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In vitro and in vivo androgen regulation of Dendropanax morbiferus leaf extract on late-onset hypogonadism
Corresponding Author(s) : Myung-A Jung
Cellular and Molecular Biology,
Vol. 64 No. 10: Issue 10
Abstract
Late-onset hypogonadism (LOH) is associated with advancing age and is caused by a deficiency in serum testosterone levels. The aim of this study was to examine the effect of a Dendropanax morbiferus H.Lév. leaf extract (DME) on LOH using TM3 cells and aging male rats as in vitro and in vivo models, respectively. The in vitro effects of DME on testosterone levels and 3β-hydroxysteroid dehydrogenase (3β-HSD) protein expression in TM3 cells were analyzed. In the in vivo experiments, DME was orally administered to rats at three doses (50, 100, and 200 mg/kg/day) for 4 weeks. DME significantly increased the testosterone levels and 3β-HSD protein expression in TM3 cells. The DME groups showed significantly increased levels of androgenic hormones such as testosterone and dehydroepiandrosterone sulfate. The sex hormone-binding globulin production was significantly lower in the DME groups than that in the control group, while the neurohormone levels in the hypothalamic–pituitary–gonadal axis markedly increased. No significant differences were observed in the glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, and prostate-specific antigen levels among the DME and control groups. The triglyceride and low-density lipoprotein cholesterol levels were significantly lower, while the high-density lipoprotein cholesterol levels were significantly higher in the DME groups than those in the control group. The latency time in the rotarod, treadmill, and swimming tests increased with the DME treatment. Furthermore, the sperm counts in the epididymis markedly increased. These results suggest that DME can be effectively used to alleviate the symptoms of LOH.
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- Nieschlag E, Swerdloff R, Behre HM, Gooren LJ, Kaufman JM, Legross JJ, et al. Investigation, treatment, and monitoring of late-onset hypogonadism in males: ISA, ISSAM, and EAU recommendations. J Androl 2006; 27:135-7.
- Feldman HA, Longcope C, Derby CA, Johannes CB, Araujo AB, Coviello AD, et al. Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts Male Aging Study. J Clin Endocrinol Metab 2002; 87:589-98.
- Heller CG, Myers GB. The male climacteric: its symptomatology, diagnosis, and treatment. JAMA 1944; 126:472-7.
- Kaufman JM, Vermeulen A. Declining gonadal function in elderly men. Baillieres Clin Endocrinol Metab 1997; 11:289-309.
- Zmuda JM, Cauley JA, Kriska A, Glynn NW, Gutai JP, Kuller LH. Longitudinal relation between endogenous testosterone and cardiovascular disease risk factors in middle-aged men. A 13-year follow-up of former Multiple Risk Factor Intervention Trial participants. Am J Epidemiol 1997; 146:609-17.
- Liverman CT, Blazer DG. Testosterone and Aging: Clinical Research Directions. The National Academies Press, Washington, D.C., 2004.
- Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder RJ, Swerdloff RS, et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2010; 95:2536-59.
- Lunenfeld B, Saad F, Hoesl CE. ISA, ISSAM and EAU recommendations for the investigation, treatment and monitoring of late-onset hypogonadism in males: scientific background and rationale. Aging Male 2005; 8:59-74.
- de Ronde W, van der Schouw YT, Pols HA, Gooren LJ, Muller M, Grobbee DE, et al. Calculation of bioavailable and free testosterone in men: a comparison of 5 published algorithms. Clin Chem 2006; 52:1777-84.
- Yates DR, Gordon M. Male Reproductive System: Fine Structure Analysis by Scanning and Transmission Electron Microscopy. Masson Pub., U.S.A., 1977
- Chang CS, Kim H, Chang KS. Provisional Checklist of Vascular Plants for the Korea Peninsula Flora. Designpost, Seoul, 2014.
- Setzer WM, Green TJ, Whitaker KW, Moriarity DM, Yancey CA, Lawton RO, et al. A cytotoxic diacetylene from Dendropanax arboreus. Planta Med 1995; 61:470-1.
- Bae KH. The Medical Plants of Korea. Kyo-Hak Publishing, Seoul, 2000
- Lee BH, Choi JH, Kim HJ. Curing and thermal behaviors of Korean Dendropanax lacquer made by acetone and wine spirit extraction methods. Prog Org Coat 2005; 52:241-5.
- Hyun TK, Kim MO, Lee HK, Kim Y, Kim E, Kim JS. Evaluation of anti-oxidant and anti-cancer properties of Dendropanax morbifera Leveille. Food Chem 2013; 141:1947-55.
