Hypoglycemic Effect of Two Mexican Medicinal Plants

Type 2 diabetes is a worldwide prevalent disease that is due to a progressive loss of adequate β-cell insulin secretion, frequently against a background of insulin resistance. In Mexican traditional medicine, the therapeutic use of hypoglycemic plants to control the disease is a common practice among type 2 diabetic patients. In the present work, we examined the traditional use of the aerial parts of Eryngium longifolium and the rhizome of Alsophila firma, consumed by people use over the day (in fasting state) to control their blood glucose levels, therefore, we aimed to assess the acute hypoglycemic effect of both plants. First, basic phytochemical profiles of both plants were determined and, subsequently, acute toxicity tests were carried out. Then, in vivo hypoglycemic tests were performed in streptozotocin-nicotinamide (STZ-NA) induced hyperglycemic Wistar rats and finally the effect of the plants on three enzymes involved in glucose metabolism was assayed in vitro. Through HPLC-DAD chromatography, caffeic acid, chlorogenic acid, rosmarinic acid, isoflavones, and glycosylated flavonoids were identified in E. longifolium, while the possible presence of flavanones or dihydroflavonols was reported in A. firma. Both plants exhibited a statistically significant hypoglycemic effect, without a dose-dependent effect. Furthermore, they inhibited glucose 6-phosphatase and fructose 1,6-bisphosphatase in in vitro assays, which could be associated with the hypoglycemic effect in vivo. Thus, this study confirmed for the first time the traditional use of the aerial part of E. longifolium and the rhizome of A. firma as hypoglycemic agents in a hyperglycemic animal model. In addition, it was concluded that their ability to regulate hyperglycemia could involve the inhibition of hepatic glucose output, which mainly controls glucose levels in the fasting state.

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Hypoglycemic Effect of Calea urticifolia (Mill.) DC.

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/6625009 ◽

2021 ◽

Vol 2021 ◽

pp. 1-10

Author(s):

Adolfo Andrade-Cetto ◽

Fernanda Espinoza-Hernández ◽

Gerardo Mata-Torres

Keyword(s):

Plant Extract ◽

Tolerance Test ◽

Glucose Absorption ◽

Hypoglycemic Effect ◽

Network Pharmacology ◽

Traditional Use ◽

Hepatic Glucose ◽

Glucose Output

The onset of type 2 diabetes (T2D) is a consequence of the progressive loss of adequate β-cell insulin secretion, which frequently occurs under a background of insulin resistance. Currently, nearly 13 million Mexicans are living with diabetes. Moreover, due to poor socioeconomic conditions and the cultural idiosyncrasies of the Mexican population, the use of medicinal plants to treat T2D is a common practice in Mexico. In the Mexican state of Hidalgo, we found the traditional use of Calea urticifolia (CU) to treat this disease. To treat T2D, people drink an infusion made from the aerial part of the plant throughout the day. With the aim of investigating whether the infusion at a traditional dose produces a hypoglycemic effect in either the fasting or postprandial state, we measured the effect of the infusion in a hyperglycemic animal model (rats administered streptozotocin (STZ) and nicotinamide (NZ)) by conducting a glucose tolerance test and constructing a blood-glucose curve. We then analyzed whether the observed effect was related to the inhibition of glucose absorption in the gut or the inhibition of hepatic glucose output (HGO) in vivo and in vitro. Furthermore, we confirmed our findings by identifying the potential targets of the infusion via a network pharmacology analysis. Through high-performance liquid chromatography (HPLC) and thin layer chromatography (TLC), we detected a number of compounds in the extract and identified two of them. The plant extract produced a highly significant hypoglycemic effect under fasting conditions and a weak hypoglycemic effect following glucose or sucrose challenge. Although the plant extract blocked only 20% of the alpha-glucosidase enzyme activity in vitro, in the pyruvate tolerance test (which measures the liberation of hepatic glucose), it significantly reduced glucose levels. Furthermore, in vitro, the extract diminished the activity of the glucose-6-phosphatase complex by 90%. In addition, by conducting TLC, we detected the presence of chlorogenic acid and rutin, which have been reported to block HGO. The results presented here provide evidence of the hypoglycemic effect of the traditionally used C. urticifolia extract and demonstrate that this effect is associated with both a reduction in glucose synthesis via gluconeogenesis due to the phytochemical composition of the extract and a slight blockage of glucose absorption in the gut.

