scholarly journals Leeches alleviates diabetic macroangiopathy by increasing nitric oxide production in rat aorta and restoring endothelium-dependent vasodilatation

Author(s):  
Zhaohui Fang ◽  
Xiu Hu ◽  
Zhi Chen ◽  
Jing Xie ◽  
Di Wu ◽  
...  

IntroductionDiabetes mellitus (DM) is a chronic metabolic disorder characterized by elevated blood glucose level over a prolonged period, leading to severe damage in tissues including the heart, blood vessels, eyes and the kidneys. Danzhi Jiangtang Capsule (DJC) is an effective drug for diabetes, but the mechanism responsible for its efficacy remains unknown. This study aimed to explore the effective ingredient of DJC that ameliorated diabetes and the possible mechanisms.Material and methodsWe orally treated streptozotocin (STZ)-induced diabetic rats with 540 mg/kg DIC or the same dose of its four active components, namely Leeches, Pseudostellaria Polysaccharides (PP), Paeonia Suffruticosa Andr (PSA) and Rehmannia Glutinosa Libosch (RGL), respectively for 8 weeks.ResultsAlthough all of these components could reduce blood glucose levels in diabetic rats, the extent of alleviation of DJC was more pronounced than all of its four ingredients. Unlike the other three components, Leeches is the only effective ingredient of DJC that decreased tetrahydrobiopterin (BH4) oxidation to activate endothelial nitric oxide synthase (eNOS), and increased nitric oxide (NO) production, leading to improved endothelium-dependent relaxation both in diabetic rats and in immortalized human mesangial cells under the stimulation of high glucose.ConclusionsLeeches could alleviate diabetic macroangiopathy by inhibiting NO release in endothelial cells under high-glucose condition.

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Bhesh Raj Sharma ◽  
Dong Young Rhyu

Lespedezahas been used for the management of diabetes in folklore medicine. The purpose of this study is to investigate the protective effects of the methanol extract ofLespedeza davurica(LD) on cytokine-inducedβ-cell damage and streptozotocin- (STZ-) induced diabetes. RINm5F cells were treated with interleukin- (IL-) 1βand interferon- (IFN-)γto induce pancreaticβ-cell damage. The exposure of LD extract significantly decreased cell death, nitric oxide (NO) production, nitric oxide synthase (iNOS) expression, and nucleus factor-kappa B (NF-κB) p65 activation. Antidiabetic effects of LD extract were observed by oral glucose tolerance test (OGTT) in normal rats and by checking the biochemical, physiological, and histopathological parameters in STZ-induced diabetic rats. In OGTT, glucose clearance levels improved by oral treatment of LD extract. The water intake, urine volume, blood glucose, and serum TG, TC, TBARS, and DPP-IV levels were significantly decreased, and liver glycogen content was significantly increased by treatment of LD extract (250 mg/kg BW) in STZ-induced diabetic rats. Also, insulin immunoreactivity of the pancreases was increased in LD extract administrated rats compared with diabetic control rats. These results indicate that LD extract may protect pancreaticβ-cell damage and regulate the blood glucose in STZ-induced diabetic rats.


1997 ◽  
Vol 8 (8) ◽  
pp. 1276-1282
Author(s):  
H Trachtman ◽  
S Futterweit ◽  
D L Crimmins

