Diabetes is a chronic disease that requires a long term management where oxidative stress plays a pivotal role in disease progression and intensifying secondary complications. In spite of all the research on diabetes ...Diabetes is a chronic disease that requires a long term management where oxidative stress plays a pivotal role in disease progression and intensifying secondary complications. In spite of all the research on diabetes and recent advances in diabetes treatments, the reality is that there is no cure for diabetes and its devastating complications. While currently available anti-diabetic therapies are effective in reducing blood glucose level, they are not without associated side effects when they are used for a long term applications. As a result, physicians and patients are inclining more towards to a safer therapy with less serious side effects in the form of medicinal foods and botanical alternatives that are suitable for chronic usage. Aloesin, an Aloe chromone, has previously been formulated with an aloe polysaccharide to give a composition called Loesyn, where it showed significant impact in reducing glycosylated hemoglobin, fasting blood glucose, fructosamine and plasma insulin level in humans. Radical scavenging activities of chromones and polysaccharides from Aloe have also been reported. Here we rationalize the relevance of use of Aloesin alone or in a standardized blend with Aloe polysaccharides, as a potential medical food to manage systemic oxidative stress and/or high blood glucose of diabetes.展开更多
BACKGROUND Constipation is a common functional gastrointestinal disorder and its etiology is multifactorial.Growing evidence suggests that intestinal dysbiosis is associated with the development of constipation.Prebio...BACKGROUND Constipation is a common functional gastrointestinal disorder and its etiology is multifactorial.Growing evidence suggests that intestinal dysbiosis is associated with the development of constipation.Prebiotics are subjected to bacterial fermentation in the gut to produce short-chain fatty acids(SCFAs),which can help relieve constipation symptoms.The prebiotic UG1601 consists of inulin,lactitol,and aloe vera gel,which are known laxatives,but randomized,controlled clinical trials that examine the effects of this supplement on gut microbiota composition are lacking.AIM To assess the efficacy of the prebiotic UG1601 in suppressing constipation-related adverse events in subjects with mild constipation.METHODS Adults with a stool frequency of less than thrice a week were randomized to receive either prebiotics or a placebo supplement for 4 wk.All participants provided their fecal and blood samples at baseline and at the end of intervention.Gastrointestinal symptoms and stool frequency were evaluated.The concentrations of serum endotoxemia markers and fecal SCFAs were determined.The relative abundance of SCFA-producing bacteria and the gut microbial community in the responders and non-responders in the prebiotics supplementation group were evaluated.RESULTS There were no significant differences in gastrointestinal symptoms between groups,although the prebiotic group showed greater symptom improvement.However,after prebiotic usage,serum cluster of differentiation(CD)14 and lipopolysaccharide(LPS)concentrations were significantly decreased(CD14,P=0.012;LPS,P<0.001).The change in LPS concentration was significantly larger in the prebiotic group than in the placebo group(P<0.001).Fecal SCFAs concentrations did not differ between groups,while the relative abundance of Roseburia hominis,a major butyrate producer,was significantly increased in the prebiotic group(P=0.045).The abundances of the phylum Firmicutes and the family Lachnospiraceae(phylum Firmicutes,class Clostridia)(P=0.009)were decreased in the responders within the prebiotic group.In addition,the proportions of the phylum Firmicutes,the class Clostridia,and the order Clostridiales were inversely correlated with several fecal SCFAs(P<0.05).CONCLUSION Alterations in gut microbiota composition,including a decrease in the phylum Firmicutes and an increase in butyrate-producing bacteria,following prebiotic UG1601 supplementation might help alleviate symptom scores and endotoxemia.展开更多
