Anti-inflammatory,Bacteriostatic and Anticancer Effects of Madecassoside

Madecassoside is a natural active component extracted from Centella asiatica.In recent years,a large number of studies have reported that madecassoside has a variety of biological activities,such as anticancer,anti-inflammatory and antibacterial effects,prevention and treatment of cardiovascular diseases,nerve damage,visceral damage and arthritis,and other pharmacological effects.In this paper,the pharmacological action and mechanism of madecassoside were reviewed to provide a theoretical basis for further research of madecassoside and drug development.

Confirmation of the Experimentally-Proven Therapeutic Utility of Madecassoside in an Aβ_1-42Infusion Rat Model of Alzheimer’s Disease by in Silico Analyses

The accumulation of amyloid β peptide 1 - 42 (Aβ1-42) in the brain of Alzheimer’s disease (AD) patients is known to be associated with neurodegeneration and memory impairment. More recently, we reported that madecassoside, an active component of Centella asiatica, improved memory impairment in an Aβ1-42 infusion rat model of AD, ameliorated neurotoxicity in SH-SY5Y cells, and inhibited in vitro Aβ1-42 fibril formation. In the present study, we investigated the utility of in silico analyses in corroborating observed in vivo and in vitro effects of madecassoside in AD to further assess the therapeutic benefits of madecassoside. The 3D structure of Aβ1-42 was downloaded from the Research Collaboratory for Structural Bioinformatics (RCSB) Protein Data Bank (PDB). The binding of madecassoside to Aβ1-42 was assessed by molecular docking. The chemical structure of madecassoside was modeled and converted to the PDB format. Madecassoside was found to successfully dock with Aβ1-42. Computational demonstration of the binding of madecassoside to Aβ1-42 further corroborated the inhibitory effect of madecassoside on Aβ1-42 fibrillogenesis which was demonstrated in our previous study. These data showed the potential utility of madecassoside as a preventive medication in Aβ1-42-induced neurodegenerative diseases such as AD.

Madecassoside impedes invasion of rheumatoid fibroblast-like synoviocyte from adjuvant arthritis rats via inhibition of NF-κB-mediated matrix metalloproteinase-13 expression

Fibroblast-like synoviocytes(FLS) play a pivotal role in Rheumatoid arthritis(RA) pathogenesis through aggressive migration and invasion. Madecassoside(Madec), a triterpenoid saponin present in Centella asiatica herbs, has a potent anti-inflammatory effect. In the present study, Madec exerted an obvious therapeutic effect in reversing the histological lesions in adjuvant-induced arthritis(AIA) rats. To recognize the anti-rheumatoid potentials of Madec, we further investigated whether Madec interfered with FLS invasion and metalloproteinase(MMP) expression. In cultures of primary FLS isolated from the AIA rats, Madec(10 and 30 μmol·L–1) was proven to considerably inhibit migration and invasion of FLS induced by interleukin 1β(IL-1β), but exhibiting no obvious effect on cell proliferation. Madec repressed IL-1β-triggered FLS invasion by prohibiting the expression of MMP-13. Additionally, Madec suppressed MMP-13 transcription via inhibiting the MMP-13 promoter-binding activity of NF-κB. Our results further showed that Madec down-regulated the translocation and phosphorylation of NF-κB as demonstrated by Western blotting and immunofluorescence assays. In conclusion, our results suggest that Madec exerts anti-RA activity via inhibiting the NF-κB/MMP-13 pathway.

A LC-ESI-MS method for the simultaneous determination of madecassoside and its metabolite madecassic acid in rat plasma: comparison pharmacokinetics in normal and collagen-induced arthritic rats

To develop a simple and highly sensitive high performance liquid chromatography with electrospray ionization mass spectrometric(LC-ESI-MS) method for the simultaneous determination of madecassoside and its major metabolite madecassic acid in rat plasma, and compare the pharmacokinetics of the two compounds in normal and collagen-induced arthritis(CIA) rats. Glycyrrhetinic acid was used as the internal standard(IS). Chromatographic separation was accomplished on an Inertsil ODS-3 column, using a gradient elution with the mobile phase composed of acetonitrile and water acidified with 0.1%(V/V) formic acid. Detection was achieved by ESI-MS under the negative selected ion monitoring(SIM) mode. In normal and CIA rats, madecassoside(30 mg·kg-1) was orally administered for 21 consecutive days from the day of arthritis onset. For madecassoside, the linear range was 10–1 000 ng·mL-1 with the square regression coefficient(r) of 0.998 9, while for madecassic acid, the linear range was 10–500 ng·mL-1 with the square regression coefficient(r) of 0.996 1. The lower limit of quantification was 10 ng·mL-1 for both analytes. The intra- and inter-day precision ranged from 1.78% to 13.42% for madecassoside and 2.30% to 14.90% for madecassic acid, and the accuracy was between –0.95% and 6.30% for madecassoside and between –1.48% and 5.34% for madecassic acid. The average recoveries of madecassoside, madecassic acid and IS from spiked plasma samples were > 81%. The developed method was successfully applied to the pharmacokinetic study of madecassoside and madecassic acid in rats after an oral administration of madecassoside. During initial 7 days of dosing, the cmax and AUC of madecassoside were greatly decreased and Vd/F was markedly increased in CIA rats, and no significant difference was observed on the first day of dosing. In contrast, the T1/2, cmax and AUC of madecassic acid were significantly increased, and Ke of madecassic acid was greatly decreased in CIA rats compared with normal rats. Along with repeated administration of madecassoside, the differences of pharmacokinetic parameters of both madecassoside and madecassic acid between CIA and normal rats gradually subsided. The pharmacokinetic characteristics of both madecassoside and madecassic acid in rats were significantly altered by arthritis status, and the differences of pharmacokinetic parameters between arthritis and normal rats coincide with the severity of arthritis.