Quantitative Proteomics Combined with Network Pharmacology Analysis
Unveils the Biological Basis of Schisandrin B in Treating Diabetic
Nephropathy

Jianying      Song; Bo      Zhang; Huiping      Zhang; Wenbo      Cheng; Peiyuan      Liu; Jun      Kang

doi:10.2174/1386207326666230505111903

Abstract

Background: Diabetic nephropathy (DN) is a major complication of diabetes. Schisandrin B (Sch) is a natural pharmaceutical monomer that was shown to prevent kidney damage caused by diabetes and restore its function. However, there is still a lack of comprehensive and systematic understanding of the mechanism of Sch treatment in DN.

Objective: We aim to provide a systematic overview of the mechanisms of Sch in multiple pathways to treat DN in rats.

Methods: Streptozocin was used to build a DN rat model, which was further treated with Sch. The possible mechanism of Sch protective effects against DN was predicted using network pharmacology and was verified by quantitative proteomics analysis.

Results: High dose Sch treatment significantly downregulated fasting blood glucose, creatinine, blood urea nitrogen, and urinary protein levels and reduced collagen deposition in the glomeruli and tubule-interstitium of DN rats. The activities of superoxide dismutase (SOD) and plasma glutathione peroxidase (GSH-Px) in the kidney of DN rats significantly increased with Sch treatment. In addition, the levels of IL-6, IL-1β, and TNF-α were significantly reduced in DN rats treated with Sch. 11 proteins that target both Sch and DN were enriched in pathways such as MAPK signaling, PI3K-Akt signaling, renal cell carcinoma, gap junction, endocrine resistance, and TNF signaling. Furthermore, quantitative proteomics showed that Xaf1 was downregulated in the model vs. control group and upregulated in the Sch-treated vs. model group. Five proteins, Crb3, Tspan4, Wdr45, Zfp512, and Tmigd1, were found to be upregulated in the model vs. control group and downregulated in the Sch vs. model group. Three intersected proteins between the network pharmacology prediction and proteomics results, Crb3, Xaf1, and Tspan4, were identified.

Conclusion: Sch functions by relieving oxidative stress and the inflammatory response by regulating Crb3, Xaf1, and Tspan4 protein expression levels to treat DN disease.

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[1]
Goldberg, R.; Rubinstein, A.M.; Gil, N.; Hermano, E.; Li, J.P.; van der Vlag, J.; Atzmon, R.; Meirovitz, A.; Elkin, M. Role of heparanase-driven inflammatory cascade in pathogenesis of diabetic nephropathy. Diabetes,  2014, 63(12), 4302-4313.
 [http://dx.doi.org/10.2337/db14-0001] [PMID: 25008182]

[2]
Ni, W.J.; Tang, L.Q.; Wei, W. Research progress in signalling pathway in diabetic nephropathy. Diabetes Metab. Res. Rev.,  2015, 31(3), 221-233.
 [http://dx.doi.org/10.1002/dmrr.2568] [PMID: 24898554]

[3]
Wang, H.; Zhang, H.; Chen, X.; Zhao, T.; Kong, Q.; Yan, M.; Zhang, B.; Sun, S.; Lan, H.Y.; Li, N.; Li, P. The decreased expression of electron transfer flavoprotein β is associated with tubular cell apoptosis in diabetic nephropathy. Int. J. Mol. Med.,  2016, 37(5), 1290-1298.
 [http://dx.doi.org/10.3892/ijmm.2016.2533] [PMID: 27035869]

[4]
Jin, H.; Piao, S.G.; Jin, J.Z.; Jin, Y.S.; Cui, Z.H.; Jin, H.F.; Zheng, H.L.; Li, J.J.; Jiang, Y.J.; Yang, C.W.; Li, C. Synergistic effects of leflunomide and benazepril in streptozotocin-induced diabetic nephropathy. Nephron, Exp. Nephrol.,  2014, 126(3), 148-156.
 [http://dx.doi.org/10.1159/000362556] [PMID: 24855017]

