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Antithrombotic Effect of Artemisinin through Phosphoprotein Regulation in U46619-induced Platelets
Biomed Sci Letters 2023;29:184-189
Published online September 30, 2023;  https://doi.org/10.15616/BSL.2023.29.3.184
© 2023 The Korean Society For Biomedical Laboratory Sciences.

Dong-Ha Lee†,*

Department of Biomedical Laboratory Science, Molecular Diagnostics Research Institute, Namseoul University, Cheonan 31020, Korea
Correspondence to: Dong-Ha Lee. Department of Biomedical Laboratory Science, Molecular Diagnostics Research Institute, Namseoul University, Cheonan 31020, Korea.
Tel: +82-41-580-2148, Fax: +82-42-580-2932, e-mail: dhlee@nsu.ac.kr
*Professor.
Received August 21, 2023; Revised September 12, 2023; Accepted September 18, 2023.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
 Abstract
Normal activation of platelets and their aggregation are crucial during hemostasis process. It appears excessive or abnormal aggregation of platelets may bring about cardiovascular diseases like stroke, atherosclerosis, and thrombosis. For this reason, finding a substance that can regulate platelet aggregation or suppress aggregation will aid in the prevention and treatment of cardiovascular diseases. Artemisinin, a compound derived from Artemisia or Scopolia plants, has shown potential in various areas such as anticancer and Alzheimer's disease research. However, the specific role and mechanisms by which artemisinin influences platelet activation and thrombus formation are not yet fully understood. This study investigated the effects of artemisinin on platelet activation and thrombus formation. This study examined the effect of artemisinin on regulation of U46619-induced platelet aggregation, granule secretion. In addition, the effects of artemisinin on phosphorylation of PI3K/Akt and MAPK pathway involved in platelet aggregation was studied. As a result, artemisinin significantly downregulated of PI3K/Akt and MAPK pathway. In addition, artemisinin significantly reduced granule secretion, and platelet aggregation was inhibited by artemisinin. Therefore, we suggest that artemisinin is an anti-platelet substance that regulates PI3K/Akt and MAPK pathway and is valuable as a therapeutic and preventive agent for platelet-derived cardiovascular disease.
Keywords : Artemisinin, MAPK, PI3K/Akt, Granule secretion, Platelet aggregation
꽌 濡

삁냼뙋 쓳吏묎낵 洹몄뿉 뵲瑜 삁쟾 삎꽦 吏삁 怨쇱젙뿉꽌 以묒슂븳 뿭븷쓣 븳떎(Xia et al., 2012). 洹몃윭굹 蹂묐━븰쟻 긽깭뿉꽌뒗 삁냼뙋씠 鍮꾩젙긽쟻쑝濡 솢꽦솕릺뼱 삁쟾씠 맆 닔 엳쑝硫, 닚솚븯뒗 삁쟾씠 삁愿쓣 李⑤떒븯뿬 뿀삁꽦 떖옣 吏덊솚 諛 뇤議몄쨷怨 媛숈 떎뼇븳 떖삁愿 吏덊솚(CVD)쓣 쑀諛쒗븷 媛뒫꽦씠 옒 븣젮졇 엳떎(Lee et al., 2014). 寃곌낵쟻쑝濡 삁냼뙋 솢꽦솕쓽 뼲젣뒗 룞留 삁쟾利 諛 삁냼뙋 愿젴 떖삁愿 吏덊솚쓽 吏꾪뻾쓣 셿솕떆궎뒗 쟾왂쑝濡 씤떇릺뼱 솕떎(Ruggeri, 2002).

쁽옱 aspirin, clopidorel 벑 뿬윭 빆삁냼뙋젣媛 媛쒕컻릺뼱 삁쟾利 삁諛⑹쓣 쐞빐 엫긽뿉꽌 쓷엳 궗슜릺怨 엳떎(Bassand, 2013). 洹몃읆뿉룄 遺덇뎄븯怨 씠윭븳 빟臾쇱 쐞옣愿 異쒗삁 諛 떖怨꾪빆吏꾧낵 媛숈 옞옱쟻씤 遺옉슜쑝濡 씤빐 궗슜씠 젣븳맂떎(Vaiyapuri et al., 2013). 뵲씪꽌, 蹂대떎 븞쟾븯怨 슚怨쇱쟻씤 빆삁냼뙋젣쓽 媛쒕컻씠 슂援щ릺怨 엳떎(Barrett et al., 2008).

