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Kota V Ramana - One of the best experts on this subject based on the ideXlab platform.
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anti inflammatory effects of Benfotiamine are mediated through the regulation of the arachidonic acid pathway in macrophages
Free Radical Biology and Medicine, 2012Co-Authors: Mohammad Shoeb, Kota V RamanaAbstract:Abstract Benfotiamine, a lipid-soluble analogue of vitamin B1, is a potent antioxidant that is used as a food supplement for the treatment of diabetic complications. Our recent study (U.C. Yadav et al., Free Radic. Biol. Med. 48:1423–1434, 2010) indicates a novel role for Benfotiamine in the prevention of bacterial endotoxin, lipopolysaccharide (LPS)-induced cytotoxicity and inflammatory response in murine macrophages. Nevertheless, it remains unclear how Benfotiamine mediates anti-inflammatory effects. In this study, we investigated the anti-inflammatory role of Benfotiamine in regulating arachidonic acid (AA) pathway-generated inflammatory lipid mediators in RAW264.7 macrophages. Benfotiamine prevented the LPS-induced activation of cPLA2 and release of AA metabolites such as leukotrienes, prostaglandin E2, thromboxane 2 (TXB2), and prostacyclin (PGI2) in macrophages. Further, LPS-induced expression of AA-metabolizing enzymes such as COX-2, LOX-5, TXB synthase, and PGI2 synthase was significantly blocked by Benfotiamine. Furthermore, Benfotiamine prevented the LPS-induced phosphorylation of ERK1/2 and expression of transcription factors NF-κB and Egr-1. Benfotiamine also prevented the LPS-induced oxidative stress and protein–HNE adduct formation. Most importantly, compared to specific COX-2 and LOX-5 inhibitors, Benfotiamine significantly prevented LPS-induced macrophage death and monocyte adhesion to endothelial cells. Thus, our studies indicate that the dual regulation of the COX and LOX pathways in AA metabolism could be a novel mechanism by which Benfotiamine exhibits its potential anti-inflammatory response.
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abstract 2397 fat soluble vitamin b1 analogue Benfotiamine prevents colon cancer cell growth and aberrant crypt foci formation in murine models of colon cancer
Cancer Research, 2011Co-Authors: Kota V Ramana, Ashish Saxena, Ravinder Tammali, Aramati B M Reddy, Satish K SrivastavaAbstract:Chronic inflammatory diseases and oxidative stress are major risk factors of colorectal cancer (CRC), the third most common cause of death among cancer patients. Although several agents such as antioxidants, plant products and nutritional supplements have been shown to have some chemopreventive effects on colon cancer, none are very effective to completely. Recent studies indicate that a fat soluble analogue of vitamin B1, Benfotiamine is an excellent antioxidant and anti-inflammatory. However, the chemo-preventive or -therapeutic efficacy of Benfotiamine in preventing CRC is not known. Our hypothesis is that Benfotiamine through its anti-oxidant and anti-inflammatory properties could be very effective in preventing CRC. We therefore investigated the role of Benfotiamine in the prevention of carcinogenic signals leading to CRC in cell culture as well as murine models of CRC. Our results show that treatment of human colon cancer cells (HT-29 and Caco-2) in culture with Benfotiamine prevented the cancer cell proliferation. Further, Benfotiamine also prevented the growth of human adenocarcinoma cells (SW480) -induced tumor growth in nude mice xenografts. Our studies also indicate that Benfotiamine prevented NF-kB-dependent survival signals and activated caspase-3 dependent apoptotic signals in colon cancer cells. Further, Benfotiamine supplementation also suppressed azoxymethane (AOM)-induced aberrant crypt foci (ACF) formation in mice and AOM-induced inflammatory changes such as activation of Cox-2 and iNOS, and carcinogenic changes such as expression of cyclin D1 and β-catenin in mice colons. In conclusion, our results indicate that Benfotiamine prevents colon cancer cell growth in culture and nude mice xenografts as well as formation of ACF in AOM-treated mice. Thus Benfotiamine supplementation could be used as an excellent chemopreventive agent for the treatment of CRC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2397. doi:10.1158/1538-7445.AM2011-2397
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protective role of Benfotiamine a fat soluble vitamin b1 analogue in lipopolysaccharide induced cytotoxic signals in murine macrophages
