Pub Date : 2015-10-06DOI: 10.4172/2167-065X.C1.010
K. Jamil
X receptors Pregnane X Receptor (PXR) and Constitutive Androstane Receptor (CAR) regulate drug toxicity and resistance, which are the leading causes of treatment failure and for which no clinically safe and effective remedy is available. PXR and CAR play central roles in activating the expression of CYP3A4, a major enzyme responsible for metabolizing more than 50% of clinically prescribed drugs, and ALAS1, a rate-limiting porphyrin biosynthesis enzyme that increases the levels of hepatotoxic Protoporphyrin IX (PPIX), both contributing to drug-induced liver toxicity. Elevated MDR1 level is associated with drug resistance. MDR1 expression is induced by CAR and PXR. While PXR is ligand-inducible, CAR is constitutively active. Therefore, inhibitors of PXR and CAR (i.e., antagonists of PXR and inverse agonists of CAR) may prevent drug-induced liver toxicity and overcome drug resistance. By using a chemical biology approach we have identified and optimized PXR antagonists and CAR inverse agonists, investigated their mechanisms of action by performing structural and functional analysis, and evaluated their in vivo activities by using humanized animal models. Our data indicate that it is feasible to prevent drug-induced liver toxicity and overcome drug resistance by targeting PXR and CAR using mechanism-guided chemical agents.
{"title":"Development and characterization of lidocaine transdermal system with Self-Emulsifying Nanosystem (SENs)","authors":"K. Jamil","doi":"10.4172/2167-065X.C1.010","DOIUrl":"https://doi.org/10.4172/2167-065X.C1.010","url":null,"abstract":"X receptors Pregnane X Receptor (PXR) and Constitutive Androstane Receptor (CAR) regulate drug toxicity and resistance, which are the leading causes of treatment failure and for which no clinically safe and effective remedy is available. PXR and CAR play central roles in activating the expression of CYP3A4, a major enzyme responsible for metabolizing more than 50% of clinically prescribed drugs, and ALAS1, a rate-limiting porphyrin biosynthesis enzyme that increases the levels of hepatotoxic Protoporphyrin IX (PPIX), both contributing to drug-induced liver toxicity. Elevated MDR1 level is associated with drug resistance. MDR1 expression is induced by CAR and PXR. While PXR is ligand-inducible, CAR is constitutively active. Therefore, inhibitors of PXR and CAR (i.e., antagonists of PXR and inverse agonists of CAR) may prevent drug-induced liver toxicity and overcome drug resistance. By using a chemical biology approach we have identified and optimized PXR antagonists and CAR inverse agonists, investigated their mechanisms of action by performing structural and functional analysis, and evaluated their in vivo activities by using humanized animal models. Our data indicate that it is feasible to prevent drug-induced liver toxicity and overcome drug resistance by targeting PXR and CAR using mechanism-guided chemical agents.","PeriodicalId":10410,"journal":{"name":"Clinical Pharmacology & Biopharmaceutics","volume":"69 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75983674","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 : 2015-09-25DOI: 10.4172/2167-065X.1000145
M. Trivedi, R. M. Tallapragada, A. Branton, Dahryn Trivedi, G. Nayak, R. Mishra, S. Jana
Study background: 2,4-Dihydroxybenzophenone (DHBP) is an organic compound used for the synthesis of pharmaceutical agents. The objective of this study was to investigate the influence of biofield energy treatment on the physical, thermal and spectral properties of DHBP. The study was performed in two groups (control and treated). The control group remained as untreated, and the treated group received Mr. Trivedi’s biofield energy treatment. Methods: The control and treated DHBP samples were further characterized by X-ray diffraction (XRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), laser particle size analyser, surface area analyser, Fourier transform infrared (FT-IR) spectroscopy, and ultra violet-visible spectroscopy (UV-vis) analysis. Results: The XRD study indicated a slight decrease in the volume of the unit cell and molecular weight of treated DHBP as compared to the control sample. However, XRD study revealed an increase in average crystallite size of the treated DHBP by 32.73% as compared to the control sample. The DSC characterization showed no significant change in the melting temperature of treated sample. The latent heat of fusion of the treated DHBP was substantially increased by 11.67% as compared to the control. However, TGA analysis showed a decrease in the maximum thermal decomposition temperature (Tmax) of the treated DHBP (257.66oC) as compared to the control sample (260.93oC). The particle size analysis showed a substantial increase in particle size (d50 and d99) of the treated DHBP by 41% and 15.8% as compared to the control sample. Additionally, the surface area analysis showed a decrease in surface area by 9.5% in the treated DHBP, which was supported by the particle size results. Nevertheless, FT-IR analysis showed a downward shift of methyl group stretch (2885→2835 cm-1) in the treated sample as compared to the control. The UV analysis showed a blue shift of absorption peak 323→318 nm in the treated sample (T1) as compared to the control. Conclusion: Altogether, the results showed significant changes in the physical, thermal and spectral properties of treated DHBP as compared to the control.
