Multi-Target Cardioprotection from Berberis kaschgarica Extract in Zebrafish via AMPK Pathway Activation

Area of Science:

• Pharmacology
• Cardiovascular Research
• Natural Products

Background:

• Heart failure (HF) pathogenesis involves oxidative stress, inflammation, and metabolic dysfunction, necessitating multi-target therapeutic agents.
• Berberis kaschgarica Rupr. (BKR) is traditionally used for cardiovascular health, but its mechanisms in HF are not well understood.

Purpose of the Study:

• To investigate the cardioprotective mechanisms of Berberis kaschgarica Rupr. extract (BKRE) against heart failure (HF).
• To validate the ethnopharmacological use of BKR in cardiovascular health.

Main Methods:

• Chemical profiling of BKRE using UPLC-MS/MS and assessment of antioxidant activity via DPPH/ABTS assays.
• Evaluation of BKRE's effects on cardiac function, apoptosis, oxidative stress, and inflammation in ISO-induced HF zebrafish models.
• Elucidation of molecular targets and pathways using network pharmacology, molecular docking, transcriptomics, and qRT-PCR.

Main Results:

• BKRE contains 14 bioactive compounds with antioxidant properties.
• BKRE dose-dependently improved cardiac function, inhibited apoptosis, reduced oxidative stress (ROS, TNF-α, IL-6), and restored antioxidant levels (GSH, T-SOD) in HF zebrafish.
• BKRE activated the AMPK-PPARα-PGC-1α pathway, potentially by interacting with ALOX5 and NQO1.

Conclusions:

• BKRE exhibits multi-mechanistic cardioprotective effects against heart failure.
• These findings support the ethnopharmacological value of BKR and suggest its potential as a therapeutic agent or functional food for HF.