Magnolol protects against ischemic-reperfusion brain damage following oxygen-glucose deprivation and transient focal cerebral ischemia

Huang,Sheng‑Yang; Tai,Shih‑Huang; Chang,Che‑Chao; Tu,Yi‑Fang; Chang,Chih‑Han; Lee,E‑Jian

doi:10.3892/ijmm.2018.3387

Magnolol protects against ischemic-reperfusion brain damage following oxygen-glucose deprivation and transient focal cerebral ischemia

Authors:
- Sheng‑Yang Huang
- Shih‑Huang Tai
- Che‑Chao Chang
- Yi‑Fang Tu
- Chih‑Han Chang
- E‑Jian Lee
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Affiliations: Institute of Biomedical Engineering, National Cheng Kung University, Tainan 70428, Taiwan, R.O.C., Neurophysiology Laboratory, Department of Surgery, National Cheng Kung University Medical Center and Medical School, Tainan 70428, Taiwan, R.O.C.
Published online on: January 15, 2018 https://doi.org/10.3892/ijmm.2018.3387
Pages: 2252-2262

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Abstract

In the present study, the neuroprotective potential of magnolol against ischemia-reperfusion brain injury was examined via in vivo and in vitro experiments. Magnolol exhibited strong radical scavenging and antioxidant activity, and significantly inhibited the production of interleukin‑6, tumor necrosis factor‑a and nitrite/nitrate (NOX) in lipopolysaccharide-stimulated BV2 and RAW 264.7 cells when applied at concentrations of 10 and 50 µM, respectively. Magnolol (100 µM) also significantly attenuated oxygen‑glucose deprivation‑induced damage in neonatal rat hippocampal slice cultures, when administered up to 4 h following the insult. In a rat model of stable ischemia, compared with a vehicle‑treated ischemic control, pretreatment with magnolol (0.01‑1 mg/kg, intravenously) significantly reduced brain infarction following ischemic stroke, and post‑treatment with magnolol (1 mg/kg) remained effective and significantly reduced infarction when administered 2 h following the onset of ischemia. Additionally, magnolol (0.3 and 1 mg/kg) significantly reduced the accumulation of superoxide anions at the border zones of infarction and reduced oxidative damage in the ischemic brain. This was assessed by measuring the levels of NOX, malondialdehyde and myeloperoxidase, the ratio of glutathione/oxidized glutathione and the immunoreactions of 8‑hydroxy‑2'‑deoxyguanosine and 4‑hydroxynonenal. Thus, magnolol was revealed to protect against ischemia‑reperfusion brain damage. This may be partly attributed to its antioxidant, radical scavenging and anti‑inflammatory effects.

