scholarly journals GlucoMedix ®, an Extract of Stevia Rebaudiana and Uncaria Tomentosa, Reduces Hyperglycemia, Hyperlipidemia, and Hypertension in Rat Models Without Toxicity: A Treatment For Metabolic Syndrome

2021 ◽  
Author(s):  
León F. Villegas Vílchez ◽  
Julio Hidalgo Ascencios ◽  
Thomas P. Dooley
Keyword(s):  
Metabolic Syndrome ◽  
Stevia Rebaudiana ◽  
Steviol Glycosides ◽  
Alcoholic Extract ◽  
Oral Toxicity ◽  
Uncaria Tomentosa ◽  
Rat Models ◽  
Dose Dependent ◽  
Oxindole Alkaloids

Abstract Background: The objective of this in vivo study is to evaluate in five rat models the pharmacologic effects and toxicity of a commercial hydro-alcoholic extract, GlucoMedix®, derived from Stevia rebaudiana and the pentacyclic chemotype of Uncaria Tomentosa (Willd.) DC, for use as a treatment for Metabolic Syndrome. The extract contains phytochemicals of Stevia (e.g., steviol glycosides) and Uncaria (e.g., pentacyclic oxindole alkaloids, but lacks tetracyclic oxindole alkaloids).Methods: The pharmacologic assessments in three rat models include reductions in chemically induced hyperglycemia, hyperlipidemia (cholesterol and triglycerides), and hypertension, all of which are comorbidities of Metabolic Syndrome. Acute toxicity and 28-day subacute toxicity were assessed in rat models at doses higher than those used in the efficacy models.Results: The acute oral toxicity was evaluated in Holtzman rats and the extract did not produce acute toxic effects or lethality, with the LD50 > 5000 mg/kg (extract wet weight). Furthermore, subacute oral toxicity was evaluated in rats for 28 days at daily doses as high as 2000 mg/kg without toxicity or abnormal clinical chemistry or hematological effects. Daily oral doses of 250 - 1000 mg/kg were used to evaluate the treatment effects in hyperglycemic (alloxan-induced and glibenclamide-controlled), hyperlipidemic (cholesterol-induced and atorvastatin-controlled), and hypertensive (L-NAME-induced and enalapril-controlled) rat models. Alloxan-induced hyperglycemia was reduced in a dose-dependent manner within 28 days or less. Cholesterol-induced hyperlipidemic rats exhibited dose-dependent reductions in cholesterol and triglycerides at 21 days. Furthermore, GlucoMedix® produced a dose-dependent decrease in systolic and diastolic arterial blood pressure in L-NAME-induced hypertensive rats at 28 days.Conclusions: The five in vivo rat models revealed that the all-natural phytotherapy GlucoMedix® is a safe and effective treatment for hyperglycemia, hyperlipidemia, and hypertension. This extract is expected to affect multiple comorbidities of Metabolic Syndrome, without any acute or subacute oral toxicity in humans. Although multiple prescription drugs are well known for the treatment of individual comorbidities of Metabolic Syndrome, no drug monotherapy concurrently treats all three comorbidities.

VCAM-1 has a tissue-specific role in mediating interleukin-4–induced eosinophil accumulation in rat models: evidence for a dissociation between endothelial-cell VCAM-1 expression and a functional role in eosinophil migration

Blood ◽  
2000 ◽  
Vol 96 (10) ◽  
pp. 3601-3609 ◽  
Author(s):  
Karen Y. Larbi ◽  
Andrew R. Allen ◽  
Frederick W. K. Tam ◽  
Dorian O. Haskard ◽  
Roy R. Lobb ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Functional Role ◽  
Interleukin 4 ◽  
Tissue Specific ◽  
Rat Models ◽  
Eosinophil Migration ◽  
Cell Adhesion Molecule 1 ◽  
Dose Dependent ◽  
Eosinophil Accumulation

