Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Feb 18;33(4):250-257.
doi: 10.7555/JBR.32.20180031. Online ahead of print.

Schizonepeta tenuifolia inhibits collagen stimulated platelet function via suppressing MAPK and Akt signaling

Bo-Ra Jeon  1 , Muhammad Irfan  1 , Minki Kim  1 , Seung Eun Lee  2 , Jeong Hoon Lee  2 , Man Hee Rhee  1
Affiliations

Schizonepeta tenuifolia inhibits collagen stimulated platelet function via suppressing MAPK and Akt signaling

Bo-Ra Jeon et al. J Biomed Res. .

Abstract

The prevalence of cardiovascular diseases (CVDs) is increasing at a rapid pace in developed countries, and CVDs are the leading cause of morbidity and mortality. Natural products and ethnomedicine have been shown to reduce the risk of CVDs. Schizonepeta (S.) tenuifolia is a medicinal plant widely used in China, Korea, and Japan and is known to exhibit anti-inflammatory, antioxidant, and immunomodulatory activities. We hypothesized that given herbal plant exhibit pharmacological activities against CVDs, we specifically explored its effects on platelet function. Platelet aggregation was evaluated using standard light transmission aggregometry. Intracellular calcium mobilization was assessed using Fura-2/AM, and granule secretion (ATP release) was measured in a luminometer. Fibrinogen binding to integrin αⅡbβ3, was assessed using flow cytometry. Phosphorylation of mitogen-activated protein kinase (MAPK) signaling molecules and activation of the protein kinase B (Akt) was assessed using Western blot assays. S. tenuifolia, extract potently and significantly inhibited platelet aggregation, calcium mobilization, granule secretion, and fibrinogen binding to integrin αⅡbβ3. Moreover, all extracts significantly inhibited MAPK and Akt phosphorylation. S. tenuifolia extract inhibited platelet aggregation and granule secretion, and attenuated collagen mediated GPVI downstream signaling, indicating the potential therapeutic effects of these plant extracts on the cardiovascular system and platelet function. We suggest that S. tenuifolia extract may be a potent candidate to treat platelet-related CVDs and to be used as an antiplatelet and antithrombotic agent.

PubMed Disclaimer

Figures

A–C: Washed platelets were pretreated with <italic>S. tenuifolia</italic> extract or vehicle for two minutes in the presence of 1 mmol/L CaCl<sub>2</sub>, and then stimulated with collagen (2.5 μg/mL), or ADP (10 μmol/L) or thrombin (0.1 U/mL) for five minutes. C: Scanning electron microscopy was performed in collagen (2.5 μg/mL) treated platelets. Representative scanning electron microscopy images of platelets treated with (a) Resting (b) Vehicle, (c) 25 μg/mL <italic>S. tenuifolia</italic>, (d) 50 μg/mL <italic>S. tenuifolia</italic>, and (e) 100 μg/mL <italic>S. tenuifolia</italic>. Graph represents the mean±SEM of experiments performed on four independent days with <italic>n</italic>=1 on each day. <sup>***</sup><italic>P</italic>&lt;0.001 <italic>vs.</italic> control.
1
Schizonepeta tenuifolia extract inhibits collagen-stimulated platelet aggregation.
A: Washed platelets were loaded with a calcium fluorophore (5 μmol/L Fura-2/AM) for one hour. Fura 2/AMloaded platelets were pretreated with <italic>S. tenuifolia</italic> extract for two minutes at 37 °C and then stimulated with collagen (2.5 μg/mL). B: After platelet aggregation was terminated, the concentration of ATP was assessed in collagen-stimulated platelets treated with <italic>S. tenuifolia</italic>, using a luminometer. Results represent the mean±SEM of experiments performed on four independent days with <italic>n</italic>=1 on each day. <sup>***</sup><italic>P</italic>&lt;0.001 <italic>vs.</italic> control.
2
The inhibitory effect of Schizonepeta tenuifolia extract on collagen-stimulated intracellular calcium concentration ([Ca2+]i) elevation and ATP secretion.
A: Flow cytometry was used to measure fibrinogen binding to collagen (2.5 μg/mL)-stimulated platelets after treatment with (a) Resting, (b) Vehicle, (c) 25 μg/mL <italic>S. tenuifolia</italic>, (d) 50 μg/mL <italic>S. tenuifolia</italic>, and (e) 100 μg/mL <italic>S. tenuifolia</italic>. B: Bar graph summarizing the inhibitory effect of <italic>S. tenuifolia</italic> extract on fibrinogen binding to integrin α<sub>Ⅱb</sub>β<sub>3</sub>. Results represent the mean±SEM of experiments performed on four independent days with <italic>n</italic>=1 on each day. <sup>***</sup><italic>P</italic>&lt;0.001 <italic>vs.</italic> control.
3
Schizonepeta tenuifolia blocks fibrinogen binding to integrin αⅡbβ3 in collagen-induced platelets.
4
4
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Maione F, De Feo V, Caiazzo E, et al Tanshinone IIA, a major component of Salvia milthorriza Bunge, inhibits platelet activation via Erk-2 signaling pathway. J Ethnopharmacol. 2014;155(2):1236–1242. doi: 10.1016/j.jep.2014.07.010. - DOI - PubMed
    1. Michel JB, Martin-Ventura JL, Nicoletti A, et al Pathology of human plaque vulnerability: mechanisms and consequences of intraplaque haemorrhages. Atherosclerosis. 2014;234(2):311–319. doi: 10.1016/j.atherosclerosis.2014.03.020. - DOI - PubMed
    1. Barrett NE, Holbrook L, Jones S, et al Future innovations in antiplatelet therapies. Br J Pharmacol. 2008;154(5):918–939. doi: 10.1038/bjp.2008.151. - DOI - PMC - PubMed
    1. Rastogi S, Pandey MM, Rawat AK Traditional herbs: a remedy for cardiovascular disorders. Phytomedicine. 2016;23(11):1082–1089. doi: 10.1016/j.phymed.2015.10.012. - DOI - PubMed
    1. Kerver JM, Yang EJ, Bianchi L, et al Dietary patterns associated with risk factors for cardiovascular disease in healthy US adults. Am J Clin Nutr. 2003;78(6):1103–1110. doi: 10.1093/ajcn/78.6.1103. - DOI - PubMed