Open Access

Peer-reviewed

Research Article

Main Article Content

Yunqi Yang
Tian Wang
Shumin Yue
Mingan Li
Lin Zhou
Fenghua Fucorresponding author

Abstract

Stroke is a devastating disease, intracerebral hemorrhage (ICH) is a devastating subtype. This study aimed to investigate whether cholinergic receptors participate in the process of Angong Niuhuang Pill (ANP) improving neurological function and relieving intestinal injury in ICH mice. The mice were treated with ANP, cholinergic receptor blockers, atropine (ATR), penehyclidine hydrochloride (PHC) or methyllycaconitine (MLA). Male CD-1 mice were randomly divided into 9 groups, Sham, ICH, ANP (0.2 g/kg), ANP plus ATR, ANP plus PHC, ANP plus MLA, ATR, PHC, MLA. ICH model is made by collagenase Ⅶ injection (0.075 U). ANP (0.2 g/kg) was administered by gavage after 30 min of ICH. MLA, ATR, PHC was given at 15 min after ICH. Neurological function was evaluated by Garcia test. Intestinal injury was observed by histological analysis. Endotoxin (ET) was measured by enzyme-linked immunosorbent assay. Compared to the Sham group, the score of Garcia test in the ICH significantly decreased. ANP increased significantly the score of ICH mice. ANP also ameliorated the intestinal injury caused by ICH. Cholinergic receptor blockers reversed partially the improvement of neurological function and intestinal injury by ANP. ANP attenuates the neurological deficits and intestinal injury in ICH mice and the protective effect of ANP may be involved in the regulation of the cholinergic system.

Keywords
Angong Niuhuang pill, intracerebral hemorrhage, neurological function, intestinal injury, cholinergic receptors

Article Details

Supporting Agencies
This work was supported by National Natural Science Foundation of China (No. 81873039).
How to Cite
Yang, Y., Wang, T., Yue, S., Li, M., Zhou, L., & Fu, F. (2021). Cholinergic receptor blockers affect the protective effect of Angong Niuhuang pill on neurologic deficits and intestinal injury in intracerebral hemorrhage mice. Journal of Pharmaceutical and Biopharmaceutical Research, 2(2), 153-160. https://doi.org/10.25082/JPBR.2020.02.002

References

  1. Van Asch CJJ, Luitse MJA, Rinkel GJE, et al. Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: a systematic review and meta-analysis. The Lancet Neurology, 2010, 9(2): 167-176. https://doi.org/10.1016/s1474-4422(09)70340-0
  2. Zhou M, Wang H, Zeng X, et al. Mortality, morbidity, and risk factors in China and its provinces, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. The Lancet, 2019, 394(10204): 1145-1158. https://doi.org/10.1016/s0140-6736(19)30427-1
  3. Wang J, Zhang X, Yang C, et al. Effect of monoacylglycerol lipase inhibition on intestinal permeability in chronic stress model. Biochemical and Biophysical Research Communications, 2020, 525(4): 962- 967. https://doi.org/10.1016/j.bbrc.2020.02.173
  4. Ji R, Shen H, Pan Y, et al. A novel risk score to predict 1-year functional outcome after intracerebral hemorrhage and comparison with existing scores. Critical Care (London, England), 2013, 17(6): R275. https://doi.org/10.1186/cc13130
  5. Hannawi Y, Hannawi B, Rao CP, et al. Stroke-associated pneumonia: major advances and obstacles. Cerebrovascular Diseases (Basel, Switzerland), 2013, 35(5): 430-443. https://doi.org/10.1159/000350199
  6. Poon MT, Fonville AF and Al-Shahi Salman R. Long-term prognosis after intracerebral haemorrhage: systematic review and meta-analysis. Journal of Neurology, Neurosurgery, and Psychiatry, 2014, 85(6): 660-667. https://doi.org/10.1136/jnnp-2013-306476
  7. Flaherty ML, Haverbusch M, Sekar P, et al. Long-term mortality after intracerebral hemorrhage. Neurology, 2006, 66(8): 1182-1186. https://doi.org/10.1212/01.wnl.0000208400.08722.7c
  8. Kalaria RN, Akinyemi R and Ihara M. Stroke injury, cognitive impairment and vascular dementia. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2016, 1862(5): 915-925. https://doi.org/10.1016/j.bbadis.2016.01.015
  9. Iglesias-Rey R, Rodr´ıguez-Y´a˜nez M, Arias S, et al. Inflammation, edema and poor outcome are associated with hyperthermia in hypertensive intracerebral hemorrhages. European Journal of Neurology, 2018, 25(9): 1161-1168. https://doi.org/10.1111/ene.13677
  10. Zhou Y, Wang Y, Wang J, et al. Inflammation in intracerebral hemorrhage: from mechanisms to clinical translation. Progress in Neurobiology, 2014, 115: 25-44. https://doi.org/10.1016/j.pneurobio.2013.11.003
  11. De Raedt S, De Vos A and De Keyser J. Autonomic dysfunction in acute ischemic stroke: an underexplored therapeutic area? Journal of the Neurological Sciences, 2015, 348(1-2): 24-34. https://doi.org/10.1016/j.jns.2014.12.007
  12. Shoup JP, Winkler J, Czap A, et al. beta-Blockers associated with no class-specific survival benefit in acute intracerebral hemorrhage. Journal of the Neurological Sciences, 2014, 336(1-2): 127-131. https://doi.org/10.1016/j.jns.2013.10.022
  13. Borovikova LV, Ivanova S, Zhang M, et al. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature, 2000, 405(6785): 458-462.
  14. Wang H, Yu M, Ochani M, et al. Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature, 2003, 421(6921): 384-388.
  15. Swor DE, Thomas LF, Maas MB, et al. Admission Heart Rate Variability is Associated with Fever Development in Patients with Intracerebral Hemorrhage. Neurocritical Care, 2019, 30(2): 244-250. https://doi.org/10.1007/s12028-019-00684-w
  16. Fern´andez-Cabezudo MJ, George JA, Bashir G, et al. Involvement of Acetylcholine Receptors in Cholinergic Pathway-Mediated Protection Against Autoimmune Diabetes. Frontiers in Immunology, 2019, 10: 1038. https://doi.org/10.3389/fimmu.2019.01038
  17. Zhang J, Zhang L, Sun X, et al. Acetylcholinesterase Inhibitors for Alzheimer’s Disease Treatment Ameliorate Acetaminophen-Induced Liver Injury in Mice via Central Cholinergic System Regulation. The Journal of Pharmacology and Experimental Therapeutics, 2016, 359(2): 374-382. https://doi.org/10.1124/jpet.116.233841
  18. Zhao L, Peng F, Guan B, et al. Whether Metal Element-Containing Herbal Formula Angong Niuhuang Pill Is Safe for Acute Brain Disorders? Biological Trace Element Research, 2015, 166(1): 41-48. https://doi.org/10.1007/s12011-015-0318-3
  19. Guo Y, Yan S, Xu L, et al. Use of angong niuhuang in treating central nervous system diseases and related research. Evidence-based Complementary and Alternative Medicine, 2014: 346918. https://doi.org/10.1155/2014/346918
