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Berberine mitigates high glucose-potentiated platelet aggregation and apoptosis by modulating aldose reductase and
Manoj Paul1, Mahadevappa Hemshekhar2, Kempaiah Kemparaju1
1Department of Studies in Biochemistry, University of Mysore, Manasagangothri, Mysuru 570006, India.
Insights
Berberine effectively inhibits high glucose-induced platelet aggregation and apoptosis in diabetes mellitus by targeting reactive oxygen species production. This suggests berberine as a potential therapeutic for diabetic vascular complications.
Area of Science:
- Biochemistry
- Pharmacology
- Endocrinology
Background:
- Diabetes mellitus (DM) is linked to increased atherothrombotic events due to platelet hyper-reactivity and apoptosis.
- Elevated reactive oxygen species (ROS) from aldose reductase (AR) and NADPH oxidase (NOX) activities contribute to platelet dysfunction in DM.
- Aspirin resistance in DM necessitates novel therapeutic strategies targeting underlying mechanisms.
Purpose of the Study:
- To investigate the inhibitory effects of berberine on high glucose-induced platelet aggregation and apoptosis.
- To elucidate the underlying mechanisms of berberine's action in platelets.
Main Methods:
- Platelet aggregation and apoptosis assays were performed on high glucose (HG)-treated platelets.
- Modulation of AR, NOX, and glutathione reductase activities by berberine was assessed.
- Analysis of calcium release, ERK activation, granule release, adhesive properties, and mitochondrial function.
Main Results:
- Berberine inhibited HG-induced platelet aggregation and superoxide production by modulating AR, NOX, and glutathione reductase.
- Berberine suppressed calcium release, ERK activation, granule release, and platelet adhesion.
- Berberine prevented p38-p53 mediated BAX activation, mitochondrial dysfunction, and apoptosis in HG-treated platelets.
Conclusions:
- Berberine exhibits significant platelet-protective effects in a high glucose environment.
- Inhibition of AR and NOX activities by berberine underlies its therapeutic potential.
- Berberine may serve as a promising therapeutic agent for managing diabetic vascular pathologies.
Abstract:
Diabetes mellitus (DM) is a serious metabolic disorder affecting millions of people worldwide. The high rate of mortality and morbidity during DM is attributed to the increased atherothrombotic events due to platelet activation and apoptosis leading to macro and micro vascular occlusions. The platelet hyper-reactivity and apoptosis during DM is accounted for the accumulated reactive oxygen species (ROS) due to increased aldose reductase (AR) and NADPH oxidase (NOX) activities. Considering aspirin insensitivity in DM patients, new therapies targeting the underlying mechanism is urgently warranted. Berberine, a benzylisoquinoline alkaloids, from Chinese folk medicine has been demonstrated with several anti-diabetic effects. Therefore, we evaluated whether berberine inhibits high glucose potentiated platelet aggregation, apoptosis and further evaluated the mechanism of its action in platelets. Berberine was found to inhibit platelet aggregation, superoxide production via modulating AR, NOX, and glutathione reductase activities in high glucose (HG) treated platelets. Correlated with this, berberine inhibited, calcium release, ERK activation, α- and dense granule release and platelet adhesive properties. In addition, berberine inhibited p38-p53 mediated BAX activation, mitochondrial dysfunction and platelet apoptosis induced by HG. The platelet protective effect of berberine by inhibiting AR and NOX in high glucose-treated platelets suggest that berberine could be developed as a potential therapeutic molecule in the treating pathologies associated with DM.
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