Pub Date : 2019-02-06DOI: 10.5772/INTECHOPEN.79739
P. Devi, Pratibha Sharma, C. Rathore, P. Negi
Resveratrol is a naturally occurring product used in the prevention and treatment of various diseases by acting as a potent defensive antioxidant. Resveratrol can be used in various fields, but the use is limited due to its poor solubility and hence low bioavail - ability. For overcoming this limitation, various drug delivery systems of resveratrol were developed. The aim of the novel drug delivery system (NDDS) is to provide a therapeu- tic amount of drug to the target site to maintain the desired drug concentration. NDDS enhances the duration of therapeutic activity, increases plasma half-life, decreases the immunogenicity, increases the stability of biopharmaceuticals, improves the solubility of low molecular weight drugs so does the bioavailability, and has a potential of targeted drug delivery. However, they have their own advantages as well as limitations. This chapter focuses on: (1) general introduction to resveratrol and its various therapeutic uses, (2) pharmacokinetic- and bioavailability-related problems of resveratrol, and (3) general about various NDDS used in resveratrol formulations.
{"title":"Novel Drug Delivery Systems of Resveratrol to Bioavailability and Therapeutic Effects","authors":"P. Devi, Pratibha Sharma, C. Rathore, P. Negi","doi":"10.5772/INTECHOPEN.79739","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.79739","url":null,"abstract":"Resveratrol is a naturally occurring product used in the prevention and treatment of various diseases by acting as a potent defensive antioxidant. Resveratrol can be used in various fields, but the use is limited due to its poor solubility and hence low bioavail - ability. For overcoming this limitation, various drug delivery systems of resveratrol were developed. The aim of the novel drug delivery system (NDDS) is to provide a therapeu- tic amount of drug to the target site to maintain the desired drug concentration. NDDS enhances the duration of therapeutic activity, increases plasma half-life, decreases the immunogenicity, increases the stability of biopharmaceuticals, improves the solubility of low molecular weight drugs so does the bioavailability, and has a potential of targeted drug delivery. However, they have their own advantages as well as limitations. This chapter focuses on: (1) general introduction to resveratrol and its various therapeutic uses, (2) pharmacokinetic- and bioavailability-related problems of resveratrol, and (3) general about various NDDS used in resveratrol formulations.","PeriodicalId":21139,"journal":{"name":"Resveratrol - Adding Life to Years, Not Adding Years to Life","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84496518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-02-06DOI: 10.5772/INTECHOPEN.79498
Vinitha M. Thadhani
Diabetes is the most common serious metabolic disorder and one of the five leading causes of death worldwide. It is characterized by persistent hyperglycemia coincident with the induction of oxidative stress and alterations in glucose and lipid metabolism– regulating enzymes. Resveratrol has immerged as one of the leading natural ingredients to combat diabetic and its complications. Despite an abundance of laboratory and animal research, there is little clinical evidence to establish resveratrol effectiveness as a thera peutic against diabetes. Further, the poor bioavailability and stability of resveratrol in humans have been a major concern for translating basic science findings into clinical utility. In this review, we embark on large, well-controlled clinical studies to confirm the efficacy of resveratrol in the management of diabetes mellitus and gain a better insight into its biological effects in humans. Further possible methods of increasing the stability and bioavailability for such trials are also discussed.
