The Mechanism of Lycium Barbarum for Liver Cancer Treatment Was Analyzed Based on Network Pharmacology
1. School of Basic Medical Sciences, Hebei Key Laboratory for Chronic Diseases, North China University of Science and Technology, Tangshan 063210, China
2. Jitang College, North China University of Science and Technology, Tangshan 063210, China
| Abstract: | Aim: The mechanism of lycium barbarum treatment liver cancer was explored based on network pharmacology. Methods: The active ingredients, action targets of Lycium barbarum and disease targets of liver cancer were searched in public database platforms TCMSP, GeneCards, DisGeNET, OMIM and TTD, and the potential target of lycium barbarum in the treatment of liver cancer was obtained by intersection of drug component target and disease target. The protein interaction network (PPI) of lycium barbarum in treating liver cancer was obtained through STRING database, and the core target was identified by Cytoscape3.9.1 software analysis. The signaling pathway of lycium barbarum on hepatocarcinoma were screened by gene ontology (GO) enrichment analysis and Genomic Encyclopedia (KEGG) pathway enrichment analysis. Results: 45 active ingredients and 430 targets of Lycium barbarum, and 6489 targets related to liver cancer were selected. There were 272 common targets of drug-disease intersection. The analysis results showed that the active components of Lycium berry mainly included δ-carotene, lano-8-enol, lano-8-ene-3beta-alcohol, 14b-pregnane, β-sitosterol, and carotenin. The core targets of lycium barbarum in the treatment of liver cancer include AKT1, TNF, EGFR, ESR1, SRC, PPARG and HSP90AA1. GO enrichment is mainly involved in biological processes such as protein phosphorylation, response to exogenous stimuli, and negative regulation of apoptosis. KEGG is mainly involved in metabolic pathway, cancer pathway, PI3K-Akt signaling pathway. Conclusions: The results of this study show that Lycium barbarum may play an important role for treatment liver cancer in protein phosphorylation, exogenous stimulus response and negative regulation of apoptosis through key targets such as AKT1, TNF, EGFR, ESR1, SRC, PPARG and HSP90AA1 in "metabolic pathway", "tumor pathway" and "PI3K-Akt signaling pathway". |
| Keywords: | Network Pharmacology; Lycium Barbarum; Liver Cancer |
| DOI: | 10.57237/j.cmf.2024.03.001 |
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收稿日期: 2024-08-05
接受日期: 2024-09-02
在线出版日期: 2024-09-09
基金
| 1. | Natural Science Foundation of Hebei Province (No: H2022209048) |
参考文献
| [1] | Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 2021; 71, 209-249. |
| [2] | Zhang DQ, Xin GJ, Ding Y, et al. Effects of Lycium barbarum polysaccharide on autophagy and apoptosis of HepG2 hepatocellular carcinoma cells. Chinese Traditional Patent Medicine 2017; 39: 2600-2602 (in Chinese). |
| [3] | Shan TY, Zhao RT, Yang SL, et al. Study on inhibition and apoptosis of Lycium barbarum polysaccharide on human hepatocellular carcinoma cell Bel-7402. Li Shi Zhen medicine and materia medica research 2010; 2: 1928-1929 (in Chinese). |
| [4] | Wei XL. The effects of lycium barbarum on the liver. Asia-Pacific T raditional Medicine 2009; 5: 145-146 (in Chinese). |
| [5] | Sun YL, Pang B, Liu X, et al. Antitumor and immunology of lycium barbarum polysaccharide in vitr. Chinese journal of gerontolog 2018; 38: 5057-5059 (in Chinese). |
