Protective effects of osthole, a natural derivative of coumarin, against intestinal ischemia-reperfusion injury in mice

Dong,Wenpeng; Zhang,Zhen; Liu,Zhengjun; Liu,Hao; Wang,Xianyue; Bi,Shenghui; Wang,Xiaowu; Ma,Tao; Zhang,Weida

doi:10.3892/ijmm.2013.1347

Protective effects of osthole, a natural derivative of coumarin, against intestinal ischemia-reperfusion injury in mice

Authors:
- Wenpeng Dong
- Zhen Zhang
- Zhengjun Liu
- Hao Liu
- Xianyue Wang
- Shenghui Bi
- Xiaowu Wang
- Tao Ma
- Weida Zhang
View Affiliations

Affiliations: Department of Cardiovascular Surgery, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, Guangdong 510010, P.R. China, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China, Department of Vascular and Endocrine Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
Published online on: April 15, 2013 https://doi.org/10.3892/ijmm.2013.1347
Pages: 1367-1374

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Intestinal ischemia/reperfusion (I/R) injury is considered to be associated with high morbidity and mortality rates. Osthole, a natural derivative of coumarin, has been shown to exert a variety of pharmacological and therapeutic effects under physiological and pathological conditions. In the present study, to investigate the protective effects of osthole against intestinal I/R injury, various doses of osthole (5, 10, 25 and 50 mg/kg) were pre-administered to mice subjected to intestinal I/R injury. A dose-dependent increase in the survival rate was observed in the osthole-treated mice. Pre-treatment with osthole (50 mg/kg) attenuated the destruction of epithelial cells within the villi induced by intestinal I/R injury, and suppressed oxidative stress, neutrophil infiltration and modulated nitric oxide (NO) levels. Moreover, the increased IκBα phosphorylation and nuclear factor (NF)-κB nuclear translocation induced by I/R injury were significantly decreased following pre-treatment with osthole. Taken together, our data demonstrate that osthole exerts protective effects against intestinal I/R injury in mice by suppressing oxidative stress, neutrophil infiltration and NO levels, partly through the inhibition of NF-κB nuclear translocation. Hence, the findings of the present study provide insight into the mechanisms through which osthole exerts its protective effects against intestinal I/R injury.

