDL and improve its lipid metabolism disorder. Meanwhile, they could also significantly reverse ox-LDL induced abnormal expression of core protein predicted by network pharmacology in RAW264.7 foam cells. Further correlation analysis revealed that the improvement effect of quercetin and kaempferol on macrophage foaming had a close correlation with the inhibition of core protein expression.
Conclusion
DBD mainly utilized active ingredients such as quercetin and kaempferol, through regulating multiple targets like TP53, AKT1, IL-6 and TNF, to stabilize ASP.
{"title":"An integrative approach for mechanistic insights into the atherosclerotic plaque-stabilizing properties of Danggui Buxue decoction","authors":"Guangzhen Zheng , Xiangyang Cao , Yi Jing , Ling Wang , Ruixue Yan , Yan Ji , Yuhan Zhang , Heng Li , Yunpeng Wang , Yingying Shi , Yadong Yu , Qingping Xiong","doi":"10.1016/j.jep.2025.119450","DOIUrl":"10.1016/j.jep.2025.119450","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Danggui Buxue Decoction (DBD), a traditional Chinese medicinal formula, has historically been used for cardiovascular health, including managing atherosclerotic plaques (ASP). However, its precise mechanisms remain elusive.</div></div><div><h3>Aim of the study</h3><div>The purpose of this study was to use a novel integrative bioinformatics analysis and experimental validation approach to provide a molecular basis for ASP's stabilization by DBD.</div></div><div><h3>Materials and methods</h3><div>A mice model of ApoE-deficient atherosclerosis fed with a high-fat diet was employed to evaluate the efficacy of DBD in stabilizing ASP. The potential mechanism underlying the stabilization effect of DBD on ASP was systematically investigated using an integrated approach combining network pharmacology, molecular docking, and molecular dynamics simulation. Additionally, an ox-LDL-induced macrophage foam cell model and multivariate statistical analysis were utilized to validate the pharmacodynamic material basis and target of DBD in stabilizing ASP.</div></div><div><h3>Results</h3><div>Firstly, it was found that DBD can significantly alleviate ASP, which was manifested as a significant reduction in the atherosclerosis index, ratio of area for plaque to lumen, and vulnerability index. Afterwards, network pharmacology investigation identified quercetin and kaempferol as the primary active compounds in DBD anti-ASP. Key core targets mainly involved TP53, AKT1, IL-6 and TNF. The main action pathways included lipid and atherosclerosis, PI3K-Akt signaling, and other pathways. Subsequently, molecular docking and molecular dynamics simulation results confirmed the strong stability of the main active compounds with the key target. Finally, the cell validation experiment <em>in vitro</em> revealed that both quercetin and kaempferol could significantly inhibit RAW264.7 macrophage foaming formation induced by ox-LDL and improve its lipid metabolism disorder. Meanwhile, they could also significantly reverse ox-LDL induced abnormal expression of core protein predicted by network pharmacology in RAW264.7 foam cells. Further correlation analysis revealed that the improvement effect of quercetin and kaempferol on macrophage foaming had a close correlation with the inhibition of core protein expression.</div></div><div><h3>Conclusion</h3><div>DBD mainly utilized active ingredients such as quercetin and kaempferol, through regulating multiple targets like TP53, AKT1, IL-6 and TNF, to stabilize ASP.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"343 ","pages":"Article 119450"},"PeriodicalIF":4.8,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399451","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}
Thai herbal Kratom (THK), a traditional Thai remedy for muscle pain, is composed of six important medicinal plants and has been traditionally used as a compressed ball for muscle pain management. This study aimed to evaluate its phytochemical composition and biological properties, including antioxidant, anti-inflammatory, and analgesic actions.
Materials and methods
The phytochemical profile was investigated, and antioxidant activity was assessed using DPPH and ABTS scavenging assays. In vivo anti-inflammatory properties were examined using carrageenan-induced rat paw edema and ethyl phenylpropiolate (EPP)-induced ear edema, while anti-nociceptive activity was explored by the hot plate test and acetic acid-induced writhing test.
Results
The ethanolic extract of THK was found to contain several potent phytochemicals, including 4-hydroxycoumarin, curcumin, mitragynine, aloin A, and limonin. HPLC analysis revealed a high concentration of mitragynine in the extract, with a value of 10.76 ± 0.50 mg/L. The extract demonstrated an antioxidant activity in DPPH and ABTS scavenging assays, with IC50 value of 275.15 ± 1.78 and 256.49 ± 6.66 μg/mL, respectively. Oral administration of THK at dose of 125–500 mg/kg exhibited promising anti-inflammatory activity in a dose-dependent manner by reducing carrageenan-induced rat paw edema. Topical application of THK (1–2 mg/ear) was shown to highly inhibit ear swelling at 120 min after EEP-induced inflammation, with values of 83%, which was more potent activity than indomethacin treatment at 30, 60, and 120 min. Furthermore, THK at 125 mg/kg significantly reduced pain response in both the hot plate and acetic acid-induced writhing tests.