{"title":"Physical, Thermal and Spectral Properties of Biofield Energy Treated 2,4-Dihydroxybenzophenone","authors":"M. Trivedi, R. M. Tallapragada, A. Branton, Dahryn Trivedi, G. Nayak, R. Mishra, S. Jana","doi":"10.4172/2167-065X.1000145","DOIUrl":"https://doi.org/10.4172/2167-065X.1000145","url":null,"abstract":"Study background: 2,4-Dihydroxybenzophenone (DHBP) is an organic compound used for the synthesis of pharmaceutical agents. The objective of this study was to investigate the influence of biofield energy treatment on the physical, thermal and spectral properties of DHBP. The study was performed in two groups (control and treated). The control group remained as untreated, and the treated group received Mr. Trivedi’s biofield energy treatment. \u0000Methods: The control and treated DHBP samples were further characterized by X-ray diffraction (XRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), laser particle size analyser, surface area analyser, Fourier transform infrared (FT-IR) spectroscopy, and ultra violet-visible spectroscopy (UV-vis) analysis. \u0000Results: The XRD study indicated a slight decrease in the volume of the unit cell and molecular weight of treated DHBP as compared to the control sample. However, XRD study revealed an increase in average crystallite size of the treated DHBP by 32.73% as compared to the control sample. The DSC characterization showed no significant change in the melting temperature of treated sample. The latent heat of fusion of the treated DHBP was substantially increased by 11.67% as compared to the control. However, TGA analysis showed a decrease in the maximum thermal decomposition temperature (Tmax) of the treated DHBP (257.66oC) as compared to the control sample (260.93oC). The particle size analysis showed a substantial increase in particle size (d50 and d99) of the treated DHBP by 41% and 15.8% as compared to the control sample. Additionally, the surface area analysis showed a decrease in surface area by 9.5% in the treated DHBP, which was supported by the particle size results. Nevertheless, FT-IR analysis showed a downward shift of methyl group stretch (2885→2835 cm-1) in the treated sample as compared to the control. The UV analysis showed a blue shift of absorption peak 323→318 nm in the treated sample (T1) as compared to the control. \u0000Conclusion: Altogether, the results showed significant changes in the physical, thermal and spectral properties of treated DHBP as compared to the control.","PeriodicalId":10410,"journal":{"name":"Clinical Pharmacology & Biopharmaceutics","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86192781","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 : 2015-09-21DOI: 10.4172/2167-065X.1000144
Delsin Sd, Mercurio Dg, Fossa Mm, Maia Campos Pmbg
Introduction: Spirulina is a unicellular blue-green alga rich in vitamins, minerals, pigments, proteins, polysaccharides, which indicates a high potential use in anti-aging cosmetic products as well as for skin protection. Preliminary studies showed antioxidant potential, immediate benefits on the skin microrelief and hydration and skin compatibility of formulations containing Spirulina extract. Thus, the objective of this study is to evaluate the long term clinical efficacy of dermocosmetic formulations containing Spirulina extract on young and mature skin using biophysical and skin imaging techniques. Methods: 40 healthy female volunteers participated in the clinical efficacy study, aged between 18- 39 (Young group) and 40- 65 (Mature group). The gel-cream formulation, supplemented, or not (vehicle - FGV) with 0.1% (w/w) of Spirulina extract (FGA) was applied twice daily on the volunteers face region. The effects were evaluated in terms of skin hydration, transepidermal water loss - TEWL, skin microrelief, sebum content and morphological and structural epidermal features before and after a 28-day-period of application of the formulations. Results: The formulation containing Spirulina extract increased stratum corneum water content and reduced the TEWL in both groups. However, a significant reduction in the older group, that received the formulation with Spirulina extract, was observed when compared to the younger group and to the vehicle formulation. Only the formulation containing the active ingredient under study reduced significantly the sebum content on the volunteer’s skin. It was also noted an improvement of the skin microrelief by the reduction of the surface roughness and after the treatment the keratinocytes were more uniformly distributed and homogeneous. Conclusion: The formulation containing Spirulina extract improved skin conditions and provided long term skin benefits such as hydration, protection of the skin barrier function and oil control. Finally, Spirulina extract stands out as a unique active ingredient for effective multifunctional dermocosmetic formulations for the care of young and mature skin.
