Anti‑inflammatory and antioxidant effects of 2, 7‑dihydroxy‑4, 6‑dimethoxy phenanthrene isolated from Dioscorea batatas Decne

다국어 초록 (Multilingual Abstract)

Our previous study showed that the ethanol extract of Dioscorea batatas Decne (Chinese yam) peel upregulated certain antioxidant enzymes and had the anti-inflammatory activity. In this study, 2, 7-dihydroxy-4, 6-dimethoxy phenanthrene (DDP) was isolated from yam peel extract as a potent antioxidative enzyme inducer through bioassay-guided fractionation using HepG2-ARE cells, and subjected to examination for its anti-inflammatory activity as well as antioxidant activity. DDP decreased the levels of inflammatory mediators in LPS-stimulated Raw 264.7 macrophage and reduced the level of reactive oxygen species in tert-butyl hydroperoxide-challenged Raw 264.7 cells. Moreover, DDP enhanced the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and its downstream heme oxygenase-1 proteins while it decreased the expression of iNOS, COX-2, proinflammatory cytokines via nuclear factor-κB pathway.
However, the combinatorial treatment with DDP and the inhibitor of Nrf2 or HO-1 activity did not affect the levels of inflammatory biomarkers, suggesting that anti-inflammatory action by DDP is achieved by the mechanism independent of Nrf2 signaling pathway. In conclusion, DDP was found to be a strong antioxidant and anti-inflammatory agent and warrants further in vivo efficacy study for future use as a functional food ingredient.

참고문헌 (Reference)

1 Wunder C, "The heme oxygenase system : its role in liver inflammation" 3 : 199-208, 2003

2 Choi YH, "The cytoprotective effect of isorhamnetin against oxidative stress is mediated by the upregulation of the Nrf2-dependent HO-1expression in C2C12myoblasts through scavenging reactive oxygen species and ERK inactivation" 35 : 145-154, 2016

3 Kim W, "Taurine chloramine stimulates efferocytosis through upregulation of Nrf2-mediated heme oxygenase-1 expression in murine, acrophages : possible involvement of carbon monoxide" 23 : 163-177, 2015

4 Woo YJ, "Suppression of Nrf2 by Chestnut Leaf extract increases chemosensitivity of breast cancer stem cells to paclitaxel" 9 : 760-, 2017

5 Medzhitov R, "Recognition of microorganisms and activation of the immune response" 449 : 819-826, 2007

6 Mittal M, "Reactive oxygen species in inflammation and tissue injury" 20 (20): 1126-1167, 2014

7 Thannickal VJ, "Reactive oxygen species in cell signaling" 279 : L1005-L1028, 2000

8 Harijith A, "Reactive oxygen species at the crossroads of inflammasome and inflammation" 5 : 352-, 2014

9 임지선, "Protective Effect of Dioscorea batatas Peel Extract Against Intestinal Inflammation" 한국식품영양과학회 21 (21): 1204-1217, 2018

10 Liu JY, "Polysaccharides from Dioscorea batatas induce tumor necrosis factor-alpha secretion via Toll-like receptor 4-mediated protein kinase signaling pathways" 56 : 9892-9898, 2008

11 Leong YW, "Phenanthrenes, dihydrophenanthrenes and bibenzyls from the orchid Bulbophyllum vaginatum" 44 : 157-165, 1997

12 Reuter S, "Oxidative stress, inflammation, and cancer: how are they linked?" 49 : 1603-1616, 2010

13 Jenner P, "Oxidative stress in Parkinson’s disease" 53 : S26-S36, 2003

14 Medzhitov R, "Origin and physiological roles of inflammation" 454 : 428-435, 2008

15 Kovacs A, "Natural phenanthrenes and their biological activity" 69 : 1084-1110, 2008

16 Xue Z, "Mono-, Bi-, and triphenanthrenes from the tubers of Cremastra appendiculata" 69 : 907-913, 2006

17 Adams M, "Inhibition of leukotriene biosynthesis by stilbenoids from Stemona species" 68 : 83-85, 2005

18 Axelrad JE, "Inflammatory bowel disease and cancer : the role of inflammation, immunosuppression, and cancer treatment" 22 : 4794-4801, 2016

19 Droge W, "Free radicals in the physiological control of cell function" 82 : 47-95, 2002

20 오지선, "Fermented Red Ginseng Extract Inhibits Cancer Cell Proliferation and Viability" 한국식품영양과학회 18 (18): 421-428, 2015

21 Zhang M, "Emerging roles of Nrf2 and phase II antioxidant enzymes in neuroprotection" 100 : 30-47, 2013

22 Chi X, "Elevation of HO-1 expression mitigates intestinal ischemia-reperfusion injury and restores tight junction function in a rat liver transplantation model" 2015 : 986075-, 2015

23 Kim BR, "Effects of glutathione on antioxidant response element-mediated gene expression and apoptosis elicited by sulforaphane" 63 : 7520-7525, 2003

24 Nikam A, "Diverse Nrf2 activators coordinated to cobalt carbonyls induce heme oxygenase-1 and release carbon monoxide in vitro and in vivo" 59 : 756-762, 2016

25 Lin YL, "Dihydrophenanthrenes from Spiranthes sinensis" 63 : 1608-1610, 2000

26 Kostecki K, "Dihydrophenanthrenes and other antifungal stilbenoids from Stemona cf. pierrei" 65 : 99-106, 2004

27 Morgan MJ, "Crosstalk of reactive oxygen species and NFkappaB signaling" 21 : 103-115, 2011

28 Kim ER, "Colorectal cancer in inflammatory bowel disease: the risk, pathogenesis, prevention and diagnosis" 20 : 9872-9881, 2014

29 Halliwell B, "Biochemistry of oxidative stress" 35 : 1147-1150, 2007

30 Aquino R, "Antiviral activity of constituents of Tamus communis" 3 : 305-309, 1991

31 Zhu H, "Antioxidants and phase 2 enzymes in macrophages: regulation by Nrf2signaling and protection against oxidative and electrophilic stress" 233 : 463-474, 2008

32 Kuhn AM, "Antioxidant signaling via Nrf2 counteracts lipopolysaccharide-mediated inflammatory responses in foam cell macrophages" 50 : 1382-1391, 2011

33 Pacher T, "Antifungal stilbenoids from Stemona collinsae" 65 : 820-827, 2002

34 Takasugi M, "Antifungal compounds from Dioscorea batatas inoculated with Pseudomonas cichorii" 26 : 371-375, 1987

35 Matsuda H, "Antiallergic phenanthrenes and stilbenes from the tubers of Gymnadenia conopsea" 70 : 847-855, 2004