1. l-Proline-based-cyclic dipeptides from Pseudomonas sp. (ABS-36) inhibit pro-inflammatory cytokines and alleviate crystal-induced renal injury in mice
- Author
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Yoshinori Fujimoto, Sajeli Begum Ahil, Hiroshi Araya, Onkar P. Kulkarni, Pragya Paramita Pal, Kirti Hira, and Ameer Basha Shaik
- Subjects
0301 basic medicine ,Proline ,Cell Survival ,medicine.medical_treatment ,Immunology ,Pharmacology ,Kidney ,Peptides, Cyclic ,Proinflammatory cytokine ,Nephropathy ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Oral administration ,Pseudomonas ,medicine ,Animals ,Immunology and Allergy ,Secretion ,Interleukin 6 ,biology ,Chemistry ,Oxalic Acid ,Dipeptides ,Acute Kidney Injury ,medicine.disease ,biology.organism_classification ,Mice, Inbred C57BL ,RAW 264.7 Cells ,030104 developmental biology ,Cytokine ,030220 oncology & carcinogenesis ,biology.protein ,Cytokines - 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.
- Published
- 2019