[5]
Tuttle, K.R.; Bakris, G.L.; Toto, R.D.; McGill, J.B.; Hu, K.; Anderson, P.W. The effect of ruboxistaurin on nephropathy in type 2 diabetes. Diabetes Care,  2005, 28(11), 2686-2690.
 [http://dx.doi.org/10.2337/diacare.28.11.2686] [PMID: 16249540]

[6]
Hu, X.; Liu, W.; Yan, Y.; Liu, H.; Huang, Q.; Xiao, Y.; Gong, Z.; Du, J. Vitamin D protects against diabetic nephropathy: Evidence-based effectiveness and mechanism. Eur. J. Pharmacol.,  2019, 845, 91-98.
 [http://dx.doi.org/10.1016/j.ejphar.2018.09.037] [PMID: 30287151]

[7]
Tuttle, K.R.; Brosius, F.C., III; Adler, S.G.; Kretzler, M.; Mehta, R.L.; Tumlin, J.A.; Tanaka, Y.; Haneda, M.; Liu, J.; Silk, M.E.; Cardillo, T.E.; Duffin, K.L.; Haas, J.V.; Macias, W.L.; Nunes, F.P.; Janes, J.M. JAK1/JAK2 inhibition by baricitinib in diabetic kidney disease: results from a Phase 2 randomized controlled clinical trial. Nephrol. Dial. Transplant.,  2018, 33(11), 1950-1959.
 [http://dx.doi.org/10.1093/ndt/gfx377] [PMID: 29481660]

[8]
Mora, C.; Navarro, J.F. Inflammation and diabetic nephropathy. Curr. Diab. Rep.,  2006, 6(6), 463-468.
 [http://dx.doi.org/10.1007/s11892-006-0080-1] [PMID: 17118230]

[9]
Araújo, L.; Silva, M.; Silva, C.; Monteiro, M.; Pereira, L.; Rocha, L.P.; Corrêa, R.; Reis, M.A.; Machado, J.R. Cytokines and T helper cells in diabetic nephropathy pathogenesis. JDM,  2016, 6(4), 230-246.
 [http://dx.doi.org/10.4236/jdm.2016.64025]

[10]
Wada, J.; Makino, H. Inflammation and the pathogenesis of diabetic nephropathy. Clin. Sci.,  2013, 124(3), 139-152.
 [http://dx.doi.org/10.1042/CS20120198] [PMID: 23075333]

[11]
Lampropoulou, I.T. Stangou, M Sarafidis, P.; Gouliovaki, A.; Giamalis, P.; Tsouchnikas, I.; Didangelos, T.; Papagianni, A. TNF-α pathway and T-cell immunity are activated early during the development of diabetic nephropathy in Type II Diabetes Mellitus. Clin. Immunol.,  2020, 215, 108423.
 [http://dx.doi.org/10.1016/j.clim.2020.108423] [PMID: 32304735]

[12]
Navarro-González, J.F.; Mora-Fernández, C. The role of inflammatory cytokines in diabetic nephropathy. J. Am. Soc. Nephrol.,  2008, 19(3), 433-442.
 [http://dx.doi.org/10.1681/ASN.2007091048] [PMID: 18256353]

[13]
Börgeson, E.; Johnson, A.M.F.; Lee, Y.S.; Till, A.; Syed, G.H.; Ali-Shah, S.T.; Guiry, P.J.; Dalli, J.; Colas, R.A.; Serhan, C.N.; Sharma, K.; Godson, C. Lipoxin A4 attenuates obesity-induced adipose inflammation and associated liver and kidney disease. Cell Metab.,  2015, 22(1), 125-137.
 [http://dx.doi.org/10.1016/j.cmet.2015.05.003] [PMID: 26052006]

[14]
Liu, W.; Wu, Y.H.; Zhang, L.; Xue, B.; Wang, Y.; Liu, B.; Liu, X.Y.; Zuo, F.; Yang, X.Y.; Chen, F.Y.; Duan, R.; Cai, Y.; Zhang, B.; Ji, Y. MicroRNA-146a suppresses rheumatoid arthritis fibroblast-like synoviocytes proliferation and inflammatory responses by inhibiting the TLR4/NF-kB signaling. Oncotarget,  2018, 9(35), 23944-23959.
 [http://dx.doi.org/10.18632/oncotarget.24050] [PMID: 29844864]