{"title":"Clinical Efficacy of Dermocosmetic Formulations Containing Spirulina Extract on Young and Mature Skin: Effects on the Skin Hydrolipidic Barrier and Structural Properties","authors":"Delsin Sd, Mercurio Dg, Fossa Mm, Maia Campos Pmbg","doi":"10.4172/2167-065X.1000144","DOIUrl":"https://doi.org/10.4172/2167-065X.1000144","url":null,"abstract":"Introduction: Spirulina is a unicellular blue-green alga rich in vitamins, minerals, pigments, proteins, polysaccharides, which indicates a high potential use in anti-aging cosmetic products as well as for skin protection. Preliminary studies showed antioxidant potential, immediate benefits on the skin microrelief and hydration and skin compatibility of formulations containing Spirulina extract. Thus, the objective of this study is to evaluate the long term clinical efficacy of dermocosmetic formulations containing Spirulina extract on young and mature skin using biophysical and skin imaging techniques. \u0000Methods: 40 healthy female volunteers participated in the clinical efficacy study, aged between 18- 39 (Young group) and 40- 65 (Mature group). The gel-cream formulation, supplemented, or not (vehicle - FGV) with 0.1% (w/w) of Spirulina extract (FGA) was applied twice daily on the volunteers face region. The effects were evaluated in terms of skin hydration, transepidermal water loss - TEWL, skin microrelief, sebum content and morphological and structural epidermal features before and after a 28-day-period of application of the formulations. \u0000Results: The formulation containing Spirulina extract increased stratum corneum water content and reduced the TEWL in both groups. However, a significant reduction in the older group, that received the formulation with Spirulina extract, was observed when compared to the younger group and to the vehicle formulation. Only the formulation containing the active ingredient under study reduced significantly the sebum content on the volunteer’s skin. It was also noted an improvement of the skin microrelief by the reduction of the surface roughness and after the treatment the keratinocytes were more uniformly distributed and homogeneous. \u0000Conclusion: The formulation containing Spirulina extract improved skin conditions and provided long term skin benefits such as hydration, protection of the skin barrier function and oil control. Finally, Spirulina extract stands out as a unique active ingredient for effective multifunctional dermocosmetic formulations for the care of young and mature skin.","PeriodicalId":10410,"journal":{"name":"Clinical Pharmacology & Biopharmaceutics","volume":"76 1","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2015-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74557130","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 : 2015-09-04DOI: 10.4172/2471-2663.1000101
M. Trivedi, A. Branton, Dahryn Trivedi, G. Nayak, M. Gangwar, S. Jana
Biofield therapies have been reported to improve the quality of life as compared to other energy medicine. The aim of the study was to evaluate the impact of Mr. Trivedi’s biofield energy treatment on Pseudomonas fluorescens (P. fluorescens) for antimicrobial sensitivity, minimum inhibitory concentration (MIC), biochemical reactions, and biotype number. P. fluorescens cells were procured from MicroBioLogics Inc., USA in sealed packs bearing the American Type Culture Collection (ATCC 49838) number and divided in control and treated group. The effect was evaluated on day 10, and 159 after biofield treatment in lyophilized state. Further study was performed on day 5, 10, and 15 after retreatment on day 159 in revived state as per study design. All experimental parameters were studied using automated MicroScan Walk-Away® system. The 16S rDNA sequencing was carried out to correlate the phylogenetic relationship of P. fluorescens with other bacterial species after treatment. The results showed improved sensitivities and decreased MIC value of aztreonam, cefepime, moxifloxacin, and tetracycline in revived and lyophilized treated sample with respect to the control. Arginine, cetrimide, kanamycin, and glucose showed altered biochemical reactions after biofield treatment with respect to control. Biotype numbers were altered along with species in lyophilized as well as in revived group. Based on nucleotides homology and phylogenetic analysis using 16S rDNA gene sequencing, treated sample was detected to be Pseudomonas entomophila (GenBank Accession Number: AY907566) with 96% identity of gene sequencing data, which was nearest homolog species to P. fluorescens (Accession No. EF672049). These findings suggest that Mr. Trivedi’s unique biofield treatment has the capability to alter changes in pathogenic P. fluorescens even in the lyophilized storage condition and can be used to modify the sensitivity of microbes against antimicrobials.
