Effect of anemoside B4 on ameliorating cerebral ischemic/reperfusion injury

Document Type : Original Article

Authors

1 Medical college, Jiujiang University, Jiujiang, Jiangxi Province 332200, China

2 Department of Basic Medicine, Chongqing Three Gorges Medical College, Chongqing 404100, China

10.22038/ijbms.2024.78569.16991

Abstract

Objective(s): Anemoside B4 (AB4) is a multifunctional compound with anti-inflammatory, anti-apoptotic, antioxidant, antiviral, and autophagy-enhancing effects. However, the role of AB4 in cerebral ischemia/reperfusion injury (CIRI) remains obscure. This experiment aims to investigate the pharmacological effects of AB4 in CIRI.
Materials and Methods: In vivo, eighty male SD rats were randomly divided into five groups: sham, MCAO/R, LD group (2.5 mg/kg), MD group (5 mg/kg), and HD group (10 mg/kg). The rats in sham and MCAO/R groups were given equal volumes of normal saline. In vitro, PC12 cells were divided into five groups: normal, OGD/R, OGD/R+AB4 (50 μM), OGD/R+AB4 (100 μM), and OGD/R+AB4 (200 μM). The cells were treated with hypoxia and hypoglycemia for 1.5 hr and reoxygenation for 24 hr.
Results: In vivo, TTC and neurological scoring tests indicated that AB4 favors promoting the recovery of the brain. The histopathologic study of the brain tissues revealed that AB4 inhibited the damage of neuron cells. The TUNEL assay found that AB4 could improve cell apoptosis and prevent the brain from injury. In vitro, the data showed that AB4 inhibited cell damage and prevented PC12 cells from OGD/R injury, reduced IL-1β content, and increased the IL-10 level. AB4 could inhibit apoptosis of PC12 cells, down-regulate Caspase 12 and BAX expression, and up-regulate Bcl-2 expression.
Conclusion: AB4 played a protective role in CIRI and could be a promising active ingredient against ischemia stroke.

