Streptozotocin(STZ)-induced type I diabetes mellitus(DM)models have been pivotal in diabetes research due to their ability to mimic the insulin-dependent hyperglyce-mia akin to human type I diabetes.However,these mode...Streptozotocin(STZ)-induced type I diabetes mellitus(DM)models have been pivotal in diabetes research due to their ability to mimic the insulin-dependent hyperglyce-mia akin to human type I diabetes.However,these models often suffer from poor induction rates and low survival post-STZ induction,especially in long-term experi-ments,necessitating insulin supplementation,which introduces additional variables to experiments.To address this,we present a novel modification to the STZ-induced DM model in C57BL/6J mice to improve survival rates without insulin supplemen-tation.Our method involves non-fasting,low-dose STZ injections dissolved in pH-neutral phosphate buffer saline instead of acidic sodium citrate buffer,administered over 5 days.We observed hyperglycemia induction in 94.28%of mice within a week post-injection,with stable high blood glucose levels,stable body weight,and minimal mortality up to 21 weeks.Notably,omitting 10%sucrose in water and fasting did not affect hyperglycemia induction.Our findings suggest that the modified protocol not only decreases the experimental effort of the researchers,but reduces animal stress and mortality,thus enhancing experimental outcomes and animal welfare.By opti-mizing the STZ-induced DM model in C57BL/6J mice,our study provides a valuable resource for researchers aiming to study diabetes and its complications while mini-mizing experimental variability and animal usage.展开更多
BACKGROUND Diabetes is known damage the liver and kidney,leading to hepatic dysfunction and kidney failure.Honey is believed to help in lowering the blood glucose levels of diabetic patients and reducing diabetic comp...BACKGROUND Diabetes is known damage the liver and kidney,leading to hepatic dysfunction and kidney failure.Honey is believed to help in lowering the blood glucose levels of diabetic patients and reducing diabetic complications.However,the effect of stingless bee honey(SBH)administration in relieving liver and kidney damage in diabetes has not been well-studied.AIM To investigate the effect of SBH administration on the kidney and liver of streptozotocin-induced(STZ;55 mg/kg)diabetic Sprague Dawley rats.METHODS The rats were grouped as follows(n=6 per group):non-diabetic(ND),untreated diabetic(UNT),metformin-treated(MET),and SBH+metformin-treated(SBME)groups.After successful diabetic induction,ND and UNT rats were given normal saline,whereas the treatment groups received SBH(2.0 g/kg and/or metformin(250 mg/kg)for 12 d.Serum biochemical parameters and histological changes using hematoxylin and eosin(H&E)and periodic acid–Schiff(PAS)staining were evaluated.RESULTS On H&E and PAS staining,the ND group showed normal architecture and cellularity of Bowman’s capsule and tubules,whereas the UNT and MET groups had an increased glomerular cellularity and thickened basement membrane.The SBH-treated group showed a decrease in hydropic changes and mild cellularity of the glomerulus vs the ND group based on H&E staining,but the two were similar on PAS staining.Likewise,the SBME-treated group had an increase in cellularity of the glomerulus on H&E staining,but it was comparable to the SBH and ND groups on PAS staining.UNT diabetic rats had tubular hydropic tubules,which were smaller than other groups.Reduced fatty vacuole formation and dilated blood sinusoids in liver tissue were seen in the SBH group.Conversely,the UNT group had high glucose levels,which subsequently increased MDA levels,ultimately leading to liver damage.SBH treatment reduced this damage,as evidenced by having the lowest fasting glucose,serum alanine transaminase,aspartate transaminase,and alkaline phosphatase levels compared to other groups,although the levels of liver enzymes were not statistically significant.CONCLUSION The cellularity of the Bowman’s capsule,as well as histological alteration of kidney tubules,glomerular membranes,and liver tissues in diabetic rats after oral SBH resembled those of ND rats.Therefore,SBH exhibited a protective hepatorenal effect in a diabetic rat model.展开更多