{"title":"Bacterial Identification Using 16S rDNA Gene Sequencing and Antibiogram Analysis on Biofield Treated Pseudomonas fluorescens","authors":"M. Trivedi, A. Branton, Dahryn Trivedi, G. Nayak, M. Gangwar, S. Jana","doi":"10.4172/2471-2663.1000101","DOIUrl":"https://doi.org/10.4172/2471-2663.1000101","url":null,"abstract":"Biofield therapies have been reported to improve the quality of life as compared to other energy medicine. The aim of the study was to evaluate the impact of Mr. Trivedi’s biofield energy treatment on Pseudomonas fluorescens (P. fluorescens) for antimicrobial sensitivity, minimum inhibitory concentration (MIC), biochemical reactions, and biotype number. P. fluorescens cells were procured from MicroBioLogics Inc., USA in sealed packs bearing the American Type Culture Collection (ATCC 49838) number and divided in control and treated group. The effect was evaluated on day 10, and 159 after biofield treatment in lyophilized state. Further study was performed on day 5, 10, and 15 after retreatment on day 159 in revived state as per study design. All experimental parameters were studied using automated MicroScan Walk-Away® system. The 16S rDNA sequencing was carried out to correlate the phylogenetic relationship of P. fluorescens with other bacterial species after treatment. The results showed improved sensitivities and decreased MIC value of aztreonam, cefepime, moxifloxacin, and tetracycline in revived and lyophilized treated sample with respect to the control. Arginine, cetrimide, kanamycin, and glucose showed altered biochemical reactions after biofield treatment with respect to control. Biotype numbers were altered along with species in lyophilized as well as in revived group. Based on nucleotides homology and phylogenetic analysis using 16S rDNA gene sequencing, treated sample was detected to be Pseudomonas entomophila (GenBank Accession Number: AY907566) with 96% identity of gene sequencing data, which was nearest homolog species to P. fluorescens (Accession No. EF672049). These findings suggest that Mr. Trivedi’s unique biofield treatment has the capability to alter changes in pathogenic P. fluorescens even in the lyophilized storage condition and can be used to modify the sensitivity of microbes against antimicrobials.","PeriodicalId":10410,"journal":{"name":"Clinical Pharmacology & Biopharmaceutics","volume":"60 1","pages":"1000101"},"PeriodicalIF":0.0,"publicationDate":"2015-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84631725","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 : 2015-08-31DOI: 10.4172/2167-065x.1000143
S. Kundu, Md. Zakir Sultan, Asma Rahman, S. Paul, S. Shikder, Shampa Kundu, Md. Shah Amran, Md. Amjad Hossain
The study on interaction and complexation of drug molecules with other drugs and various metal ions is an important field of research in the chemical, biochemical, medicinal and pharmacological point of views. The biological action of the drug-metal complexes may affect stability and usual activities of drugs through changing pharmacokinetic and pharmacodynamic properties. The analgesic activity was evaluated by acetic acid induced writhing test in mice. In this experiment, aspirin with magnesium sulfate at the dose of 300 mg, 600 mg and 1.5 g/60 kg body weight, Paracetamol with magnesium sulfate at the dose of 500 mg, at the dose of 1 g and of 2.5 g /60 kg body weight and Naproxen with magnesium sulfate at the dose of 500 mg, at the dose of 1 g and at the dose of 2.5 g/60 kg body weight at a ratio of 1:1, 1:2 and 2:1. It was observed that % inhibition of writhing test of all complex drug of aspirin, paracetamol and naproxen with magnesium sulfate at different ratio were less than the main drug i.e. analgesic activity were lower than the main drug. It is concluded that magnesium sulfate while formed complex as well as mixed with aspirin, paracetamol and naproxen at different ratio suppress the analgesic activity of main drug.
