• Korean Journal of Pharmacognosy
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• v.52 no.1
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• pp.26-33
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• 2021

During blood vessel damage, an essential step in the hemostatic process is platelet activation. However, it is important to properly control platelet activation, as various cardiovascular diseases, such as stroke, atherosclerosis, and myocardial infarction, are also caused by excessive platelet activation. Found primarily in the roots of plants of the genus Artemisia or Scopolia, isoscopoletin has been studied to demonstrate its potential pharmacological effects against Alzheimer's disease and anticancer, but the mechanisms and roles involved in thrombus formation and platelet aggregation are insufficient. This study investigated the effect of isoscopoletin on U46619-induced human platelet activation. As a result, isoscopoletin significantly increased the levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) dose-dependently. In addition, isoscopoletin significantly phosphorylated inositol 1, 4, 5-triphosphate receptor (IP3R) and vasodilator-stimulated phosphprotein (VASP), which are known substrates for cAMP-dependent kinases and cGMP-dependent kinases. Phosphorylated IP3R by isoscopoletin inhibited Ca2+ mobilization from the dense tubular system Ca2+ channels to cytosol, and phosphorylated VASP was involved in the inhibition of fibrinogen binding through αIIb/β3 inactivation in the platelet membrane. Isoscopoletin finally reduced thrombin-induced fibrin clotting production. Therefore, this study suggests that isoscopoletin has a potent antiplatelet effect and may be helpful for platelet-related thrombotic diseases.

• Journal of Applied Biological Chemistry
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• v.63 no.3
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• pp.235-241
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• 2020

An essential component of the hemostatic process during vascular damage is platelet activation. However, many cardiovascular diseases, such as atherosclerosis, thrombosis, and myocardial infarction, can develop due to excessive platelet activation. Isoscopoletin, found primarily in plant roots of the genus Artemisia or Scopolia, has been studied to demonstrate potential pharmacological effects on Alzheimer's disease and anticancer, but its mechanisms and role in relation to thrombus formation and platelet aggregation have not yet been discovered. This research investigated the effect of isoscopoletin on collagen-induced human platelet activation. As a result, isoscopoletin strongly increased cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) levels in a concentration-dependent manner. In addition, isoscopoletin greatly phosphorylated inositol 1,4,5-triphosphate receptor (IP₃R) and vasodilator-stimulated phosphoprotein (VASP), known substrates of cAMP-dependent kinase and cGMP dependent kinase. Phosphorylation of IP₃R by isoscopoletin induced Ca²⁺ inhibition from the dense tubular system Ca²⁺ channels, and VASP phosphorylation was involved in fibrinogen binding inhibition by inactivating αIIb/β₃ in the platelet membrane. Isoscopoletin finally reduced thrombin-induced fibrin clot production and finally reduced thrombus formation. Therefore, this research suggests that isoscopoletin has strong antiplatelet effects and is likely to be helpful for thrombotic diseases involving platelets by acting as a prophylactic and therapeutic agent.

• Korean Journal of Pharmacognosy
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• v.51 no.3
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• pp.151-157
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• 2020

When blood vessels are damaged, a rapid hemostatic reaction occurs to minimize blood loss and maintain normal circulation. Platelet activation and aggregation is essential in this process. However, excessive platelet aggregation or abnormal platelet aggregation may be the cause of cardiovascular disease, such as thrombosis, stroke and atherosclerosis. Therefore, it is important to prevent and treat cardiovascular disease by finding substances that can regulate platelet activation and suppress aggregation reactions. Isoscopoletin, which is mainly found in the roots of plants Artemisia or Scopolia, has been reported to have potential pharmacological effects on anticancer and Alzheimer's disease, but its role and mechanisms for platelet aggregation and thrombus formation are unknown. This study confirmed the effect of isoscopoletin on major regulation of collageninduced human platelet aggregation, TXA₂ production and intracellular granular secretion (ATP and serotonin release). In addition, the effects of isoscopoletin on phosphorylation of phosphorylated proteins PI3K/Akt and MAPK involved in signal transduction in platelet aggregation was studied. As a result, isoscopoletin significantly inhibited the phosphorylation of PI3K/Akt and MAPK, significantly inhibiting platelet aggregation through TXA₂ production and intracellular granular secretion (ATP and serotonin release). Therefore, we suggest that isoscopoletin is an anti-platelet substance that regulates phosphorylation of phosphorus proteins such as PI3K/Akt and MAPK and is valuable as a preventive and therapeutic agent for platelet-derived cardiovascular disease.