꽭룷 궡 떊샇 쟾떖뿉 옉슜븯뒗 씤궛솕 슚냼뱾 以묒뿉꽌 Mitogen-activated protein kinases (MAPK)쓽 湲곕뒫뿉 븳 뿰援ш 袁몄엳 씠猷⑥뼱졇 솕떎(Adam et al., 2010). MAPK뿉 냽븯뒗 떒諛깆쭏濡 ERK, JNK 諛 p38 MAPK씠 諛앺졇 엳怨, 씠 떒諛깆쭏뱾 궗엺쓽 삁냼뙋뿉꽌룄 솗씤릺怨 엳쑝硫, 삁냼뙋 옄洹 쑀룄젣뿉 쓽빐 씤궛솕 맖쑝濡쒖뜥 솢꽦쓣 굹궦떎怨 蹂닿퀬릺뼱 엳떎(Kramer et al., 1995; Bugaud et al., 1999; Nadal-Wollbold et al., 2002). MAPK쓽 씤궛솕뒗 삁냼뙋 궡 怨쇰┰ 遺꾨퉬瑜 쑀諛쒗븯뿬 삁냼뙋 쓳吏묒뿉룄 愿뿬븳떎怨 븣젮졇 엳떎(Patrono, 1994; Flevaris et al., 2009). 삉븳, 씤궛솕 떒諛깆쭏 以 PI3K/Akt 寃쎈줈뿉 븳 寃껊룄 옒 蹂닿퀬릺뼱 엳뒗뜲, 씠뱾씠 솢꽦솕맆 븣 삁냼뙋쓽 dense 怨쇰┰ 遺꾨퉬媛 珥됱쭊릺怨 씠뱾쓣 넻빐 삁냼뙋 쓳吏묒쓣 룷븿븳 삁냼뙋 湲곕뒫씠 議곗젅맂떎怨 븣젮졇 엳떎(Chuang et al., 2013).

Artemisinin 슚怨쇱쟻씤 留먮씪由ъ븘 移섎즺젣濡쒖꽌 삤옖 엫긽 궗슜 뿭궗瑜 媛吏 쟾넻 쓽븰젣엯땲떎. Artemisinin怨 洹 뙆깮臾쇰뱾 옒 븣젮吏 빆留먮씪由ъ븘 듅꽦 쇅뿉룄 빆븫, 빆뿼利 諛 빆븣윭吏 옉슜쓣 룷븿븳 愿묐쾾쐞븳 移섎즺 슚怨쇰 엯利앺뻽쑝硫, 씠윭븳 쑀씡븳 슚怨쇨 닔留롮 遺꾩옄 몴쟻쓽 議곗젅뿉 湲곗씤맂떎怨 蹂닿퀬릺뿀떎(Wang et al., 2017; Wong et al., 2017; Yao et al., 2018). 삉븳, 理쒓렐 뿰援ъ뿉꽌뒗 artemisinin怨 洹 쑀룄泥댁쓽 떊寃 蹂댄샇 듅꽦쓣 媛뺤“븯뿬 떎뼇븳 뇤 옣븷쓽 삁諛 諛 移섎즺뿉 옞옱쟻씤 쑀슜꽦쓣 굹궡뿀떎(Das et al., 2014; Xu et al., 2017; Zeng et al., 2017; Fang et al., 2019; Zhao et al., 2019). 듅엳, 븳 뿰援ъ뿉꽌뒗 artemisinin씠 ERK1/2/CREB/BCL-2 떊샇 寃쎈줈쓽 솢꽦솕瑜 넻빐 뿀삁꽦 뇤議몄쨷 쑀諛 꽭룷궗硫몄쓣 빟솕떆궗 닔 엳쓬쓣 엯利앺뻽떎(Peng et al., 2022).