Free Radical Biology and Medicine, 2010Co-Authors: Umesh C S Yadav, Satish K Srivastava, Nilesh M Kalariya, Kota V RamanaAbstract:Abstract This study was designed to investigate the molecular mechanisms by which Benfotiamine, a lipid-soluble analogue of vitamin B1, affects lipopolysaccharide (LPS)-induced inflammatory signals leading to cytotoxicity in the mouse macrophage cell line RAW264.7. Benfotiamine prevented LPS-induced apoptosis, expression of the Bcl-2 family of proapoptotic proteins, caspase-3 activation, and PARP cleavage and altered mitochondrial membrane potential and release of cytochrome c and apoptosis-inducing factor and phosphorylation and subsequent activation of p38-MAPK, stress-activated kinases (SAPK/JNK), protein kinase C, and cytoplasmic phospholipase A2 in RAW cells. Further, phosphorylation and degradation of inhibitory κB and consequent activation and nuclear translocation of the redox-sensitive transcription factor NF-κB were significantly prevented by Benfotiamine. The LPS-induced increased expression of cytokines and chemokines and the inflammatory marker proteins iNOS and COX-2 and their metabolic products NO and PGE2 was also blocked significantly. Thus, our results elucidate the molecular mechanism of the anti-inflammatory action of Benfotiamine in LPS-induced inflammation in murine macrophages. Benfotiamine suppresses oxidative stress-induced NF-κB activation and prevents bacterial endotoxin-induced inflammation, indicating that vitamin B1 supplementation could be beneficial in the treatment of inflammatory diseases.
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original contributionprotective role of Benfotiamine a fat soluble vitamin b1 analogue in lipopolysaccharide induced cytotoxic signals in murine macrophages
Free Radical Biology and Medicine, 2010Co-Authors: Umesh C S Yadav, Satish K Srivastava, Nilesh M Kalariya, Kota V RamanaAbstract:This study was designed to investigate the molecular mechanisms by which Benfotiamine, a lipid-soluble analogue of vitamin B1, affects lipopolysaccharide (LPS)-induced inflammatory signals leading to cytotoxicity in the mouse macrophage cell line RAW264.7. Benfotiamine prevented LPS-induced apoptosis, expression of the Bcl-2 family of proapoptotic proteins, caspase-3 activation, and PARP cleavage and altered mitochondrial membrane potential and release of cytochrome c and apoptosis-inducing factor and phosphorylation and subsequent activation of p38-MAPK, stress-activated kinases (SAPK/JNK), protein kinase C, and cytoplasmic phospholipase A2 in RAW cells. Further, phosphorylation and degradation of inhibitory κB and consequent activation and nuclear translocation of the redox-sensitive transcription factor NF-κB were significantly prevented by Benfotiamine. The LPS-induced increased expression of cytokines and chemokines and the inflammatory marker proteins iNOS and COX-2 and their metabolic products NO and PGE2 was also blocked significantly. Thus, our results elucidate the molecular mechanism of the anti-inflammatory action of Benfotiamine in LPS-induced inflammation in murine macrophages. Benfotiamine suppresses oxidative stress-induced NF-κB activation and prevents bacterial endotoxin-induced inflammation, indicating that vitamin B1 supplementation could be beneficial in the treatment of inflammatory diseases.
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prevention of endotoxin induced uveitis in rats by Benfotiamine a lipophilic analogue of vitamin b1
Investigative Ophthalmology & Visual Science, 2009Co-Authors: Umesh C S Yadav, Sumitra Subramanyam, Kota V RamanaAbstract:PURPOSE: To study the amelioration of ocular inflammation in endotoxin-induced uveitis (EIU) in rats by Benfotiamine, a lipid-soluble analogue of thiamine. METHODS: EIU in Lewis rats was induced by subcutaneous injection of lipopolysaccharide (LPS) followed by treatment with Benfotiamine. The rats were killed 3 or 24 hours after LPS injection, eyes were enucleated, aqueous humor (AqH) was collected, and the number of infiltrating cells, protein concentration, and inflammatory marker levels were determined. Immunohistochemical analysis of eye sections was performed to determine the expression of inducible-nitric oxide synthase (iNOS), cyclooxygenase (Cox)-2, protein kinase C (PKC), and transcription factor NF-kappaB. RESULTS: Infiltrating leukocytes, protein concentrations, and inflammatory cytokines and chemokines were significantly elevated in the AqH of EIU rats compared with control rats, and Benfotiamine treatment suppressed these increases. Similarly increased expression of inflammatory markers iNOS and Cox-2 in ciliary body and retinal wall was also significantly inhibited by Benfotiamine. The increased phosphorylation of PKC and the activation of NF-kappaB in the ciliary body and in the retinal wall of EIU rat eyes were suppressed by Benfotiamine. CONCLUSIONS: These results suggest that Benfotiamine suppresses oxidative stress-induced NF-kappaB-dependent inflammatory signaling leading to uveitis. Therefore, Benfotiamine could be used as a novel therapeutic agent for the treatment of ocular inflammation, especially uveitis.