UP446 has been used in both joint supplements and prescription medical food. The purpose of this study was to evaluate the pharmaceutical safety of UP446 via acute and 26-week repeated oral dose toxicity study in SD r...UP446 has been used in both joint supplements and prescription medical food. The purpose of this study was to evaluate the pharmaceutical safety of UP446 via acute and 26-week repeated oral dose toxicity study in SD rats. In acute toxicity study, UP446 was administered by oral gavage to Sprague-Dawley rats (5 males and 5 females) at a dose of 5000 mg/kg. In 26-week repeated oral dose toxicity study, UP446 at doses of 500, 1000 and 2000 mg/kg/day were given orally to groups of rats (10 rats/dose/sex) for 26-week. UP446 at a dose of 5000 mg/kg produced no treatment-related acute toxicity or mortality in any of the animals tested during 14 days of the study. In 26-week repeated dose toxicity study, there was no significant difference in body weight between the control and all treatment groups. Blackish stool and soft stool was observed in one male in the 1000 mg/kg group and in some males and females of 2000 mg/kg group. However, these changes of stool were not considered to be toxic effects because neither histopathological change in gastrointestinal tracks (GIT) nor body weight change were detected. No drug induced abnormalities were found as of body weights, food consumption, ophthalmological examinations, urinalysis, hematology, clinical chemistry, organ weights and gross necropsy in any animals in the dosing groups. These results suggest that the oral lethal dose of UP446 for male and female rats is in excess of 5000 mg/kg and the no observed adverse effect level (NOAEL) of the UP446 for both male and female rats is considered to be greater than 2000 mg/kg/day.展开更多
Nutrigenomic studies were conducted to uncover the mechanism of action for the hypoglycemic and insulin sensitizing effects of UP780. From high fat diet-induced obesity mouse model for UP780, livers and white adipose ...Nutrigenomic studies were conducted to uncover the mechanism of action for the hypoglycemic and insulin sensitizing effects of UP780. From high fat diet-induced obesity mouse model for UP780, livers and white adipose tissues (WAT) from groups of lean control, high fat diet (HFD), and HFD treated with UP780 were collected for microarray study. Microarray generated gene expression changes were applied to Ingenuity Pathway Analysis for changes in canonical metabolic and signaling pathways. Microarray was validated by quantitative reverse transcriptase-polymerase chain reaction (QPCR), Western blots, liver triglyceride, liver cholesterol, liver steatosis, and insulin ELISA. UP780 treatment decreased liver gene expressions for multiple enzymes involved in fatty acid biosynthesis and triglyceride production. UP780 treatment increased gene expressions globally for the insulin receptor signaling pathway in WAT. Both liver triglyceride and liver cholesterol levels were significantly reduced by UP780 over HFD. The reduction of liver fat was confirmed by microscopic analysis of liver steatosis. Finally, UP780 significantly decreased fasting plasma insulin level over HFD. The mechanism of action for UP780 indicated a reduction of liver fat accumulation and an enhancement in adipose tissue insulin signaling pathway. This provided mechanistic explanation for the in vivo UP780 effects of enhanced insulin sensitiveity and decreased blood glucose in mouse diabetes and prediabetes models.展开更多
OBJECTIVE: Though the initial etiologies of arthritis are multifactorial, clinically, patients share the prime complaints of the disease, pain. Here the authors assessed the analgesic and anti-inflammatory effects of...OBJECTIVE: Though the initial etiologies of arthritis are multifactorial, clinically, patients share the prime complaints of the disease, pain. Here the authors assessed the analgesic and anti-inflammatory effects of UP1304, a composite that contains a standardized blend of extracts from the rhizome of Curcuma /onga and the root bark of Morus a/ba, on rats with carrageenan-induced paw edema. METHODS: A plant library was screened for bradykinin receptor antagonists./n vivo, the anti- inflammatory and analgesic effects of the standardized composite, UP1304, were evaluated in rats with carrageenan-induced paw edema using oral dose ranges of 100-400 mg/kg. Ibuprofen, at a dose of 200 mg/kg, was used as a reference compound. In vitro, cycleoxygenase (COX) and lipoxygenase (LOX) inhibition assays were performed to evaluate the degree of inflammation. RESULTS: Statistically significant improvements in pain resistance and paw edema suppression were observed in animals treated with UP1304, when compared to vehicle-treated rats. Results from the highest dose of UP1304 (400 mg/kg) were similar to those achieved by ibuprofen treatment at 200 mg/kg. /n vitro, UP1304 showed dose-dependent inhibition of the enzymatic activities of COX and LOX. A half-maximal inhibitory concentration of 9.6 tJg/mL for bradykinin B1 inhibition was calculated for the organic extract of C./onga. Curcumin showed Ki values of 2.73 and 58 IJg/mL for bradykinin receptors B1 and B2, respectively. CONCLUSION: Data presented here suggest that UP1304, analgesic and anti-inflammatory agent of botanical origin, acted as a bradykinin receptor B1 and B2 antagonist, and inhibited COX and LOX enzyme activities. This compound should be considered for the management of symptoms associated with arthritis.展开更多