[15]
Hu, S.; Zuo, H.; Qi, J.; Hu, Y.; Yu, B. Analysis of Effect of Schisandra in the treatment of myocardial infarction based on three-mode gene ontology network. Front. Pharmacol.,  2019, 10, 232.
 [http://dx.doi.org/10.3389/fphar.2019.00232] [PMID: 30949047]

[16]
Thandavarayan, R.A.; Giridharan, V.V.; Arumugam, S.; Suzuki, K.; Ko, K.M.; Krishnamurthy, P.; Watanabe, K.; Konishi, T. Schisandrin B prevents doxorubicin induced cardiac dysfunction by modulation of DNA damage, oxidative stress and inflammation through inhibition of MAPK/p53 signaling. PLoS One,  2015, 10(3), e0119214.
 [http://dx.doi.org/10.1371/journal.pone.0119214] [PMID: 25742619]

[17]
Xu, Y.; Liu, Z.; Sun, J.; Pan, Q.; Sun, F.; Yan, Z.; Hu, X. Schisandrin B prevents doxorubicin-induced chronic cardiotoxicity and enhances its anticancer activity in vivo. PLoS One,  2011, 6(12), e28335.
 [http://dx.doi.org/10.1371/journal.pone.0028335] [PMID: 22164272]

[18]
Lee, T.H.; Jung, C.H.; Lee, D.H. Neuroprotective effects of Schisandrin B against transient focal cerebral ischemia in Sprague–Dawley rats. Food Chem. Toxicol.,  2012, 50(12), 4239-4245.
 [http://dx.doi.org/10.1016/j.fct.2012.08.047] [PMID: 22960133]

[19]
Wang, J.W.; Liang, F.Y.; Ouyang, X.S.; Li, P.B.; Pei, Z.; Su, W.W. Evaluation of neuroactive effects of ethanol extract of Schisandra chinensis, Schisandrin, and Schisandrin B and determination of underlying mechanisms by zebrafish behavioral profiling. Chin. J. Nat. Med.,  2018, 16(12), 916-925.
 [http://dx.doi.org/10.1016/S1875-5364(18)30133-X] [PMID: 30595216]

[20]
Yu, B.; Sheng, D.; Tan, Q. Determination of Schisandrin A and Schisandrin B in Traditional Chinese Medicine Preparation Huganpian Tablet by RP-HPLC. Chem. Pharm. Bull.,  2019, 67(7), 713-716.
 [http://dx.doi.org/10.1248/cpb.c18-00968] [PMID: 31006725]

[21]
Qin, J.H.; Lin, J.R.; Ding, W.F.; Wu, W.H. Schisandrin B improves the renal function of IgA nephropathy rats through inhibition of the NF-κB signalling pathway. Inflammation,  2019, 42(3), 884-894.
 [http://dx.doi.org/10.1007/s10753-018-0943-z] [PMID: 30519926]

[22]
Xu, J.; Lu, C.; Liu, Z.; Zhang, P.; Guo, H.; Wang, T. Schizandrin B protects LPS-induced sepsis via TLR4/NF-κB/MyD88 signaling pathway. Am. J. Transl. Res.,  2018, 10(4), 1155-1163.
 [PMID: 29736208]

[23]
Li, M.; Jin, J.; Li, J.; Guan, C.W.; Wang, W.W.; Qiu, Y.W.; Huang, Z.Y. Schisandrin B protects against nephrotoxicity induced by cisplatin in HK-2 cells via Nrf2-ARE activation. Yao Xue Xue Bao,  2012, 47(11), 1434-1439.
 [PMID: 23387073]