Conclusion
This study found that the ethanolic extract of THK possesses significant anti-inflammatory and analgesic activities in vivo, supporting its traditional use for muscle pain management.
{"title":"In vivo analgesic, anti-inflammatory activities, and phytochemical profile of Thai herbal Kratom recipe, a traditional Thai herbal medicine for muscle pain relief","authors":"Kanchapat Mahaprom , Julalak Chokpaisarn , Nongluk Kunworarath , Wanhuda Paduka , Sathianpong Phoopha , Surasak Limsuwan , Oratai Neamsuvan","doi":"10.1016/j.jep.2025.119442","DOIUrl":"10.1016/j.jep.2025.119442","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Thai herbal Kratom (THK), a traditional Thai remedy for muscle pain, is composed of six important medicinal plants and has been traditionally used as a compressed ball for muscle pain management. This study aimed to evaluate its phytochemical composition and biological properties, including antioxidant, anti-inflammatory, and analgesic actions.</div></div><div><h3>Materials and methods</h3><div>The phytochemical profile was investigated, and antioxidant activity was assessed using DPPH and ABTS scavenging assays. <em>In vivo</em> anti-inflammatory properties were examined using carrageenan-induced rat paw edema and ethyl phenylpropiolate (EPP)-induced ear edema, while anti-nociceptive activity was explored by the hot plate test and acetic acid-induced writhing test.</div></div><div><h3>Results</h3><div>The ethanolic extract of THK was found to contain several potent phytochemicals, including 4-hydroxycoumarin, curcumin, mitragynine, aloin A, and limonin. HPLC analysis revealed a high concentration of mitragynine in the extract, with a value of 10.76 ± 0.50 mg/L. The extract demonstrated an antioxidant activity in DPPH and ABTS scavenging assays, with IC<sub>50</sub> value of 275.15 ± 1.78 and 256.49 ± 6.66 μg/mL, respectively. Oral administration of THK at dose of 125–500 mg/kg exhibited promising anti-inflammatory activity in a dose-dependent manner by reducing carrageenan-induced rat paw edema. Topical application of THK (1–2 mg/ear) was shown to highly inhibit ear swelling at 120 min after EEP-induced inflammation, with values of 83%, which was more potent activity than indomethacin treatment at 30, 60, and 120 min. Furthermore, THK at 125 mg/kg significantly reduced pain response in both the hot plate and acetic acid-induced writhing tests.</div></div><div><h3>Conclusion</h3><div>This study found that the ethanolic extract of THK possesses significant anti-inflammatory and analgesic activities <em>in vivo</em>, supporting its traditional use for muscle pain management.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"343 ","pages":"Article 119442"},"PeriodicalIF":4.8,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390943","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 : 2025-02-08DOI: 10.1016/j.jep.2025.119380
Irene Puspa Dewi , Dachriyanus , Yufri Aldi , Nor Hadiani Ismail , Che Puteh Osman , Purnawan Pontana Putra , Fatma Sri Wahyuni
Ethnopharmacological relevance
Garcinia cowa Roxb. commonly known as asam kandis in Indonesia and Cha muang in Thailand, has been extensively utilized as traditional medicine. This plant contains compounds such as xanthones, phloroglucinol, depsidones, terpenoids, steroids, and flavonoids. These compounds have been extensively studied for various bioactivities. However, the utilization of this plant as an anti-inflammatory agent is still limited.
Aim of the study
This study aims to evaluate newly derived compounds from Garcinia cowa Roxb., focusing on their ADMET profiles (Absorption, Distribution, Metabolism, Excretion, and Toxicity) and anti-inflammatory bioactivity. The assessment will be carried out using a combination of in silico and in vitro experiments to determine their pharmacological potential as anti-inflammatory agents.
Materials and methods
Isolation of compounds from Garcinia cowa Roxb. was carried out using column chromatography, purified with radial chromatography, and recycling HPLC. The compounds' structures were evaluated for their ADMET profiles and anti-inflammatory bioactivity using the NF-ĸB protein (PDB Code: 2RAM) as the target. The in vitro experiment was conducted using Raw 264.7 macrophages cell to assess cytotoxicity, phagocytic activity, IL-6, and TNF-α secretion. The determination of the anti-inflammatory mechanism is carried out by testing the activity of NF-ĸB and IKB-α using the Western blot method.
