EFFECT OF RHUBARB FREE ANTHRAQUINONES ON OBESITY IN RATS AND ITS POTENTIAL MECHANISM

Authors

  • GUIFANG ZHANG School of Pharmacy and State Key Laboratory of Applied Organic Chemistry, Lanzhou University-730000, China
  • HAIJIAO WANG School of Pharmacy and State Key Laboratory of Applied Organic Chemistry, Lanzhou University-730000, China
  • SAEED ULLAH KHATTAK Centre of Biotechnology and Microbiology, University of Peshawar, Peshawar, Pakistan
  • HUIJUAN LV School of Pharmacy and State Key Laboratory of Applied Organic Chemistry, Lanzhou University-730000, China
  • LIFANG WANG School of Pharmacy and State Key Laboratory of Applied Organic Chemistry, Lanzhou University-730000, China
  • XUEFENG LI School of Basic Medical Sciences, Lanzhou University, Lanzhou-730000, China
  • XIUXIA SUN School of Pharmacy and State Key Laboratory of Applied Organic Chemistry, Lanzhou University-730000, China
  • YANBIN SHI School of Pharmacy and State Key Laboratory of Applied Organic Chemistry, Lanzhou University-730000, China. Collaborative Innovation Center for Northwestern Chinese Medicine, Lanzhou-730000 University, China https://orcid.org/0000-0001-5333-9866

DOI:

https://doi.org/10.22159/ijap.2023v15i6.49272

Keywords:

Rhubarb free anthraquinones, Anti-obesity, Network pharmacology, Molecular docking, Mechanism of action

Abstract

Objective: The study was to confirm the effect of rhubarb-free anthraquinones (RhA) on anti-obesity and preliminarily explore the possible mechanism of action of RhA.

Methods: The obesity model of rats was induced by a high-fat diet to evaluate the effect of RhA on weight reduction and their potential mechanism based on network pharmacology and molecular docking as well as Western blotting analysis.

Results: RhA significantly reduced body weight, lipid-body ratio and Lee's index of the obese model rats. The level of low-density lipoprotein cholesterol significantly was decreased, and the number of fat droplets and fat cells in the liver tissue of the obese model rats was significantly reduced after treatment. The anti-obesity-related core proteins mainly targeted by RhA were predicted as MAPK8, MAPK14 and CASP3. Aloe-emodin, rhein, emodin, chrysophanol, and physcion had high affinity with these proteins. The relative expression of CASP3 and MAPK8 in the obese model rats was increased at gene and proteins levels after treatment.

Conclusion: RhA had significant weight-reducing and blood lipid-lowering effect of obese rats, and they may mainly intervene in obesity by up-regulating the expression levels of MAPK8 and CASP3 protein involved in fat metabolism.

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References

Ethan L, Harold EB. Cancer and Obesity: An Obesity Medicine Association (OMA) Clinical Practice Statement (CPS). Obesity Pillars. 2022;3:100026. doi: 10.1016/j.obpill.2022.100.26.

Zhang L, Wang Z, Wang X, Chen Z, Shao L, TianY, Zheng C, et al. Prevalence of overweight and obesity in China: Results from a cross-sectional study of 441 thousand adults, 2012–2015. Obes Res Clin Pract. 2020;14(2):119-126. doi: 10.1016/j.orcp.2020.02.005. PMID 32139330.

Kyuwan L, Laura K, Christina M D C, Joanne E M. The Impact of Obesity on Breast Cancer Diagnosis and Treatment. Curr Oncol Rep. 2019;21(5):41. doi: 10.1007/s11912-019-0787-1. PMID 30919143.

Chaudhari D, Crisostomo C, Ganote C, Youngberg G. Acute Oxalate Nephropathy Associated with Orlistat: A Case Report with a Review of the Literature. Case Rep Nephrol. 2013;2013:124604. doi: 10.1155/2013/124604. PMID 24527242.

Fujioka K (2015). Safety and tolerability of medications approved for chronic weight management. Obesity (Silver Spring). 2015;23 Suppl 1:S7-11. doi: 10.1002/oby.21094. PMID 25900872.