{"title":"Resveratrol in Management of Diabetes and Obesity: Clinical Applications, Bioavailability, and Nanotherapy","authors":"Vinitha M. Thadhani","doi":"10.5772/INTECHOPEN.79498","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.79498","url":null,"abstract":"Diabetes is the most common serious metabolic disorder and one of the five leading causes of death worldwide. It is characterized by persistent hyperglycemia coincident with the induction of oxidative stress and alterations in glucose and lipid metabolism– regulating enzymes. Resveratrol has immerged as one of the leading natural ingredients to combat diabetic and its complications. Despite an abundance of laboratory and animal research, there is little clinical evidence to establish resveratrol effectiveness as a thera peutic against diabetes. Further, the poor bioavailability and stability of resveratrol in humans have been a major concern for translating basic science findings into clinical utility. In this review, we embark on large, well-controlled clinical studies to confirm the efficacy of resveratrol in the management of diabetes mellitus and gain a better insight into its biological effects in humans. Further possible methods of increasing the stability and bioavailability for such trials are also discussed.","PeriodicalId":21139,"journal":{"name":"Resveratrol - Adding Life to Years, Not Adding Years to Life","volume":"22 5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85572730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-11-05DOI: 10.5772/INTECHOPEN.77852
T. Hsieh, B. Doonan, Joseph M. Wu
Transcription factor c-myc is frequently amplified/overexpressed in human cancers. One event c-myc controls is metabolic reprogramming or the addiction for glucose and/or glutamine as nutrients. Rewiring of metabolic circuitry provides cancer cells with a gain-of-survival advan - tage. Accordingly, the aversion of two types of oncogenic-distinct metabolic addictions via c-myc control offers an anti-tumorigenic approach. Resveratrol reportedly inhibits the uptake/ transport of glucose or glutamine and reduces c-myc expression in cancer cells. Whether c-myc control by resveratrol involves quinone reductase NQO2 is unknown. NQO2 expressing (shRNA08) and knockdown (shRNA25) CWR22Rv1 prostate cancer cells were generated and used to study the role of NQO2 in growth and cell cycle control. Immunoblot analyses were used to evaluate the changes of cell cycle-associated proteins. NQO2 in mediating degradation of cyclin D1 via AKT/GSK-3β by resveratrol was tested by determining AKT and chymotryp - sin-like proteasome activities. Molecular modeling and pull-down/deletion assays were used to evaluate the interaction between NQO2 and AKT. Resveratrol interacts with NQO2, a qui - none reductase that plays a key role in resveratrol-induced AKT/GSK3β-mediated degradation of cyclin D1. In this chapter, we unravel control of expression and stability of c-myc by the res - veratrol-NQO2 axis as an approach to overcome c-myc-mediated metabolic reprogramming. that NQO2 NF-kB activation; NQO2 deletion potentiates the induction of apoptosis by abolishing TNF-induced cell survival kinases JNK, AKT, p38, and p44/p42 MAPK NQO2 C/EBPα proteasomes target dimeric NQO2 its other functions. novel pertain to c-myc T58 NQO2-knockdown cells, NQO2: AKT controls stability c-myc AKT/GSK3β-c-myc T-58 phosphorylation, by regulation of activity and functioning of the proteasome. Results of these studies will provide support for the as yet untested hypothesis regarding the indirect role of NQO2 in controlling AKT → GSK3β → c-myc T58 phosphorylation → c-myc degradation by proteasome, and the direct role of res veratrol acting as a metabolic switch to shut off c-myc-mediated metabolic reprogramming in cancer cells.
