Buddleja globosa (matico) prevents collagen-induced platelet activation by decreasing phospholipase C-gamma 2 and protein kinase C phosphorylation signaling

10.1016/j.jtcme.2017.02.005

Manuel Fuentes；Cesar Sepúlveda；Marcelo Alarcón；Iván Palomo；Eduardo Fuentes

Buddleja globosa ； Matico ； Platelet ； Collagen ； Phospholipase C-gamma 2

Journal of Traditional and Complementary Medicine

8卷1期（2018 / 01 / 01）

66 - 71

英文

Platelets play a key role in thrombosis and cardiovascular diseases. Medicinal plants could be one of the most important factors that influence risks for platelet activation. Buddleja globosa (known as ＂matico＂) is a medicinal plant with many biological activities. The high content of polyphenols suggest that matico could have antiplatelet activity. The present study was aimed at evaluating mechanisms of antiplatelet action of an extract of matico. We demonstrated that matico extract at low concentrations and in a concentration dependent manner (0.05-1 mg/mL) was a potent inhibitor of platelet aggregation in response to collagen, convulsion and ADP (IC_(50) values was 61 mg/mL, 72 μg/mL and 290 μg/mL, respectively). In this sense matico extract exerted the greatest antiaggregant activity induced by collagen. Similarly, matico showed a decrease in % of positive platelet for P-selectina (vehicle, 0.01, 0.05, 0.1, 0.5 and 1 mg/mL were 32 ± 2%, 29 ± 2 (p ＜ 0.05), 19 ± 1 (p ＜ 0.01), 15 ± 2 (p ＜ 0.01), 10 ± 1% (p ＜ 0.01) and 7 ± 2% (p ＜ 0.01), respectively) and PAC-1 binding (vehicle, 0.01, 0.05, 0.1, 0.5 and 1 mg/mL were 59 ± 1, 58 ± 3 (n.s), 55 ± 2 (p ＜ 0.05), 50 ± 2 (p ＜ 0.01), 38 ± 1 (p ＜ 0.01), 36 ± 2 (p ＜ 0.01). The cellular mechanism for the antiplatelet activity of matico might be mediated by the inhibition of phospholipase C-gamma 2 and protein kinase C phosphorylation. This beneficial property of matico may be of importance in thrombosis, in which platelet activation and aggregation are important determinants of thrombus initiation and development, and may contribute to the beneficial effects of matico intake in the prevention of cardiovascular diseases.

