title: Renal Protective Effects of Low Molecular Weight of Inonotus obliquus Polysaccharide (LIOP) on HFD/STZ-Induced Nephropathy in Mice.
abstract: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease in diabetes mellitus. Oxidative stress, insulin resistance and pro-inflammatory cytokines have been shown to play an important role in pathogeneses of renal damage on type 2 diabetes mellitus (DM). Inonotus obliquus (IO) is a white rot fungus that belongs to the family Hymenochaetaceae; it has been used as an edible mushroom and exhibits many biological activities including anti-tumor, anti-oxidant, anti-inflammatory and anti-hyperglycemic properties. Especially the water-soluble Inonotus obliquus polysaccharides (IOPs) have been previously reported to significantly inhibit LPS-induced inflammatory cytokines in mice and protect from streptozotocin (STZ)-induced diabetic rats. In order to identify the nephroprotective effects of low molecular weight of IOP fraction (LIOP), from the fruiting bodies of Inonotus obliquus, high-fat diet (HFD) plus STZ-induced type 2-like diabetic nephropathy C57BL/6 mice were investigated in this study. Our data showed that eight weeks of administration of 10-100 kDa, LIOP (300 mg/kg) had progressively increased their sensitivity to glucose (less insulin tolerance), reduced triglyceride levels, elevated the HDL/LDL ratio and decreased urinary albumin/creatinine ratio(ACR) compared to the control group. By pathological and immunohistochemical examinations, it was indicated that LIOP can restore the integrity of the glomerular capsules and increase the numbers of glomerular mesangial cells, associated with decreased expression of TGF-β on renal cortex in mice. Consistently, three days of LIOP (100 μg/mL) incubation also provided protection against STZ + AGEs-induced glucotoxicity in renal tubular cells (LLC-PK1), while the levels of NF-κB and TGF-β expression significantly decreased in a dose-dependent manner. Our findings demonstrate that LIOP treatment could ameliorate glucolipotoxicity-induced renal fibrosis, possibly partly via the inhibition of NF-κB/TGF-β1 signaling pathway in diabetic nephropathy mice.
authors.affiliation: Department of Traditional Chinese Medicine, En Chu Kong Hospital, New Taipei City 237, Taiwan. cyrb61401@gmail.com.
authors.forename: Yen-Jung
authors.initials: YJ
authors.lastname: Chou
authors.affiliation: Division of Nephrology, Department of Medicine; Chi-Mei Medical Center, Tainan 710, Taiwan. rockiekan@ntu.edu.tw.|Department of Biological Science and Technology, Chung Hwa University of Medical Technology, Tainan 717, Taiwan. rockiekan@ntu.edu.tw.
authors.forename: Wei-Chih
authors.initials: WC
authors.lastname: Kan
authors.affiliation: Department of Traditional Chinese Medicine, En Chu Kong Hospital, New Taipei City 237, Taiwan. jenny7710203@gmail.com.
authors.forename: Chieh-Min
authors.initials: CM
authors.lastname: Chang
authors.affiliation: Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan. yijen0426@gmail.com.
authors.forename: Yi-Jen
authors.initials: YJ
authors.lastname: Peng
authors.affiliation: Division of Nephrology, Department of Medicine; Chi-Mei Medical Center, Tainan 710, Taiwan. why8@ms61.hinet.net.|Department of Sports Management, College of Leisure and Recreation Management, Chia Nan University of Pharmacy and Science, Tainan 717, Taiwan. why8@ms61.hinet.net.
authors.forename: Hsien-Yi
authors.initials: HY
authors.lastname: Wang
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan. jushisa1114@gmail.com.
authors.forename: Wen-Chun
authors.initials: WC
authors.lastname: Yu
authors.affiliation: Institute of Biotechnology, Southern Taiwan University of Science and Technology, Tainan 710, Taiwan. 4A1H0004@stust.edu.tw.
authors.forename: Yu-Hsuan
authors.initials: YH
authors.lastname: Cheng
authors.affiliation: Institute of Biotechnology, Southern Taiwan University of Science and Technology, Tainan 710, Taiwan. zoe82232@gmail.com.
authors.forename: Yu-Rou
authors.initials: YR
authors.lastname: Jhang
authors.affiliation: Department of Life Science, Fu Jen Catholic University, New Taipei City 242, Taiwan. 079336@mail.fju.edu.tw.
authors.forename: Hsia-Wei
authors.initials: HW
authors.lastname: Liu
authors.affiliation: Institute of Biotechnology, Southern Taiwan University of Science and Technology, Tainan 710, Taiwan. jjchuu@stust.edu.tw.|Pharmacy, Wei Gong Memorial Hospital, Miaoli 351, Taiwan. jjchuu@stust.edu.tw.
authors.forename: Jiunn-Jye
authors.initials: JJ
authors.lastname: Chuu
mesh_terms: D000363:Agaricales / Q000378:metabolism*; D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D003928:Diabetic Nephropathies / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D048690:Fruiting Bodies, Fungal / Q000378:metabolism; D062610:Fungal Polysaccharides / Q000008:administration & dosage* / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D007328:Insulin / Q000097:blood; D050527:Mesangial Cells / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008970:Molecular Weight; D013311:Streptozocin / Q000009:adverse effects*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
chemical_list: D062610:Fungal Polysaccharides; D007328:Insulin; D016212:Transforming Growth Factor beta; D014280:Triglycerides; D013311:Streptozocin
keywords: Inonotus obliquus; NF-κB; TGF-β; advanced glycation end products (AGE); diabetic nephropathy; polysaccharides; renal fibrosis