Umesh C S Yadav - One of the best experts on this subject based on the ideXlab platform.
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original contributionprotective role of Benfotiamine a fat soluble vitamin b1 analogue in lipopolysaccharide induced cytotoxic signals in murine macrophages
Free Radical Biology and Medicine, 2010Co-Authors: Umesh C S Yadav, Satish K Srivastava, Nilesh M Kalariya, Kota V RamanaAbstract:This study was designed to investigate the molecular mechanisms by which Benfotiamine, a lipid-soluble analogue of vitamin B1, affects lipopolysaccharide (LPS)-induced inflammatory signals leading to cytotoxicity in the mouse macrophage cell line RAW264.7. Benfotiamine prevented LPS-induced apoptosis, expression of the Bcl-2 family of proapoptotic proteins, caspase-3 activation, and PARP cleavage and altered mitochondrial membrane potential and release of cytochrome c and apoptosis-inducing factor and phosphorylation and subsequent activation of p38-MAPK, stress-activated kinases (SAPK/JNK), protein kinase C, and cytoplasmic phospholipase A2 in RAW cells. Further, phosphorylation and degradation of inhibitory κB and consequent activation and nuclear translocation of the redox-sensitive transcription factor NF-κB were significantly prevented by Benfotiamine. The LPS-induced increased expression of cytokines and chemokines and the inflammatory marker proteins iNOS and COX-2 and their metabolic products NO and PGE2 was also blocked significantly. Thus, our results elucidate the molecular mechanism of the anti-inflammatory action of Benfotiamine in LPS-induced inflammation in murine macrophages. Benfotiamine suppresses oxidative stress-induced NF-κB activation and prevents bacterial endotoxin-induced inflammation, indicating that vitamin B1 supplementation could be beneficial in the treatment of inflammatory diseases.
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protective role of Benfotiamine a fat soluble vitamin b1 analogue in lipopolysaccharide induced cytotoxic signals in murine macrophages
Free Radical Biology and Medicine, 2010Co-Authors: Umesh C S Yadav, Satish K Srivastava, Nilesh M Kalariya, Kota V RamanaAbstract:Abstract This study was designed to investigate the molecular mechanisms by which Benfotiamine, a lipid-soluble analogue of vitamin B1, affects lipopolysaccharide (LPS)-induced inflammatory signals leading to cytotoxicity in the mouse macrophage cell line RAW264.7. Benfotiamine prevented LPS-induced apoptosis, expression of the Bcl-2 family of proapoptotic proteins, caspase-3 activation, and PARP cleavage and altered mitochondrial membrane potential and release of cytochrome c and apoptosis-inducing factor and phosphorylation and subsequent activation of p38-MAPK, stress-activated kinases (SAPK/JNK), protein kinase C, and cytoplasmic phospholipase A2 in RAW cells. Further, phosphorylation and degradation of inhibitory κB and consequent activation and nuclear translocation of the redox-sensitive transcription factor NF-κB were significantly prevented by Benfotiamine. The LPS-induced increased expression of cytokines and chemokines and the inflammatory marker proteins iNOS and COX-2 and their metabolic products NO and PGE2 was also blocked significantly. Thus, our results elucidate the molecular mechanism of the anti-inflammatory action of Benfotiamine in LPS-induced inflammation in murine macrophages. Benfotiamine suppresses oxidative stress-induced NF-κB activation and prevents bacterial endotoxin-induced inflammation, indicating that vitamin B1 supplementation could be beneficial in the treatment of inflammatory diseases.
