Hypoglycaemic activity of 2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione in streptozotocin-induced diabetic mice through ameliorating metabolic function and regulating peroxisome proliferator-activated receptor γ

Abstract

IntroductionDiabetes mellitus is characterized by hyperglycaemia causing changes in plasma lipoproteins, which leads to insulin resistance, secretion defects or both. The present study aimed to evaluate the ability of 2-dodecyl-6-methoxy-cyclohexa-2,5-diene-1,4-dione (DMDD) isolated from Averrhoa carambola L. roots to lower hyperglycaemia and to investigate its potential mechanism in diabetic mice.Material and methodsDMDD was isolated using a column chromatographic technique. Experimental mice were fed with a high-fat diet for a month and were intravenously injected with streptozotocin (80 mg/kg, single dose). Diabetic mice were orally administered DMDD (12.5, 25, 50 mg/kg) and 50 mg/kg pioglitazone for 15 days. Fasting blood glucose (FBG), fasting blood insulin (FINS), pancreatic insulin content, interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), as well as serum total cholesterol (TC), triglyceride (TG) and free fatty acid (FFA) were determined. Adipose tissue was assessed by histological examination, immunohistochemistry, western blot and reverse transcription-polymerase chain reaction methods.ResultsDMDD significantly increased the insulin level (all p < 0.05). In contrast, FBG, IL-6, TNF-α, TC, TG and FFA were significantly decreased (all p < 0.05). However, DMDD induced the activation of adipocyte peroxisome proliferator-activated receptor γ (PPAR-γ), confirmed by increased protein and mRNA expression of PPAR-γ.ConclusionsDMDD possessed hypoglycaemic activity due to its potential mechanism involving PPARγ-mediated adipocyte endocrine regulation.

Outcomes of transition from premixed and intensive insulin therapies to insulin aspart/degludec co-formulation in type 2 diabetes mellitus: a real-world experience

“…The occurrence of hypoglycaemia episodes is a limiting factor to provide adequate metabolic control in insulin-treated DM patients, particularly for those with unstable diabetes [25]. The risk of hypoglycaemia is directly related to increased glycaemic variability [26][27][28]. Therefore, one of the purposes is to reduce the fluctuations in glucose levels during the evaluation and development of new treatments [29].…”

A Simplified Streptozotocin-Induced Diabetes Model in Nude Mice

“…5). Согласно опубликованным данным, содержание инсулина в ПЖ мыши колеблется в широких пределах: у здоровых животных -от 2.5 до 80 мкг/г, у животных со стрептозотоциновым диабетом -от 0.2 до 20 мкг/г веса ПЖ [3,8,12]. Такая вариабельность объясняется межлинейными, возрастными и половыми различиями животных, разной длительностью и тяжестью диабета, разнообразием материала (целая ПЖ, отдельные доли ПЖ) и методов экстракции инсулина.…”

“…Даже небольшой объем цитратного буфера с такими низкими значениями pH может вызвать раздражение брюшины и существенный сдвиг кислотно-щелочного равновесия. Поэтому многие исследователи используют для растворения СТЗ нейтральные среды -фосфатный солевой буфер, сбалансированный солевой раствор Хэнка, 0.9% NaCl [4,6,8].…”

Uncovering the Pharmacological Mechanism of 2-Dodecyl-6-Methoxycyclohexa-2,5 -Diene-1,4-Dione Against Lung Cancer Based on Network Pharmacology and Experimental Evaluation

“…The anticancer effects of natural products and their secondary metabolites are widely used in the treatment of tumors, including paclitaxel, vincristine, etoposide and camptothecin ( Ouyang et al, 2014 ). 2-dodecyl-6-methoxycyclohexa-2, 5-diene-1,4-dione (DMDD), an active quinonoids from the roots of Averrhoa carambola L. , exhibits various biological effects, including antidiabetic ( Kintoko et al, 2018 ), antidiabetic nephropathy ( Lu et al, 2019 ) and anti-breast cancer ( Gao et al, 2015 ; Chen et al, 2017 ; Zhou et al, 2020 ) activities. The various biological activities and low toxicity of DMDD make it a promising candidate for clinical development.…”