- Moon HI. Antidiabetic effects of dendropanoxide from leaves of Dendropanax morbifera Leveille in normal and streptozotocin-induced diabetic rats. Hum Exp Toxicol 2011; 30:870-5.
- Chung IM, Kim MV, Park WH, Moon HI. Antiatherogenic activity of Dendropanax morbifera essential oil in rats. Pharmazie 2009; 64:547-9.
- Park SE, Sapkota K, Choi JH, Kim MK, Kim YH, Kim KM, et al. Rutin from Dendropanax morbifera Leveille protects human dopaminergic cells against rotenone induced cell injury through inhibiting JNK and p38 MAPK signaling. Neurochem Res 2014; 39:707-18.
- Park BY, Min BS, Oh SR, Kim JH, Kim TJ, Kim DH, et al. Isolation and anticomplement activity of compounds from Dendropanax morbifera. J Ethnopharmacol 2004; 90:403-8.
- Jung MA, Oh KN, Choi EJ, Kim YJ, Bae D, Oh DR, et al. Effect of aqueous extract of Dendropanax morbifera leaf on sexual behavior in male rats. J Food Nutr Res 2017; 5:518-21.
- Friedwald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18:499-502.
- Noh YH, Kim DH, Kim JY, Park J, Kim OH, Han D, et al. Improvement of andropause symptoms by dandelion and rooibos extract complex CRS-10 in aging male. Nutr Res Pract 2012; 6:505-12.
- Tan WS, Ng CJ, Khoo EM, Low WH, Tan HM. The triad of erectile dysfunction, testosterone deficiency syndrome and metabolic syndrome: findings from a multi-ethnic Asian men study (The Subang Men's Health Study). Aging Male 2011; 14:231-6.
- Arlt W, Haas J, Callies F, Reincke M, Hübler D, Oettel M, et al. Biotransformation of oral dehydroepiandrosterone in elderly men: significant increase in circulating estrogens. J Clin Endocrinol Metab 1999; 84:2170-6.
- Sattler F, Bhasin S, He J, Chou CP, Castaneda-Sceppa C, Yarasheski K, et al. Testosterone threshold levels and lean tissue mass targets needed to enhance skeletal muscle strength and function: the HORMA trial. J Gerontol A Biol Sci Med Sci 2011; 66:122-9.
- Chauhann NS, Dixit VK. Effects of Bryonia laciniosa seeds on sexual behavior of male rats. Int J Imp Res 2010; 22:190-5.
- Morgentaler A. Two years of testosterone therapy associated with decline in prostate-specific antigen in a man with untreated prostate cancer. J Sex Med 2009; 6:574-7.
- Bornman MS, Rief S. Serum testosterone levels in South African men and the onset of androgen decline in ageing males. S Afr J Surg 2007; 45:62-4.
- Wang MC, Valenzuela LA, Murphy GP, Chu TM. Purification of a human prostate specific antigen. Invest Urol 1979; 17:159-63.
- Gruenewald DA, Matsumoto AM. Age-related decreases in serum gonadotropin levels and gonadotropin-releasing hormone gene expression in the medical preoptic area of the male rat are dependent upon testicular feedback. Endocrinology 1991; 129:2442-50
References
Nieschlag E, Swerdloff R, Behre HM, Gooren LJ, Kaufman JM, Legross JJ, et al. Investigation, treatment, and monitoring of late-onset hypogonadism in males: ISA, ISSAM, and EAU recommendations. J Androl 2006; 27:135-7.
Feldman HA, Longcope C, Derby CA, Johannes CB, Araujo AB, Coviello AD, et al. Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts Male Aging Study. J Clin Endocrinol Metab 2002; 87:589-98.
Heller CG, Myers GB. The male climacteric: its symptomatology, diagnosis, and treatment. JAMA 1944; 126:472-7.
Kaufman JM, Vermeulen A. Declining gonadal function in elderly men. Baillieres Clin Endocrinol Metab 1997; 11:289-309.
Zmuda JM, Cauley JA, Kriska A, Glynn NW, Gutai JP, Kuller LH. Longitudinal relation between endogenous testosterone and cardiovascular disease risk factors in middle-aged men. A 13-year follow-up of former Multiple Risk Factor Intervention Trial participants. Am J Epidemiol 1997; 146:609-17.
Liverman CT, Blazer DG. Testosterone and Aging: Clinical Research Directions. The National Academies Press, Washington, D.C., 2004.
Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder RJ, Swerdloff RS, et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2010; 95:2536-59.