Results
We successfully analyzed the structure of a new compound from the bark of Garcinia cowa Roxb., named Garciacowanin (NC). In silico analysis suggests that the drug shows promising absorption potential, there are concerns related to its metabolism and toxicity that warrant further investigation during the development process and does not show mutagenic properties based on the negative AMES test results. There is a risk of hepatotoxicity (liver damage) and the drug can also interfere with the hERG II ion channel, which can cause side effects on the heart. The compound can affect the NF-ĸB protein, while in vitro studies have demonstrated its ability to suppress phagocytic activity, as well as the production of IL-6 and TNF-α. Western blot analysis suggests that NC's anti-inflammatory mechanism functions via the NF-ĸB signaling pathway.
Conclusion
NC has the potential to be developed as an anti-inflammatory agent with a mechanism of inhibiting the inflammatory response through the NF-ĸB signaling pathway.
{"title":"A new xanthone from Garcinia cowa Roxb. and its anti-inflammatory activity","authors":"Irene Puspa Dewi , Dachriyanus , Yufri Aldi , Nor Hadiani Ismail , Che Puteh Osman , Purnawan Pontana Putra , Fatma Sri Wahyuni","doi":"10.1016/j.jep.2025.119380","DOIUrl":"10.1016/j.jep.2025.119380","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Garcinia cowa</em> Roxb. commonly known as asam kandis in Indonesia and Cha muang in Thailand, has been extensively utilized as traditional medicine. This plant contains compounds such as xanthones, phloroglucinol, depsidones, terpenoids, steroids, and flavonoids. These compounds have been extensively studied for various bioactivities. However, the utilization of this plant as an anti-inflammatory agent is still limited.</div></div><div><h3>Aim of the study</h3><div>This study aims to evaluate newly derived compounds from <em>Garcinia cowa</em> Roxb., focusing on their ADMET profiles (Absorption, Distribution, Metabolism, Excretion, and Toxicity) and anti-inflammatory bioactivity. The assessment will be carried out using a combination of in silico and in vitro experiments to determine their pharmacological potential as anti-inflammatory agents.</div></div><div><h3>Materials and methods</h3><div>Isolation of compounds from <em>Garcinia cowa</em> Roxb. was carried out using column chromatography, purified with radial chromatography, and recycling HPLC. The compounds' structures were evaluated for their ADMET profiles and anti-inflammatory bioactivity using the NF-ĸB protein (PDB Code: 2RAM) as the target. The in vitro experiment was conducted using Raw 264.7 macrophages cell to assess cytotoxicity, phagocytic activity, IL-6, and TNF-α secretion. The determination of the anti-inflammatory mechanism is carried out by testing the activity of NF-ĸB and IKB-α using the Western blot method.</div></div><div><h3>Results</h3><div>We successfully analyzed the structure of a new compound from the bark of <em>Garcinia cowa</em> Roxb., named Garciacowanin (NC). In silico analysis suggests that the drug shows promising absorption potential, there are concerns related to its metabolism and toxicity that warrant further investigation during the development process and does not show mutagenic properties based on the negative AMES test results. There is a risk of hepatotoxicity (liver damage) and the drug can also interfere with the hERG II ion channel, which can cause side effects on the heart. The compound can affect the NF-ĸB protein, while in vitro studies have demonstrated its ability to suppress phagocytic activity, as well as the production of IL-6 and TNF-α. Western blot analysis suggests that NC's anti-inflammatory mechanism functions via the NF-ĸB signaling pathway.</div></div><div><h3>Conclusion</h3><div>NC has the potential to be developed as an anti-inflammatory agent with a mechanism of inhibiting the inflammatory response through the NF-ĸB signaling pathway.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"343 ","pages":"Article 119380"},"PeriodicalIF":4.8,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390978","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 : 2025-02-08DOI: 10.1016/j.jep.2025.119458
Yan Liu , Luxin Li , Ye Sun , Siyi Wang , Peng Jiang , Qingshan Chen , Lili Zhang , Zhichao Hao , Xu Yang , Jiujiang Yan , Juan Pan , Wei Guan , Zhenpeng Xu , Yuanyuan Zhou , Shaowa Lv , Haixue Kuang , Bingyou Yang
