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.

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

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.

3'-O-ß-d-glucopyranosyl-α,4,2',4',6'-pentahydroxy-dihydrochalcone, from Bark of Eysenhardtia polystachya 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-ß-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 < 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 < 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.

Protection of silver nanoparticles using Eysenhardtia polystachya in peroxide-induced pancreatic ß-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 ß 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 ß-cell survival, insulin secretion, enhanced hyperglycemia, and hyperlipidemia in glucose-induced diabetic zebrafish. EP/AgNPs also showed protection of the pancreatic ß-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.

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-ß-d-glucopyranoside (1), α,3,2',4'-tetrahydroxy-4-methoxy-dihydrochalcone-3'-C-ß-glucopyranosy-6'-O-ß-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-ß-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 (∙OH), nitric oxide radicals (NO∙), superoxide anion radical (O2∙-), radical cation (ABTS∙+), 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.