Aged garlic extract inhibits human platelet aggregation by altering intracellular signaling and platelet shape change
Open accessAbstract
Background Increased platelet aggregation plays a pivotal role in the etiology of cardiovascular disease. Upon platelet aggregation, an increase in free cytoplasmic Ca(2+) results in the inhibition of soluble guanylyl cyclase (sGC) and adenylyl cyclase (AC), leading to a decrease in cyclic guaninosine-5'-monophosphate (cGMP) and cAMP, respectively. This leads to the activation of the glycoprotein IIb/IIIa (GPIIb/IIIa) fibrinogen receptor, resulting in platelet shape change. Aged garlic extract (AGE) decreases platelet aggregation; however, the mechanisms involved are not clearly defined.Objective Our objective was to investigate the effects of AGE on intraplatelet cell signaling and platelet shape change.Methods Platelets from 14 participants were studied. Platelet aggregation was induced by ADP in the presence of AGE up to a concentration of 6.25% (vol:vol) alone or in combination with 3-morpholinosydnonimine (Sin-1), a nitric oxide donor. The experiments with AGE were repeated in the presence of 3-isobutyl-1-methylxanthine (IBMX), a phosphodiesterase inhibitor. In a series of separate experiments, platelet aggregation was induced in the presence of either 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), an sGC inhibitor, or 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ22536), an AC inhibitor, or a combination of both in the presence of IBMX and AGE. Intraplatelet cGMP and cAMP were measured. The platelets were also subjected to scanning electron microscopic analysis, and their binding to fibrinogen was determined.Results AGE decreased platelet aggregation at all concentrations tested; this decrease was more marked in the presence of Sin-1 and ranged between 15% and 67%.The presence of IBMX also led to a decrease (17-35%) in platelet aggregation at all AGE concentrations and a significant decrease in the amounts of cGMP (24-41%) and cAMP (19-70%), respectively, in the presence of ODQ and SQ22536. The presence of AGE significantly inhibited the binding of activated platelets to fibrinogen, preventing changes in platelet shape.Conclusion These results indicate that AGE inhibits platelet aggregation by increasing cyclic nucleotides and inhibiting fibrinogen binding and platelet shape change.
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AGE prevents both ADP-activated platelets binding to immobilized fibrinogen and platelet aggregation by inhibiting GPIIb/IIIa receptor and increasing cAMP.
“The AGE was reported to prevent both ADP-activated platelets binding to immobilized fibrinogen and platelet aggregation by inhibiting GPIIb/IIIa receptor and increasing cAMP [124].”
From Chemical Constituents and Pharmacological Activities of Garlic (Allium sativum L.): A Review (2020) · cites this paper as [124]
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- Authors
- Rahman, K., Lowe, G. M., & Smith, S.
- Affiliations
- Liverpool John Moores University (GB)
- Corresponding author
- Rahman, Khalid
- ORCID
- Rahman, Khalid
- Venue
- The Journal of Nutrition
- Publisher
- Elsevier BV
- Published
- 2016-02
- Volume
- 146
- Issue
- 2
- Pages
- 410S-415S
- ISSN
- 0022-3166 (ISSN-L)
- OpenAlex
- W2234762803
- Cited by
- 43
- References
- 35
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 2 · 2023: 2 · 2022: 8 · 2021: 4 · 2020: 4 · 2019: 5 · 2018: 6 · 2017: 4 · 2016: 1
- FWCI
- 5.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Liverpool John Moores University (acceptedVersion)
- Funders
- Wakunaga of America Co. Ltd.
- Topics
- Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Garlic and Onion Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Antiplatelet Therapy and Cardiovascular Diseases
- Keywords
- aged garlic extract, platelet aggregation, intracellular signaling, cyclic GMP, cyclic AMP, soluble guanylate cyclase, adenylate cyclase, nitric oxide, platelet shape change, fibrinogen binding, glycoprotein IIb/IIIa receptor, ADP, cardiovascular disease, dietary bioactive compounds, phosphodiesterase inhibition, nitric oxide synthase
- MeSH terms
- Cyclic AMP, Blood Platelets, Cardiovascular Agents, Fibrinogen, Garlic, Cyclic GMP, Humans, Nitric Oxide, Phosphodiesterase Inhibitors, Plant Extracts, Platelet Aggregation, 1-Methyl-3-isobutylxanthine, Signal Transduction
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