Protective Effects And Mechanisms Of Asiaticoside And Mangineferin On The Spinal Cord Injury In Rats

Background: The pathological process of Spinal Cord Injury(SCI)comprises primary injury and secondary injury,with the former an irreversible injury in direct response to violence,and the latter a series of physiological and biochemical reactions such as ischemia,edema,electrolyte disturbances which follow the primary injury.Both hypoxia-ischemia and inflammation can cause the production and release of Reactive Oxygen Species(ROS),and the massive accumulation of ROS leads to the oxidative injury of local tissues,as well as the apoptosis and necrosis of neurons.Therefore,it has long been a research focus to find effective drugs for the prevention of secondary apoptosis of spinal cord neurons.Asiaticoside(AS)are the main active ingredients in Centella asiatica.The clinical treatment is mainly used in the treatment of skin injury,wound healing,scar repair,etc.In recent years,it has been found that total triterpenes of C.asiatica and its main monomer components have many pharmacological activities on the nervous system,such as anti-depression,anti-dementia,protection of spinal cord injury and spinal cord nerve cell degeneration,anti-brain ischemia injury,analgesia,anti-seizure,etc.This paper gives an overview of research progress of the pharmacological effects of the C.asiatica compound on the nervous system,hoping to provide a theoretical basis for the research and application of this compound in the treatment of nervous system diseases and new drug development.Asiaticoside has potent pharmacological activity and broader pharmacological effects,including anti-oxidant,antidepressant and hepatic protection effects,and the inhibition of tumor cell proliferation.However,the mechanism underlying the effects of asiaticoside on neurological pain in spinal cord injury(SCI)remain to be fully elucidated.Mangiferin(MAG)is one such naturally occurring polyphenol that is widely found in many herbs such as Mangifera indica L and Anemarrhena asphodeloides Bunge.In the mangiferin molecule,four aromatic hydroxyl groups determine its strong antiradical and antioxidant properties.Numerous published in vitro and in vivo studies about mangiferin,demonstrated many pharmacological activities on inflammation,oxidative stress,tumor growth,microorganism infections,metabolic regulations,immune regulations,and radioprotection.The neuroprotective role of naturally occurring mangiferin has recently been a focus of attention.Mangiferin has antioxidant,antiviral,apoptosis regulating,anti?inflammatory,antitumor and antidiabetic effects,which can also inhibit osteoclast formation and bone resorption.However,whether mangiferin ameliorates the neurological pain of spinal cord injury(SCI)in rat S remains to be elucidated.Objective: To study the effects of Asiaticoside and Mangiferin,we use the model of acute spinal cord injury in rats to explore its possible protective mechanisms,and to provide a theoretical basis of AS for the treatment of SCI.Methods:(1)The 75 male Sprague-Dawley rats were randomly assigned into five groups.The sham group(n=15),received only physiological saline(0.1 ml/100 g,intraperitoneally).The SCI group(n=15)received no treatment following SCI,the ASI(30)group(n=15)received asiaticoside at doses of 30 mg/kg once a day for 7 days following SCI(15),the ASI(60)group(n=15)received asiaticoside at a dose of 60 mg/kg once a day for 7 days following SCI,the MPSS group(n=15)received 100 mg/kg MPSS following SCI.Following SCI,the evaluation of locomotor recovery was evaluated using the Basso,Beattie and Bresnahan(BBB).The water content of the spinal cord was also determined to measure its effects on the SCI rats.Following treatment with asiaticoside for seven consecutive days,the serum levels of MDA,SOD,GSH,GSH-PX,i NOS,NF-?B p65,TNF-?,IL-1??IL-6 and p38-MAPK were analyzed.(2)All rats were randomly divided into five groups: control group(Con;n=15),in which normal rats that received physiological saline(0.1 ml/100 g,i.p.)once a day for 30 days;SCI group(SCI;n=15),in which the SCI rats received physiological saline(0.1 ml/100 g,i.p.)once a day for 30 days;MPSS group(n=15),in which SCI rats were treated with 100 mg/kg MPSS(i.p.)once a day for 30 days;mangiferin group(MAN 20;n=15),in which SCI rats were treated with mangiferin at a dose of 20 mg/kg once a day for 30 days;mangiferin group(MAN 40;n=15),in which SCI rats were treated with mangiferin at a dose of 40 mg/kg once a day for 30 days.Following SCI,the evaluation of locomotor recovery was evaluated using the Basso,Beattie and Bresnahan(BBB).The water content of the spinal cord was also determined to measure its effects on the SCI rats.Following treatment with mangiferin for 30 consecutive days,the serum levels of MDA,CAT,SOD,GSH-PX,NF-?B p65,TNF-?,IL-1?,IL-6,Bcl-2,Bax,caspase-3 and caspase-9 were analyzed.Results: Asiaticoside and mangiferin could reduce the water content of injured spinal cord and improve the BBB score of SCI rat model.Asiaticoside and mangiferin could decrease the expression of MDA,i NOS NF-?B,TNF-?,IL-1? and IL-6 and increase the expression of SOD,GSH,CAT and GSH-PX.Asiaticoside also could suppressed the expression of p38-MAPK.In addition,mangiferin significantly reduced the protein expression of Bax and promoted the protein expression of Bcl-2 in the SCI rat model.Finally,mangiferin markedly suppressed the expression of caspase-3/9.Conclusion: Asiaticoside attenuates SCI through antioxidant and anti-inflammatory effects,and through inhibition of the p38-MAPK mechanism.Mangiferin attenuated contusive SCI in the rats through regulating oxidative stress,inflammation and the Bcl-2 and Bax pathway.