acteoside and Diabetes-Mellitus

Diabetic nephropathy (DN) was a major cause of end-stage renal failure and a common microvascular complication in patients with diabetes mellitus (DM). Acteoside (ACT) was the main ingredient extracted from the leaves of Rehmannia glutinosa, which had the functions of entering the lung, moisturizing the skin and relieving itching, nourishing yin and tonifying the kidney, cooling blood, and stopping bleeding. ACT had attracted worldwide interest because of its therapeutic effects on DM and its complications.. To clarify the metabolic profiles and targets of ACT in db/db mice based on metabolomics and network pharmacology studies.. Db/db mice were used to observe the biochemical indices and histopathological changes in the kidney to evaluate the pharmacological effects of ACT on DN. Untargeted metabolomics studies were performed to investigate by UHPLC-LTQ-Orbitrap MS on urine, serum, and kidney samples. The key targets and pathways were analyzed by network pharmacology. For the pathways enriched by untargeted metabolomics, targeted metabolomics by UHPLC-QQQ-MS/MS was performed in kidney samples for validation. Sensitive biomarkers in kidney samples were evaluated. The effect of ACT on the improvement of DN from the perspective of metabolism of small molecules in vivo was described.. ACT could delay the progression of DN and improve the degree of histopathological damage to the kidney. The pathways were focused on amino acid metabolism by untargeted metabolomics. Through network pharmacology analysis, the effect pathways were related to signal transduction, carbohydrate, lipid, amino acid metabolism and mainly affected the endocrine and immune systems. Amino acid metabolism was disturbed in the kidney of db/db mice, which could be callback by ACT, such as tryptophan, glutamine, cysteine, leucine, threonine, proline, phenylalanine, histidine, serine, arginine, asparagine by targeted metabolomics.. In conclusion, this study provided strong support for ACT on DN treatment in clinics. Meanwhile, the Rehmannia glutinosa was used fully to raise the income level of farmers economically, while achieving the social benefit of empowering rural revitalization.

Topics: Animals; Arginine; Diabetes Mellitus; Diabetic Nephropathies; Metabolome; Metabolomics; Mice; Network Pharmacology; Tandem Mass Spectrometry

Reactive oxygen species (ROS) accumulation plays a pivotal role in the onset of cell damage induced by hyperglycemia and represents one of the major factors in the pathogenesis of diabetic retinopathy. In this study, we tested the antioxidants cyanidin-3-O-glucoside (C3G) and verbascoside (Verb) in the protection of retinal endothelium against glucose toxicity ". Increasing amounts (5-50 μM) of C3G, Verb or the combination of both compounds were tested in Human Retinal Endothelial Cells (HREC) grown with normal glucose (5 mM, NG) or high glucose (25 mM, HG).. Reduced cell viability and enhanced ROS levels (evaluated by MTT and H2DCFDA assays, respectively) in HG-stimulated HREC were restored by C3G and Verb in a dose-dependent manner, achieving the maximum protection in the presence of both compounds. Moreover, co-treatment with C3G and Verb worked better than each single molecule alone in the prevention of the disruption of blood-retinal-barrier-like properties by HG in a confluent HREC monolayer, as assessed by trans endothelial electrical resistance (TEER) and Na-Fluorescein permeability assays. Accordingly, C3G and Verb together also better counteracted the HG-induced down-regulation of the tight junction membrane proteins Zonula Occludens-1 and VE-Cadherin evaluated by immunocytochemical and Western blot analyses.. In conclusion, our data indicate that C3G and Verb could efficiently protect the retinal endothelium against high glucose damage.