{"title":"c-Myc Metabolic Addiction in Cancers Counteracted by Resveratrol and NQO2","authors":"T. Hsieh, B. Doonan, Joseph M. Wu","doi":"10.5772/INTECHOPEN.77852","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.77852","url":null,"abstract":"Transcription factor c-myc is frequently amplified/overexpressed in human cancers. One event c-myc controls is metabolic reprogramming or the addiction for glucose and/or glutamine as nutrients. Rewiring of metabolic circuitry provides cancer cells with a gain-of-survival advan - tage. Accordingly, the aversion of two types of oncogenic-distinct metabolic addictions via c-myc control offers an anti-tumorigenic approach. Resveratrol reportedly inhibits the uptake/ transport of glucose or glutamine and reduces c-myc expression in cancer cells. Whether c-myc control by resveratrol involves quinone reductase NQO2 is unknown. NQO2 expressing (shRNA08) and knockdown (shRNA25) CWR22Rv1 prostate cancer cells were generated and used to study the role of NQO2 in growth and cell cycle control. Immunoblot analyses were used to evaluate the changes of cell cycle-associated proteins. NQO2 in mediating degradation of cyclin D1 via AKT/GSK-3β by resveratrol was tested by determining AKT and chymotryp - sin-like proteasome activities. Molecular modeling and pull-down/deletion assays were used to evaluate the interaction between NQO2 and AKT. Resveratrol interacts with NQO2, a qui - none reductase that plays a key role in resveratrol-induced AKT/GSK3β-mediated degradation of cyclin D1. In this chapter, we unravel control of expression and stability of c-myc by the res - veratrol-NQO2 axis as an approach to overcome c-myc-mediated metabolic reprogramming. that NQO2 NF-kB activation; NQO2 deletion potentiates the induction of apoptosis by abolishing TNF-induced cell survival kinases JNK, AKT, p38, and p44/p42 MAPK NQO2 C/EBPα proteasomes target dimeric NQO2 its other functions. novel pertain to c-myc T58 NQO2-knockdown cells, NQO2: AKT controls stability c-myc AKT/GSK3β-c-myc T-58 phosphorylation, by regulation of activity and functioning of the proteasome. Results of these studies will provide support for the as yet untested hypothesis regarding the indirect role of NQO2 in controlling AKT → GSK3β → c-myc T58 phosphorylation → c-myc degradation by proteasome, and the direct role of res veratrol acting as a metabolic switch to shut off c-myc-mediated metabolic reprogramming in cancer cells.","PeriodicalId":21139,"journal":{"name":"Resveratrol - Adding Life to Years, Not Adding Years to Life","volume":"69 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81321281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-11-05DOI: 10.5772/INTECHOPEN.78977
A. Stacchiotti, G. Favero, R. Rezzani
Reduced calorie intake is a religious and medical practice known since very old times, but its direct influence on life span in all organisms, included humans, has been dem onstrated in the modern era. Not only periodic fasting, but also natural or synthetic compounds that mimic this phenomenon are growing to slow aging and the onset of chronic morbidities. Resveratrol (RSV), a plant polyphenol, is an elixir of longevity for simple organisms and preclinical rodent models even if a beneficial role in humans is still debated. Its main rejuvenating mechanism copes with the activation of specific longevity genes called sirtuins. Among seven known mammalian sirtuins, sirtuin 1 is the most studied. This pleiotropic nicotinamide adenine dinucleotide (NAD)-based deacetylase maintains longevity by removing acetyl group in nuclear histones, transcription factors, and other DNA repairing proteins. Actually, an exciting challenge is to discover and test novel sirtuin 1 activators to extend life span and to treat age-associated disabilities. This chapter updates on the antiaging effect of RSV and sirtuin 1 activators in experimental animals and in humans. Finally, pros and cons on RSV analogues and sirtuin 1 activa tors tested in preclinical and clinical trials to hamper neurological deficit, cardiovascular complications, bone and muscle and cancer are discussed.
