Xiaoyaosan decoction regulates food intake and body weight via the leptin-leptin receptor-proopiomelanocortin pathway in rats with chronic immobilization stress
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摘要
OBJECTIVE: To evaluate the effects of the Xiaoyaosan(XYS) decoction on the food intake and body weight of rats with chronic immobilization stress(CIS), as well as the concentration of serum leptin and the expression of feeding-related neuropeptides [leptin receptor(Ob-R), proopiomelanocortin(POMC), and α-melanocyte-stimulating hormone(α-MSH)] in the hypothalamic arcuate nucleus(ARC).METHODS: We subjected rats to CIS for 3 h a day.The rats were randomly divided into the following groups: control group, 7-day stress group, 21-day stress group and XYS-treated group. The rats in the two stress groups were exposed to CIS for 7 or 21 d.The rats in the XYS-treated group were also exposed to CIS for 21 d and were intragastrically administered the XYS decoction before stress. The body weight and food intake of the rats were measured every day. The content of leptin in serum andα-MSH in the ARC were detected by ELISA, and the expression of neuropeptides in the ARC was assayed by immunofluorescence, Western blot and q RT-PCR.RESULTS: The food intake and body weight of rats exposed to CIS were lower than those of control rats. The serum leptin, and expression levels of ObR, POMC and α-MSH in the ARC were significantly higher than those in the control rats. Treatment with the XYS decoction improved the appetite and the body weight, and down-regulated serum leptin and Ob-R, POMC and α-MSH in hypothalamus ARC.CONCLUSION: The leptin-Ob-R-POMC pathway might be the part of the mechanism underlying XYS's improvement of somatic symptoms such as reduction in food intake and body weight related to CIS.
OBJECTIVE: To evaluate the effects of the Xiaoyaosan(XYS) decoction on the food intake and body weight of rats with chronic immobilization stress(CIS), as well as the concentration of serum leptin and the expression of feeding-related neuropeptides [leptin receptor(Ob-R), proopiomelanocortin(POMC), and α-melanocyte-stimulating hormone(α-MSH)] in the hypothalamic arcuate nucleus(ARC).METHODS: We subjected rats to CIS for 3 h a day.The rats were randomly divided into the following groups: control group, 7-day stress group, 21-day stress group and XYS-treated group. The rats in the two stress groups were exposed to CIS for 7 or 21 d.The rats in the XYS-treated group were also exposed to CIS for 21 d and were intragastrically administered the XYS decoction before stress. The body weight and food intake of the rats were measured every day. The content of leptin in serum andα-MSH in the ARC were detected by ELISA, and the expression of neuropeptides in the ARC was assayed by immunofluorescence, Western blot and q RT-PCR.RESULTS: The food intake and body weight of rats exposed to CIS were lower than those of control rats. The serum leptin, and expression levels of ObR, POMC and α-MSH in the ARC were significantly higher than those in the control rats. Treatment with the XYS decoction improved the appetite and the body weight, and down-regulated serum leptin and Ob-R, POMC and α-MSH in hypothalamus ARC.CONCLUSION: The leptin-Ob-R-POMC pathway might be the part of the mechanism underlying XYS's improvement of somatic symptoms such as reduction in food intake and body weight related to CIS.
OBJECTIVE: To evaluate the effects of the Xiaoyaosan(XYS) decoction on the food intake and body weight of rats with chronic immobilization stress(CIS), as well as the concentration of serum leptin and the expression of feeding-related neuropeptides [leptin receptor(Ob-R), proopiomelanocortin(POMC), and α-melanocyte-stimulating hormone(α-MSH)] in the hypothalamic arcuate nucleus(ARC).METHODS: We subjected rats to CIS for 3 h a day.The rats were randomly divided into the following groups: control group, 7-day stress group, 21-day stress group and XYS-treated group. The rats in the two stress groups were exposed to CIS for 7 or 21 d.The rats in the XYS-treated group were also exposed to CIS for 21 d and were intragastrically administered the XYS decoction before stress. The body weight and food intake of the rats were measured every day. The content of leptin in serum andα-MSH in the ARC were detected by ELISA, and the expression of neuropeptides in the ARC was assayed by immunofluorescence, Western blot and q RT-PCR.RESULTS: The food intake and body weight of rats exposed to CIS were lower than those of control rats. The serum leptin, and expression levels of ObR, POMC and α-MSH in the ARC were significantly higher than those in the control rats. Treatment with the XYS decoction improved the appetite and the body weight, and down-regulated serum leptin and Ob-R, POMC and α-MSH in hypothalamus ARC.CONCLUSION: The leptin-Ob-R-POMC pathway might be the part of the mechanism underlying XYS's improvement of somatic symptoms such as reduction in food intake and body weight related to CIS.
