Top

BMC Complementary Medicine and Therapies

Published in:

Open Access 01-12-2024 | Stroke | Research

Neuroprotective effects of methanolic extract from Chuanxiong Rhizoma in mice with middle cerebral artery occlusion-induced ischemic stroke: suppression of astrocyte- and microglia-related inflammatory response

Authors: Chiyeon Lim, Sehyun Lim, So-Jung Moon, Suin Cho

Published in: BMC Complementary Medicine and Therapies | Issue 1/2024

Abstract

Background

In traditional Asian medicine, dried rhizomes of Ligusticum chuanxiong Hort. (Chuanxiong Rhizoma [CR]) have long been used to treat pain disorders that affect the head and face such as headaches. Furthermore, they have been used primarily for blood circulation improvement or as an analgesic and anti-inflammatory medicine. This study aimed to investigate the neuroprotective effects of a methanol extract of CR (CRex) on ischemic stroke in mice caused by middle cerebral artery occlusion (MCAO).

Methods

C57BL/6 mice were given a 1.5-h transient MCAO (MCAO control and CRex groups); CRex was administered in the mice of the CRex group at 1,000–3,000 mg/kg either once (single dose) or twice (twice dose) before MCAO. The mechanism behind the neuroprotective effects of CRex was examined using the following techniques: brain infarction volume, edema, neurological deficit, novel object recognition test (NORT), forepaw grip strength, and immuno-fluorescence staining.

Results

Pretreating the mice with CRex once at 1,000 or 3,000 mg/kg and twice at 1,000 mg/kg 1 h before MCAO, brought about a significantly decrease in the infarction volumes. Furthermore, pretreating mice with CRex once at 3,000 mg/kg 1 h before MCAO significantly suppressed the reduction of forepaw grip strength of MCAO-induced mice. In the MCAO-induced group, preadministration of CRex inhibited the reduction in the discrimination ratio brought on by MCAO in a similar manner. CRex exhibited these effects by suppressing the activation of astrocytes and microglia, which regulated the inflammatory response.

Conclusions

This study proposes a novel development for the treatment of ischemic stroke and provides evidence favoring the use of L. chuanxiong rhizomes against ischemic stroke.

Available only for authorised users

Venkat P, Chopp M, Chen J. Models and mechanisms of vascular dementia. Exp Neurol. 2015;272:97–108. https://doi.org/10.1016/j.expneurol.2015.05.006.CrossRefPubMedPubMedCentral

Mittal SH, Goel D. Mortality in ischemic stroke score: a predictive score of mortality for acute ischemic stroke. Brain Circ. 2017;3(1):29–34. https://doi.org/10.4103/2394-8108.203256.CrossRefPubMedPubMedCentral

Shah B, Bartaula B, Adhikari J, Neupane HS, Shah BP, Poudel G. Predictors of in-hospital mortality of acute ischemic stroke in adult population. J Neurosci Rural Pract. 2017;8(4):591–4. https://doi.org/10.4103/jnrp.jnrp_265_17.CrossRefPubMedPubMedCentral

Hilbrich L, Truelsen T, Yusuf S. Stroke and cardiovascular diseases: the need for a global approach for prevention and drug development. Int J Stroke. 2007;2(2):104–8. https://doi.org/10.1111/j.1747-4949.2007.00118.x.CrossRefPubMed

Sims NR, Muyderman H. Mitochondria, oxidative metabolism and cell death in stroke. Biochim Biophys Acta. 2010;1802(1):80–91. https://doi.org/10.1016/j.bbadis.2009.09.003.CrossRefPubMed

Zhang Q, Fu X, Wang J, Yang M, Kong L. Treatment effects of ischemic stroke by berberine, baicalin, and jasminoidin from Huang-Lian-Jie-Du-Decoction (HLJDD) explored by an integrated metabolomics approach. Oxid Med Cel Longev. 2017;2017:9848594. https://doi.org/10.1155/2017/9848594.CrossRef

