Akaishi T, Yamamoto S, Abe K. 2020. The
synthetic curcumin derivative CNB-001
attenuates thrombin-stimulated microglial
inflammation by inhibiting the ERK and
p38 MAPK pathways. Biol Pharm Bull,
43: 138-144.
Arsenault KA, Hirsh J, Whitlock RP,
Eikelboom JW. 2012. Direct thrombin
inhibitors in cardiovascular disease. Nat
Rev Cardiol, 9: 402-414.
Avan A, Quint K, Nicolini F, Funel N,
Frampton A, Maftouh M, Pelliccioni S,
Schuurhuis GJ, Peters GJ, Giovannetti E.
2013. Enhancement of the antiproliferative
activity of gemcitabine by modulation of
c-Met pathway in pancreatic cancer. Curr
Pharm Des, 19: 940-950.
Basha R, Connelly SF, Sankpal UT, Nagaraju
GP, Patel H, Vishwanatha JK, Simecka
JW. 2016. Small molecule tolfenamic acid
and dietary spice curcumin treatment
enhances antiproliferative effect in
pancreatic cancer cells via suppressing
Sp1, disrupting NF-kB translocation to
nucleus and cell cycle phase distribution. J
Nutr Biochem, 31: 77-87.
Capodanno D, Bhatt DL, Eikelboom JW, Fox
KA, Geisler T, Gibson CM, Mehran R.
2020. Dual-pathway inhibition for
secondary and tertiary antithrombotic
prevention in cardiovascular disease. Nat
Rev Cardiol, 17: 242-257.
Carney DH, Stiernberg J, Fenton JW. 1984.
Initiation of proliferative events by human
α‐thrombin requires both receptor binding
and enzymic activity. J Cell Biochem, 26:
181-195.
Cirino G, Cicala C, Bucci MR, Sorrentino L,
Maraganore JM, Stone SR. 1996.
Thrombin functions as an inflammatory
mediator through activation of its receptor.
J Exp Med, 183: 821-827.
Coughlin SR. 2000. Thrombin signalling and
protease-activated receptors. Nature, 407:
258-264.
Crawley J, Zanardelli S, Chion C, Lane D.
2007. The central role of thrombin in
hemostasis. J Thromb Haemost, 5: 95-101.
Ebrahimi S, Jaberi N, Avan A, Ryzhikov M,
Keramati MR, Parizadeh MR, Hassanian
SM. 2017. Role of thrombin in the
pathogenesis of central nervous system
inflammatory diseases. J Cell Physiol,
232: 482-485.
Ebrahimi S, Rahmani F, Behnam‐Rassouli R,
Hoseinkhani F, Parizadeh MR, Keramati
MR, Khazaie M, Avan A, Hassanian SM.
2017. Proinflammatory signaling
functions of thrombin in cancer. J Cell
Physiol, 232: 2323-2329.
Farkas S, Hornung M, Sattler C, Guba M,
Steinbauer M, Anthuber M, Herfarth H,
Schlitt J, Geissler EK. 2006. Rapamycin
decreases leukocyte migration in vivo and
effectively reduces experimentally
induced chronic colitis. Int J Colorectal
Dis , 21: 747-753.
Fitzgerald DJ, FitzGerald GA. 1989. Role of
thrombin and thromboxane A2 in
reocclusion following coronary
thrombolysis with tissue-type
plasminogen activator. Proc Natl Acad
Sci, 86: 7585-7589.
Frank PG, Lisanti MP. 2008. ICAM-1: role in
inflammation and in the regulation of
vascular permeability. Am J Physiol Heart
Circ Physiol, 295: 926-927.
Hashemzehi M, Behnam‐Rassouli R,
Hassanian SM, Moradi‐Binabaj M,
Moradi‐Marjaneh R, Rahmani F, Fiuji H,
Jamili M, Mirahmadi M, Boromand N,
Piran M, Jafari M, Sahebkar A, Avan A,
Khazaei M. 2018. Phytosomal‐curcumin
antagonizes cell growth and migration,
induced by thrombin through AMP‐Kinase
in breast cancer. J Cell Biochem, 119:
5996-6007.
Hernández M, Wicz S, Santamaría MH, Corral
RS. 2018. Curcumin exerts antiinflammatory and vasoprotective effects
through amelioration of NFAT-dependent
endothelin-1 production in mice with acute
Chagas cardiomyopathy. Mem Inst
Oswaldo Cruz , 113: e180171.
Jian MY, Alexeyev MF, Wolkowicz PE,
Curcumin inhibits permeability induced by thrombin
AJP, Vol. 13, No. 1, Jan-Feb 2023 107
Zmijewski JW, Creighton JR. 2013.
Metformin-stimulated AMPK-α1
promotes microvascular repair in acute
lung injury. Am J Physiol Lung Cell Mol
Physiol , 305: L844-L855.
Lee SY, Moon SJ, Kim EK, Seo HB, Yang EJ,
Son HJ, Cho ML. 2017. Metformin
suppresses systemic autoimmunity in
Roquinsan/san mice through inhibiting B
cell differentiation into plasma cells via
regulation of AMPK/mTOR/STAT3. J
Immunol, 198: 2661-2670.
Liu J, Chen L, Zhang X, Pan L, Jiang L. 2020.
The protective effects of juglanin in
cerebral ischemia reduce blood–brain
barrier permeability via inhibition of
VEGF/VEGFR2 signaling. Drug Des
Devel Ther , 14: 3165-3176.
Liu Y, Tang G, Li Y, Wang Y, Chen X, Gu X,
Yang GY. 2014. Metformin attenuates
blood-brain barrier disruption in mice
following middle cerebral artery
occlusion. J Neuroinflammation, 11: 177-
189.