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Oral DhHP-6 for the Treatment of Type 2 Diabetes Mellitus

International Journal of Molecular Sciences ◽

10.3390/ijms20061517 ◽

2019 ◽

Vol 20 (6) ◽

pp. 1517 ◽

Cited By ~ 1

Author(s):

Kai Wang ◽

Yu Su ◽

Yuting Liang ◽

Yanhui Song ◽

Liping Wang

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Blood Glucose ◽

Enzymatic Activity ◽

Glucose Levels ◽

Blood Glucose Levels

Type 2 diabetes mellitus (T2DM) is associated with pancreatic β-cell dysfunction which can be induced by oxidative stress. Deuterohemin-βAla-His-Thr-Val-Glu-Lys (DhHP-6) is a microperoxidase mimetic that can scavenge reactive oxygen species (ROS) in vivo. In our previous studies, we demonstrated an increased stability of linear peptides upon their covalent attachment to porphyrins. In this study, we assessed the utility of DhHP-6 as an oral anti-diabetic drug in vitro and in vivo. DhHP-6 showed high resistance to proteolytic degradation in vitro and in vivo. The degraded DhHP-6 product in gastrointestinal (GI) fluid retained the enzymatic activity of DhHP-6, but displayed a higher permeability coefficient. DhHP-6 protected against the cell damage induced by H2O2 and promoted insulin secretion in INS-1 cells. In the T2DM model, DhHP-6 reduced blood glucose levels and facilitated the recovery of blood lipid disorders. DhHP-6 also mitigated both insulin resistance and glucose tolerance. Most importantly, DhHP-6 promoted the recovery of damaged pancreas islets. These findings suggest that DhHP-6 in physiological environments has high stability against enzymatic degradation and maintains enzymatic activity. As DhHP-6 lowered the fasting blood glucose levels of T2DM mice, it thus represents a promising candidate for oral administration and clinical therapy.

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Hypoglycemic Activity of Medicinal Plants Used among the Cakchiquels in Guatemala for the Treatment of Type 2 Diabetes

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/2168603 ◽

2019 ◽

Vol 2019 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Adolfo Andrade-Cetto ◽

Elda Carola Cruz ◽

Christian Alan Cabello-Hernández ◽

René Cárdenas-Vázquez

Keyword(s):

Type 2 Diabetes ◽

Hypoglycemic Effect ◽

Hypoglycemic Agents ◽

Limb Amputation ◽

Control Group ◽

High Blood Glucose ◽

Major Health Problem ◽

Control Drug

Type 2 diabetes (T2D) is a major health problem worldwide. In this condition, the organism can produce insulin but becomes resistant to it; thus the insulin is ineffective. High blood glucose levels are a result of insulin resistance and insulin deficiency; they produce diabetes-associated complications such as kidney failure, blindness, cardiovascular disease, and lower-limb amputation. In Guatemala, there were over 752.700 cases of the disease in 2017 with prevalence of 8.4 (IDF, 2017). The use of plants for medicinal purposes has been practiced in the country since pre-Hispanic times. Among the Cakchiquels, the aerial parts of Hamelia patens Jacq., Neurolaena lobata (L.) R.Br. ex Cass., and Solanum americanum Mill. and the cortex of Croton guatemalensis Lotsy are used to treat type 2 diabetes. The aim of the present study was to confirm the hypoglycemic effect of the plants under normal conditions and under maltose and sucrose tolerance tests, as well as to test the activity of the plant extracts in vitro against alpha-glucosidases types I and II. In agreement with the traditional usage of the plants, in normal conditions without a sugar load, the extracts produced a statistically significant hypoglycemic effect similar to the control drug glibenclamide. When the sugar load was maltose, only Croton and Solanum produced a statistically significant (p < 0.05) hypoglycemic effect compared to the control drug, but when the sugar was sucrose, Croton and Hamelia produced a statistically significant effect (p < 0.05) beginning at 30 min compared to the control group, while Solanum did so at 60 min and Neurolaena at 90 min. In vitro assays showed that the extracts inhibited yeast alpha-glucosidases but not the rat intestinal ones. Of the tested plants, Croton exert an effect both under sugars' tests and under a normal tolerance test; these results suggest the potential use of this plant. The results presented here provided evidence based on the use of these plants as hypoglycemic agents in the treatment of type 2 diabetes.

