Preclinical Investigations
on Anti-fibrotic Potential
of Long-Term Oral Therapy of Sodium Astragalosidate in Animal Models
of Cardiac and Renal Fibrosis
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.