Network pharmacology and experimental validation to elucidate the pharmacological mechanisms of OATF against kidney stones
IntroductionOrthosiphon aristatus (Blume) Miq. (OA) is widely used in folk medicine to treat kidney stones (KS). Its total flavonoids (OATF) are the primary active constituents responsible for its therapeutic effects. However, the exact mechanism of action (MOA) remains unclear. This study aimed to...
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1575270/full |
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| author | Sisi Dai Sisi Dai Qi Fang Hong-Yan Li Rui Sun Hui-Yong Zhang Wei Wu Wei Wu |
| author_facet | Sisi Dai Sisi Dai Qi Fang Hong-Yan Li Rui Sun Hui-Yong Zhang Wei Wu Wei Wu |
| author_sort | Sisi Dai |
| collection | DOAJ |
| description | IntroductionOrthosiphon aristatus (Blume) Miq. (OA) is widely used in folk medicine to treat kidney stones (KS). Its total flavonoids (OATF) are the primary active constituents responsible for its therapeutic effects. However, the exact mechanism of action (MOA) remains unclear. This study aimed to investigate the pharmacological activity of OATF against KS and elucidate its underlying MOA.MethodsNetwork pharmacology and molecular docking were utilized to predict the potential targets and pathways of OATF. An animal model of calcium oxalate crystal deposition was created using intraperitoneal injections of ethylene glycol (EG) and ammonium chloride (AC), alongside a model using human renal tubular epithelial cells (HK-2) induced by supersaturated oxalate (Ox) to investigate the pharmacological mechanisms of OATF against oxidative stress and apoptosis. The effects of OATF on crystal deposition and renal damage were assessed using hematoxylin-eosin (H&E) and periodic acid-Schiff (PAS) staining. Renal tubular damage and apoptosis were evaluated via TUNEL staining. The MOA was explored using Western blotting analyses.ResultsNetwork pharmacological analysis identified the EGFR/PI3K/AKT pathway as a key mechanism in KS. In vitro experimental results demonstrated that OATF effectively protected HK-2 cells from oxidative stress, inhibited calcium oxalate crystal adhesion, and reduced apoptosis. In vivo, OATF significantly decreased serum creatinine (SCR), serum calcium (Ca), serum phosphorus (P), and blood urea nitrogen (BUN) levels in CaOx-induced Sprague-Dawley (SD) rats, indicating its protective effects against KS.ConclusionOATF effectively inhibited kidney stone formation and mitigated renal injury by attenuating oxidative stress and apoptosis through activation of the EGFR/PI3K/AKT pathway. These findings highlight OATF’s therapeutic potential for KS management and provide a scientific basis for its traditional use in herbal medicine. |
| format | Article |
| id | doaj-art-ca94e839a24b4832b3f81f8eeff2c89e |
| institution | OA Journals |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-ca94e839a24b4832b3f81f8eeff2c89e2025-08-20T02:15:24ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-05-011610.3389/fphar.2025.15752701575270Network pharmacology and experimental validation to elucidate the pharmacological mechanisms of OATF against kidney stonesSisi Dai0Sisi Dai1Qi Fang2Hong-Yan Li3Rui Sun4Hui-Yong Zhang5Wei Wu6Wei Wu7School of Life Sciences, Zhuhai College of Science and Technology, Zhuhai, ChinaCollege of Life Sciences, Jilin University, Changchun, ChinaKey Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang, ChinaKey Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang, ChinaKey Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang, ChinaDepartment of Traditional Chinese Medicine, The Forth Affiliated Hospital of China Medical University, Shenyang, ChinaSchool of Life Sciences, Zhuhai College of Science and Technology, Zhuhai, ChinaSchool of Basic Medical Sciences, Peking University Health Science Center, Beijing, ChinaIntroductionOrthosiphon aristatus (Blume) Miq. (OA) is widely used in folk medicine to treat kidney stones (KS). Its total flavonoids (OATF) are the primary active constituents responsible for its therapeutic effects. However, the exact mechanism of action (MOA) remains unclear. This study aimed to investigate the pharmacological activity of OATF against KS and elucidate its underlying MOA.MethodsNetwork pharmacology and molecular docking were utilized to predict the potential targets and pathways of OATF. An animal model of calcium oxalate crystal deposition was created using intraperitoneal injections of ethylene glycol (EG) and ammonium chloride (AC), alongside a model using human renal tubular epithelial cells (HK-2) induced by supersaturated oxalate (Ox) to investigate the pharmacological mechanisms of OATF against oxidative stress and apoptosis. The effects of OATF on crystal deposition and renal damage were assessed using hematoxylin-eosin (H&E) and periodic acid-Schiff (PAS) staining. Renal tubular damage and apoptosis were evaluated via TUNEL staining. The MOA was explored using Western blotting analyses.ResultsNetwork pharmacological analysis identified the EGFR/PI3K/AKT pathway as a key mechanism in KS. In vitro experimental results demonstrated that OATF effectively protected HK-2 cells from oxidative stress, inhibited calcium oxalate crystal adhesion, and reduced apoptosis. In vivo, OATF significantly decreased serum creatinine (SCR), serum calcium (Ca), serum phosphorus (P), and blood urea nitrogen (BUN) levels in CaOx-induced Sprague-Dawley (SD) rats, indicating its protective effects against KS.ConclusionOATF effectively inhibited kidney stone formation and mitigated renal injury by attenuating oxidative stress and apoptosis through activation of the EGFR/PI3K/AKT pathway. These findings highlight OATF’s therapeutic potential for KS management and provide a scientific basis for its traditional use in herbal medicine.https://www.frontiersin.org/articles/10.3389/fphar.2025.1575270/fullOrthosiphon aristatuskidney stoneapoptosisnetwork pharmacologyEGFR/PI3K/Akt |
| spellingShingle | Sisi Dai Sisi Dai Qi Fang Hong-Yan Li Rui Sun Hui-Yong Zhang Wei Wu Wei Wu Network pharmacology and experimental validation to elucidate the pharmacological mechanisms of OATF against kidney stones Frontiers in Pharmacology Orthosiphon aristatus kidney stone apoptosis network pharmacology EGFR/PI3K/Akt |
| title | Network pharmacology and experimental validation to elucidate the pharmacological mechanisms of OATF against kidney stones |
| title_full | Network pharmacology and experimental validation to elucidate the pharmacological mechanisms of OATF against kidney stones |
| title_fullStr | Network pharmacology and experimental validation to elucidate the pharmacological mechanisms of OATF against kidney stones |
| title_full_unstemmed | Network pharmacology and experimental validation to elucidate the pharmacological mechanisms of OATF against kidney stones |
| title_short | Network pharmacology and experimental validation to elucidate the pharmacological mechanisms of OATF against kidney stones |
| title_sort | network pharmacology and experimental validation to elucidate the pharmacological mechanisms of oatf against kidney stones |
| topic | Orthosiphon aristatus kidney stone apoptosis network pharmacology EGFR/PI3K/Akt |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1575270/full |
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