• Korean Journal of Pharmacognosy
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• v.24 no.4
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• pp.296-298
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• 1993

From the benzene soluble and butanol soluble portions of Dystaenia takeshimana Kitagawa which is indigenous to Korea, umbelliferone, skimmin, isoscopoletin, ${\beta}-sitosterol$, campesterol and stigmasterol have been isolated and identified on the basis of spectral data.

• Korean Journal of Medicinal Crop Science
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• v.5 no.4
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• pp.302-306
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• 1997

One flavan 3-ol derivative was isolated from the stem of Acer mono Max, along with two known coumarins. On the basis of spectroscopic evidence, the structures of these compounds were established as (-) - epicatechin, scopoletin and isoscopoletin. Antioxidative activity of (-) - epicatechin was examined by the DPPH free radical scavenging method. Antioxidative activity of (-) - epicatechin $(RC_{50}\;:\;7.5\;{mu}g)$ was more greater than those of ${\alpha}-tocopherol\;(RC_{50}\;:\;12\;{mu}g)$ and $BHA\;(RC_{50}\;:\;14\;{mu}g)$.

• Natural Product Sciences
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• v.12 no.3
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• pp.129-133
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• 2006

Four coumarins (1-4) and one polyacetylene (5) were isolated from the roots of Anglica purpuraefolia Chung (Umbelliferae) through repeated column chromatography. Four coumarins, isoscopoletin (1), oxypeucedanin hydrate (2), arnottinin (3) and isokhellactone (4), and a polyacetylene, (+)-9(Z), 17-octadecadience-12,14-diyne-1,11,16-triol (5), were identified by spectroscopic analysis including two dimensional NMR and mass. These compounds were examined for their anti-complement activity against the classical pathway of the complement system. However, compounds 1-5 were inactive in this assay system.

• Natural Product Sciences
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• v.24 no.3
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• pp.171-180
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• 2018

Artemisia capillaris has been widely used as an alternative therapy for treating obesity and atopic dermatitis. It has been used as a hepatoprotactant. It is also used for ameliorating inflammatory reactions. Although there are several investigations on other Artemisia species, there is no systematic study describing the role of A. capillaris MeOH extract, its solvent soluble fractions, or derived anti-inflammatory principal components in regulating inflammatory conditions. Therefore, the objective of this study was to elucidate anti-inflammatory mechanisms of A. capillaris. Results revealed that MeOH extract of A. capillaris could decrease LPS-stimulated NO secretion. Of tested fractions, $CH_2Cl_2$, EtOAc, and n-BuOH strongly inhibited NO release from RAW264.7 cells. Bioactive mediators derived from $CH_2Cl_2$ and n-BuOH fractions elicited potent anti-inflammatory actions and strikingly abrogated LPS-triggered NO accumulation in RAW264.7 cells. Of particular interest, capillin and isoscopoletin possessed the most potent NO suppressive effects. Western blot analysis validated the molecular mechanism of NO inhibition and showed that capillin and isoscopoletin significantly down-regulated iNOS and COX-2 protein expression. Taken together, our results provide the first evidence that MeOH extract, $CH_2Cl_2$, EtOAc, and n-BuOH fractions from A. capillaris and its derived lead candidates can potently suppress inflammatory responses in macrophages by hampering NO release and down-regulating iNOS and COX-2 signaling.