Citral is renoprotective for focal segmental glomerulosclerosis by inhibiting oxidative stress and apoptosis and activating Nrf2 pathway in mice.
The pathogenesis of focal segmental glomerulosclerosis (FSGS) is considered to be associated with oxidative stress, mononuclear leukocyte recruitment and infiltration, and matrix production and/or matrix degradation, although the exact etiology and pathogenic pathways remain to be determined. Establishment of a pathogenesis-based therapeutic strategy for the disease is clinically warranted. Citral (3,7-dimethyl-2,6-octadienal), a major active compound in Litseacubeba, a traditional Chinese herbal medicine, can inhibit oxidant activity, macrophage and NF-κB activation. In the present study, first, we used a mouse model of FSGS with the features of glomerular epithelial hyperplasia lesions (EPHLs), a key histopathology index of progression of FSGS, peri-glomerular inflammation, and progressive glomerular hyalinosis/sclerosis. When treated with citral for 28 consecutive days at a daily dose of 200 mg/kg of body weight by gavage, the FSGS mice showed greatly reduced EPHLs, glomerular hyalinosis/sclerosis and peri-glomerular mononuclear leukocyte infiltration, suggesting that citral may be renoprotective for FSGS and act by inhibiting oxidative stress and apoptosis and early activating the Nrf2 pathway. Meanwhile, a macrophage model involved in anti-oxidative and anti-inflammatory activities was employed and confirmed the beneficial effects of citral on the FSGS model.
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, R.O.C ; Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, R.O.C.
Shun-Min
SM
Yang
Kuo-Feng
KF
Hua
Yu-Chuan
YC
Lin
Ann
A
Chen
Jia-Ming
JM
Chang
Louis
L
Kuoping Chao
Chen-Lung
CL
Ho
Shuk-Man
SM
Ka
D000080462:Acyclic Monoterpenes; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D018932:Chemokine CCL2 / Q000378:metabolism; D004195:Disease Models, Animal; D005923:Glomerulosclerosis, Focal Segmental / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D039821:Monoterpenes / Q000494:pharmacology*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D050199:Podocytes / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
D000080462:Acyclic Monoterpenes; D018932:Chemokine CCL2; D039821:Monoterpenes; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495636:Nfe2l2 protein, mouse; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D020928:Mitogen-Activated Protein Kinases; C007076:citral