Objective:To assess the effect of oral treatment of methanolic extract of the aerial parts of Astragalus adscendens in streptozotocin-induced diabetic rats.Methods:In order to induce diabetes,rats intraperitoneally re...Objective:To assess the effect of oral treatment of methanolic extract of the aerial parts of Astragalus adscendens in streptozotocin-induced diabetic rats.Methods:In order to induce diabetes,rats intraperitoneally received streptozotocin at 65 mg/kg.Sixty adult male Wistar rats were allocated into six groups(10 rats per each)including the healthy control group,the diabetic group as well as the diabetic group treated with Astragalus adscendens methanolic extract at 50,100,and 200 mg/kg per day or glibenclamide(0.6 mg/kg/day)for 28 d.The effects of Astragalus adscendens methanolic extract on the levels of glucose,insulin,alanine aminotransferase,alkaline phosphatase,aspartate aminotransferase,bilirubin,creatinine,urea,uric acid,total protein,albumin,triglyceride,cholesterol,α-amylase,oxidant/antioxidant enzymes,and inflammatory cytokines were evaluated.Real time-PCR was also used for measuring the gene expression of caspase-3,Bcl2,and Bax.Results:The levels of glucose,cholesterol,triglyceride,creatinine,urea,uric acid,alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,bilirubin,and malondialdehyde considerably declined(P<0.001)in diabetic rats after treatment with Astragalus adscendens methanolic extract especially at a dose of 200 mg/kg.In addition,treatment with Astragalus adscendens methanolic extract noticeably increased the level of insulin,total protein,and albumin as well as improved the activities of catalase,glutathione peroxidase,and superoxide dismutase,as well as the expression levels of TNF-α,IL-1β,caspase-3,Bcl2 and Bax(P<0.001)compared to the diabetic control group.The extract also inhibitedα-amylase in a dose-dependent manner with an IC_(50)value of 19.6μg/mL.Conclusions:Astragalus adscendens methanolic extract shows potent antidiabetic,anti-inflammatory,anti-apoptotic,and antioxidant effects in diabetic rats.However,more studies are needed to verify the underlying mechanism of the effect of this plant extract and test its efficacy in clinical trials.展开更多
Background: Moringa oleifera plant is popularly known for its rich phytoconstituents and nutritional value and important medicinal values in both traditional and modern systems of medicine. We explored the present stu...Background: Moringa oleifera plant is popularly known for its rich phytoconstituents and nutritional value and important medicinal values in both traditional and modern systems of medicine. We explored the present study for measurements of microelements, amino acid, phenolic content in hydro-al-coholic flower and leaf extracts of Moringa oleifera along with anti-diabetic activity in Streptozotocin (STZ)-induced diabetic male Wistar rats. Methodology: The micronutrients were determined by using atomic absorption spectrophotometer at 285 nm and 422 nm for Calcium (Ca), phosphorus (P), Iron (Fe), and Zinc (Zn), etc. The trace elements were also measured by spectrophotometer. The essential amino acid was determined by using Amino acid analyser. The total phenolic content in hydro-alcoholic extracts (flower and leaf) M. oleifera measured the absorbance at 760 nm by UV spectrophotometer. The screening of anti-diabetic activity HAFE and HALE of Moringa oleifera at two different dose of 100 and 200 mg/kg b.w. for 21 days were performed by determining the changes in biochemical parameters. Result and Discussion: The results revels that the presence of micronutrients, trace elements and amino acids in both flower and leaf of M. oleifera. The hydrolaocholic extracts of HAFE and HALE at 200 mg/kg b.w. showed significant antidiabetic activity compared with standard Glibenclamide. Whereas dose at 100 mg/kg b.w. showed moderate activity. Conclusion: In conclusion, the M. oleifera exhibits more effectiveness against STZ-induced diabetes. The HAFE and HALF extracts exhibited significant anti-diabetic property and active components may be isolated and clinical studies is required for further evaluation. Because of the rich source of phytoconstients, nutritional elements will be helpful in processed food products as dietary supplements especially for malnutrition in children in the current era.展开更多
