morphinans and Nephritis

Sinomenine (SIN) is a purified alkaloid from the Chinese herb Sinomenium acutum. Previous studies demonstrated that SIN possesses anti-inflammatory and anti-apoptotic properties. We thus in the present report conducted studies to examine its impact on ischemia reperfusion (IR) induced renal injury. Precondition of mice with 200 mg/kg of SIN provided significant protection for mice against IR-induced renal injury as manifested by the attenuated serum creatinine (Cre) and blood urea nitrogen (BUN) along with less severity for histological changes and tubular cell apoptosis. In line with these results, treatment of mice with SIN suppressed IR-induced inflammatory infiltration and the expression of chemokine CXCL-10, adhesion molecule ICAM-1, and cytokines TNF-а/IL-6. Mechanistic studies revealed that SIN inhibits NF-κB transcriptional activity to suppress IR-induced inflammatory response in the kidney, while it attenuates MAP kinase signaling to prevent tubular cells undergoing apoptosis after IR insult. Altogether, our data support that SIN could be a useful therapeutic agent for prevention and treatment of IR-induced renal injury in the clinical settings.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Biomarkers; Blood Urea Nitrogen; Chemokine CXCL10; Creatinine; Cytoprotection; Disease Models, Animal; Inflammation Mediators; Intercellular Adhesion Molecule-1; Interleukin-6; Kidney Tubules; Male; MAP Kinase Signaling System; Mice; Mice, Inbred C57BL; Morphinans; Nephritis; NF-kappa B; Reperfusion Injury; Time Factors; Tumor Necrosis Factor-alpha

Sinomenine has been used to treat autoimmune diseases for centuries. However, little is known about its exact mechanisms of action. Whether sinomenine has an effect on programmed death‑1 (PD‑1) ligands (PD‑Ls) in vivo remains unclear. The present study aimed to determine the effect of sinomenine on the expression of PD‑L1 and PD‑L2 in peripheral blood mononuclear cells (PBMCs). A total of 25 patients with mesangial proliferative nephritis (MsPGN) were treated with sinomenine and followed up for 3 months. The expression of PD‑L1 and PD‑L2 was studied by using real‑time RT‑PCR and flow cytometric analysis, and recorded at months 0, 1 and 3 within the PBMCs. The intra‑renal expression of PD‑L1 and PD‑L2 was studied by immunohistochemistry. The results revealed that the PBMCs from the MsPGN patients expressed high levels of PD‑L1 at the mRNA and protein levels compared with the healthy donors. Immunohistochemistry revealed an increased PD‑L1 expression in the renal tissues from the MsPGN patients. Sinomenine was observed to have a significant effect in decreasing the PD‑L1 expression in the PBMCs. The present study therefore suggests a novel mechanism for the therapeutic effects of sinomenine on MsPGN in vivo.

Topics: Adult; B7-H1 Antigen; Female; Flow Cytometry; Gene Expression Regulation; Glomerular Mesangium; Humans; Leukocytes, Mononuclear; Male; Morphinans; Nephritis; Nephrotic Syndrome; Programmed Cell Death 1 Receptor; Sclerosis