[24]
Mou, Z.; Feng, Z.; Xu, Z.; Zhuang, F.; Zheng, X.; Li, X.; Qian, J.; Liang, G. Schisandrin B alleviates diabetic nephropathy through suppressing excessive inflammation and oxidative stress. Biochem. Biophys. Res. Commun.,  2019, 508(1), 243-249.
 [http://dx.doi.org/10.1016/j.bbrc.2018.11.128] [PMID: 30477745]

[25]
Li, S.; Zhang, B.; Jiang, D.; Wei, Y.; Zhang, N. Herb network construction and co-module analysis for uncovering the combination rule of traditional Chinese herbal formulae. BMC Bioinformatics,  2010, 11(Suppl. 11), S6-S17.
 [http://dx.doi.org/10.1186/1471-2105-11-S11-S6] [PMID: 21172056]

[26]
Zhao, S.; Li, S. Network-based relating pharmacological and genomic spaces for drug target identification. PLoS One,  2010, 5(7), e11764.
 [http://dx.doi.org/10.1371/journal.pone.0011764] [PMID: 20668676]

[27]
Wu, X.; Jiang, R.; Zhang, M.Q.; Li, S. Network-based global inference of human disease genes. Mol. Syst. Biol.,  2008, 4(1), 189-199.
 [http://dx.doi.org/10.1038/msb.2008.27] [PMID: 18463613]

[28]
Azushima, K.; Gurley, S.B.; Coffman, T.M. Modelling diabetic nephropathy in mice. Nat. Rev. Nephrol.,  2018, 14(1), 48-56.
 [http://dx.doi.org/10.1038/nrneph.2017.142] [PMID: 29062142]

[29]
Ge, J.; Miao, J.J.; Sun, X.Y.; Yu, J.Y. Huangkui capsule, an extract from Abelmoschus manihot (L.) medic, improves diabetic nephropathy via activating peroxisome proliferator–activated receptor (PPAR)-α/γ and attenuating endoplasmic reticulum stress in rats. J. Ethnopharmacol.,  2016, 189, 238-249.
 [http://dx.doi.org/10.1016/j.jep.2016.05.033] [PMID: 27224243]

[30]
Wiśniewski, J.R.; Zougman, A.; Nagaraj, N.; Mann, M. Universal sample preparation method for proteome analysis. Nat. Methods,  2009, 6(5), 359-362.
 [http://dx.doi.org/10.1038/nmeth.1322] [PMID: 19377485]

[31]
Li, S.; Chen, Y.T.; Ding, Q.Y.; Dai, J.Y.; Duan, X.C.; Hu, Y.J.; Lai, X.X.; Liu, Q.F.; Niu, M.; Xiang, R.W. Network pharmacology evaluation method guidance-draft. WJTCM,  2021, 7(1), 146-154.

[32]
Meza Letelier, C.E.; San Martín Ojeda, C.A.; Ruiz Provoste, J.J.; Frugone Zaror, C.J. Pathophysiology of diabetic nephropathy: A literature review. Medwave,  2017, 17(1), e6839.
 [http://dx.doi.org/10.5867/medwave.2017.01.6839] [PMID: 28112712]

[33]
Gao, H.; Wu, H. Maslinic acid activates renal AMPK/SIRT1 signaling pathway and protects against diabetic nephropathy in mice. BMC Endocr. Disord.,  2022, 22(1), 25-35.
 [http://dx.doi.org/10.1186/s12902-022-00935-6] [PMID: 35042497]

[34]
Carmona, M.D.; Paco-Meza, L.M.; Ortega, R.; Cañadillas, S.; Caballero-Villarraso, J.; Blanco, A.; Herrera, C. Hypoxia preconditioning increases the ability of healthy but not diabetic rat-derived adipose stromal/stem cells (ASC) to improve histological lesions of streptozotocin-induced diabetic nephropathy. Pathol. Res. Pract.,  2022, 230, 153756.
 [http://dx.doi.org/10.1016/j.prp.2021.153756] [PMID: 35032832]

