Litsea japonica extract inhibits neuronal apoptosis and the accumulation of advanced glycation end products in the diabetic mouse retina

Kim,Junghyun; Kim,Chan‑Sik; Lee,Yun Mi; Sohn,Eunjin; Jo,Kyuhyung; Kim,Jin Sook

doi:10.3892/mmr.2015.3543

Litsea japonica extract inhibits neuronal apoptosis and the accumulation of advanced glycation end products in the diabetic mouse retina

Authors:
- Junghyun Kim
- Chan‑Sik Kim
- Yun Mi Lee
- Eunjin Sohn
- Kyuhyung Jo
- Jin Sook Kim
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Affiliations: Korean Medicine Based Herbal Drug Development Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 305‑811, Republic of Korea
Published online on: March 24, 2015 https://doi.org/10.3892/mmr.2015.3543
Pages: 1075-1081
Copyright: © Kim et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

The retinal accumulation of advanced glycation end products (AGEs) is a condition, which is found in diabetic retinopathy. The purpose of the present study was to investigate the protective effect of Litsea japonica extract (LJE) and to elucidate its underlying protective mechanism in model diabetic db/db mice. Male, 7 ‑week‑old db/db mice were treated with LJE (100 or 250 mg/kg body weight) once a day orally for 12 weeks. The expression levels of AGEs and their receptor (RAGE) were subsequently assessed by immunohistochemistry. An electrophoretic mobility shift assay and southwestern histochemistry were used to detect activated nuclear factor κB (NF‑κB). The immunohistochemical analysis demonstrated that LJE significantly reduced the expression levels of the AGEs and RAGE in the neural retinas of the db/db mice. LJE markedly inhibited the apoptosis of retinal ganglion cells. In addition, LJE suppressed the activation of NF‑κB. These results suggested that LJE may be beneficial for the treatment of diabetes‑induced retinal neurodegeneration, and the ability of LJE to attenuate retinal ganglion cell loss may be mediated by inhibition of the accumulation of AGEs.

