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

Abstract

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 µg/ml and a ½ MNTD of 4.75 µg/ml for 3 h and stimulated with 0.1 µg/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‑κB, 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.

Inhibitory Effects of Raw-Extract Centella asiatica (RECA) on Acetylcholinesterase, Inflammations, and Oxidative Stress Activities via In Vitro and In Vivo

“…These inhibitory effects were associated with the reduction of ROS level and stimulation of GSH content, indicating the role of RECA in oxidative balance. A study done by Sasmita et al [56] indicated that cells treated with the madecassoside at a maximum non-toxic dose (MNTD) were able to suppress the intracellular ROS generations by downregulating the gene and protein expression of pro-neuroinflammatory components. Therefore, the antioxidative properties observed in RECA could be attributed to the high proportion of madecassoside in the extract.…”

Madecassoside Protects Against LPS-Induced Acute Lung Injury via Inhibiting TLR4/NF-κB Activation and Blood-Air Barrier Permeability

“…Evidence showed that MA prevented the releases of proinflammatory cytokines by repressing the activation of MAPK and NF-kB signaling pathway and enhancing the expression of heme oxygenase-1 (HO-1) and nuclear factor E2related factor 2 (Nrf2) during LPS/D-GalN-induced liver injury (Wang et al, 2018). Other reports also demonstrated that MA had antineuroinflammatory effects and concentrationdependently restrained the expression of proinflammatory cytokines, nitric oxide synthase, cyclooxygenase-2, and nuclear factor kappa-B (NF-kB) pathway induced by LPS (Sasmita et al, 2018). Moreover, Cao et al also proved that MA prevented the LPS-induced sepsis and the protective mechanisms were associated with inhibiting inflammatory response induced by LPS (Cao et al, 2010).…”

Madecassoside protects retinal pigment epithelial cells against hydrogen peroxide-induced oxidative stress and apoptosis through the activation of Nrf2/HO-1 pathway

“…Madecassoside (MADE) is a major bioactive triterpenoid saponin isolated from Centella asiatica that has been found to exert various pharmacological activities including antioxidative effect [ 10–12 ]. MADE was reported to have the reactive oxygen species (ROS) scavenging activity [ 11 , 13 ]. MADE exerts protective effect on hydrogen peroxide (H 2 O 2 )-induced oxidative stress and autophagy in human melanocytes [ 10 ].…”