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Multi-Target Cardioprotection from Berberis kaschgarica Extract in Zebrafish via AMPK Pathway Activation
Alhar Baishan1,2,3,4, Dilihuma Dilimulati1,2,3,4, Alifeiye Aikebaier1,2,3,4
1Department of Pharmacology, School of Pharmacy, Xinjiang Medical University, Urumqi 830017, China.
Insights
Berberis kaschgarica Rupr. extract (BKRE) shows promise for heart failure (HF) treatment. This natural compound improves cardiac function and reduces oxidative stress and inflammation, validating its traditional use.
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.
Abstract:
Background: Heart failure (HF) has a complex pathogenesis involving oxidative stress, inflammation, and energy metabolism disorders, and requires multi-target agents. Berberis kaschgarica Rupr. (BKR) is used in Uyghur folk medicine to improve cardiovascular health, but its cardioprotective mechanisms against HF remain unclear. Methods: UPLC-MS/MS was used to identify BKRE components; DPPH/ABTS assays evaluated antioxidant activity. The MTC of BKRE was determined in zebrafish, and its effects on ISO-induced HF zebrafish were assessed via cardiac function, apoptosis, oxidative stress, and inflammation indicators. Network pharmacology, molecular docking, transcriptomics, and qRT-PCR clarified targets and pathways. Results: BKRE contained 14 bioactive flavonoids/alkaloids with favorable drug-likeness, showing concentration-dependent DPPH and ABTS scavenging. In HF zebrafish, BKRE (5/10/20 μg/mL) dose-dependently improved cardiac function, inhibited apoptosis, reduced ROS and TNF-α/IL-6, restored GSH/T-SOD, activated the AMPK-PPARα-PGC-1α pathway by binding ALOX5/NQO1, etc. Conclusions: BKRE exerts multi-mechanistic cardioprotective effects, validating BKR's ethnopharmacological value and highlighting it as a promising HF agent/functional food.
