• 대한한의학회지
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• 제34권2호
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• pp.51-58
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• 2013

Objectives: The aim of this study was to examine the antithrombotic effects of the four herbal ingredients (Mume Fructus, MF; Santali Albi Lignum, SAL; Amomi Tsao-Ko Fructus, ATF; and Amomi Fructus, AF) of modified Jeho-tang (MJHT) in a ferric chloride ($FeCl_3$)-induced carotid arterial thrombosis model. Methods: Thirty minutes prior to a 35% $FeCl_3$ application, Sprague-Dawley (SD) rats were injected with saline, MF, SAL, ATF or AF (100 mg/kg, intraperitoneal injection), respectively. The effect of the MJHT ingredients was examined for time to occlusion (TTO) and thrombus weight (TW) in a $FeCl_3$-induced thrombosis model. Histological analysis was performed to examine the effect of the MJHT ingredients on collagen fiber damage using hematoxylin & eosin and Masson's trichrome staining. Results: Compared with vehicle treatment, MF, SAL and ATF treatment delayed TTO (vehicle, $8.11{\pm}0.60$ min; MF, $16.67{\pm}1.03$ min; SAL, $17.50{\pm}1.52$ min and ATF, $13.33{\pm}1.21$ min; P < 0.001) and inhibited thrombus formation (vehicle, $0.79{\pm}0.03$ mg/mm; MF, $0.61{\pm}0.07$ mg/mm; SAL, $0.57{\pm}0.03$ mg/mm and ATF, $0.72{\pm}0.02$ mg/mm; P < 0.001). In addition, each herbal ingredient of MJHT except for AF prevented the collagen fiber damage induced by a 35% $FeCl_3$ application. These results indicate that the MJHT ingredients MF ${\geq}$ SAL ${\geq}$ ATF ${\geq}$ AF possess antithrombotic activity in a $FeCl_3$-induced carotid arterial thrombosis. Conclusions: Altogether, these results are the first evidence that the MJHT ingredients MF, SAL and ATF have the ability to prevent vascular damage and thrombus formation in $FeCl_3$-induced carotid arterial thrombosis.

• Natural Product Sciences
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• 제19권3호
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• pp.251-257
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• 2013

We investigated the antithrombotic effect of Acorus gramineus Soland (A. gramineus) from Korea and Acorus tatarinowii Schott (A. tatarinowii) from China in a rat model of arterial thrombosis induced by ferric chloride ($FeCl_3$). Thirty minutes prior to a 35% $FeCl_3$ application, Sprague Dawley rats were intraperitoneally injected with saline, A. gramineus and A. tatarinowii (100 mg/kg), respectively. Occlusion time of rats injected with A. gramineus was delayed significantly compared to that of the vehicle and A. tatarinowii. Thrombus weight was meaningfully decreased in rats injected with A. gramineus compared to the vehicle. Additionally, A. gramineus inhibited collagen fiber damage in vessel compared to the vehicle, but A. tatarinowii did not show a significant effect. Our results show that A. gramineus and A. tatarinowii from the same genus have different antithrombotic effects, and especially A. gramineus has a better antithrombotic effect than A. tatarinowii.

• 대한본초학회지
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• 제28권5호
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• pp.33-38
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• 2013

