Chromolaena odorata (L.) King and Robinson (Siam weed) extract has been used to stop bleeding and in wound healing in many tropical countries. However, its detailed mechanisms have not been elucidated. In this study, we examined the molecular mechanisms by which Siam weed extract (SWE) affected hemostatic and wound healing activities. SWE promoted Balb/c 3T3 fibroblast cell migration and proliferation. Subsequently, we found that heme oxygenase-1 (HO-1), the accelerating wound healing enzyme, was increased at the transcriptional and translational levels by SWE treatments. The HO-1 promoter analyzed with luciferase assay was also increased by treatment of SWE in a dose-dependent manner. This induction may be mediated by several kinase pathways including MEK, p38MAPK, AKT, and JNK. Quantitative real-time PCR using undifferentiated promonocytic cell lines revealed that thromboxane synthase (TXS), a potent vasoconstrictor and platelet aggregator, was increased and MMP-9, an anti platelet aggregator, was decreased in the presence of SWE. Our studies presented that SWE accelerated hemostatic and wound healing activities by altering the expression of genes, including HO-1, TXS, and MMP-9. 1. Introduction Wound healing is an intricate process in which usually the skin repairs itself after injury. The process is divided into four overlapping phases: hemostasis (cessation of bleeding), inflammation, proliferation, and remodeling [1]. Hemostasis is mainly controlled by thromboxane synthase (TXS), which converts prostaglandin H2 into thromboxane A2, a potent vasoconstrictor and platelet aggregator [2]. Plasminogen activator inhibitor type 1 (PAI-1) also plays a role in hemostasis by inhibition of fibrinolysis, which prevents failure of the hemostatic process [3]. Subsequently, neutrophils release free radicals to kill bacteria in the inflammation phase [4, 5], and heme and heme proteins also accumulate at the local site of the wound. These heme and heme proteins have prooxidative and proinflammatory properties by inducing the expression of adhesion molecules, causing vascular permeability and leukocyte infiltration. These actions initiate wound healing process. Heme oxygenase-1 (HO-1) has antiinflammatory and antioxidant activities and is responsible for a wide range of wound healing functions. It converts heme into biliverdin/bilirubin, iron and carbon monoxide, which are potent antioxidant products. The overexpression of HO-1 helps to accelerate wound healing such as amelioration of inflammation, proliferation and protection against endothelial cell apoptosis
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