孔令东
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- 姓名:孔令东
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博士生导师
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光学
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孔令东,教授,1985、1990和1996年分别在南京中医药大学获中药专业学士、硕士和博士学位。1985年至1993年在该校任助教和讲师。1996年进入南京大学生物学博士后流动站,1998年4月被聘任为南京大学植物学副教授。2000年获教育部首批高等学校骨干教师资助计划。2003年10月被聘任为教授,2004年4月担任博士生导师。
1985年至1996年在南京中医学院工作期间,参与完成卫生部药典委员会委托项目1项,参与完成国家“八五”科技攻关项目2项、江苏省级课题3项。完成江苏省科技成果鉴定项目3项。1996年10月作为第二完成人获“八五”国家科技攻关重大科技成果、1997年度国家中医药管理局中医药科技进步二等奖。1996年12月作为第三完成人获江苏省教委科技进步二等奖。2001年获江苏省教委首届优秀博士论文奖。
1996年在南京大学工作期间,先后承担和参加各类科研项目10余项。在中药抗抑郁和痛风方面,1998年负责完成中国博士后科学基金一项。2000年作为第二主持人完成国家科技部中药现代化和产业化重点攻关项目和省自然基金项目各一项。2002-2003年负责完成教育部首批高等学校骨干教师资助计划、国家和江苏省自然科学基金项目各一项。1999年和2003年江苏省自然科学基金结题等级均为优等。分别作为第1、1、2和6完成人完成江苏省科技成果鉴定项目4项。在中国申请有关药物新用途专利5项。已在国际“SCI”学术榜刊物上发表中药研究论文21篇,在国内自然科学核心刊物上发表论文35篇。现承担国家自然科学基金项目二项,江苏省自然科学基金项目一项。
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10
孔令东, Ling Dong Kong, , Ren Xiang Tan, Anthony Yiu Ho Woo and Christopher Hon Ki Cheng
Pharmacology & Toxicology 2001, 88, 75-80.,-0001,():
-1年11月30日
Psoralen and isopsoralen, furocoumarins isolated from the plant Psoralea corylifolia L., were demonstrated to exhibit in vitro inhibitory actions on monoamine oxidase (MAO) activities in rat brain mitochondria, preferentially inhibiting MAO-A activity over MAO-B activity. This inhibition of enzyme activities was found to be dose-dependent and reversible. For MAO-A, the IC50 values are 15.2±1.3μM psoralen and 9.0±0.6μM isopsoralen. For MAO-B, the IC50 values are 61.8±4.3μM psoralen and 12.8±0.5μM isopsoralen. Lineweaver-Burk transformation of the inhibition data indicates that inhibition by both psoralen and isopsoralen is non-competitive for MAO-A. The Ki values were calculated to be 14.0μM for psoralen and 6.5μM for isopsoralen. On the other hand, inhibition by both psoralen and isopsoralen is competitive for MAO-B. The Ki values were calculated to be 58.1μM for psoralen and 10.8μM for isopsoralen. These inhibitory actions of psoralen and isopsoralen on rat brain mitochondrial MAO activities are discussed in relation to their toxicities and their potential applications to treat affective disorders.
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【期刊论文】Glycosides and xanthine oxidase inhibitors from Conyza bonariensis
孔令东, L.D. Kong a, Z. Abliz b, C.X. Zhou a, L.J. Li b, C.H.K. Cheng c, R.X. Tan a, *
Phytochemistry 58(2001)645-651,-0001,():
-1年11月30日
Fractionation of the xanthine oxidase inhibitory methanol extract of Conyza bonariensis afforded three glycosides, in addition to nine known compounds including amyrin, b-sitostero1 daucosterol, syringic acid 3-hydroxy-5-methoxybenzoic acid, eugenol 4-Oglucopyranoside, and luteolin, apigenin and takakin 8-O-glucuronide. The structures of the glycosides were established by a combination of spectroscopic methods (IR, MS, 1Hand 13C NMR, DEPT, COSY, HMQC and HMBC) as 4-hydroxypyridin-3-carboxylic acid 4-O-glucopyranoside, 8-hydroxy-6,7-dihydrolinalool 8-O-glucopyranoside and bonaroside [viz. 1,3,4,12-tetrahydroxy-2-(9-hexadecenoylamino) octadecane 1-O-glucopyranoside]. The in vitro enzyme assay showed that syringic acid and takakin 8-O-glucuronide displayed weak inhibitory activity against xanthine oxidase with IC50 values of 500±41μM and 170±12μM, respectively.
