Preclinical Investigations on Anti-fibrotic Potential of Long-Term Oral Therapy of Sodium Astragalosidate in Animal Models of Cardiac and Renal Fibrosis
© 2024 The Authors. Published by American Chemical Society..
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:7 |
|---|---|
| Enthalten in: |
ACS pharmacology & translational science - 7(2024), 2 vom: 09. Feb., Seite 421-431 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Chen, Xiao-Yi [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
|---|
| Anmerkungen: |
Date Revised 16.02.2024 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
|---|
| doi: |
10.1021/acsptsci.3c00264 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM368473775 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM368473775 | ||
| 003 | DE-627 | ||
| 005 | 20240216232853.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240215s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1021/acsptsci.3c00264 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1296.xml |
| 035 | |a (DE-627)NLM368473775 | ||
| 035 | |a (NLM)38357273 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Chen, Xiao-Yi |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Preclinical Investigations on Anti-fibrotic Potential of Long-Term Oral Therapy of Sodium Astragalosidate in Animal Models of Cardiac and Renal Fibrosis |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 16.02.2024 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a © 2024 The Authors. Published by American Chemical Society. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 700 | 1 | |a Wang, Tian-Tian |e verfasserin |4 aut | |
| 700 | 1 | |a Shen, Qing |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Hao |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Zhan-Hua |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Xi-Na |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Xiao-Feng |e verfasserin |4 aut | |
| 700 | 1 | |a Qing, Lin-Sen |e verfasserin |4 aut | |
| 700 | 1 | |a Luo, Pei |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t ACS pharmacology & translational science |d 2018 |g 7(2024), 2 vom: 09. Feb., Seite 421-431 |w (DE-627)NLM294010823 |x 2575-9108 |7 nnns |
| 773 | 1 | 8 | |g volume:7 |g year:2024 |g number:2 |g day:09 |g month:02 |g pages:421-431 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1021/acsptsci.3c00264 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 7 |j 2024 |e 2 |b 09 |c 02 |h 421-431 | ||