Properties of flavonoids isolated from the bark of eysenhardtia polystachya and their effect on oxidative stress in streptozotocin-induced diabetes mellitus in mice

"Six new flavonoids 2′,4′-dihydroxychalcone-6′-O-β-D-glucopyranoside (1), α,3,2′,4′-tetrahydroxy-4-methoxy-dihydrochalcone-3′-C-β-glucopyranosy-6′-O-β-D-glucopyranoside (2), 7-hydroxy-5,8′-dimethoxy-6′α-L-rhamnopyranosyl-8-(3-phenyl-trans-acryloyl)-1-benzopyran-2-one (3), 6′7-dihydroxy-5,8-dimethoxy-8(3-phenyl-trans-acryloyl)-1-benzopyran-2-one (4), 9-hydroxy-3,8-dimethoxy-4-prenylpterocarpan (5), and α,4,4′-trihydroxydihydrochalcone-2′-O-β-D-glucopyranoside (6) were isolated from bark of Eysenhardtia polystachya.Antidiabetic activity of compounds 1–5 in terms of their cellular antioxidant and free radical scavenging and also in streptozotocin- (STZ-) induced diabetic mice was evaluated on liver transaminases, lipid peroxidation, total bilirubin, total protein, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (CSH-Px), and glutathione reductase (GSH). Results indicated that 1–5 scavenged 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl (), nitric oxide radicals (), superoxide anion radical (), radical cation (), and hydrogen peroxide (H2O2) radical, and protection against H2O2 induced BSA damage was also observed. Furthermore, 1–5 showed ability to decrease the oxidative stress in H9c2 cell. Diabetic mice present high levels of lipid peroxide, total protein, SGPT, SGOT, ALP, and TB. However, treatment of STZ-induced diabetes in mice with 1–5 reduced levels of these enzymes leading to protector effect of liver. In addition, with treatment with 1–5, increases in radical scavenging enzymes of CSH-Px, SOD, GSH, and CAT have also been observed in diabetic mice. The antioxidant properties of compounds 1–5 are a promising strategy for ameliorating therapeutic effects by avoiding disorders in the normal redox reactions in healthy cells which consequently could alleviate complications of diabetes.

Protection of silver nanoparticles using Eysenhardtia polystachya in peroxide-induced pancreatic beta-Cell damage and their antidiabetic properties in zebrafish

"Background: The aim was to explore the efficacy of extract of Eysenhardtia polystachya-loaded silver nanoparticles (EP/AgNPs) on pancreatic β cells, INS-1 cells, and zebrafish as a valuable model for the study of diabetes mellitus. Materials and methods: EP/AgNPs were synthesized using methanol/water bark extract of E. polystachya and characterized using various physicochemical techniques. Results: Immersion of adult zebrafish in 111 mM glucose solution resulted in a sustained hyperglycemic, hyperlipidemic state, and serum insulin levels decreased. The synthesized EP/AgNPs showed an absorption peak at 413 nm on ultraviolet–visible spectroscopy, revealing the surface plasmon resonance of the nanoparticles. Transmission electron microscopy indicated that most of the particles were spherical, with a diameter of 10–12 nm, a polydispersity index of 0.197, and a zeta potential of -32.25 mV, suggesting high stability of the nanoparticles. EP/AgNPs promote pancreatic β-cell survival, insulin secretion, enhanced hyperglycemia, and hyperlipidemia in glucose-induced diabetic zebrafish. EP/AgNPs also showed protection of the pancreatic β-cell line INS-1 against hydrogen peroxide-induced oxidative injury. Conclusion: The results indicate that EP/AgNPs have good antidiabetic activity and therefore could be used to prevent the development of diabetes.