Conyza bonariensis, Asteraceae, 4-Hydroxypyridin-3-carboxylic acid 4-O-glucopyranoside, 8-Hydroxy-6,, 7-dihydrolinalool 8-O-glucopyranoside, Bonaroside, Syringic acid, Takakin 8-O-glucuronide
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【期刊论文】Antidepressant activity of aqueous extracts of Curcuma longa in mice
孔令东, Z.F. Yu, L.D. Kong*, Y. Chen
Journal of Ethnopharmacology 83(2002)161-165,-0001,():
-1年11月30日
Curcuma longa (turmeric) is a well-known indigenous herbal medicine. The aqueous extracts, when administered orally to the mice from 140 to 560mg/kg for 14 days, were able to elicit dose-dependent relation of immobility reduction in the tail suspension test and the forced swimming test in mice. The effects of the extracts at the dose of 560mg/kg were more potent than that of reference antidepressant fluoxetine. The extracts, at the dose of 140mg/kg or above for 14 days, significantly inhibited the monoamine oxidize A (MAO) activity in mouse whole brain at a dose-dependent manner, however, oral administration of the extract only at a dose of 560mg/kg produced observable MAO B inhibitory activity in animal brain. Fluoxetine showed only a tendency to inhibit MAO A and B activity in animal brain in the study. Neither the extracts of C. longa nor fluoxetine, at the doses tested, produced significant effects on locomotor activity. These results demonstrated that C. longa had specifically antidepressant effects in vivo. The activity of C. longa in antidepression may mediated in part through MAO A inhibition in mouse brain.
Curcuma longa, Antidepressant activity, Immobility, MAO A, MAO B
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孔令东, Jian-Mei Li a, Ling-Dong Kong a, *, Ye-Min Wang a, Christopher H.K. Cheng b, Wei-Yun Zhang c, Wen-Zhi Tan a
Life Sciences 74(2003)55-73,-0001,():
-1年11月30日
There is increasing evidence that psychological stress and depression trigger changes in various biochemical parameters in animals and in human subjects. In order to study these effects, the impact of chronic mild stress (CMS) on rats, and of the subsequent administration of Banxia-houpu decoction and fluoxetine, were studied regarding their effects on the following biochemical parameters: 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels in various brain regions, natural killer (NK) cell and lymphokineactivated killer (LAK) cell activities in spleen, serum lipid profiles including total cholesterol (TC), high density lipoprotein cholesterol (HDLc), low density lipoprotein cholesterol (LDLc) and triglyceride (TG), liver superoxide dismutase (SOD) and nitric oxide synthase (NOS) activities, serum malondialdehyde (MDA), and interleukin-2 (IL-2) levels. The effects of drug administration on preference behavior for consumption of sucrose solution were also assessed. Rats subjected to CMS exhibited a reduction in sucrose intake, 5-HT, 5-HIAA, IL-2, TC, HDLc and LDLc levels, as well as, diminished NK cell and LAK cell activities. Conversely, liver SOD and NOS activities and serum TG and MDA levels were increased following CMS exposures. Administration of Banxia-houpu decoction and fluoxetine produced beneficial effects on the stressed rats by improving sucrose consumption. This behavioral change was accompanied by amelioration of numbers CMS-induced biochemical changes. Banxiahoupu decoction is a traditional Chinese prescription containing pinellia tuber, magnolia bark, hoelen, perilla herb and ginger rhizome, and has been used for centuries in China to treat mental diseases including depression and schizophrenia. However, the pharmacological profile of the decoction is different from that of fluoxetine. These findings uggest that the therapeutic actions of Banxia-houpu decoction are due to a combination of multiple biochemical effects, and may help to elucidate the mechanisms through which distinct biochemical parameters play a role in the etiology of depression.
Chronic mild stress, Depression, Chinese medicine, Banxia-houpu decoction
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孔令东, Yusong Guo, Lingdong Kong*, Yemin Wang and Zhiqi Huang
PHYTOTHERAPY RESEARCH Phytother. Res. 18, 204-207(2004),-0001,():
-1年11月30日
Banxia-houpu decoction, a traditional Chinese medicine has been used in the treatment of depression. The present study confirmed that oral administration of polysaccharides from Banxia-houpu decoction, exhibited a reduction in the immobility time in the tail suspension and in the forced swimming tests in mice in a timedependent manner. This effect at a dose of 320mg/kg was more potent than that at a dose of 640mg/kg. The polysaccharides from Banxia-houpu decoction were active in animal models of depression with comparable effects to known antidepressants. The oral administration of the polysaccharides at a low dose for 4 weeks resulted in a significant increase in the monoamine neurotransmitter 5-hydroxytryptamine (5-HT) and dopamine (DA) levels in whole mouse brain, but produced no significant increase in 5-hydroxyindoleacetic acid (5-HIAA) and norepinephrine (NE) concentrations. The effect of polysaccharides on the brain neurotransmitter levels appeared to be quite different from the effect of fluoxetine, a serotonin specific reuptake inhibitor. The results indicate that the mode of action of polysaccharides from Banxia-houpu decoction in depression might be related to both 5-HT and DA systems. Copyright.