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prevention of endotoxin induced uveitis in rats by Benfotiamine a lipophilic analogue of vitamin b1
Investigative Ophthalmology & Visual Science, 2009Co-Authors: Umesh C S Yadav, Sumitra Subramanyam, Kota V RamanaAbstract:PURPOSE: To study the amelioration of ocular inflammation in endotoxin-induced uveitis (EIU) in rats by Benfotiamine, a lipid-soluble analogue of thiamine. METHODS: EIU in Lewis rats was induced by subcutaneous injection of lipopolysaccharide (LPS) followed by treatment with Benfotiamine. The rats were killed 3 or 24 hours after LPS injection, eyes were enucleated, aqueous humor (AqH) was collected, and the number of infiltrating cells, protein concentration, and inflammatory marker levels were determined. Immunohistochemical analysis of eye sections was performed to determine the expression of inducible-nitric oxide synthase (iNOS), cyclooxygenase (Cox)-2, protein kinase C (PKC), and transcription factor NF-kappaB. RESULTS: Infiltrating leukocytes, protein concentrations, and inflammatory cytokines and chemokines were significantly elevated in the AqH of EIU rats compared with control rats, and Benfotiamine treatment suppressed these increases. Similarly increased expression of inflammatory markers iNOS and Cox-2 in ciliary body and retinal wall was also significantly inhibited by Benfotiamine. The increased phosphorylation of PKC and the activation of NF-kappaB in the ciliary body and in the retinal wall of EIU rat eyes were suppressed by Benfotiamine. CONCLUSIONS: These results suggest that Benfotiamine suppresses oxidative stress-induced NF-kappaB-dependent inflammatory signaling leading to uveitis. Therefore, Benfotiamine could be used as a novel therapeutic agent for the treatment of ocular inflammation, especially uveitis.
Pitchai Balakumar - One of the best experts on this subject based on the ideXlab platform.
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the defensive effect of Benfotiamine in sodium arsenite induced experimental vascular endothelial dysfunction
Biological Trace Element Research, 2010Co-Authors: Sanjali Verma, Krishna Reddy, Pitchai BalakumarAbstract:The present study has been designed to investigate the effect of Benfotiamine, a thiamine derivative, in sodium arsenite-induced vascular endothelial dysfunction (VED) in rats. Sodium arsenite (1.5 mg−1 kg−1 day−1 i.p., 2 weeks) was administered in rats to produce VED. The development of VED was assessed by employing isolated aortic ring preparation and estimating the serum and aortic concentrations of nitrite/nitrate. Further, the integrity of vascular endothelium in thoracic aorta was assessed by scanning electron microscopy. Moreover, the oxidative stress was assessed by estimating serum thiobarbituric acid reactive substances (TBARS) and aortic superoxide anion generation. The administration of sodium arsenite markedly produced VED by attenuating acetylcholine-induced endothelium-dependent relaxation, decreasing serum and aortic concentrations of nitrite/nitrate, and impairing the integrity of vascular endothelium. Further, sodium arsenite produced oxidative stress by increasing serum TBARS and aortic superoxide generation. The treatment with Benfotiamine (25, 50, and 100 mg−1 kg−1 day−1 p.o.) or atorvastatin (30 mg−1 kg−1 day−1 p.o., a standard agent) prevented sodium arsenite-induced VED and oxidative stress. However, the beneficial effects of Benfotiamine in preventing the sodium arsenite-induced VED were attenuated by co-administration with N-omega-nitro-l-arginine methyl ester (L-NAME) (25 mg−1 kg−1 day−1, i.p.), an inhibitor of NOS. Thus, it may be concluded that Benfotiamine reduces oxidative stress and activates endothelial nitric oxide synthase to enhance the generation and bioavailability of NO and subsequently improves the integrity of vascular endothelium to prevent sodium arsenite-induced experimental VED.
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the multifaceted therapeutic potential of Benfotiamine
Pharmacological Research, 2010Co-Authors: Pitchai Balakumar, Ankur Rohilla, Pawan Krishan, P Solairaj, Arunachalam ThangathirupathiAbstract:Thiamine, known as vitamin B1, plays an essential role in energy metabolism. Benfotiamine (S-benzoylthiamine O-monophoshate) is a synthetic S-acyl derivative of thiamine. Once absorbed, Benfotiamine is dephosphorylated by ecto-alkaline phosphatase to lipid-soluble S-benzoylthiamine. Transketolase is an enzyme that directs the precursors of advanced glycation end products (AGEs) to pentose phosphate pathway. Benfotiamine administration increases the levels of intracellular thiamine diphosphate, a cofactor necessary for the activation transketolase, resulting in the reduction of tissue level of AGEs. The elevated level of AGEs has been implicated in the induction and progression of diabetes-associated complications. Chronic hyperglycemia accelerates the reaction between glucose and proteins leading to the formation of AGEs, which form irreversible cross-links with many macromolecules such as collagen. In diabetes, AGEs accumulate in tissues at an accelerated rate. Experimental studies have elucidated that binding of AGEs to their specific receptors (RAGE) activates mainly monocytes and endothelial cells and consequently induces various inflammatory events. Moreover, AGEs exaggerate the status of oxidative stress in diabetes that may additionally contribute to functional changes in vascular tone control observed in diabetes. The anti-AGE property of Benfotiamine certainly makes it effective for the treatment of diabetic neuropathy, nephropathy and retinopathy. Interestingly, few recent studies demonstrated additional non-AGE-dependent pharmacological actions of Benfotiamine. The present review critically analyzed the multifaceted therapeutic potential of Benfotiamine.