Purpose: This study was conducted in order to evaluate the antidiabetic effects of the aqueous extract of Lippia multiflora supplemented with magnesium on some biochemical markers of the kidneys and liver in type 2 di...Purpose: This study was conducted in order to evaluate the antidiabetic effects of the aqueous extract of Lippia multiflora supplemented with magnesium on some biochemical markers of the kidneys and liver in type 2 diabetic rats. Method: 7 groups of 4 STZ-diabetic rats received separately orally Glucophage<sup>®</sup> (Glu 10 mg/kg), the plant extract (LiMAE 200 - 600 mg/kg) and the plant extract supplemented with magnesium (LiMAE-Mg 200 - 600 mg/kg). After a daily treatment of 21 days, serum biochemical parameters were assayed in 16 hr-fasted rats. Results: Diabetes caused a significant (p Conclusion: The addition of magnesium to the extract of Lippia multiflora caused a greater reduction in the levels of urea, creatinine, ALT and AST increased in STZ-diabetic rats. Magnesium would therefore enhance the nephroprotective and hepatoprotective effects of Lippia multiflora in diabetic rats.展开更多
Background: Few studies have often focused on medicinal plant mixtures, yet the most used in low-and middle-income areas as alternative drug to treat diseases. Objective: To evaluate the antidiabetic effects of Emilia...Background: Few studies have often focused on medicinal plant mixtures, yet the most used in low-and middle-income areas as alternative drug to treat diseases. Objective: To evaluate the antidiabetic effects of Emilia coccinea (Ec) (Asteraceae), Scoparia dulcis (Sd) (Plantaginaceae) and Tetracarpidium conophorum (Tc) (Euphorbiaceae) aqueous extracts mixture (EcSdTc) in rats. Methodology: Single plant aqueous extracts (Ec, Sd and Tc) and their mixtures (EcSd, EcTc, SdTc and EcSdTc) (each at the doses of 125 and 250 mg/kg body weight respectively) were evaluated in acute administration on blood glucose in normal, glucose-overloaded and diabetic rats;then EcSdTc mixture was assessed in prolonged administration (21 days) on blood glucose, body weight, serum biochemical and antioxidant parameters in diabetic rats. Diabetes was induced by single intraperitoneal administration of streptozotocin (STZ;50 mg/kg), and glibenclamide (10 mg/kg) was used as standard drug. Results: In acute administration, EcTc250, EcSdTc125, SdTc250, SdTc125, EcSd250, and EcSdTc250 extracts mixtures reduced (p Conclusion: EcSdTc aqueous extracts mixture has potent hypoglycemic and antidiabetic effects, probably due to their bioactive compounds synergistic and/or additive actions, justifying its traditional use as alternative remedies.展开更多
Diabetes mellitus (DM) is a metabolic disease caused by the absence or dysfunction of insulin;a hormone secreted by the pancreatic beta cell (β-cell) whenever blood glucose exceeds the normal physiological value. The...Diabetes mellitus (DM) is a metabolic disease caused by the absence or dysfunction of insulin;a hormone secreted by the pancreatic beta cell (β-cell) whenever blood glucose exceeds the normal physiological value. The long-term effects of the disease on the body’s organs are one of the leading causes of death in the world. To alleviate this global burden of DM, a number of studies have been conducted to lower blood glucose levels in patients. For genetic and ethical reasons, humans are far from being appropriate subjects in such investigations and the use of animal models has therefore been the way forward. Streptozotocin (STZ) is a glucosamine-nitrosourea compound that selectively destroys β-cells and has been widely used to induce Type I diabetes in several animal species. Recent literature has shown that a non-diabetic dose of STZ, combined with a high-fat diet (HFD), can mimic Type II diabetes. Yet, researchers seldom provide data to corroborate the high sensitivity of STZ on these animal models. In addition, there are few reports of potentially fatal effects of the use of STZ as a supplement in obese HFD animals when attempting to induce Type II diabetes. The present review article highlights the parameters that could be at the origin of the extreme sensitivity and vulnerability of obese animals to STZ.展开更多