Banxia-houpu decoction, tail suspension test (, TST), , forced swimming test (, FST), , neurotransmitter levels.,
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孔令东, Weiyun Zhang, , Jianmei Li, Jixiao Zhu, Zhenqiu Shi, Yong Wang and Lingdong Kong*
PHYTOTHERAPY RESEARCH Phytother. Res. 18, 200-203(2004),-0001,():
-1年11月30日
Banxia-houpu decoction is a safe and effective traditional Chinese medicinal formula used in the treatment of mild and manic-depressive disorders for centuries. There has been increasing interest in its therapeutic application in depression. However, the mechanisms behind behavioural changes are still poorly understood. Chronic mild stress (CMS)-induced preference behaviour change has been used as a model to predict the clinical efficacy of many types of antidepressant treatment. Both EtOH and water extracts (AE and WE) of Banxia-houpu decoction exhibited a significantly increased sucrose intake in the CMS model in rats, but there was no effect in unstressed animals. In the present study, it was found that the c-fos expression in cerebral cortex, hippocampus and striatum corpora were very high in the CMS model in rats. WE and AE at a dose of 130mg/kg exhibited a significantly decreased c-fos expression in the cerebral regions in CMS model in rats, respectively. The former was more potent than the latter. However, no significant changes in the c-fos expression were observed in unstressed rats treated with the decoction. Fluoxetine not only significantly reduced cfos expression in all regions in the CMS model in rats, but only showed a marked decrease in c-fos expression in the hippocampus in unstressed animals. A different molecular mechanism of Banxia-houpu decoction and fluoxetine may be implied. The cerebral cortex, hippocampus and striatum conpora might be important structural substrates in the central nervous system mediating the section of the Banxia-houpu decoction on preference behaviour in CMS-induced rats, and fos protein might be the common substrate of the signal transduction process of the decoction. Copyright.
Banxia-houpu decoction, CMS model, c-fos immunohistochemistry.,
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【期刊论文】Inhibition of MAO A and B by some plant-derived alkaloids, phenols and anthraquinones
孔令东, L.D. Kong a, Christopher H.K. Cheng b, R.X. Tan a, *
Journal of Ethnopharmacology 91(2004)351-355,-0001,():
-1年11月30日
A total of seventeen phytochemicals including seven alkaloids (piperine, strychnine, brucine, stachydrine, tetrandrine, frangchinoline and sinomenine), four phenols (paeonol, honokiol, magnolol and eugenol) and six anthraquinones (emodin, rhein, chrysorphanol, aloe-emodin, physcion and 1,8-dihydroxyanthraquinone) was examined for inhibitory activity of monoamine oxidase (MAO) A and B from rat brain mitochondrial. Among these compounds, piperine and paeonol were found to be inhibitory against MAO A in a dose-dependent manner with IC50 values of 49.3 and 54.6μM, respectively. Piperine, paeonol and emodin were shown to inhibit MAO B in a dose-dependent manner with the IC50 data of 91.3, 42.5 and 35.4μM, respectively. Lineweaver-Burk transformation of the inhibition data indicated that the inhibitory action of piperine onMAO A was of mixed type, and that of paeonol on the same type of the enzyme was of non-competitive type. For piperine, the Ki and KI were determined to be 35.8 and 25.7μM, respectively. For paeonol, the Ki was estimated to be 51.1μM. The inhibition of piperine and paeonol on MAO B was of competitive type with Ki values of 79.9 and 38.2μM, respectively. The inhibition of emodin on MAO B was of mixed type with the Ki and KI data of 15.1 and 22.9μM, respectively. The present investigation showed that the phytochemicals piperine, paeonol and emodin are potent MAO inhibitors whereas other compounds were inactive against any type of MAO at 100μM in the present assay.