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The multifaceted therapeutic potential of Benfotiamine
Pharmacological Research, 2010Co-Authors: Pitchai Balakumar, Ankur Rohilla, Pawan Krishan, P Solairaj, Arunachalam ThangathirupathiAbstract:Thiamine, known as vitamin B1, plays an essential role in energy metabolism. Benfotiamine (S-benzoylthiamine O-monophoshate) is a synthetic S-acyl derivative of thiamine. Once absorbed, Benfotiamine is dephosphorylated by ecto-alkaline phosphatase to lipid-soluble S-benzoylthiamine. Transketolase is an enzyme that directs the precursors of advanced glycation end products (AGEs) to pentose phosphate pathway. Benfotiamine administration increases the levels of intracellular thiamine diphosphate, a cofactor necessary for the activation transketolase, resulting in the reduction of tissue level of AGEs. The elevated level of AGEs has been implicated in the induction and progression of diabetes-associated complications. Chronic hyperglycemia accelerates the reaction between glucose and proteins leading to the formation of AGEs, which form irreversible cross-links with many macromolecules such as collagen. In diabetes, AGEs accumulate in tissues at an accelerated rate. Experimental studies have elucidated that binding of AGEs to their specific receptors (RAGE) activates mainly monocytes and endothelial cells and consequently induces various inflammatory events. Moreover, AGEs exaggerate the status of oxidative stress in diabetes that may additionally contribute to functional changes in vascular tone control observed in diabetes. The anti-AGE property of Benfotiamine certainly makes it effective for the treatment of diabetic neuropathy, nephropathy and retinopathy. Interestingly, few recent studies demonstrated additional non-AGE-dependent pharmacological actions of Benfotiamine. The present review critically analyzed the multifaceted therapeutic potential of Benfotiamine. © 2010 Elsevier Ltd.
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ameliorative effect of combination of Benfotiamine and fenofibrate in diabetes induced vascular endothelial dysfunction and nephropathy in the rat
Molecular and Cellular Biochemistry, 2009Co-Authors: Pitchai Balakumar, Vishal Arvind Chakkarwar, Manjeet SinghAbstract:The study has been designed to investigate the effect of Benfotiamine and fenofibrate in diabetes-induced experimental vascular endothelial dysfunction (VED) and nephropathy. The single administration of streptozotocin (STZ) (50 mg/kg, i.p.) produced diabetes, which was noted to develop VED and nephropathy in 8 weeks. The diabetes produced VED by attenuating acetylcholine-induced endothelium dependent relaxation, impairing the integrity of vascular endothelium, decreasing serum nitrite/nitrate concentration and increasing serum TBARS and aortic superoxide anion generation. Further, diabetes altered the lipid profile by increasing the serum cholesterol, triglycerides and decreasing the high density lipoprotein. The nephropathy was noted to be developed in the diabetic rat that was assessed in terms of increase in serum creatinine, blood urea, proteinuria, and glomerular damage. The Benfotiamine (70 mg/kg, p.o.) and fenofibrate (32 mg/kg, p.o.) or lisinopril (1 mg/kg, p.o., a standard agent) treatments were started in diabetic rats after 1 week of STZ administration and continued for 7 weeks. The treatment with Benfotiamine and fenofibrate either alone or in combination attenuated diabetes-induced VED and nephropathy. In addition, the combination of Benfotiamine and fenofibrate was noted to be more effective in attenuating the diabetes-induced VED and nephropathy when compared to treatment with either drug alone or lisinopril. Treatment with fenofibrate normalizes the altered lipid profile in diabetic rats, whereas Benfotiamine treatment has no effect on lipid alteration in diabetic rats. It may be concluded that diabetes-induced oxidative stress, lipids alteration, and consequent development of VED may be responsible for the induction of nephropathy in diabetic rats. Concurrent administration of Benfotiamine and fenofibrate may provide synergistic benefits in preventing the development of diabetes-induced nephropathy by reducing the oxidative stress and lipid alteration, preventing the VED and subsequently improving the renal function.