Zhang G, Li J, Lyu H, Qian C, Li X. Comparative pharmacokinetics of rhubarb anthraquinones loaded nanoemulsion by different plasma drug concentration calculation methods. Acta. Poloniae. Pharmaceutica - Drug Research. 2021;78:475-483. doi: 10.32383/APPDR/141601.

Huang H, Liu Z, Qi X, Gao N, Chang J, Yang M, et al. Rhubarb granule promotes diethylnitrosamine-induced liver tumorigenesis by activating the oxidative branch of pentose phosphate pathway via G6PD in rats. J Ethnopharmacol. 2021;281:114479. doi: 10.1016/j.jep.2021.114479. PMID 34343647.

Gao C, Li G, Wang T, Gao L, Wang F, Shang H, et al. Rhubarb extract relieves constipation by stimulating mucus production in the colon and altering the intestinal flora. Biomed Pharmacother. 2021;138:111479. doi: 10.1016/j.biopha.2021.111479. PMID 33774313.

Wang Y, Zhang J, Xu Z, Zhang G, Lv H, Wang X, et al. Identification and action mechanism of lipid regulating components from Rhei Radix et rhizoma. J Ethnopharmacol. 2022;292:115179. doi: 10.1016/j.jep.2022.115179. PMID 35278606.

Fang JY, Huang TH, Chen WJ, Aljuffali IA, Hsu CY. Rhubarb hydroxyanthraquinones act as antiobesity agents to inhibit adipogenesis and enhance lipolysis. Biomed Pharmacother. 2022;146:112497. doi: 10.1016/j.biopha.2021.112497. PMID 34891117.

Régnier M, Rastelli M, Morissette A, Suriano F, Roy T.L, Pilon G, Delzenne N.M, Marette A, Hul V.M, Cani P.D. Rhubarb Supplementation Prevents Diet-Induced Obesity and Diabetes in Association with Increased Akkermansia muciniphila in Mice. Nutrients. 2020;12(10):2932. doi: 10.3390/nu12102932. PMID 32987923.

Li S, Zhang B. Traditional Chinese medicine network pharmacology: theory, methodology and application. Chin J Nat Med. 2013;11(2):110-20. doi: 10.1016/S1875-5364(13)60037-0. PMID 23787177.

Zhang R, Zhu X, Bai H, Ning K. Network pharmacology databases for traditional Chinese medicine: review and assessment. Front Pharmacol. 2019;10:123. doi: 10.3389/fphar.2019.00123. PMID 30846939

Fotis C, Antoranz A, Hatziavramidis D, SakellaropoulosT, Alexopoulos LG. Network-based technologies for early drug discovery. Drug Discov Today. 2018;23:626–635. doi: 10.1016/j.drudis.2017.12.001. PMID 29294361.

Reni. A, Dewi. S. Solid dispersion as a potential approach to improve dissolution and bioavailability of curcumin from turmeric (curcuma longa l.). Int J App Pharm. 2023;15:37-47. doi:10.22159/ijap.2023v15i5.48295.

Ru J, Li P, Wang J, Zhou W, Li B, Huang C, et al. TCMSP: a database of systems pharmacology for drug discovery from herbal medicines. J Cheminform. 2014;6:13. doi: 10.1186/1758-2946-6-13. PMID 24735618.

Shang J, Li Q, Jiang T, Bi L, Lu Y, Jiao J, et al. Systems pharmacology, proteomics and in vivo studies identification of mechanisms of cerebral ischemia injury amelioration by Huanglian Jiedu Decoction. J Ethnopharmacol. 2022;293:115244. doi: 10.1016/j.jep.2022.115244. PMID 35378193.

Qin T, Wu L, Hua Q, Song Z, Pan Y, Liu T. Prediction of the mechanisms of action of Shenkang in chronic kidney disease: A network pharmacology study and experimental validation. J Ethnopharmacol. 2020;246:112128. doi: 10.1016/j.jep.2019.112128. PMID 31386888.

