医学
纤维化
药理学
体内
肾
生物利用度
口服
免疫印迹
内科学
化学
生物
生物化学
生物技术
基因
作者
Xiaoyi Chen,Tiantian Wang,Qing Shen,Hongxia Ma,Zhanhua Li,Xi-Na Yu,Xin Huang,Lin-Sen Qing,Pei Luo
出处
期刊:ACS pharmacology & translational science
[American Chemical Society]
日期:2024-01-12
卷期号:7 (2): 421-431
标识
DOI:10.1021/acsptsci.3c00264
摘要
In traditional Chinese medicine, Radix Astragali has played a vital role in treating progressive fibrotic diseases. One of its main active components, astragaloside IV, is a promising anti-fibrotic treatment despite its extremely low bioavailability. Our study aimed to optimize sodium astragalosidate (SA) by salt formation to improve solubility and oral absorption for anti-fibrotic therapy in vivo. Isoproterenol-induced myocardial fibrosis rat models and obese BKS-db mice presenting diabetic kidney fibrosis were used in this study. Daily oral administration of SA (20 mg/kg) for 14 days ameliorated cardiac fibrosis by reducing collagen accumulation and fibrosis-related inflammatory signals, including TNF-α, IL-1β, and IL-6. In db/db mice, SA (5,10, and 20 mg/kg per day for 8 weeks) dose-dependently alleviated lipid metabolism impairment and renal dysfunction when administered orally. Furthermore, Western blot and immunohistochemistry analyses demonstrated that SA treatment inhibited renal fibrosis by suppressing TGF-β1/Smads signaling. Taken together, our findings provide the oral-route medication availability of SA, which thus might offer a novel lead compound in preclinical trial-enabling studies for developing a long-term therapy to treat and prevent fibrosis.
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