In vitro inhibitory activity of Acca sellowiana fruit extract on end products of advanced glycation

"Introduction Hyperglycemia plays an important role in the pathogenesis of diabetic complications, as it increases protein glycation, as well as the progressive accumulation of advanced glycation end products (AGEs), which are complex structures that produce fluorescence. The glycation reaction raises the levels of protein carbonyl, N ?-(carboxymethyl)lysine (CML), and fructosamine and decreases the level of thiol groups. Methods In the present study, the antiglycation activity was determined by fluorescence intensity using the bovine serum albumin (BSA)/glucose, CML method, and the level of fructosamine. The oxidation of proteins was determined by the carbonyl protein content and thiol groups. Results The results show that the hexane extract of Acca sellowiana (FOH) at different concentrations (0.30-5 mg/ml) significantly inhibited the formation of AGEs in the BSA/glucose model during the 4 weeks of the study. FOH reduced the levels of fructosamine and CML. Our results showed a significant effect of FOH in the prevention of oxidative damage of proteins, as well as an effect on the oxidation of thiol groups and carbonyl proteins. Conclusion The present study indicates that FOH is effective in inhibiting the glycation of proteins in vitro, so it can prevent or ameliorate the chronic conditions of diabetes associated with the formation of AGEs.

Evaluation of the Antidiabetic and Antihyperlipidemic Activity of Spondias purpurea Seeds in a Diabetic Zebrafish Model

Diabetes mellitus (DM) is a serious chronic degenerative disease characterized by high levels of glucose in the blood. It is associated with an absolute or relative deficiency in the production and/or action of insulin. Some of the complications associated with DM are heart disease, retinopathy, kidney disease, and neuropathy; therefore, new natural alternatives are being sought to control the disease. In this work, we evaluate the antidiabetic effect of Spondias purpurea seed methanol extract (CSM) in vitro and in a glucose-induced diabetic zebrafish model. CSM is capable of lowering blood glucose and cholesterol levels, as well as forming advanced glycation end-products, while not presenting toxic effects at the concentrations evaluated. These data show that CSM has a promising antidiabetic effect and may be useful in reducing some of the pathologies associated with diabetes mellitus

Phytochemical and Pharmacological Study of the Eysenhardtia Genus

The participation of natural products in health care has been remarkable, and today they continue to play a key role in the discovery and development of new treatments. Phytochemical studies together with pharmacological tests have managed to integrate bioactive agents as an alternative solution to reduce or regulate the problems caused by diseases. The Eysenhardtia genus is a family of plants that are rich in secondary metabolites, which have shown potential activity in the control and mitigation of urinary disorders, diabetes, oxidative stress, protein glycosylation, microbial infections, inflammation, pain or discomfort, muscle contractions, cytotoxicity, or as a cellular or neuronal signaling modulator. These conditions generally appear in comorbid diseases, which motivated the bibliographic review associated with the plant. This document presents the beneficial actions produced by Eysenhardtia extracts and/or bioactives to inhibit, control, or reduce the complications or discomfort of degenerative diseases and thus generate new therapeutic alternatives

Antidiabetic Activity of Aloe vera Leaves

This research evaluated the potential of using the methanol extract of Aloe vera (L.) Burm.f (AVM) to prevent the formation of AGEs by means of the BSA/glucose assay, BSA-methylglyoxal assay, arginine-methylglyoxal assay, fructosamine, Nɛ-(carboxymethyl) lysine (CML), thiol groups, and carbonyl protein in vitro. The effect of AVM was also evaluated with regard to inhibiting the enzymes α-amylase, α-glucosidase, and pancreatic lipase. For this, the plant was dried, ground, and subsequently macerated with methanol. Aloe vera methanol extract (AVM) significantly decreased the formation of AGEs, as well as the formation of fructosamine, CML, and carbonyl protein. The concentration of 5 mg/ml of AVM presented the best results. AVM significantly inhibited the α-amylase and α-glucosidase enzymes. As regards the content of thiol groups, a significant increase was observed during the four weeks of the experiment. So, we can conclude that Aloe vera methanol extract decreases the formation of AGEs and may inhibit the increase in postprandial glucose, suggesting that AVM can prevent diabetes complications associated with AGE

Antioxidant activity and in vitro antiglycation of the fruit of Spondias purpurea