BACKGROUND Lomatogonium rotatum(LR)is traditionally used in Mongolian folk medicine as a hypoglycemic agent,but its evidence-based pharmacological effects and mechanisms of action have not been fully elucidated.AIM To...BACKGROUND Lomatogonium rotatum(LR)is traditionally used in Mongolian folk medicine as a hypoglycemic agent,but its evidence-based pharmacological effects and mechanisms of action have not been fully elucidated.AIM To emphasize the hypoglycemic action mechanism of LR in a type 2 diabetic rat model and examine potential biomarkers to obtain mechanistic understanding regarding serum metabolite modifications.METHODS A high-fat,high-sugar diet and streptozotocin injection-induced type 2 diabetic rat model was established.The chemical composition of the LR was identified by high performance liquid chromatography.LR extract administrated as oral gavage at 0.5 g/kg,2.5 g/kg,and 5 g/kg for 4 wk.Anti-diabetic effects of LR extract were evaluated based on histopathological examination as well as the measurement of blood glucose,insulin,glucagon-like peptide 1(GLP-1),and lipid levels.Serum metabolites were analyzed using an untargeted metabolomics approach.RESULTS According to a chemical analysis,swertiamarin,sweroside,hesperetin,coumarin,1.7-dihydroxy-3,8-dimethoxyl xanthone,and 1-hydroxy-2,3,5 trimethoxanone are the principal active ingredients in LR.An anti-diabetic experiment revealed that the LR treatment significantly increased plasma insulin and GLP-1 levels while effectively lowering blood glucose,total cholesterol,triglycerides,low-density lipoprotein cholesterol,and oral glucose tolerance test compared to the model group.Furthermore,untargeted metabolomic analysis of serum samples detected 236 metabolites,among which 86 were differentially expressed between the model and the LR group.It was also found that LR considerably altered the levels of metabolites such as vitamin B6,mevalonate-5P,Dproline,L-lysine,and taurine,which are involved in the regulation of the vitamin B6 metabolic pathway,selenium amino acid metabolic pathway,pyrimidine metabolic pathway,and arginine and proline metabolic pathways.CONCLUSION These findings indicated that LR may have a hypoglycemic impact and that its role may be related to changes in the serum metabolites and to facilitate the release of insulin and GLP-1,which lower blood glucose and lipid profiles.展开更多
文摘Streptozotocin(STZ)-induced type I diabetes mellitus(DM)models have been pivotal in diabetes research due to their ability to mimic the insulin-dependent hyperglyce-mia akin to human type I diabetes.However,these models often suffer from poor induction rates and low survival post-STZ induction,especially in long-term experi-ments,necessitating insulin supplementation,which introduces additional variables to experiments.To address this,we present a novel modification to the STZ-induced DM model in C57BL/6J mice to improve survival rates without insulin supplemen-tation.Our method involves non-fasting,low-dose STZ injections dissolved in pH-neutral phosphate buffer saline instead of acidic sodium citrate buffer,administered over 5 days.We observed hyperglycemia induction in 94.28%of mice within a week post-injection,with stable high blood glucose levels,stable body weight,and minimal mortality up to 21 weeks.Notably,omitting 10%sucrose in water and fasting did not affect hyperglycemia induction.Our findings suggest that the modified protocol not only decreases the experimental effort of the researchers,but reduces animal stress and mortality,thus enhancing experimental outcomes and animal welfare.By opti-mizing the STZ-induced DM model in C57BL/6J mice,our study provides a valuable resource for researchers aiming to study diabetes and its complications while mini-mizing experimental variability and animal usage.
基金Ministry of Higher Education,Malaysia for Fundamental Research Grant Scheme FRGS/1/2019/SKK06/USM/03/6,No.291983-329281.
