Honokiol, a small molecular weight natural product, alleviates experimental mesangial proliferative glomerulonephritis.
Glomerulonephritis (GN) is still the most common cause of end-stage renal disease. Accumulation of glomerular macrophages, proliferation of mesangial cells, and deposition of extracellular matrix proteins are pathobiological hallmarks of GN. Pharmacological interventions that can inhibit these insults may be beneficial in the retardation of the progression of GN. Honokiol originally isolated from Magnolia officinalis, shows antioxidative, anti-inflammatory, and antiproliferative activities in a variety of inflammation models. In this study, we first investigated the in vivo effects of honokiol on rat anti-Thy1 nephritis. Anti-Thy1 nephritis was induced in Wistar rats by injecting mouse anti-rat Thy1 antibodies intravenously. Nephritic rats were randomly assigned to receive honokiol (2.5 mg/kg, twice a day) or vehicle and were killed at various time points. Glomerular histology and immunohistopathology and urine protein excretion were studied. Western blotting was conducted for markers of proliferation. Adhesion molecules, chemokine, and extracellular matrix gene expression were evaluated by Northern blotting. Honokiol-treated nephritic rats excreted less urinary protein and had lower glomerular cellularity and sclerosis. The increased intraglomerular proliferating cell nuclear antigen and Akt phosphorylation in nephritic rats could be abolished by the treatment of honokiol. Honokiol also alleviated glomerular monocyte chemoattractant protein-1 and intracellular adhesion molecule-1, similar to type I (alpha1) collagen and fibronectin mRNA levels of nephritic rats. These results indicate that honokiol may have therapeutic potential in mesangial proliferative GN.
Chiang
C-K
CK
Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Sheu
M-L
ML
Hung
K-Y
KY
Wu
K-D
KD
Liu
S-H
SH
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001713:Biphenyl Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005765:Gastrointestinal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015432:Glomerulonephritis, Membranoproliferative / Q000188:drug therapy*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D017705:Lignans / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D011507:Proteinuria / Q000517:prevention & control; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018800:Thy-1 Antigens / Q000276:immunology; D000498:Allyl Compounds; D010636:Phenols
D001713:Biphenyl Compounds; D018932:Chemokine CCL2; D016326:Extracellular Matrix Proteins; D005765:Gastrointestinal Agents; D018799:Intercellular Adhesion Molecule-1; D017705:Lignans; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D018800:Thy-1 Antigens; C491766:Ccl2 protein, rat; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols