Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Deciphering Multi-target Pharmacological Mechanism of Cucurbita pepo Seeds against Kidney Stones: Network Pharmacology and Molecular Docking Approach

Author(s): Aqsa Shahzadi, Usman Ali Ashfaq*, Mohsin Khurshid*, Muhammad Atif Nisar, Asad Syed and Ali H. Bahkali

Volume 30, Issue 4, 2024

Published on: 10 January, 2024

Page: [295 - 309] Pages: 15

DOI: 10.2174/0113816128271781231104151155

Price: $65

Abstract

Background: Urolithiasis is a prevalent condition with significant morbidity and economic implications. The economic burden associated with urolithiasis primarily stems from medical expenses. Previous literature suggests that herbal plants, including Cucurbita pepo, have lithotriptic capabilities. C. pepo is an annual, herbaceous, widely grown, and monoecious vegetative plant known for its antioxidants, fibers, and fatty acids. Recent studies on C. pepo seeds have shown therapeutic potential in reducing bladder stones and urodynamic illnesses, like kidney stones. However, the precise molecular and pharmacological mechanisms are unclear.

Objective: In this research, we employed network pharmacology and molecular docking to examine the active compounds and biological mechanisms of Cucurbita pepo against kidney stones.

Methods: Active constituents were obtained from previous studies and the IMPPAT database, with their targets predicted using Swiss target prediction. Kidney stone-associated genes were collected from DisGeNET and GeneCards. The active constituent-target-pathway network was constructed using Cytoscape, and the target protein-protein interaction network was generated using the STRING database. Gene enrichment analysis of C. pepo core targets was conducted using DAVID. Molecular docking was performed to identify potential kidney stone-fighting agents.

Results: The findings revealed that Cucurbita pepo contains 18 active components and has 192 potential gene targets, including AR, EGFR, ESR1, AKT1, MAPK3, SRC, and MTOR. Network analysis demonstrated that C. pepo seeds may prevent kidney stones by influencing disease-related signaling pathways. Molecular docking indicated that key kidney stone targets (mTOR, EGFR, AR, and ESR1) effectively bind with active constituents of C. pepo.

Conclusion: These findings provide insight into the anti-kidney stone effects of Cucurbita pepo at a molecular level. In conclusion, this study contributes to understanding the potential of Cucurbita pepo in combating kidney stones and lays the foundation for further research.

Keywords: Cucurbita pepo, lithotriptic, urolithiasis, herbal medicine, signaling pathways, gene targets.