Prabhakaran S, Ruff I, Bernstein RA. Acute stroke intervention: a systematic review. JAMA. 2015;313(14):1451–62. https://doi.org/10.1001/jama.2015.3058.CrossRefPubMed

Li W, Tang Y, Chen Y, Duan J. Advances in the chemical analysis and biological activities of chuanxiong. Molecules. 2012;17(9):10614–51. https://doi.org/10.3390/molecules170910614.CrossRefPubMedPubMedCentral

Gao J, Chen G, He Q, Li J, Wang J. Analysis of Chinese patent medicine prescriptions for Qi stagnation and blood stasis syndrome. Zhongguo Zhong Yao Za Zhi. 2017;42(1):187–91. https://doi.org/10.19540/j.cnki.cjcmm.20161222.005.CrossRefPubMed

10.

Yang K, Zeng L, Ge A, Shi Y, Zhu X, Liu W, Ge J. The effect of Hedysarum multijugum Maxim.-Chuanxiong rhizoma compound on ischemic stroke: a research based on network and experimental pharmacology. Oxid Med Cell Longev. 2020;2020:6072380. https://doi.org/10.1155/2020/6072380.CrossRefPubMedPubMedCentral

11.

Zheng XW, Shan CS, Xu QQ, Wang Y, Shi Y, Wang Y, Zheng G. Buyang Huanwu decoction targets SIRT1/VEGF pathway to promote angiogenesis after cerebral ischemia/reperfusion injury. Front Neurosci. 2018;12:911. https://doi.org/10.3389/fnins.2018.00911.CrossRefPubMedPubMedCentral

12.

Or TCT, Yang CLH, Law AHY, Li JCB, Lau ASY. Isolation and identification of anti-inflammatory constituents from Ligusticum Chuanxiong and their underlying mechanisms of action on microglia. Neuropharmacology. 2011;60(6):823–31. https://doi.org/10.1016/j.neuropharm.2010.12.002.CrossRefPubMed

13.

Yu B, Yao Y, Zhang X, Ruan M, Zhang Z, Xu L, Liang T, Lu J. Synergic neuroprotection between Ligusticum Chuanxiong Hort and borneol against ischemic stroke by neurogenesis via modulating reactive astrogliosis and maintaining the blood-brain barrier. Front Pharmacol. 2021;12:666790.CrossRefPubMedPubMedCentral

14.

Zhang D, Peng R, Wang X, Zuo H, Lyu L, Yang F, Hu Y. A network pharmacology-based study on the quality control markers of antithrombotic herbs: using Salvia miltiorrhiza - Ligusticum chuanxiong as an example. J Ethnopharmacol. 2022;292:115197. https://doi.org/10.1016/j.jep.2022.115197.CrossRefPubMed

15.

Li B, Xu X, Wang X, Yu H, Li X, Tao W, Wang Y, Yang L. A systems biology approach to understanding the mechanisms of action of Chinese herbs for treatment of cardiovascular disease. Int J Mol Sci. 2012;13(10):13501–20. https://doi.org/10.3390/ijms131013501.CrossRefPubMedPubMedCentral

16.

Lopez MS, Vemuganti R. Modeling transient focal ischemic stroke in rodents by intraluminal filament method of middle cerebral artery occlusion. Methods Mol Biol. 2018;1717:101–13. https://doi.org/10.1007/978-1-4939-7526-6_9.CrossRefPubMed

17.

Biose IJ, Chastain WH, Wang H, Ouvrier B, Bix GJ. Optimizing intraluminal monofilament model of ischemic stroke in middle-aged Sprague-Dawley rats. BMC Neurosci. 2022;23(1):75. https://doi.org/10.1186/s12868-022-00764-2.CrossRefPubMedPubMedCentral

18.