文摘BACKGROUND Diabetes is known damage the liver and kidney,leading to hepatic dysfunction and kidney failure.Honey is believed to help in lowering the blood glucose levels of diabetic patients and reducing diabetic complications.However,the effect of stingless bee honey(SBH)administration in relieving liver and kidney damage in diabetes has not been well-studied.AIM To investigate the effect of SBH administration on the kidney and liver of streptozotocin-induced(STZ;55 mg/kg)diabetic Sprague Dawley rats.METHODS The rats were grouped as follows(n=6 per group):non-diabetic(ND),untreated diabetic(UNT),metformin-treated(MET),and SBH+metformin-treated(SBME)groups.After successful diabetic induction,ND and UNT rats were given normal saline,whereas the treatment groups received SBH(2.0 g/kg and/or metformin(250 mg/kg)for 12 d.Serum biochemical parameters and histological changes using hematoxylin and eosin(H&E)and periodic acid–Schiff(PAS)staining were evaluated.RESULTS On H&E and PAS staining,the ND group showed normal architecture and cellularity of Bowman’s capsule and tubules,whereas the UNT and MET groups had an increased glomerular cellularity and thickened basement membrane.The SBH-treated group showed a decrease in hydropic changes and mild cellularity of the glomerulus vs the ND group based on H&E staining,but the two were similar on PAS staining.Likewise,the SBME-treated group had an increase in cellularity of the glomerulus on H&E staining,but it was comparable to the SBH and ND groups on PAS staining.UNT diabetic rats had tubular hydropic tubules,which were smaller than other groups.Reduced fatty vacuole formation and dilated blood sinusoids in liver tissue were seen in the SBH group.Conversely,the UNT group had high glucose levels,which subsequently increased MDA levels,ultimately leading to liver damage.SBH treatment reduced this damage,as evidenced by having the lowest fasting glucose,serum alanine transaminase,aspartate transaminase,and alkaline phosphatase levels compared to other groups,although the levels of liver enzymes were not statistically significant.CONCLUSION The cellularity of the Bowman’s capsule,as well as histological alteration of kidney tubules,glomerular membranes,and liver tissues in diabetic rats after oral SBH resembled those of ND rats.Therefore,SBH exhibited a protective hepatorenal effect in a diabetic rat model.
文摘Objective:To assess the effect of oral treatment of methanolic extract of the aerial parts of Astragalus adscendens in streptozotocin-induced diabetic rats.Methods:In order to induce diabetes,rats intraperitoneally received streptozotocin at 65 mg/kg.Sixty adult male Wistar rats were allocated into six groups(10 rats per each)including the healthy control group,the diabetic group as well as the diabetic group treated with Astragalus adscendens methanolic extract at 50,100,and 200 mg/kg per day or glibenclamide(0.6 mg/kg/day)for 28 d.The effects of Astragalus adscendens methanolic extract on the levels of glucose,insulin,alanine aminotransferase,alkaline phosphatase,aspartate aminotransferase,bilirubin,creatinine,urea,uric acid,total protein,albumin,triglyceride,cholesterol,α-amylase,oxidant/antioxidant enzymes,and inflammatory cytokines were evaluated.Real time-PCR was also used for measuring the gene expression of caspase-3,Bcl2,and Bax.Results:The levels of glucose,cholesterol,triglyceride,creatinine,urea,uric acid,alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,bilirubin,and malondialdehyde considerably declined(P<0.001)in diabetic rats after treatment with Astragalus adscendens methanolic extract especially at a dose of 200 mg/kg.In addition,treatment with Astragalus adscendens methanolic extract noticeably increased the level of insulin,total protein,and albumin as well as improved the activities of catalase,glutathione peroxidase,and superoxide dismutase,as well as the expression levels of TNF-α,IL-1β,caspase-3,Bcl2 and Bax(P<0.001)compared to the diabetic control group.The extract also inhibitedα-amylase in a dose-dependent manner with an IC_(50)value of 19.6μg/mL.Conclusions:Astragalus adscendens methanolic extract shows potent antidiabetic,anti-inflammatory,anti-apoptotic,and antioxidant effects in diabetic rats.However,more studies are needed to verify the underlying mechanism of the effect of this plant extract and test its efficacy in clinical trials.
