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<p>3-(4-Hydroxy-3-methoxyphenyl) propionic acid (HMPA) is an in vivo metabolite of 4-hydroxy-3-methoxycinnamic acid that is widely distributed in plants. This study investigated the protective effects of HMPA against adenine-induced chronic kidney disease by using Saa3 promoter-driven luciferase reporter mice (Saa3-luc mice) that were previously established to monitor tubulointerstitial nephritis. In vivo bioluminescence imaging revealed that HMPA treatment attenuated the adenine-induced signal in mice. Concordantly, this study found that HMPA supplementation effectively prevented renal inflammation and fibrosis without causing tubulointerstitial damage and decreased blood urea nitrogen (BUN) and plasma creatinine concentrations. In addition, the gene expression profiles supported the preventive effect of HMPA on renal inflammation and fibrosis in an adenine-induced chronic kidney disease model. This study also showed that Saa3-luc mice have the advantage of early prediction of renal disease (3 days after adenine diet) and that HMPA supplementation did not show any signal intensity in the kidneys of mice administered adenine for 3 days. Since 2,8-dihydroxyadenine (2,8-DHA), enzymatically produced from dietary adenine, results in the deposition of 2,8-DHA crystals in the renal tubules, we established a method to measure 2,8-DHA concentration and showed that HMPA supplementation prevented the increase in blood 2,8-DHA levels. Finally, we used a mouse model of hyperuricemia induced by potassium oxonate injection and showed that HMPA supplementation reduced the blood uric acid concentration. This study indicates that HMPA could be useful for the prevention of kidney disease and hyperuricemia.</p>

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3-(4-Hydroxy-3-methoxyphenyl) propionic acid prevents renal fibrosis and inflammation in CKD mice induced by adenine

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月1日

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  • Haruka Osedo,
  • Kurumi Ei,
  • Mikoto Oda,
  • Ayane Kudo,
  • Susumu Yoshino,
  • Takashi Tagawa,
  • Hiroshige Kuwahara,
  • Nobuo Yamaguchi,
  • Siyi Chen,
  • Rahmawati Aisyah,
  • Hidemasa Bono,
  • Thanutchaporn Kumrungsee,
  • Noriyuki Yanaka

摘要

3-(4-Hydroxy-3-methoxyphenyl) propionic acid (HMPA) is an in vivo metabolite of 4-hydroxy-3-methoxycinnamic acid that is widely distributed in plants. This study investigated the protective effects of HMPA against adenine-induced chronic kidney disease by using Saa3 promoter-driven luciferase reporter mice (Saa3-luc mice) that were previously established to monitor tubulointerstitial nephritis. In vivo bioluminescence imaging revealed that HMPA treatment attenuated the adenine-induced signal in mice. Concordantly, this study found that HMPA supplementation effectively prevented renal inflammation and fibrosis without causing tubulointerstitial damage and decreased blood urea nitrogen (BUN) and plasma creatinine concentrations. In addition, the gene expression profiles supported the preventive effect of HMPA on renal inflammation and fibrosis in an adenine-induced chronic kidney disease model. This study also showed that Saa3-luc mice have the advantage of early prediction of renal disease (3 days after adenine diet) and that HMPA supplementation did not show any signal intensity in the kidneys of mice administered adenine for 3 days. Since 2,8-dihydroxyadenine (2,8-DHA), enzymatically produced from dietary adenine, results in the deposition of 2,8-DHA crystals in the renal tubules, we established a method to measure 2,8-DHA concentration and showed that HMPA supplementation prevented the increase in blood 2,8-DHA levels. Finally, we used a mouse model of hyperuricemia induced by potassium oxonate injection and showed that HMPA supplementation reduced the blood uric acid concentration. This study indicates that HMPA could be useful for the prevention of kidney disease and hyperuricemia.