뇤議몄쨷쑝濡 몴릺뒗 CVD뒗 삁냼뙋 쓳吏묎낵 諛젒븳 愿젴씠 엳吏留, 삁냼뙋 쓳吏묎낵 삁쟾 삎꽦뿉 븳 artemisinin쓽 뿭븷怨 湲곗쟾 븘吏 諛앺吏吏 븡븯떎. 뵲씪꽌, 蹂 뿰援ъ뿉꽌뒗 artemisinin쓽 삁냼뙋 쓳吏묒뼲젣 슚怨쇱 씠 怨쇱젙뿉꽌 artemisinin媛 PI3K/Akt MAPK쓽 씤궛솕 떒諛깆쭏 諛 삁냼뙋 怨쇰┰ 遺꾨퉬뿉 뼱뼡 쁺뼢쓣 誘몄튂뒗吏 뿰援ы븯떎.

옱猷 諛 諛⑸쾿

궗엺 삁냼뙋 遺쑀븸 以鍮

궗엺 삁냼뙋 뭾遺 삁옣(PRP) 븳 쟻떗옄궗 寃쎄린삁븸썝뿉꽌 쉷뱷븯떎. PRP뒗 삁냼뙋쓣 닔吏묓븯湲 쐞빐 1,300 횞g쓽 냽룄濡 10遺꾧컙 썝떖 遺꾨━릺뿀怨, 씠썑, 2.7 mM KCl, 138 mM NaCl, 12 mM NaHCO3, 0.49 mM MgCl2, 0.36 mM NaH2PO4, 5.5 mM glucose쓣 븿쑀븯뒗 쁽긽슜 踰꾪띁(pH 7.4)濡 2쉶 꽭泥숉븯떎. 쁽긽슜 踰꾪띁瑜 씠슜븯뿬 理쒖쥌 냽룄 108 cells/mL濡 쁽긽븯뿬 삁냼뙋 遺쑀븸쓣 以鍮꾪븯怨, 삩뿉꽌쓽 삁냼뙋 쓳吏묒쓣 諛⑹븯湲 쐞빐 紐⑤뱺 젅李⑤뒗 25꼦뿉꽌 吏꾪뻾븯떎. 떎뿕 怨쇱젙 궓꽌슱븰援 湲곌깮紐낆쑄由ъ쐞썝쉶쓽 듅씤(1041479-HR-201803-003)쓣 諛쏆븘꽌 닔뻾븯떎.

삁냼뙋 쓳吏묐뒫

108 cells/mL쓽 삁냼뙋 遺쑀븸뿉 떎뼇븳 냽룄쓽 artemisinin (Fig. 1)쓣 泥④븯뿬 37꼦뿉꽌 3遺 룞븞 諛곗뼇븯떎. 洹 썑, 2 mM CaCl2 U46619쓣 옄洹뱀쓣 쐞빐 泥④븯怨, 異붽쟻쑝濡 5遺 룞븞 諛섏쓳븯떎. 떎뿕 쉶쟾냽룄媛 1,000 rpm씤 삁냼뙋 쓳吏묎린(Chrono-Log Co., Havertown, PA, USA)瑜 궗슜븯뿬 吏꾪뻾릺뿀怨, 쓳吏묒쑉 鍮 닾怨쇰룄쓽 利앷瑜 湲곕컲쑝濡 怨꾩궛릺뿀쑝硫, 쁽긽슜 踰꾪띁쓽 닾怨쇰룄瑜 李몄“媛믪쑝濡 궗슜븯떎. Artemisinin 理쒖쥌 냽룄 0.1% DMSO뿉 쓽빐 슜빐릺뿀쑝硫, 紐⑤뱺 떎뿕뿉꽌 룞씪븳 냽룄쓽 DMSO媛 泥④릺뿀떎.

Fig. 1. The structure of artemisinin. Chemical formula: C15H22O5, Molar mass: 282.33 g/moL.