引文
1 Mizuno M,Siddique K,Baum M,et al.Prenatal programming of hypertension induces sympathetic overactivity in response to physical stress.Hypertension 2013;61(1):180-186.
2 Wang Z,Zhang DD,Hui S,et al.Effect of tribulus terrestris saponins on behavior and neuroendocrine in chronic mild stess depression rats.J Tradit Chin Med 2013;33(2):228-232.
3 Sohlberg S.Personality,life stress and the course of eating disorders.Acta Psychiatr Scand Suppl 1990;361:29-33.
4 Vallès A,MartíO,García A,et al.Single exposure to stressors causes long-lasting,stress-dependent reduction of food intake in rats.Am J Physiol Regul Integr Comp Physiol 2000;279(3):R1138-R1144.
5 Monteiro F,Abraham ME,Sahakari SD,et al.Effect of immobilization stress on food intake,body weight and weights of various organs in rat.Indian J Physiol Pharmacol 1989;33(3):186-190.
6 Lenard NR,Berthoud HR.Central and peripheral regulation of food intake and physical activity:pathways and genes.Obesity(Silver Spring)2008;16(Suppl3):s11-s22.
7 Yu YH,Deng C,Huang XF.Obese reversal by a chronic energy restricted diet leaves an increased Arc NPY/AgRP,but no alteration in POMC/CART,mRNA expression in diet-induced obese mice.Behav Brain Res 2009;205(1):50-56.
8 Oh TS,Cho H,Cho JH,et al.Hypothalamic AMPK-induced autophagy increases food intake by regulating NPYand POMC expression.Autophagy 2016;12(11):2009-2025.
9 Yoo SB,Ryu V,Park EY,et al.The arcuate NPY,POMC,and CART expressions responding to food deprivation are exaggerated in young female rats that experienced neonatal maternal separation.Neuropeptides 2011;45(5):343-349.
10 Wu J,Zou DJ.The research progress of leptin receptor.Sheng Li Ke Xue Jin Zhan 2000;31(2):143-146.
11 Wang HX,Lei ZH,Ding F,et al.Localization of long form leptin receptor mRNA in the hypothalamus in the pig studied by in situ hybridization.Nanjing Nong Ye Da Xue Xue Bao 2002;25(1):80-84.
12 Baskin DG,Schwartz MW,Seeley RJ,et al.Leptin receptor long-form splice-variant protein expression in neuron cell bodies of the brain and colocalization with nuropeptide Y mRNA in the arcuate nucleus.J Histochem Cytochem 1999;47(3):353-362.
13 Münzberg H,Huo L,Nillni EA,et al.Role of signal transducer and activator of transcription 3 in regulation of hypothalamic proopiomelanocortin gene expression by leptin.Endocrinology 2003;144(5):2121-2131.
14 Wang SX,Chen JX,Yue GX,et al.Xiaoyaosan decoction regulates changes in neuropeptide y and leptin receptor in the rat arcuate nucleus after chronic immobilization stress.Evid Based Complement Alternat Med 2012;2012:381278.
15 Jiang YM,Li XJ,Meng ZZ,et al.Effects of Xiaoyaosan on stress-induced anxiety-like behavior in rats:involvement of CRF1 receptor.Evid Based Complement Alternat Med 2016;2016:1238426.
16 Chen JX,Wei L,Zhao X,et al.Effects of the Chinese traditional prescription Xiaoyaosan decoction on chronic immobilization stress-induced changes in behavior and brain BDNF,TrkB,and NT-3 in rats.Cell Mol Neurobiol 2008;28(5):745-755.
17 Meng ZZ,Chen JX,Jiang YM,et al.Effect of xiaoyaosan decoction on learning and memory deficit in rats induced by chronic immobilization stress.Evid Based Complement Alternat Med 2013;2013:297154.
18 Li N,Liu Q,Li XJ,et al.TCM Formula Xiaoyaosan decoction improves depressive-like behaviors in rats with Type 2 diabetes.Evid Based Complement Alternat Med2015;2015:415243.
19 Stanley S,Wynne K,Mc Gowan B,et al.Hormonal regulation of food intake.Physiol Rev 2005;85(4):1131-1158.
20 Lecklin A,Lundell L,Paananen L,et al.Receptor subtypes Y1 and Y5 mediate neuropeptide Y induced feeding in the guinea-pig.Br J Pharmacol 2002;135(8):2029-2037.
21 Sun Z,Zhang ZC,Ma L,et al.Effects of acupuncture on appetite regulating factors NPY and leptin of obese rats.Zhong Guo Xing Wei Yi Xue Ke Xue 2005;14(12):1057-1059.
22 Hu CY,Li YW.Overview on the physiological functions of neuropeptide Y(NPY).Sheng Wu Xue Za Zhi 2011;28(2):66-68.
23 Cheung CC,Clifton DK,Steiner RA.Proo-piomelanocortion neurons are direct targets for leptin in the hypothalamus.Endocrinology 1997;138(10):4489-4492.