文摘Diabetes is a chronic disease that requires a long term management where oxidative stress plays a pivotal role in disease progression and intensifying secondary complications. In spite of all the research on diabetes and recent advances in diabetes treatments, the reality is that there is no cure for diabetes and its devastating complications. While currently available anti-diabetic therapies are effective in reducing blood glucose level, they are not without associated side effects when they are used for a long term applications. As a result, physicians and patients are inclining more towards to a safer therapy with less serious side effects in the form of medicinal foods and botanical alternatives that are suitable for chronic usage. Aloesin, an Aloe chromone, has previously been formulated with an aloe polysaccharide to give a composition called Loesyn, where it showed significant impact in reducing glycosylated hemoglobin, fasting blood glucose, fructosamine and plasma insulin level in humans. Radical scavenging activities of chromones and polysaccharides from Aloe have also been reported. Here we rationalize the relevance of use of Aloesin alone or in a standardized blend with Aloe polysaccharides, as a potential medical food to manage systemic oxidative stress and/or high blood glucose of diabetes.
基金Supported by the Unigen,Inc.the Mid-Career Research Program of the National Research Foundation of Korea,No.2015R1A2A2A01004607the Basic Science Research Program of the National Research Foundation of Korea,No.NRF-2016R1A6A3A11934151
文摘BACKGROUND Constipation is a common functional gastrointestinal disorder and its etiology is multifactorial.Growing evidence suggests that intestinal dysbiosis is associated with the development of constipation.Prebiotics are subjected to bacterial fermentation in the gut to produce short-chain fatty acids(SCFAs),which can help relieve constipation symptoms.The prebiotic UG1601 consists of inulin,lactitol,and aloe vera gel,which are known laxatives,but randomized,controlled clinical trials that examine the effects of this supplement on gut microbiota composition are lacking.AIM To assess the efficacy of the prebiotic UG1601 in suppressing constipation-related adverse events in subjects with mild constipation.METHODS Adults with a stool frequency of less than thrice a week were randomized to receive either prebiotics or a placebo supplement for 4 wk.All participants provided their fecal and blood samples at baseline and at the end of intervention.Gastrointestinal symptoms and stool frequency were evaluated.The concentrations of serum endotoxemia markers and fecal SCFAs were determined.The relative abundance of SCFA-producing bacteria and the gut microbial community in the responders and non-responders in the prebiotics supplementation group were evaluated.RESULTS There were no significant differences in gastrointestinal symptoms between groups,although the prebiotic group showed greater symptom improvement.However,after prebiotic usage,serum cluster of differentiation(CD)14 and lipopolysaccharide(LPS)concentrations were significantly decreased(CD14,P=0.012;LPS,P<0.001).The change in LPS concentration was significantly larger in the prebiotic group than in the placebo group(P<0.001).Fecal SCFAs concentrations did not differ between groups,while the relative abundance of Roseburia hominis,a major butyrate producer,was significantly increased in the prebiotic group(P=0.045).The abundances of the phylum Firmicutes and the family Lachnospiraceae(phylum Firmicutes,class Clostridia)(P=0.009)were decreased in the responders within the prebiotic group.In addition,the proportions of the phylum Firmicutes,the class Clostridia,and the order Clostridiales were inversely correlated with several fecal SCFAs(P<0.05).CONCLUSION Alterations in gut microbiota composition,including a decrease in the phylum Firmicutes and an increase in butyrate-producing bacteria,following prebiotic UG1601 supplementation might help alleviate symptom scores and endotoxemia.
