Phytochemicals as weapons against drug resistance

Authors

DOI:

https://doi.org/10.14719/pst.2495

Keywords:

ABC transporters, efflux pump modulation, Gram-negative bacteria, MDR, nano-biotics, PDR, uro-pathogens

Abstract

Phytochemicals are plant-based products with high medicinal value. These metabolites effectively target disease-causing microbes. Drug-resistant pathogens have developed mechanisms to sustain themselves even with inhibitors. Drug resistance has emerged as a global giant, causing all available treatment options to fail. The solution to this problem is in the phytochemicals of plants with antibacterial and drug resistance modulation properties. Phytochemicals might be able to get rid of efflux pumps, drug-modulating enzymes, resistance genes, quorum sensing, and biofilm, all of which cause pathogens to be resistant to drugs. Moreover, anti-obesogenic and cardioprotective properties are also observed in phytochemicals. Additionally, studies show the success of phytochemical-based nanoparticles in drug resistance regulation. This review emphasizes phytochemicals' different mechanisms of action and their derivatives in curbing drug-resistant pathogens and cancer cells.

Downloads

Download data is not yet available.

Author Biographies

Deshpande K Medini, Department of Life Sciences, Christ (Deemed to be University), Bangalore-560029, India

 

 

Pappuswamy Manikantan, Department of Life Sciences, Christ (Deemed to be) University

 

 

Chaudhary Aditi, Department of Life Sciences, Christ (Deemed to be University), Bangalore-560029, India

 

 

Kadanthottu Sebastian Joseph, Department of Life Sciences, Christ (Deemed to be University), Bangalore-560029, India

 

 

Alagamuthu Karthick Kumar, Selvamm Arts and Science College (Autonomous), Namakkal, Tamil Nadu

 

 

References

Yang L, Wen KS, Ruan X, Zhao YX, Wei F, Wang Q. Response of plant secondary metabolites to environmental factors. Molecules. 2018;23(4):762.

Sharma A, Sharma S, Kumar A, Kumar V, Sharma AK. Plant secondary metabolites: An introduction of their chemistry and biological significance with physicochemical aspect. InPlant Secondary Metabolites: Physico-Chemical Properties and Therapeutic Applications 2022 pp. 1-45. Singapore: Springer Nature Singapore. https://doi.org/10.1007/978-981-16-4779-6_1

Roy M, Datta A. Fundamentals of Phytochemicals. In: Roy M, Datta A, editors. Cancer Genetics and Therapeutics: Focus on Phytochemicals [Internet]. Singapore: Springer; 2019 p. 49–81. Available from: https://doi.org/10.1007/978-981-13-9471-3_3

Bansal A, Priyadarsini C, Bansal A, Priyadarsini C. Medicinal Properties of Phytochemicals and Their Production. In: Natural Drugs from Plants. IntechOpen; 2021. Available from: https://www.intechopen.com/chapters/77565

Pagliaro B, Santolamazza C, Simonelli F, Rubattu S. Phytochemical Compounds and Protection from Cardiovascular Diseases: A State of the Art. BioMed Res Int. 2015;2015:e918069.

Antimicrobial resistance [Internet]. Available from: https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance [cited 2023 Sep 17]

Kurt Yilmaz N, Schiffer CA. Introduction: Drug Resistance. Chem Rev. 2021;121(6):3235–7.

Suganya T, Packiavathy IA, Aseervatham G, Carmona A, Rashmi V, Mariappan S, Devi NR, Ananth DA. Tackling multiple-drug-resistant bacteria with conventional and complex phytochemicals. Frontiers in Cellular and Infection Microbiology. 2022;12:883839.

Vasan N, Baselga J, Hyman DM. A view on drug resistance in cancer. Nature. 2019;575(7782):299-309.

Mansoori B, Mohammadi A, Davudian S, Shirjang S, Baradaran B. The Different Mechanisms of Cancer Drug Resistance: A Brief Review. Adv Pharm Bull. 2017;7(3):339–48.

