Decursinol Angelate Ameliorates Dextran Sodium Sulfate-Induced Colitis by Modulating Type 17 Helper T Cell Responses

Angelica gigas has been used as a Korean traditional medicine for pain relief and gynecological health. Although the extracts are reported to have an anti-inflammatory property, the bioactive compounds of the herbal plant and the effect on T cell responses are unclear. In this study, we identified decursinol angelate (DA) as an immunomodulatory ingredient of A. gigas and demonstrated its suppressive effect on type 17 helper T (Th17) cell responses. Helper T cell culture experiments revealed that DA impeded the differentiation of Th17 cells and IL-17 production without affecting the survival and proliferation of CD4 T cells. By using a dextran sodium sulfate (DSS)-induced colitis model, we determined the therapeutic potential of DA for the treatment of ulcerative colitis. DA treatment attenuated the severity of colitis including a reduction in weight loss, colon shortening, and protection from colonic tissue damage induced by DSS administration. Intriguingly, Th17 cells concurrently with neutrophils in the colitis tissues were significantly decreased by the DA treatment. Overall, our experimental evidence reveals for the first time that DA is an anti-inflammatory compound to modulate inflammatory T cells, and suggests DA as a potential therapeutic agent to manage inflammatory conditions associated with Th17 cell responses.

Pharmaceutical Studies on “Dang-Gui” in Korean Journals

A crude drug “Dang-Gui”, belonging to the genus Angelica, has been used as a traditional herbal medicine in Asia. Various studies have investigated the chemical components and pharmacological activities of Dang-Gui worldwide. However, domestic research results published in Korean are undervalued in international academia due to language barriers. Therefore, it is necessary to summarize the domestic research findings systematically for greater accessibility. This review focuses on the results published in four Korean pharmaceutical journals between 1970 and 2018, which detail the botanical, phytochemical, and pharmacological properties of three Angelica species (A. gigas, A. sinensis, and A. acutiloba) used as “Dang-Gui” in Korea, China, and Japan.

Preventive effect of Angelica gigas Nakai extract oral administration on dry eye syndrome

Objective: To identify the preventive effect of Angelica gigas Nakai (A. gigas Nakai) extract in a benzalkonium chloride-induced dry eye model. Methods: A total of 28 mice were divided into 4 groups: 1) Normal group: mice received only saline; 2) positive control group: mice received an oral solution without A. gigas Nakai extract at 10:00 a.m. and 0.2% benzalkonium chloride eye drops at 2:00 p.m.; 3) A. gigas Nakai extract (5 mg); 4) A. gigas Nakai extract (10 mg). Both group 3) and group 4) received an oral solution with A. gigas Nakai extract (either 5 mg/kg or 10 mg/kg) at 10:00 a.m. and 0.2% benzalkonium chloride eye drops at 2:00 p.m. After 14 d of follow-up, tear volume measurement and fluorescein staining were evaluated for the recovery effects on ocular surface. Histologic analysis was conducted by hematoxylin and eosin staining. Apoptosis on ocular epithelium layer was examined using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining. Expression of TNF- α was also measured using western blot analysis. Results: An increase in both the tear volume and the sustained fluorescein staining scores was observed, demonstrating the preventive effects of A. gigas Nakai extract. Structure changes such as irregularity of the epithelial layer and corneal epithelial cell death were inhibited in the A. gigas Nakai extract groups. Expression of TNF- α moderately declined; however, its expression level was still higher, compared to the normal group. Conclusions: Results from the current study show the significant preventive effect of A. gigas Nakai extract in a mouse model of benzalkonium chloride-induced dry eye syndrome. Thus, A. gigas Nakai extract could be considered as an oral preventive agent for dry eye syndrome in the future. http://www.apjtm.org/article.asp?issn=1995-7645;year=2018;volume=11;issue=6;spage=369;epage=375;aulast=Lee;type=2.

