Dietary Resveratrol Butyrate Monoester Supplement Improves Hypertension and Kidney Dysfunction in a Young Rat Chronic Kidney Disease Model

Abstract

Chronic kidney disease (CKD) remains a public health problem. Certain dietary supplements can assist in the prevention of CKD progression. In this regard, resveratrol is a polyphenol and has a potential therapeutic role in alleviating CKD. We previously utilized butyrate in order to improve the bioavailability of resveratrol via esterification and generated a resveratrol butyrate monoester (RBM). In this study, the hypothesis that RBM supplementation is able to protect against kidney dysfunction and hypertension was tested by using an adenine-induced CKD model. For this purpose, three-week-old male Sprague Dawley rats (n = 40) were equally categorized into: group 1—CN (sham control); group 2—CKD (adenine-fed rats); group 3—REV (CKD rats treated with 50 mg/L resveratrol); group 4—MEL (CKD rats treated with 25 mg/L RBM); and group 5—MEH (CKD rats treated with 50 mg/L RBM). At the end of a 12-week period, the rats were then euthanized. The adenine-fed rats displayed hypertension and kidney dysfunction, which were attenuated by dietary supplementation with RBM. The CKD-induced hypertension coincided with: decreased nitric oxide (NO) bioavailability; augmented renal protein expression of a (pro)renin receptor and angiotensin II type 1 receptor; and increased oxidative stress damage. Additionally, RBM and resveratrol supplementation shaped distinct gut microbiota profiles in the adenine-treated CKD rats. The positive effect of high-dose RBM was shown together with an increased abundance of the genera Duncaniella, Ligilactobacillus, and Monoglobus, as well as a decrease in Eubacterium and Schaedierella. Importantly, the mechanism of action of the RBM supplementation may be related to the restoration of NO, rebalancing of the RAS, a reduction in oxidative stress, and alterations to the gut microbiota. Moreover, RBM supplementation shows promise for the purposes of improving CKD outcomes and hypertension. As such, further translation to human studies is warranted.

Physalis alkekengi L. Calyx Extract Alleviates Glycolipid Metabolic Disturbance and Inflammation by Modulating Gut Microbiota, Fecal Metabolites, and Glycolipid Metabolism Gene Expression in Obese Mice

“…The current study demonstrated that the relative abundance of Monoglobus significantly decreased in PC treatment and was positively correlated with the level of proinflammatory factors. A previous study showed that Monoglobus might have a protective effect on chronic kidney disease [70]. Therefore, the specific effects of Monoglobus on the host under the disease state requires further clarification.…”

Endothelial Dysfunction in Superior Mesenteric Arteries Isolated from Adenine-Induced Renal Failure in Model Rats

“…Various adenine-treatment protocols, using concentrations and durations-different from that in the original protocol established by Yokozawa et al 18) -have since been used, leading to variations in the induced renal dysfunction. [22][23][24] Here, we used rats orally treated with adenine at 600 mg/kg for 10 d, which exhibited stable kidney dysfunction, as established by previous reports. 16,17) Furthermore, we confirmed renal dysfunction because serum creatinine and BUN were elevated in the rats.…”

Application of resveratrol butyric acid derivatives in the processing, physicochemical characterization, and the shelf‐life extension of Chinese sausages low in sodium nitrite

“…The previous studies published by our team also successfully esterified RSV with butyric acid-forming RBEs, which exhibited more excellent hydrogen peroxide scavenging activity than RSV (Tain et al, 2021) while effectively inhibiting fatty acidinduced lipid accumulation in HepG2 cells (Tain et al, 2020). The efficacy of resveratrol in preventing hypertension and kidney damage in young rats with chronic kidney disease is comparable to that of resveratrol, although it is dose-independent (Tain et al, 2023). RBEs have been shown to have preventative effects in pregnant and lactating rats supplemented with drinking water, protecting offspring from hypertension due to maternal di-2-ethyl hexyl phthalate (DEHP) exposure.…”

“…RBEs were synthesized and isolated following the approach of Shih et al (2021) and Tain et al (2023). Briefly, trans-RSV (91.3 g, 0.2 mol) was mixed with butyric acid (80 g, 0.22 mol) in 1 L of anhydrous tetrahydrofuran (THF), then N-ethyl-N 0 -(3-dimethylaminopropyl) carbodiimide (EDC; 68.4 g, 0.22 mol) and 4-dimethylaminopyridine (DMAP; 53.8 g, 0.11 mol) were added, followed with nitrogen stirring at room temperature for 48 h. The reaction process was protected from light throughout, while the flasks were wrapped with aluminum foil.…”

“…RBEs have been shown to have preventative effects in pregnant and lactating rats supplemented with drinking water, protecting offspring from hypertension due to maternal di-2-ethyl hexyl phthalate (DEHP) exposure. The beneficial effects were attributed to a reduction in oxidative damage, increased plasma butyrate concentration, downregulation of short-chain fatty acids (SCFAs) receptor expression, reduced downstream signaling of the acryl hydrocarbon receptor (AHR) pathway, and alteration of the gut microflora (Tain et al, 2023). Moreover, RBEs have been found to inhibit the formation of fat cells by regulating the expression of adipogenic proteins while enhancing the p-AMPK/ AMPK ratio (Shih et al, 2022).…”