| [6] | Han YH, Liu XX. Lycium barbarum polysaccharide promotes apoptosis of hepatocellular carcinoma cells in rats. Modern Food Science and Technology 2019; 36: 7-11 (in Chinese). |
| [7] | Zhang DQ, XinGJ. Lycium barbarum polysaccharide inhibits VEGF expression, migration and invasion in SMMC-7721 hepatocellular carcinoma cells. Chinese journal of histochemistry and cytochemistry 2019; 28: 26-31 (in Chinese). |
| [8] | Hao W, Wang SF, Zhao J, et al. Effects of extraction methods on immunology activity and chemical profiles of Lycium barbarum polysaccharides. J Pharm Biomed Anal 2020; 185: 113219. |
| [9] | Miranda MR, Vestuto V, Amodio G, et al. Antitumor Mechanisms of Lycium barbarum Fruit: An Overview of In Vitro and In Vivo Potential. Life (Basel) 2024; 14: 420. |
| [10] | Jiang SJ, Xiao X, Li J, et al. Lycium barbarum polysaccharide-glycoprotein ameliorates ionizing radiation-induced epithelial injury by regulating oxidative stress and ferroptosis via the Nrf2 pathway. Free Radic Biol Med 2023; 204: 84-94. |
| [11] | Zheng H, Liang X, Zhou H, et al. Integrated gut microbiota and fecal metabolome analyses of the effect of Lycium barbarum polysaccharide on D-galactose-induced premature ovarian insufficiency. Food Funct 2023; 14: 7209-7221. |
| [12] | Zheng X, Wang J, Bi F, et al. Protective effects of Lycium barbarum polysaccharide on ovariectomy-induced cognition reduction in aging mice. Int J Mol Med 2021; 48: 121. |
| [13] | Kwok SS, Wong FS, Shih KC, et al. Lycium barbarum Polysaccharide Suppresses Expression of Fibrotic Proteins in Primary Human Corneal Fibroblasts. J Clin Med. 2020; 9: 3572. |
| [14] | Lai S, Liu C, Liu C, et al. Lycium barbarum polysaccharide-glycoprotein promotes osteogenesis in hPDLSCs via ERK activation. Oral Dis. 2023; 29: 3503-3513. |
| [15] | Lu L, Mi J, Jin B, et al. Inhibitory effects of the anthocyanins from Lycium ruthenicum Murray on angiotensin-I-converting enzyme: in vitro and molecular docking studies. J Sci Food Agric 2023; 103: 7164-7175. |
| [16] | Guo S, Qi M, Li H, et al. The Protective Effect of Lycium Ruthenicum Murr Anthocyanins in Cr (VI)-Induced Mitophagy in DF-1 Cells. Life (Basel) 2022; 12: 1115. |
| [17] | Peng Y, Yan Y, Wan P, et al. Gut microbiota modulation and anti-inflammatory properties of anthocyanins from the fruits of Lycium ruthenicum Murray in dextran sodium sulfate-induced colitis in mice. Free Radic Biol Med 2019; 136: 96-108. |
| [18] | Li L, Jia Q, Zhang H, et al. Tissue lipidomics, network pharmacology, and molecular docking to explore the therapeutic mechanism of anthocyanins from Lycium ruthenicum Murr. against gouty arthritis. Food Funct 2023; 14: 7011-7023. |
| [19] | Chen Z, Wu A, Jin H, et al. Beta-Sitosterol attenuates liver injury in a rat model of chronic alcohol intake. Arch Pharm Res 2020; 43: 1197-1206. |
| [20] | Wang C, Ma C, Gong L, et al. Preventive and therapeutic role of betaine in liver disease: A review on molecular mechanisms. Eur J Pharmacol 2021; 912: 174604. |
| [21] | Jiang YP, Yang JM, Ye RJ, et al. Protective effects of betaine on diabetic induced disruption of the male mice blood-testis barrier by regulating oxidative stress-mediated p38 MAPK pathways. Biomed Pharmacother 2019; 120: 109474. |
| [22] | Ma J, Meng X, Kang SY, et al. Regulatory effects of the fruit extract of Lycium chinense and its active compound, betaine, on muscle differentiation and mitochondrial biogenesis in C2C12 cells. Biomed Pharmacother 2019; 118: 109297. |