꽭룷룆꽦

꽭룷룆꽦쓣 룊媛븯湲 쐞빐 삁냼뙋 꽭룷吏덈줈遺꽣쓽 lactate dehydrogenase (LDH) 諛⑹텧쓣 痢≪젙븯떎. 108 cells/mL쓽 삁냼뙋 遺쑀븸쓣 떎뼇븳 냽룄쓽 artemisinin怨 븿猿 떎삩뿉꽌 2떆媛 룞븞 諛곗뼇븯떎. 씠썑, 12,000 횞g쓽 냽룄濡 2遺꾧컙 썝떖 遺꾨━븯뿬 긽痢듭븸쓣 LDH EIA kit瑜 궗슜븯뿬 Synergy HT multi-reader (BioTek Instruments, Winooski, VT, USA)濡 痢≪젙븯뿬 怨꾩궛븯떎. 諛⑹텧맂 LDH쓽 뼇쓣 痢≪젙븯뿬 議곌뎔怨 鍮꾧탳븯뿬 굹궡뿀떎.

ATP 諛 serotonin 諛⑹텧웾

108 cells/mL쓽 삁냼뙋 遺쑀븸뿉 떎뼇븳 냽룄쓽 artemisinin쓣 泥④븯뿬 37꼦뿉꽌 3遺 룞븞 諛곗뼇븯떎. 洹 썑, 2 mM CaCl2 U46619쓣 옄洹뱀쓣 쐞빐 泥④븯怨, 異붽쟻쑝濡 5遺 룞븞 諛섏쓳븯떎. 諛섏쓳 李④슫 2 mM EDTA瑜 泥④븯뿬 以묐떒릺뿀怨, 썝떖 遺꾨━瑜 넻빐 긽痢듭븸뿉 諛⑹텧맂 serotonin怨 ATP쓣 Synergy HT multi-reader (BioTek Instruments, Winooski, VT, USA濡) 諛 ATP assay kit serotonin assay kit瑜 궗슜븯뿬 痢≪젙븯떎.

Western Immunoblotting

삁냼뙋 쓳吏묐컲쓳 썑 1X lysis buffer瑜 泥④븯뿬 諛섏쓳쓣 醫낃껐븯떎. 삁냼뙋 슜빐븸 궡 떒諛깆쭏쓽 냽룄뒗 BCA 떒諛깆쭏 kit (Pierce Biotechnology, Rockford, IL, USA)瑜 궗슜븯뿬 痢≪젙븯怨, 珥 15 關g쓽 떒諛깆쭏쓣 쟾湲곗쁺룞븯뿬 遺꾨━븯怨 8% SDS-PAGE瑜 넻빐 PVDF 留됱쑝濡 씠룞떆耳곕떎. 뿬湲곗뿉 1:1,000쑝濡 씗꽍맂 1李 빆泥대 泥섎━븯怨, 洹 썑 1:2,000쑝濡 씗꽍맂 2李 빆泥대 泥섎━븯떎. 떒諛깆쭏 諛대뱶쓽 떆媛곹솕뒗 ECL 떆빟(Thermo Fisher Scientific, Seoul, Korea)瑜 궗슜븯뿬 닔뻾릺뿀떎.

넻怨 遺꾩꽍

떎뿕 寃곌낵뒗 룊洹 짹 몴以렪李 몴떆릺뿀怨, 넻怨꾩쟻 쑀쓽꽦 Student's t-寃젙 삉뒗 遺꾩궛 遺꾩꽍(ANOVA)쓣 궗슜븯뿬 뙋젙릺뿀쑝硫, 쑀쓽닔以 P<0.05濡 꽕젙릺뿀떎. 遺꾩궛 遺꾩꽍쓣 넻빐 洹몃9 媛 룊洹 궗씠뿉 쑀쓽븳 李⑥씠媛 엳뒗 寃쎌슦, Scheffe쓽 諛⑸쾿쓣 궗슜븯뿬 異붽 궗썑 遺꾩꽍씠 닔뻾릺뿀怨, 씠瑜 넻빐 떎뿕 洹몃9媛꾩쓽 쑀쓽븳 李⑥씠瑜 떇蹂꾪븷 닔 엳뒗 룷愿꾩쟻씤 뜲씠꽣 遺꾩꽍씠 媛뒫븯떎.