Loeffen R, Winckers K, Ford I, Jukema JW,
Robertson M, Stott DJ, Spronk HM, Ten
Cate H, Lowe GD. 2015. Associations
between thrombin generation and the risk
of cardiovascular disease in elderly
patients: results from the PROSPER
Study. J Gerontol A Biol Sci Med Sci, 70:
982-988.
Madamanchi NR, Li S, Patterson C, Runge MS.
2001. Thrombin regulates vascular smooth
muscle cell growth and heat shock proteins
via the JAK-STAT pathway. J Biol Chem,
276: 18915-18924.
Maithilikarpagaselvi N, Sridhar MG,
Swaminathan RP, Zachariah B. 2016.
Curcumin prevents inflammatory
response, oxidative stress and insulin
resistance in high fructose fed male Wistar
rats: Potential role of serine kinases. Chem
Biol Interact, 244: 187-194.
Malik AB, Fenton JW. 1992. Thrombinmediated increase in vascular endothelial
permeability. Paper presented at the
Seminars in thrombosis and hemostasis.
Miller NJ, Rice-Evans C, Davies MJ,
Gopinathan V, Milner A. 1993. A novel
method for measuring antioxidant capacity
and its application to monitoring the
antioxidant status in premature neonates.
Clin Sci (Lond), 84: 407-412.
Motterlini R, Foresti R, Bassi R, Green CJ.
2000. Curcumin, an antioxidant and antiinflammatory agent, induces heme
oxygenase-1 and protects endothelial cells
against oxidative stress. Free Radic Biol
Med, 28, 1303-1312.
Narayanan S. 1999. Multifunctional roles of
thrombin. Ann Clin Lab Sci, 29: 275-280.
Nathan AS, Sen S, Yeh RW. 2017. The risk of
bleeding with the use of antiplatelet agents
for the treatment of cardiovascular disease.
Expert Opin Drug Saf, 16: 561-572.
Norris LA. 2003. Blood coagulation. Best Pract
Res Clin Obstet Gynaecol, 17: 369-383.
Oakley R, Tharakan B. 2014. Vascular
hyperpermeability and aging. Aging dis, 5:
114-125.
Park CS, Bang BR, Kwon HS, Moon KA, Kim
TB, Lee KY, Moon HB, Cho YS. 2012.
Metformin reduces airway inflammation
and remodeling via activation of AMPactivated protein kinase. Biochem
pharmacol, 84: 1660-1670.
Parrales A, López E, Lee-Rivera I, LópezColomé AM. 2013. ERK1/2-dependent
activation of mTOR/mTORC1/p70S6K
regulates thrombin-induced RPE cell
proliferation. Cell signal, 25: 829-838.
Pervin R, Kanner B, Marx G, Razin E. 1985.
Thrombin-induced degranulation of
cultured bone marrow-derived mast cells:
effect on calcium uptake. J Immunol, 56:
667-672.
Rahman A, Anwar KN, True AL, Malik AB.
1999. Thrombin-induced p65 homodimer
binding to downstream NF-κB site of the
promoter mediates endothelial ICAM-1
expression and neutrophil adhesion. J
Immunol, 162: 5466-5476.
Rahmani F, Amerizadeh F, Hassanian SM,
Hashemzehi M, Nasiri SN, Fiuji H, Ferns
GA, Khazaei M, Avan A. 2019. PNU‐
74654 enhances the antiproliferative
effects of 5‐FU in breast cancer and
antagonizes thrombin‐induced cell growth
via the Wnt pathway. J Cell Physiol, 234:
14123-14132.
Rickles FR, Patierno S, Fernandez PM. 2003.
Tissue factor, thrombin, and cancer. Chest,
124: 58S-68S.
Strukova S. 2001. Thrombin as a regulator of
inflammation and reparative processes in
tissues. Biochem, 66: 8-18.
Sugama Y, Tiruppathi C, Andersen T, Fenton J,
Malik A. 1992. Thrombin-induced
expression of endothelial P-selectin and
Rahmani et al.
AJP, Vol. 13, No. 1, Jan-Feb 2023 108
intercellular adhesion molecule-1: a
mechanism for stabilizing neutrophil
adhesion. J Cell Biol, 119: 935-944.
Sumagin R, Lomakina E, Sarelius IH. 2008.
Leukocyte-endothelial cell interactions are
linked to vascular permeability via ICAM1-mediated signaling. Am J Physiol Heart
Circ Physiol, 295: H969-H977.
Tharakan B, Hunter FA, Smythe WR, Childs
EW. 2010. Curcumin inhibits reactive
oxygen species formation and vascular
hyperpermeability following
haemorrhagic shock. Clin Exp Pharmacol
Physiol, 37: 939-944.
Vesey DA, Cheung CW, Kruger WA, Poronnik
P, Gobe G, Johnson DW. 2005. Thrombin
stimulates proinflammatory and
proliferative responses in primary cultures
of human proximal tubule cells. Kidney
int, 67: 1315-1329.
Zhang Y, Xiang H, Liu J, Li D, Fang Z, Zhang
H. 2017. Study on the mechanism of
AMPK signaling pathway and its effect on
apoptosis of human hepatocellular
carcinoma SMMC-7721 cells by
curcumin. Eur Rev Med Pharmacol Sci,
21: 1144-1150.
Zhong YC, Zhang T, Di W, Li WP. 2013.
Thrombin promotes epithelial ovarian
cancer cell invasion by inducing epithelialmesenchymal transition. J Gynecol Oncol,
24: 265-272.
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