Abstract Eosinophil accumulation has been associated with the pathogenesis of numerous allergic inflammatory disorders. Despite the great interest in this response, many aspects of eosinophil accumulation remain unknown. This is particularly true with respect to tissue-specific mechanisms that may regulate the accumulation of eosinophils in different organs. This study addressed this issue by investigating and comparing the roles of α4-integrins and vascular cell adhesion molecule 1 (VCAM-1) adhesion pathways in interleukin 4 (IL-4)–induced eosinophil accumulation in 2 different rat models of inflammation, namely pleural and cutaneous inflammation. Similar to our previous findings in studies in rat skin, locally administered IL-4 induced a time- and dose-dependent accumulation of eosinophils in rat pleural cavities, a response that was associated with generation of the chemokine eotaxin. The IL-4–induced eosinophil accumulation in skin and pleural cavities was totally inhibited by an antirat α4-integrins monoclonal antibody (mAb) (TA-2). In contrast, whereas an antirat VCAM-1 mAb (5F10) totally blocked the response in skin, IL-4–induced eosinophil accumulation in rat pleural cavities was not affected by VCAM-1 blockade. A radiolabeled mAb technique demonstrated that endothelial-cell VCAM-1 expression was induced in response to IL-4 in both skin and pleural membrane. The results indicate that although endothelial-cell VCAM-1 is present in skin and pleura, a functional role for it in IL-4–induced eosinophil accumulation was evident only in skin. These findings suggest the existence of tissue-specific adhesive mechanisms in regulating leukocyte migration in vivo and demonstrate a dissociation between VCAM-1 expression and eosinophil accumulation.

scholarly journals Safety Evaluation of Bifidobacterium lactis BL-99 and Lacticaseibacillus paracasei K56 and ET-22 in vitro and in vivo

2021 ◽  
Vol 12 ◽  
Author(s):  
Hongyun Lu ◽  
Wen Zhao ◽  
Wei-Hsien Liu ◽  
Ting Sun ◽  
Hanghang Lou ◽  
...  
Keyword(s):  
Safety Evaluation ◽  
Toxicity Tests ◽  
Human Consumption ◽  
Oral Toxicity ◽  
Bifidobacterium Lactis ◽  
Consumer Concerns ◽  
Healthy Diets ◽  
Dose Dependent

Probiotics have been reported to play a major role in maintaining the balance of microbiota in host. Consumption of food with probiotics has increased with consumer concerns regarding healthy diets and wellness. Correspondingly, safety evaluation of probiotics for human consumption has become increasingly important in food industry. Herein, we aimed to test the safety of Bifidobacterium lactis BL-99 and Lacticaseibacillus paracasei K56 and ET-22 strains in vitro and in vivo. In results, these strains were found to be negative for mucin degradation and platelet aggregation test. Additionally, the three strains were susceptible to eight antibiotics. In accordance with bacterial reversion mutation (Ames) assay, the tested strains had no genetic mutagenicity. Finally, it was confirmed that there were no dose-dependent mortality and toxicity throughout multidose oral toxicity tests in rats. Our findings demonstrated that B. lactis BL-99 and L. paracasei K56 and ET-22 can achieve the generally recognized as safe (GRAS) status as probiotics in the future.

scholarly journals CHEMICAL ANALYSIS, ANTIOXIDANT, ANTI-INFLAMMATORY AND ANTINOCICEPTIVE EFFECTS OF ACETONE EXTRACT OF ALGERIAN SOLENOSTEMMA ARGEL (DELILE) HAYNE LEAVES

2020 ◽  
pp. 72-81
Author(s):  
DAOUIA KELTOUM BENMAAROUF ◽  
DIANA C. G. A. PINTO ◽  
BERNARD CHINA ◽  
SAFIA ZENIA ◽  
KHEIRA BOUZID BENDESARI ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Granuloma Formation ◽  
Paw Edema ◽  
Oral Toxicity ◽  
Traditional Use ◽  
Anti Inflammatory ◽  
Dose Dependent