<div><h3>Ethnopharmacological relevance</h3><div>Rheumatoid Arthritis (RA), a chronic inflammatory autoimmune condition, presents a substantial challenge to public health. <em>Dictamnus dasycarpus</em> Turcz. (<em>D. dasycarpus</em>) is a traditional Chinese medicinal plant recognized for its anti-inflammatory properties and is increasingly being utilized as a potential anti-RA agent, but the underlying mechanism is still unclear.</div></div><div><h3>Aim of the study</h3><div>The objective of this research is to elucidate the potential active components and therapeutic properties of <em>D. dasycarpus</em> in experimental RA-induced DBA/1J mice, and to uncover the pharmacological basis of its action.</div></div><div><h3>Materials and methods</h3><div>Surface plasmon resonance (SPR) was employed to ascertain the specificity of interactions between protein targets and <em>D. dasycarpus</em> active ingredients for treating RA. The extract of <em>D. dasycarpus</em> was obtained by HP-20 microresin column chromatography, and its chemical composition was assessed using UPLC-Orbitrap-MS. This study utilized a collagen-induced arthritis (CIA) mouse model for <em>in vivo</em> experimentation. Body weight, foot thickness measurements, arthritis scores, immune organ index, and serum antibody levels of mice were used as indicators to evaluate the effects of <em>D. dasycarpus</em> components in treating RA. The serum levels of inflammatory factors in mice were measured using a cytokine antibody microarray assay. Additionally, this study quantified the protein expression levels associated with inflammatory responses through a combination of immunohistochemical staining and western blotting analyses.</div></div><div><h3>Results</h3><div>This research investigated the interaction between <em>D. dasycarpus</em> active components and target proteins, including PTPN14, using a BIACORE system. The screened active components were identified as alkaloids through mass spectrometry. The UPLC-Orbitrap-MS analysis revealed that alkaloids were the predominant constituents in the 60% EtOH extract of <em>D. dasycarpus</em>. Alkaloid components significantly reduced the arthritis index, foot swelling, and serum antibody levels of IgG1, IgG 2a, and IgG 2b in CIA mice. Histological staining results indicated that alkaloid components mitigate disease exacerbations in CIA mice. Bioinformatics analysis and protein level detection results show that the therapeutic mechanism of <em>D. dasycarpus</em> in managing RA could be attributed to the suppression of the IL-17 signaling pathway.</div></div><div><h3>Conclusion</h3><div>This study was based on clarifying the therapeutic effect of <em>D. dasycarpus</em> on RA, identifies its effective chemical components as alkaloids. It systematically elucidates the pharmacological mechanisms of alkaloids in treating RA, thereby laying a crucial theoretical foundation for further exploration of the active constituents of <em>D. dasycarpus</em>.</
{"title":"Dictamnus dasycarpus turcz. Attenuates collagen-induced rheumatoid arthritis in DBA/1J mice through inhibiting IL-17 signaling pathway","authors":"Yan Liu , Luxin Li , Ye Sun , Siyi Wang , Peng Jiang , Qingshan Chen , Lili Zhang , Zhichao Hao , Xu Yang , Jiujiang Yan , Juan Pan , Wei Guan , Zhenpeng Xu , Yuanyuan Zhou , Shaowa Lv , Haixue Kuang , Bingyou Yang","doi":"10.1016/j.jep.2025.119458","DOIUrl":"10.1016/j.jep.2025.119458","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Rheumatoid Arthritis (RA), a chronic inflammatory autoimmune condition, presents a substantial challenge to public health. <em>Dictamnus dasycarpus</em> Turcz. (<em>D. dasycarpus</em>) is a traditional Chinese medicinal plant recognized for its anti-inflammatory properties and is increasingly being utilized as a potential anti-RA agent, but the underlying mechanism is still unclear.</div></div><div><h3>Aim of the study</h3><div>The objective of this research is to elucidate the potential active components and therapeutic properties of <em>D. dasycarpus</em> in experimental RA-induced DBA/1J mice, and to uncover the pharmacological basis of its action.</div></div><div><h3>Materials and methods</h3><div>Surface plasmon resonance (SPR) was employed to ascertain the specificity of interactions between protein targets and <em>D. dasycarpus</em> active ingredients for treating RA. The extract of <em>D. dasycarpus</em> was obtained by HP-20 microresin column chromatography, and its chemical composition was assessed using UPLC-Orbitrap-MS. This study utilized a collagen-induced arthritis (CIA) mouse model for <em>in vivo</em> experimentation. Body weight, foot thickness measurements, arthritis scores, immune organ index, and serum antibody levels of mice were used as indicators to evaluate the effects of <em>D. dasycarpus</em> components in treating RA. The serum levels of inflammatory factors in mice were measured using a cytokine antibody microarray assay. Additionally, this study quantified the protein expression levels associated with inflammatory responses through a combination of immunohistochemical staining and western blotting analyses.