Topics: Antioxidants; Diabetes Mellitus; Diabetic Retinopathy; Endothelial Cells; Glucose; Glucosides; Humans; Reactive Oxygen Species

The deleterious effects of diabetes mellitus (DM) over development are apparently due to an increase in oxidative stress. Some antioxidants could prevent developmental alterations produced by diabetic state. Extracts of plants of the genus Buddleja are used traditionally for Mexican indigens to ameliorate some diseases. The purpose of this work was to evaluate the effect of the extract of Buddleja cordata over diabetic embryopathy.. Two experimental approaches were used: an in vivo study and an in vitro model. In the first, rats were treated with streptozotocin, streptozotocin plus methanolic extract of B. cordata, or none. Females were sacrificed at gestational day (GD) 19, and biochemical clinical parameters were measured; also, the fetuses were obtained and morphologically analyzed. In the in vitro model, a verbascoside-enriched fraction (VEF) of the extract was used in whole embryo culture in order to search for the mechanisms for embryoprotection effect over hyperglycemia-induced malformations.. In the in vivo experiments, B. cordata extract reduces the frequency and severity of fetal malformations produced by chemically induced diabetes, and additionally partially ameliorates the diabetic condition; in the in vitro model, both severity and frequency of embryo dysmorphogenesis were reduced by the VEF; also, this fraction reduces lipoperoxidation without affecting the activity of the antioxidant enzymes.. The results suggest that verbascoside of methanolic extract and enriched fraction can directly affect the redox state, and thus, prevents the embryotoxicity mediated by oxidative stress, in embryos of diabetic pregnancy.

Topics: Animals; Buddleja; Diabetes Mellitus; Disease Models, Animal; Fetal Diseases; Glucosides; Phenols; Pregnancy; Rats

This study was designed to investigate the protective effects and mechanisms of acteoside on DKD in diabetes male db/db mice and high glucose-induced HK-2 cells. The diabetes db/db mice were divided randomly into model group, metformin group, irbesartan group, and acteoside group. We observed the natural product of acteoside exhibiting a significant effect in renal protection through analyzing of biochemical indicators and endogenous metabolites, histopathological observations, and western blotting. HK-2 cells subjected to high glucose were used in invitro experiments. The molecular mechanisms of them were investigated by RT-PCR and western blot. Acteoside prevents high glucose-induced HK-2 cells and diabetes db/db mice by inhibiting NADPH/oxidase-TGF-β/Smad signaling pathway. Acteoside regulated the disturbed metabolic pathway of lipid metabolism, glyoxylate and dicarboxylate metabolism, and arachidonic acid metabolism. We discovered the natural product of acteoside exhibiting a significant effect in renal protection. This study paved the way for further exploration of pathogenesis, early diagnosis, and development of a new therapeutic agent for DKD.

Topics: Animals; Biological Products; Cell Line; Diabetes Mellitus; Diabetic Nephropathies; Glucosides; Humans; Kidney; Male; Mice; NADP; NADPH Oxidases; Phenols; Signal Transduction; Smad Proteins; Transforming Growth Factor beta

Diabetes is a chronic disease associated with triglyceride metabolism disorder, being an etiological factor in fatty liver disease, hypertension, and cardiovascular diseases. Diet-based therapy including energy balance and herbal supplements is a suitable approach to ameliorate progression of the disease. Leaves of Lippia triphylla (lemon verbena) from the family Verbenaceae are a foodstuff used as a tea drink or cooking seasoning, with confirmed safety during long-term use. We report herein the regulatory effect of L. triphylla extract (LTE) and its major compound acteoside (ACT) on abnormal liver lipid metabolism. Both LTE and ACT administration significantly decreased serum and hepatic lipid content, increased the phosphorylation level of the energy metabolism moderator adenosine 5'-monophosphate-activated protein kinase (AMPK), and reduced two major markers of lipid synthesis, viz. acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), with an obvious enhancement in ACC phosphorylation. Furthermore, ACT promoted lipolysis and fatty acid oxidation by increasing messenger RNA (mRNA) expression of adipose triglyceride lipase (ATGL) and carnitine palmitoyltransferase (CPT)-1. These results provide scientific evidence for the development of functional foods containing L. triphylla extract and acteoside for treatment of diabetes-associated lipid metabolism disorder.

Topics: Acetyl-CoA Carboxylase; AMP-Activated Protein Kinases; Animals; Carnitine O-Palmitoyltransferase; Diabetes Mellitus; Fatty Acid Synthase, Type I; Glucosides; Lipase; Lipid Metabolism; Lipolysis; Lippia; Liver; Male; Mice; Mice, Inbred C57BL; Oxidation-Reduction; Phenols; Phosphorylation; Plant Extracts; Plant Leaves; Triglycerides