白藜芦醇及衍生物的研究进展
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摘要
白藜芦醇是一种具有不同生物活性的多酚化合物,已被证明具有显著的益处,包括抗肿瘤、抗氧化应激、抗炎、对神经及心血管系统的保护作用等。但是,低生物利用度妨碍了其治疗应用。因此,以二苯乙烯为基础得到的白藜芦醇衍生物或类似物受到更多的关注,它们比白藜芦醇有着较高的生物利用度和较低的生物毒性。本文对白藜芦醇和白藜芦醇衍生物的化学结构及其生物活性进行综述,为进一步研发新的白藜芦醇衍生物提供参考。
Resveratrol is a kind of polyphenolic substance with different biological activities and has been identified to have significant advantages including anti-tumor,anti-oxidative stress,anti-inflammatory,protective effects on the nervous and cardiovascular systems, etc. Howeverthe low bioavailability hampers its therapeutic applications. Therefore, resveratrol derivatives or analogs based on stilbene have been paid much attention to,which have higher bioavailability and lower biotoxicity than those of resveratrol. This article reviews the chemical structure and biological activity of resveratrol and resveratrol derivatives in order to provide a reference for the further research and development of new resveratrol derivatives.
Resveratrol is a kind of polyphenolic substance with different biological activities and has been identified to have significant advantages including anti-tumor,anti-oxidative stress,anti-inflammatory,protective effects on the nervous and cardiovascular systems, etc. Howeverthe low bioavailability hampers its therapeutic applications. Therefore, resveratrol derivatives or analogs based on stilbene have been paid much attention to,which have higher bioavailability and lower biotoxicity than those of resveratrol. This article reviews the chemical structure and biological activity of resveratrol and resveratrol derivatives in order to provide a reference for the further research and development of new resveratrol derivatives.
引文
1 Biasutto L,Mattarei A,Azzolini M,et al. Resveratrol derivatives as a pharmacological tool. Ann N Y Acad Sci,2017,1403:27-37.
2 Kursvietiene L,Staneviciene I,Mongirdiene A,et al. J Multiplicity of effects and health benefits of resveratrol. Medicina,2016,52:148-155.
3 Cottart CH,Nivet-Antoine V,Beaudeux JL. Review of recent data on the metabolism,biological effects,and toxicity of resveratrol in humans.Mol Nutr Food Res,2014,58:7-21.
4 Thiel G,Rssler OG. Resveratrol regulates gene transcription via activation of stimulus-responsive transcription factors. Pharmacol Res,2017,117:166-176.
5 Park,EJ,Pezzuto JM. The pharmacology of resveratrol in animals and humans. Biochim Biophys Acta,2015,1852:1071-1113.
6 Wicklow B,Wittmeier K,T’Jong GW,et al. Proposed trial:safety and efficacy of resveratrol for the treatment of non-alcoholic fatty liver disease(NAFLD)and associated insulin resistance in adolescents who are overweight or obese adolescents-Rationale and protocol. Biochem Cell Boil,2015,93:522-530.
7 Yang,Y,Li C,Li H,et al. Differential sensitivities of bladder cancer cell lines to resveratol are unrelated to its metabolic profile. Oncotarget,2017,8:40289-40304.
8 Bitterman,JL,Chung JH. Metabolic effects of resveratrol:Addressing the controversies. Cell Mol Life Sci,2015,72:1473-1488.
9 Weiskirchen S,Weiskirchen R. Resveratrol:How much wine do you have to drink to stay healthy? Adv Nutr,2016,7:706-718.
10 Yang T,Wang L,Zhu M,et al. Properties and molecular mechanisms of resveratrol:A review. Die Pharm,2015,70:501-506.
11 Mikula-PietrasikJ,Kuczmarska A,Ksiazek K. Biological multifunctionality of resveratrol and its derivatives. Postepy Biochem,2015,61:336-343.
12 Kulkarni SS,Canto C. The molecular targets of resveratrol. Biochim.Biophys Acta,2015,1852:1114-1123.
13 Keylor MH,Matsuura BS,Stephenson CR. Chemistry and biology of resveratrol-derived natural products. Chem Rev,2015,115:8976-9027.
14 Li C,Xu X,Tao Z,et al. Resveratrol derivatives:an updated patent review(2012-2015). Expert Opinion on Therapeutic Patents,2016,26:1189-1200.
15 Waqas N,Zhou Zq,Deng S,et al. Therapeutic versatility of resveratrol derivatives. Nutrients,2017,9:979-983.
16 Androutsopoulos VP,Fragiadaki I,Spandidos DA,et al. The resveratrol analogue,3,4,5,4’-trans-tetramethoxystilbene,inhibits the growth of a375 melanoma cells through multiple anticancer modes of action. Int J Oncol,2016,49:1305-1314.