[35]
Nagib, A.M.; Elsayed Matter, Y.; Ashry Gheith, O.; Fathi Refaie, A.; Othman, N.F.; Al-Otaibi, T. Diabetic nephropathy following posttransplant diabetes mellitus. Exp. Clin. Transplant.,  2019, 17(2), 138-146.
 [http://dx.doi.org/10.6002/ect.2018.0157] [PMID: 30945628]

[36]
Selby, N.M.; Taal, M.W. An updated overview of diabetic nephropathy: Diagnosis, prognosis, treatment goals and latest guidelines. Diabetes Obes. Metab.,  2020, 22(S1), 3-15.
 [http://dx.doi.org/10.1111/dom.14007] [PMID: 32267079]

[37]
Markell, M.S.; Friedman, E.A. Diabetic Nephropathy: Management of the end-stage patient. Diabetes Care,  1992, 15(9), 1226-1238.
 [http://dx.doi.org/10.2337/diacare.15.9.1226] [PMID: 1396019]

[38]
Matsui, T.; Nakashima, S.; Nishino, Y.; Ojima, A.; Nakamura, N.; Arima, K.; Fukami, K.; Okuda, S.; Yamagishi, S. Dipeptidyl peptidase-4 deficiency protects against experimental diabetic nephropathy partly by blocking the advanced glycation end products-receptor axis. Lab. Invest.,  2015, 95(5), 525-533.
 [http://dx.doi.org/10.1038/labinvest.2015.35] [PMID: 25730373]

[39]
Malek, V.; Sharma, N.; Sankrityayan, H.; Gaikwad, A.B. Concurrent neprilysin inhibition and renin-angiotensin system modulations prevented diabetic nephropathy. Life Sci.,  2019, 221, 159-167.
 [http://dx.doi.org/10.1016/j.lfs.2019.02.027] [PMID: 30769114]

[40]
Yoon, J.; Park, J.; Kim, H.; Jin, H.G.; Kim, H.; Ahn, Y.; Kim, Y.; Lee, H.; Lee, Y.; Kang, D. Dianthus superbus improves glomerular fibrosis and renal dysfunction in diabetic nephropathy model. Nutrients,  2019, 11(3), 553.
 [http://dx.doi.org/10.3390/nu11030553] [PMID: 30841605]

[41]
Kang, J.S.; Lee, S.J.; Lee, J.H.; Kim, J.H.; Son, S.S.; Cha, S.K.; Lee, E.S.; Chung, C.H.; Lee, E.Y. Angiotensin II-mediated MYH9 downregulation causes structural and functional podocyte injury in diabetic kidney disease. Sci. Rep.,  2019, 9(1), 7679-7691.
 [http://dx.doi.org/10.1038/s41598-019-44194-3] [PMID: 31118506]

[42]
Ruggenenti, P.; Cravedi, P.; Remuzzi, G. The RAAS in the pathogenesis and treatment of diabetic nephropathy. Nat. Rev. Nephrol.,  2010, 6(6), 319-330.
 [http://dx.doi.org/10.1038/nrneph.2010.58] [PMID: 20440277]

[43]
Harel, Z.; Gilbert, C.; Wald, R.; Bell, C.; Perl, J.; Juurlink, D.; Beyene, J.; Shah, P.S. The effect of combination treatment with aliskiren and blockers of the renin-angiotensin system on hyperkalaemia and acute kidney injury: Systematic review and meta-analysis. BMJ,  2012, 344, e42.
 [http://dx.doi.org/10.1136/bmj.e42] [PMID: 22232539]

[44]
Kimura, Y.; Kuno, A.; Tanno, M.; Sato, T.; Ohno, K.; Shibata, S.; Nakata, K.; Sugawara, H.; Abe, K.; Igaki, Y.; Yano, T.; Miki, T.; Miura, T. Canagliflozin, a sodium–glucose cotransporter 2 inhibitor, normalizes renal susceptibility to type 1 cardiorenal syndrome through reduction of renal oxidative stress in diabetic rats. J. Diabetes Investig.,  2019, 10(4), 933-946.
 [http://dx.doi.org/10.1111/jdi.13009] [PMID: 30663266]