Tian S, Wang J, Li Y, Li D, Xu L, Hou T. The application of in silico drug-likeness predictions in pharmaceutical research. Adv Drug Deliv Rev. 2015;86:2-10. doi: 10.1016/j.addr.2015.01.009. PMID 25666163.

Kohl M, Wiese S, Warscheid B. Cytoscape: software for visualization and analysis of biological networks. Methods Mol Biol. 2011;696:291-303. doi: 10.1007/978-1-60761-987-1_18. PMID 21063955.

Wu L, Chen Y, Chen M, Yang Y, Che Z, Li Q, et al. Application of network pharmacology and molecular docking to elucidate the potential mechanism of Astragalus-Scorpion against prostate cancer. Andrologia. 2021;53(9):e14165. doi: 10.1111/and.14165. PMID 34185887.

Yeung N, Cline MS, Kuchinsky A, Smoot ME, Bader GD. Exploring biological networks with Cytoscape software. Curr Protoc Bioinformatics. 2008;Chapter8:8.13.1-8.13.20. doi: 10.1002/0471250953.bi0813s23. PMID 18819078.

Szklarczyk D, Franceschini A, Kuhn M, Simonovic M, Roth A, Minguez P et al. The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Res. 2011;39(Database issue):D561-8. doi: 10.1093/nar/gkq973. PMID 21045058.

Szklarczyk D, Gable A.L, Lyon D, Junge A, Wyder S, Huerta-Cepas J, et al. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 2019;47(D1):D607-D613. doi: 10.1093/nar/gky1131. PMID 30476243.

Zhang YL, Yin Q, Peng HM, Huang R, Zhou JW, Liu LH et al. Network pharmacology analysis and experimental validation to explore the mechanism of Hanchuan Zupa Granule in asthma. J Ethnopharmacol. 2021;281:114534. doi: 10.1016/j.jep.2021.114534. PMID 34419609.

Dong Y, Zhao Q, Wang Y. Network pharmacology-based investigation of potential targets of astragalus membranaceous-angelica sinensis compound acting on diabetic nephropathy. Sci Rep. 2021;11(1):19496. doi: 10.1038/s41598-021-98925-6. PMID 34593896.

Wang X, He Q, Chen Q, Xue B, Wang J, Wang T et al. Network pharmacology combined with metabolomics to study the mechanism of Shenyan Kangfu Tablets in the treatment of diabetic nephropathy. J Ethnopharmacol. 2021;270:113817. doi: 10.1016/j.jep.2021.113817. PMID 33444720.

Duan C, Li Y, Dong X, Xu W, Ma Y. Network Pharmacology and Reverse Molecular Docking-Based Prediction of the Molecular Targets and Pathways for Avicularin Against Cancer. Comb Chem High Throughput Screen. 2019;22(1):4-12. doi: 10.2174/1386207322666190206163409. PMID 30727880.

Tong H, Yu M, Fei C, Ji D, Dong J, Su L et al. Bioactive constituents and the molecular mechanism of Curcumae Rhizoma in the treatment of primary dysmenorrhea based on network pharmacology and molecular docking. Phytomedicine. 2021;86:153558. doi: 10.1016/j.phymed.2021.153558. PMID 33866197.

Zhang L, Han L, Wang X, Wei Y, Zheng J, Zhao L et al. Exploring the mechanisms underlying the therapeutic effect of Salvia miltiorrhiza in diabetic nephropathy using network pharmacology and molecular docking. Biosci Rep. 2021;41(6):BSR20203520. doi: 10.1042/BSR20203520. PMID 33634308.

Pinzi L, Rastelli G. Molecular Docking: Shifting Paradigms in Drug Discovery. Int J Mol Sci. 2019;20(18):4331. doi: 10.3390/ijms20184331. PMID 31487867.

Liu C, Liu J, Zheng Y, Qu J, Yang W, Tang X, et al. Subchronic oral toxicity study of rhubarb extract in Sprague-Dawley rats. Regul Toxicol Pharmacol. 2021;123:104921. doi: 10.1016/j.yrtph.2021.104921. PMID 33894279.