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Metallic Elements (Cu, Zn, Ni and Mn) Toxicity Effects Determination on a Fresh Water Fish Cyprinus Carpio (Common Carp) Laboratory Acclimatized

Revista de Chimie ◽

10.37358/rc.17.8.5750 ◽

2017 ◽

Vol 68 (8) ◽

pp. 1711-1715

Author(s):

Stefania Gheorghe ◽

Gabriela Geanina Vasile ◽

Cristina Gligor ◽

Irina Eugenia Lucaciu ◽

Mihai Nita Lazar

Keyword(s):

Cyprinus Carpio ◽

Aquatic Organisms ◽

Control Fish ◽

Toxicity Tests ◽

Fresh Water Fish ◽

Metallic Elements ◽

Mn Toxicity ◽

Vitro Effect

Metallic elements copper (Cu), zinc (Zn), nickel (Ni) and manganese (Mn) are some of the most commonly found in water and sediment samples collected from the Danube - Danube Delta. These elements are important as essential micronutrients, being normally present at low concentrations in biological organisms, but in high concentrations they become toxic with immediate and delayed effects. The role of this metals is still controversial, that�s why bioconcentration potential is so important. In this non-clinical study, we tested in vitro effect of heavy metals on carp, Cyprinus carpio, reproducing in vivo presence of Cu, Zn, Ni and Mn in the Romanian�s surface water. The toxicity tests were performed according to OECD 203 by detecting the average (50%) lethal concentration - LC50 on aquatic organisms (freshwater fish) at 96h. The results pointed out that, copper value for LC 50 at 96h was estimated as 3.4 mg/L (concentrations tested in the range of 0.1 - 4.75 mg/L). Zinc value for LC 50 at 96h was estimated as 20.8 mg/L (concentrations tested in the range of 0.028 � 29.6 mg/L). Nickel value for LC 50 at 96h was estimated as 40.1 mg/L (concentrations tested in the range of 0.008 - 84.5 mg/L). For manganese the mortality effects has recorded at LC 50 at 96h at estimated value higher than 53 mg/L (concentrations tested in the range of 0.04 - 53.9 mg/L). The accuracy of the testing metals concentration was insured by the screening of the dilution water, as well as food and control fish, acclimated in laboratory conditions.

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Ethnomedicinal uses, Phytochemistry and Pharmacological Aspects of the Genus Berberis Linn: A Comprehensive Review

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207323999201102141206 ◽

2020 ◽

Vol 23 ◽

Author(s):

Roohi Mohi-ud-din ◽

Reyaz Hassan Mir ◽

Prince Ahad Mir ◽

Saeema Farooq ◽

Syed Naiem Raza ◽

...

Keyword(s):

Chemical Constituents ◽

Pharmacological Activities ◽

Traditional Use ◽

Comprehensive Review ◽

Wide Range ◽

Anti Cancer ◽

Comprehensive Survey ◽

Ethnomedicinal Uses

Background: Genus Berberis (family Berberidaceae), which contains about 650 species and 17 genera worldwide, has been used in folklore and various traditional medicine systems. Berberis Linn. is the most established group among genera with around 450-500 species across the world. This comprehensive review will not only help researchers for further evaluation but also provide substantial information for future exploitation of species to develop novel herbal formulations. Objective: The present review is focussed to summarize and collect the updated review of information of Genus Berberis species reported to date regarding their ethnomedicinal information, chemical constituents, traditional/folklore use, and reported pharmacological activities on more than 40 species of Berberis. Conclusion: A comprehensive survey of the literature reveals that various species of the genus possess various phytoconstituents mainly alkaloids, flavonoid based compounds isolated from different parts of a plant with a wide range of pharmacological activities. So far, many pharmacological activities like anti-cancer, anti-hyperlipidemic, hepatoprotective, immunomodulatory, anti-inflammatory both in vitro & in vivo and clinical study of different extracts/isolated compounds of different species of Berberis have been reported, proving their importance as a medicinal plant and claiming their traditional use.