Ru J, Li P, Wang J, Zhou W, Li B, Huang C, Li P, Guo Z, Tao W, Yang Y, Xu X, Li Y, Wang Y, Yang L. TCMSP: a database of systems pharmacology for drug discovery from herbal medicines. J Cheminform. 2014;6:13.CrossRefPubMedPubMedCentral

19.

Jiwa NS, Garrard P, Hainsworth AH. Experimental models of vascular dementia and vascular cognitive impairment: a systematic review. J Neurochem. 2010;115(4):814–28. https://doi.org/10.1111/j.1471-4159.2010.06958.x.CrossRefPubMed

20.

Lee S, Lim C, Lee M, Kim C, Kim H, Lee B, Cho S. Assessing neuroprotective effects of Glycyrrhizae Radix et rhizoma extract using a transient middle cerebral artery occlusion mouse model. J Vis Exp. 2018;142. https://doi.org/10.3791/58454.

21.

Zhang B, Zhang HX, Shi ST, Bai Y, Zhe X, Zhang S, Li Y. Interleukin-11 treatment protected against cerebral ischemia/reperfusion injury. Biomed Pharmacother. 2019;115:108816. https://doi.org/10.1016/j.biopha.2019.108816.CrossRefPubMed

22.

Ismael S, Zhao L, Nasoohi S, Ishrat T. Inhibition of the NLRP3-inflammasome as a potential approach for neuroprotection after stroke. Sci Rep. 2018;8(1):5971–x. https://doi.org/10.1038/s41598-018-24350-x.CrossRefPubMedPubMedCentral

23.

Denninger JK, Smith BM, Kirby ED. Novel object recognition and object location behavioral testing in mice on a budget. J Vis Exp. 2018;141. https://doi.org/10.3791/58593.

24.

Tahamtan M, Allahtavakoli M, Abbasnejad M, Roohbakhsh A, Taghipour Z, Taghavi M, Khodadadi H, Shamsizadeh A. Exercise preconditioning improves behavioral functions following transient cerebral ischemia induced by 4-vessel occlusion (4-VO) in rats. Arch Iran Med. 2013;16(12):697–704.PubMed

25.

Ludwin SK, Kosek JC, Eng LF. The topographical distribution of S-100 and GFA proteins in the adult rat brain: an immunohistochemical study using horseradish peroxidase-labelled antibodies. J Comp Neurol. 1976;165(2):197–207. https://doi.org/10.1002/cne.901650206.CrossRefPubMed

26.

Guo Z, Su Y, Lou H. GFAP-positive progenitor cell production is concentrated in specific encephalic regions in young adult mice. Neurosci Bull. 2018;34(5):769–78. https://doi.org/10.1007/s12264-018-0228-4.CrossRefPubMedPubMedCentral

27.

Liu Q, Bhuiyan MIH, Liu R, Song S, Begum G, Young CB, Foley LM, Chen F, Hitchens TK, Cao G, Chattopadhyay A, He L, Sun D. Attenuating vascular stenosis-induced astrogliosis preserves white matter integrity and cognitive function. J Neuroinflammation. 2021;18(1):187–8. https://doi.org/10.1186/s12974-021-02234-8.CrossRefPubMedPubMedCentral

28.

Su K, Su S, Ko C, Cheng Y, Huang S, Chao J. Ethnopharmacological survey of traditional Chinese medicine pharmacy prescriptions for dysmenorrhea. Front Pharmacol. 2021;12:746777. https://doi.org/10.3389/fphar.2021.746777.CrossRefPubMedPubMedCentral

29.

Du J, Xie X, Xiong L, Sun C, Peng C. Research progress of chemical constituents and pharmacological activities of essential oil of Ligusticum Chuanxiong. Zhongguo Zhong Yao Za Zhi. 2016;41(23):4328–33. https://doi.org/10.4268/cjcmm20162306.CrossRefPubMed

30.