寃곌낵 諛 怨좎같

U46619 쑀룄쓽 삁냼뙋 쓳吏묒뿉 誘몄튂뒗 artemisinin쓽 슚뒫

TXA2 쑀궗泥대줈 븣젮吏 U46619 (0.5 關M)濡 삁냼뙋 쓳吏묒쓣 쑀룄븯쓣 븣, 80.5짹2.1%쓽 넂 쓳吏묒쑉濡 쓳吏묒씠 씪뼱궗떎(Fig. 2A). 洹몃윭굹 50~500 關M 踰붿쐞濡 떎뼇븳 냽룄쓽 artemisinin씠 泥④릺뿀쓣 븣, Fig. 2A뿉 굹궦 寃곌낵뿉꽌 蹂댁뿬吏벏씠, artemisinin 삁냼뙋 쓳吏묒쓣 슚怨쇱쟻쑝濡 뼲젣븯떎. Artemisinin쓽 half-maximal inhibitory concentration (IC50)뒗 326.31 關M쑝濡 寃곗젙릺뿀쑝硫, artemisinin쓽 泥④濡 씤븳 꽭룷룆꽦 愿李곕릺吏 븡븯떎 (Fig. 2B, C). 씠윭븳 寃곌낵뒗 artemisinin씠 꽭룷룆꽦 뾾씠 U46619 쑀룄쓽 삁냼뙋 쓳吏묒쓣 뼲젣븯뒗 슚怨쇨 엳쓬쓣 蹂댁뿬以떎.

Fig. 2. Effects of artemisinin on U46619-induced platelet aggregation. (A) Effects of artemisinin pretreatment on U46619-stimulated platelet aggregation. (B) IC50 value of artemisinin on U46619-induced platelet aggregation. (C) Cytotoxicity of artemisinin on human platelets. Data are expressed as mean 짹 SD (n=4). *P<0.05, **P<0.001 compared with the U46619-stimulated platelets.

PI3K/Akt뿉 誘몄튂뒗 artemisinin쓽 슚뒫

PI3K/Akt媛 삁냼뙋 궡 怨쇰┰쓽 諛⑹텧뿉 愿뿬븯뒗 떒諛깆쭏濡 븣젮졇 엳쑝誘濡, 蹂 뿰援ъ뿉꽌뒗 artemisinin씠 PI3K/ Akt쓽 씤궛솕뿉 뼱뼡 쁺뼢쓣 誘몄튂뒗吏 솗씤븯떎. 洹 寃곌낵, Fig. 3뿉꽌 굹궦 諛붿 媛숈씠, U46619뒗 PI3k/Akt쓽 씤궛솕瑜 媛뺥븯寃 利앷떆耳곌퀬, artemisinin씠 U46619씠 利앷떆궓 PI3k/Akt쓽 씤궛솕瑜 냽룄쓽議댁쟻쑝濡 뼲젣떆耳곕떎. 씠뒗 artemisinin媛 U46619 쑀룄쓽 삁냼뙋뿉꽌 PI3k/Akt쓽 씤궛솕瑜 쑀쓽븯寃 뼲젣븷 닔 엳뒗 臾쇱쭏엫쓣 遺꾨챸엳 븳 寃껋씠떎.

Fig. 3. Effects of artemisinin on PI3K and Akt phosphorylation. Western blotting was determined as described in "Materials and Methods" section. Data are expressed as mean 짹 SD (n=4). aP< 0.05 compared with no-stimulated platelets, *P<0.05, **P<0.001 compared with the U46619-stimulated platelets.