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1	Mizutani M, Kern TS and Lorenzi M: Accelerated death of retinal microvascular cells in human and experimental diabetic retinopathy. J Clin Invest. 97:2883–2890. 1996. View Article : Google Scholar : PubMed/NCBI
2	Asnaghi V, Gerhardinger C, Hoehn T, Adeboje A and Lorenzi M: A role for the polyol pathway in the early neuroretinal apoptosis and glial changes induced by diabetes in the rat. Diabetes. 52:506–511. 2003. View Article : Google Scholar : PubMed/NCBI
3	Barber AJ, Lieth E, Khin SA, Antonetti DA, Buchanan AG and Gardner TW: Neural apoptosis in the retina during experimental and human diabetes. Early onset and effect of insulin. J Clin Invest. 102:783–791. 1998. View Article : Google Scholar : PubMed/NCBI
4	Kern TS and Barber AJ: Retinal ganglion cells in diabetes. J Physiol. 586:4401–4408. 2008. View Article : Google Scholar : PubMed/NCBI
5	Brownlee M: Advanced protein glycosylation in diabetes and aging. Annu Rev Med. 46:223–234. 1995. View Article : Google Scholar : PubMed/NCBI
6	Koga K, Yamagishi S, Okamoto T, et al: Serum levels of glucose-derived advanced glycation end products are associated with the severity of diabetic retinopathy in type 2 diabetic patients without renal dysfunction. Int J Clin Pharmacol Res. 22:13–17. 2002.PubMed/NCBI
7	Miura J, Yamagishi S, Uchigata Y, et al: Serum levels of non-carboxymethyllysine advanced glycation endproducts are correlated to severity of microvascular complications in patients with Type 1 diabetes. J Diabetes Complications. 17:16–21. 2003. View Article : Google Scholar
8	Hammes HP, Alt A, Niwa T, et al: Differential accumulation of advanced glycation end products in the course of diabetic retinopathy. Diabetologia. 42:728–736. 1999. View Article : Google Scholar : PubMed/NCBI
9	Lecleire-Collet A, Tessier LH, Massin P, et al: Advanced glycation end products can induce glial reaction and neuronal degeneration in retinal explants. Br J Ophthalmol. 89:1631–1633. 2005. View Article : Google Scholar : PubMed/NCBI
10	Kasper M, Roehlecke C, Witt M, et al: Induction of apoptosis by glyoxal in human embryonic lung epithelial cell line L132. Am J Respir Cell Mol Biol. 23:485–491. 2000. View Article : Google Scholar : PubMed/NCBI
11	Kaji Y, Amano S, Usui T, et al: Expression and function of receptors for advanced glycation end products in bovine corneal endothelial cells. Invest Ophthalmol Vis Sci. 44:521–528. 2003. View Article : Google Scholar : PubMed/NCBI
12	Yamagishi S, Inagaki Y, Amano S, Okamoto T, Takeuchi M and Makita Z: Pigment epithelium-derived factor protects cultured retinal pericytes from advanced glycation end product-induced injury through its antioxidative properties. Biochem Biophys Res Commun. 296:877–882. 2002. View Article : Google Scholar : PubMed/NCBI
13	Deane R, Du Yan S, Submamaryan RK, et al: RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain. Nat Med. 9:907–913. 2003. View Article : Google Scholar : PubMed/NCBI
14	Hammes HP, Martin S, Federlin K, Geisen K and Brownlee M: Aminoguanidine treatment inhibits the development of experimental diabetic retinopathy. Proc Natl Acad Sci USA. 88:11555–11558. 1991. View Article : Google Scholar : PubMed/NCBI
15	Kern TS and Engerman RL: Pharmacological inhibition of diabetic retinopathy: aminoguanidine and aspirin. Diabetes. 50:1636–1642. 2001. View Article : Google Scholar : PubMed/NCBI
16	Kern TS, Tang J, Mizutani M, et al: Response of capillary cell death to aminoguanidine predicts the development of retinopathy: comparison of diabetes and galactosemia. Invest Ophthalmol Vis Sci. 41:3972–3978. 2000.PubMed/NCBI
17	Vasan S, Foiles PG and Founds HW: Therapeutic potential of AGE inhibitors and breakers of AGE protein cross-links. Expert Opin Investig Drugs. 10:1977–1987. 2001. View Article : Google Scholar
18	Harris CS, Beaulieu LP, Fraser MH, et al: Inhibition of advanced glycation end product formation by medicinal plant extracts correlates with phenolic metabolites and antioxidant activity. Planta Med. 77:196–204. 2011. View Article : Google Scholar
19	Lee SY, Min BS, Kim JH, et al: Flavonoids from the leaves of Litsea japonica and their anti-complement activity. Phytother Res. 19:273–276. 2005. View Article : Google Scholar : PubMed/NCBI
20	Min BS, Lee SY, Kim JH, et al: Lactones from the leaves of Litsea japonica and their anti-complement activity. J Nat Prod. 66:1388–1390. 2003. View Article : Google Scholar : PubMed/NCBI