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Benfotiamine attenuates nicotine and uric acid induced vascular endothelial dysfunction in the rat
Pharmacological Research, 2008Co-Authors: Pitchai Balakumar, Ramica Sharma, Manjeet SinghAbstract:Abstract The study has been designed to investigate the effect of Benfotiamine, a thiamine derivative, in nicotine and uric acid-induced vascular endothelial dysfunction (VED) in rats. Nicotine (2 mg kg −1 day −1 , i.p., 4 weeks) and uric acid (150 mg kg −1 day −1 , i.p., 3 weeks) were administered to produce VED in rats. The development of VED was assessed by employing isolated aortic ring preparation and estimating serum and aortic concentration of nitrite/nitrate. Further, the integrity of vascular endothelium was assessed using the scanning electron microscopy (SEM) of thoracic aorta. Moreover, the oxidative stress was assessed by estimating serum thiobarbituric acid reactive substances (TBARS) and aortic superoxide anion generation. The administration of nicotine and uric acid produced VED by impairing the integrity of vascular endothelium and subsequently decreasing serum and aortic concentration of nitrite/nitrate and attenuating acetylcholine-induced endothelium dependent relaxation. Further, nicotine and uric acid produced oxidative stress, which was assessed in terms of increase in serum TBARS and aortic superoxide generation. However, treatment with Benfotiamine (70 mg kg −1 day −1 , p.o.) or atorvastatin (30 mg kg −1 day −1 p.o., a standard agent) markedly prevented nicotine and uric acid-induced VED and oxidative stress by improving the integrity of vascular endothelium, increasing the concentration of serum and aortic nitrite/nitrate, enhancing the acetylcholine-induced endothelium dependent relaxation and decreasing serum TBARS and aortic superoxide anion generation. Thus, it may be concluded that Benfotiamine reduces the oxidative stress and consequently improves the integrity of vascular endothelium and enhances the generation of nitric oxide to prevent nicotine and uric acid-induced experimental VED.
Satish K Srivastava - One of the best experts on this subject based on the ideXlab platform.
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abstract 2397 fat soluble vitamin b1 analogue Benfotiamine prevents colon cancer cell growth and aberrant crypt foci formation in murine models of colon cancer
Cancer Research, 2011Co-Authors: Kota V Ramana, Ashish Saxena, Ravinder Tammali, Aramati B M Reddy, Satish K SrivastavaAbstract:Chronic inflammatory diseases and oxidative stress are major risk factors of colorectal cancer (CRC), the third most common cause of death among cancer patients. Although several agents such as antioxidants, plant products and nutritional supplements have been shown to have some chemopreventive effects on colon cancer, none are very effective to completely. Recent studies indicate that a fat soluble analogue of vitamin B1, Benfotiamine is an excellent antioxidant and anti-inflammatory. However, the chemo-preventive or -therapeutic efficacy of Benfotiamine in preventing CRC is not known. Our hypothesis is that Benfotiamine through its anti-oxidant and anti-inflammatory properties could be very effective in preventing CRC. We therefore investigated the role of Benfotiamine in the prevention of carcinogenic signals leading to CRC in cell culture as well as murine models of CRC. Our results show that treatment of human colon cancer cells (HT-29 and Caco-2) in culture with Benfotiamine prevented the cancer cell proliferation. Further, Benfotiamine also prevented the growth of human adenocarcinoma cells (SW480) -induced tumor growth in nude mice xenografts. Our studies also indicate that Benfotiamine prevented NF-kB-dependent survival signals and activated caspase-3 dependent apoptotic signals in colon cancer cells. Further, Benfotiamine supplementation also suppressed azoxymethane (AOM)-induced aberrant crypt foci (ACF) formation in mice and AOM-induced inflammatory changes such as activation of Cox-2 and iNOS, and carcinogenic changes such as expression of cyclin D1 and β-catenin in mice colons. In conclusion, our results indicate that Benfotiamine prevents colon cancer cell growth in culture and nude mice xenografts as well as formation of ACF in AOM-treated mice. Thus Benfotiamine supplementation could be used as an excellent chemopreventive agent for the treatment of CRC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2397. doi:10.1158/1538-7445.AM2011-2397