Objective: To investigate the qualitative composition of the acetonic extract from leaves of S. argel (AESA) and their anti-inflammatory and analgesic properties in vivo. Methods: AESA profile was established by UHPLC/DAD/ESI-MS2. AESA was subjected to the acute oral toxicity study according to the OECD-420 method. Antioxydant activity of AESA was performed by DPPH radical scavenging assay. Anti-inflammatory effects of AESA were determined in two animal models: carrageenan-induced paw edema in rats and cotton pellet-induced granuloma formation in rats. Further, anti-nociceptives activities of AESA were assessed by hot plate test, acetic acid-induced abdominal writhing test and formalin test. Results: The in vivo AESA toxicity was low. AESA expresses a maximum radical scavenging activity with a IC50 value of 36,05 μg/ml. The AESA at 250 and 400 mg/kg significantly reduced carrageen an induced paw edema by 70.09% and 85.53% 6h after carrageenan injection, respectively. AESA produced significant dose-dependent anti-inflammatory effect against cotton pellets-induced granuloma formation in rats. In addition, AESA at 250 and 400 mg/kg significantly reduced acetic acid-induced writhing by 56.83 and 80.41%, respectively. Oral administration of 250 and 400 mg/kg of AESA caused a significant dose dependent anti-nociceptive effect in both neurogenic and inflammatory phases of formalin-induced licking. AESA also impacted the pain latency in the hot plat test. Conclusion: These data suggest that AESA possesses antioxidant, anti-inflammatory and anti-nociceptive effects. These results support the traditional use of S. argel to cure pain and inflammatory diseases in the Algerian Sahara.

scholarly journals Phytopharmacological Evaluation of Alcoholic Extract of Berberis aristata Leaf in the Treatment of Gastric Ulcer

2020 ◽  
Vol 13 (1) ◽  
pp. 1-5
Author(s):  
Ratnaker Singh ◽  
Y. Trilochana
Keyword(s):  
Acute Toxicity ◽  
Crude Extract ◽  
Antioxidant Activities ◽  
Ethanolic Extract ◽  
Total Phenolic ◽  
Antiulcer Activity ◽  
Alcoholic Extract ◽  
Dose Dependent

For over a century, peptic ulcer has been one of the most common gastrointestinal tract (GIT) disorder. There are number of drugs are now available for treatment. Drugs of herbal origin reduce the offensive factors and have proved to be safe, clinically effective, relatively less expensive, globally competitive, and with better patient tolerance.This study was performed to assess the anti-ulcer activity on different parts of B.aristata. Apart from that, acute toxicity, qualitative chemical analysis, total phenolic content (TPC), total flavonoid content(TFC) and in vitro antioxidant activities were evaluated. The potentially active plant part was selected for screening as gastro protective, in vivo antioxidant and antisecretory activities in ulcerated rats.The 50% ethanolic extract of B. aristata were subjected to preliminary phytochemical screening, estimation of TFC and TPC. The crude extract from the leaves of B. aristata gave best antiulcer activity among flower and stem. In acute toxicity studies, the administration of the crude extract of B. aristata leaves did not reveal any adverse effects or toxicity in rats at fourteen days observations.The results of these studies have shown that ethylexract of B.aristata leaf (EEBAL) produced a significant dose dependent ulcerprotective, antioxidant and antisecretory activity by blocking the activity of proton pump, protecting from antioxidants produced during stress induced ulcer and by enhancing glycoprotein levels.

Evaluation of Anti-hyperuricemic Activity of the Alcoholic Extract of Dried Capparis moonii Wight Fruits in Wistar Rats

2021 ◽  
pp. 3173-3178
Author(s):  
Shruti Ramesh Shettigar ◽  
Vanita G. Kanase
Keyword(s):  
Wistar Rats ◽  
The Body ◽  
Alcoholic Extract ◽  
Phenol Red ◽  
Acute Oral Toxicity ◽  
Oral Toxicity ◽  
Dried Fruits ◽  
Treatment Agent ◽  
Dose Dependent ◽  
Potassium Oxonate

Evaluation of anti-hyperuricemic activity of alcoholic extract of Capparis moonii Wight fruits in Wistar rats, by utilizing Indian caper typically occurring in the Konkan area which grows full-fledged in the hot and dry atmosphere that can be generally found throughout asia. The dried fruits of Capparis moonii W. were extracted using absolute ethanol to get an alcoholic extract. Acute oral toxicity studies were performed to decide the doses. The anti-hyperuricemic activity was estimated by the phenol red excretion in rats and the potassium oxonate induced hyperuricemia models respectively. The alcoholic extract showed dose-dependent mode of action where the higher concentration of 200 mg/kg showed higher amount of retention of phenol red in the blood suggesting that it has better ability to secrete urate out of the body of rats as compared to 100mg/kg. Also in potassium oxonate induced hyperuricemia, similar results were obtained with significant reduction in serum uric acid levels and serum creatinine levels as compared to 100mg/kg. The conclusion of this study was that; it proved that Capparis moonii W. alcoholic extract of the fruits can be beneficial as anti-hyperuricemic treatment agent. It would be encouraging to undertake further studies in future to decode the exact mechanism.

