Indigo Leaves-Induced Pulmonary Arterial Remodeling without Right Ventricular Hypertrophy in Rats
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- Tsunematsu Honoka
- Department of Medical Pharmacology, Tokushima University Graduate School of Biomedical Sciences
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- Imanishi Masaki
- Department of Medical Pharmacology, Tokushima University Graduate School of Biomedical Sciences
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- Uemura Yuka
- Department of Medical Pharmacology, Tokushima University Graduate School of Biomedical Sciences
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- Higaki Yoshiya
- Department of Medical Pharmacology, Tokushima University Graduate School of Biomedical Sciences
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- Morisaki Miyu
- Department of Medical Pharmacology, Tokushima University Graduate School of Biomedical Sciences
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- Katsura Akari
- Department of Medical Pharmacology, Tokushima University Graduate School of Biomedical Sciences
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- Miyamoto Licht
- Laboratory of Pharmacology and Food Science, Department of Nutrition and Life Science, Faculty of Health and Medical Sciences, Kanagawa Institute of Technology
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- Funamoto Masafumi
- Department of Pharmacology, Tokushima University Graduate School of Biomedical Sciences
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- Ichimura-Shimizu Mayuko
- Department of Pathology and Laboratory Medicine, Tokushima University Graduate School of Biomedical Sciences
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- Horinouchi Yuya
- Department of Pharmaceutical Care and Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Tokushima Bunri University
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- Ikeda Yasumasa
- Department of Pharmacology, Tokushima University Graduate School of Biomedical Sciences
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- Tsuneyama Koichi
- Department of Pathology and Laboratory Medicine, Tokushima University Graduate School of Biomedical Sciences
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- Tsuchiya Koichiro
- Department of Medical Pharmacology, Tokushima University Graduate School of Biomedical Sciences
説明
<p>Indigo naturalis (IN), derived from the leaves of the indigo plant, is a traditional Chinese medicine that has historically been used for its anti-inflammatory properties in the treatment of various diseases, including ulcerative colitis (UC). However, long-term use of IN in UC patients is incontrovertibly associated with the onset of pulmonary arterial hypertension (PAH). To investigate the mechanisms by which IN induces PAH, we focused on the raw material of IN, indigo leaves (IL). Only the condition of long-term chronic (6 months) and high-dose (containing 5% IL in the control diet) administration of IL induced medial thickening in the pulmonary arteries without right ventricular hypertrophy in our rat model. IL administration for a month did not induce pulmonary arterial remodeling but increased endothelin-1 (ET-1) expression levels within endothelial cell (EC) layers in the lungs. Gene Expression Omnibus analysis showed that ET-1 is a key regulator of PAH and that the IL component indican and its metabolite IS induced ET-1 mRNA expression via reactive oxygen species-dependent mechanism. We identified the roles of indican and IS in ET-1 expression in ECs, which were linked to pulmonary arterial remodeling in an animal model.</p>
収録刊行物
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- Ｂｉｏｌｏｇｉｃａｌ ＆ Ｐｈａｒｍａｃｅｕｔｉｃａｌ Ｂｕｌｌｅｔｉｎ
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Ｂｉｏｌｏｇｉｃａｌ ＆ Ｐｈａｒｍａｃｅｕｔｉｃａｌ Ｂｕｌｌｅｔｉｎ 47 (7), 1350-1359, 2024-07-30
公益社団法人 日本薬学会