« Previous Next »
[1]
Sofia NH, Walter TM, Sanatorium T. Prevalence and risk factors of kidney stone. Glob J Res Anal 2016; 5(3): 183-7.
[2]
Ansari A, Singh S, Khinchi M, Shama P, Mahaver M. A brief review on: Kidney stone. Asian J Pharmaceut Res Devel 2017; 5(2): 1-9.
[3]
Liu Y, Chen Y, Liao B, et al. Epidemiology of urolithiasis in Asia. Asian J Urol 2018; 5(4): 205-14.
[http://dx.doi.org/10.1016/j.ajur.2018.08.007] [PMID: 30364478]
[4]
Wang Z, Zhang Y, Wei W. Effect of dietary treatment and fluid intake on the prevention of recurrent calcium stones and changes in urine composition: A meta-analysis and systematic review. PLoS One 2021; 16(4): e0250257.
[http://dx.doi.org/10.1371/journal.pone.0250257] [PMID: 33872340]
[5]
Aggarwal R, Srivastava A, Jain SK, Sud R, Singh R. Renal stones: A clinical review. Eur Med J Urol 2017; 5(1): 98-103.
[http://dx.doi.org/10.33590/emjurol/10310556]
[6]
Ljunghall S, Danielson BG. A prospective study of renal stone recurrences. Br J Urol 1984; 56(2): 122-4.
[http://dx.doi.org/10.1111/j.1464-410X.1984.tb05346.x] [PMID: 6498430]
[7]
Khan F, Haider MF, Singh MK, Sharma P, Kumar T, Neda EN. A comprehensive review on kidney stones, its diagnosis and treatment with allopathic and ayurvedic medicines. Urol Nephrol Open Access J 2019; 7(4): 69-74.
[http://dx.doi.org/10.15406/unoaj.2019.07.00247]
[8]
Singh VK, Rai PK. Kidney stone analysis techniques and the role of major and trace elements on their pathogenesis: A review. Biophys Rev 2014; 6(3-4): 291-310.
[http://dx.doi.org/10.1007/s12551-014-0144-4] [PMID: 28510032]
[9]
Alelign T, Petros B. 2018; Kidney stone disease: An update on current concepts. Adv Urol 2018; 2018: 3068365.
[http://dx.doi.org/10.1155/2018/3068365]
[10]
Kamboj VP. Herbal medicine. Curr Sci 2000; 78(1): 35-9.
[11]
Gunjan M, Naing TW, Saini RS, Ahmad A, Naidu JR, Kumar I. Marketing trends & future prospects of herbal medicine in the treatment of various disease. World J Pharm Res 2015; 4(9): 132-55.
[12]
Omotayo FO, Borokini TI. Comparative phytochemical and ethnomedicinal survey of selected medicinal plants in Nigeria. Sci Res Essays 2012; 7(9): 989-99.
[13]
Paris HS, Yonash N, Portnoy V, Mozes-Daube N, Tzuri G, Katzir N. Assessment of genetic relationships in Cucurbita pepo (Cucurbitaceae) using DNA markers. Theor Appl Genet 2003; 106(6): 971-8.
[http://dx.doi.org/10.1007/s00122-002-1157-0] [PMID: 12671744]
[14]
Adnan M, Gul S, Batool S, et al. A review on the ethnobotany, phytochemistry, pharmacology and nutritional composition of Cucurbita pepo L. J Phytopharmacol 2017; 6(2): 133-9.
[http://dx.doi.org/10.31254/phyto.2017.6211]
[15]
Ratnam N, Naijibullah M, Ibrahim M. A review on Cucurbita pepo. Int J Pharm Phytochem Res 2017; 9: 1190-4.
[16]
Zdunczyk Z, Minakowski D, Frejnagel S, Flis M. Comparative study of the chemical composition and nutritional value of pumpkin seed cake, soybean meal and casein. Nahrung 1999; 43(6): 392-5.
[http://dx.doi.org/10.1002/(SICI)1521-3803(19991201)43:6<392::AID-FOOD392>3.0.CO;2-2]
[17]
Adepoju A, Adebanjo A. Effect of consumption of Cucurbita pepo seeds on haematological and biochemical parameters. Afr J Pharm Pharmacol 2009; 5(1): 18-22.
[http://dx.doi.org/10.5897/AJPP10.186]
[18]
Suphakarn VS, Yarnnon C, Ngunboonsri P. The effect of pumpkin seeds on oxalcrystalluria and urinary compositions of children in hyperendemic area. Am J Clin Nutr 1987; 45(1): 115-21.
[http://dx.doi.org/10.1093/ajcn/45.1.115] [PMID: 3799495]
[19]
Xu Z, Jin-Zhi O, Yong-Shang Z, Balla TY, Xi-Cai Z, Si-Wei Z. Effect of the extracts of pumpkin seeds on the urodynamics of rabbits: An experimental study. J Tongji Med Univ 1994; 14(4): 235-8.
[http://dx.doi.org/10.1007/BF02897676] [PMID: 7760436]
[20]
Thakur N, Jain SK, Saxena R. Evaluation of diuretic and antinephrolithiatic activity of Cucurbita pepo seed in experimental rats. J Drug Deliv Ther 2022; 12(4-S): 93-5.
[http://dx.doi.org/10.22270/jddt.v12i4-S.5523]
[21]
Luo T, Lu Y, Yan S, Xiao X, Rong X, Guo J. Network pharmacology in research of Chinese medicine formula: Methodology, application and prospective. Chin J Integr Med 2020; 26(1): 72-80.