文摘Background: Moringa oleifera plant is popularly known for its rich phytoconstituents and nutritional value and important medicinal values in both traditional and modern systems of medicine. We explored the present study for measurements of microelements, amino acid, phenolic content in hydro-al-coholic flower and leaf extracts of Moringa oleifera along with anti-diabetic activity in Streptozotocin (STZ)-induced diabetic male Wistar rats. Methodology: The micronutrients were determined by using atomic absorption spectrophotometer at 285 nm and 422 nm for Calcium (Ca), phosphorus (P), Iron (Fe), and Zinc (Zn), etc. The trace elements were also measured by spectrophotometer. The essential amino acid was determined by using Amino acid analyser. The total phenolic content in hydro-alcoholic extracts (flower and leaf) M. oleifera measured the absorbance at 760 nm by UV spectrophotometer. The screening of anti-diabetic activity HAFE and HALE of Moringa oleifera at two different dose of 100 and 200 mg/kg b.w. for 21 days were performed by determining the changes in biochemical parameters. Result and Discussion: The results revels that the presence of micronutrients, trace elements and amino acids in both flower and leaf of M. oleifera. The hydrolaocholic extracts of HAFE and HALE at 200 mg/kg b.w. showed significant antidiabetic activity compared with standard Glibenclamide. Whereas dose at 100 mg/kg b.w. showed moderate activity. Conclusion: In conclusion, the M. oleifera exhibits more effectiveness against STZ-induced diabetes. The HAFE and HALF extracts exhibited significant anti-diabetic property and active components may be isolated and clinical studies is required for further evaluation. Because of the rich source of phytoconstients, nutritional elements will be helpful in processed food products as dietary supplements especially for malnutrition in children in the current era.
文摘Purpose: This study was conducted in order to evaluate the antidiabetic effects of the aqueous extract of Lippia multiflora supplemented with magnesium on some biochemical markers of the kidneys and liver in type 2 diabetic rats. Method: 7 groups of 4 STZ-diabetic rats received separately orally Glucophage<sup>®</sup> (Glu 10 mg/kg), the plant extract (LiMAE 200 - 600 mg/kg) and the plant extract supplemented with magnesium (LiMAE-Mg 200 - 600 mg/kg). After a daily treatment of 21 days, serum biochemical parameters were assayed in 16 hr-fasted rats. Results: Diabetes caused a significant (p Conclusion: The addition of magnesium to the extract of Lippia multiflora caused a greater reduction in the levels of urea, creatinine, ALT and AST increased in STZ-diabetic rats. Magnesium would therefore enhance the nephroprotective and hepatoprotective effects of Lippia multiflora in diabetic rats.
文摘Background: Few studies have often focused on medicinal plant mixtures, yet the most used in low-and middle-income areas as alternative drug to treat diseases. Objective: To evaluate the antidiabetic effects of Emilia coccinea (Ec) (Asteraceae), Scoparia dulcis (Sd) (Plantaginaceae) and Tetracarpidium conophorum (Tc) (Euphorbiaceae) aqueous extracts mixture (EcSdTc) in rats. Methodology: Single plant aqueous extracts (Ec, Sd and Tc) and their mixtures (EcSd, EcTc, SdTc and EcSdTc) (each at the doses of 125 and 250 mg/kg body weight respectively) were evaluated in acute administration on blood glucose in normal, glucose-overloaded and diabetic rats;then EcSdTc mixture was assessed in prolonged administration (21 days) on blood glucose, body weight, serum biochemical and antioxidant parameters in diabetic rats. Diabetes was induced by single intraperitoneal administration of streptozotocin (STZ;50 mg/kg), and glibenclamide (10 mg/kg) was used as standard drug. Results: In acute administration, EcTc250, EcSdTc125, SdTc250, SdTc125, EcSd250, and EcSdTc250 extracts mixtures reduced (p Conclusion: EcSdTc aqueous extracts mixture has potent hypoglycemic and antidiabetic effects, probably due to their bioactive compounds synergistic and/or additive actions, justifying its traditional use as alternative remedies.