17 Androutsopoulos VP,Fragiadaki I,Tosca A. Activation of ERK1/2 is required for the antimitotic activity of the resveratrol analogue 3,4,5,4 ’-tetramethoxystilbene(DMU-212)in human melanoma cells. Exp Dermatol,2015,24:632-634.
18 Li F, Zhu W, Gonzalez FJ. Potential role of CYP1B1 in the development and treatment of metabolic diseases. Pharmacol Ther,2017,178:18-30.
19 Nguyen GT,Gertz M,Steegborn C. Crystal structures of Sirt3 complexes with 40-bromo-resveratrol reveal binding sites and inhibition mechanism. Chem Boil,2013,20:1375-1385.
20 Cho S,Namkoong K,Shin M,et al. Cardiovascular Protective Effects and Clinical Applications of Resveratrol. J Med Food,2017,20:323-334.
21 Wu H,Li GN,Xie J,et al. Resveratrol ameliorates myocardial fibrosis by inhibiting ROS/ERK/TGF-b/periostin pathway in STZ-induced diabetic mice. BMC Cardiovasc Disord,2016,16:5.
22 Dorri Mashhadi F,Zavvar Reza J,Jamhiri M,et al. The effect of resveratrol on angiotensin II levels and the rate of transcription of its receptors in the rat cardiac hypertrophy model. J Physiol Sci,2016,67:303-309.
23 Guo Y, Zhang L, Li F,et al. Restoration of sirt1 function by pterostilbene attenuates hypoxia-reoxygenation injury in cardiomyocytes.Eur J Pharmacol,2016,776:26-33.
24 Liu B,Luo XJ,Yang ZB,et al. Inhibition of NOX/VPO1 pathway and inflammatory reaction by trimethoxystilbene in prevention of cardiovascular remodeling in hypoxia-induced pulmonary hypertensive rats. J Cardiovasc Pharmacol,2014,63:567-576.
25 Zhang L,Dai F,Cui L,et al. Novel role for TRPC4 in regulation of macroautophagy by a small molecule in vascular endothelial cells.Biochim Biophys Acta,2015,1853:377-387.
26 Jennings BL,Anderson LJ,Estes AM,et al. Involvement of cytochrome P-450 1B1 in renal dysfunction,injury,and inflammation associated with angiotensin ii-induced hypertension in rats. Am J physiol,2012,302 :F408-E420.
27 Tang YL,Chan SW. A review of the pharmacological effects of piceatannol on cardiovascular diseases. Phytother Res,2014,28:1581-1588.
28 Liu Z,Jiang C,Zhang J,et al. Resveratrol inhibits inflammation and ameliorates insulin resistant endothelial dysfunction via regulation of AMP-activated protein kinase and sirtuin 1 activities. J Diabetes,2016,8:324-335.
29 Grosch S,Niederberger E,Geisslinger G. Investigational drugs targeting the prostaglandin E2 signaling pathway for the treatment of inflammatory pain. Expert Opin Investig Drugs,2017,26:51-61.
30 Rothschild DE,Mc Daniel DK,Ringel-Scaia VM,et al. Modulating inflammation through the negative regulation of NF-κB signaling. J Leukoc Biol,2018,93:346-352.
31 Bellezza I,Giambanco I,Minelli A. Nrf2-Keap1 signaling in oxidative and reductive stress. Biochim Biophys Acta,2018,1865:721-733.
32 Zhao H,Chen S,Gao K,et al. Resveratrol protects against spinal cord injury by activating autophagy and inhibiting apoptosis mediated by the SIRT1/AMPK signaling pathway. Neurosci,2017,348:241-251.
33 Jiang Z,Chen K,Cheng L,et al. Resveratrol and cancer treatment:updates. Ann. N Y Acad Sci,2017,1403:59-69.
34 Remsberg CM,Yanez JA,Ohgami Y,et al. Pharmacometrics of pterostilbene:Preclinical pharmacokinetics and metabolism,anticancer,antiinflammatory,antioxidant and analgesic activity. Phytother Res PTR,2008,22:169-179.
35 Chang J,Rimando A,Pallas M,et al. Low-dose pterostilbene,but not resveratrol,is a potent neuromodulator in aging and Alzheimer’s disease. Neurobiology of Aging,2012,33:792-797.
36 Karalis F,Soubasi V,Georgiou T,et al. Nakas,constantina simeonidou,olympia guiba-tziampiri,evangelia spandou. Resveratrol ameliorates hypoxia/ischemia-induced behavioral deficits and brain injury in the neonatal rat brain. Brain Research,2011,92:1425.
37 Chang J,Rimando A,Pallas M,et al. Low-dose pterostilbene,but not resveratrol,is a potent neuromodulator in aging and alzheimer’s disease. Neurobiol Aging,2012,33:2062-2071.