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1	Traystman RJ, Kirsch JR and Koehler RC: Oxygen radical mechanisms of brain injury following ischemia and reperfusion. J Appl Physiol (1985). 71:1185–1195. 1991. View Article : Google Scholar
2	Bramlett HM and Dietrich WD: Pathophysiology of cerebral ischemia and brain trauma: Similarities and differences. J Cereb Blood Flow Metab. 24:133–150. 2004. View Article : Google Scholar : PubMed/NCBI
3	Clemens JA: Cerebral ischemia: Gene activation, neuronal injury, and the protective role of antioxidants. Free Radic Biol Med. 28:1526–1531. 2000. View Article : Google Scholar : PubMed/NCBI
4	Chan PH: Reactive oxygen radicals in signaling and damage in the ischemic brain. J Cereb Blood Flow Metab. 21:2–14. 2001. View Article : Google Scholar : PubMed/NCBI
5	Lee EJ, Chen HY, Lee MY, Chen TY, Hsu YS, Hu YL, Chang GL and Wu TS: Cinnamophilin reduces oxidative damage and protects against transient focal cerebral ischemia in mice. Free Radic Biol Med. 39:495–510. 2005. View Article : Google Scholar : PubMed/NCBI
6	Lee EJ, Lee MY, Chen HY, Hsu YS, Wu TS, Chen ST and Chang GL: Melatonin attenuates gray and white matter damage in a mouse model of transient focal cerebral ischemia. J Pineal Res. 38:42–52. 2005. View Article : Google Scholar
7	Shen YC, Sung YJ and Chen CF: Magnolol inhibits Mac-1 (CD11b/CD18)-dependent neutrophil adhesion: Relationship with its antioxidant effect. Eur J Pharmacol. 343:79–86. 1998. View Article : Google Scholar : PubMed/NCBI
8	Wang Y, Li CY, Lin IH, Lee AR and Hu MK: Synthesis and radical scavenging of novel magnolol derivatives. J Pharm Pharmacol. 54:1697–1703. 2002. View Article : Google Scholar
9	Chen HY, Hung YC, Lee EJ, Chen TY, Chuang IC and Wu TS: The protective efficacy of magnolol in hind limb ischemia-reperfusion injury. Phytomedicine. 16:976–981. 2009. View Article : Google Scholar : PubMed/NCBI
10	Chang CP, Hsu YC and Lin MT: Magnolol protects against cerebral ischaemic injury of rat heatstroke. Clin Exp Pharmacol Physiol. 30:387–392. 2003. View Article : Google Scholar : PubMed/NCBI
11	Teng CM, Yu SM, Chen CC, Huang YL and Huang TF: EDRF-release and Ca+(+)-channel blockade by magnolol, an antiplatelet agent isolated from Chinese herb Magnolia officinalis, in rat thoracic aorta. Life Sci. 47:1153–1161. 1990. View Article : Google Scholar : PubMed/NCBI
12	Lee MM, Huang HM, Hsieh MT, Chen CS, Yeh FT and Kuo JS: Anti-inflammatory and neuroprotective effects of magnolol in chemical hypoxia in rat cultured cortical cells in hypoglycemic media. Chin J Physiol. 43:61–67. 2000.PubMed/NCBI
13	Lee MM, Hseih MT, Kuo JS, Yeh FT and Huang HM: Magnolol protects cortical neuronal cells from chemical hypoxia in rats. Neuroreport. 9:3451–3456. 1998. View Article : Google Scholar : PubMed/NCBI
14	Lin YR, Chen HH, Ko CH and Chan MH: Neuroprotective activity of honokiol and magnolol in cerebellar granule cell damage. Eur J Pharmacol. 537:64–69. 2006. View Article : Google Scholar : PubMed/NCBI
15	Lee WT, Lin MH, Lee EJ, Hung YC, Tai SH, Chen HY, Chen TY and Wu TS: Magnolol reduces glutamate-induced neuronal excitotoxicity and protects against permanent focal cerebral ischemia up to 4 hours. PLoS One. 7:e399522012. View Article : Google Scholar : PubMed/NCBI
16	Watanabe K, Watanabe H, Goto Y, Yamaguchi M, Yamamoto N and Hagino K: Pharmacological properties of magnolol and honokiol extracted from Magnolia officinalis: Central depressant effects. Planta Med. 49:103–108. 1983. View Article : Google Scholar : PubMed/NCBI
17	Lin SP, Tsai SY, Lee Chao PD, Chen YC and Hou YC: Pharmacokinetics, bioavailability, and tissue distribution of magnolol following single and repeated dosing of magnolol to rats. Planta Med. 77:1800–1805. 2011. View Article : Google Scholar : PubMed/NCBI
