Anti-TNF monoclonal antibody, clone NQ7-YU33 [Pacific Blue™]

Pterodon pubescens fruits are popularly used because of their analgesic and anti-inflammatory actions, which are attributed to the isolated compounds with a vouacapan skeleton. This work aimed to evaluate the antiproliferative and anti-inflammatory effects of a P. pubescens fruit dichloromethane extract and the vouacapan diterpene furan isomers mixture (1:1) (6 alpha -hydroxy-7 beta -acetoxy-vouacapan-17 beta -oate methyl ester and 6 alpha -acetoxy-7 beta -hydroxy-vouacapan-17 beta -oate methyl ester isomers) in HaCaT cells using the cell migration and the BrDU incorporation assay. Levels of IL-8 were measured by ELISA after TNF- alpha stimulation. HPLC/DAD analysis of the extract revealed the expressive presence of vouacapan diterpene furan isomers mixture. P. pubescens extract (1.5625-25 mu g/mL) and vouacapan diterpene furan isomers mixture (3.125-50 mu M) inhibited cell proliferation as indicated by a decreased BrdU-incorporation. For the evaluation of cell migration, time-lapse microscopy was used. P. pubescens presented inhibition on cell migration at all concentrations tested (3.125-12.5 mu g/mL), whereas for the VDFI mixture, the inhibition was only observed at the highest concentrations (12.5 and 25 mu M) tested. Furthermore P. pubescens extract and vouacapan diterpene furan isomers mixture significantly decreased IL-8 levels. Our results showed antiproliferative and anti-inflammatory effects on HaCaT cells treated with the extract and the vouacapan isomers mixture, without affecting cell viability. These activities could be attributed to the voucapan molecular structures. In conclusion, topical products developed of P. pubescens extract or the voucapan isomers mixture should be further studied as a potential product for local treatment against hyperproliferative lesions as in psoriasis vulgaris, representing an alternative treatment approach.

Geniposide (GE) can effectively inhibit diabetic nephropathy (DN), but its mechanism is unclear. The objective of this study was to explore the antidiabetic nephropathy effects of GE both in high fat diet/streptozotocin-induced DN mice and in high glucose-induced podocyte model. Renal function in DN mice was evaluated by levels of serum creatinine (Scr) and blood urea nitrogen (BUN). Renal inflammation was appraised by pro-inflammatory cytokines: Tumor necrosis factor alpha (TNF-alpha), Interleukin 6 (IL-6) and IL-1 beta via ELISA assay. Renal histopathology analysis was conducted via hematoxylin and eosin, Masson and periodic acid-silver metheramine staining. Cellular viability was measured by Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay. Moreover, the related proteins p-NF-kappa B, ASC, Cleave-IL-1 beta, NLRP3, Cleave-Caspase-1 and GSDMD-N in AMPK/SIRT1/NF-kappa B pathway were assayed by Western blotting. In order to further investigate the effects of GE on podocytes, we also assessed these protein levels in AMPK/SIRT1/NF-kappa B pathway after siRNA-AMPK intervention by Western blotting. GE alleviated renal dysfunction as evidenced by decreased levels of Scr, BUN, TNF-alpha, IL-6 and IK-1 beta. Histological examination revealed GE effectively attenuated kidney damage, including glomerular basement membrane thickening and inflammatory cells infiltration. AMPK, p-AMPK and SIRT1 levels were obviously decreased both in DN mice and in podocyte model, but GE reversed these changes. The protein expressions in APMK/SIRT1/NF-kappa B pathway were significantly decreased by GE treatment. These results suggested that GE could efficiently block oxidative stress and inflammatory responses accompanied with pyroptosis, thus inhibiting the development of DN, and its mechanism might be related to APMK/SIRT1/NF-kappa B pathway.