Centers for Disease Control and Prevention (U.S.). Antibiotic resistance threats in the United States, 2019 [Internet]. Centers for Disease Control and Prevention (U.S.); 2019 Nov [cited 2023 Feb 27]. Available from: https://stacks.cdc.gov/view/cdc/82532

Henderson PJF, Maher C, Elbourne LDH, Eijkelkamp BA, Paulsen IT, Hassan KA. Physiological Functions of Bacterial “Multidrug” Efflux Pumps. Chem Rev. 2021;121(9):5417–78.

Yadav H, Mahalvar A, Pradhan M, Yadav K, Kumar Sahu K, Yadav R. Exploring the potential of phytochemicals and nanomaterial: A boon to antimicrobial treatment. Med Drug Discov. 2023;17:100151.

Tiwari P, Khare T, Shriram V, Bae H, Kumar V. Plant synthetic biology for producing potent phyto-antimicrobials to combat antimicrobial resistance. Biotechnol Adv. 2021;48:107729.

Khare T, Anand U, Dey A, Assaraf YG, Chen ZS, Liu Z, Kumar V. Exploring phytochemicals for combating antibiotic resistance in microbial pathogens. Frontiers in pharmacology. 2021;12:720726.

Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2012;18(3):268–81.

Jubair N, Rajagopal M, Chinnappan S, Abdullah NB, Fatima A. Review on the Antibacterial Mechanism of Plant-Derived Compounds against Multidrug-Resistant Bacteria (MDR). Evid Based Complement Alternat Med. 2021;2021:e3663315.

Bukowski K, Kciuk M, Kontek R. Mechanisms of Multidrug Resistance in Cancer Chemotherapy. Int J Mol Sci. 2020;21(9):3233.

Juan-Carlos PDM, Perla-Lidia PP, Stephanie-Talia MM, Mónica-Griselda AM, Luz-María TE. ABC transporter superfamily. An updated overview, relevance in cancer multidrug resistance and perspectives with personalized medicine. Mol Biol Rep. 2021;48(2):1883–901.

Kumar A, Jaitak V. Natural products as multidrug resistance modulators in cancer. Eur J Med Chem. 2019;176:268–91.

Wink M. Current Understanding of Modes of Action of Multicomponent Bioactive Phytochemicals: Potential for Nutraceuticals and Antimicrobials. Annu Rev Food Sci Technol. 2022;13(1):337–59.

Roy M, Datta A, Roy M, Datta A. Improvement of Cancer Therapy Using Phytochemicals. Cancer Genetics and Therapeutics: Focus on Phytochemicals. 2019:139-64.

Recent advances in phytochemical-based Nano-formulation for drug-resistant Cancer. Med Drug Discov. 2021;10:100082.

Zhao X, Yu Z, Ding T. Quorum-Sensing Regulation of Antimicrobial Resistance in Bacteria. Microorganisms. 2020;8(3):425.

Qais FA, Khan MS, Ahmad I. Broad-spectrum quorum sensing and biofilm inhibition by green tea against gram-negative pathogenic bacteria: Deciphering the role of phytocompounds through molecular modelling. Microb Pathog. 2019;126:379–92.

Robben PM, Ayalew MD, Chung KK, Ressner RA. Multi-Drug-Resistant Organisms in Burn Infections. Surg Infect. 2021 Feb;22(1):103–12.

Ali SS, El-Zawawy NA, Al-Tohamy R, El-Sapagh S, Mustafa AM, Sun J. Lycium shawii Roem. & Schult.: A new bioactive antimicrobial and antioxidant agent to combat multi-drug/pan-drug resistant pathogens of wound burn infections. J Tradit Complement Med. 2020;10(1):13–25.

Qin S, Xiao W, Zhou C, Pu Q, Deng X, Lan L, et al. Pseudomonas aeruginosa: pathogenesis, virulence factors, antibiotic resistance, interaction with host, technology advances and emerging therapeutics. Signal Transduct Target Ther. 2022;7(1):1–27.

Rajkumari J, Borkotoky S, Murali A, Busi S. Anti-quorum sensing activity of Syzygium jambos (L.) Alston against Pseudomonas aeruginosa PAO1 and identification of its bioactive components. South Afr J Bot. 2018;118:151–7.

Samreen, Qais FA, Ahmad I. Anti-quorum sensing and biofilm inhibitory effect of some medicinal plants against gram-negative bacterial pathogens: in vitro and in silico investigations. Heliyon. 2022;8(10):e11113.