</div></div><div><h3>Results</h3><div>This research investigated the interaction between <em>D. dasycarpus</em> active components and target proteins, including PTPN14, using a BIACORE system. The screened active components were identified as alkaloids through mass spectrometry. The UPLC-Orbitrap-MS analysis revealed that alkaloids were the predominant constituents in the 60% EtOH extract of <em>D. dasycarpus</em>. Alkaloid components significantly reduced the arthritis index, foot swelling, and serum antibody levels of IgG1, IgG 2a, and IgG 2b in CIA mice. Histological staining results indicated that alkaloid components mitigate disease exacerbations in CIA mice. Bioinformatics analysis and protein level detection results show that the therapeutic mechanism of <em>D. dasycarpus</em> in managing RA could be attributed to the suppression of the IL-17 signaling pathway.</div></div><div><h3>Conclusion</h3><div>This study was based on clarifying the therapeutic effect of <em>D. dasycarpus</em> on RA, identifies its effective chemical components as alkaloids. It systematically elucidates the pharmacological mechanisms of alkaloids in treating RA, thereby laying a crucial theoretical foundation for further exploration of the active constituents of <em>D. dasycarpus</em>.</","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"343 ","pages":"Article 119458"},"PeriodicalIF":4.8,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143387766","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 : 2025-02-08DOI: 10.1016/j.jep.2025.119465
Wenrui Huang, Tianyun Liu, Yue Yu, Xingyan Ou, Lei Chen, Xiaoxuan Tang, Xingzi Fang, Jing Ling, XueLian Du
<p><strong>Ethnopharmacological relevance: </strong>Conventional hormonal treatments for endometriosis (EMs) are often associated with significant side effects. In recent years, many clinical trials and studies have highlighted the remarkable efficacy of Chinese patent medicines (CPMs) in alleviating endometriosis-related pain, reducing CA125 markers, regulating hormone levels, and preventing symptom recurrence. Numerous randomized controlled trials (RCTs) have been conducted on CPMs such as Shaofu Zhuyu Decoction (SZD), Dan'e Fukang Plaster (DFP), Sanjie Zhentong Capsule (SZC), Guizhi Fuling Capsule (GFC), Xiaojin Capsule (XC), Gongliu Xiao Capsule (GLXC), Xuefu Zhuyu Capsule (XZC), Jingtong Yushu Granule (JYG), Zhitong Huazheng Capsule (ZHC), and Kuntai Capsule (KTC) for the treatment of endometriosis. However, these studies have yet to be evaluated through a network meta-analysis (NMA) compliant with PRISMA standards.</p><p><strong>Aim of the study: </strong>This study aimed to compare the efficacy and safety of ten CPMs for treating EMs through a NMA on RCTs.</p><p><strong>Materials and methods: </strong>PubMed, Cochrane, Embase, Web of Science, China National Knowledge Infrastructure, VIP Information, WanFang, and China Biomedicine databases were searched up to October 2024 for studies on the efficacy and safety of CPMs in treating EMs. Two researchers independently screened the studies, extracted data, and assessed quality using the Cochrane Risk of Bias 2.0 tool and the Confidence in Network Meta-Analysis framework. The NMA was conducted using Bayesian methods with StataSE and Rstudio, generating network diagrams, league tables, and Surface Under the Cumulative Ranking (SUCRA) line charts. This study was registered with PROSPERO (CRD42023477523).</p><p><strong>Results: </strong>148 eligible trials involving 10 CPMs and 16198 participants were included in this NMA; all subsequent estimates refer to the comparison with conventional therapies. All 10 CPMs effectively improved the total effective rate and VAS pain scores. SZC induced the most significant improvement in total effective rate(compared to hormone therapy: risk ratio 5.51, 95% confidence interval 4.21 to 7.2, SUCRA 86.3%, moderate confidence of evidence; compared to GnRH-a: 4.74, (3.18 to 7), moderate confidence of evidence). DFP proved to be the most effective CPM for lowering the VAS pain scores. (compared to hormone therapy: mean difference -2.1, (-2.94 to -1.29), 78.8%, moderate confidence of evidence; and GnRH-a (-2.07, (-2.73 to -1.41), low confidence of evidence). Moreover, this study demonstrated the safety of CPMs, particularly in reducing hormonal and liver-related side effects. Specific CPMs like XZC, SZC, DFP, KTC, and GFC showed markedly lower relative risks of adverse events when compared to conventional therapies.</p><p><strong>Conclusion: </strong>; Chinese patent medicine may effectively treat EMs, excelling in total effective rate, pain relief, CA125 reduction, an