  20. Liu H, Yan Y, Pang P, et al. Angong Niuhuang Pill as adjuvant therapy for treating acute cerebral infarction and intracerebral hemorrhage: A meta-analysis of randomized controlled trials. Journal of Ethnopharmacology, 2019, 237: 307-313. https://doi.org/10.1016/j.jep.2019.03.043
  21. Wu S, Lv H, Wang W, et al. Effects of Angong Niuhuang Pill on intestinal mucosal barrierin intracerebral hemorrhage mice. Pharmacology and Clinics of ChineseMateria Medica. 2018, 34(01):6- 10.
  22. Klebe D, Iniaghe L, Burchell S, et al. Intracerebral Hemorrhage in Mice. Methods in Molecular Biology (Clifton, N.J.), 2018, 1717: 83-91. https://doi.org/10.1007/978-1-4939-7526-6_7
  23. Garcia JH, Wagner S, Liu KF, et al. Neurological deficit and extent of neuronal necrosis attributable to middle cerebral artery occlusion in rats. Statistical validation. Stroke, 1995, 26(4): 627-635. https://doi.org/10.1161/01.str.26.4.627
  24. Novosad VL, Richards JL, Phillips NA, et al. Regional susceptibility to stress-induced intestinal injury in the mouse. American Journal of Physiology-Gastrointestinal and Liver Physiology, 2013, 305(6): G418-G426. https://doi.org/10.1152/ajpgi.00166.2013
  25. Stanley D, Mason LJ, Mackin KE, et al. Translocation and dissemination of commensal bacteria in post-stroke infection. Nature Medicine, 2016, 22(11): 1277-1284. https://doi.org/10.1038/nm.4194
  26. Cheng Y, Zan J, Song Y, et al. Evaluation of intestinal injury, inflammatory response and oxidative stress following intracerebral hemorrhage in mice. International Journal of Molecular Medicine, 2018, 42(4): 2120-2128. https://doi.org/10.3892/ijmm.2018.3755
  27. Klingensmith NJ, Coopersmith CM. The Gut as the Motor of Multiple Organ Dysfunction in Critical Illness. Critical Care Clinics, 2016, 32(2): 203-212. https://doi.org/10.1016/j.ccc.2015.11.004
  28. Lebois EP, Thorn C, Edgerton JR, et al. Muscarinic receptor subtype distribution in the central nervous system and relevance to aging and Alzheimer’s disease. Neuropharmacology, 2018, 136(Part C): 362-373. https://doi.org/10.1016/j.neuropharm.2017.11.018
  29. Saternos HC, Almarghalani DA, Gibson HM, et al. Distribution and function of the muscarinic receptor subtypes in the cardiovascular system. Physiological Genomics, 2018, 50(1): 1-9. https://doi.org/10.1152/physiolgenomics.00062.2017
  30. Tangsucharit P, Takatori S, Zamami Y, et al. Muscarinic acetylcholine receptor M1 and M3 subtypes mediate acetylcholine-induced endothelium-independent vasodilatation in rat mesenteric arteries. Journal of Pharmacological Sciences, 2016, 130(1): 24-32. https://doi.org/10.1016/j.jphs.2015.12.005
  31. Wang Y, Lin D, Tan H, et al. Penehyclidine hydrochloride preconditioning provides pulmonary and systemic protection in a rat model of lung ischaemia reperfusion injury. European Journal of Pharmacology, 2018, 839: 1-11. https://doi.org/10.1016/j.ejphar.2018.09.012
  32. Liu Z, Wen G, Hua W, et al. Comparision of the effect of penehyclidine hydrochloride and atropine on gastrointestinal hormone in mice. Journal of Clinical Anesthesiology, 2012, 28(07): 25-44.
  33. Shu Y, Yang Y and Zhang P. Neuroprotective effects of penehyclidine hydrochloride against cerebral ischemia/reperfusion injury in mice. Brain Research Bulletin, 2016, 121: 115-123. https://doi.org/10.1016/j.brainresbull.2016.01.008
  34. Singleton KD and Wischmeyer PE. Oral glutamine enhances heat shock protein expression and improves survival following hyperthermia. Shock. 2006, 25(3): 295-299. https://doi.org/10.1097/01.shk.0000196548.10634.02
  35. Sun J, Li F, Chen J, et al. Effect of ketamine on NF-kappa B activity and TNF-alpha production in endotoxin-treated rats. Annals of Clinical and Laboratory Science, 2004, 34(2): 181-186.
  36. Bahramabadi R, Fathollahi MS, Hashemi SM, et al. Serum Levels of IL-6, IL-8, TNF-α, and TGF-β in Chronic HBV-Infected Patients: Effect of Depression and Anxiety. Laboratory Medicine, 2017, 49(1): 41-46. https://doi.org/10.1093/labmed/lmx064
  37. Lopes PC. LPS and neuroinflammation: a matter of timing. Inflammopharmacology, 2016, 24(5): 291-293. https://doi.org/10.1007/s10787-016-0283-2