Wang J, Wang L, Zhou H, Liang X, Zhang M, Tang Y, Wang J, Mao J. The isolation, structural features and biological activities of polysaccharide from Ligusticum Chuanxiong: a review. Carbohydr Polym. 2022;285:118971. https://doi.org/10.1016/j.carbpol.2021.118971.CrossRefPubMed

31.

Wang M, Yao M, Liu J, Takagi N, Yang B, Zhang M, Xu L, Ren J, Fan X, Tian F. Ligusticum Chuanxiong exerts neuroprotection by promoting adult neurogenesis and inhibiting inflammation in the hippocampus of ME cerebral ischemia rats. J Ethnopharmacol. 2020;249:112385.CrossRefPubMed

32.

Smith HK, Russell JM, Granger DN, Gavins FN. Critical differences between two classical surgical approaches for middle cerebral artery occlusion-induced stroke in mice. J Neurosci Methods. 2015;249:99–105. https://doi.org/10.1016/j.jneumeth.2015.04.008.CrossRefPubMed

33.

Bejot Y, Delpont B, Giroud M. Rising stroke incidence in young adults: more epidemiological evidence, more questions to be answered. J Am Heart Assoc. 2016;5(5):e003661.CrossRefPubMedPubMedCentral

34.

Poisson SN, Glidden D, Johnston SC, Fullerton HJ. Deaths from stroke in US young adults, 1989–2009. Neurology. 2014;83(23):2110–5. https://doi.org/10.1212/WNL.0000000000001042.CrossRefPubMedPubMedCentral

35.

Roth S, Liesz A. Stroke research at the crossroads - where are we heading? Swiss Med Wkly. 2016;146:w14329. https://doi.org/10.4414/smw.2016.14329.CrossRefPubMed

36.

Sander R. Prevention and treatment of acute ischaemic stroke. Nurs Older People. 2013;25(8):34–8. https://doi.org/10.7748/nop2013.10.25.8.34.e438.CrossRefPubMed

37.

Alberts MJ, Ovbiagele B. Current strategies for ischemic stroke prevention: role of multimodal combination therapies. J Neurol. 2007;254(10):1414–26. https://doi.org/10.1007/s00415-007-0569-9.CrossRefPubMed

38.

Shah FA, Li T, Kury LTA, Zeb A, Khatoon S, Liu G, Yang X, Liu F, Yao H, Khan A, Koh PO, Jiang Y, Li S. Pathological comparisons of the hippocampal changes in the transient and permanent middle cerebral artery occlusion rat models. Front Neurol. 2019;10:1178. https://doi.org/10.3389/fneur.2019.01178.CrossRefPubMedPubMedCentral

39.

Zhan C, Yang J. Protective effects of isoliquiritigenin in transient middle cerebral artery occlusion-induced focal cerebral ischemia in rats. Pharmacol Res. 2006;53(3):303–9. https://doi.org/10.1016/j.phrs.2005.12.008.CrossRefPubMed

40.

Emberson J, Lees KR, Lyden P, Blackwell L, Albers G, Bluhmki E, Brott T, Cohen G, Davis S, Donnan G, Grotta J, Howard G, Kaste M, Koga M, von Kummer R, Lansberg M, Lindley RI, Murray G, Olivot JM, Parsons M, Tilley B, Toni D, Toyoda K, Wahlgren N, Wardlaw J, Whiteley W, del Zoppo GJ, Baigent C, Sandercock P, Hacke W, et al. Stroke thrombolysis trialists’ Collaborative Group. Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet. 2014;384(9958):1929–35. https://doi.org/10.1016/S0140-6736(14)60584-5.CrossRefPubMedPubMedCentral

41.

Goyal M, Menon BK, van Zwam WH, Dippel DWJ, Mitchell PJ, Demchuk AM, Dávalos A, Majoie CBLM, van der Lugt A, de Miquel MA, Donnan GA, Roos YBWEM, Bonafe A, Jahan R, Diener H, van den Berg LA, Levy EI, Berkhemer OA, Pereira VM, Rempel J, Millán M, Davis SM, Roy D, Thornton J, Román LS, Ribó M, Beumer D, Stouch B, Brown S, Campbell BCV, van Oostenbrugge RJ, Saver JL, Hill MD, Jovin TG, HERMES collaborators. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet. 2016;387(10029):1723–31. https://doi.org/10.1016/S0140-6736(16)00163-X.CrossRefPubMed

42.