{"title":"Efficacy and Safety of Chinese Patent Medicines Combined with Conventional Therapies for Endometriosis: A Systematic Review and Bayesian Network Meta-Analysis.","authors":"Wenrui Huang, Tianyun Liu, Yue Yu, Xingyan Ou, Lei Chen, Xiaoxuan Tang, Xingzi Fang, Jing Ling, XueLian Du","doi":"10.1016/j.jep.2025.119465","DOIUrl":"https://doi.org/10.1016/j.jep.2025.119465","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Conventional hormonal treatments for endometriosis (EMs) are often associated with significant side effects. In recent years, many clinical trials and studies have highlighted the remarkable efficacy of Chinese patent medicines (CPMs) in alleviating endometriosis-related pain, reducing CA125 markers, regulating hormone levels, and preventing symptom recurrence. Numerous randomized controlled trials (RCTs) have been conducted on CPMs such as Shaofu Zhuyu Decoction (SZD), Dan'e Fukang Plaster (DFP), Sanjie Zhentong Capsule (SZC), Guizhi Fuling Capsule (GFC), Xiaojin Capsule (XC), Gongliu Xiao Capsule (GLXC), Xuefu Zhuyu Capsule (XZC), Jingtong Yushu Granule (JYG), Zhitong Huazheng Capsule (ZHC), and Kuntai Capsule (KTC) for the treatment of endometriosis. However, these studies have yet to be evaluated through a network meta-analysis (NMA) compliant with PRISMA standards.</p><p><strong>Aim of the study: </strong>This study aimed to compare the efficacy and safety of ten CPMs for treating EMs through a NMA on RCTs.</p><p><strong>Materials and methods: </strong>PubMed, Cochrane, Embase, Web of Science, China National Knowledge Infrastructure, VIP Information, WanFang, and China Biomedicine databases were searched up to October 2024 for studies on the efficacy and safety of CPMs in treating EMs. Two researchers independently screened the studies, extracted data, and assessed quality using the Cochrane Risk of Bias 2.0 tool and the Confidence in Network Meta-Analysis framework. The NMA was conducted using Bayesian methods with StataSE and Rstudio, generating network diagrams, league tables, and Surface Under the Cumulative Ranking (SUCRA) line charts. This study was registered with PROSPERO (CRD42023477523).</p><p><strong>Results: </strong>148 eligible trials involving 10 CPMs and 16198 participants were included in this NMA; all subsequent estimates refer to the comparison with conventional therapies. All 10 CPMs effectively improved the total effective rate and VAS pain scores. SZC induced the most significant improvement in total effective rate(compared to hormone therapy: risk ratio 5.51, 95% confidence interval 4.21 to 7.2, SUCRA 86.3%, moderate confidence of evidence; compared to GnRH-a: 4.74, (3.18 to 7), moderate confidence of evidence). DFP proved to be the most effective CPM for lowering the VAS pain scores. (compared to hormone therapy: mean difference -2.1, (-2.94 to -1.29), 78.8%, moderate confidence of evidence; and GnRH-a (-2.07, (-2.73 to -1.41), low confidence of evidence). Moreover, this study demonstrated the safety of CPMs, particularly in reducing hormonal and liver-related side effects. Specific CPMs like XZC, SZC, DFP, KTC, and GFC showed markedly lower relative risks of adverse events when compared to conventional therapies.</p><p><strong>Conclusion: </strong>; Chinese patent medicine may effectively treat EMs, excelling in total effective rate, pain relief, CA125 reduction, an","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119465"},"PeriodicalIF":4.8,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390925","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 : 2025-02-08DOI: 10.1016/j.jep.2025.119457
Rao Zhong, Changlin Wen, Yi Qiu, Xuemei Shen, Zhenhua Sun, Li Peng, Tao Liu, Shiyuan Huang, Xi Peng
Ethnopharmacological relevance: As a traditional Chinese herb, Glycyrrhiza uralensis Fisch. exhibits a range of pharmacological activities, including anti-inflammatory, immunomodulatory and antifibrotic, which suggests its therapeutic potential for inflammatory bowel disease, and related mechanisms need to be further clarified.
Aim of the study: To evaluate in vivo anti-inflammatory effects of Glycyrrhiza uralensis Fisch. aqueous extract (GE) on 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced acute experimental colitis rat model and its potential mechanisms.
Materials and methods: The protective effects of GE on IBD were evaluated in vivo using a TNBS and 75% ethanol-induced ulcerative colitis (UC) model. The evaluated clinical and anatomical indexes included body weight, colon length, disease activity index (DAI) score, Colonic Mucosal Damage Index (CMDI) score. The percentages of T, B lymphocytes, NK cells, and macrophages in the colon, spleen and peripheral blood were investigated by flow cytometry. Colon tissues were stained with Hematoxylin and Eosin (H&E) for histopathological examination. After using transcriptome sequencing to screen targeted genes, the expression of related genes was detected by Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR) and Western blot (WB).
