Preclinical evidence of the effect of icariin on diabetic nephropathy: a systematic review and meta-analysis

Abstract

Background: Icariin (ICA), a bioactive flavonoid derived from Epimedium species, has demonstrated anti-inflammatory and anti-fibrotic properties in preclinical studies, suggesting potential therapeutic effects on diabetic nephropathy (DN). However, systematic evaluation of its efficacy remains unclear.

Objective: The purpose of this study is to evaluate the efficacy of Icariin on DN by preclinical evidence and meta-analysis. Meanwhile, the main possible action mechanisms of Icariin against DN were also summarized.

Methods: As of October 1, 2024, we conducted a systematic search across seven prominent Chinese and English databases (CNKI, Wanfang, CBM, PubMed, Cochrane Library, Embase, and Web of Science) to identify studies investigating the therapeutic effects of icariin on DN. PROSPERO has released a summary protocol (registration number: CRD42024564001).

Results: This meta-analysis encompassed nine studies, involving a total of 308 animals, and revealed that icariin significantly reduced blood glucose, SCR, BUN, 24 h UP, 24 h UV, KI, MDA, and IL-1β levels, while augmenting antioxidant enzyme activities (SOD and GPX). Furthermore, ICA lowered TG and TC, indicative of its potential in mitigating risk factors. However, direct comparisons between ICA and angiotensin II receptor blockers (ARB) yielded no statistically significant differences in DN treatment outcomes (p > 0.05). The greatest effects were recorded in high-dose (> 30 mg/kg/day) groups rather than in low-dose (< 30 mg/kg/day) groups. For time-response effects, subgroup analysis indicated that intervention duration of ICA can influence the treatment effect, and more beneficial effects were observed when studies had a drug administration time of < 8 weeks.

Conclusion: Based on an analysis of existing experimental evidence, icariin displays promise in slowing the progression of diabetic nephropathy. To validate its anti-diabetic nephropathy efficacy with greater precision and ensure its readiness for clinical translation, further confirmatory animal studies are warranted.

Keywords: Animal experiment; Diabetic nephropathy; Icariin; Meta-analysis; Systematic review.

Fig. 1

The chemical structure of icariin

Fig. 2

Flow chart of selecting process

Fig. 3

Publication year of the included studies

Fig. 4

Characteristics of included studies

Fig. 5

Forest plot: effect of ICA on FBG A and RBG B level

Fig. 6

Forest plot: effect of ICA on SCR A and BUN B level

Fig. 7

Forest plot: effect of ICA on 24 h UP A, 24 h UV B and KI C level

Fig. 8

Forest plot: effect of ICA on MDA A, SOD B and GPX C level

Fig. 9

Forest plot: effect of exosome on IL-1β level

Fig. 10

Forest plot: effect of ICA on TG A and TC C level

Fig. 11

Forest plot: effect of ICA on TGF-β1 A, α-SMA B, Nrf2 C and LC3-II D level

Fig. 12

Funnel plots for SCR A, BUN B, 24 h UP C and KI D of publication bias

Fig. 13

Mechanism of ICA in the treatment of Diabetic Nephropathy