"Hyperglycemia in diabetes mellitus causes irreversible life-threatening micro- and macrovascular complications. There is evidence that the glycation reaction leads to a chemical modification of the proteins contributing to the complications of diabetes. It is known that advanced glycation end products (AGEs) are formed by glycation and oxidation reactions called glycoxidation. CML, a nonfluorescent AGE, has become a biomarker of glycoxidative damage; other AGEs appear to induce oxidative stress, which results in cytotoxicity. To determine antioxidant activity, the FRAP, DPPH, and TEAC tests were used, as well as the polyphenols content using Folin-Ciocalteu’s method. To evaluate the antiglycation activity, the BSA/glucose system was used, and the fructosamine concentration, protein carbonyl content, thiol, and CML groups were determined. The results obtained show that the hexane extract of the fruit of Spondias purpurea (CFH) effectively inhibits the glycation reaction, in addition to increasing the thiol groups and decreasing levels of fructosamine, protein carbonyl, and CML. In addition, CFH presented significant antioxidant activity. CFH inhibits the glycation reaction; therefore, it can help prevent complications related to AGEs in diabetes mellitus; it also reduces oxidative stress and is effective in protecting proteins from oxidative damage.

Evaluation of the Antidiabetic Potential of Extracts of Urtica dioica, Apium graveolens, and Zingiber officinale in Mice, Zebrafish, and Pancreatic β-Cell

Medicinal plants are commonly used in the treatment of diabetes, particularly as they contain flavonoids and phenolic compounds. The present study aims to investigate the activities of a polyherbal formulation made from Urtica dioica, Apium graveolens, and Zingiber officinale (UAZ) against streptozotocin–nicotinamide ((STZ-NA)-induced type 2 diabetes in CD1 mice, glucose-induced type 2 diabetes (T2DM) in zebrafish, and high glucose-induced damage in RINm5F pancreatic β-cells. In fasting mice, plasma glucose, glycosylated hemoglobin (HbA1C), lipid hydroperoxides (LOOH), thiobarbituric acid reactive substances (TBARS), and lipid profiles were significantly increased, whereas insulin, enzymatic antioxidants, and carbohydrate metabolic enzymes were altered significantly in diabetic mice. Zebrafish had similar glucose levels, liver enzymes, and lipid profiles compared to mice. The study investigated the effects of the extract in enhancing cell viability, insulin secretion, and reducing lipid peroxidation and intracellular reactive oxygen species (ROS) levels in RINm5F cells damaged by high glucose. All the above biochemical parameters were enhanced in both mice and zebrafish treated; the combined extract UAZ normalized all the biochemical parameters. The medicinal plant extracts, used either separately or in combination, ameliorated the adverse effect of glucose on cell viability and functionality of beta-RINm5F cells

3′-<em>O</em>-β-<span style="font-variant: small-caps;">d</span>-glucopyranosyl-α,4,2′,4′,6′-pentahydroxy-dihydrochalcone, from Bark of <em>Eysenhardtia polystachya</em> Prevents Diabetic Nephropathy via Inhibiting Protein Glycation in STZ-Nicotinamide Induced Diabetic Mice

Previous studies have shown that accumulation of advanced glycation end products (AGEs) can be the cause of diabetic nephropathy (DN) in diabetic patients. Dihydrochalcone 3′-O-β-d-glucopyranosyl α,4,2′,4′,6′-pentahydroxy–dihydrochalcone (1) is a powerful antiglycation compound previously isolated from Eysenhardtia polystachya. The aim was to investigate whether (1) was able to protect against diabetic nephropathy in streptozotocin (STZ)-induced diabetic mice, which displayed renal dysfunction markers such as body weight, creatinine, uric acid, serum urea, total urinary protein, and urea nitrogen in the blood (BUN). In addition, pathological changes were evaluated including glycated hemoglobin (HbA1c), advanced glycation end products (AGEs) in the kidney, as well as in circulation level and pro-inflammatory markers ICAM-1 levels in diabetic mice. After 5 weeks, these elevated markers of dihydrochalcone treatment (25, 50 and 100 mg/kg) were significantly (p &lt; 0.05) attenuated. In addition, they ameliorate the indices of renal inflammation as indicated by ICAM-1 markers. The kidney and circulatory AGEs levels in diabetic mice were significantly (p &lt; 0.05) attenuated by (1) treatment. Histological analysis of kidney tissues showed an important recovery in its structure compared with the diabetic group. It was found that the compound (1) attenuated the renal damage in diabetic mice by inhibiting AGEs formation