Keywords

Main Subjects

References

1. Mathias K, Machado RS, Stork S, Dos Santos D, Joaquim L, Generoso J, et al. Blood-brain barrier permeability in the ischemic stroke: An update. Microvasc Res 2024; 151:104621.
2. Liu X, Xie C, Wang Y, Xiang J, Chen L, Yuan J, et al. Ferritinophagy and ferroptosis in cerebral ischemia reperfusion injury. Neurochem Res 2024; 49: 1965-1979.
3. Zheng T, Jiang T, Huang Z, Ma H, Wang M. Role of traditional Chinese medicine monomers in cerebral ischemia/reperfusion injury: A review of the mechanism. Front Pharmacol 2023; 14: 1220862-1220881.
4. Zhao L, Li H, Gao Q, Xu J, Zhu Y, Zhai M, et al. Berberine attenuates cerebral ischemia-reperfusion injury induced neuronal apoptosis by down-regulating the CNPY2 signaling pathway. Front Pharmacol 2021; 12: 609693-609704.
5. Chen M, Liu M, Luo Y, Cao J, Zeng F, Yang L, et al. Celastrol protects against cerebral ischemia/reperfusion injury in mice by inhibiting glycolysis through targeting HIF-1alpha/PDK1 axis. Oxid Med Cell Longev 2022; 2022: 7420507-7420520.
6. Fu J, Yu L, Yu Q, Yu N, Xu F, Li S. Ginsenoside compound K reduces ischemia/reperfusion-induced neuronal apoptosis by inhibiting PTP1B-mediated IRS1 tyrosine dephosphorylation. J Ginseng Res 2023; 47: 274-282.
7. Tang Z, Yang G, Liao Z, Chen F, Chen S, Wang W, et al. Tanshinone IIA reduces AQP4 expression and astrocyte swelling after OGD/R by inhibiting the HMGB1/RAGE/NF-kappaB/IL-6 pro-inflammatory axis. Sci Rep 2022; 12: 14110-14121.
8. Xue R, Gao S, Zhang Y, Cui X, Mo W, Xu J, et al. A meta-analysis of resveratrol protects against cerebral ischemia/reperfusion injury: Evidence from rats studies and insight into molecular mechanisms. Front Pharmacol 2022; 13: 988836-988858.
9. Zhong J, Tan L, Chen M, He C. Pharmacological activities and molecular mechanisms of Pulsatilla saponins. Chin Med 2022; 17: 59-70.
10. Gao XD, Ye WC, Yu AC, Zhang Y, Tan RX, Li M, et al. Pulsatilloside A and anemoside A3 protect PC12 cells from apoptosis induced by sodium cyanide and glucose deprivation. Planta Med 2003; 69:171-174.
11. Peng Z, Li M, Tan X, Xiang P, Wang H, Luo Y, et al. MiR-211-5p alleviates focal cerebral ischemia-reperfusion injury in rats by down-regulating the expression of COX2. Biochem Pharmacol 2020; 177: 113983.
12. Mizuma A, Yenari MA. Anti-inflammatory targets for the treatment of reperfusion injury in stroke. Front Neurol 2017; 8: 467-476.
13. Jayaraj RL, Azimullah S, Beiram R, Jalal FY, Rosenberg GA. Neuroinflammation: Friend and foe for ischemic stroke. J Neuroinflammation 2019; 16: 142-155.
14. Petrovic-Djergovic D, Goonewardena SN, Pinsky DJ. Inflammatory Disequilibrium in Stroke. Circ Res 2016; 119:142-158.
15. Guo C, Yue Y, Wang B, Chen S, Li D, Zhen F, et al. Anemoside B4 alleviates arthritis pain via suppressing ferroptosis-mediated inflammation. J Cell Mol Med 2024; 28: e18136-18149.
16. He L, Zhang Y, Kang N, Wang Y, Zhang Z, Zha Z, et al. Anemoside B4 attenuates nephrotoxicity of cisplatin without reducing anti-tumor activity of cisplatin. Phytomedicine 2019; 56:136-146.
17. Ma H, Zhou Z, Chen L, Wang L, Muge Q. Anemoside B4 prevents chronic obstructive pulmonary disease through alleviating cigarette smoke-induced inflammatory response and airway epithelial hyperplasia. Phytomedicine 2022; 107: 154431.
18. Yuan R, He J, Huang L, Du LJ, Gao H, Xu Q, et al. Anemoside B4 protects against acute lung injury by attenuating inflammation through blocking NLRP3 inflammasome activation and TLR4 dimerization. J Immunol Res 2020; 2020: 7502301-7502313.
19. Hollville E, Romero SE, Deshmukh M. Apoptotic cell death regulation in neurons. FEBS J 2019; 286: 3276-3298.
20. Wong FK, Marin O. Developmental cell death in the cerebral cortex. Annu Rev Cell Dev Biol 2019; 35: 523-542.
21. Cheng K, Wang Z, Bai J, Xiong J, Chen J, Ni J. Research advances in the application of vagus nerve electrical stimulation in ischemic stroke. Front Neurosci 2022; 16: 1043446-1043458.
22. Yuan J, Najafov A, Py BF. Roles of caspases in necrotic cell death. Cell 2016; 167:1693-1704.
23. Shimoke K, Matsuki Y, Fukunaga K, Matsumura Y, Fujita E, Sugihara K, et al. Appearance of nuclear-sorted caspase-12 fragments in cerebral cortical and hippocampal neurons in rats damaged by autologous blood clot embolic brain infarctions. Cell Mol Neurobiol 2011; 31:795-802.
24. Siddiqui WA, Ahad A, Ahsan H. The mystery of BCL2 family: Bcl-2 proteins and apoptosis: An update. Arch Toxicol 2015; 89: 289-317.
25. McCabe C, Arroja MM, Reid E, Macrae IM. Animal models of ischaemic stroke and characterisation of the ischaemic penumbra. Neuropharmacology 2018; 134:169-177.
26. Huo K, Xu J, Wei M, Ma K, Wang J, Han J. Solasonine ameliorates cerebral ischemia-reperfusion injury via suppressing TLR4/MyD88/NF-kappaB pathway and activating AMPK/Nrf2/HO-1 pathway. Int Immunopharmacol 2023; 124:110862.
27. Zhou S, Gao X, Chen C, Zhang J, Zhang Y, Zhang L, et al. Porcine cardiac blood - Salvia miltiorrhiza root alleviates cerebral ischemia reperfusion injury by inhibiting oxidative stress induced apoptosis through PI3K/AKT/Bcl-2/Bax signaling pathway. J Ethnopharmacol 2023; 316:116698.
28. Pei L, He L. Hepatoprotective effect of anemoside B4 against sepsis-induced acute liver injury through modulating the mTOR/p70S6K-mediated autophagy. Chem Biol Interact 2021; 345:109534.
29. Zhang Y, Zha Z, Shen W, Li D, Kang N, Chen Z, et al. Anemoside B4 ameliorates TNBS-induced colitis through S100A9/MAPK/NF-kappaB signaling pathway. Chin Med 2021; 16: 11-26.
30. Li YH, Zou M, Han Q, Deng LR, Weinshilboum RM. Therapeutic potential of triterpenoid saponin anemoside B4 from Pulsatilla chinensis. Pharmacol Res 2020; 160:105079.
31. Hu Y, Chen X, Duan H, Hu Y, Mu X. Chinese herbal medicinal ingredients inhibit secretion of IL-6, IL-8, E-selectin and TXB2 in LPS-induced rat intestinal microvascular endothelial cells. Immunopharmacol Immunotoxicol 2009; 31: 550-555.
32. Hu Y, Chen X, Duan H, Hu Y, Mu X. Pulsatilla decoction and its active ingredients inhibit secretion of NO, ET-1, TNF-alpha, and IL-1 alpha in LPS-induced rat intestinal microvascular endothelial cells. Cell Biochem Funct 2009; 27:284-288.
33. Gong Q, Wang M, Jiang Y, Zha C, Yu D, Lei F, et al. The abrupt pathological deterioration of cisplatin-induced acute kidney injury: Emerging of a critical time point. Pharmacol Res Perspect 2021; 9:e00895-905.
34. Han Q, Deng LR, Zou M, Tang HZ, Huang CY, Chen FJ, et al. Anemoside B4 protects against chronic relapsing colitis in mice by modulating inflammatory response, colonic transcriptome and the gut microbiota. Phytomedicine 2022; 106:154416.
35. Ma H, Zhou M, Duan W, Chen L, Wang L, Liu P. Anemoside B4 prevents acute ulcerative colitis through inhibiting of TLR4/NF-kappaB/MAPK signaling pathway. Int Immunopharmacol 2020; 87:106794-106805.
36. Li J, Zuo SS, Qiu XX, He LL, Wang ML, Feng YL, et al. [Study on therapeutic effect and its related mechanism of anemoside B4 on ischemia reperfusion injury induced by renal artery and vein ligation in rats]. Zhongguo Zhong Yao Za Zhi 2020; 45: 617-622.
Iranian Journal of Basic Medical Sciences
Volume 28, Issue 1
January 2025
Pages 49-55

Files

Share

How to cite

Statistics