38 Angeles DC,Ho P,Dymock BW,et al. Antioxidants inhibit neuronal toxicity in Parkinson’s disease-linked LRRK2. Ann Clin Transl Neurol,2016,3:288-294.
39 Nguyen CB,Kotturi H,Waris G,et al.(Z)-3,5,40-trimethoxystilbene limits hepatitis c and cancer pathophysiology byblocking microtubule dynamics and cell-cycle progression. Cancer Res,2016,76:4887-4896.
40 Nagaradja E,Bentabed-Ababsa G,Scalabrini M,et al. Deprotometalationiodolysis and computed CH acidity of 1,2,3-and 1,2,4-triazoles.Application to the synthesis of resveratrol analogues. Bioorg Med Chem,2015,23:6355-6363.
41 Han YS,Quashie PK,Mesplede T. A resveratrol analog termed 3,30,4 ,40,5,50-hexahydroxy-trans-stilbene is a potent HIV-1 inhibitor. J Med Virol,2015,87:2054-2060.
2 Kursvietiene L,Staneviciene I,Mongirdiene A,et al. J Multiplicity of effects and health benefits of resveratrol. Medicina,2016,52:148-155.
3 Cottart CH,Nivet-Antoine V,Beaudeux JL. Review of recent data on the metabolism,biological effects,and toxicity of resveratrol in humans.Mol Nutr Food Res,2014,58:7-21.
4 Thiel G,Rssler OG. Resveratrol regulates gene transcription via activation of stimulus-responsive transcription factors. Pharmacol Res,2017,117:166-176.
5 Park,EJ,Pezzuto JM. The pharmacology of resveratrol in animals and humans. Biochim Biophys Acta,2015,1852:1071-1113.
6 Wicklow B,Wittmeier K,T’Jong GW,et al. Proposed trial:safety and efficacy of resveratrol for the treatment of non-alcoholic fatty liver disease(NAFLD)and associated insulin resistance in adolescents who are overweight or obese adolescents-Rationale and protocol. Biochem Cell Boil,2015,93:522-530.
7 Yang,Y,Li C,Li H,et al. Differential sensitivities of bladder cancer cell lines to resveratol are unrelated to its metabolic profile. Oncotarget,2017,8:40289-40304.
8 Bitterman,JL,Chung JH. Metabolic effects of resveratrol:Addressing the controversies. Cell Mol Life Sci,2015,72:1473-1488.
9 Weiskirchen S,Weiskirchen R. Resveratrol:How much wine do you have to drink to stay healthy? Adv Nutr,2016,7:706-718.
10 Yang T,Wang L,Zhu M,et al. Properties and molecular mechanisms of resveratrol:A review. Die Pharm,2015,70:501-506.
11 Mikula-PietrasikJ,Kuczmarska A,Ksiazek K. Biological multifunctionality of resveratrol and its derivatives. Postepy Biochem,2015,61:336-343.
12 Kulkarni SS,Canto C. The molecular targets of resveratrol. Biochim.Biophys Acta,2015,1852:1114-1123.
13 Keylor MH,Matsuura BS,Stephenson CR. Chemistry and biology of resveratrol-derived natural products. Chem Rev,2015,115:8976-9027.
14 Li C,Xu X,Tao Z,et al. Resveratrol derivatives:an updated patent review(2012-2015). Expert Opinion on Therapeutic Patents,2016,26:1189-1200.
15 Waqas N,Zhou Zq,Deng S,et al. Therapeutic versatility of resveratrol derivatives. Nutrients,2017,9:979-983.
16 Androutsopoulos VP,Fragiadaki I,Spandidos DA,et al. The resveratrol analogue,3,4,5,4’-trans-tetramethoxystilbene,inhibits the growth of a375 melanoma cells through multiple anticancer modes of action. Int J Oncol,2016,49:1305-1314.
17 Androutsopoulos VP,Fragiadaki I,Tosca A. Activation of ERK1/2 is required for the antimitotic activity of the resveratrol analogue 3,4,5,4 ’-tetramethoxystilbene(DMU-212)in human melanoma cells. Exp Dermatol,2015,24:632-634.
18 Li F, Zhu W, Gonzalez FJ. Potential role of CYP1B1 in the development and treatment of metabolic diseases. Pharmacol Ther,2017,178:18-30.
19 Nguyen GT,Gertz M,Steegborn C. Crystal structures of Sirt3 complexes with 40-bromo-resveratrol reveal binding sites and inhibition mechanism. Chem Boil,2013,20:1375-1385.
20 Cho S,Namkoong K,Shin M,et al. Cardiovascular Protective Effects and Clinical Applications of Resveratrol. J Med Food,2017,20:323-334.
21 Wu H,Li GN,Xie J,et al. Resveratrol ameliorates myocardial fibrosis by inhibiting ROS/ERK/TGF-b/periostin pathway in STZ-induced diabetic mice. BMC Cardiovasc Disord,2016,16:5.