1. Cheng, HL,Zhang, LJ,Liang, YH(2013).Antiinflammatory and antioxidant flavonoids and phenols from Cardiospermum halicacabum (Dao Di Ling).J Tradit Complement Med,3,33-40.
   連結：
2. Dwivedi, S,Chopra, D(2014).Revisiting Terminalia arjuna e an ancient cardiovascular drug.J Tradit Complement Med,4,224-231.
   連結：
3. Lin, HH,Charles, AL,Hsieh, CW,Lee, YC,Ciou, JY(2014).Antioxidant effects of 14 Chinese traditional medicinal herbs against human low-density lipoprotein oxidation.J Tradit Complement Med,5,51-55.
   連結：
4. Agullo, G,Gamet-Payrastre, L,Manenti, S(1997).Relationship between flavonoid structure and inhibition of phosphatidylinositol 3-kinase: a comparison with tyrosine kinase and protein kinase C inhibition.Biochem Pharmacol,53,1649-1657.
5. Aragão, GF,Carneiro, LM,Júnior, AP,Bandeira, PN,Lemos, TL,Viana, GSDB(2007).Anti-platelet activity of α.-and β.-amyrin, isomeric mixture from Protium hepta-phyllum.Pharm Biol,45,343-349.
6. Backhouse, N,Delporte, C,Apablaza, C(2008).Antinociceptive activity of Buddleja globosa (matico) in several models of pain.J Ethnopharmacol,119,160-165.
7. Backhouse, N,Rosales, L,Apablaza, C(2008).Analgesic, anti-inflammatory and antioxidant properties of Buddleja globosa, Buddlejaceae.J Ethnopharmacol,116,263-269.
8. Bukhari, IA,Gilani, AH,Meo, SA,Saeed, A(2016).Analgesic, anti-inflammatory and anti-platelet activities of Buddleja crispa.BMC Complement Altern Med,16,016-1021.
9. Bustamante, S,Álvareza, N(2015).Fundamentación preclínica del uso etnomédico de matico (Buddleja globosa Hope).Rev Fitoter,15,37-51.
10. Campo, G,Marchesini, J,Bristot, L(2012).The in vitro effects of verbascoside on human platelet aggregation.J Thromb Thrombolysis,34,318-325.
11. Campo, G,Pavasini, R,Biscaglia, S(2015).Platelet aggregation values in patients with cardiovascular risk factors are reduced by verbascoside treatment. A randomized study.Pharmacol Res,97,1-6.
12. Carnevale, R,Loffredo, L,Pignatelli, P(2012).Dark chocolate inhibits platelet isoprostanes via NOX2 down-regulation in smokers.J Thromb Haemost,10,125-132.
13. Ching, J,Chua, TK,Chin, LC(2010).Beta-amyrin from Ardisia elliptica Thunb. Is more potent than aspirin in inhibiting collagen-induced platelet aggregation.Indian J Exp Biol,48,275-279.
14. Diaz, AM,Abad, MJ,Fernandez, L,Silvan, AM,De Santos, J,Bermejo, P(2004).Phenyl-propanoid glycosides from Scrophularia scorodonia: in vitro anti-inflammatory activity.Life Sci.,74,2515-2526.
15. Estomba, D,Ladio, A,Lozada, M(2006).Medicinal wild plant knowledge and gathering patterns in a Mapuche community from North-western Patagonia.J Ethnopharmacol,103,109-119.
16. Fuentes, E,Badimon, L,Caballero, J(2014).Protective mechanisms of adenosine 5’ -monophosphate in platelet activation and thrombus formation.Thromb Haemost,111,491-507.
17. Guerrero, JA,Lozano, ML,Castillo, J,Benavente-Garcia, O,Vicente, V,Rivera, J(2005).Flavonoids inhibit platelet function through binding to the thromboxane A2 receptor.J Thromb Haemost,3,369-376.
18. Hasmeda, M,Kweifio-Okai, G,Macrides, T,Polya, GM(1999).Selective inhibition of eukaryote protein kinases by anti-inflammatory triterpenoids.Planta Med,65,14-18.
19. Herbert, JM,Maffrand, JP,Taoubi, K,Augereau, JM,Fouraste, I,Gleye, J(1991).Verbas-coside isolated from Lantana camara, an inhibitor of protein kinase C.J Nat Prod,54,1595-1600.
20. Houghton, PJ,Hikino, H(1989).Anti-hepatotoxic activity of extracts and constituents of Buddleja species.Planta Medica,55,123-126.
21. Houghton, PJ,Mensah, AY(1999).Biologically Active Compounds from Buddleja Species.Phytochemicals in Human Health Protection, Nutrition, and Plant Defense
22. Kim, AJ,Lim, HJ,Ro, H(2014).Low-dose aspirin for prevention of cardiovascular disease in patients with chronic kidney disease.PLoS One,9
23. Lee, JY,Woo, E-R,Kang, KW(2005).Inhibition of lipopolysaccharide-inducible nitric oxide synthase expression by acteoside through blocking of AP-1 activation.J Ethnopharmacol,97,561-566.
24. Letelier, ME,Jones, R,López, C(2012).Safety profile and wound healing properties of a standardized Buddleja globosa hope (matico) extract in sprague-dawley rats.Rev Farmacol Chile,5,13-19.
25. Liao, Y-H,Houghton, PJ,Hoult, J(1999).Novel and known constituents from Buddleja species and their activity against leukocyte eicosanoid generation.J Nat Prod,62,1241-1245.
26. Mahlke, JD,Boligon, AA,Machado, MM,Athayde, ML(2012).In vitro toxicity, antiplatelet and acetylcholinesterase inhibition of Buddleja thyrsoides Lam. leaves.Nat Prod Res.,26,2223-2226.
27. Medeiros, R,Otuki, MF,Avellar, MC,Calixto, JB(2007).Mechanisms underlying the inhibitory actions of the pentacyclic triterpene alpha-amyrin in the mouse skin inflammation induced by phorbol ester 12-O-tetradecanoylphorbol-13-acetate.Eur J Pharmacol,559,227-235.
28. Mensah, A,Sampson, J,Houghton, P(2001).Effects of Buddleja globosa leaf and its constituents relevant to wound healing.J Ethnopharmacol,77,219-226.
29. Munoz, MEL,Salas, EAO(2014).Munoz MEL, Salas EAO. Use of a standardised dry extract of leaves of Buddleja globosa hope, BG-126, for the treatment and prevention of gastrointestinal disorders caused by treatment with nitrofurantoin and other antimicrobials. Google Pat. 2014:1-19. Publication number US8852654 B2..
30. Niedergang, F,Alcover, A,Knight, CG(2000).Convulxin binding to platelet receptor GPVI: competition with collagen related peptides.Biochem Biophys Res Commun,273,246-250.
31. Palomo, GI,Icaza, NG,Mujica, EV(2007).Prevalence of cardiovascular risk factors in adult from Talca, Chile.Rev Med Chil,135,904-912.
32. Pardo, F,Perich, F,Villarroel, L,Torres, R(1993).Isolation of verbascoside, an antimi-crobial constituent of Buddleja globosa leaves.J Ethnopharmacol,39,221-222.
33. Pignatelli, P,Di Santo, S,Buchetti, B,Sanguigni, V,Brunelli, A,Violi, F(2006).Polyphenols enhance platelet nitric oxide by inhibiting protein kinase C-dependent NADPH oxidase activation: effect on platelet recruitment.Faseb J.,20,1082-1089.
34. Ruggeri, ZM(1997).Mechanisms initiating platelet thrombus formation.Thromb Haemost,78,611-616.
35. Waltenberger, B,Mocan, A,Smejkal, K,Heiss, EH,Atanasov, AG(2016).Natural products to counteract the epidemic of cardiovascular and metabolic disorders.Molecules,21
36. Willoughby, S,Holmes, A,Loscalzo, J(2002).Platelets and cardiovascular disease.Eur J Cardiovasc Nurs,1,273-288.