Hughes D, Andersson DI. Environmental and genetic modulation of the phenotypic expression of antibiotic resistance. FEMS Microbiol Rev. 2017;41(3):374–91.

Depardieu F, Podglajen I, Leclercq R, Collatz E, Courvalin P. Modes and Modulations of Antibiotic Resistance Gene Expression. Clin Microbiol Rev. 2007;20(1):79–114.

Moriguchi K, Zoolkefli FIRM, Abe M, Kiyokawa K, Yamamoto S, Suzuki K. Targeting Antibiotic Resistance Genes Is a Better Approach to Block Acquisition of Antibiotic Resistance Than Blocking Conjugal Transfer by Recipient Cells: A Genome-Wide Screening in Escherichia coli. Front Microbiol. 2020;10:2939.

Kang J, Liu L, Liu M, Wu X, Li J. Antibacterial activity of gallic acid against Shigella flexneri and its effect on biofilm formation by repressing mdoH gene expression. Food Control. 2018;;94:147–54.

Li T, Lu Y, Zhang H, Wang L, Beier RC, Jin Y, Wang W, Li H, Hou X. Antibacterial activity and membrane-targeting mechanism of aloe-emodin against Staphylococcus epidermidis. Frontiers in Microbiology. 2021;12:621866.

El-Shouny WA, Ali SS, Hegazy HM, Abd Elnabi MK, Ali A, Sun J. Syzygium aromaticum L.Traditional herbal medicine against cagA and vacA toxin genes-producing drug resistant Helicobacter pylori. J Tradit Complement Med. 2020;10(4):366–77.

Egorov AM, Ulyashova MM, Rubtsova MYu. Bacterial Enzymes and Antibiotic Resistance. Acta Naturae. 2018;10(4):33–48.

Sah SK, Rasool U, Hemalatha S. Andrographis paniculata extract inhibit growth, biofilm formation in multidrug resistant strains of Klebsiella pneumoniae. J Tradit Complement Med. 2020;10(6):599–604.

Mohanty H, Pachpute S, Yadav RP. Mechanism of drug resistance in bacteria: efflux pump modulation for designing of new antibiotic enhancers. Folia Microbiol (Praha). 2021;66(5):727–39.

Du D, Wang-Kan X, Neuberger A, van Veen HW, Pos KM, Piddock LJV, et al. Multidrug efflux pumps: structure, function and regulation. Nat Rev Microbiol. 2018;16(9):523–39.

Oyedara OO, Fadare OA, Franco-Frías E, Heredia N, García S. Computational assessment of phytochemicals of medicinal plants from Mexico as potential inhibitors of Salmonella enterica efflux pump AcrB protein. J Biomol Struct Dyn. 2023;41(5):1776–89.

Dwivedi GR, Tyagi R, Sanchita, Tripathi S, Pati S, Srivastava SK, Darokar MP, Sharma A. Antibiotics potentiating potential of catharanthine against superbug Pseudomonas aeruginosa. Journal of Biomolecular Structure and Dynamics. 2018;36(16):4270-84.

Tinoush B, Shirdel I, Wink M. Phytochemicals: Potential Lead Molecules for MDR Reversal. Front Pharmacol. 2020;11:832.

Ranjan A, Ramachandran S, Gupta N, Kaushik I, Wright S, Srivastava S, et al. Role of Phytochemicals in Cancer Prevention. Int J Mol Sci. 2019;20(20):4981.

Cho CJ, Yu CP, Wu CL, Ho JY, Yang CW, Yu DS. Decreased drug resistance of bladder cancer using phytochemicals treatment. Kaohsiung J Med Sci. 2021;37(2):128–35.

Mora Lagares L, Novi? M. Recent Advances on P-Glycoprotein (ABCB1) Transporter Modelling with In Silico Methods. International Journal of Molecular Sciences. 2022;23(23):14804.

Kemboi D, Siwe-Noundou X, Krause RW, Langat MK, Tembu VJ. Euphorbia diterpenes: An update of isolation, structure, pharmacological activities and structure–activity relationship. Molecules. 2021;26(16):5055.