Kim JS. tPA helpers in the treatment of acute ischemic stroke: are they ready for clinical use? J Stroke. 2019;21(2):160–74. https://doi.org/10.5853/jos.2019.00584.CrossRefPubMedPubMedCentral

43.

Nair A, Morsy MA, Jacob S. Dose translation between laboratory animals and human in preclinical and clinical phases of drug development. Drug Dev Res. 2018;79(8):373–82. https://doi.org/10.1002/ddr.21461.CrossRefPubMed

44.

Bratina P, Rapp K, Barch C, Kongable G, Donnarumma R, Spilker J, Daley S, Braimah J, Sailor S. Pathophysiology and mechanisms of acute ischemic stroke. The NINDS rt-PA stroke Study Group. J Neurosci Nurs. 1997;29(6):356–60. https://doi.org/10.1097/01376517-199712000-00004.CrossRefPubMed

45.

Kasner SE, Grotta JC. Ischemic stroke. Neurol Clin. 1998;16(2):355–72. https://doi.org/10.1016/s0733-8619(05)70068-2.CrossRefPubMed

46.

Barlow SJ. Identifying the brain regions associated with acute spasticity in patients diagnosed with an ischemic stroke. Somatosens Mot Res. 2016;33(2):104–11. https://doi.org/10.1080/08990220.2016.1197114.CrossRefPubMed

47.

Cramer SC, Richards LG, Bernhardt J, Duncan P. Cognitive deficits after stroke. Stroke. 2023;54(1):5–9. https://doi.org/10.1161/STROKEAHA.122.041775.CrossRefPubMed

48.

Webb AJS, Werring DJ. New insights into cerebrovascular pathophysiology and hypertension. Stroke. 2022;53(4):1054–64. https://doi.org/10.1161/STROKEAHA.121.035850.CrossRefPubMedPubMedCentral

Title: Neuroprotective effects of methanolic extract from Chuanxiong Rhizoma in mice with middle cerebral artery occlusion-induced ischemic stroke: suppression of astrocyte- and microglia-related inflammatory response
Authors: Chiyeon Lim
Sehyun Lim
So-Jung Moon
Suin Cho
Publication date: 01-12-2024
Publisher: BioMed Central
Keyword: Stroke
Published in: BMC Complementary Medicine and Therapies / Issue 1/2024
Electronic ISSN: 2662-7671
DOI: https://doi.org/10.1186/s12906-024-04454-w

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Neuroprotective effects of methanolic extract from Chuanxiong Rhizoma in mice with middle cerebral artery occlusion-induced ischemic stroke: suppression of astrocyte- and microglia-related inflammatory response

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2024

Daoyin therapy in chronic neck pain: study protocol for a randomized controlled trial

In vitro antimicrobial and antibiofilm screening of eighteen Iranian medicinal plants

Cepharanthine synergistically promotes methylprednisolone pharmacodynamics against human peripheral blood mononuclear cells possibly via regulation of P-glycoprotein/glucocorticoid receptor translocation

Development and characterization of a topical gel, containing lavender (Lavandula angustifolia) oil loaded solid lipid nanoparticles

Retraction Note: Gastroprotective effect of desmosdumotin C isolated from Mitrella kentii against ethanol-induced gastric mucosal hemorrhage in rats: possible involvement of glutathione, heat-shock protein-70, sulfhydryl compounds, nitric oxide, and anti-Helicobacter pylori activity

Biochanin A abrogates osteoclastogenesis in type 2 diabetic osteoporosis via regulating ROS/MAPK signaling pathway based on integrating molecular docking and experimental validation