PI3K/Akt 寃쎈줈뒗 삁냼뙋쓽 솢꽦솕 怨쇱젙뿉꽌 꽭룷 궡 떊샇 쟾떖씠 씪뼱굹뒗뜲 옉슜븯硫, 씠뱾쓽 씤궛솕媛 삁냼뙋 쓳吏 諛 dense 怨쇰┰ 遺꾨퉬瑜 룷븿븳 삁냼뙋쓽 湲곕뒫뿉꽌 二쇱슂븳 뿭븷쓣 떞떦븳떎怨 蹂닿퀬릺뼱 엳떎(Chuang et al., 2013). 蹂 뿰援ъ뿉꽌 솗씤븳 寃곌낵濡 蹂 븣, artemisinin씠 PI3K/Akt 寃쎈줈 씤떒諛깆쭏쓽 씤궛솕瑜 븯뼢議곗젅 븿쑝濡쒖뜥 삁냼뙋쓽 怨쇰┰ 遺꾨퉬 諛 삁냼뙋 쓳吏묒쓣 뼲젣븯쓣 寃껋씠씪怨 삁긽맂떎.

MAPK pathway뿉 誘몄튂뒗 artemisinin쓽 슚뒫

蹂 뿰援ъ뿉꽌 artemisinin씠 MAPK (mitogen-activated protein kinase) 寃쎈줈濡 븣젮吏 씤떒諛깆쭏뱾씠 씤궛솕 씠뿉 쓽빐 쑀룄릺뒗 삁냼뙋 怨쇰┰ 諛⑹텧뿉 誘몄튂뒗 슚뒫쓣 솗씤븯떎. Fig. 4瑜 蹂대㈃ 븣 닔 엳벏씠, U46619濡 쑀룄븯쓣 븣, ERK/JNK/p38쓽 씤궛솕媛 씪뼱궗怨, artemisinin뿉 쓽빐 紐⑤몢 쑀쓽쟻쑝濡 媛먯냼릺뿀떎. 씠뒗 artemisinin씠 MAPK 寃쎈줈 씤떒諛깆쭏뱾쓽 씤궛솕瑜 뼲젣븯뿬 삁냼뙋 쓳吏묒쓽 떊샇 쟾떖 怨쇱젙쓣 議곗젅븯怨 엳쓬쓣 굹궦떎.

Fig. 4. Western blotting was determined as described in "Materials and Methods" section. Data are expressed as mean 짹 SD (n=4). aP<0.05 compared with no-stimulated platelets, *P<0.05 compared with the U46619-stimulated platelets.

븵 꽑 뿰援щ뱾쓣 궡렣蹂 븣, 궗엺쓽 삁냼뙋뿉뒗 MAPK媛 떎웾 議댁옱븯怨 엳怨, 뿬윭 옉슜젣뱾뿉 쓽빐 삁냼뙋씠 솢꽦솕맆 븣, MAPK媛 씤궛솕媛 씪뼱굹硫댁꽌 삁냼뙋 쓳吏묒씠 珥됱쭊릺룄濡 湲곕뒫븳떎怨 븣젮졇 엳떎(Kramer et al., 1995; Bugaud et al., 1999; Nadal-Wollbold et al., 2002). 蹂 뿰援ъ쓽 寃곌낵瑜 넻빐, artemisinin씠 MAPK 寃쎈줈 씤떒諛깆쭏쓽 씤궛솕瑜 븯뼢議곗젅 븿쑝濡쒖뜥 삁냼뙋 궡 怨쇰┰ 遺꾨퉬 諛 삁냼뙋 쓳吏묒쓣 뼲젣븯뒗뜲 湲곗뿬븯뒗 寃껋쑝濡 삁긽맂떎.