[http://dx.doi.org/10.1007/s11655-019-3064-0] [PMID: 30941682]
[22]
Dong Y, Hao L, Fang K. A network pharmacology perspective for deciphering potential mechanisms of action of Solanum nigrum L. in bladder cancer. BMC Complement Med Ther 2021; 21: 45.
[23]
Kitchen DB. Computer-aided drug discovery research at a global contract research organization. J Comput Aided Mol Des 2017; 31(3): 309-18.
[http://dx.doi.org/10.1007/s10822-016-9991-3] [PMID: 27804014]
[24]
Noor F, Rehman A, Ashfaq UA, et al. Integrating network pharmacology and molecular docking approaches to decipher the multi- target pharmacological mechanism of Abrus precatorius L. acting on diabetes. Pharmaceuticals (Basel) 2022; 15(4): 414.
[http://dx.doi.org/10.3390/ph15040414] [PMID: 35455411]
[25]
Zhang X, Shen T, Zhou X, et al. Network pharmacology based virtual screening of active constituents of Prunella vulgaris L. and the molecular mechanism against breast cancer. Sci Rep 2020; 10(1): 15730.
[http://dx.doi.org/10.1038/s41598-020-72797-8] [PMID: 32978480]
[26]
Tabassum S, Khalid HR, Haq W, et al. Implementation of system pharmacology and molecular docking approaches to explore active compounds and mechanism of ocimum sanctum against tuberculosis. Processes (Basel) 2022; 10(2): 298.
[http://dx.doi.org/10.3390/pr10020298]
[27]
Perez Gutierrez RM. Review of Cucurbita pepo (pumpkin) its phytochemistry and pharmacology. Med Chem 2016; 6(1): 12-21.
[28]
Ethiraj S, Balasundaram J. Phytochemical and biological activity of Cucurbita seed extract. J Adv Biotechnol 2016; 6(1): 813-21.
[http://dx.doi.org/10.24297/jbt.v6i1.4821]
[29]
Kotova EE, Kotov SA, Gontova TM, Kotov AG. Study of qualitative and quantitative content of amino acids in pumpkin seeds for further standardization of the herbal drug. Eur Pharm J 2020; 67(1): 27-32.
[http://dx.doi.org/10.2478/afpuc-2020-0001]
[30]
Mohanraj K, Karthikeyan BS, Vivek-Ananth RP, et al. IMPPAT: A curated database of Indian medicinal plants, phytochemistry and therapeutics. Sci Rep 2018; 8(1): 4329.
[http://dx.doi.org/10.1038/s41598-018-22631-z] [PMID: 29531263]
[31]
Rashid F, Javaid A, Mahmood-ur-Rahman , et al. Integrating pharmacological and computational approaches for the phytochemical analysis of Syzygium cumini and its anti-diabetic potential. Molecules 2022; 27(17): 5734.
[http://dx.doi.org/10.3390/molecules27175734] [PMID: 36080496]
[32]
Li AP. Screening for human ADME/Tox drug properties in drug discovery. Drug Discov Today 2001; 6(7): 357-66.
[http://dx.doi.org/10.1016/S1359-6446(01)01712-3] [PMID: 11267922]
[33]
Tao W, Xu X, Wang X, et al. Network pharmacology-based prediction of the active ingredients and potential targets of Chinese herbal Radix Curcumae formula for application to cardiovascular disease. J Ethnopharmacol 2013; 145(1): 1-10.
[http://dx.doi.org/10.1016/j.jep.2012.09.051] [PMID: 23142198]
[34]
Gfeller D, Grosdidier A, Wirth M, Daina A, Michielin O, Zoete V. SwissTargetPrediction: A web server for target prediction of bioactive small molecules. Nucleic Acids Res 2014; 42(W1): W32-8.
[http://dx.doi.org/10.1093/nar/gku293] [PMID: 24792161]
[35]
Zhang MM, Wang D, Lu F, et al. Identification of the active substances and mechanisms of ginger for the treatment of colon cancer based on network pharmacology and molecular docking. BioData Min 2021; 14(1): 1-16.
[http://dx.doi.org/10.1186/s13040-020-00232-9] [PMID: 33430939]
[36]
Huang D, Sherman BT, Tan Q, et al. The DAVID gene functional classification tool: A novel biological module-centric algorithm to functionally analyze large gene lists. Genome Biol 2007; 8(9): R183.
[http://dx.doi.org/10.1186/gb-2007-8-9-r183] [PMID: 17784955]
[37]
Li H, Hung A, Yang AWH. Herb-target virtual screening and network pharmacology for prediction of molecular mechanism of Danggui Beimu Kushen Wan for prostate cancer. Sci Rep 2021; 11(1): 6656.
[http://dx.doi.org/10.1038/s41598-021-86141-1] [PMID: 33758314]
[38]
Lu X, Zheng Y, Wen F, et al. Study of the active ingredients and mechanism of Sparganii rhizoma in gastric cancer based on HPLC-Q-TOF-MS/MS and network pharmacology. Sci Rep 2021; 11(1): 1905.
[http://dx.doi.org/10.1038/s41598-021-81485-0] [PMID: 33479376]
