Inhibition of Collagen-Induced Platelet Aggregation by the Secobutanolide Secolincomolide A from Lindera obtusiloba Blume

Abstract

Atherothrombosis is one of the main underlying cause of cardiovascular diseases. In addition to treating atherothrombosis with antithrombotic agents, there is growing interest in the role of natural food products and biologically active ingredients for the prevention and treatment of cardiovascular diseases. This study aimed to investigate the effect of secolincomolide A (3) isolated from Lindera obtusiloba Blume on platelet activity and identify possible signaling pathways. In our study, the antiplatelet activities of 3 were measured by collagen-induced platelet aggregation and serotonin secretion in freshly isolated rabbit platelets. Interestingly, 3 effectively inhibited the collagen-induced platelet aggregation and serotonin secretion via decreased production of diacylglycerol, arachidonic acid, and cyclooxygenase-mediated metabolites such as thromboxane B2 (TXB2), and prostaglandin D2 (PGD2). In accordance with the antiplatelet activities, 3 prolonged bleeding time and attenuated FeCl3-induced thrombus formation in arterial thrombosis model. Notably, 3 abolished the phosphorylation of phospholipase Cγ2 (PLCγ2), spleen tyrosine kinase (Syk), p47, extracellular signal-regulated kinase 1/2 (ERK1/2), protein kinase B (Akt) by inhibiting the activation of the collagen receptor, glycoprotein VI (GPVI). Taken together, our results indicate the therapeutic potential of 3 in antiplatelet action through inhibition of the GPVI-mediated signaling pathway and the COX-1-mediated AA metabolic pathways.

Plants-Derived Biomolecules as Potent Antiviral Phytomedicines: New Insights on Ethnobotanical Evidences against Coronaviruses

“…It contains several bioactive components, such as flavonoids, isoquinoline alkaloids, sesquiterpene lactones and tannins [ 68 , 69 ]. Moreover, L. aggregate has also showed other biological activities such as antiviral, anti-tumor, anti-inflammatory, antimicrobial and anti-diabetic activities [ 48 , 69 , 70 ]. L. aggregate leaves can also be used to drink as tea, due to their protective effect against oxidative stress [ 70 ].…”

“…Moreover, L. aggregate has also showed other biological activities such as antiviral, anti-tumor, anti-inflammatory, antimicrobial and anti-diabetic activities [ 48 , 69 , 70 ]. L. aggregate leaves can also be used to drink as tea, due to their protective effect against oxidative stress [ 70 ]. In 2005, Shi-you Li et al investigated the effect and efficacy of L. aggregate roots against SARS-CoV-1 [ 50 ].…”

Synthesis and Biological Evaluation of Thio-Derivatives of 2-Hydroxy-1,4-Naphthoquinone (Lawsone) as Novel Antiplatelet Agents

“…These platelets, via the GPVI receptor, bind directly to collagen triggering platelet activation (Nieswandt and Watson, 2003). In this context, our results suggest that pretreatment of platelets with compound 6 down-regulates the GPVI-mediated signaling pathway (Jung et al, 2017).…”

Therapeutic Potential of Lindera obtusiloba: Focus on Antioxidative and Pharmacological Properties

“…In addition, Secolincomolide A inhibited the activation of the collagen receptor, glycoprotein VI (GPVI) and inhibited phosphorylation of spleen tyrosine kinase (Syk) p47, phospholipase Cγ2 (PLCγ2), extracellular signal-regulated kinase 1/2 (ERK1/2) and protein kinase B (Akt). The researchers concluded that Secolincomolide A inhibits the GPVI-mediated signalling pathway and the COX-1-mediated arachidonic acid (AA) metabolism pathway [ 18 ]. Overall, both extracts and compounds isolated from LO have shown antiplatelet and antithrombotic effects in both in vitro and in vivo models through modulating different molecular pathways.…”

“…Both extracts of the different parts of LO and its bioactive compounds have been reported to contain numerous antioxidative compounds, such as polyphenols, lignans, neolignans, flavonoids, and butenolides. The neuroprotective, cytotoxic, anti-inflammatory, anti-allergic, and antithrombotic properties of these bioactive compounds have been reported [ 15 , 16 , 17 , 18 ]. Therefore, LO presents a rich source of bioactive compounds, particularly antioxidants that have been investigated in many diseases associated with oxidative stress.…”