Korean red ginseng (Panax ginseng) ameliorates type 1 diabetes and restores immune cell compartments Young Joo Hong a , Nayoung Kim b , Karim Lee a , Chung Hee Sonn a , Jung Eun Lee a , Sung Tae Kim a , In Ho Baeg c , Kyung-Mi Lee a,n a Global Research Lab, Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul, South Korea b Asan Institute for Life Sciences, Asan Medical Center, Seoul, South Korea c Ginseng Research Center, KGC Research Institute, Korea Ginseng Corporation, Daejeon, Korea article info Article history: Received 26 February 2012 Received in revised form 19 July 2012 Accepted 7 August 2012 Available online 19 August 2012 Keywords: Korean red ginseng Type 1 diabetes Prophylaxis Hypoglycemia Lymphocytes abstract Ethnopharmacological relevance: Historical records reveal that in traditional medicine, a disease similar to diabetes was treated with ginseng. Korean red ginseng has been considered beneficial as a dietary supplement for its anti-diabetic potential. Aim: This study was designed to investigate the prophylactic potential of Korean red ginseng (KRG) extract (Panax ginseng C.A. Meyer Radix Rubra) in a well-established mouse model of Type 1 diabetes (T1D). Materials and methods: The prophylactic effect of KRG extract was evaluated in mice fed with KRG extract for two weeks prior to induction of diabetes by streptozotocin (STZ) administration. Glucose levels and glucose challenge test results of KRG-treated diabetic mice were compared to those of untreated diabetic mice and healthy control mice. Examination of the immune compartments in lymphoid organs and immunohistochemical staining of pancreas for islet cell morphology and insulin producing beta cells were performed. Results: KRG extract significantly lowered blood glucose levels to an average of 250 mg/dl from 350 mg/dl and improved glucose challenge testing when applied as prophylaxis. Histological findings indicated that KRG extract protected against STZ-induced destruction of pancreatic tissue and restored insulin secretion. Strikingly, this effect was accompanied by restoration of lymphocytes in secondary lymphoid organs, suggesting that KRG extract facilitated immune homeostasis. Conclusion: This is the first report to demonstrate the prophylactic function of KRG extract in ameliorating the hyperglycemia of T1D. Immune compartments of diabetic mice were found to be preserved in KRG-treated mice suggesting that Korean red ginseng may benefit T1D patients, not only for its hypoglycemic but also for its immunomodulatory effects. & 2012 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Unlike Type 2 diabetes (T2D), a metabolic disorder character- ized by insulin resistance, Type 1 diabetes (T1D) is a chronic autoimmune disease resulting from an attack of pancreatic islet cells by primarily CD4 þ and CD8 þ T cells (Bach, 1994) secreting Th1 cytokines, IFN-g and TNF-a (Tisch and Wang, 2008). Once pancreatic b cell destruction is initiated, an asymptomatic phase follows, that is accompanied by the presence of serum autoanti- bodies against insulin, glutamic acid decarboxylase 65 (GAD65), and insulinoma-associated tyrosine phosphatase (IA-2) (Tisch and Wang, 2008). Typical signs of T1D are high glucose levels in blood and urine and inefficient glucose tolerance accompanied by low serum insulin levels. In addition, T1D patients exhibit impaired immune cell functions (Peleg et al., 2007) and altered cytokine production (Foss et al., 2007), resulting in a high risk of infectious complications. Historically, traditional use of ginseng has been used for the treatment of hyperglycemia and diabetes (Ackerknecht, 1982; Bensky and Gamble, 1993). Accumulating data highlight the beneficial effect of Panax ginseng (Asian ginseng) and Panax quinquefolius (American ginseng) (Block and Mead, 2003; Nam et al., 2005; Sotaniemi et al., 1995; Yeh et al., 2003) as supple- ments to conventional anti-diabetic treatment regimens. The ginseng extract has been shown to improve diabetic conditions of both T1D (Kimura et al., 1981a; Kimura et al., 1981b) and T2D animal models (Chung et al., 2001; Dey et al., 2003; Kim et al., 2005; Lim et al., 2009; Liu et al., 2005; Mollah et al., 2009) as well Contents lists available at SciVerse ScienceDirect journal homepage: www.elsevier.com/locate/jep Journal of Ethnopharmacology 0378-8741/$ - see front matter & 2012 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jep.2012.08.009 Abbreviations: GLUT, glucose transporter; NOD, non-obese diabetes; PDLN, pancreatic-draining lymph nodes; STZ, streptozotocin; T1D, type 1 diabetes; T2D, type 2 diabetes n Corresponding author. Tel.: þ82 2 920 6253; fax: þ82 2 920 6252. E-mail addresses: kyunglee@korea.ac.kr, kml60637@gmail.com (K.-M. Lee). Journal of Ethnopharmacology 144 (2012) 225–233