[45]
Wang, M.; Zhang, X.; Ni, T.; Wang, Y.; Wang, X.; Wu, Y.; Zhu, Z.; Li, Q. Comparison of new oral hypoglycemic agents on risk of urinary tract and genital infections in type 2 diabetes: A network meta-analysis. Adv. Ther.,  2021, 38(6), 2840-2853.
 [http://dx.doi.org/10.1007/s12325-021-01759-x] [PMID: 33999339]

[46]
Lin, Q.N.; Liu, Y.D.; Guo, S.E.; Zhou, R.; Huang, Q.; Zhang, Z.M.; Qin, X. Schisandrin B ameliorates high-glucose-induced vascular endothelial cells injury by regulating the Noxa/Hsp27/NF-κB signaling pathway. Biochem. Cell Biol.,  2019, 97(6), 681-692.
 [http://dx.doi.org/10.1139/bcb-2018-0321] [PMID: 30817212]

[47]
Feng, S.; Qiu, B.; Zou, L.; Liu, K.; Xu, X.; Zhu, H. Schisandrin B elicits the Keap1-Nrf2 defense system via carbene reactive metabolite which is less harmful to mice liver. Drug Des. Devel. Ther.,  2018, 12, 4033-4046.
 [http://dx.doi.org/10.2147/DDDT.S176561] [PMID: 30568426]

[48]
Liu, Q.; Song, J.; Li, H.; Dong, L.; Dai, S. Schizandrin B inhibits the cis DDP induced apoptosis of HK 2 cells by activating ERK/NF-κB signaling to regulate the expression of survivin. Int. J. Mol. Med.,  2018, 41(4), 2108-2116.
 [http://dx.doi.org/10.3892/ijmm.2018.3409] [PMID: 29393335]

[49]
Lai, Q.; Luo, Z.; Wu, C.; Lai, S.; Wei, H.; Li, T.; Wang, Q.; Yu, Y. Attenuation of cyclosporine A induced nephrotoxicity by schisandrin B through suppression of oxidative stress, apoptosis and autophagy. Int. Immunopharmacol.,  2017, 52, 15-23.
 [http://dx.doi.org/10.1016/j.intimp.2017.08.019] [PMID: 28846887]

[50]
Pessoa, E.A.; Convento, M.B.; Castino, B.; Leme, A.M.; de Oliveira, A.S.; Aragão, A.; Fernandes, S.M.; Carbonel, A.; Dezoti, C.; Vattimo, M.F.; Schor, N.; Borges, F.T. Beneficial effects of isoflavones in the kidney of obese rats are mediated by PPAR-gamma expression. Nutrients,  2020, 12(6), 1624-1643.
 [http://dx.doi.org/10.3390/nu12061624] [PMID: 32492810]

[51]
Toda, N.; Mukoyama, M.; Yanagita, M.; Yokoi, H. CTGF in kidney fibrosis and glomerulonephritis. Inflamm. Regen.,  2018, 38(1), 14-21.
 [http://dx.doi.org/10.1186/s41232-018-0070-0] [PMID: 30123390]

[52]
Ran, J.; Ma, C.; Xu, K.; Xu, L.; He, Y.; Moqbel, S.A.A.; Hu, P.; Jiang, L.; Chen, W.; Bao, J.; Xiong, Y.; Wu, L. Schisandrin B ameliorated chondrocytes inflammation and osteoarthritis via suppression of NF-κB and MAPK signal pathways. Drug Des. Devel. Ther.,  2018, 12, 1195-1204.
 [http://dx.doi.org/10.2147/DDDT.S162014] [PMID: 29785089]

[53]
Kim, N.H. Podocyte hypertrophy in diabetic nephropathy. Nephrology,  2005, 10(s2), S14-S16.
 [http://dx.doi.org/10.1111/j.1440-1797.2005.00450.x] [PMID: 16174280]

