Madecassoside activates anti-neuroinflammatory mechanisms by inhibiting lipopolysaccharide-induced microglial inflammation

Neurodegeneration is typically preceded by neuroinflammation generated by the nervous system to protect itself from tissue damage, however, excess neuroinflammation may inadvertently cause more harm to the surrounding tissues. Attenuating neuroinflammation with non-steroidal anti-inflammatory drugs can inhibit neurodegeneration. However, such treatments induce chronic side effects, including stomach ulcers. Madecassoside, a triterpene derived from Centella asiatica, is considered to be an alternative treatment of inflammation. In the present study, the anti-neuroinflammatory properties of madecassoside were assessed in BV2 microglia cells, which were pre-treated with madecassoside at a maximum non-toxic dose (MNTD) of 9.50 g/ml and a 1/2 MNTD of 4.75 g/ml for 3 h and stimulated with 0.1 g/ml lipopolysaccharide (LPS). The effect of madecassoside was assessed by determining reactive oxygen species (ROS) levels in all groups. Furthermore, the expression of pro- and anti-neuroinflammatory genes and proteins were analyzed using reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. The results demonstrated that ROS levels in cells treated with the MNTD of madecassoside were significantly reduced compared with cells treated with LPS alone (P<0.05). The expression of pro-neuroinflammatory genes, including inducible nitric oxide synthase, cyclooxygenase-2, signal transducer and activator of transcription 1 and nuclear factor-B, were significantly downregulated in a dose-independent manner following treatment with madecassoside. Conversely, the anti-neuroinflammatory component heme oxygenase 1 was significantly upregulated by 175.22% in the MNTD-treated group, compared with cells treated with LPS alone (P<0.05). The gene expression profiles of pro- and anti-inflammatory genes were also consistent with the results of western blotting. The results of the present study suggest that madecassoside may be a potent anti-neuroinflammatory agent. The antioxidative properties of madecassoside, which serve a major role in anti-neuroinflammation, indicate that this compound may be a functional natural anti-neuroinflammatory agent, therefore, further in vivo or molecular studies are required.