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protective role of Benfotiamine a fat soluble vitamin b1 analogue in lipopolysaccharide induced cytotoxic signals in murine macrophages
Free Radical Biology and Medicine, 2010Co-Authors: Umesh C S Yadav, Satish K Srivastava, Nilesh M Kalariya, Kota V RamanaAbstract:Abstract This study was designed to investigate the molecular mechanisms by which Benfotiamine, a lipid-soluble analogue of vitamin B1, affects lipopolysaccharide (LPS)-induced inflammatory signals leading to cytotoxicity in the mouse macrophage cell line RAW264.7. Benfotiamine prevented LPS-induced apoptosis, expression of the Bcl-2 family of proapoptotic proteins, caspase-3 activation, and PARP cleavage and altered mitochondrial membrane potential and release of cytochrome c and apoptosis-inducing factor and phosphorylation and subsequent activation of p38-MAPK, stress-activated kinases (SAPK/JNK), protein kinase C, and cytoplasmic phospholipase A2 in RAW cells. Further, phosphorylation and degradation of inhibitory κB and consequent activation and nuclear translocation of the redox-sensitive transcription factor NF-κB were significantly prevented by Benfotiamine. The LPS-induced increased expression of cytokines and chemokines and the inflammatory marker proteins iNOS and COX-2 and their metabolic products NO and PGE2 was also blocked significantly. Thus, our results elucidate the molecular mechanism of the anti-inflammatory action of Benfotiamine in LPS-induced inflammation in murine macrophages. Benfotiamine suppresses oxidative stress-induced NF-κB activation and prevents bacterial endotoxin-induced inflammation, indicating that vitamin B1 supplementation could be beneficial in the treatment of inflammatory diseases.
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original contributionprotective role of Benfotiamine a fat soluble vitamin b1 analogue in lipopolysaccharide induced cytotoxic signals in murine macrophages
Free Radical Biology and Medicine, 2010Co-Authors: Umesh C S Yadav, Satish K Srivastava, Nilesh M Kalariya, Kota V RamanaAbstract:This study was designed to investigate the molecular mechanisms by which Benfotiamine, a lipid-soluble analogue of vitamin B1, affects lipopolysaccharide (LPS)-induced inflammatory signals leading to cytotoxicity in the mouse macrophage cell line RAW264.7. Benfotiamine prevented LPS-induced apoptosis, expression of the Bcl-2 family of proapoptotic proteins, caspase-3 activation, and PARP cleavage and altered mitochondrial membrane potential and release of cytochrome c and apoptosis-inducing factor and phosphorylation and subsequent activation of p38-MAPK, stress-activated kinases (SAPK/JNK), protein kinase C, and cytoplasmic phospholipase A2 in RAW cells. Further, phosphorylation and degradation of inhibitory κB and consequent activation and nuclear translocation of the redox-sensitive transcription factor NF-κB were significantly prevented by Benfotiamine. The LPS-induced increased expression of cytokines and chemokines and the inflammatory marker proteins iNOS and COX-2 and their metabolic products NO and PGE2 was also blocked significantly. Thus, our results elucidate the molecular mechanism of the anti-inflammatory action of Benfotiamine in LPS-induced inflammation in murine macrophages. Benfotiamine suppresses oxidative stress-induced NF-κB activation and prevents bacterial endotoxin-induced inflammation, indicating that vitamin B1 supplementation could be beneficial in the treatment of inflammatory diseases.
Xiangfei Li - One of the best experts on this subject based on the ideXlab platform.