Hyperglycemia directly contributes to the development of diabetic nephropathy. A high-serum glucose concentration alters intraglomerular hemodynamics and promotes deposition of extracellular matrix in the kidney. Nitric oxide (NO) is a short-lived messenger molecule that participates in the regulation of renal blood flow, GFR, and mesangial matrix accumulation. Therefore, in this study it was tested whether high glucose directly modulates NO synthesis by rat mesangial cells in vitro by measuring the accumulation of nitrite, the stable metabolite of NO, in the incubation media. Raising the external glucose concentration to 33.3 mM for 24 to 72 h reduced nitrite levels in cell supernatants in a time-dependent manner to a nadir of 14 +/- 3% of the amount in normal glucose media (5.6 mM) (P < 0.01). The decline in NO synthesis in high glucose media was paralleled by decreased cyclic guanosine monophosphate generation; however, there was no alteration in rat mesangial cell expression of inducible NO synthase protein. The suppressive effect of high glucose on NO production by mesangial cells was not modified by inhibition of protein kinase C (H-7), the addition of antioxidants (vitamin E or superoxide dismutase), or a pan-specific anti-transforming growth factor-beta antibody. An elevated ambient glucose caused a time-dependent reduction in mesangial cell L-arginine content. Addition of L-arginine (10 to 20 mM) to external media partially reversed the inhibitory effect of high glucose on mesangial cell NO production in a dose-dependent manner. The highest dose of L-arginine (20 mM) increased mesangial cell L-arginine content to comparable levels in normal and high glucose media. These results indicate that high glucose causes depletion of L-arginine in mesangial cells and compromises NO synthesis. Limitation in the metabolic precursor and other, as yet unidentified, factors act to reduce NO production by mesangial cells in the presence of an elevated ambient glucose level, a change that may play a role in the development of diabetic glomerulosclerosis.


2019 ◽  
Vol 19 (4) ◽  
pp. 503-510 ◽  
Author(s):  
Mohamed Eddouks ◽  
Farid Khallouki ◽  
Robert W. Owen ◽  
Morad Hebi ◽  
Remy Burcelin

Aims: Arganimide A (4,4-dihydroxy-3,3-imino-di-benzoic acid) is a compound belonging to a family of aminophenolics found in fruit of Argania spinosa. The purpose of this study was to investigate the glucose and lipid lowering activity of Arganimide A (ARG A). Methods: The effect of a single dose and daily oral administration of Arganimide A (ARG A) on blood glucose levels and plasma lipid profile was tested in normal and streptozotocin (STZ) diabetic rats at a dose of 2 mg/kg body weight. Results: Single oral administration of ARG A reduced blood glucose levels from 26.50±0.61 mmol/L to 14.27±0.73 mmol/L (p<0.0001) six hours after administration in STZ diabetic rats. Furthermore, blood glucose levels were decreased from 5.35±0.30 mmol/L to 3.57±0.17 mmol/L (p<0.0001) and from 26.50±0.61 mmol/L to 3.67±0.29 mmol/L (p<0.0001) in normal and STZ diabetic rats, respectively, after seven days of treatment. Moreover, no significant changes in body weight in normal and STZ rats were shown. According to the lipid profile, the plasma triglycerides levels were decreased significantly in diabetic rats after seven days of ARG treatment (p<0.05). Moreover, seven days of ARG A treatment decreased significantly the plasma cholesterol concentrations (p<0.001). Conclusion: ARG A possesses glucose and lipid-lowering activity in diabetic rats and this natural compound may be beneficial in the treatment of diabetes.


2019 ◽  
Vol 19 (3) ◽  
pp. 292-301
Author(s):  
Omar Farid ◽  
Naoufel Ali Zeggwagh ◽  
Fadwa EL Ouadi ◽  
Mohamed Eddouks

Objective: The aim of this work was to evaluate the antihyperglycemic activity of aerial parts aqueous extract (A.P.A.E) of Mentha pulegium (M. pulegium) on blood glucose levels in normal and streptozotocin(STZ)-induced diabetic rat. The glucose tolerance was evaluated in normal rats. Moreover, the histological sections and morphometric analysis at the liver and pancreas have been carried out in this investigation both in normal and STZ-diabetic rats. Methods: The effect of A.P.A.E of M. pulegium (20 mg/kg) on blood glucose levels was investigated in normal and diabetic rats (n=6). Histopathological changes in liver and pancreas were examined under phase contrast microscope and a preliminary screening for various bioactive constituents was realized according to standard methods. Key Findings: Both single and repeated oral administration of A.P.A.E (20 mg/kg) caused a significant reduction in blood glucose levels in STZ-diabetic rats (p<0.0001). The morphometric analysis and histological sections realized in pancreas and liver have showed the beneficial effect of the A.P.A.E in cellular population. According to oral glucose tolerance test (OGTT), the aqueous extract has revealed an improvement of glucose tolerance in normal rat. Furthermore, the preliminary phytochemical screening of A.P.A.E of M. pulegium has demonstrated the presence of various metabolite compounds including polyphenols, flavonoids, terpenoids tannins, cyanidins, sesquiterpenes, and glycosides. Conclusion: We conclude that the A.P.A.E of M. pulegium (20 mg/kg) exhibits a potent antihyperglycemic activity in STZ diabetic rats.