{"title":"Resveratrol and SIRT1 Activators for the Treatment of Aging and Age-Related Diseases","authors":"A. Stacchiotti, G. Favero, R. Rezzani","doi":"10.5772/INTECHOPEN.78977","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.78977","url":null,"abstract":"Reduced calorie intake is a religious and medical practice known since very old times, but its direct influence on life span in all organisms, included humans, has been dem onstrated in the modern era. Not only periodic fasting, but also natural or synthetic compounds that mimic this phenomenon are growing to slow aging and the onset of chronic morbidities. Resveratrol (RSV), a plant polyphenol, is an elixir of longevity for simple organisms and preclinical rodent models even if a beneficial role in humans is still debated. Its main rejuvenating mechanism copes with the activation of specific longevity genes called sirtuins. Among seven known mammalian sirtuins, sirtuin 1 is the most studied. This pleiotropic nicotinamide adenine dinucleotide (NAD)-based deacetylase maintains longevity by removing acetyl group in nuclear histones, transcription factors, and other DNA repairing proteins. Actually, an exciting challenge is to discover and test novel sirtuin 1 activators to extend life span and to treat age-associated disabilities. This chapter updates on the antiaging effect of RSV and sirtuin 1 activators in experimental animals and in humans. Finally, pros and cons on RSV analogues and sirtuin 1 activa tors tested in preclinical and clinical trials to hamper neurological deficit, cardiovascular complications, bone and muscle and cancer are discussed.","PeriodicalId":21139,"journal":{"name":"Resveratrol - Adding Life to Years, Not Adding Years to Life","volume":"56 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90944626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-11-05DOI: 10.5772/INTECHOPEN.78965
A. Carrizzo, C. Izzo, C. Vecchione
Resveratrol (RSV) is a natural nonflavonoid polyphenol compound containing a stilbene structure similar to that of estrogen diethylstilbestrol. It is a fat-soluble compound exist-ing in cis-, trans-, and piceid isomeric forms, isolated for the first time in 1940 from a plant used in traditional Chinese and Japanese medicine. Although initially used for cancer therapy, it has shown beneficial effects against most cardiovascular and cerebrovascular diseases. Its beneficial effects are mainly related to its antioxidant properties. Here, we review the metabolism and the ability of RSV to modulate redox signaling and to interact with multiple molecular targets of different intracellular pathways exerting protective effects against cardio-cerebrovascular diseases and metabolic disorders such as diabetes, reporting evidence in animal models and its efficacy and toxicity in humans. The aim of this chapter is to highlight the mechanisms, the biology, and the potential use of resvera- trol to prevent, protect and aid cardio- and cerebrovascular diseases.
{"title":"Protective Activity of Resveratrol in Cardio- and Cerebrovascular Diseases","authors":"A. Carrizzo, C. Izzo, C. Vecchione","doi":"10.5772/INTECHOPEN.78965","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.78965","url":null,"abstract":"Resveratrol (RSV) is a natural nonflavonoid polyphenol compound containing a stilbene structure similar to that of estrogen diethylstilbestrol. It is a fat-soluble compound exist-ing in cis-, trans-, and piceid isomeric forms, isolated for the first time in 1940 from a plant used in traditional Chinese and Japanese medicine. Although initially used for cancer therapy, it has shown beneficial effects against most cardiovascular and cerebrovascular diseases. Its beneficial effects are mainly related to its antioxidant properties. Here, we review the metabolism and the ability of RSV to modulate redox signaling and to interact with multiple molecular targets of different intracellular pathways exerting protective effects against cardio-cerebrovascular diseases and metabolic disorders such as diabetes, reporting evidence in animal models and its efficacy and toxicity in humans. The aim of this chapter is to highlight the mechanisms, the biology, and the potential use of resvera- trol to prevent, protect and aid cardio- and cerebrovascular diseases.","PeriodicalId":21139,"journal":{"name":"Resveratrol - Adding Life to Years, Not Adding Years to Life","volume":"74 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86335738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-11-05DOI: 10.5772/INTECHOPEN.79338
Sage Arbor
The molecular mechanisms underlying the quality and quantity of life extension appear to sometimes be orthogonal. For example, while resveratrol has continued to prove beneficial in reducing obesity, it has had less efficacy in extending lifespan. On the other hand, rapamycin and the chemically similar rapalogs extend lifespan across genera of life from yeast, to nematodes, to mice. Caloric restriction (CR) and bioavailable small molecules, which mimic a fasted state, upregulate autophagy, catabolism of fats over anabolism of carbohydrates, and decrease oxidative stress and inflammation. CR mimics are currently being investigated to elucidate the best dosage, route of administration, timing in life, where best to inhibit in the mTOR pathway, and effects of long-term use on mTORC1 verse mTORC2 complexes. Comparisons between rapamycin, resveratrol, and metformin targets, downstream pathway effects, dosage, and clinical trials will be discussed.
