Long-Term Supplementation of Microencapsulated ursodeoxycholic Acid Prevents Hypertension in a Mouse Model of Insulin Resistance

Abstract

Hypertension is a significant comorbidity associated with insulin resistance and type-2 diabetes. Limited evidence show that ursodeoxycholic acid (UDCA) has some anti-hypertensive effects. However, the potential effect of UDCA on hypertension induced by type-2 diabetic insulin resistance has not been reported. In C57Bl6 wild-type mice, insulin resistance was induced by the chronic ingestion of diet enriched in fat and fructose (HFF). HFF mice were randomized to treatment with UDCA or candersartan incorporated into the diet to achieve an ingested dose of approximately 70 mg/kg/day of UDCA or 3 mg/kg/day respectively. Systolic and diastolic blood pressure were measured with tail-cuff method. At 4 weeks of dietary treatment systolic and diastolic blood pressure were comparable in HFF and low-fat (LF) control mice. Co-administration of candesartan at 4 weeks significantly decreased systolic and diastolic blood pressure, UDCA showed no anti-hypertensive effect at 4 weeks. At 24 weeks of dietary intervention, HFF fed mice had substantially elevated systolic blood pressure compared to LF controls. The provision of UDCA substantially attenuated the dietary HFF induced increase in systolic blood pressure concomitant with significantly lower plasma angiotensin II. The anti-hypertensive effect of UDCA in HFF mice was comparable to candesartan. The data suggests that long term supplementation of UDCA effectively lowers hypertension in a dietary induced model of type-2 diabetic insulin resistance.

Blood-Brain Barrier Dysfunction Precedes Cognitive Decline and Neurodegeneration in Diabetic Insulin Resistant Mouse Model: An Implication for Causal Link

“…Mice were randomly allocated to either control or diabetic group ( n = 20). The sample size was determined based on previous studies (Al-Salami et al, 2017 ; Mamo et al, 2017 ). Mice in control group received standard low-fat (LF) chow (AIN-93M, Specialty Feeds, WA, Australia), while diabetic group received a pro-diabetic diet containing high fat and fructose (HFF; 30% (w/w) lard, 0.5% (w/w) cholesterol and 15% (w/w) fructose (SF14-088, see Supplementary Tables S1, S2 for detail).…”

Pharmacological and Advanced Cell Respiration Effects, Enhanced by Toxic Human-Bile Nano-Pharmaceuticals of Probucol Cell-Targeting Formulations

“…PB-LVSA (F1-without ULCA as control) and PB-ULCA-LVSA (F2-with ULCA as test) microcapsules were prepared using our established system (BÜCHI Labortechnik AG, Flawil, Switzerland) based on our developed technology: the ionic gelation vibrational jet flow technique [29,55]. Multiple parameters were used, including a frequency of 1800 Hz with a constant air pressure of 350 mbar, and a liquid flow rate of 5 mL/min; these parameters were constant for both microcapsules.…”

“…In gastrointestinal (GI) fluid, the hydrated LVSA matrix changes into the porous, insoluble acid matrix and when it reaches higher pH values (the small intestine), the alginate acid matrix is transformed into a soluble viscous layer that breaks down the polymer integrity and releases drugs from the microcapsules [53,54]. Previously, our lab has demonstrated that sodium alginate-based formulation improved pharmacokinetics and pharmacodynamics responses with optimized structural, chemical, and physical compatibility and improved targeted delivery [31,55,56]. This study is a preliminary study to elucidate the application of our ionic gelation vibrational jet flow technology in nano/microcapsule production, before moving a step further toward an in vivo animal study of anti-oxidant for T2DM.…”

Bile acid bio-nanoencapsulation improved drug targeted-delivery and pharmacological effects via cellular flux: 6-months diabetes preclinical study

“…The bile acids CDCA, LCA and UDCA concentrations in plasma, tissues and faeces will also be measured. The study is a continuation of ongoing work in our laboratory examining the preclinical efficacy of dual ingredient antioxidant-bile acid microcapsules in diabetes mellitus with published hypoglycaemic effects of controlled groups 3,11,14,[27][28][29][30][31][32][33][34][35] .…”