Li X, Wei S, Niu S, Ma X, Li H, Jing M, et al. Network pharmacology prediction and molecular docking-based strategy to explore the potential mechanism of Huanglian Jiedu Decoction against sepsis. Comput Biol Med. 2022;144:105389. doi: 10.1016/j.compbiomed.2022.105389. PMID 35303581.

Xie Y, Shao R, Lin Y, Wang C, Tan Y, Xie W, et al. Improved Therapeutic Efficiency against Obesity through Transdermal Drug Delivery Using Microneedle Arrays. Pharmaceutics. 2021;13(6):827. doi: 10.3390/pharmaceutics13060827. PMID 34199630.

Yuan C, Wang MH, Wang F, Chen PY, Ke XG, Yu B, et al. Network pharmacology and molecular docking reveal the mechanism of Scopoletin against non-small cell lung cancer. Life Sci. 2021;270:119105. doi: 10.1016/j.lfs.2021.119105. PMID 33497736.

Cui Q, Zhang YL, Ma YH, Yu HY, Zhao XZ, Zhang LH, et al. A network pharmacology approach to investigate the mechanism of Shuxuening injection in the treatment of ischemic stroke. J Ethnopharmacol. 2020;257:112891. doi: 10.1016/j.jep.2020.112891. PMID 32315738.

Dhanunjava S, Chitra V. Potential herb-drug interaction of decalepis hamiltonii via P-GP mediated pharmacokinetic interaction with fexofenadine in rats:an in situ and in vivo study. Int J App Pharm. 2023;15(5):128-133. doi: 10.22159/ijap.2023v15i5.48677.

Nounagnon MS, Dah-Nouvlessounon D, N'Tcha C, Legba B, Baba-Moussa L. Phytochemistry and biological activities of crateva adansonii extracts. Int J Pharm Pharm Sci. 2018;10(9):62-67. doi: 10.22159/ijpps.2018v10i9.27197.

Fan W, Chang J, Fu P. Endocrine therapy resistance in breast cancer: current status, possible mechanisms and overcoming strategies. Future Med Chem. 2015;7(12):1511-9. doi: 10.4155/fmc.15.93. PMID 26306654.

Chen JQ, Brown TR, Russo J. Regulation of energy metabolism pathways by estrogens and estrogenic chemicals and potential implications in obesity associated with increased exposure to endocrine disruptors. Biochim Biophys Acta. 2009;1793(7):1128-43. doi: 10.1016/j.bbamcr.2009.03.009. PMID 19348861.

Gérard C, Brown KA. Obesity and breast cancer - Role of estrogens and the molecular underpinnings of aromatase regulation in breast adipose tissue. Mol Cell Endocrinol. 2018;466:15-30. doi: 10.1016/j.mce.2017.09.014. PMID 28919302.

Nasrin S, Islam MN, Tayab MA, Nasrin MS, Siddique MA, Emran TB et al. Chemical profiles and pharmacological insights of Anisomeles indica Kuntze: An experimental chemico-biological interaction. Biomed Pharmacother. 2022;149:112842. doi: 10.1016/j.biopha.2022.112842. PMID 35325851.

Published

07-11-2023

How to Cite

ZHANG, G., WANG, H., KHATTAK, S. U., LV, H., WANG, . L., LI, X., SUN, X., & SHI, Y. (2023). EFFECT OF RHUBARB FREE ANTHRAQUINONES ON OBESITY IN RATS AND ITS POTENTIAL MECHANISM. International Journal of Applied Pharmaceutics, 15(6), 142–152. https://doi.org/10.22159/ijap.2023v15i6.49272

Issue

Vol 15, Issue 6 (Nov-Dec), 2023

Section

Original Article(s)

Copyright (c) 2023 GUIFANG ZHANG, HAIJIAO WANG, SAEED ULLAK KHATTAK, HUIJUAN LV, LIFANG WANG, XUEFENG LI, XIUXIA SUN, YANBIN SHI

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

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