Preventive effect of Angelica gigas Nakai extract oral administration on dry eye syndrome

Objective:To identify the preventive effect of Angelica gigas Nakai (A. gigas Nakai) extract in a benzalkonium chloride-induced dry eye model.Methods:A total of 28 mice were divided into 4 groups: 1) Normal group: mice received only saline; 2) positive control group: mice received an oral solution without A. gigas Nakai extract at 10:00 a.m. and 0.2% benzalkonium chloride eye drops at 2:00 p.m.; 3) A. gigas Nakai extract (5 mg); 4) A. gigas Nakai extract (10 mg). Both group 3) and group 4) received an oral solution with A. gigas Nakai extract (either 5 mg/kg or 10 mg/kg) at 10:00 a.m. and 0.2% benzalkonium chloride eye drops at 2:00 p.m. After 14 d of follow-up, tear volume measurement and fluorescein staining were evaluated for the recovery effects on ocular surface. Histologic analysis was conducted by hematoxylin and eosin staining. Apoptosis on ocular epithelium layer was examined using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining. Expression of TNF- α was also measured using western blot analysis.Results:An increase in both the tear volume and the sustained fluorescein staining scores was observed, demonstrating the preventive effects of A. gigas Nakai extract. Structure changes such as irregularity of the epithelial layer and corneal epithelial cell death were inhibited in the A. gigas Nakai extract groups. Expression of TNF- α moderately declined; however, its expression level was still higher, compared to the normal group.Conclusions:Results from the current study show the significant preventive effect of A. gigas Nakai extract in a mouse model of benzalkonium chloride-induced dry eye syndrome. Thus, A. gigas Nakai extract could be considered as an oral preventive agent for dry eye syndrome in the future.

Protective effect of decursin and decursinol angelate-rich Angelica gigas Nakai extract on dextran sulfate sodium-induced murine ulcerative colitis

OBJECTIVE@#To investigate the anti-inflammatory effects of decursin and decursinol angelate-rich Angelica gigas Nakai (AGNE) on dextran sulfate sodium (DSS)-induced murine ulcerative colitis (UC).@*METHODS@#The therapeutic effect of an AGNE was analyzed in a mouse model of UC induced by DSS. Disease activity index values were measured by clinical signs such as a weight loss, stool consistency, rectal bleeding and colon length. A histological analysis was performed using hematoxylin and eosin staining. Key inflammatory cytokines and mediators including IL-6, TNF-α, PGE, COX-2 and HIF-1α were assayed by enzyme-linked immunosorbent assay or western blotting.@*RESULTS@#Treatment with the AGNE at 10, 20, and 40 mg/kg alleviated weight loss, decreased disease activity index scores, and reduced colon shortening in mice with DSS-induced UC. AGNE inhibited the production of IL-6 and TNF-α in serum and colon tissue. Moreover, AGNE suppressed the increased expression of COX-2 and HIF-1α and the increased production of PGE in colon tissue were observed in mice with DSS-induced UC. Additionally, histological damage was also alleviated by AGNE treatment.@*CONCLUSIONS@#The findings of this study verified that AGNE significantly improves clinical symptoms and reduces the activity of various inflammatory mediators. These results indicate the AGNE has the therapeutic potential in mice with DSS-induced UC.

Protective effect of decursin and decursinol angelate-rich Angelica gigas Nakai extract on dextran sulfate sodium-induced murine ulcerative colitis

Objective To investigate the anti-inflammatory effects of decursin and decursinol angelate-rich Angelica gigas Nakai (AGNE) on dextran sulfate sodium (DSS)-induced murine ulcerative colitis (UC). Methods The therapeutic effect of an AGNE was analyzed in a mouse model of UC induced by DSS. Disease activity index values were measured by clinical signs such as a weight loss, stool consistency, rectal bleeding and colon length. A histological analysis was performed using hematoxylin and eosin staining. Key inflammatory cytokines and mediators including IL-6, TNF-α PGE