Neto S, Duarte N, Pedro C, Spengler G, Molnár J, Ferreira MJU. Effective MDR reversers through phytochemical study of Euphorbia boetica. Phytochem Anal. 2019;30(5):498–511.

Teng YN, Huang BH, Huang SY, Wu IT, Wu TS, Lee TE, et al. Cinnamophilin overcomes cancer multi-drug resistance via allosterically modulating human P-glycoprotein on both drug binding sites and ATPase binding sites. Biomed Pharmacother. 2021;144:112379.

Debnath P, Huirem RS, Dutta P, Palchaudhuri S. Epithelial-mesenchymal transition and its transcription factors. Biosci Rep. 2022;42(1):BSR20211754.

Dahmardeh Ghalehno A, Boustan A, Abdi H, Aganj Z, Mosaffa F, Jamialahmadi K. The Potential for Natural Products to Overcome Cancer Drug Resistance by Modulation of Epithelial-Mesenchymal Transition. Nutr Cancer. 2022;74(8):2686–712.

Farrerol overcomes the invasiveness of lung squamous cell carcinoma cells by regulating the expression of inducers of epithelial mesenchymal transition. Microb Pathog. 2019;131:278–82.

Chakraborty N, Jha D, Roy I, Kumar P, Gaurav SS, Marimuthu K, et al. Nanobiotics against antimicrobial resistance: harnessing the power of nanoscale materials and technologies. J Nanobiotechnology. 2022;20(1):375.

Role of capping agents in the application of nanoparticles in biomedicine and environmental remediation: recent trends and future prospects - PubMed [Internet]. [cited 2023 Sep 17]. Available from: https://pubmed.ncbi.nlm.nih.gov/33225973/

Anjum S, Hashim M, Malik SA, Khan M, Lorenzo JM, Abbasi BH, et al. Recent Advances in Zinc Oxide Nanoparticles (ZnO NPs) for Cancer Diagnosis, Target Drug Delivery, and Treatment. Cancers. 2021;13(18):4570.

Jagdish R, Nehra K. Bryophyllum pinnatum mediated synthesis of zinc oxide nanoparticles: characterization and application as biocontrol agents for multi-drug-resistant uropathogens. Heliyon. 2022;8(10):e11080.

Al Mashud MdA, Moinuzzaman Md, Hossain MdS, Ahmed S, Ahsan G, Reza A, et al. Green synthesis of silver nanoparticles using Cinnamomum tamala (Tejpata) leaf and their potential application to control multidrug resistant Pseudomonas aeruginosa isolated from hospital drainage water. Heliyon. 2022;8(7):e09920.

Khare T, Mahalunkar S, Shriram V, Gosavi S, Kumar V. Embelin-loaded chitosan gold nanoparticles interact synergistically with ciprofloxacin by inhibiting efflux pumps in multidrug-resistant Pseudomonas aeruginosa and Escherichia coli. Environ Res. 2021;199:111321.

Halder A, Jethwa M, Mukherjee P, Ghosh S, Das S, Helal Uddin ABM, et al. Lactoferrin-tethered betulinic acid nanoparticles promote rapid delivery and cell death in triple negative breast and laryngeal cancer cells. Artif Cells Nanomedicine Biotechnol. 2020 1;48(1):1362–71.

Isleem RM, Alzaharna MM, Sharif FA. Synergistic anticancer effect of combining metformin with olive (Olea europaea L.) leaf crude extract on the human breast cancer cell line MCF-7. J Med Plants 2020;8(2):30-7.

Plumbagin Enhances the Anticancer Efficacy of Cisplatin by Increasing Intracellular ROS in Human Tongue Squamous Cell Carcinoma [Internet]. [cited 2023 Feb 27]. Available from: https://www.hindawi.com/journals/omcl/2020/5649174/

?igu AB, Toma VA, Mo? AC, Jurj A, Moldovan CS, Fischer-Fodor E, et al. The Synergistic Antitumor Effect of 5-Fluorouracil Combined with Allicin against Lung and Colorectal Carcinoma Cells. Molecules. 2020;25(8):1947.