{"title":"The Study of Analgesic Activity of Complexes of Magnesium Sulfate with Aspirin, Paracetamol and Naproxen","authors":"S. Kundu, Md. Zakir Sultan, Asma Rahman, S. Paul, S. Shikder, Shampa Kundu, Md. Shah Amran, Md. Amjad Hossain","doi":"10.4172/2167-065x.1000143","DOIUrl":"https://doi.org/10.4172/2167-065x.1000143","url":null,"abstract":"The study on interaction and complexation of drug molecules with other drugs and various metal ions is an important field of research in the chemical, biochemical, medicinal and pharmacological point of views. The biological action of the drug-metal complexes may affect stability and usual activities of drugs through changing pharmacokinetic and pharmacodynamic properties. The analgesic activity was evaluated by acetic acid induced writhing test in mice. In this experiment, aspirin with magnesium sulfate at the dose of 300 mg, 600 mg and 1.5 g/60 kg body weight, Paracetamol with magnesium sulfate at the dose of 500 mg, at the dose of 1 g and of 2.5 g /60 kg body weight and Naproxen with magnesium sulfate at the dose of 500 mg, at the dose of 1 g and at the dose of 2.5 g/60 kg body weight at a ratio of 1:1, 1:2 and 2:1. It was observed that % inhibition of writhing test of all complex drug of aspirin, paracetamol and naproxen with magnesium sulfate at different ratio were less than the main drug i.e. analgesic activity were lower than the main drug. It is concluded that magnesium sulfate while formed complex as well as mixed with aspirin, paracetamol and naproxen at different ratio suppress the analgesic activity of main drug.","PeriodicalId":10410,"journal":{"name":"Clinical Pharmacology & Biopharmaceutics","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88943506","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 : 2015-08-18DOI: 10.4172/2167-065X.1000142
Patrícia Maia Campos Mbg, M. O. Melo, L. S. Calixto, M. Fossa
The aim of this study was to evaluate the clinical efficacy of an oral supplementation based on hydrolyzed collagen and vitamins in the improvement of aged skin conditions using biophysical and skin imaging techniques. In this doubleblind, placebo-controlled trials, 60 woman aged between 40-60 years were randomized to receive the product containing hydrolyzed collagen and vitamins (Group A) or the placebo (Group B), once daily for 90-days period. Skin elasticity, dermis echogenicity, hydration and, number of pores and wrinkles were measured before and at the end of the study. The results showed an improvement of the dermis echogenicity and skin elasticity, as well as a reduction of wrinkles and total amount of pores on the skin of the group A when compared with placebo group. Thus, it was concluded that oral supplementation under study present itself as a potential to act effectively on aged skin. Finally, the study contributes to the improvement of effective strategies to skin care beyond topical products use.