Comparison on polysaccharide among five species of Angelicae Radix / 中草药

Objective: Comparing the quality among five species of Angelicae Radix (Danggui) samples, i.e. Chinese Danggui (CDG, the roots of Angelica sinensis), Japanese Danggui (JDG, the roots of A. acutiloba), Korean Danggui (KDG, the roots of A. gigas), Lovage root (LR, the roots of Levisticum officinale), and Angelica archangelica root (AAR, the roots of A. archangelica) by evaluating the contents of their bioactive components. Methods: The 3,5-dinitrosalicylic acid colorimetric method (DNS method) was developed to quantify the amount of polysaccharides in a total of 46 species of Angelicae Radix collected from different countries based on the optimization of sampling, comparing the differences of polysaccharide among various species of Angelicae Radix, etc. Results: The contents of polysaccharides were found to be significantly different among the five species of Angelicae Radix. The order from high to low amount was AAR (162.5 mg/g, n=9), LR (142.3 mg/g, n=4), JDG (126.8 mg/g, n=13), KDG (126.8 mg/g, n=13), and CDG (80.75 mg/g, n=12). For JDG sample, the contents of polysaccharide were significant variety among samples cultivated in Japan (131.37 mg/g, n=3), China (184.29 mg/g, n=4), and Korea (94.98 mg/g, n=4). Conclusion: The developed DNS method is suitable to accurately quantify the amount of polysaccharide in Angelicae Radix. The pharmaceutical efficacy is variety among the five Angelicae Radix resulting from the various contents of polysaccharide. These herbs can not be mixed or substituted in clinical use.

An ethanolic extract of Angelica gigas improves atherosclerosis by inhibiting vascular smooth muscle cell proliferation / 한국실험동물학회지

The effects of an ethanolic extract of Angelica gigas (EAG) on the vascular smooth muscle cell (VSMC) proliferation and high-cholesterol diet-induced hypercholesterolemia and atherosclerosis were investigated. Rat aortic VSMCs were stimulated with platelet-derived growth factor-BB (25 ng/mL) for the induction of DNA synthesis and cell proliferation. EAG (1-10 microg/mL) significantly inhibited both the thymidine incorporation and cell proliferation in a concentration-dependent manner. Hypercholesterolemia was induced by feeding male New Zealand white rabbits with 0.5% cholesterol in diet for 10 weeks, during which EAG (1% in diet) was given for the final 8 weeks after 2-week induction of hypercholesterolemia. Hypercholesterolemic rabbits exhibited great increases in serum total cholesterol and low-density lipoproteins (LDL) levels, and finally severe atheromatous plaque formation covering 28.4% of the arterial walls. EAG significantly increased high-density lipoproteins (HDL), slightly decreased LDL, and potentially reduced the atheroma area to 16.6%. The results indicate that EAG attenuates atherosclerosis not only by inhibiting VASC proliferation, but also by increasing blood HDL levels. Therefore, it is suggested that EAG could be an alternative or an adjunct therapy for the improvement of hypercholesterolemia and atherosclerosis.

Ethanol extract of Angelica gigas inhibits croton oil-induced inflammation by suppressing the cyclooxygenase - prostaglandin pathway

The anti-inflammatory effects of an ethanol extract of Angelica gigas (EAG) were investigated in vitro and in vivo using croton oil-induced inflammation models. Croton oil (20 microgram/mL) up-regulated mRNA expression of cyclooxygenase (COX)-I and COX-II in the macrophage cell line, RAW 264.7, resulting in the release of high concentrations of prostaglandin E2 (PGE2). EAG (1~10 microgram/mL) markedly suppressed croton oil-induced COX-II mRNA expression and PGE2 production. Application of croton oil (5% in acetone) to mouse ears caused severe local erythema, edema and vascular leakage, which were significantly attenuated by oral pre-treatment with EAG (50~500 mg/kg). Croton oil dramatically increased blood levels of interleukin (IL)-6 and PGE2 without affecting tumor-necrosis factor (TNF)-alpha and nitric oxide (NO) levels. EAG pre-treatment remarkably lowered IL-6 and PGE2, but did not alter TNF-alpha or NO concentrations. These results indicate that EAG attenuates inflammatory responses in part by blocking the COX-PGE2 pathway. Therefore, EAG could be a promising candidate for the treatment of inflammatory diseases.