文摘UP446 has been used in both joint supplements and prescription medical food. The purpose of this study was to evaluate the pharmaceutical safety of UP446 via acute and 26-week repeated oral dose toxicity study in SD rats. In acute toxicity study, UP446 was administered by oral gavage to Sprague-Dawley rats (5 males and 5 females) at a dose of 5000 mg/kg. In 26-week repeated oral dose toxicity study, UP446 at doses of 500, 1000 and 2000 mg/kg/day were given orally to groups of rats (10 rats/dose/sex) for 26-week. UP446 at a dose of 5000 mg/kg produced no treatment-related acute toxicity or mortality in any of the animals tested during 14 days of the study. In 26-week repeated dose toxicity study, there was no significant difference in body weight between the control and all treatment groups. Blackish stool and soft stool was observed in one male in the 1000 mg/kg group and in some males and females of 2000 mg/kg group. However, these changes of stool were not considered to be toxic effects because neither histopathological change in gastrointestinal tracks (GIT) nor body weight change were detected. No drug induced abnormalities were found as of body weights, food consumption, ophthalmological examinations, urinalysis, hematology, clinical chemistry, organ weights and gross necropsy in any animals in the dosing groups. These results suggest that the oral lethal dose of UP446 for male and female rats is in excess of 5000 mg/kg and the no observed adverse effect level (NOAEL) of the UP446 for both male and female rats is considered to be greater than 2000 mg/kg/day.
文摘Nutrigenomic studies were conducted to uncover the mechanism of action for the hypoglycemic and insulin sensitizing effects of UP780. From high fat diet-induced obesity mouse model for UP780, livers and white adipose tissues (WAT) from groups of lean control, high fat diet (HFD), and HFD treated with UP780 were collected for microarray study. Microarray generated gene expression changes were applied to Ingenuity Pathway Analysis for changes in canonical metabolic and signaling pathways. Microarray was validated by quantitative reverse transcriptase-polymerase chain reaction (QPCR), Western blots, liver triglyceride, liver cholesterol, liver steatosis, and insulin ELISA. UP780 treatment decreased liver gene expressions for multiple enzymes involved in fatty acid biosynthesis and triglyceride production. UP780 treatment increased gene expressions globally for the insulin receptor signaling pathway in WAT. Both liver triglyceride and liver cholesterol levels were significantly reduced by UP780 over HFD. The reduction of liver fat was confirmed by microscopic analysis of liver steatosis. Finally, UP780 significantly decreased fasting plasma insulin level over HFD. The mechanism of action for UP780 indicated a reduction of liver fat accumulation and an enhancement in adipose tissue insulin signaling pathway. This provided mechanistic explanation for the in vivo UP780 effects of enhanced insulin sensitiveity and decreased blood glucose in mouse diabetes and prediabetes models.
文摘OBJECTIVE: Though the initial etiologies of arthritis are multifactorial, clinically, patients share the prime complaints of the disease, pain. Here the authors assessed the analgesic and anti-inflammatory effects of UP1304, a composite that contains a standardized blend of extracts from the rhizome of Curcuma /onga and the root bark of Morus a/ba, on rats with carrageenan-induced paw edema. METHODS: A plant library was screened for bradykinin receptor antagonists./n vivo, the anti- inflammatory and analgesic effects of the standardized composite, UP1304, were evaluated in rats with carrageenan-induced paw edema using oral dose ranges of 100-400 mg/kg. Ibuprofen, at a dose of 200 mg/kg, was used as a reference compound. In vitro, cycleoxygenase (COX) and lipoxygenase (LOX) inhibition assays were performed to evaluate the degree of inflammation. RESULTS: Statistically significant improvements in pain resistance and paw edema suppression were observed in animals treated with UP1304, when compared to vehicle-treated rats. Results from the highest dose of UP1304 (400 mg/kg) were similar to those achieved by ibuprofen treatment at 200 mg/kg. /n vitro, UP1304 showed dose-dependent inhibition of the enzymatic activities of COX and LOX. A half-maximal inhibitory concentration of 9.6 tJg/mL for bradykinin B1 inhibition was calculated for the organic extract of C./onga. Curcumin showed Ki values of 2.73 and 58 IJg/mL for bradykinin receptors B1 and B2, respectively. CONCLUSION: Data presented here suggest that UP1304, analgesic and anti-inflammatory agent of botanical origin, acted as a bradykinin receptor B1 and B2 antagonist, and inhibited COX and LOX enzyme activities. This compound should be considered for the management of symptoms associated with arthritis.