{"title":"An Oral Supplementation Based on Hydrolyzed Collagen and Vitamins Improves Skin Elasticity and Dermis Echogenicity: A Clinical Placebo- Controlled Study","authors":"Patrícia Maia Campos Mbg, M. O. Melo, L. S. Calixto, M. Fossa","doi":"10.4172/2167-065X.1000142","DOIUrl":"https://doi.org/10.4172/2167-065X.1000142","url":null,"abstract":"The aim of this study was to evaluate the clinical efficacy of an oral supplementation based on hydrolyzed collagen and vitamins in the improvement of aged skin conditions using biophysical and skin imaging techniques. In this doubleblind, placebo-controlled trials, 60 woman aged between 40-60 years were randomized to receive the product containing hydrolyzed collagen and vitamins (Group A) or the placebo (Group B), once daily for 90-days period. Skin elasticity, dermis echogenicity, hydration and, number of pores and wrinkles were measured before and at the end of the study. The results showed an improvement of the dermis echogenicity and skin elasticity, as well as a reduction of wrinkles and total amount of pores on the skin of the group A when compared with placebo group. Thus, it was concluded that oral supplementation under study present itself as a potential to act effectively on aged skin. Finally, the study contributes to the improvement of effective strategies to skin care beyond topical products use.","PeriodicalId":10410,"journal":{"name":"Clinical Pharmacology & Biopharmaceutics","volume":"16 1","pages":"1-6"},"PeriodicalIF":0.0,"publicationDate":"2015-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82467045","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 : 2015-07-29DOI: 10.4172/2167-065X.1000140
Johnson J. Liu, Mingwei Chen, Deming Gou, Jun Lu, Shufeng Zhou
Johnson J Liu1*, Mingwei Chen2, Deming Gou3, Jun Lu4 and Shu-Feng Zhou5 1School of Medicine, Faculty of Health, University of Tasmania, Hobart, Tasmania 7001, Australia 2The First Affiliated Hospital of Xi’an Jiaotong University, Shaanxi 710061, China 3College of Life Sciences, Shenzhen University, Guangdong 518060, China 4School of Inter Professional Health Studies, and School of Applied Sciences, Faculty of Health and Environmental Sciences, and Institute of Biomedical Technology, Auckland University of Technology, Auckland 1142, New Zealand 5Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, Florida 33612, USA
{"title":"Systems Pharmacology for the Study of Anticancer Drugs: Promises and Challenges","authors":"Johnson J. Liu, Mingwei Chen, Deming Gou, Jun Lu, Shufeng Zhou","doi":"10.4172/2167-065X.1000140","DOIUrl":"https://doi.org/10.4172/2167-065X.1000140","url":null,"abstract":"Johnson J Liu1*, Mingwei Chen2, Deming Gou3, Jun Lu4 and Shu-Feng Zhou5 1School of Medicine, Faculty of Health, University of Tasmania, Hobart, Tasmania 7001, Australia 2The First Affiliated Hospital of Xi’an Jiaotong University, Shaanxi 710061, China 3College of Life Sciences, Shenzhen University, Guangdong 518060, China 4School of Inter Professional Health Studies, and School of Applied Sciences, Faculty of Health and Environmental Sciences, and Institute of Biomedical Technology, Auckland University of Technology, Auckland 1142, New Zealand 5Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, Florida 33612, USA","PeriodicalId":10410,"journal":{"name":"Clinical Pharmacology & Biopharmaceutics","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84021895","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 : 2015-07-22DOI: 10.4172/2167-065X.1000139