2020 ◽  
Vol 10 (1) ◽  
pp. 61-68 ◽  
Author(s):  
Morad Hebi ◽  
Mohamed Eddouks

Background: Corrigiola telephiifolia Pourr, is a perennial species, woody distributed throughout the north of Africa. This plant is used in traditional Mediterranean preparations and has many traditional uses especially treatment of diabetes. Aim/Methods: The current research was carried out to evaluate the antidiabetic effect of Aerial Parts of Aqueous Extract (APAE) of Corrigiola telephiifolia (C. telephiifolia) on both normal and streptozotocin (STZ)-induced diabetic rats treated at a dose of 5 mg/kg for fifteen days. Additionally, the histopathological changes in the liver, morphometric analysis, Oral Glucose Tolerance Test (OGTT) in normal rats and preliminary phytochemical screening for various components were realized. Results: Single oral administration of the APAE of C. telephiifolia (5mg/kg) showed no significant change in glycaemia of normal and STZ-induced diabetic rats. In contrast, repeated oral administration of C. telephiifolia reduced blood glucose levels from 4.11 ± 0.10 mmol/L to 3.16 ± 0.16 mmol/L (p<0.01) 15 days after administration in normal rats. Furthermore, blood glucose levels decreased from 17.84 ± 1.75mmol/L to 1.93 ± 0.33 mmol/L (p<0.0001) in STZ diabetic rats after fifteen days of treatment. According to the oral glucose tolerance test, C. telephiifolia (5 mg/kg) was shown to prevent significantly the increase in blood glucose levels in normal treated rats 30 min after glucose administration when compared to the control group. Also, the liver architecture of diabetic rats treated by C. telephiifolia was improved when compared with the liver architecture of untreated diabetic rats. Concerning the preliminary phytochemical screening of C. telephiifolia, several compounds have been found such as polyphenols, flavonoids, saponins, mucilage and terpenoids. Conclusion: The results show that the aqueous extract of C. telephiifolia possesses significant antihyperglycemic activity.


2021 ◽  
pp. 1-8
Author(s):  
Jae-Hun Lee ◽  
Sang Hee Ji ◽  
Jae Yun Jung ◽  
Min Young Lee ◽  
Chi-Kyou Lee

Introduction: Diabetes mellitus (DM) is a systemic disease characterized by hyperglycemia and several pathological changes. DM-related hearing dysfunctions are associated with histological changes. Here, we explore hearing function and synaptic changes in the inner hair cells (IHCs) of rats with streptozotocin (STZ)-induced diabetes. Methods: STZ was injected to trigger diabetes. Rats with DM were exposed to narrow-band noise (105 dB SPL) for 2 h, and hearing function was analyzed 1, 3, 7, and 14 days later. Both the hearing threshold and the peak 1 amplitude of the tone auditory brainstem response were assessed. After the last functional test, animals were sacrificed for histological evaluation. Results: We found no changes in the baseline hearing threshold; however, the peak 1 amplitude at the low frequency (4 kHz) was significantly higher in both DM groups than in the control groups. The hearing threshold had not fully recovered at 14 days after diabetic rats were exposed to noise. The peak 1 amplitude at the higher frequencies (16 and 32 kHz) was significantly larger in both DM groups than in the control groups. The histological analysis revealed that the long-term DM group had significantly more synapses in the 16 kHz region than the other groups. Conclusions: We found that high blood glucose levels increased peak 1 amplitudes without changing the hearing threshold. Diabetic rats were less resilient in threshold changes and were less vulnerable to peak 1 amplitude and synaptic damage than control animals.