文摘Diabetes mellitus (DM) is a metabolic disease caused by the absence or dysfunction of insulin;a hormone secreted by the pancreatic beta cell (β-cell) whenever blood glucose exceeds the normal physiological value. The long-term effects of the disease on the body’s organs are one of the leading causes of death in the world. To alleviate this global burden of DM, a number of studies have been conducted to lower blood glucose levels in patients. For genetic and ethical reasons, humans are far from being appropriate subjects in such investigations and the use of animal models has therefore been the way forward. Streptozotocin (STZ) is a glucosamine-nitrosourea compound that selectively destroys β-cells and has been widely used to induce Type I diabetes in several animal species. Recent literature has shown that a non-diabetic dose of STZ, combined with a high-fat diet (HFD), can mimic Type II diabetes. Yet, researchers seldom provide data to corroborate the high sensitivity of STZ on these animal models. In addition, there are few reports of potentially fatal effects of the use of STZ as a supplement in obese HFD animals when attempting to induce Type II diabetes. The present review article highlights the parameters that could be at the origin of the extreme sensitivity and vulnerability of obese animals to STZ.
基金Supported by the National Natural Science Foundation of China,No.82260773 and 81803845Central Government Guided Local Scientific and Technological Development Project,No.2021ZY0015Science and Technology Young Talents Development Project of Inner Mongolia Autonomous Region,No.NJYT22048.
文摘BACKGROUND Lomatogonium rotatum(LR)is traditionally used in Mongolian folk medicine as a hypoglycemic agent,but its evidence-based pharmacological effects and mechanisms of action have not been fully elucidated.AIM To emphasize the hypoglycemic action mechanism of LR in a type 2 diabetic rat model and examine potential biomarkers to obtain mechanistic understanding regarding serum metabolite modifications.METHODS A high-fat,high-sugar diet and streptozotocin injection-induced type 2 diabetic rat model was established.The chemical composition of the LR was identified by high performance liquid chromatography.LR extract administrated as oral gavage at 0.5 g/kg,2.5 g/kg,and 5 g/kg for 4 wk.Anti-diabetic effects of LR extract were evaluated based on histopathological examination as well as the measurement of blood glucose,insulin,glucagon-like peptide 1(GLP-1),and lipid levels.Serum metabolites were analyzed using an untargeted metabolomics approach.RESULTS According to a chemical analysis,swertiamarin,sweroside,hesperetin,coumarin,1.7-dihydroxy-3,8-dimethoxyl xanthone,and 1-hydroxy-2,3,5 trimethoxanone are the principal active ingredients in LR.An anti-diabetic experiment revealed that the LR treatment significantly increased plasma insulin and GLP-1 levels while effectively lowering blood glucose,total cholesterol,triglycerides,low-density lipoprotein cholesterol,and oral glucose tolerance test compared to the model group.Furthermore,untargeted metabolomic analysis of serum samples detected 236 metabolites,among which 86 were differentially expressed between the model and the LR group.It was also found that LR considerably altered the levels of metabolites such as vitamin B6,mevalonate-5P,Dproline,L-lysine,and taurine,which are involved in the regulation of the vitamin B6 metabolic pathway,selenium amino acid metabolic pathway,pyrimidine metabolic pathway,and arginine and proline metabolic pathways.CONCLUSION These findings indicated that LR may have a hypoglycemic impact and that its role may be related to changes in the serum metabolites and to facilitate the release of insulin and GLP-1,which lower blood glucose and lipid profiles.