22 Dorri Mashhadi F,Zavvar Reza J,Jamhiri M,et al. The effect of resveratrol on angiotensin II levels and the rate of transcription of its receptors in the rat cardiac hypertrophy model. J Physiol Sci,2016,67:303-309.
23 Guo Y, Zhang L, Li F,et al. Restoration of sirt1 function by pterostilbene attenuates hypoxia-reoxygenation injury in cardiomyocytes.Eur J Pharmacol,2016,776:26-33.
24 Liu B,Luo XJ,Yang ZB,et al. Inhibition of NOX/VPO1 pathway and inflammatory reaction by trimethoxystilbene in prevention of cardiovascular remodeling in hypoxia-induced pulmonary hypertensive rats. J Cardiovasc Pharmacol,2014,63:567-576.
25 Zhang L,Dai F,Cui L,et al. Novel role for TRPC4 in regulation of macroautophagy by a small molecule in vascular endothelial cells.Biochim Biophys Acta,2015,1853:377-387.
26 Jennings BL,Anderson LJ,Estes AM,et al. Involvement of cytochrome P-450 1B1 in renal dysfunction,injury,and inflammation associated with angiotensin ii-induced hypertension in rats. Am J physiol,2012,302 :F408-E420.
27 Tang YL,Chan SW. A review of the pharmacological effects of piceatannol on cardiovascular diseases. Phytother Res,2014,28:1581-1588.
28 Liu Z,Jiang C,Zhang J,et al. Resveratrol inhibits inflammation and ameliorates insulin resistant endothelial dysfunction via regulation of AMP-activated protein kinase and sirtuin 1 activities. J Diabetes,2016,8:324-335.
29 Grosch S,Niederberger E,Geisslinger G. Investigational drugs targeting the prostaglandin E2 signaling pathway for the treatment of inflammatory pain. Expert Opin Investig Drugs,2017,26:51-61.
30 Rothschild DE,Mc Daniel DK,Ringel-Scaia VM,et al. Modulating inflammation through the negative regulation of NF-κB signaling. J Leukoc Biol,2018,93:346-352.
31 Bellezza I,Giambanco I,Minelli A. Nrf2-Keap1 signaling in oxidative and reductive stress. Biochim Biophys Acta,2018,1865:721-733.
32 Zhao H,Chen S,Gao K,et al. Resveratrol protects against spinal cord injury by activating autophagy and inhibiting apoptosis mediated by the SIRT1/AMPK signaling pathway. Neurosci,2017,348:241-251.
33 Jiang Z,Chen K,Cheng L,et al. Resveratrol and cancer treatment:updates. Ann. N Y Acad Sci,2017,1403:59-69.
34 Remsberg CM,Yanez JA,Ohgami Y,et al. Pharmacometrics of pterostilbene:Preclinical pharmacokinetics and metabolism,anticancer,antiinflammatory,antioxidant and analgesic activity. Phytother Res PTR,2008,22:169-179.
35 Chang J,Rimando A,Pallas M,et al. Low-dose pterostilbene,but not resveratrol,is a potent neuromodulator in aging and Alzheimer’s disease. Neurobiology of Aging,2012,33:792-797.
36 Karalis F,Soubasi V,Georgiou T,et al. Nakas,constantina simeonidou,olympia guiba-tziampiri,evangelia spandou. Resveratrol ameliorates hypoxia/ischemia-induced behavioral deficits and brain injury in the neonatal rat brain. Brain Research,2011,92:1425.
37 Chang J,Rimando A,Pallas M,et al. Low-dose pterostilbene,but not resveratrol,is a potent neuromodulator in aging and alzheimer’s disease. Neurobiol Aging,2012,33:2062-2071.
38 Angeles DC,Ho P,Dymock BW,et al. Antioxidants inhibit neuronal toxicity in Parkinson’s disease-linked LRRK2. Ann Clin Transl Neurol,2016,3:288-294.
39 Nguyen CB,Kotturi H,Waris G,et al.(Z)-3,5,40-trimethoxystilbene limits hepatitis c and cancer pathophysiology byblocking microtubule dynamics and cell-cycle progression. Cancer Res,2016,76:4887-4896.
40 Nagaradja E,Bentabed-Ababsa G,Scalabrini M,et al. Deprotometalationiodolysis and computed CH acidity of 1,2,3-and 1,2,4-triazoles.Application to the synthesis of resveratrol analogues. Bioorg Med Chem,2015,23:6355-6363.
41 Han YS,Quashie PK,Mesplede T. A resveratrol analog termed 3,30,4 ,40,5,50-hexahydroxy-trans-stilbene is a potent HIV-1 inhibitor. J Med Virol,2015,87:2054-2060.