View Figures

View References

1	Yasuhara H: Acute mesenteric ischemia: the challenge of gastroenterology. Surg Today. 35:185–195. 2005. View Article : Google Scholar : PubMed/NCBI
2	Berland T and Oldenburg WA: Acute mesenteric ischemia. Curr Gastroenterol Rep. 10:341–346. 2008. View Article : Google Scholar
3	Ozacmak VH, Sayan H, Arslan SO, Altaner S and Aktas RG: Protective effect of melatonin on contractile activity and oxidative injury induced by ischemia and reperfusion of rat ileum. Life Sci. 76:1575–1588. 2005. View Article : Google Scholar : PubMed/NCBI
4	Shibata C, Balsiger BM, Anding WJ, Duenes JA, Miller VM and Sarr MG: Functional changes in nonadrenergic, noncholinergic inhibitory neurons in ileal circular smooth muscle after small bowel transplantation in rats. Dig Dis Sci. 43:2446–2454. 1998. View Article : Google Scholar
5	Blikslager AT, Moeser AJ, Gookin JL, Jones SL and Odle J: Restoration of barrier function in injured intestinal mucosa. Physiol Rev. 87:545–564. 2007. View Article : Google Scholar : PubMed/NCBI
6	Szabo A, Vollmar B, Boros M and Menger MD: In vivo fluorescence microscopic imaging for dynamic quantitative assessment of intestinal mucosa permeability in mice. J Surg Res. 145:179–185. 2008. View Article : Google Scholar : PubMed/NCBI
7	Santora RJ, Lie ML, Grigoryev DN, Nasir O, Moore FA and Hassoun HT: Therapeutic distant organ effects of regional hypothermia during mesenteric ischemia-reperfusion injury. J Vasc Surg. 52:1003–1014. 2010. View Article : Google Scholar : PubMed/NCBI
8	Vasileiou I, Kostopanagiotou G, Katsargyris A, Klonaris C, Perrea D and Theocharis S: Toll-like receptors: a novel target for therapeutic intervention in intestinal and hepatic ischemiareperfusion injury? Expert Opin Ther Targets. 14:839–853. 2010. View Article : Google Scholar : PubMed/NCBI
9	Shah PC, Brolin RE, Amenta PS and Deshmukh DR: Effect of aging on intestinal ischemia and reperfusion injury. Mech Ageing Dev. 107:37–50. 1999. View Article : Google Scholar : PubMed/NCBI
10	Esposito E and Cuzzocrea S: Role of nitroso radicals as drug targets in circulatory shock. Br J Pharmacol. 157:494–508. 2009. View Article : Google Scholar : PubMed/NCBI
11	Barocelli E, Ballabeni V, Ghizzardi P, et al: The selective inhibition of inducible nitric oxide synthase prevents intestinal ischemia-reperfusion injury in mice. Nitric Oxide. 14:212–218. 2006. View Article : Google Scholar : PubMed/NCBI
12	Nakano H, Nakajima A, Sakon-Komazawa S, Piao JH, Xue X and Okumura K: Reactive oxygen species mediate crosstalk between NF-kappaB and JNK. Cell Death Differ. 13:730–737. 2006. View Article : Google Scholar : PubMed/NCBI
13	Hoult JR and Paya M: Pharmacological and biochemical actions of simple coumarins: natural products with therapeutic potential. Gen Pharmacol. 27:713–722. 1996. View Article : Google Scholar : PubMed/NCBI
14	Chou SY, Hsu CS, Wang KT, Wang MC and Wang CC: Antitumor effects of osthole from Cnidium monnieri: an in vitro and in vivo study. Phytother Res. 21:226–230. 2007. View Article : Google Scholar
15	Zhang Q, Qin L, He W, et al: Coumarins from Cnidium monnieri and their antiosteoporotic activity. Planta Med. 73:13–19. 2007.PubMed/NCBI
16	Liang HJ, Suk FM, Wang CK, et al: Osthole, a potential antidiabetic agent, alleviates hyperglycemia in db/db mice. Chem Biol Interact. 181:309–315. 2009. View Article : Google Scholar : PubMed/NCBI
17	Liu J, Zhang W, Zhou L, Wang X and Lian Q: Anti-inflammatory effect and mechanism of osthole in rats. Zhong Yao Cai. 28:1002–1006. 2005.PubMed/NCBI
18	Chiu PR, Lee WT, Chu YT, Lee MS, Jong YJ and Hung CH: Effect of the Chinese herb extract osthole on IL-4-induced eotaxin expression in BEAS-2B cells. Pediatr Neonatol. 49:135–140. 2008. View Article : Google Scholar : PubMed/NCBI
19	Chao X, Zhou J, Chen T, et al: Neuroprotective effect of osthole against acute ischemic stroke on middle cerebral ischemia occlusion in rats. Brain Res. 1363:206–211. 2010. View Article : Google Scholar : PubMed/NCBI
20	Li F, Gong Q, Wang L and Shi J: Osthole attenuates focal inflammatory reaction following permanent middle cerebral artery occlusion in rats. Biol Pharm Bull. 35:1686–1690. 2012. View Article : Google Scholar : PubMed/NCBI
21	Zhou F, Zhong W, Xue J, Gu ZL and Xie ML: Reduction of rat cardiac hypertrophy by osthole is related to regulation of cardiac oxidative stress and lipid metabolism. Lipids. 47:987–994. 2012. View Article : Google Scholar : PubMed/NCBI
22	Souza DG, Soares AC, Pinho V, et al: Increased mortality and inflammation in tumor necrosis factor-stimulated gene-14 transgenic mice after ischemia and reperfusion injury. Am J Pathol. 160:1755–1765
23	Fleming SD, Monestier M and Tsokos GC: Accelerated ischemia/reperfusion-induced injury in autoimmunity-prone mice. J Immunol. 173:4230–4235. 2004. View Article : Google Scholar : PubMed/NCBI
24	Nathan C: Nitric oxide as a secretory product of mammalian cells. FASEB J. 6:3051–3064. 1992.PubMed/NCBI
25	Tak PP and Firestein GS: NF-kappaB: a key role in inflammatory diseases. J Clin Invest. 107:7–11. 2001. View Article : Google Scholar : PubMed/NCBI
26	Hsieh MT, Hsieh CL, Wang WH, Chen CS, Lin CJ and Wu CR: Osthole improves aspects of spatial performance in ovariectomized rats. Am J Chin Med. 32:11–20. 2004. View Article : Google Scholar : PubMed/NCBI