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Benfotiamine a lipid soluble analog of vitamin b1 improves the mitochondrial biogenesis and function in blunt snout bream megalobrama amblycephala fed high carbohydrate diets by promoting the ampk pgc 1β nrf 1 axis
Frontiers in Physiology, 2018Co-Authors: Chao Xu, Dingdong Zhang, Li Zhang, Xiangfei LiAbstract:This study evaluated the effects of Benfotiamine on the growth performance and mitochondrial biogenesis and function of Megalobrama amblycephala fed high-carbohydrate diets. Fish (45.25 ± 0.34 g) were randomly fed six diets: the control diet (30% carbohydrate, C), the high-carbohydrate diet (43% carbohydrate, HC) and the HC diet supplemented with different Benfotiamine levels (0.7125 (HCB1), 1.425 (HCB2), 2.85 (HCB3) and 5.7 (HCB4) mg/kg) for 12 weeks. High-carbohydrate levels remarkably decreased weight gain rate, specific growth rate, relative feed intake, feed conversion ratio, p-AMPKα/t-AMPKα ratio, peroxisome proliferator activated receptor-γ coactivator-1β (PGC-1β) and nuclear respiratory factor-1 (NRF-1) protein expression, complexes I, III and IV activities and hepatic transcriptions of cytochrome B (CYT-B) and cytochrome c oxidase-2 (COX-2), whereas the opposite was true for plasma glucose, glycated serum protein, advanced glycation end products and insulin levels, tissue glycogen and lipid contents, hepatic adenosine triphosphate (ATP) and adenosine monophosphate (AMP) contents and ATP/AMP ratio, complexes V activities and the expressions of AMP-activated protein kinase α-2 (AMPKα-2), PGC-1β, NRF-1, mitochondrial transcription factor A (TFAM), mitofusin-1 (Mfn-1), optic atrophy-1 (Opa-1), dynamin-related protein-1 (Drp-1), fission-1 (Fis-1), mitochondrial fission factor (Mff) and ATP synthase-6 (ATP-6). As for Benfotiamine supplementation, HCB2 diet remarkably increased weight gain rate, specific growth rate, tissue glycogen and lipid contents, AMP contents, p-AMPKα/t-AMPKα ratio, PGC-1β and NRF-1 levels, complexes I, III, IV and V activities and hepatic transcriptions of AMPKα-2, PGC-1β, NRF-1, TFAM, Mfn-1, Opa-1, CYT-B, COX-2 and ATP-6, while the opposite was true for the remaining indicators. Overall, 1.425 mg/kg Benfotiamine improved the growth performance and mitochondrial biogenesis and function of fish fed high-carbohydrate diets through the activation of AMPK/PGC-1β/NRF-1 axis, the up-regulation of mitochondrial complexes activities and transcriptions as well as the enhancement of mitochondrial fusion coupled with the depression of mitochondrial fission.
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long term administration of Benfotiamine benefits the glucose homeostasis of juvenile blunt snout bream megalobrama amblycephala fed a high carbohydrate diet
Aquaculture, 2017Co-Authors: Chao Xu, Guangzhen Jiang, Bingke Wang, Xiangfei LiAbstract:Abstract This study aimed to investigate the effects of Benfotiamine on growth performance, glucose homeostasis and intermediary glucose metabolism of blunt snout bream ( Megalobrama amblycephala ). A total of 240 fish (average body weight: 24.24 ± 0.05 g) were randomly distributed into 12 tanks and fed three diets (control, diet with 30% carbohydrate; HC, diet with 43% carbohydrate; HCB, HC diet supplemented with 2.85 mg/kg Benfotiamine) for 12 weeks. The results indicated that fish fed the HCB diet had a lower specific growth rate and feed conversion ratio compared to those fed the control and HC diets, whereas protein efficiency ratio, nitrogen retention efficiency and energy retention efficiency showed an opposite trend. Additionally, fish offered HCB diet showed relatively high values of whole-body lipid contents, tissue glycogen and lipid contents and plasma insulin levels, whereas plasma levels of glucose, advanced glycation end products and glycated serum protein significantly decreased compared with other treatments. Furthermore, Benfotiamine improved the glucose tolerance of fish fed HC diet after a glucose load. High carbohydrate intake significantly up-regulated the mRNA levels of glucokinase, pyruvate kinase, glucose transporter 2, glycogen synthase, fatty acid synthetase and glucose-6-phosphate dehydrogenase, whereas the opposite was true for phosphoenolpyruvate carboxykinase, fructose-1,6-biphosphatase, glucose-6-phosphatase, carnitine palmitoyl transferase I and acyl-CoA oxidase. This also held true for fish fed HCB diet except for fatty acid oxidation process which was further enhanced. Overall, these findings suggested that Benfotiamine benefited the glucose metabolism of Megalobrama amblycephala fed high-carbohydrate diet through the stimulation of glycolysis, glycogenesis, lipogenesis and fatty acid oxidation coupled with the depression of gluconeogenesis. Statement of relevance This study investigated the effects of dietary Benfotiamine supplementation on growth performance, glucose homeostasis and intermediary metabolism of blunt snout bream. The data obtained here will facilitate our understanding of the potential mechanisms concerning the beneficial effects of Benfotiamine on the carbohydrate metabolism of fish. It is also helpful for the development of low-protein and high-energy feed for fish.