1994 ◽  
Vol 267 (1) ◽  
pp. F190-F195 ◽  
Author(s):  
H. Tsukahara ◽  
Y. Krivenko ◽  
L. C. Moore ◽  
M. S. Goligorsky

It has been hypothesized that fluctuations of the ionic composition in the interstitium of juxtaglomerular apparatus (JGA) modulate the function of extraglomerular mesangial cells (MC), thereby participating in tubuloglomerular feedback (TGF) signal transmission. We examined the effects of isosmotic reductions in ambient sodium concentration ([Na+]) and [Cl-] on cytosolic calcium concentration ([Ca2+]i) in cultured rat MC. Rapid reduction of [Na+] or [Cl-] in the bath induced a concentration-dependent rise in [Ca2+]i. MC are much more sensitive to decreases in ambient [Cl-] than to [Na+]; a decrease in [Cl-] as small as 14 mM was sufficient to elicit a detectable [Ca2]i response. These observations suggest that MC can be readily stimulated by modest perturbations of extracellular [Cl-]. Next, we examined whether activation of MC by lowered ambient [Cl-] influences cellular nitric oxide (NO) production. Using an amperometric NO sensor, we found that a 13 mM decrease in ambient [Cl-] caused a rapid, Ca2+/calmodulin-dependent rise in NO release from MC. This response was not inhibitable by dexamethasone, indicating the involvement of the constitutive rather than the inducible type of NO synthase in MC. In addition, the NO release was blunted by indomethacin pretreatment, suggesting that a metabolite(s) of cyclooxygenase regulates the activation of NO synthase in MC. Our findings that small perturbations in external [Cl-] stimulate MC to release NO, a highly diffusible and rapidly acting vasodilator, provide a possible mechanism to explain the transmission of the signal for the TGF response within the JGA.


Author(s):  
Ganga Rajum ◽  
Hema Sundar Reddy T ◽  
Hema Sundar Reddy T

  Objective: The present study was aimed to evaluate antihyperglycemic and antihyperlipidemic activities of methanolic extract of Aristolochia bracteolata (MEAB) against dexamethasone-induced diabetic rat model.Methods: Methanolic extract was prepared by soxhlet extraction and was evaluated for antihyperglycemic and antihyperlipidemic activity using dexamethasone-induced model. The MEAB was administered orally at a dose of 200 and 400 mg/kg body weight glibenclamide was used as standard drug. On 0th and 11th day, blood was collected by retro-orbit plexus.Results: In this model blood glucose levels were determined on 0th and 11th days and MEAB significantly reduced the blood glucose levels in diabetic rats. The effect of MEAB on serum lipid profile such as total cholesterol (TC), triglycerides (TGs), low-density lipoprotein (LDL), very LDL (VLDL), and high-density lipoprotein (HDL) was also measured on the 11th day in the diabetic rats. Significant reduction in TC, TGs, LDL, and VLDL levels and improvement in HDL level were observed in diabetic rats.Conclusion: From the results, it was found that the MEAB possess antihyperglycemic and antihyperlipidemic activities.


Author(s):  
Biswaranjan Ray ◽  
Santosh Kumar Mahapatra ◽  
Pradipta Kumar Behera ◽  
Ashok K Panigrahi

Objective: As per the ethnopharmacological information has Butea monosperma been used to treat diabetes mellitus by the tribal people of tropical and subtropical areas. However, there is no much more scientific report available about the antidiabetic property of the leaves of the plant. Hence, the study was undertaken to evaluate the antidiabetic effect of ethanolic extract of B. monosperma on blood levels of adrenaline-induced and glucose feed diabetic rabbits.Methods: The three different doses of the extracts (100, 200, and 400 mg/kg) were administered orally to an experimental animal. The animals were induced diabetics by adrenaline and high glucose diet. Blood glucose level was measured accordingly. For antidiabetic activity, photocolorimeter was used to monitoring the blood glucose level with crest kit box (GOP-POD method).Results: The extracts showed considerable dose-dependent activity. However, the dose 400 mg/kg showed considerable lower of blood glucose level. p<0.01 indicates the significance result. 8 hrs reading 182.5±3.83 for 400 mg does is most effective for reducing blood sugar.Conclusion: The study indicates that the ethanolic extract of B. monosperma leaves possesses antidiabetic properties which suggest the presence of biologically active components.


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