[54]
Liu, W.T.; Peng, F.F.; Li, H.Y.; Chen, X.W.; Gong, W.Q.; Chen, W.J.; Chen, Y.H.; Li, P.L.; Li, S.T.; Xu, Z.Z.; Long, H.B. Metadherin facilitates podocyte apoptosis in diabetic nephropathy. Cell Death Dis.,  2016, 7(11), e2477.
 [http://dx.doi.org/10.1038/cddis.2016.335] [PMID: 27882943]

[55]
Sun, H.J.; Xiong, S.P.; Cao, X.; Cao, L.; Zhu, M.Y.; Wu, Z.Y.; Bian, J.S. Polysulfide-mediated sulfhydration of SIRT1 prevents diabetic nephropathy by suppressing phosphorylation and acetylation of p65 NF-κB and STAT3. Redox Biol.,  2021, 38, 101813.
 [http://dx.doi.org/10.1016/j.redox.2020.101813] [PMID: 33279869]

[56]
Almeida, V.M.; Dias, Ê.R.; Souza, B.C.; Cruz, J.N.; Santos, C.B.R.; Leite, F.H.A.; Queiroz, R.F.; Branco, A. Methoxylated flavonols from Vellozia dasypus Seub ethyl acetate active myeloperoxidase extract: in vitro and in silico assays. J. Biomol. Struct. Dyn.,  2022, 40(16), 7574-7583.
 [http://dx.doi.org/10.1080/07391102.2021.1900916] [PMID: 33739225]

[57]
Alves, F.S.; Rodrigues Do Rego, J.A.; Da Costa, M.L.; Lobato Da Silva, L.F.; Da Costa, R.A.; Cruz, J.N.; Brasil, D.D.S.B. Spectroscopic methods and in silico analyses using density functional theory to characterize and identify piperine alkaloid crystals isolated from pepper (Piper Nigrum L.). J. Biomol. Struct. Dyn.,  2020, 38(9), 2792-2799.
 [http://dx.doi.org/10.1080/07391102.2019.1639547] [PMID: 31282297]

[58]
Tsukita, S. Tight Junctions. In: Encyclopedia of Biological Chemistry; , 2013, pp. 392-395.

[59]
Sun, P.H.; Zhu, L.M.; Qiao, M.M.; Zhang, Y.P.; Jiang, S.H.; Wu, Y.L.; Tu, S.P. The XAF1 tumor suppressor induces autophagic cell death via upregulation of Beclin-1 and inhibition of Akt pathway. Cancer Lett.,  2011, 310(2), 170-180.
 [http://dx.doi.org/10.1016/j.canlet.2011.06.037] [PMID: 21788101]

[60]
Ma, X.; Verweij, E.W.E.; Siderius, M.; Leurs, R.; Vischer, H.F. Identification of TSPAN4 as novel histamine H4 receptor interactor. Biomolecules,  2021, 11(8), 1127-1142.
 [http://dx.doi.org/10.3390/biom11081127] [PMID: 34439793]

[61]
Ma, C.; Wang, W.; Wang, Y.; Sun, Y.; Kang, L.; Zhang, Q.; Jiang, Y. TMT-labeled quantitative proteomic analyses on the longissimus dorsi to identify the proteins underlying intramuscular fat content in pigs. J. Proteomics,  2020, 213, 103630.
 [http://dx.doi.org/10.1016/j.jprot.2019.103630] [PMID: 31881348]

[62]
Wu, Y.; Li, E.; Wang, Z.; Shen, T.; Shen, C.; Liu, D.; Gao, Q.; Li, X.; Wei, G. TMIGD1 Inhibited abdominal adhesion formation by alleviating oxidative stress in the mitochondria of peritoneal mesothelial cells. Oxid. Med. Cell. Longev.,  2021, 2021, 9993704.
 [http://dx.doi.org/10.1155/2021/9993704] [PMID: 34426761]

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DOI https://dx.doi.org/10.2174/1386207326666230505111903	Print ISSN 1386-2073
Publisher Name Bentham Science Publisher	Online ISSN 1875-5402

Combinatorial Chemistry & High Throughput Screening

Quantitative Proteomics Combined with Network Pharmacology Analysis Unveils the Biological Basis of Schisandrin B in Treating Diabetic Nephropathy

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