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l-Proline-based-cyclic Dipeptides From Pseudomonas Sp. (ABS-36) Inhibit Pro-Inflammatory Cytokines and Alleviate Crystal-Induced Renal Injury in Mice

Sajeli Begum Ahil, Kirti Hira, Ameer Basha Shaik, Pragya Paramita Pal, Onkar Prakash Kulkarni, Hiroshi Araya, Yoshinori Fujimoto

Int Immunopharmacol. 2019 Aug;73:395-404.

PMID: 31151077

Abstract:

Study on the constituents of bioactive culture broth extract (CBE) of Pseudomonas sp. (ABS-36) explored the secretion of an array of cyclic dipeptides (CDPs) and twenty of them had been isolated and reported in the present paper. Six major CDPs [(cyclo(Leu-Pro) (1), cyclo(Val-Pro) (2), cyclo(Leu-hydroxy-Pro) (9), cyclo(Pro-Tyr) (10), cyclo(Pro-Ala) (11) and cyclo(Gly-Pro) (12)] exhibited pan cytokine inhibition effect by inhibiting key pro-inflammatory cytokines IL-1β, TNF-α and IL-6 tested under various cell based assays. With this background, the effect of these six CDPs in treating renal inflammation was screened using crystal-induced nephropathy model in mice at 50 mg/kg body weight through oral administration. cis-Cyclo(Val-Pro) (2) exhibited 57% inhibition of plasma IL-1β protein expression and 35.2% inhibition of elevated blood urea nitrogen. Further, cis-cyclo(Val-Pro) (2) attenuated renal injury as demonstrated by significant reduction of mRNA expressions of IL-1β (P < 0.01) and kidney injury marker-1 (P < 0.001). Furthermore, evaluation of tubular-necrosis, -dilation and -cast in the histological sections exhibited moderate protection of renal tissues by cis-cyclo(Val-Pro) (2). All the tested CDPs reduced the nitrite production and were interestingly non-cytotoxic.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP3705279 Cyclo-Gly-Pro Cyclo-Gly-Pro 3705-27-9 Price
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