The anti-inflammatory activity of resveratrol in acute kidney injury: a systematic review and meta‐analysis of animal studies

Abstract

Context Accumulated experimental evidence suggests that resveratrol (RSV) may have an effect on acute kidney injury (AKI) by inhibiting inflammation. However, the credibility of the evidence for this practice is unclear. Objective This study investigated the effect of RSV on AKI and the underlying mechanism. Methods We searched PubMed, EMBASE, and Web of Science from 2005 to April 2022 for controlled animal trials assessing the effect of conventional resveratrol versus placebo on renal function outcome after AKI. This study was registered within the International Prospective Register of Systematic Reviews (PROSPERO) as number CRD42022329596. Results We retrieved 455 studies, 25 studies comprising data of 436 animals that met the inclusion criteria. Our meta-analysis suggested that RSV treatment was significantly associated with lower levels of serum creatinine (Scr) and blood urea nitrogen (BUN). The greatest effects were recorded in low-dose (<20 mg/kg/day) groups rather than in high-dose (> 20 mg/kg/day) groups. For time-response effects, subgroup analysis indicated that intervention duration of RSV can influence the treatment effect, and more beneficial effects were observed when studies had a drug administration time of <2 weeks. Discussion and conclusions This systematic review of animal AKI studies showed a consistently favourable effect of RSV as compared to placebo on renal function outcomes that increased with lower TNF-α, IL-6, and IL-1β. RSV has a more beneficial effect on SA-AKI animal models than the others. When the RSV intervention dose was low (< 20 mg/kg/day) and the intervention time was <2 weeks, more benefits could be observed.

A short treatment with resveratrol after a renal ischaemia–reperfusion injury prevents maladaptive repair and long‐term chronic kidney disease in rats

“…These studies demonstrated reductions in serum nitrogen products, TNFα, IL‐6 and IL‐1β. This collective evidence underscores the consistency across studies supporting anti‐inflammatory effects of RSV in the context of AKI (Cao et al., 2022). Here, we add that both acute‐phase cytokines and profibrotic signals exhibit a significant overexpression early in the natural history of the disease and that RSV administration effectively normalizes both processes, which is closely related to the long‐term benefits observed.…”

“…Existing evidence shows that RSV reduces acute-phase cytokines and glomerulosclerosis in spontaneously hypertensive rats (Xue et al, 2016), while also reducing NFκB activity during AKI (Li et al, 2018;Yeung et al, 2004) and attenuating cytokine expression and extracellular matrix expansion after unilateral ureteral obstruction (Liang et al, 2014). Indeed, a meta-analysis conducted by Cao et al (2022) comprising 25 studies that focused on various AKI models, such as IRI, drug-induced and sepsis-induced AKI, and pretreatment with RSV yielded consistent results. These studies demonstrated reductions in serum nitrogen products, TNFα, IL-6 and IL-1β.…”

“…Indeed, a meta‐analysis conducted by Cao et al. (2022) comprising 25 studies that focused on various AKI models, such as IRI, drug‐induced and sepsis‐induced AKI, and pretreatment with RSV yielded consistent results. These studies demonstrated reductions in serum nitrogen products, TNFα, IL‐6 and IL‐1β.…”

Exploring the multimodal health‐promoting properties of resveratrol: A comprehensive review

“…Clinical medications depend heavily on the effects of dose and time response. No animal studies on the dose–response and time‐response effects of RESV in the treatment of AKI were reported (Cao et al., 2022 ). To reduce AKI induced by sepsis in a rat model, RESV upregulated SIRT1 expression, reduced the release of inflammatory molecules, and promoted NF‐κB‐P65 deacetylation (Gan et al., 2017 ).…”

“…Clinical medications depend heavily on the effects of dose and time response. No animal studies on the dose-response and time-response effects of RESV in the treatment of AKI were reported(Cao et al, 2022). To reduce AKI induced by sepsis in a rat model, RESV upregulated SIRT1 expression, reduced the release of inflammatory molecules, and promoted NF-κB-P65 deacetylation(Gan et al, 2017).The treatment with RESV inhibited the intercellular adhesion molecule 1 (ICAM-1), IL-1, iNOS, and mRNA expression in human coronary arterial endothelial cells stimulated by TNFα, was one of the results of numerous in vitro studies that demonstrated the antiinflammatory effects of RESV in cardiac tissue(Huang et al, 2017).RESV's anti-inflammatory potential on CVDs attributed to several mechanisms, including reduction of monocyte adhesion to endothelial cells, suppression of NF-кB and JAK (Janus kinase)/STAT signal pathways, upregulation of anti-inflammatory cytokines, and inhibition of the production of pro-inflammatory mediators like TNFα, IL-1, and IL-6(Gal et al, 2021).…”