Lunenfeld B, Saad F, Hoesl CE. ISA, ISSAM and EAU recommendations for the investigation, treatment and monitoring of late-onset hypogonadism in males: scientific background and rationale. Aging Male 2005; 8:59-74.
de Ronde W, van der Schouw YT, Pols HA, Gooren LJ, Muller M, Grobbee DE, et al. Calculation of bioavailable and free testosterone in men: a comparison of 5 published algorithms. Clin Chem 2006; 52:1777-84.
Yates DR, Gordon M. Male Reproductive System: Fine Structure Analysis by Scanning and Transmission Electron Microscopy. Masson Pub., U.S.A., 1977
Chang CS, Kim H, Chang KS. Provisional Checklist of Vascular Plants for the Korea Peninsula Flora. Designpost, Seoul, 2014.
Setzer WM, Green TJ, Whitaker KW, Moriarity DM, Yancey CA, Lawton RO, et al. A cytotoxic diacetylene from Dendropanax arboreus. Planta Med 1995; 61:470-1.
Bae KH. The Medical Plants of Korea. Kyo-Hak Publishing, Seoul, 2000
Lee BH, Choi JH, Kim HJ. Curing and thermal behaviors of Korean Dendropanax lacquer made by acetone and wine spirit extraction methods. Prog Org Coat 2005; 52:241-5.
Hyun TK, Kim MO, Lee HK, Kim Y, Kim E, Kim JS. Evaluation of anti-oxidant and anti-cancer properties of Dendropanax morbifera Leveille. Food Chem 2013; 141:1947-55.
Moon HI. Antidiabetic effects of dendropanoxide from leaves of Dendropanax morbifera Leveille in normal and streptozotocin-induced diabetic rats. Hum Exp Toxicol 2011; 30:870-5.
Chung IM, Kim MV, Park WH, Moon HI. Antiatherogenic activity of Dendropanax morbifera essential oil in rats. Pharmazie 2009; 64:547-9.
Park SE, Sapkota K, Choi JH, Kim MK, Kim YH, Kim KM, et al. Rutin from Dendropanax morbifera Leveille protects human dopaminergic cells against rotenone induced cell injury through inhibiting JNK and p38 MAPK signaling. Neurochem Res 2014; 39:707-18.
Park BY, Min BS, Oh SR, Kim JH, Kim TJ, Kim DH, et al. Isolation and anticomplement activity of compounds from Dendropanax morbifera. J Ethnopharmacol 2004; 90:403-8.
Jung MA, Oh KN, Choi EJ, Kim YJ, Bae D, Oh DR, et al. Effect of aqueous extract of Dendropanax morbifera leaf on sexual behavior in male rats. J Food Nutr Res 2017; 5:518-21.
Friedwald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18:499-502.
Noh YH, Kim DH, Kim JY, Park J, Kim OH, Han D, et al. Improvement of andropause symptoms by dandelion and rooibos extract complex CRS-10 in aging male. Nutr Res Pract 2012; 6:505-12.
Tan WS, Ng CJ, Khoo EM, Low WH, Tan HM. The triad of erectile dysfunction, testosterone deficiency syndrome and metabolic syndrome: findings from a multi-ethnic Asian men study (The Subang Men's Health Study). Aging Male 2011; 14:231-6.
Arlt W, Haas J, Callies F, Reincke M, Hübler D, Oettel M, et al. Biotransformation of oral dehydroepiandrosterone in elderly men: significant increase in circulating estrogens. J Clin Endocrinol Metab 1999; 84:2170-6.
Sattler F, Bhasin S, He J, Chou CP, Castaneda-Sceppa C, Yarasheski K, et al. Testosterone threshold levels and lean tissue mass targets needed to enhance skeletal muscle strength and function: the HORMA trial. J Gerontol A Biol Sci Med Sci 2011; 66:122-9.
Chauhann NS, Dixit VK. Effects of Bryonia laciniosa seeds on sexual behavior of male rats. Int J Imp Res 2010; 22:190-5.
Morgentaler A. Two years of testosterone therapy associated with decline in prostate-specific antigen in a man with untreated prostate cancer. J Sex Med 2009; 6:574-7.
Bornman MS, Rief S. Serum testosterone levels in South African men and the onset of androgen decline in ageing males. S Afr J Surg 2007; 45:62-4.
Wang MC, Valenzuela LA, Murphy GP, Chu TM. Purification of a human prostate specific antigen. Invest Urol 1979; 17:159-63.
Gruenewald DA, Matsumoto AM. Age-related decreases in serum gonadotropin levels and gonadotropin-releasing hormone gene expression in the medical preoptic area of the male rat are dependent upon testicular feedback. Endocrinology 1991; 129:2442-50