삁냼뙋 怨쇰┰ 遺꾨퉬뿉 誘몄튂뒗 artemisinin쓽 슚뒫

삁냼뙋뿉꽌쓽 怨쇰┰ 諛⑹텧 삁냼뙋 쓳吏묒쓣 利앺룺븯뒗뜲 以묒슂븯湲곗뿉 artemisinin씠 ATP 諛 serotonin쓽 怨쇰┰ 遺꾨퉬뿉 뼱뼡 쁺뼢쓣 二쇰뒗吏 궡렣蹂댁븯떎. 洹 寃곌낵, 넀긽릺吏 븡 꽭룷뿉꽌쓽 ATP 諛⑹텧웾씠 0.20짹0.02 關M뿉꽌 U46619뿉 쓽빐 8.10짹0.33 關M濡 媛뺥븯寃 利앷릺뒗 寃껋쓣 솗씤븯떎. 洹몃윭굹, artemisinin (50~500 關M)뿉 쓽빐 利앷맂 ATP 諛⑹텧씠 냽룄쓽議댁쟻쑝濡 뼲젣릺뿀떎(Fig. 5A). 삉븳, 넀긽릺吏 븡 꽭룷뿉꽌 serotonin 諛⑹텧씠 8.65짹0.58 ng/108 cells뿀뜕 寃껋씠 U46619뿉 쓽빐 150.36짹1.30 ng/108 cells濡 겕寃 利앷븯뒗 寃껋쓣 솗씤븯떎. 洹몃윭굹, U46619뿉 쓽빐 利앷맂 serotonin 諛⑹텧웾룄 artemisinin (50~500 關M)뿉 쓽빐 35.66짹3.57 ng/108 cells源뚯 媛뺥븯寃 媛먯냼릺뒗 寃껋쓣 븣 닔 엳뿀떎(Fig. 5B). 씠 寃곌낵뱾 artemisinin씠 삁냼뙋 궡 怨쇰┰ 遺꾨퉬瑜 媛뺥븯寃 媛먯냼떆궎硫댁꽌 삁냼뙋 쓳吏묒쓣 뼲젣븯怨 엳쓬쓣 蹂댁뿬以떎.

Fig. 5. Effects of artemisinin on granule secretion. (A) Effects of artemisinin on ATP release. (B) Effects of artemisinin on serotonin release. Measurement of ATP and serotonin release was described in "Materials and Methods" section. Data are expressed as mean 짹 SD (n=4). aP<0.05 compared with no-stimulated platelets, *P< 0.05, **P<0.001 compared with the U46619-stimulated platelets.

삁냼뙋 궡 怨쇰┰ 遺꾨퉬媛 珥됱쭊맆 븣, 삁냼뙋쓽 솢꽦솕媛 쑀룄릺怨 넀긽맂 삁愿쑝濡 닚솚븯뒗 삁냼뙋쓽 젏李 諛 쓳吏묒쓣 珥됰컻맖쑝濡쒖뜥 삁쟾 삎꽦씠 옒 씪뼱궃떎怨 븣젮졇 엳떎(Calderwood, 2004). 洹몃윭誘濡, 蹂 뿰援щ 넻빐 artemisinin씠 U46619씠 쑀룄븳 삁냼뙋 궡 怨쇰┰쓽 ATP 諛 serototnin 諛⑹텧쓣 냽룄쓽議댁쟻쑝濡 뼲젣븯硫댁꽌 삁냼뙋 솢꽦솕 諛 삁냼뙋 쓳吏 뼲젣뿉 湲곕뒫븳떎뒗 寃껋쓣 紐낇솗엳 븯떎.

씠윭븳 寃곌낵뒗 artemisinin씠 PI3K/Akt 諛 MAPK쓽 씤궛솕瑜 뼲젣븿쑝濡쒖뜥 꽭룷 궡 怨쇰┰ 遺꾨퉬(serotoinin 諛 ATP 諛⑹텧)瑜 媛먯냼븯怨 寃곌낵쟻쑝濡 삁냼뙋 쓳吏묒쓣 뼲젣븯뒗 臾쇱쭏濡쒖뜥 湲곕뒫븯怨 엳쓬쓣 떆궗븳떎. 寃곕줎쟻쑝濡, 슦由щ뒗 artemisinin씠 삁냼뙋 쓳吏 諛 삁쟾 삎꽦怨 愿젴맂 떖삁愿 吏덊솚뿉 븳 삁諛 삉뒗 移섎즺젣濡쒖꽌쓽 媛뒫꽦쓣 媛吏怨 엳쓬쓣 젣븞븳떎.

ACKNOWLEDGEMENT

Funding for this paper was provided by Namseoul University year 2023.

CONFLICT OF INTEREST

The authors declare no conflict of interest.

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