Glycyrrhizin Attenuates Rat Ischemic Spinal Cord Injury by Suppressing Inflammatory Cytokines and HMGB1

Overview

Journal Acta Pharmacol Sin

Specialty Pharmacology

Date 2011 Dec 14

PMID 22158106

Citations 35

Authors

Gu Gong

Li-Bang Yuan

Ling Hu

Wei Wu

Liang Yin

Jing-Li Hou

Ying-Hai Liu

Le-Shun Zhou

Affiliations

Soon will be listed here.

Abstract

Aim: To investigate the neuroprotective effect of glycyrrhizin (Gly) against the ischemic injury of rat spinal cord and the possible role of the nuclear protein high-mobility group box 1 (HMGB1) in the process.

Methods: Male Sprague-Dawley rats were subjected to 45 min aortic occlusion to induce transient lumbar spinal cord ischemia. The motor functions of the animals were assessed according to the modified Tarlov scale. The animals were sacrificed 72 h after reperfusion and the lumbar spinal cord segment (L2-L4) was taken out for histopathological examination and Western blotting analysis. Serum inflammatory cytokine and HMGB1 levels were analyzed using ELISA.

Results: Gly (6 mg/kg) administered intravenously 30 min before inducing the transient lumbar spinal cord ischemia significantly improved the hind-limb motor function scores, and reduced the number of apoptotic neurons, which was accompanied by reduced levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in the plasma and injured spinal cord. Moreover, the serum HMGB1 level correlated well with the serum TNF-α, IL-1β and IL-6 levels during the time period of reperfusion.

Conclusion: The results suggest that Gly can attenuate the transient spinal cord ischemic injury in rats via reducing inflammatory cytokines and inhibiting the release of HMGB1.

Citing Articles

Neuroprotective Potential of Glycyrrhizic Acid in Ischemic Stroke: Mechanisms and Therapeutic Prospects.

Li Y, Wu J, Du F, Tang T, Lim J, Karuppiah T Pharmaceuticals (Basel). 2024; 17(11).

PMID: 39598404 PMC: 11597102. DOI: 10.3390/ph17111493.

Inhibition of HMGB1 Attenuates Spinal Cord Edema by Reducing the Expression of Na-K-Cl Cotransporter-1 and Na/H Exchanger-1 in Both Astrocytes and Endothelial Cells After Spinal Cord Injury in Rats.

Li M, Lv J, Wang Z, Wang L, Qin Z, Deng C J Neurotrauma. 2023; 40(23-24):2522-2540.

PMID: 36815608 PMC: 10698785. DOI: 10.1089/neu.2022.0318.

Oxidative Stress-Induced HMGB1 Translocation in Myenteric Neurons Contributes to Neuropathy in Colitis.

Stavely R, Sahakian L, Filippone R, Stojanovska V, Bornstein J, Sakkal S Biomolecules. 2022; 12(12).

PMID: 36551259 PMC: 9776169. DOI: 10.3390/biom12121831.

Glycyrrhizin through liquorice intake modulates ACE2 and HMGB1 levels-A pilot study in healthy individuals with implications for COVID-19 and ARDS.

Buder F, Selejan S, Hohl M, Kindermann M, Herr C, Lepper P PLoS One. 2022; 17(10):e0275181.

PMID: 36251689 PMC: 9576069. DOI: 10.1371/journal.pone.0275181.

Neuroprotective effects of adrenomedullin in experimental traumatic brain injury model in rats.

Emmez G, Bulduk E, Yildirim Z Ulus Travma Acil Cerrahi Derg. 2022; 28(6):736-742.

PMID: 35652861 PMC: 10443013. DOI: 10.14744/tjtes.2021.01954.

References

Watanabe T, Kubota S, Nagaya M, Ozaki S, Nagafuchi H, Akashi K . The role of HMGB-1 on the development of necrosis during hepatic ischemia and hepatic ischemia/reperfusion injury in mice. J Surg Res. 2005; 124(1):59-66. DOI: 10.1016/j.jss.2004.10.019. View

Qin S, Wang H, Yuan R, Li H, Ochani M, Ochani K . Role of HMGB1 in apoptosis-mediated sepsis lethality. J Exp Med. 2006; 203(7):1637-42. PMC: 2118346. DOI: 10.1084/jem.20052203. View

Arase Y, Ikeda K, Murashima N, Chayama K, Tsubota A, Koida I . The long term efficacy of glycyrrhizin in chronic hepatitis C patients. Cancer. 1997; 79(8):1494-500. DOI: 10.1002/(sici)1097-0142(19970415)79:8<1494::aid-cncr8>3.0.co;2-b. View

