Sesquiterpene lactones; Damsin and neoambrosin suppress cytokine-mediated inflammation in complete Freund's adjuvant rat model via shutting Akt/ERK1/2/STAT3 signaling.

ETHNOPHARMACOLOGIAL RELEVANCE: Although Damsissa (Ambrosia maritima) is traditionally used as anti-inflammatory and diuretic, the biological activity and mechanism of action of its major constituents are to be elucidated. AIM: to decipher the anti-arthritic potential of damsin (DMS) and neoambrosin (NMS) and to unfold their molecular signaling in complete Freund's adjuvant (CFA)-induced arthritis model. MATERIALS AND METHODS: the right hind paw was inoculated with CFA (0.1 ml) at day 0 and 7 while treatments were started from the 14th day and continued for 2 weeks. Rats were randomly assigned into 4 groups; normal group (NRML), CFA-induced arthritis group, CFA-induced arthritis treated with DMS and NMS (10 mg/kg/day) as 3rd and 4th group; respectively. RESULTS: Throughout experimental period, treatments ameliorated the increase of paw volume, knee joint diameter and nociception tests as reflected in open field arena. Also, DSM and NMS suppressed phosphorylation of Akt, STAT-3, ERK1/2 which was further mirrored by inactivation of GSK3ß and downregulation of MCP-1 together with CCN1 and NF-kß in hind paw tissue. Concomitantly, inflammation markers; TNF-α, IL-6, -12 were lowered as confirmed microscopically during examination of hind paw tissue. CONCLUSION: DSM and NMS-induced suppression of NF-kß subdues clinical features of RA most probably through repression of Akt/ERK1/2/STAT3 pathway. Therefore, DMS and NMS can serve as safe and effective treatment for rheumatoid arthritis, one of the most disabling chronic, inflammatory and painful autoimmune disease.

A New Flavonoid C-Glycoside from Celtis australis L. and Celtis occidentalis L. Leaves and Potential Antioxidant and Cytotoxic Activities.

A major development over the past two decades has been the realization that free radical induced lipid peroxidation and DNA damage are associated with major health problems, e.g. cancer and ageing. Plant-derived antioxidants are increasingly found beneficial in protecting against these diseases. Celtis australis L. and Celtis occidentalis L. are two plants that have a variety of uses in folk medicine but have not been evaluated before for their antioxidant and cytotoxic properties. Therefore, the extracts of both plants' leaves were investigated for these activities, as well as isolation of the bioactive compounds responsible for the activities. Molecular structures of the compounds were elucidated by UV, HRESIMS, 1D ((1)H and (13)C) and 2D ((1)H-(13)C HSQC and (1)H-(13)C HMBC) NMR analyses. The ethanolic and aqueous extracts, n-butanol fractions and the isolated major compound were tested for their antioxidant activity using DPPH radical scavenging assay, xanthine oxidase-induced generation of superoxide radical and lipid peroxidation assay by thiobarbituric acid-reactive substances (TBARS) method using rat tissue homogenates. Cytotoxic activities were studied using standard MTT assay. A novel flavonoid C-triglycoside, 4‴-α-rhamnopyranosyl-2″-O-ß-d-galactopyranosylvitexin, was isolated from both plants' leaves, together with seven known flavonoids. The n-butanol fractions and the major compound 2″-O-ß-galactopyranosylvitexin showed significant antioxidant activities, more pronounced than the tested standards BHT and dl-α-tocopherol in most tests. All extracts showed variable cytotoxic activities. This study provides strong evidence for the antioxidant and cytotoxic activities of the extracts of Celtis australis L. and Celtis occidentalis L. leaves, which were attributed to the polar n-butanol fractions and the major isolated flavonoid 2″-galactosylvitexin.