Study on the Mechanism of Galangin on Hyperuricemic Nephropathy Based on Metabolomics and Network Pharmacology

被引:1
作者
Qumu, Daermu [1 ]
Tian, Mu [2 ]
Li, Hengxi [1 ]
Yang, Xiujuan [1 ]
Han, Binhui [1 ]
Wei, Lanting [1 ]
Li, Bo [1 ]
Ma, Mengxue [1 ]
He, Junjie [1 ]
Shao, Xiaoni [1 ]
机构
[1] Southwest Minzu Univ, Coll Pharm, Chengdu, Sichuan, Peoples R China
[2] Southwest Minzu Univ, Coll Food Sci & Technol, Chengdu, Sichuan, Peoples R China
基金
中国国家自然科学基金;
关键词
galangin; hyperuricemic nephropathy; metabolomics; network pharmacology; signaling pathways; NF-KAPPA-B; COLORECTAL-CANCER; XANTHINE-OXIDASE; CELL-DEATH; URIC-ACID; EXPRESSION; KIDNEY; P53; NEPHROTOXICITY; TRANSPORTERS;
D O I
10.1002/mnfr.70029
中图分类号
TS2 [食品工业];
学科分类号
0832 ;
摘要
Galangin (GAL), a flavonol found in Alpinia officinarum and propolis, is a promising functional food. This study investigated the therapeutic effects and mechanisms of GAL in mice with hyperuricemic nephropathy (HN) by focusing on renal metabolomics and network pharmacology. In this study, we conducted untargeted metabolomic analysis and network pharmacology prediction. Subsequently, a compound-reaction-enzyme-gene network was constructed based on the results of metabolomics and network pharmacology to elucidate potential connections. The results demonstrated that GAL can improve renal interstitial fibrosis and inflammatory infiltration and reduce serum levels of uric acid (UA), urea nitrogen (UREA), and creatinine (CREA). Metabolome analysis indicated that GAL affected thiamine, pyrimidine, nicotinate, nicotinamide, pyruvate, glyoxylate, and dicarboxylate metabolism. Network pharmacology and experimental results showed that GAL reduced the key target expression of the tumor protein P53 (TP53), tumor necrosis factor (TNF), signal transducer and activator of transcription 3 (STAT3), heat shock protein 90 alpha family class A member 1 (HSP90aa1), albumin (ALB), and caspase-3 (CASP3). GAL also downregulated the expression of Janus kinase 2 (JAK2), phospho-JAK2 (P-JAK2), and phospho-STAT3 (P-STAT3). Furthermore, a joint analysis of the metabolome and network pharmacology showed that GAL can reverse HN through amino acid metabolism, nucleotide metabolism, energy metabolism, and endocrine system pathways. GAL can alleviate HN effectively and might play synergistic therapeutic roles through regulating metabolic profiles and the JAK2/STAT3 signaling pathway.
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页数:19
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共 63 条
[1]   A review on the ethnomedicinal uses, phytochemistry and pharmacology of Alpinia officinarum Hance [J].
Abubakar, Ibrahim Babangida ;
Malami, Ibrahim ;
Yahaya, Yakubu ;
Sule, Sahabi Manga .
JOURNAL OF ETHNOPHARMACOLOGY, 2018, 224 :45-62
[2]   Metabolic Benefits of Six-month Thiamine Supplementation in Patients With and Without Diabetes Mellitus Type 2 [J].
Al-Attas, Omar ;
Al-Daghri, Nasser ;
Alokail, Majed ;
Abd-Alrahman, Sherif ;
Vinodson, Benjamin ;
Sabico, Shaun .
CLINICAL MEDICINE INSIGHTS-ENDOCRINOLOGY AND DIABETES, 2014, 7 :1-6
[3]   Asymptomatic hyperuricaemia in chronic kidney disease: mechanisms and clinical implications [J].
Anders, Hans-Joachim ;
Li, Qiubo ;
Steiger, Stefanie .
CLINICAL KIDNEY JOURNAL, 2023, 16 (06) :928-938
[4]   Allopurinol, Benzbromarone, or a Combination in Treating Patients with Gout: Analysis of a Series of Outpatients [J].
Azevedo, Valderilio Feijo ;
Buiar, Pedro Grachinski ;
Giovanella, Laura Helena ;
Severo, Carolina Rossetti ;
Carvalho, Mauricio .
INTERNATIONAL JOURNAL OF RHEUMATOLOGY, 2014, 2014
[5]   THE COMPARTMENTATION OF PHOSPHORYLATED THIAMINE DERIVATIVES IN CULTURED NEUROBLASTOMA-CELLS [J].
BETTENDORFF, L .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 1994, 1222 (01) :7-14
[6]   Galangin inhibited ferroptosis through activation of the PI3K/AKT pathway in vitro and in vivo [J].
Chen, Ke ;
Xue, Ran ;
Geng, Yaping ;
Zhang, Shenshen .
FASEB JOURNAL, 2022, 36 (11)
[7]   Anti-inflammatory mechanism of galangin in lipopolysaccharide-stimulated microglia: Critical role of PPAR-γ signaling pathway [J].
Choi, Min-Ji ;
Lee, Eun-Jung ;
Park, Jin-Sun ;
Kim, Su-Nam ;
Park, Eun-Mi ;
Kim, Hee-Sun .
BIOCHEMICAL PHARMACOLOGY, 2017, 144 :120-131
[8]   Monosodium urate crystals regulate a unique JNK-dependent macrophage metabolic and inflammatory response [J].
Cobo, Isidoro ;
Cheng, Anyan ;
Murillo-Saich, Jessica ;
Coras, Roxana ;
Torres, Alyssa ;
Abe, Yohei ;
Lana, Addison J. ;
Schlachetzki, Johannes ;
Liu-Bryan, Ru ;
Terkeltaub, Robert ;
Sanchez-Lopez, Elsa ;
Glass, Christopher K. ;
Guma, Monica .
CELL REPORTS, 2022, 38 (10)
[9]   Urine and serum NMR-based metabolomics in pre-procedural prediction of contrast-induced nephropathy [J].
Dalili, Nooshin ;
Chashmniam, Saeed ;
Khoormizi, Seyed Mojtaba Heydari ;
Salehi, Lida ;
Jamalian, Seyed Ali ;
Nafar, Mohsen ;
Kalantari, Shiva .
INTERNAL AND EMERGENCY MEDICINE, 2020, 15 (01) :95-103
[10]   Network pharmacology-based investigation of potential targets of astragalus membranaceous-angelica sinensis compound acting on diabetic nephropathy [J].
Dong, Youzi ;
Zhao, Quanlin ;
Wang, Yuguo .
SCIENTIFIC REPORTS, 2021, 11 (01)