The synergistic anti-proliferative effect of the combination of diosmin and BEZ-235 (dactolisib) on the HCT-116 colorectal cancer cell line occurs through inhibition of the PI3K/Akt/mTOR/NF-?B axis | SpringerLink [Internet]. [cited 2023 Feb 27]. Available from: https://link.springer.com/article/10.1007/s11033-020-05327-4

Lee SH, Lee YJ. Synergistic anticancer activity of resveratrol in combination with docetaxel in prostate carcinoma cells. Nutr Res Pract. 2020;15(1):12–25.

Konuk HB, Ergüden B. Phenolic –OH group is crucial for the antifungal activity of terpenoids via disruption of cell membrane integrity. Folia Microbiol (Praha). 2020;65(4):775–83.

Sharifzadeh A, Khosravi AR, Shokri H, Shirzadi H. Potential effect of 2-isopropyl-5-methylphenol (thymol) alone and in combination with fluconazole against clinical isolates of Candida albicans, C. glabrata and C. krusei. J Mycol Médicale. 2018;28(2):294–9.

Pumival P, Tadtong S, Athikomkulchai S, Chittasupho C. Antifungal Activity and the Chemical and Physical Stability of Microemulsions Containing Citrus hystrix DC Leaf Oil. Nat Prod Commun. 2020;15(9):1934578X20957755.

Murugan DD, Balan D, Wong P. Adipogenesis and therapeutic potentials of antiobesogenic phytochemicals: Insights from preclinical studies. Phytother Res. 2021;35(11):5936–60.

Wu LY, Chen CW, Chen LK, Chou HY, Chang CL, Juan CC. Curcumin Attenuates Adipogenesis by Inducing Preadipocyte Apoptosis and Inhibiting Adipocyte Differentiation. Nutrients. 2019;11(10):2307.

Liébana-García R, Olivares M, Rodríguez-Ruano SM, Tolosa-Enguís V, Chulia I, Gil-Martínez L, et al. The Allium Derivate Propyl Propane Thiosulfinate Exerts Anti-Obesogenic Effects in a Murine Model of Diet-Induced Obesity. Nutrients. 2022;14(3):440.

Men X, Han X, Lee SJ, Oh G, Park KT, Han JK, et al. Anti-Obesogenic Effects of Sulforaphane-Rich Broccoli (Brassica oleracea var. italica) Sprouts and Myrosinase-Rich Mustard (Sinapis alba L.) Seeds In Vitro and In Vivo. Nutrients. 2022;14(18):3814.

Saad B, Ghareeb B, Kmail A. Metabolic and Epigenetics Action Mechanisms of Antiobesity Medicinal Plants and Phytochemicals. Evid-Based Complement Altern Med ECAM. 2021;2021:9995903.

Ahmad B, Friar EP, Vohra MS, Garrett MD, Serpell CJ, Fong IL, et al. Mechanisms of action for the anti-obesogenic activities of phytochemicals. Phytochemistry. 2020;180:112513.

Phytochemical characterization of Morus nigra fruit ultrasound?assisted ethanolic extract for its cardioprotective potential - Maqsood - 2022 - Journal of Food Biochemistry - Wiley Online Library [Internet]. [cited 2023 Sep 17]. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1111/jfbc.14335

Epure A, Pârvu AE, Vlase L, Benedec D, Hanganu D, Gheldiu AM, et al. Phytochemical Profile, Antioxidant, Cardioprotective and Nephroprotective Activity of Romanian Chicory Extract. Plants. 2021;10(1):64.

Zeng Y, Xiong Y, Yang T, Wang Y, Zeng J, Zhou S, et al. Icariin and its metabolites as potential protective phytochemicals against cardiovascular disease: From effects to molecular mechanisms. Biomed Pharmacother. 2022;147:112642.

Published

16-10-2023 — Updated on 23-10-2023

Versions

How to Cite

1.
Kruttika J, Medini DK, Stena Jesima R, Keerthi GR, Manikantan P, Aditi C, Kuppusamy Alagesan P, Joseph KS, Karthick Kumar A. Phytochemicals as weapons against drug resistance. Plant Sci. Today [Internet]. 2023 Oct. 23 [cited 2024 Dec. 27];10(sp2):212-9. Available from: https://horizonepublishing.com/journals/index.php/PST/article/view/2495

Issue

Section

Special issue on Mini Reviews

Most read articles by the same author(s)