24 Finn PD,Cunningham MJ,Pau KY,et al.The stimulatory effect of leptin on the neuroendocrine reproductive axis of the monkey.Endocrinology 1998;139(11):4652-4662.
25 Quennell JH,Mulligan AC,Tups A,et al.Leptin indirectly regulates gonadotropin-releasing hormone neuronal function.Endocrinology 2009;150(6):2805-2812.
26 Hagan MM,Rushing PA,Schwartz MW,et al.Role of the CNS melanocortin system in the response to overfeeding.J Neurosci 1999;19(6):2362-2367.
27 Zhang HH,Zhang J,Guo XZ.The conceive outline of establishing self-rating Xiaoyaosan symptom of geriatric depression scale.Liaoning Zhong Yi Za Zhi 2009;36(10):1691-1692.
28 Hou J,Xiao L,Yang JP.Effect of platform-over-water stress on neuroendocrine internal secretion and thymus apoptosis and the regulative role of Jiawei Xiaoyao pill.Zhong Guo Lin Chuang Kang Fu 2005;9(44):100-102.
29 Fan LR.Curative effect observation of Xiaoyaosan on anxiety and depression after apoplexy.Shi Yong Zhong Xi Yi Jie He Lin Chuang 2013;13(4):52-53.
30 Xiao F,Xu BY,Li Y,et al.Effect of Jiawei Xiaoyao San on anxiety and depression in patients with psychological stress insomnia.Zhong Hua Zhong Yi Yao Xue Kan 2009;27(5):962-963.
31 Liu YY,Guo XL,Zhao HB,et al.Behavior evaluation of rat model with stagnation of liver Qi and spleen deficiency syndrome regulating by Xiaoyao San extract.Zhong Hua Zhong Yi Yao Za Zhi 2013;28(7):2138-2141.
32 Zhou J,Su R,Fan JP.The research progress of Xiaoyao powder main chemical components and their antidepressant effects.Zhong Guo Zhong Yi Ji Chu Yi Xue Za Zhi2014;20(2):278-279.
33 Miao YL.The pharmacological research situation of Xiaoyao San.Zhong Guo Chu Fang Yao 2014;12(9):141-142.
34 Li MT,Xiang H.The research progress in active ingredients and pharmacological effects of Xiaoyao San.Zhong Yao Cai 2010;33(12):1968-1972.
2 Wang Z,Zhang DD,Hui S,et al.Effect of tribulus terrestris saponins on behavior and neuroendocrine in chronic mild stess depression rats.J Tradit Chin Med 2013;33(2):228-232.
3 Sohlberg S.Personality,life stress and the course of eating disorders.Acta Psychiatr Scand Suppl 1990;361:29-33.
4 Vallès A,MartíO,García A,et al.Single exposure to stressors causes long-lasting,stress-dependent reduction of food intake in rats.Am J Physiol Regul Integr Comp Physiol 2000;279(3):R1138-R1144.
5 Monteiro F,Abraham ME,Sahakari SD,et al.Effect of immobilization stress on food intake,body weight and weights of various organs in rat.Indian J Physiol Pharmacol 1989;33(3):186-190.
6 Lenard NR,Berthoud HR.Central and peripheral regulation of food intake and physical activity:pathways and genes.Obesity(Silver Spring)2008;16(Suppl3):s11-s22.
7 Yu YH,Deng C,Huang XF.Obese reversal by a chronic energy restricted diet leaves an increased Arc NPY/AgRP,but no alteration in POMC/CART,mRNA expression in diet-induced obese mice.Behav Brain Res 2009;205(1):50-56.
8 Oh TS,Cho H,Cho JH,et al.Hypothalamic AMPK-induced autophagy increases food intake by regulating NPYand POMC expression.Autophagy 2016;12(11):2009-2025.
9 Yoo SB,Ryu V,Park EY,et al.The arcuate NPY,POMC,and CART expressions responding to food deprivation are exaggerated in young female rats that experienced neonatal maternal separation.Neuropeptides 2011;45(5):343-349.
10 Wu J,Zou DJ.The research progress of leptin receptor.Sheng Li Ke Xue Jin Zhan 2000;31(2):143-146.
11 Wang HX,Lei ZH,Ding F,et al.Localization of long form leptin receptor mRNA in the hypothalamus in the pig studied by in situ hybridization.Nanjing Nong Ye Da Xue Xue Bao 2002;25(1):80-84.
12 Baskin DG,Schwartz MW,Seeley RJ,et al.Leptin receptor long-form splice-variant protein expression in neuron cell bodies of the brain and colocalization with nuropeptide Y mRNA in the arcuate nucleus.J Histochem Cytochem 1999;47(3):353-362.