27	Zhang Y, Xie ML, Zhu LJ and Gu ZL: Therapeutic effect of osthole on hyperlipidemic fatty liver in rats. Acta Pharmacol Sin. 28:398–403. 2007. View Article : Google Scholar : PubMed/NCBI
28	Zhang Y, Xie ML, Xue J and Gu ZL: Osthole regulates enzyme protein expression of CYP7A1 and DGAT2 via activation of PPARalpha/gamma in fat milk-induced fatty liver rats. J Asian Nat Prod Res. 10:807–812. 2008. View Article : Google Scholar : PubMed/NCBI
29	Luszczki JJ, Andres-Mach M, Cisowski W, Mazol I, Glowniak K and Czuczwar SJ: Osthole suppresses seizures in the mouse maximal electroshock seizure model. Eur J Pharmacol. 607:107–109. 2009. View Article : Google Scholar : PubMed/NCBI
30	Li XX, Hara I and Matsumiya T: Effects of osthole on postmenopausal osteoporosis using ovariectomized rats; comparison to the effects of estradiol. Biol Pharm Bull. 25:738–742. 2002. View Article : Google Scholar : PubMed/NCBI
31	He W, Liu JX, Zhou YM, et al: Protective effects of osthole on cerebral ischemia-reperfusion injury in rats and its mechanism. Chin Pharmacol Bull. 24:1528–1530. 2008.
32	Liu WB, Huo JL, Fei Z, Men XL and Li J: Neuroprotection of osthole against transient global brain ischemia in rats. Chin J Neurosurg Dis Res. 8:118–121. 2009.
33	Flessas II, Papalois AE, Toutouzas K, Zagouri F and Zografos GC: Effects of lazaroids on intestinal ischemia and reperfusion injury in experimental models. J Surg Res. 166:265–274. 2009. View Article : Google Scholar : PubMed/NCBI
34	Song F, Xie ML, Zhu LJ, Zhang KP, Xue J and Gu ZL: Experimental study of osthole on treatment of hyperlipidemic and alcoholic fatty liver in animals. World J Gastroenterol. 12:4359–4363. 2006.PubMed/NCBI
35	Sun F, Xie ML, Xue J and Wang HB: Osthole regulates hepatic PPAR alpha-mediated lipogenic gene expression in alcoholic fatty liver murine. Phytomedicine. 17:669–673. 2010. View Article : Google Scholar : PubMed/NCBI
36	Liu WB, Zhou J, Qu Y, et al: Neuroprotective effect of osthole on MPP⁺-induced cytotoxicity in PC12 cells via inhibition of mitochondrial dysfunction and ROS production. Neurochem Int. 57:206–215. 2010.PubMed/NCBI
37	Naito Y, Takagi T, Ichikawa H, et al: A novel potent inhibitor of inducible nitric oxide inhibitor, ONO-1714, reduces intestinal ischemia-reperfusion injury in rats. Nitric Oxide. 10:170–177. 2004. View Article : Google Scholar : PubMed/NCBI
38	Suzuki Y, Deitch EA, Mishima S, Lu Q and Xu D: Inducible nitric oxide synthase gene knockout mice have increased resistance to gut injury and bacterial translocation after an intestinal ischemia-reperfusion injury. Crit Care Med. 28:3692–3696. 2000. View Article : Google Scholar
39	Zou L, Attuwaybi B and Kone BC: Effects of NF-kappa B inhibition on mesenteric ischemia-reperfusion injury. Am J Physiol Gastrointest Liver Physiol. 284:G713–G721. 2003. View Article : Google Scholar : PubMed/NCBI
40	Souza DG, Vieira AT, Pinho V, et al: NF-kappaB plays a major role during the systemic and local acute inflammatory response following intestinal reperfusion injury. Br J Pharmacol. 145:246–254. 2005. View Article : Google Scholar : PubMed/NCBI
41	Altavilla D, Squadrito F, Campo GM, et al: The lazaroid, U-74389G, inhibits inducible nitric oxide synthase activity, reverses vascular failure and protects against endotoxin shock. Eur J Pharmacol. 369:49–55. 1999. View Article : Google Scholar : PubMed/NCBI
42	Nakamura T, Kodama N, Arai Y, et al: Inhibitory effect of oxycoumarins isolated from the Thai medicinal plant Clausena guillauminii on the inflammation mediators, iNOS, TNF-alpha, and COX-2 expression in mouse macrophage RAW 264.7. J Nat Med. 63:21–27. 2009. View Article : Google Scholar : PubMed/NCBI
43	Liao PC, Chien SC, Ho CL, et al: Osthole regulates inflammatory mediator expression through modulating NF-kappaB, mitogen-activated protein kinases, protein kinase C, and reactive oxygen species. J Agric Food Chem. 58:10445–10451. 2010. View Article : Google Scholar
44	Duggan M, Engelberts D, Jankov RP, et al: Hypocapnia attenuates mesenteric ischemia-reperfusion injury in a rat model. Can J Anaesth. 52:262–268. 2005. View Article : Google Scholar : PubMed/NCBI
45	Spanos CP, Papaconstantinou P, Spanos P, Karamouzis M, Lekkas G and Papaconstantinou C: The effect of L-arginine and aprotinin on intestinal ischemia-reperfusion injury. J Gastrointest Surg. 11:247–255. 2007. View Article : Google Scholar : PubMed/NCBI
46	Bjorck M, Bergqvist D, Rasmussen I, Piehl E and Haglund U: An experimental porcine model of partial ischaemia of the distal colon. Eur J Surg. 163:843–850. 1997.PubMed/NCBI
47	Grootjans J, Lenaerts K, Derikx JP, et al: Human intestinal ischemia-reperfusion-induced inflammation characterized: experiences from a new translational model. Am J Pathol. 176:2283–2291. 2010. View Article : Google Scholar
48	Robinson JW, Mirkovitch V, Winistorfer B and Saegesser F: Response of the intestinal mucosa to ischaemia. Gut. 22:512–527. 1981. View Article : Google Scholar : PubMed/NCBI
49	Ji HJ, Hu JF, Wang YH, Chen XY, Zhou R and Chen NH: Osthole improves chronic cerebral hypoperfusion induced cognitive deficits and neuronal damage in hippocampus. Eur J Pharmacol. 636:96–101. 2010. View Article : Google Scholar : PubMed/NCBI