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Molecular and Cellular Mechanisms of Metformin in Cervical Cancer

Cancers ◽

10.3390/cancers13112545 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2545

Author(s):

Ya-Hui Chen ◽

Po-Hui Wang ◽

Pei-Ni Chen ◽

Shun-Fa Yang ◽

Yi-Hsuan Hsiao

Keyword(s):

Cervical Cancer ◽

Potential Role ◽

Treatment Options ◽

Cellular Mechanisms ◽

Anticancer Effects ◽

Clinical Benefits ◽

Underlying Mechanisms

Cervical cancer is one of the major gynecologic malignancies worldwide. Treatment options include chemotherapy, surgical resection, radiotherapy, or a combination of these treatments; however, relapse and recurrence may occur, and the outcome may not be favorable. Metformin is an established, safe, well-tolerated drug used in the treatment of type 2 diabetes; it can be safely combined with other antidiabetic agents. Diabetes, possibly associated with an increased site-specific cancer risk, may relate to the progression or initiation of specific types of cancer. The potential effects of metformin in terms of cancer prevention and therapy have been widely studied, and a number of studies have indicated its potential role in cancer treatment. The most frequently proposed mechanism underlying the diabetes–cancer association is insulin resistance, which leads to secondary hyperinsulinemia; furthermore, insulin may exert mitogenic effects through the insulin-like growth factor 1 (IGF-1) receptor, and hyperglycemia may worsen carcinogenesis through the induction of oxidative stress. Evidence has suggested clinical benefits of metformin in the treatment of gynecologic cancers. Combining current anticancer drugs with metformin may increase their efficacy and diminish adverse drug reactions. Accumulating evidence is indicating that metformin exerts anticancer effects alone or in combination with other agents in cervical cancer in vitro and in vivo. Metformin might thus serve as an adjunct therapeutic agent for cervical cancer. Here, we reviewed the potential anticancer effects of metformin against cervical cancer and discussed possible underlying mechanisms.

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Experimental Type 2 Diabetes Differently Impacts on the Select Functions of Bone Marrow-Derived Multipotent Stromal Cells

Cells ◽

10.3390/cells10020268 ◽

2021 ◽

Vol 10 (2) ◽

pp. 268

Author(s):

Jonathan Ribot ◽

Cyprien Denoeud ◽

Guilhem Frescaline ◽

Rebecca Landon ◽

Hervé Petite ◽

...

Keyword(s):

Type 2 Diabetes ◽

Bone Marrow ◽

Stromal Cells ◽

Adipogenic Differentiation ◽

Therapeutic Modality ◽

Multipotent Stromal Cells ◽

Cell Therapies

Bone marrow-derived multipotent stromal cells (BMMSCs) represent an attractive therapeutic modality for cell therapy in type 2 diabetes mellitus (T2DM)-associated complications. T2DM changes the bone marrow environment; however, its effects on BMMSC properties remain unclear. The present study aimed at investigating select functions and differentiation of BMMSCs harvested from the T2DM microenvironment as potential candidates for regenerative medicine. BMMSCs were obtained from Zucker diabetic fatty (ZDF; an obese-T2DM model) rats and their lean littermates (ZL; controls), and cultured under normoglycemic conditions. The BMMSCs derived from ZDF animals were fewer in number, with limited clonogenicity (by 2-fold), adhesion (by 2.9-fold), proliferation (by 50%), migration capability (by 25%), and increased apoptosis rate (by 2.5-fold) compared to their ZL counterparts. Compared to the cultured ZL-BMMSCs, the ZDF-BMMSCs exhibited (i) enhanced adipogenic differentiation (increased number of lipid droplets by 2-fold; upregulation of the Pparg, AdipoQ, and Fabp genes), possibly due to having been primed to undergo such differentiation in vivo prior to cell isolation, and (ii) different angiogenesis-related gene expression in vitro and decreased proangiogenic potential after transplantation in nude mice. These results provided evidence that the T2DM environment impairs BMMSC expansion and select functions pertinent to their efficacy when used in autologous cell therapies.

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3D Environment Is Required In Vitro to Demonstrate Altered Bone Metabolism Characteristic for Type 2 Diabetics

International Journal of Molecular Sciences ◽

10.3390/ijms22062925 ◽

2021 ◽

Vol 22 (6) ◽

pp. 2925

Author(s):

Victor Häussling ◽

Romina H Aspera-Werz ◽

Helen Rinderknecht ◽

Fabian Springer ◽

Christian Arnscheidt ◽

...

