Therapeutic effect of various ginsenosides on rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease which causes disability and threatens the health of humans. Therefore, it is of great significance to seek novel effective drugs for RA. It has been reported that various ginsenoside monomers are able to treat RA. However, it is still unclear which ginsenoside is the most effective and has the potential to be developed into an anti-RA drug. METHODS: The ginsenosides, including Rg1, Rg3, Rg5, Rb1, Rh2 and CK, were evaluated and compared for their therapeutic effect on RA. In in vitro cell studies, methotrexate (MTX) and 0.05% dimethyl sulfoxide (DMSO) was set as a positive control group and a negative control group, respectively. LPS-induced RAW264.7 cells and TNF-α-induced HUVEC cells were cultured with MTX, DMSO and six ginsenosides, respectively. Cell proliferation was analyzed by MTT assay and cell apoptosis was carried out by flow cytometry. CIA mice model was developed to evaluate the therapeutic efficacy of ginsenosides. The analysis of histology, immunohistochemistry, flow cytometry and cytokine detections of the joint tissues were performed to elucidate the action mechanisms of ginsenosides. RESULTS: All six ginsenosides showed good therapeutic effect on acute arthritis compared with the negative control group, Ginsenoside CK provided the most effective treatment ability. It could significantly inhibit the proliferation and promote the apoptosis of RAW 264.7 and HUVEC cells, and substantially reduce the swelling, redness, functional impairment of joints and the pathological changes of CIA mice. Meanwhile, CK could increase CD8 + T cell to down-regulate the immune response, decrease the number of activated CD4 + T cell and proinflammatory M1-macrophages, thus resulting in the inhibition of the secretion of proinflammatory cytokine such as TNF-α and IL-6. CONCLUSION: Ginsenoside CK was proved to be a most potential candidate among the tested ginsenosides for the treatment of RA, with a strong anti-inflammation and immune modulating capabilities.

Enhanced anti-amnestic effect of donepezil by Ginkgo biloba extract (EGb 761) via further improvement in pro-cholinergic and antioxidative activities.

ETHNOPHARMACOLOGICAL RELEVANCE: EGb 761 is a standardized dry extract of Ginkgo biloba L. leaves traditionally used by Eastern Asia and has been associated with beneficial effects on neurodegeneration disorders, including Alzheimer's disease. AIM OF THE STUDY: Since beneficial interactions between EGb 761 and donepezil have been observed in previous clinical studies, the current study was proposed aiming to further explore related mechanisms from both pharmacokinetics and pharmacodynamics aspects. MATERIALS AND METHODS: Pharmacodynamic interactions were studied in scopolamine-induced cognitive impairment rats received two-weeks treatment of vehicle, EGb 761 and/or donepezil by the Morris water maze test and ex vivo evaluation of biomarkers of cholinergic transmission and oxidative stress in rat brain. In the meantime, pharmacokinetic profiles of donepezil and bilobalide were obtained and compared among all treatment groups. In addition, impact of the bioavailable EGb 761 components on donepezil brain penetration was evaluated with the hCMEC/D3 cell monolayer model. RESULTS: Scopolamine-induced rats with co-treatment of EGb 761 and donepezil had significantly improved cognitive function in the Morris water maze test with increased brain levels of superoxide dismutase and decreased brain levels of acetylcholinesterase and malondialdehyde than that with treatment of only EGb 761 or donepezil. Despite such beneficial pharmacodynamics outcomes, the two-week co-treatment of EGb 761 and donepezil did not alter the plasma pharmacokinetics and brain uptake of donepezil or bilobalide, which was further verified in the hCMEC/D3 monolayer model. CONCLUSION: Co-administration of EGb 761 and donepezil exerted better anti-amnestic effect via further enhanced pro-cholinergic and antioxidative effects of EGb 761 or donepezil in scopolamine-induced cognitive impairment rat without alteration in their systemic/brain exposure.