Molecular Docking Guided Screening of Phytoconstituents from Artemisia iwayomogi as Potential PPARδ Agonists

Metabolic syndrome is a disease condition characterized by decreased insulin sensitivity, hyperlipidemia, abdominal obesity, hypertension, and myocardial diseases, primarily related to a high-fat diet and lack of physical exercise. Peroxisome proliferator-activated receptor (PPAR) δ stimulation changes the body’s energy fuel preference to fats from sugar. PPARδ is expressed universally in all tissues of the human body, particularly those involving lipid metabolism. PPARδ is an evolving pharmacological target for the pharmacotherapeutics of diseases linked to metabolic syndrome. Artemisia iwayomogi ethanol extract was reported as PPARδ agonist and reduced diet-induced overweight via stimulation of fatty acid oxidation in the skeletal muscles. The present study is designed to evaluate in silico some phytoconstituents, including 4 coumarins, 12 flavonoids, 5 phenolic compounds and 7 caffeoyl-quinic acid derivatives found in A. iwayomogi to explore their binding mode and interactions with the PPARδ protein. A total of 28 compounds evaluated in silico, 16 compounds displayed good binding free energy, and significant docking interactions with the binding site residues of PPARδ protein supporting the in vitro PPARδ agonistic activity of A. iwayomogi extract. Amongst these, scopolin, patuletin, patuletin-3-glucoside, 1,2-bis(4-hydroxy-3-methoxyphenyl)prop-1,3-diol, 3-caffeoylquinic acid, and 1,3-dicaffeoylquinic acid displayed most significant binding interactions with binding site residues of PPARδ. This information can be utilized for developing potent and non-toxic natural PPARδ agonists for the management of disorders related to metabolic syndrome.

In vitro and in vivo anti-aging effects of compounds isolated from Artemisia iwayomogi

In Korean folk medicine, Artemisia iwayomogi has largely been employed for the improvement of diabetic complications and hepatic function as well as in the treatment of female diseases and skin whitening. Accordingly, the present study sought to assess cosmeceutical activity of Artemisia iwayomogi. Through activity-guided fractionation, scopolin (AI-1), 2,4-dihydroxy-6-methoxy-acetophenone 4-O-β-D-glucoside (AI-2), scopoletin (AI-3), kaempferol-3-O-methyl ether (AI-4) and luteolin (AI-5) were isolated from ethyl acetate and water fractions of Artemisia iwayomogi. Of them, AI-4 and AI-5 exhibited strong antioxidative and whitening effects. In addition, AI-1, AI-3, AI-4, and AI-5 demonstrated considerable anti-wrinkle performances. According to results of quantitative analysis of compounds isolated from Artemisia iwayomogi, scopolin (AI-1) is a major component of Artemisia iwayomogi. Moreover, O/W type cream made by water fraction which included scopolin showed unwrinkling effect for 8 weeks when it was applied to face in an in vivo study. Specific contributions of Artemisia iwayomogi were as follows: AI-1, 1.21 mg/g; AI-2, 0.26 mg/g; AI-3, 0.38 mg/g; AI-4, 0.01 mg/g; and AI-5, 0.04 mg/g.

Artemisia iwayomogiplusCurcuma longaSynergistically Ameliorates Nonalcoholic Steatohepatitis in HepG2 Cells

The combination ofArtemisia iwayomogiandCurcuma longaradix is frequently prescribed for liver diseases in TKM. However, the synergic effects of the two herbs on nonalcoholic steatohepatitis (NASH) have not yet been studied. Therefore, we investigated the anti-NASH effects of the water extract ofA. iwayomogi(AI),C. longaradix (CL), and combination of the two herbs (ACE). Hepatic steatosis and NASH were induced in HepG2 cells by treatment with palmitic acid (PA, for 6 h) with/without pretreatment of ACE (25 or 50 μg/mL), AI (50 or 100 μg/mL), CL (50 or 100 μg/mL), curcumin (5 μg/mL), or scopoletin (5 μg/mL). The PA treatment (200 μM) drastically altered intracellular triglyceride levels, total cholesterol, and expression levels of genes related to lipid metabolism (CD36, SREBP1c, PPAR-γ, and PPAR-α), whereas pretreatment with ACE significantly attenuated these alterations. ACE also protected HepG2 cells from PA- (300 μM-) induced endoplasmic reticulum (ER) stress and apoptosis and attenuated the related key molecules including GRP78, eIF2, and CHOP, respectively. In conclusion, we found synergic effects ofA. iwayomogiandC. longaon NASH, supporting the clinical potential for fatty liver disorders. In addition, modulation of ER stress-relative molecules would be involved in its underlying mechanism.

Inhibitory Effect of Chemical Constituents Isolated from Artemisia iwayomogi on Polyol Pathway and Simultaneous Quantification of Major Bioactive Compounds

Blocking the polyol pathway plays an important role preventing diabetic complications. Therefore, aldose reductase (AR) and advanced glycation endproducts (AGEs) formation has significant effect on diabetic complications. Artemisia iwayomogi has long been used as treatment of various diseases in Korea. However, no literatures have reported on AR and AGEs formation inhibitory activities of A. iwayomogi. For these reasons, we aimed to assess that A. iwayomogi had potential as anti-diabetic complications agents. We led to isolation of two coumarins (1 and 2), nine flavonoids (3–11), five caffeoylquinic acids (12–16), three diterpene glycosides (17–19), and one phenolic compound (20) from A. iwayomogi. Among them, hispidulin (4), 6-methoxytricin (6), arteanoflavone (7), quercetin-3-gentiobioside (10), 1,3-di-O-caffeoylquinic acid (13), and suavioside A (18) were first reported on the isolation from A. iwayomogi. Not only two coumarins (1 and 2), nine flavonoids (3–11), and five caffeoylquinic acids (12–16) but also extracts showed significant inhibitor on AR and AGEs formation activities. We analyzed contents of major bioactive compounds in Korea’s various regions of A. iwayomogi. Overall, we selected Yangyang, Gangwon-do, from June, which contained the highest amounts of bioactive compounds, as suitable areas for cultivating A. iwayomogi as preventive or therapeutic agent in the treatment of diabetic complications.