Keyword(s):

Bone Metabolism ◽

In Vitro Model ◽

Bone Diseases ◽

3D Environment ◽

Type 2 Diabetics ◽

Mineralized Matrix ◽

Vitro Model

A large British study, with almost 3000 patients, identified diabetes as main risk factor for delayed and nonunion fracture healing, the treatment of which causes large costs for the health system. In the past years, much progress has been made to treat common complications in diabetics. However, there is still a lack of advanced strategies to treat diabetic bone diseases. To develop such therapeutic strategies, mechanisms leading to massive bone alterations in diabetics have to be well understood. We herein describe an in vitro model displaying bone metabolism frequently observed in diabetics. The model is based on osteoblastic SaOS-2 cells, which in direct coculture, stimulate THP-1 cells to form osteoclasts. While in conventional 2D cocultures formation of mineralized matrix is decreased under pre-/diabetic conditions, formation of mineralized matrix is increased in 3D cocultures. Furthermore, we demonstrate a matrix stability of the 3D carrier that is decreased under pre-/diabetic conditions, resembling the in vivo situation in type 2 diabetics. In summary, our results show that a 3D environment is required in this in vitro model to mimic alterations in bone metabolism characteristic for pre-/diabetes. The ability to measure both osteoblast and osteoclast function, and their effect on mineralization and stability of the 3D carrier offers the possibility to use this model also for other purposes, e.g., drug screenings.

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Evidence for the Involvement of the Glc7-Reg1 Phosphatase and the Snf1-Snf4 Kinase in the Regulation of INO1 Transcription in Saccharomyces cerevisiae

Genetics ◽

10.1093/genetics/152.1.73 ◽

1999 ◽

Vol 152 (1) ◽

pp. 73-87 ◽

Cited By ~ 6

Author(s):

Margaret K Shirra ◽

Karen M Arndt

Keyword(s):

Rna Polymerase Ii ◽

Glucose Repression ◽

Snf1 Kinase ◽

Glucose Levels ◽

Recessive Mutations ◽

Mutant Strains ◽

Rna Polymerase Ii Transcription ◽

Two Hybrid

AbstractBinding of the TATA-binding protein (TBP) to the promoter is a pivotal step in RNA polymerase II transcription. To identify factors that regulate TBP, we selected for suppressors of a TBP mutant that exhibits promoter-specific defects in activated transcription in vivo and severely reduced affinity for TATA boxes in vitro. Dominant mutations in SNF4 and recessive mutations in REG1, OPI1, and RTF2 were isolated that specifically suppress the inositol auxotrophy of the TBP mutant strains. OPI1 encodes a repressor of INO1 transcription. REG1 and SNF4 encode regulators of the Glc7 phosphatase and Snf1 kinase, respectively, and have well-studied roles in glucose repression. In two-hybrid assays, one SNF4 mutation enhances the interaction between Snf4 and Snf1. Suppression of the TBP mutant by our reg1 and SNF4 mutations appears unrelated to glucose repression, since these mutations do not alleviate repression of SUC2, and glucose levels have little effect on INO1 transcription. Moreover, mutations in TUP1, SSN6, and GLC7, but not HXK2 and MIG1, can cause suppression. Our data suggest that association of TBP with the TATA box may be regulated, directly or indirectly, by a substrate of Snf1. Analysis of INO1 transcription in various mutant strains suggests that this substrate is distinct from Opi1.

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Antidiabetic Properties of Naringenin: A Citrus Fruit Polyphenol

Biomolecules ◽

10.3390/biom9030099 ◽

2019 ◽

Vol 9 (3) ◽

pp. 99 ◽

Cited By ~ 16

Author(s):

Danja J. Den Hartogh ◽

Evangelia Tsiani

Keyword(s):

Insulin Resistance ◽

Animal Studies ◽

Citrus Fruit ◽

Epidemiological Studies ◽

Personal Health ◽

Current Review ◽

Vegetables And Fruits

Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by insulin resistance and hyperglycemia and is associated with personal health and global economic burdens. Current strategies/approaches of insulin resistance and T2DM prevention and treatment are lacking in efficacy resulting in the need for new preventative and targeted therapies. In recent years, epidemiological studies have suggested that diets rich in vegetables and fruits are associated with health benefits including protection against insulin resistance and T2DM. Naringenin, a citrus flavanone, has been reported to have antioxidant, anti-inflammatory, hepatoprotective, nephroprotective, immunomodulatory and antidiabetic properties. The current review summarizes the existing in vitro and in vivo animal studies examining the anti-diabetic effects of naringenin.

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