Evidence map›Paper›PMID 41201496›Full record

ArticleJournal of advanced research2026

Pomegranate peel extract alleviates diabetic retinopathy by suppressing the PI3K/AKT/HIF-1α/VEGF pathway and gut microbiota modulation.

Qi-Dong Ren, Mei-Rong Li, Mohamed A Farag, Lin-Lin Qiu, Yan-Ao Wang, Dan Liu, Hao-Ran Liu, Jin-Yue Sun, Ning-Yang Li, Chao Liu

Abstract read
In one paragraph

Article in Journal of advanced research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Qi-Dong RenKey Laboratory of Novel Food Resources Processing, Ministry of Agriculture and Rural Affairs/Institute of Food & Nutrition Science and Technology, Shandong Academy of Agricultural Sciences/Tea Research Institute, Shandong Academy of Agricultural Sciences, Jinan 250100, China.
Mei-Rong LiKey Laboratory of Novel Food Resources Processing, Ministry of Agriculture and Rural Affairs/Institute of Food & Nutrition Science and Technology, Shandong Academy of Agricultural Sciences/Tea Research Institute, Shandong Academy of Agricultural Sciences, Jinan 250100, China.
Mohamed A FaragDepartment of Pharmacognosy, Faculty of Pharmacy, Cairo University, 11562 Cairo, Egypt.
Lin-Lin QiuKey Laboratory of Novel Food Resources Processing, Ministry of Agriculture and Rural Affairs/Institute of Food & Nutrition Science and Technology, Shandong Academy of Agricultural Sciences/Tea Research Institute, Shandong Academy of Agricultural Sciences, Jinan 250100, China.
Yan-Ao WangKey Laboratory of Novel Food Resources Processing, Ministry of Agriculture and Rural Affairs/Institute of Food & Nutrition Science and Technology, Shandong Academy of Agricultural Sciences/Tea Research Institute, Shandong Academy of Agricultural Sciences, Jinan 250100, China.
Dan LiuShandong Provincial Center of Forest and Grass Germplasm Resources, Jinan 250102, China.
Hao-Ran LiuShandong Meiguolai Food Co., Ltd., Zaozhuang 277399, China.
Jin-Yue SunKey Laboratory of Novel Food Resources Processing, Ministry of Agriculture and Rural Affairs/Institute of Food & Nutrition Science and Technology, Shandong Academy of Agricultural Sciences/Tea Research Institute, Shandong Academy of Agricultural Sciences, Jinan 250100, China. Electronic address: moon_s731@hotmail.com.
Ning-Yang LiCollege of Food Science and Engineering, Ocean University of China, Qingdao 266003, China. Electronic address: ningyangli@126.com.
Chao LiuKey Laboratory of Novel Food Resources Processing, Ministry of Agriculture and Rural Affairs/Institute of Food & Nutrition Science and Technology, Shandong Academy of Agricultural Sciences/Tea Research Institute, Shandong Academy of Agricultural Sciences, Jinan 250100, China. Electronic address: liuchao555@126.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionDiabetic retinopathy (DR) is a severe microvascular complication of diabetes mellitus. Pomegranate peel extract (PPE) has shown potential in mitigating various diabetic complications, yet its role in DR remains unexplored.

objectiveTo investigate the beneficial effects and underlying action mechanisms of PPE in managing DR.

methodsPPE was extracted using 50 % ethanol. The effects and underlying mechanisms of PPE on DR were evaluated in streptozotocin (STZ)-induced DR rats and high-glucose-incubated adult retinal pigment epithelial cell line (ARPE-19) cells. Phenotypic parameters, network pharmacology (NP), and gut microbiota metagenomic analysis were employed to elucidate the impact and mechanisms of PPE in DR.

resultsIn DR rats, oral administration of PPE significantly mitigated retinal damage. NP analysis indicated potential mechanisms, involving the hypoxia-inducible factor-1/vascular endothelial growth factor (HIF-1/VEGF), phosphoinositide 3-kinase/protein kinase B (PI3K/AKT), and reactive oxygen species (ROS) pathways. PPE suppressed oxidative stress and inhibited the activation of PI3K/AKT/HIF-1α/VEGF pathway in the retina of DR rats and high-glucose-incubated ARPE-19 cells. Moreover, PPE improved gut microbiota dysbiosis in DR rats, particularly increasing Akkermansia muciniphila, which likely contributed to reduced inflammation and oxidative stress.

conclusionPPE exhibited therapeutic effects in DR by directly alleviating retinal damage via the suppression of oxidative stress and inhibition of PI3K/AKT/HIF-1α/VEGF pathway, as well as indirectly modulating gut microbiota. These findings suggested that PPE may serve as a promising nutraceutical for DR management.

Indexed as

Diabetic RetinopathyGastrointestinal MicrobiomePlant ExtractsPomegranateAnimalsCell LineDiabetes Mellitus, ExperimentalHumansHypoxia-Inducible Factor 1, alpha SubunitMaleOxidative StressPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktRatsRats, Sprague-DawleyReactive Oxygen SpeciesHif1a protein, ratHypoxia-Inducible Factor 1, alpha SubunitPhosphatidylinositol 3-KinasesPlant ExtractsProto-Oncogene Proteins c-aktReactive Oxygen SpeciesVascular Endothelial Growth Factor Avascular endothelial growth factor A, ratDiabetic retinopathygut microbiotaHIF-1α/VEGFPI3K/AKTPomegranate peelRetinal pigment epithelium

Identifiers

PMID41201496
PMCPMC13316503

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.