Results: The decrease of food intake, soft feces, and colon histopathological injury were observed in colitis rats, which were alleviated by GE, with the best therapeutic effect in the 100 mg/kg GE group. The average CMDI scores of colon in UC rats were decreased from 4.0 to 1.5. The percentages of CD161a+ NK cells, CD68+ total macrophages, CD68+/CD161a+ M1 type macrophages, CD3+ T lymphocytes, and CD45RA+ B lymphocytes were decreased in the spleen and colon. The transcriptomics analysis of colon showed that the results were mainly related to the TNF signaling pathway and NF-κB signaling pathway. The RT-qPCR and WB results determined that the upregulated expression of nucleotide-binding oligomerization domain 2 (NOD2), receptor-interacting protein 2 (RIP2), nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α) in the colon of the colitis rats were downregulated by GE treatment.
Conclusion: The research results indicate that GE can exert therapeutic effects on TNBS-induced UC in rats by alleviating cell injury and inflammatory responses, and its mechanisms may be related to the regulation of NOD2/RIP2/NF-κB signaling pathway.
{"title":"Anti-Inflammatory and Immunomodulatory Effects of Glycyrrhiza uralensis Fisch. on Ulcerative Colitis in Rats: Role of Nucleotide-binding oligomerization domain 2/Receptor-interacting protein 2/Nuclear factor-kappa B Signaling Pathway.","authors":"Rao Zhong, Changlin Wen, Yi Qiu, Xuemei Shen, Zhenhua Sun, Li Peng, Tao Liu, Shiyuan Huang, Xi Peng","doi":"10.1016/j.jep.2025.119457","DOIUrl":"https://doi.org/10.1016/j.jep.2025.119457","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>As a traditional Chinese herb, Glycyrrhiza uralensis Fisch. exhibits a range of pharmacological activities, including anti-inflammatory, immunomodulatory and antifibrotic, which suggests its therapeutic potential for inflammatory bowel disease, and related mechanisms need to be further clarified.</p><p><strong>Aim of the study: </strong>To evaluate in vivo anti-inflammatory effects of Glycyrrhiza uralensis Fisch. aqueous extract (GE) on 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced acute experimental colitis rat model and its potential mechanisms.</p><p><strong>Materials and methods: </strong>The protective effects of GE on IBD were evaluated in vivo using a TNBS and 75% ethanol-induced ulcerative colitis (UC) model. The evaluated clinical and anatomical indexes included body weight, colon length, disease activity index (DAI) score, Colonic Mucosal Damage Index (CMDI) score. The percentages of T, B lymphocytes, NK cells, and macrophages in the colon, spleen and peripheral blood were investigated by flow cytometry. Colon tissues were stained with Hematoxylin and Eosin (H&E) for histopathological examination. After using transcriptome sequencing to screen targeted genes, the expression of related genes was detected by Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR) and Western blot (WB).</p><p><strong>Results: </strong>The decrease of food intake, soft feces, and colon histopathological injury were observed in colitis rats, which were alleviated by GE, with the best therapeutic effect in the 100 mg/kg GE group. The average CMDI scores of colon in UC rats were decreased from 4.0 to 1.5. The percentages of CD161a<sup>+</sup> NK cells, CD68<sup>+</sup> total macrophages, CD68<sup>+</sup>/CD161a<sup>+</sup> M1 type macrophages, CD3<sup>+</sup> T lymphocytes, and CD45RA<sup>+</sup> B lymphocytes were decreased in the spleen and colon. The transcriptomics analysis of colon showed that the results were mainly related to the TNF signaling pathway and NF-κB signaling pathway. The RT-qPCR and WB results determined that the upregulated expression of nucleotide-binding oligomerization domain 2 (NOD2), receptor-interacting protein 2 (RIP2), nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α) in the colon of the colitis rats were downregulated by GE treatment.</p><p><strong>Conclusion: </strong>The research results indicate that GE can exert therapeutic effects on TNBS-induced UC in rats by alleviating cell injury and inflammatory responses, and its mechanisms may be related to the regulation of NOD2/RIP2/NF-κB signaling pathway.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119457"},"PeriodicalIF":4.8,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390982","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: It is well known that Shaoyao Decoction (SYD), as a commonly used formula of traditional Chinese medicine (TCM) has a beneficial effect on the treatment of ulcerative colitis (UC). It is found that SYD can also prevent colitis-associated colorectal cancer (CAC). However, its potential anti-cancer mechanism is still waiting to be revealed.
Aims of the study: The aim of this study is to investigate the underlying mechanisms of SYD in inhibiting CAC through silico analysis as well as animal experiment validation.
