The novel arthritis-drug substance MCS-18 attenuates the antibody productionin vivo

Abstract

These findings suggest that MCS-18 could be a potent, non-toxic antagonist or a down-regulator of TLR signalling pathway. Investigations on further models are needed to establish ifMCS-18 may influence particularly the production of RA-specific auto-antibodies, too.

MCS-18, a novel natural product isolated from Helleborus purpurascens, inhibits dendritic cell activation and prevents autoimmunity as shown in vivo using the EAE model

“…The immunosuppressive in vivo activity of MCS-18 in the EAE model correlates very well with the observed suppressive in vitro activities on DC and T-cells as well as with the recently reported attenuation of the T-celldependent antibody production in vivo (Kerek et al, 2007).…”

“…In the first biological assays MCS-18 was described to induce significant in vitro up-regulation of the immune modulatory cytokines IL-10 and TGF-b (Szegli et al, 2005). In addition, it has recently been discovered that MCS-18 efficiently downregulates T-cell-dependent antibody formation in mice, where Toll-like-receptors (TLR) blockade might be involved (Kerek et al, 2007). These data correlate well with the traditional use of Helleborus in the Balkan region, where this medicinal plant has been used since ancient times, e.g.…”

“…In fact, recently it has been reported that, in mice, MCS-18 leads to a strong attenuation of antibody production (Kerek et al, 2007). As a putative mechanism the interference of MCS-18 with the signaling network of TLR has been suggested and experimentally underlined.…”

Natural compounds with important medical potential found in Helleborus sp.

“…MCS-18 leads to a strong attenuation of antibodies against tetanus toxoid if administered together with the Ab elicitor Freund's Complete or TLR antagonists in various combinations. These findings suggest that MCS-18 could be a potent, non-toxic antagonist or a down-regulator of the TLR signaling pathway [92]. MCS-18 proved to be a potent antagonist of the capsaicin activated vanilloid type pain receptors (TRPV1) and explains its local analgesic action [93].…”

MCS-18, a novel natural plant product prevents autoimmune diabetes

“…Furthermore, in vitro treatment with MCS-18 led to a modulation of murine DC and B-cells, which was accompanied by an impaired dysfunction of DC-maturation and immunoglobulin secretion [16]. In addition, MCS-18 also down-regulates T cell dependent murine antibody production in vivo [17]. First clinical trials have already been conducted in patients suffering from periarthritis-scapulo-humeralis (PHS), supporting the clinical safety and efficacy of MCS-18 in humans [18].…”