Objectives : The aim of this study was to examine anti-thrombotic effect of traditional herbal extracts in a rat model of ferric chloride ($FeCl_3$)-induced carotid arterial thrombosis. Methods : Thirty minutes prior to a 35% $FeCl_3$ application, Sprague Dawley(SD) rats were injected with the 10 types of traditional herbal extracts (100mg/kg, intraperitoneal injection), respectively. The effect of these herbal extracts was examined for time to occlusion(TTO) using the Laser doppler flow meter and measured for thrombus weight (TW) in $FeCl_3$-induced thrombosis model. Results : In the TTO, Salvia miltiorrhiza (Sm, $2.30{\pm}0.28$ min, p<0.001) and Santalum album (Sa, $2.19{\pm}0.19$ min, p<0.001) showed significantly delayed TTO more than twice compared with Saline-treated group. Cnidium officinale (Co), Psoralea corylifolia (Pc), Scutellatia baicalensis (Sba), Panax notoginseng (Pn), Angelica tenuissima (At), Scrophularia buergeriana (Sbu), Rhus verniciflua (Rv) and Picrasma quassioides (Pq), except for Rhus verniciflua (Rv) also meaningfully impeded TTO more than one fold. In addition, Salvia miltiorrhiza, Santalum album, Cnidium officinale, Psoralea corylifolia and Scutellatia baicalensis significantly reduced TW more than 10% compared with Saline-treated group. Especially, Salvia miltiorrhiza and Santalum album showed the most excellent anti-thrombotic effect among the 10 herbal extracts tested on the restoration of altered TTO and TW. Conclusions : These results suggest that Sm and Sa extracts have outstanding anti-thrombotic effect in $FeCl_3$-induced thrombosis model and is potentially useful as herbal medicines for the treatment and prevention of thrombosis.

• The Korean Journal of Physiology and Pharmacology
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• 제25권1호
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• pp.59-68
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• 2021

Arterial thrombosis and its associated diseases are considered to constitute a major healthcare problem. Arterial thrombosis, defined as blood clot formation in an artery that interrupts blood circulation, is associated with many cardiovascular diseases. Oxidative stress is one of many important factors that aggravates the pathophysiological process of arterial thrombosis. Apurinic/apyrimidinic endonuclease 1/redox factor-1 (Ref-1) has a multifunctional role in cells that includes the regulation of oxidative stress and anti-inflammatory function. The aim of this study was to investigate the therapeutic effect of adenovirus-mediated Ref-1 overexpression on arterial thrombosis induced by 60% FeCl3 solution in rats. Blood flow was measured to detect the time to occlusion, thrombus formation was detected by hematoxylin and eosin staining, reactive oxygen species (ROS) levels were detected by high-performance liquid chromatography, and the expression of tissue factor and other proteins was detected by Western blot. FeCl3 aggravated thrombus formation in carotid arteries and reduced the time to artery occlusion. Ref-1 significantly delayed arterial obstruction via the inhibition of thrombus formation, especially by downregulating tissue factor expression through the Akt-GSK3β-NF-κB signaling pathway. Ref1 also reduced the expression of vascular inflammation markers ICAM-1 and VCAM-1, and reduced the level of ROS that contributed to thrombus formation. The results showed that adenovirus-mediated Ref-1 overexpression reduced thrombus formation in the rat carotid artery. In summary, Ref-1 overexpression had anti-thrombotic effects in a carotid artery thrombosis model and could be a target for the treatment of arterial thrombosis.

• 대한임상검사과학회지
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• 제43권4호
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• pp.179-187
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• 2011

Animal models are important tools in thrombosis research and preclinical drug development. In recent studies, ferric chloride ($FeCl_3$) has been widely used to induce arterial thrombosis in a variety of species. The purpose of this study was to find an optimal concentration of $FeCl_3$ and validate this model suited better for thrombosis research. A small piece of filter paper, soaked in $FeCl_3$ solution (10, 20 or 35%, v/v, in distilled water) was topically applied on the carotid artery of SD rats to measure the time to occlusion (TTO) and thrombus weight (TW) to ascertain 35%, as an optimal $FeCl_3$ concentration ($8.63{\pm}0.92min$; p =0.000, $0.79{\pm}0.03mg/mm$; p =0.000, respectively). To validate this experimental model, Ginkgo biloba special extract EGb761 (5, 10 or 30 mg/kg) as a reference agent administered by peritoneal route for 1h prior to the induction of thrombosis, showed significantly delayed TTO in a dose dependent manner ($18.50{\pm}2.17$, $29.17{\pm}1.83$, and $38.00{\pm}1.79min$, respectively) and significantly reduced TW and repaired collagen fibre in the injured vessel compare to vehicle group. Our results provide a simple, reproducible and well controlled in vivo screening system to induce thrombosis in rats by the topical application of 35% $FeCl_3$ to assess the efficacy of the new anti-thrombotic agents.