| [23] | BARBOSA J M, ALENCAR A A, NUNES X P, et al. Sources of alpha-, beta-, gamma-, delta- and epsilon-carotenes: A twentieth century review [J]. REVISTA BRASILEIRA DE FARMACOGNOSIA-BRAZILIAN JOURNAL OF PHARMACOGNOSY, 2008, 18(1): 135-154. |
| [24] | Wu H, Chen G, Wang J, et al. TIM-4 interference in Kupffer cells against CCL4-induced liver fibrosis by mediating Akt1/Mitophagy signalling pathway. Cell Prolif. 202; 53: e12731. |
| [25] | Sadaqat M, Qasim M, Tahir Ul Qamar M, et al. Advanced network pharmacology study reveals multi-pathway and multi-gene regulatory molecular mechanism of Bacopa monnieri in liver cancer based on data mining, molecular modeling, and microarray data analysis. Comput Biol Med 2023; 161: 107059. |
| [26] | Wu LX, Xu YC, Pantopoulos K, et al. Glycophagy mediated glucose-induced changes of hepatic glycogen metabolism via OGT1-AKT1-FOXO1 (Ser238) pathway. J Nutr Biochem 2023; 117: 109337. |
| [27] | Wan X, Zhou M, Huang F, et al. AKT1-CREB stimulation of PDGFRalpha expression is pivotal for PTEN deficient tumor development. Cell Death Dis 2021; 12: 172. |
| [28] | Zhao H, Wu L, Yan G, et al. Inflammation and tumor progression: signaling pathways and targeted intervention. Signal Transduct Target Ther 2021; 6: 263. |
| [29] | Qi D, Lu M, Xu P, et al. Transcription factor ETV4 promotes the development of hepatocellular carcinoma by driving hepatic TNF-alpha signaling. Cancer Commun (Lond). 2023; 43: 1354-1372. |
| [30] | Jin H, Shi Y, Lv Y, et al. EGFR activation limits the response of liver cancer to Lenvatinib. Nature 2021; 595: 730-734. |
| [31] | Lazcanoiturburu N, García-Sáez J, González-Corralejo C, et al. Lack of EGFR catalytic activity in hepatocytes improves liver regeneration following DDC-induced cholestatic injury by promoting a pro-restorative inflammatory response. J Pathol 2022; 258: 312-324. |
| [32] | Ye Q, Liu Y, Zhang G, et al. Deficiency of gluconeogenic enzyme PCK1 promotes metabolic-associated fatty liver disease through PI3K/AKT/PDGF axis activation in male mice. Nat Commun 2023; 14: 1402. |
| [33] | Wang M, Zhang J, Gong N. Role of the PI3K/Akt signaling pathway in liver ischemia reperfusion injury: a narrative review. Ann Palliat Med 2022; 11: 806-817. |
| [34] | Li J, Wang T, Liu P, et al. Hesperetin ameliorates hepatic oxidative stress and inflammation via the PI3K/AKT-Nrf2-ARE pathway in oleic acid-induced HepG2 cells and a rat model of high-fat diet-induced NAFLD. Food Funct 2021; 12: 3898-3918. |
| [35] | Gao YY, Li J, Huang J, et al. Effects of Lycium barbarum polysaccharide on the photoinduced autophagy of retinal pigment epithelium cells. Int J Ophthalmol. 202; 15: 23-30. |
| [36] | Yu Y, Wu X, Pu J, et al. Lycium barbarum polysaccharide protects against oxygen glucose deprivation/reoxygenation-induced apoptosis and autophagic cell death via the PI3K/Akt/mTOR signaling pathway in primary cultured hippocampal neurons. Biochem Biophys Res Commun 2018; 495: 1187-1194. |
| [37] | Xiao J, Zhu Y, Liu Y, et al. Lycium barbarum polysaccharide attenuates alcoholic cellular injury through TXNIP-NLRP3 inflammasome pathway. Int J Biol Macromol 2014; 69: 73-78. |
| [38] | Llovet JM, Kelley RK, Villanueva A, et al. Hepatocellular carcinoma. Nat Rev Dis Primers 2021; 7: 6. |
| [39] | Liu S, Xu P. Advancements in tyrosine kinase-mediated regulation of innate nucleic acid sensing. Zhejiang Da Xue Xue Bao Yi Xue Ban 2024; 53: 35-46. |
