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ORIGINAL RESEARCH article

Front. Pharmacol.

Sec. Renal Pharmacology

Procyanidin displayed a synergistic effect with roxadustat on renal anemia in mice

Provisionally accepted
Mingyang CuiMingyang Cui1Zhe WangZhe Wang2Jiaxin ShiJiaxin Shi1Wenbin WuWenbin Wu1Jin TaoJin Tao1Yujing HanYujing Han3Zihui YangZihui Yang4Junjie LuoJunjie Luo1Yongting LuoYongting Luo1Peng AnPeng An1*Mingyue SunMingyue Sun5*
  • 1China Agricultural University Department of Nutrition and Health, Beijing, China
  • 2Beijing National Day Wonder School, Beijing, China
  • 3Beijing No.35 High Schoola, Beijing, China
  • 4Beijing No.8 High School, Beijing, China
  • 5China Academy of Chinese Medical Sciences Xiyuan Hospital, Beijing, China

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Renal anemia is a common complication of chronic kidney disease (CKD) and is typically treated with erythropoiesis-stimulating agents (ESAs), iron supplements, or drugs such as roxadustat. However, these treatments are often associated with increased cardiovascular risks. New strategies are needed to enhance efficacy and reduce adverse effects. Procyanidin, found in black goji berries, mulberries, and hawthorns, is known in traditional Chinese medicine to improve kidney function, erythropoiesis, and circulation due to its anti-inflammatory, antioxidant, and vasoprotective properties. This study investigated the effect of procyanidin on renal anemia and its potential synergistic effect with roxadustat. CKD mice were treated with 250 mg/kg/day of procyanidin, 5 mg/kg/day of roxadustat, or both for three weeks. Procyanidin improved erythropoiesis, alleviated kidney injury, enhanced kidney function, and promoted iron absorption and mobilization. Roxadustat primarily improved erythropoiesis and iron metabolism. The combination of procyanidin and roxadustat significantly enhanced erythropoiesis, kidney function, and iron metabolism while reducing inflammatory cytokines (IL-6, TNF-α, IL-1β, MCP-1), injury and fibrosis markers (KIM-1, α-SMA), and increasing the expression of iron-related genes (Hamp1 in liver, Dmt1, Dcytb in intestine). Moreover, procyanidin reduced the thrombopoiesis induced by roxadustat. These findings suggest that combining procyanidin with roxadustat may enhance therapeutic outcomes in renal anemia and reduce drug-related side effects.

Keywords: Renal anemia, kidney injury, procyanidin, roxadustat, iron metabolism

Received: 03 Aug 2025; Accepted: 24 Oct 2025.

Copyright: © 2025 Cui, Wang, Shi, Wu, Tao, Han, Yang, Luo, Luo, An and Sun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Peng An, an-peng@cau.edu.cn
Mingyue Sun, sun_moon25@163.com

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material