Danielisova V, Chavko M . Comparative effects of the N-methyl-D-aspartate antagonist MK-801 and the calcium channel blocker KB-2796 on neurologic and metabolic recovery after spinal cord ischemia. Exp Neurol. 1998; 149(1):203-8. DOI: 10.1006/exnr.1997.6680. View

Muller S, Ronfani L, Bianchi M . Regulated expression and subcellular localization of HMGB1, a chromatin protein with a cytokine function. J Intern Med. 2004; 255(3):332-43. DOI: 10.1111/j.1365-2796.2003.01296.x. View

Goldstein R, Gallowitsch-Puerta M, Yang L, Rosas-Ballina M, Huston J, Czura C . Elevated high-mobility group box 1 levels in patients with cerebral and myocardial ischemia. Shock. 2006; 25(6):571-4. DOI: 10.1097/01.shk.0000209540.99176.72. View

Hirose K, Okajima K, Taoka Y, Uchiba M, Tagami H, Nakano K . Activated protein C reduces the ischemia/reperfusion-induced spinal cord injury in rats by inhibiting neutrophil activation. Ann Surg. 2000; 232(2):272-80. PMC: 1421140. DOI: 10.1097/00000658-200008000-00018. View

Pineau I, Lacroix S . Proinflammatory cytokine synthesis in the injured mouse spinal cord: multiphasic expression pattern and identification of the cell types involved. J Comp Neurol. 2006; 500(2):267-85. DOI: 10.1002/cne.21149. View

Nakayama T, Harada N, Asano M, Nomura N, Saito T, Mishima A . Atrial natriuretic peptide reduces ischemia/reperfusion-induced spinal cord injury in rats by enhancing sensory neuron activation. J Pharmacol Exp Ther. 2007; 322(2):582-90. DOI: 10.1124/jpet.107.120725. View

10.

Xu J, Beckman J, Hogan E, Hsu C . Xanthine oxidase in experimental spinal cord injury. J Neurotrauma. 1991; 8(1):11-8. DOI: 10.1089/neu.1991.8.11. View

11.

Kim J, Lim C, Yu Y, Lee J . Induction and subcellular localization of high-mobility group box-1 (HMGB1) in the postischemic rat brain. J Neurosci Res. 2007; 86(5):1125-31. DOI: 10.1002/jnr.21555. View

12.

Faraco G, Fossati S, Bianchi M, Patrone M, Pedrazzi M, Sparatore B . High mobility group box 1 protein is released by neural cells upon different stresses and worsens ischemic neurodegeneration in vitro and in vivo. J Neurochem. 2007; 103(2):590-603. DOI: 10.1111/j.1471-4159.2007.04788.x. View

13.

Wang H, Li W, Goldstein R, Tracey K, Sama A . HMGB1 as a potential therapeutic target. Novartis Found Symp. 2007; 280:73-85. View

14.

Wang Q, Ding Q, Zhou Y, Gou X, Hou L, Chen S . Ethyl pyruvate attenuates spinal cord ischemic injury with a wide therapeutic window through inhibiting high-mobility group box 1 release in rabbits. Anesthesiology. 2009; 110(6):1279-86. DOI: 10.1097/ALN.0b013e3181a160d6. View

15.

Jiang W, Bell C, Pisetsky D . The relationship between apoptosis and high-mobility group protein 1 release from murine macrophages stimulated with lipopolysaccharide or polyinosinic-polycytidylic acid. J Immunol. 2007; 178(10):6495-503. DOI: 10.4049/jimmunol.178.10.6495. View

16.

Taoka Y, Okajima K, Murakami K, Johno M, NARUO M . Role of neutrophil elastase in compression-induced spinal cord injury in rats. Brain Res. 1998; 799(2):264-9. DOI: 10.1016/s0006-8993(98)00459-4. View

17.

Beattie M, Farooqui A, Bresnahan J . Review of current evidence for apoptosis after spinal cord injury. J Neurotrauma. 2000; 17(10):915-25. DOI: 10.1089/neu.2000.17.915. View

18.

Sun N, Chao C . The cytokine activity of HMGB1--extracellular escape of the nuclear protein. Chang Gung Med J. 2005; 28(10):673-82. View

19.

Agee J, Flanagan T, Blackbourne L, Kron I, Tribble C . Reducing postischemic paraplegia using conjugated superoxide dismutase. Ann Thorac Surg. 1991; 51(6):911-4; discussion 914-5. DOI: 10.1016/0003-4975(91)91004-f. View

20.

Klebanoff S, Vadas M, Harlan J, Sparks L, Gamble J, Agosti J . Stimulation of neutrophils by tumor necrosis factor. J Immunol. 1986; 136(11):4220-5. View