13 Münzberg H,Huo L,Nillni EA,et al.Role of signal transducer and activator of transcription 3 in regulation of hypothalamic proopiomelanocortin gene expression by leptin.Endocrinology 2003;144(5):2121-2131.
14 Wang SX,Chen JX,Yue GX,et al.Xiaoyaosan decoction regulates changes in neuropeptide y and leptin receptor in the rat arcuate nucleus after chronic immobilization stress.Evid Based Complement Alternat Med 2012;2012:381278.
15 Jiang YM,Li XJ,Meng ZZ,et al.Effects of Xiaoyaosan on stress-induced anxiety-like behavior in rats:involvement of CRF1 receptor.Evid Based Complement Alternat Med 2016;2016:1238426.
16 Chen JX,Wei L,Zhao X,et al.Effects of the Chinese traditional prescription Xiaoyaosan decoction on chronic immobilization stress-induced changes in behavior and brain BDNF,TrkB,and NT-3 in rats.Cell Mol Neurobiol 2008;28(5):745-755.
17 Meng ZZ,Chen JX,Jiang YM,et al.Effect of xiaoyaosan decoction on learning and memory deficit in rats induced by chronic immobilization stress.Evid Based Complement Alternat Med 2013;2013:297154.
18 Li N,Liu Q,Li XJ,et al.TCM Formula Xiaoyaosan decoction improves depressive-like behaviors in rats with Type 2 diabetes.Evid Based Complement Alternat Med2015;2015:415243.
19 Stanley S,Wynne K,Mc Gowan B,et al.Hormonal regulation of food intake.Physiol Rev 2005;85(4):1131-1158.
20 Lecklin A,Lundell L,Paananen L,et al.Receptor subtypes Y1 and Y5 mediate neuropeptide Y induced feeding in the guinea-pig.Br J Pharmacol 2002;135(8):2029-2037.
21 Sun Z,Zhang ZC,Ma L,et al.Effects of acupuncture on appetite regulating factors NPY and leptin of obese rats.Zhong Guo Xing Wei Yi Xue Ke Xue 2005;14(12):1057-1059.
22 Hu CY,Li YW.Overview on the physiological functions of neuropeptide Y(NPY).Sheng Wu Xue Za Zhi 2011;28(2):66-68.
23 Cheung CC,Clifton DK,Steiner RA.Proo-piomelanocortion neurons are direct targets for leptin in the hypothalamus.Endocrinology 1997;138(10):4489-4492.
24 Finn PD,Cunningham MJ,Pau KY,et al.The stimulatory effect of leptin on the neuroendocrine reproductive axis of the monkey.Endocrinology 1998;139(11):4652-4662.
25 Quennell JH,Mulligan AC,Tups A,et al.Leptin indirectly regulates gonadotropin-releasing hormone neuronal function.Endocrinology 2009;150(6):2805-2812.
26 Hagan MM,Rushing PA,Schwartz MW,et al.Role of the CNS melanocortin system in the response to overfeeding.J Neurosci 1999;19(6):2362-2367.
27 Zhang HH,Zhang J,Guo XZ.The conceive outline of establishing self-rating Xiaoyaosan symptom of geriatric depression scale.Liaoning Zhong Yi Za Zhi 2009;36(10):1691-1692.
28 Hou J,Xiao L,Yang JP.Effect of platform-over-water stress on neuroendocrine internal secretion and thymus apoptosis and the regulative role of Jiawei Xiaoyao pill.Zhong Guo Lin Chuang Kang Fu 2005;9(44):100-102.
29 Fan LR.Curative effect observation of Xiaoyaosan on anxiety and depression after apoplexy.Shi Yong Zhong Xi Yi Jie He Lin Chuang 2013;13(4):52-53.
30 Xiao F,Xu BY,Li Y,et al.Effect of Jiawei Xiaoyao San on anxiety and depression in patients with psychological stress insomnia.Zhong Hua Zhong Yi Yao Xue Kan 2009;27(5):962-963.
31 Liu YY,Guo XL,Zhao HB,et al.Behavior evaluation of rat model with stagnation of liver Qi and spleen deficiency syndrome regulating by Xiaoyao San extract.Zhong Hua Zhong Yi Yao Za Zhi 2013;28(7):2138-2141.
32 Zhou J,Su R,Fan JP.The research progress of Xiaoyao powder main chemical components and their antidepressant effects.Zhong Guo Zhong Yi Ji Chu Yi Xue Za Zhi2014;20(2):278-279.
33 Miao YL.The pharmacological research situation of Xiaoyao San.Zhong Guo Chu Fang Yao 2014;12(9):141-142.
34 Li MT,Xiang H.The research progress in active ingredients and pharmacological effects of Xiaoyao San.Zhong Yao Cai 2010;33(12):1968-1972.
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