[39]
Mering C, Huynen M, Jaeggi D, Schmidt S, Bork P, Snel B. STRING: A database of predicted functional associations between proteins. Nucleic Acids Res 2003; 31(1): 258-61.
[http://dx.doi.org/10.1093/nar/gkg034] [PMID: 12519996]
[40]
Berman HM, Battistuz T, Bhat TN, et al. The protein data bank. Acta Crystallogr D Biol Crystallogr 2002; 58(6): 899-907.
[http://dx.doi.org/10.1107/S0907444902003451] [PMID: 12037327]
[41]
Studio D. Discovery Studio. 2008. Available From: https://en.wikipedia.org/wiki/Discovery_Studio
[42]
Dallakyan S, Olson AJ. Small-molecule library screening by docking with PyRx. Chemical biology. Springer 2015; pp. 243-50.
[http://dx.doi.org/10.1007/978-1-4939-2269-7_19]
[43]
Martinez X, Chavent M, Baaden M. Visualizing protein structures - tools and trends. Biochem Soc Trans 2020; 48(2): 499-506.
[http://dx.doi.org/10.1042/BST20190621] [PMID: 32196545]
[44]
Chow SC. Bioavailability and bioequivalence in drug development. Wiley Interdiscip Rev Comput Stat 2014; 6(4): 304-12.
[http://dx.doi.org/10.1002/wics.1310] [PMID: 25215170]
[45]
Daina A, Michielin O, Zoete V. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep 2017; 7(1): 42717.
[http://dx.doi.org/10.1038/srep42717] [PMID: 28256516]
[46]
Khan SR, Pearle MS, Robertson WG, et al. Kidney stones. Nat Rev Dis Primers 2016; 2(1): 16008.
[http://dx.doi.org/10.1038/nrdp.2016.8] [PMID: 27188687]
[47]
Hoffman A, Braun MM, Khayat M. Kidney disease: Kidney stones. FP Essent 2021; 509: 33-8.
[PMID: 34643363]
[48]
Frassetto L, Kohlstadt I. Treatment and prevention of kidney stones: An update. Am Fam Physician 2011; 84(11): 1234-42.
[PMID: 22150656]
[49]
Garbens A, Pearle MS. Causes and prevention of kidney stones: Separating myth from fact. BJU Int 2021; 128(6): 661-6.
[http://dx.doi.org/10.1111/bju.15532] [PMID: 34192414]
[50]
Chen Z, Wang X, Li Y, et al. Comparative network pharmacology analysis of classical TCM prescriptions for chronic liver disease. Front Pharmacol 2019; 10: 1353.
[http://dx.doi.org/10.3389/fphar.2019.01353] [PMID: 31824313]
[51]
Berger SI, Iyengar R. Network analyses in systems pharmacology. Bioinformatics 2009; 25(19): 2466-72.
[http://dx.doi.org/10.1093/bioinformatics/btp465] [PMID: 19648136]
[52]
Liang J, Wang M, Olounfeh KM, Zhao N, Wang S, Meng F. Network pharmacology-based identifcation of potential targets of the flower of Trollius chinensis bunge acting on anti-inflammatory effectss. Sci Rep 2019; 9(1): 8109.
[http://dx.doi.org/10.1038/s41598-019-44538-z] [PMID: 31147584]
[53]
Batool S, Javed MR, Aslam S, et al. Network pharmacology and bioinformatics approach reveals the multi-target pharmacological mechanism of Fumaria indica in the treatment of liver cancer. Pharmaceuticals (Basel) 2022; 15(6): 654.
[http://dx.doi.org/10.3390/ph15060654] [PMID: 35745580]
[54]
Saleem U, Shehzad A, Shah S, et al. Antiparkinsonian activity of Cucurbita pepo seeds along with possible underlying mechanism. Metab Brain Dis 2021; 36(6): 1231-51.
[http://dx.doi.org/10.1007/s11011-021-00707-6] [PMID: 33759084]
[55]
Damiano R, Cai T, Fornara P, Franzese CA, Leonardi R, Mirone V. The role of Cucurbita pepo in the management of patients affected by lower urinary tract symptoms due to benign prostatic hyperplasia: A narrative review. Arch Ital Urol Androl 2016; 88(2): 136-43.
[http://dx.doi.org/10.4081/aiua.2016.2.136] [PMID: 27377091]
[56]
Liang L, Li L, Tian J, et al. Androgen receptor enhances kidney stone-CaOx crystal formation via modulation of oxalate biosynthesis & oxidative stress. Mol Endocrinol 2014; 28(8): 1291-303.
[http://dx.doi.org/10.1210/me.2014-1047] [PMID: 24956378]
[57]
Gui Y, Dai C. mTOR signaling in kidney diseases. Kidney360 2020; 1(11): 1319-27.
[http://dx.doi.org/10.34067/KID.0003782020] [PMID: 35372878]
[58]
Unno R, Kawabata T, Taguchi K, et al. Deregulated MTOR (mechanistic target of rapamycin kinase) is responsible for autophagy defects exacerbating kidney stone development. Autophagy 2020; 16(4): 709-23.
[http://dx.doi.org/10.1080/15548627.2019.1635382] [PMID: 31257986]

Rights & Permissions Print Cite
Article Metrics
27
3
© 2024 Bentham Science Publishers | Privacy Policy