A. Al-Achi, D. Kota
Insulin is a polypeptide hormone produced by the β cells present in Islets of Langerhans of the pancreas. Either failure to produce (type 1 diabetes) or utilize insulin (type 2 diabetes) causes diabetes mellitus. Insulin administration is used to treat type 1 diabetes. The common route for insulin administration is via subcutaneous injection. The oral insulin delivery has been proposed, however it suffers from poor bioavailability which is mainly due to the presence of proteolytic enzymes (pepsin, trypsin, and chymotrypsin) in the gastrointestinal (GI) tract. Protecting insulin from these enzymes when given orally might improve its bioavailability. In general, condensed tannins have been shown to reduce the activity of digestive enzymes. Epigallocatechin-3-gallate (EGCG) is the most abundant tannin component found in green tea. The present study investigated the ability of EGCG to protect insulin, through the formation of EGCGinsulin complex, from the proteolytic enzyme action by pepsin and trypsin/chymotrypsin, in vitro. The amount of insulin remaining in the presence and absence of EGCG following incubation with either simulated gastric fluid (SGF) containing pepsin or simulated intestinal fluid (SIF) containing trypsin/chymotrypsin at two different temperatures (25°C and 37°C) for 1 hour and 7 hours was determined using an HPLC technique. The results showed that the presence of proteolytic enzymes (pepsin or trypsin/chymotrypsin) and absence of EGCG in the sample negatively affected the stability of insulin in solution. In the presence of EGCG, insulin was partially protected from trypsin/chymotrypsin but it was not protected from the action of pepsin. Insulin degradation was more pronounced at 37°C than that at 25°C (p = 0.0188). The initial concentration of insulin present (10 IU/mL or 20 IU/mL) or the time of incubation (1 h vs. 7 h) had no influence on the stability of insulin in the sample (p = 0.2842 and p = 0.2114, respectively). In conclusion, EGCG was not able to protect insulin against the proteolytic activity of pepsin. However, EGCG was shown to have some protective effect on insulin against the degradative effect of trypsin/chymotrypsin at room temperature, in vitro. Furthermore, this protection was greatly weakened at 37°C, which suggested that the protective action of EGCG would not be present in vivo.
胰岛素是一种多肽激素，由存在于胰腺朗格汉斯岛的β细胞产生。要么不能产生胰岛素(1型糖尿病)，要么不能利用胰岛素(2型糖尿病)导致糖尿病。胰岛素用于治疗1型糖尿病。胰岛素给药的常见途径是皮下注射。口服胰岛素已被提出，但其生物利用度较差，这主要是由于胃肠道中存在蛋白水解酶(胃蛋白酶、胰蛋白酶和凝乳胰蛋白酶)。口服胰岛素时保护胰岛素不受这些酶的影响可能会提高其生物利用度。一般来说，浓缩单宁已被证明可以降低消化酶的活性。表没食子儿茶素-3-没食子酸酯(EGCG)是绿茶中最丰富的单宁成分。本研究在体外研究了EGCG在胃蛋白酶和胰蛋白酶/凝乳胰蛋白酶的蛋白水解酶作用下，通过形成EGCG -胰岛素复合物保护胰岛素的能力。在含胃蛋白酶的模拟胃液(SGF)或含胰蛋白酶/凝乳胰蛋白酶的模拟肠液(SIF)中，在两种不同温度(25°C和37°C)孵育1小时和7小时后，使用HPLC技术测定存在和不存在EGCG时的胰岛素残留量。结果表明，样品中蛋白水解酶(胃蛋白酶或胰蛋白酶/凝乳胰蛋白酶)的存在和EGCG的缺失会对胰岛素在溶液中的稳定性产生负面影响。在EGCG存在的情况下，胰岛素对胰蛋白酶/凝乳胰蛋白酶有部分保护作用，但对胃蛋白酶没有保护作用。胰岛素降解在37°C时比在25°C时更为明显(p = 0.0188)。胰岛素初始浓度(10 IU/mL或20 IU/mL)和孵育时间(1 h vs. 7 h)对样品中胰岛素的稳定性没有影响(p = 0.2842和p = 0.2114)。综上所述，EGCG不能保护胰岛素抵抗胃蛋白酶的蛋白水解活性。然而，在室温下，EGCG被证明对胰岛素具有一定的保护作用，抵抗胰蛋白酶/凝乳胰蛋白酶的降解作用。此外，在37℃时，这种保护作用大大减弱，这表明EGCG在体内不存在保护作用。
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Pub Date : 2015-07-16DOI: 10.4172/2167-065X.1000e117
Murnane Ks
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