scholarly journals Steviol Glycosides Modulate Glucose Transport in Different Cell Types

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Benedetta Rizzo ◽  
Laura Zambonin ◽  
Cristina Angeloni ◽  
Emanuela Leoncini ◽  
Francesco Vieceli Dalla Sega ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Glucose Transport ◽  
Molecular Mechanisms ◽  
Neuroblastoma Cells ◽  
Stevia Rebaudiana ◽  
Cell Types ◽  
Akt Pathway ◽  
Steviol Glycosides ◽  
Human Neuroblastoma

Extracts fromStevia rebaudianaBertoni, a plant native to Central and South America, have been used as a sweetener since ancient times. Currently,Steviaextracts are largely used as a noncaloric high-potency biosweetener alternative to sugar, due to the growing incidence of type 2 diabetes mellitus, obesity, and metabolic disorders worldwide. Despite the large number of studies onSteviaand steviol glycosidesin vivo, little is reported concerning the cellular and molecular mechanisms underpinning the beneficial effects on human health. The effect of four commercialSteviaextracts on glucose transport activity was evaluated in HL-60 human leukaemia and in SH-SY5Y human neuroblastoma cells. The extracts were able to enhance glucose uptake in both cellular lines, as efficiently as insulin. Our data suggest that steviol glycosides could act by modulating GLUT translocation through the PI3K/Akt pathway since treatments with both insulin andSteviaextracts increased the phosphorylation of PI3K and Akt. Furthermore,Steviaextracts were able to revert the effect of the reduction of glucose uptake caused by methylglyoxal, an inhibitor of the insulin receptor/PI3K/Akt pathway. These results corroborate the hypothesis thatSteviaextracts could mimic insulin effects modulating PI3K/Akt pathway.

scholarly journals In VitroandIn VivoAntileishmanial Effects ofPistacia khinjuk against Leishmania tropicaandLeishmania major

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Behrouz Ezatpour ◽  
Ebrahim Saedi Dezaki ◽  
Hossein Mahmoudvand ◽  
Mojgan Azadpour ◽  
Fatemeh Ezzatkhah
Keyword(s):  
Leishmania Major ◽  
Alcoholic Extract ◽  
Leishmania Tropica ◽  
Reference Drug ◽  
Pistacia Khinjuk ◽  
Antileishmanial Activities ◽  
Dose Dependent ◽  
Intracellular Amastigote

The present study aims to evaluate thein vitroandin vivoantileishmanial activities ofPistacia khinjukStocks (Anacardiaceae) alcoholic extract and to compare its efficacy with a reference drug, meglumine antimoniate (MA, Glucantime), againstLeishmania tropicaandLeishmania major. This extract (0–100 µg/mL) was evaluatedin vitroagainst promastigote and intracellular amastigote forms ofL. tropica(MRHO/IR/75/ER) and then tested on cutaneous leishmaniasis (CL) in male BALB/c mice withL. majorto reproduce the antileishmanial activity topically.In vitro,P. khinjukextract significantly (P<0.05) inhibited the growth rate of promastigote (IC50 58.6±3.2 µg/mL) and intramacrophage amastigotes (37.3±2.5 µg/mL) ofL. tropicaas a dose-dependent response. In thein vivoassay, after 30 days of treatment, 75% recovery was observed in the infected mice treated with 30% extract. After treatment of the subgroups with the concentration of 20 and 30% ofP. khinjukextract, mean diameter of lesions was significantly (P<0.05) reduced. To conclude, the present investigation demonstrated thatP. veraextract hadin vitroandin vivoeffectiveness againstL. major. Obtained findings also provide the scientific evidences that natural plants could be used in the traditional medicine for the prevention and treatment of CL.

