Salvianolic Acid A Protects Against Angiotensin II-Induced Hypertensive Kidney Disease by Targeting TLR4 and...

Area of Science:

• Pharmacology
• Nephrology
• Molecular Biology

Background:

• Hypertensive nephropathy (HN) is a major cause of end-stage renal disease, driven by Angiotensin II (Ang II)-induced inflammation, apoptosis, and fibrosis.
• Salvianolic acid A (SAA), a natural compound, possesses anti-inflammatory properties, but its efficacy in HN is not well-established.

Purpose of the Study:

• To investigate the therapeutic potential of Salvianolic acid A (SAA) in a mouse model of hypertensive nephropathy (HN).
• To elucidate the molecular mechanisms underlying SAA's protective effects against Ang II-induced kidney injury.

Main Methods:

• Hypertensive nephropathy was induced in mice using Angiotensin II (Ang II) infusion.
• Mice were treated with SAA (10 or 20 mg/kg/day) or vehicle.
• In vitro studies utilized NRK-52E cells to examine SAA's effects on inflammatory and apoptotic pathways.
• Network pharmacology, pull-down assays, DARTS, and molecular docking were employed to identify SAA's molecular targets.

Main Results:

• SAA treatment significantly improved renal function and reduced inflammation, tubular cell apoptosis, and interstitial fibrosis in Ang II-induced HN mice, independent of systemic blood pressure.
• In vitro, SAA inhibited the TLR4/PI3K/AKT/NF-κB signaling pathway by suppressing PI3K and AKT phosphorylation and NF-κB activation.
• SAA directly interacted with TLR4, and its protective effects were dependent on TLR4 signaling.

Conclusions:

• Salvianolic acid A (SAA) demonstrates significant protective effects against Angiotensin II-induced hypertensive nephropathy.
• SAA acts by inhibiting the TLR4/MyD88/PI3K/AKT/NF-κB signaling axis.
• SAA represents a promising therapeutic candidate for hypertensive kidney injury, targeting the TLR4 pathway.