Piperine, Paeonol, Emodin, Monoamine oxidase
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孔令东, Ying Wang, Ji Xiao Zhu, Ling Dong Kong, Cheng Yang, Christopher Hon Ki Cheng and Xin Zhang
Basic & Clinical Pharmacology & Toxicology 2004, 94, 232-237.,-0001,():
-1年11月30日
In this study we have investigated the effects of administration of procyanidins from grape seeds on serum uric acid levels in a model of hyperuricaemia in mice pretreated with oxonate, as well as the xanthine dehydrogenase and xanthine oxidase activities in mouse liver in vivo. The procyanidins, when orally administered to the oxonate-pretreated hyperuricaemic mice, were able to elicit a dose-dependent hypouricaemic effect. At a dose of 400mg/kg for 3 days, the serum urate levels of the oxonate-pretreated mice were not different from the normal mice. In addition, the hepatic activities of xanthine dehydrogenase and xanthine oxidase in the procyanidins-treated mice were found to decrease significantly. However, the hypouricaemic effects observed in the experimental animals did not seem to parallel the changes in xanthine dehydrogenase and xanthine oxidase activities, implying that the procyanidins might be acting via other mechanisms apart from simple inhibition of enzyme activities. Furthermore, the procyanidin-treated animals exhibited normal growth while the allopurinol-treated animals exhibited some retarded growth. These results demonstrated for the first time that the procyanidins from grape seeds possess in vivo urate-lowering activities. The potential application of these natural compounds in the treatment of hyperuricaemia is discussed.
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孔令东, Ji Xiao Zhu, Ying Wang, Ling Dong Kong∗, Cheng Yang, Xin Zhang
Journal of Ethnopharmacology 93(2004)133-140,-0001,():
-1年11月30日
The hypouricemic actions of Biota orientalis (BO) extract and its flavonoid constituents quercetin and rutin, were in vivo examined using oxonate-induced hyperuricemic mice. Quercetin and rutin, when administered three times orally to the oxonate-induced hyperuricemic mice, were able to elicit dose-dependent hypouricemic effects. The effects of quercetin and rutin were more potent than that of Biota orientalis extract at the same dose of 100mg/kg. At doses of 50mg/kg of quercetin or above, or at doses of 100mg/kg of rutin or above, the serum urate levels of the oxonate-pretreated mice were not different from normal mice. In addition, Biota orientalis extract, quercetin and rutin, when tested in vivo on mouse liver homogenates, elicited significant inhibitory actions on the xanthine dehydrogenase/xanthine oxidase (XDH/XO) activities. The effects of quercetin and rutin resulted less potent than that of allopurinol. However, intraperitoneal administration at the same scheme did not produce any observable hypouricemic effect. These hypouricemic effects are partly due to the inhibition of XDH/XO activities in mouse liver. The pharmacological profile of the flavonoids is partly different from that of allopurinol. Such hypouricemic action and inhibition of the enzyme activity of quercetin and rutin may be responsible for a part of the beneficial effects of Biota orientalis extract on hyperuricemia and gout. The effects of quercetin and rutin on serum urate levels in hyperuricemic mice induced by oxonate and the inhibition of enzyme activities in mouse liver are discussed in relation to their absorption and metabolism, and their potential application to treat gout and hyperuricemia.
Biota orientalis, Quercetin, Rutin, Hyperuricemic mice, Serum uric acid levels, Xanthine dehydrogenase/, xanthine oxidase activities
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孔令东, Ling Dong Kong a, ∗, Chen Yang a, Fei Ge a, Hai Dong Wang b, Yu Song Guo a
Journal of Ethnopharmacology 93(2004)325-330,-0001,():
-1年11月30日
Ermiao wan, which is composed of phellodendri cortex and atractylodis rhizome, is described as eliminating heat, excreting dampness and anti-edema prescription in traditional Chinese medical literatures including Danxi's Experiences in Medicine and State Pharmacopoeia of People's Republic of China. So it is being used clinically in the treatment of gout and hyperuricemia in China. In the present study, the water extracts of Ermiao wan and phellodendri cortex at 840 and 480mg/kg/day orally for 7 days were demonstrated to possess in vivo potent hypouricemic effects both in hyperuricemic mice pretreated with oxonate and in normal mice, respectively. In the hyperuricemic animals, the effect of Ermiao wan was equal to that of the reference drug allopurinol (at 10mg/kg/day orally for 7 days), but in the normal mice, the former was weaker than latter. In addition, both Ermiao wan and phellodendri cortex were found to have in vivo relatively inhibitory effects on mouse liver xanthine dehydrogenase (XDH) and xanthine oxidase (XO) activities at the same dose described above. These inhibitory effects were weaker than that observed for allopurinol. Atractylodis rhizome at 340mg/kg/day orally for 7 days did not show any effects on the above experiments. These results suggested that atractylodis rhizomes assisted and enhanced the effect of phellodendri cortex on reduction of serum uric acid level in hyperuricemic mice, and hypouricemic effects of Ermiao wan and phellodendri cortex may be achieved by other mechanism partly instead of the XDH and XO inhibition.
Ermiao wan, Phellodendri cortex, Atractylodis rhizome, Hyperuricemia, Hypouricemic effect, Xanthine dehydrogenase, Xanthine oxidase
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