18	Chapman SN, Mehndiratta P, Johansen MC, McMurry TL, Johnston KC and Southerland AM: Current perspectives on the use of intravenous recombinant tissue plasminogen activator (tPA) for treatment of acute ischemic stroke. Vasc Health Risk Manag. 10:75–87. 2014.PubMed/NCBI
19	Lee EJ, Chen HY, Hung YC, Chen TY, Lee MY, Yu SC, Chen YH, Chuang IC and Wu TS: Therapeutic window for cinnamophilin following oxygen-glucose deprivation and transient focal cerebral ischemia. Exp Neurol. 217:74–83. 2009. View Article : Google Scholar : PubMed/NCBI
20	Chen TY, Lin MH, Lee WT, Huang SY, Chen YH, Lee AC, Lin HW and Lee EJ: Nicotinamide inhibits nuclear factor-kappa B translocation after transient focal cerebral ischemia. Crit Care Med. 40:532–537. 2012. View Article : Google Scholar
21	Tai SH, Hung YC, Lee EJ, Lee AC, Chen TY, Shen CC, Chen HY, Lee MY, Huang SY and Wu TS: Melatonin protects against transient focal cerebral ischemia in both reproductively active and estrogen-deficient female rats: The impact of circulating estrogen on its hormetic dose-response. J Pineal Res. 50:292–303. 2011. View Article : Google Scholar : PubMed/NCBI
22	Chen TY, Tai SH, Lee EJ, Huang CC, Lee AC, Huang SY and Wu TS: Cinnamophilin offers prolonged neuroprotection against gray and white matter damage and improves functional and electrophysiological outcomes after transient focal cerebral ischemia. Crit Care Med. 39:1130–1137. 2011. View Article : Google Scholar : PubMed/NCBI
23	Juan WS, Huang SY, Chang CC, Hung YC, Lin YW, Chen TY, Lee AH, Lee AC, Wu TS and Lee EJ: Melatonin improves neuroplasticity by upregulating the growth-associated protein-43 (GAP-43) and NMDAR postsynaptic density-95 (PSD-95) proteins in cultured neurons exposed to glutamate excitotoxicity and in rats subjected to transient focal cerebral ischemia even during a long-term recovery period. J Pineal Res. 56:213–223. 2014. View Article : Google Scholar
24	Anderson ME: Determination of glutathione and glutathione disulfide in biological samples. Methods Enzymol. 113:548–555. 1985. View Article : Google Scholar : PubMed/NCBI
25	Belayev L, Alonso OF, Busto R, Zhao W and Ginsberg MD: Middle cerebral artery occlusion in the rat by intraluminal suture. Neurological and pathological evaluation of an improved model. Stroke. 27:1616–1623. 1996. View Article : Google Scholar : PubMed/NCBI
26	Clark WM, Rinker LG, Lessov NS, Hazel K, Hill JK, Stenzel-Poore M and Eckenstein F: Lack of interleukin-6 expression is not protective against focal central nervous system ischemia. Stroke. 31:1715–1720. 2000. View Article : Google Scholar : PubMed/NCBI
27	Hsieh MT, Chueh FY and Lin MT: Magnolol decreases body temperature by reducing 5-hydroxytryptamine release in the rat hypothalamus. Clin Exp Pharmacol Physiol. 25:813–817. 1998. View Article : Google Scholar : PubMed/NCBI
28	Danton GH and Dietrich WD: Inflammatory mechanisms after ischemia and stroke. J Neuropathol Exp Neurol. 62:127–136. 2003. View Article : Google Scholar : PubMed/NCBI
29	Ishikawa M, Sekizuka E, Sato S, Yamaguchi N, Inamasu J, Bertalanffy H, Kawase T and Iadecola C: Effects of moderate hypothermia on leukocyte-endothelium interaction in the rat pial microvasculature after transient middle cerebral artery occlusion. Stroke. 30:1679–1686. 1999. View Article : Google Scholar : PubMed/NCBI
30	Nakashima M, Niwa M, Iwai T and Uematsu T: Involvement of free radicals in cerebral vascular reperfusion injury evaluated in a transient focal cerebral ischemia model of rat. Free Radic Biol Med. 26:722–729. 1999. View Article : Google Scholar : PubMed/NCBI
31	Sugawara T and Chan PH: Reactive oxygen radicals and pathogenesis of neuronal death after cerebral ischemia. Antioxid Redox Signal. 5:597–607. 2003. View Article : Google Scholar : PubMed/NCBI