① Elamod showed anti-inflammatory and analgesic effects on both acute and chronic models of inflammation (e.g., rat keratan gum foot-plantar swelling model, adjuvant-induced arthritis model). ② Elamod, unlike conventional NSAIDs, did not show ulcer-like adverse effects in the digestive tract in fasted rats.

③ Elamod inhibited the increase in bradykinin

in kaolin-induced inflammatory response.

④ Elamod was similar to selective cyclooxygenase-2 (COX-2) in inhibiting the arachidonic acid cascade reaction, effectively inhibited the release of prostaglandins from fibroblasts in vitro, and reduced the amount of PGE2 in inflammatory secretions in a model of inflammatory response to foot and plantar swelling, without affecting PG levels in the gastrointestinal tract mucosa of the model rats. ① In mouse B-cell cultures, elamectin significantly reduced IgM production and isotype switching to IgG1 by induction of lipopolysaccharide and/or IL-4.

② In human plasmacytoma cell line culture (ARH-77 cell line), elamod inhibited spontaneous IgG antibody production but did not affect cell proliferation. ③ In human peripheral blood B cells induced by autologous T cells and anti-CD3 antibodies, elamod inhibited both IgM and IgG production.

④ Elamod inhibits immunoglobulin production in B cells but does not result in a blocking effect.

⑤ In experimental models of chronic rheumatoid disease (e.g., AIA rats and MRI/lpr rats), rheumatoid lesions improved with concomitant improvement in hyperimmunoglobulinemia. Elamod inhibits the production of IL-1β, TNFα, IL-6, IL-8, and MPC-1. In synoviocytes derived from human rheumatoid patients, elamectin significantly reduced the production of IL-6, IL-8, and colony-stimulating factor, and Kawakami found that elamectin inhibited the up-regulation of co-stimulatory molecules, including CD54, CD58, and CD106, in synoviocytes stimulated with IFN-γ.

The MCP-1 production induced by intravenous TNFα was significantly inhibited after oral administration of elamod at doses of 30-100 mg/kg in a rat model of subcutaneous airway inflammation. Elamod at concentrations of 10-30 mg/kg was able to reduce plasma levels of TNFα and IFN-γ, in addition to lowering aminotransferases in a murine model of hepatitis induced by cutanein A. Pro-inflammatory factors such as IL-1, IL-6, and TNF-α are key factors in the pathogenesis of RA and are closely related to RA disease activity. These pro-inflammatory factors also activate osteoclasts and promote bone resorption, leading to the occurrence of bone loss. Inhibition of IL-1, IL-6, TNF-α and other pro-inflammatory factors can have the dual effect of controlling RA and RA-induced bone loss.

In the CIA rat model, MRI test results showed that elamod could almost completely inhibit the inflammation and intramedullary edema of CIA; at the same time, the results of X-ray flat film and CT test showed that elamod could also significantly inhibit bone resorption and joint destruction. Elamod promoted osteoblast differentiation in in vitro assays and BMP-2-mediated bone formation in in vivo assays, an effect thought to be associated with increased Osx expression.

Osx plays a central role in bone differentiation and bone formation. In the bone marrow stromal cell line ST2 cells, Osx was barely expressed in the absence of rhBMP-2; in the presence of rhBMP-2, elamodulin-stimulated expression of Osx could be increased more than threefold. In MC3T3-E1 cells, the expression of Osx was not dependent on rhBMP-2, and elamectin was able to directly stimulate the expression of Osx and promote osteoblast differentiation.

Further studies revealed that elamod was able to dose-dependently stimulate osteocalcin secretion from ST2 and MC3T3-E1 cells; in the presence of rhBMP-2, it increased intracellular calcium content in ST2 cells by 14-fold, resulting in the formation of mineralized nodules; and in an in vivo model of mice, it increased the calcium content in auditory ossicles by 1.7-fold.