Materials and methods: The primary active compounds, potential therapeutic targets and intervening signaling pathways, which SYD might inhibit the CAC process were predicted by network pharmacology analysis combined with our previous research result of high performance liquid chromatography (HPLC). We attempted to validate the acquired hub targets from molecular docking combined with the Gene Expression Profiling Interactive Analysis (GEPIA), the Human Protein Atlas (HPA), and the cBioPortal database comprehensively. Subsequently, an animal model of CAC mice induced by Azioximethane (AOM) and dextran sulfate sodium (DSS) was constructed and treated with SYD for 14 weeks, and tumor-related physical indicators were evaluated after sacrificed. In addition, samples of colon tissues were obtained for histologic and protein level studies to verify the predicted mechanism.
Results: We obtained 167 active ingredients of SYD and predicted 148 potential targets through network pharmacology analysis, among which quercetin, berberine, kaempferol, wogonin and naringenin were selected as core drug ingredients, and TP53, AKT1, CASP3, PTGS2 and CCND1 were identified and included into the range of core targets. GO and KEGG analyses suggested that the PI3K-Akt signaling pathway may hold a crucial role in CAC prevention and treatment by promoting apoptosis and inhibiting tumor proliferation. In the animal experiment, both SYD and SASP treatments improved the inflammatory condition and pathological damage of the colon in mice. After treatment with SYD and SASP, it was found that a decrease of Cyclin D1, and Survivin expression levels and increase of p53, Cleaved caspase-3 expression levels could be mediated by decreasing the phosphorylation levels of PI3K and Akt proteins in the colon tissues of mice.
Conclusion: The results of our study provide supports that SYD effectively inhibits CAC based on modulating PI3K-Akt signaling pathway to suppress tumor proliferation process as well as to promote tumor apoptosis process.
{"title":"In silico and animal studies on the anti-cancer mechanisms of Shaoyao Decoction against colitis-associated colorectal cancer.","authors":"Bingwei Yang, Chenglei Wang, Xue Chen, Haoyu Zhai, Ying Wu, Muyao Cui, Jiahe Wu, Weidong Li, Baojin Hua","doi":"10.1016/j.jep.2025.119444","DOIUrl":"https://doi.org/10.1016/j.jep.2025.119444","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>It is well known that Shaoyao Decoction (SYD), as a commonly used formula of traditional Chinese medicine (TCM) has a beneficial effect on the treatment of ulcerative colitis (UC). It is found that SYD can also prevent colitis-associated colorectal cancer (CAC). However, its potential anti-cancer mechanism is still waiting to be revealed.</p><p><strong>Aims of the study: </strong>The aim of this study is to investigate the underlying mechanisms of SYD in inhibiting CAC through silico analysis as well as animal experiment validation.</p><p><strong>Materials and methods: </strong>The primary active compounds, potential therapeutic targets and intervening signaling pathways, which SYD might inhibit the CAC process were predicted by network pharmacology analysis combined with our previous research result of high performance liquid chromatography (HPLC). We attempted to validate the acquired hub targets from molecular docking combined with the Gene Expression Profiling Interactive Analysis (GEPIA), the Human Protein Atlas (HPA), and the cBioPortal database comprehensively. Subsequently, an animal model of CAC mice induced by Azioximethane (AOM) and dextran sulfate sodium (DSS) was constructed and treated with SYD for 14 weeks, and tumor-related physical indicators were evaluated after sacrificed. In addition, samples of colon tissues were obtained for histologic and protein level studies to verify the predicted mechanism.</p><p><strong>Results: </strong>We obtained 167 active ingredients of SYD and predicted 148 potential targets through network pharmacology analysis, among which quercetin, berberine, kaempferol, wogonin and naringenin were selected as core drug ingredients, and TP53, AKT1, CASP3, PTGS2 and CCND1 were identified and included into the range of core targets. GO and KEGG analyses suggested that the PI3K-Akt signaling pathway may hold a crucial role in CAC prevention and treatment by promoting apoptosis and inhibiting tumor proliferation. In the animal experiment, both SYD and SASP treatments improved the inflammatory condition and pathological damage of the colon in mice. After treatment with SYD and SASP, it was found that a decrease of Cyclin D1, and Survivin expression levels and increase of p53, Cleaved caspase-3 expression levels could be mediated by decreasing the phosphorylation levels of PI3K and Akt proteins in the colon tissues of mice.</p><p><strong>Conclusion: </strong>The results of our study provide supports that SYD effectively inhibits CAC based on modulating PI3K-Akt signaling pathway to suppress tumor proliferation process as well as to promote tumor apoptosis process.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119444"},"PeriodicalIF":4.8,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390930","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号