PMID- 32112899 OWN - NLM STAT- MEDLINE DCOM- 20210105 LR - 20210105 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 254 DP - 2020 May 23 TI - Korean red ginseng attenuates hyperglycemia-induced renal inflammation and fibrosis via accelerated autophagy and protects against diabetic kidney disease. PG - 112693 LID - S0378-8741(19)34471-X [pii] LID - 10.1016/j.jep.2020.112693 [doi] AB - ETHNOPHARMACOLOGICAL RELEVANCE: Panax ginseng C.A. Mey. (Korean ginseng) has been widely used in traditional medicine to treat diabetes mellitus for thousands of years. It also plays a key role in health maintenance owing to its anti-oxidant and anti-fatigue properties, and is quite popular as a dietary supplement. AIM OF THE STUDY: This study was designed to offer a complementary and alternative medicine to manage the diabetic kidney disease (DKD), which causes long-term damage to the renal structure. We also investigated the regulation of the autophagy mechanism, which is the underlying the pathogenesis of DKD. MATERIALS AND METHODS: The effect of Korean red ginseng (KRG) on DKD was evaluated using human kidney proximal tubular cells and streptozotocin (STZ)-treated Sprague-Dawley rat models. In vitro experiments were conducted to evaluate the proteins related to fibrosis and autophagy. This was followed by in vivo experiments involving rats treated with single intraperitoneal administration of STZ (60 mg/kg) and then with KRG solution orally for 4 weeks. Proteins related to renal injury, fibrosis, and autophagy were determined by immunoblotting. Hematoxylin and eosin (H&E), Periodic acid-Schiff (PAS), Sirius red, and immunostaining were processed for histological studies. RESULTS: KRG diminished the levels of metabolic measurements and blood parameters. Western blotting showed a decreased expression of proteins, such as TGF-beta1, KIM1, and AGE, which are responsible for renal inflammation, injury, and fibrosis. Histological studies also supported these results and revealed that the KRG-treated groups recovered from renal injury and fibrosis. Furthermore, the autophagy marker, LC3, was upregulated, whereas p62 was downregulated. The levels of proteins related to the autophagy mechanism, such as ATG7, increased, while mammalian target of rapamycin (mTOR) decreased with the KRG treatment and exhibited accelerated autophagy compared to the STZ alone group. CONCLUSIONS: KRG can suppress renal inflammation, injury, and fibrosis by blocking TGF-beta1 activation and can induce cellular autophagy. Therefore, this study strongly suggests that KRG exhibits a renoprotective effect against the STZ-induced DKD. CI - Copyright (c) 2020 Elsevier B.V. All rights reserved. FAU - Karunasagara, Shanika AU - Karunasagara S AD - Department of Veterinary Medicine & Institute of Veterinary Science, Chungnam National University, Daejeon, 34134, Republic of Korea. FAU - Hong, Geum-Lan AU - Hong GL AD - Department of Veterinary Medicine & Institute of Veterinary Science, Chungnam National University, Daejeon, 34134, Republic of Korea. FAU - Park, Se-Ra AU - Park SR AD - Samsung Biomedical Research Institute, Seoul, 06351, Republic of Korea. FAU - Lee, Na-Hyun AU - Lee NH AD - Department of Veterinary Medicine & Institute of Veterinary Science, Chungnam National University, Daejeon, 34134, Republic of Korea. FAU - Jung, Da-Young AU - Jung DY AD - Department of Veterinary Medicine & Institute of Veterinary Science, Chungnam National University, Daejeon, 34134, Republic of Korea. FAU - Kim, Tae-Won AU - Kim TW AD - Department of Veterinary Medicine & Institute of Veterinary Science, Chungnam National University, Daejeon, 34134, Republic of Korea. FAU - Jung, Ju-Young AU - Jung JY AD - Department of Veterinary Medicine & Institute of Veterinary Science, Chungnam National University, Daejeon, 34134, Republic of Korea. Electronic address: jyjung@cnu.ac.kr. LA - eng PT - Journal Article DEP - 20200226 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Plant Extracts) RN - 0 (Protective Agents) SB - IM MH - Animals MH - Anti-Inflammatory Agents/pharmacology/*therapeutic use MH - Autophagy/drug effects MH - Cell Line MH - Diabetes Mellitus, Experimental/blood/complications/*drug therapy/pathology MH - Diabetic Nephropathies/blood/*drug therapy/pathology MH - Fibrosis MH - Humans MH - Hyperglycemia/blood/complications/*drug therapy/pathology MH - Kidney/drug effects/pathology MH - Male MH - *Panax MH - Phytotherapy MH - Plant Extracts/pharmacology/*therapeutic use MH - Protective Agents/pharmacology/*therapeutic use MH - Rats, Sprague-Dawley OTO - NOTNLM OT - Diabetic kidney disease OT - Korean red ginseng OT - LC3 OT - Streptozotocin OT - TGF-beta1 COIS- Declaration of competing interest None. EDAT- 2020/03/01 06:00 MHDA- 2021/01/06 06:00 CRDT- 2020/03/01 06:00 PHST- 2019/11/08 00:00 [received] PHST- 2020/02/10 00:00 [revised] PHST- 2020/02/20 00:00 [accepted] PHST- 2020/03/01 06:00 [pubmed] PHST- 2021/01/06 06:00 [medline] PHST- 2020/03/01 06:00 [entrez] AID - S0378-8741(19)34471-X [pii] AID - 10.1016/j.jep.2020.112693 [doi] PST - ppublish SO - J Ethnopharmacol. 2020 May 23;254:112693. doi: 10.1016/j.jep.2020.112693. Epub 2020 Feb 26.