21	Sohn EJ, Kim J, Kim CS, et al: The extract of Litsea japonica reduced the development of diabetic nephropathy via the inhibition of advanced Glycation end products accumulation in db/db mice. Evid-Based Compl Alt Med. 2013:7694162013.
22	Sohn EJ, Kim CS, Kim YS, et al: Effects of magnolol (5,5′-diallyl-2,2′-dihydroxybiphenyl) on diabetic nephropathy in type 2 diabetic Goto-Kakizaki rats. Life Sci. 80:468–475. 2007. View Article : Google Scholar
23	Hernández-Presa MA, Gómez-Guerrero C and Egido J: In situ non-radioactive detection of nuclear factors in paraffin sections by Southwestern histochemistry. Kidney Int. 55:209–214. 1999. View Article : Google Scholar : PubMed/NCBI
24	Yamagishi S, Takeuchi M, Matsui T, Nakamura K, Imaizumi T and Inoue H: Angiotensin II augments advanced glycation end product-induced pericyte apoptosis through RAGE overexpression. FEBS Lett. 579:4265–4270. 2005. View Article : Google Scholar : PubMed/NCBI
25	Romeo G, Liu WH, Asnaghi V, Kern TS and Lorenzi M: Activation of nuclear factor-kappaB induced by diabetes and high glucose regulates a proapoptotic program in retinal pericytes. Diabetes. 51:2241–2248. 2002. View Article : Google Scholar : PubMed/NCBI
26	Kowluru RA, Koppolu P, Chakrabarti S and Chen S: Diabetes-induced activation of nuclear transcriptional factor in the retina and its inhibition by antioxidants. Free Radic Res. 37:1169–1180. 2003. View Article : Google Scholar
27	Hammes HP, Federoff HJ and Brownlee M: Nerve growth factor prevents both neuroretinal programmed cell death and capillary pathology in experimental diabetes. Mol Med. 1:527–534. 1995.PubMed/NCBI
28	Kerrigan LA, Zack DJ, Quigley HA, Smith SD and Pease ME: TUNEL-positive ganglion cells in human primary open-angle glaucoma. Arch Ophthalmol. 115:1031–1035. 1997. View Article : Google Scholar : PubMed/NCBI
29	Chiarelli F, Catino M, Tumini S, et al: Advanced glycation end products in adolescents and young adults with diabetic angiopathy. Pediatr Nephrol. 14:841–846. 2000. View Article : Google Scholar : PubMed/NCBI
30	Ono Y, Aoki S, Ohnishi K, Yasuda T, Kawano K and Tsukada Y: Increased serum levels of advanced glycation end-products and diabetic complications. Diabetes Res Clin Pract. 41:131–137. 1998. View Article : Google Scholar : PubMed/NCBI
31	Funk RH and Schmidt KG: Characteristic features of optic nerve ganglion cells and approaches for neuroprotection. From intracellular to capillary processes and therapeutic considerations. Ophthalmologe. 101:1062–1070. 2004.In German. View Article : Google Scholar : PubMed/NCBI
32	Yamagishi S, Hsu CC, Taniguchi M, et al: Receptor-mediated toxicity to pericytes of advanced glycosylation end products: a possible mechanism of pericyte loss in diabetic microangiopathy. Biochem Biophys Res Commun. 213:681–687. 1995. View Article : Google Scholar : PubMed/NCBI
33	Yamagishi S, Amano S, Inagaki Y, et al: Advanced glycation end products-induced apoptosis and overexpression of vascular endothelial growth factor in bovine retinal pericytes. Biochem Biophys Res Commun. 290:973–978. 2002. View Article : Google Scholar : PubMed/NCBI
34	Yamagishi S, Nakamura K and Matsui T: Advanced glycation end products (AGEs) and their receptor (RAGE) system in diabetic retinopathy. Curr Drug Discov Technol. 3:83–88. 2006. View Article : Google Scholar : PubMed/NCBI
35	Lee EH, Song DG, Lee JY, Pan CH, Um BH and Jung SH: Flavonoids from the leaves of Thuja orientalis inhibit the aldose reductase and the formation of advanced glycation endproducts. J Korean Soc Appl Biol Chem. 52:448–455. 2009. View Article : Google Scholar
36	Jang DS, Kim JM, Lee YM, et al: Flavonols from Houttuynia cordata with protein Glycation and Aldose reductase inhibitory activity. Nat Prod Sci. 12:210–213. 2006.
37	Matsuda H, Wang T, Managi H and Yoshikawa M: Structural requirements of flavonoids for inhibition of protein glycation and radical scavenging activities. Bioorg Med Chem. 11:5317–5323. 2003. View Article : Google Scholar : PubMed/NCBI
38	Kim J, Kim KM, Kim CS, et al: Puerarin inhibits the retinal pericyte apoptosis induced by advanced glycation end products in vitro and in vivo by inhibiting NADPH oxidase-related oxidative stress. Free Radic Biol Med. 53:357–365. 2012. View Article : Google Scholar : PubMed/NCBI
39	Wu T, Chiang SK, Chau FY and Tso MO: Light-induced photoreceptor degeneration may involve the NF kappaB/caspase-1 pathway in vivo. Brain Res. 967:19–26. 2003. View Article : Google Scholar : PubMed/NCBI
40	Choi JS, Kim JA, Kim DH, et al: Failure to activate NF-kappaB promotes apoptosis of retinal ganglion cells following optic nerve transection. Brain Res. 883:60–68. 2000. View Article : Google Scholar : PubMed/NCBI