VCAM-1 has a tissue-specific role in mediating interleukin-4–induced eosinophil accumulation in rat models: evidence for a dissociation between endothelial-cell VCAM-1 expression and a functional role in eosinophil migration

Blood ◽  
2000 ◽  
Vol 96 (10) ◽  
pp. 3601-3609 ◽  
Author(s):  
Karen Y. Larbi ◽  
Andrew R. Allen ◽  
Frederick W. K. Tam ◽  
Dorian O. Haskard ◽  
Roy R. Lobb ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Functional Role ◽  
Interleukin 4 ◽  
Tissue Specific ◽  
Rat Models ◽  
Eosinophil Migration ◽  
Cell Adhesion Molecule 1 ◽  
Dose Dependent ◽  
Eosinophil Accumulation

Eosinophil accumulation has been associated with the pathogenesis of numerous allergic inflammatory disorders. Despite the great interest in this response, many aspects of eosinophil accumulation remain unknown. This is particularly true with respect to tissue-specific mechanisms that may regulate the accumulation of eosinophils in different organs. This study addressed this issue by investigating and comparing the roles of α4-integrins and vascular cell adhesion molecule 1 (VCAM-1) adhesion pathways in interleukin 4 (IL-4)–induced eosinophil accumulation in 2 different rat models of inflammation, namely pleural and cutaneous inflammation. Similar to our previous findings in studies in rat skin, locally administered IL-4 induced a time- and dose-dependent accumulation of eosinophils in rat pleural cavities, a response that was associated with generation of the chemokine eotaxin. The IL-4–induced eosinophil accumulation in skin and pleural cavities was totally inhibited by an antirat α4-integrins monoclonal antibody (mAb) (TA-2). In contrast, whereas an antirat VCAM-1 mAb (5F10) totally blocked the response in skin, IL-4–induced eosinophil accumulation in rat pleural cavities was not affected by VCAM-1 blockade. A radiolabeled mAb technique demonstrated that endothelial-cell VCAM-1 expression was induced in response to IL-4 in both skin and pleural membrane. The results indicate that although endothelial-cell VCAM-1 is present in skin and pleura, a functional role for it in IL-4–induced eosinophil accumulation was evident only in skin. These findings suggest the existence of tissue-specific adhesive mechanisms in regulating leukocyte migration in vivo and demonstrate a dissociation between VCAM-1 expression and eosinophil accumulation.

CD40L induces inflammation and adipogenesis in adipose cells – a potential link between metabolic and cardiovascular disease

2010 ◽  
Vol 103 (04) ◽  
pp. 788-796 ◽  
Author(s):  
Isabel Platzer ◽  
Sandra Ernst ◽  
Carina Walter ◽  
Philipp Rudolf ◽  
Katja Zirlik ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Metabolic Functions ◽  
The Metabolic Syndrome ◽  
Mitogen Activated Protein ◽  
Potential Link ◽  
Functional Relevance ◽  
Dose Dependent ◽  
Adipose Cells

SummaryCD40L figures prominently in atherogenesis. Recent data demonstrate elevated levels of sCD40L in the serum of patients with the metabolic syndrome (MS). This study investigated the role of CD40L in pro-inflammatory gene expression and cellular differentiation in adipose tissue to obtain insight into mechanisms linking the MS with atherosclerosis. Human adipocytes and preadipocytes expressed CD40 but not CD40L. Stimulation with recombinant CD40L or membranes over-expressing CD40L induced a time- and dose-dependent expression of IL-6, MCP-1, IL-8, and PAI-1. Supernatants of CD40L-stimulated adipose cells activated endothelial cells, suggesting a systemic functional relevance of our findings. Neutralising antibodies against CD40L attenuated these effects substantially. Signalling studies revealed the involvement of mitogen-activated protein kinases and NFκB. Furthermore, stimulation with CD40L resulted in enhanced activation of C/EBPα and PPARγ and promoted adipogenesis of preadipose cells in the presence and absence of standard adipogenic conditions. Finally, patients suffering from the metabolic syndrome with high levels of sCD40L also displayed high levels of IL-6, in line with the concept that CD40L may induce the expression of inflammatory cytokines in vivo in this population. Our data reveal potent metabolic functions of CD40L aside from its known pivotal pro-inflammatory role within plaques. Our data suggest that CD40L may mediate risk at the interface of metabolic and atherothrombotic disease.

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