{"title":"Where and How in the mTOR Pathway Inhibitors Fight Aging: Rapamycin, Resveratrol, and Metformin","authors":"Sage Arbor","doi":"10.5772/INTECHOPEN.79338","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.79338","url":null,"abstract":"The molecular mechanisms underlying the quality and quantity of life extension appear to sometimes be orthogonal. For example, while resveratrol has continued to prove beneficial in reducing obesity, it has had less efficacy in extending lifespan. On the other hand, rapamycin and the chemically similar rapalogs extend lifespan across genera of life from yeast, to nematodes, to mice. Caloric restriction (CR) and bioavailable small molecules, which mimic a fasted state, upregulate autophagy, catabolism of fats over anabolism of carbohydrates, and decrease oxidative stress and inflammation. CR mimics are currently being investigated to elucidate the best dosage, route of administration, timing in life, where best to inhibit in the mTOR pathway, and effects of long-term use on mTORC1 verse mTORC2 complexes. Comparisons between rapamycin, resveratrol, and metformin targets, downstream pathway effects, dosage, and clinical trials will be discussed.","PeriodicalId":21139,"journal":{"name":"Resveratrol - Adding Life to Years, Not Adding Years to Life","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86554842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-11-05DOI: 10.5772/INTECHOPEN.79104
M. Ememe, A. Sackey, J. Ayo
This chapter evaluated resveratrol supplementation on laboratory animals, cats, pigs, horses, dogs, cattle and birds. Resveratrol (3, 5, 4′-trihydroxystilbene) is a stilbenoid, a derivate of stilbene. It is found in some plants such as red grape, grape products, cocoa, peanuts, raspberries, mulberries, strawberry and Japanese knotweed roots. The most important dietary source of resveratrol is red wine, and it is often assumed to be an important factor in the French Paradox, a term used to describe the observation that the French population has a very low incidence of cardiovascular disease, despite a diet high in saturated fats. Research has shown some therapeutic effects of resveratrol ranging from antioxidant, anti-inflammatory, cardioprotective, antiatherogenic, antiaging, anti- platelet aggregation, anticancer, antidiabetic, antitumor, and immunomodulatory activi -ties. In laboratory animals, benefits of resveratrol comprise antitumor effects while in cats it has shown to improve hepatic function. In pigs, the antibiotic and antiviral effects of resveratrol have been illustrated. The anti-inflammatory and antioxidative properties of resveratrol in horses and cattle were also reviewed. The supplement was shown to be useful as an antibiotic and an aid in improving alertness in dogs. Resveratrol also showed to increase growth performance in birds. It is therefore concluded that use of resveratrol is a potent aid in improving animal production and health.
{"title":"Evaluation of Resveratrol Supplementation on Laboratory Animals, Cats, Pigs, Horses, Dogs, Cattle, and Birds","authors":"M. Ememe, A. Sackey, J. Ayo","doi":"10.5772/INTECHOPEN.79104","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.79104","url":null,"abstract":"This chapter evaluated resveratrol supplementation on laboratory animals, cats, pigs, horses, dogs, cattle and birds. Resveratrol (3, 5, 4′-trihydroxystilbene) is a stilbenoid, a derivate of stilbene. It is found in some plants such as red grape, grape products, cocoa, peanuts, raspberries, mulberries, strawberry and Japanese knotweed roots. The most important dietary source of resveratrol is red wine, and it is often assumed to be an important factor in the French Paradox, a term used to describe the observation that the French population has a very low incidence of cardiovascular disease, despite a diet high in saturated fats. Research has shown some therapeutic effects of resveratrol ranging from antioxidant, anti-inflammatory, cardioprotective, antiatherogenic, antiaging, anti- platelet aggregation, anticancer, antidiabetic, antitumor, and immunomodulatory activi -ties. In laboratory animals, benefits of resveratrol comprise antitumor effects while in cats it has shown to improve hepatic function. In pigs, the antibiotic and antiviral effects of resveratrol have been illustrated. The anti-inflammatory and antioxidative properties of resveratrol in horses and cattle were also reviewed. The supplement was shown to be useful as an antibiotic and an aid in improving alertness in dogs. Resveratrol also showed to increase growth performance in birds. It is therefore concluded that use of resveratrol is a potent aid in improving animal production and health.","PeriodicalId":21139,"journal":{"name":"Resveratrol - Adding Life to Years, Not Adding Years to Life","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79789829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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