MECHANISM OF ANTIMICROBIAL ACTION OF SINAPIC ACID INCORPORATED IRON OXIDE NANOFORMULATION AGAINST ORAL PATHOGENS
DOI:
https://doi.org/10.22159/ajpcr.2025v18i11.55991Keywords:
Sinapic acid, Fe2O3 nanoparticles, Antimicrobial activity, Oral pathogensAbstract
Objective: This study aimed to synthesize and characterize sinapic acid-incorporated Fe₂O3 nanoparticles (NPs) and to evaluate their antimicrobial mechanism of action against key oral pathogens.
Methods: Fe2O3 NPs were synthesized using cinnamon extract and subsequently functionalized with sinapic acid. The nanoformulation was characterized using ultraviolet (UV)–visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), and transmission electron microscopy (TEM) to confirm particle formation, surface functionalization, and morphology. Antimicrobial activity was assessed through agar well diffusion, time-kill curve, protein leakage, and cytoplasmic leakage assays against Streptococcus mutans, Lactobacillus spp., Candida albicans, Staphylococcus aureus, and Enterococcus faecalis.
Results: UV–visible spectra showed a characteristic absorption peak near 350 nm, confirming NP formation, while FTIR spectra indicated the presence of phenolic functional groups stabilizing the surface. TEM analysis revealed quasi-spherical NPs with an average size of ~20 nm. The nanoformulation displayed concentration-dependent antimicrobial activity, with S. mutans and Lactobacillus spp. showing inhibition zones >40 mm at 150 μg/mL. Time-kill assays demonstrated rapid reduction of microbial load, while leakage assays confirmed significant protein and cytoplasmic efflux, indicative of membrane disruption.
Conclusion: Sinapic acid-incorporated Fe2O3 NPs exert antimicrobial activity through a dual mechanism involving membrane disruption and reactive oxygen species (ROS) generation. Their nanoscale size, stability, and functionalization enhance efficacy compared to plain Fe2O3 NPs. These findings highlight their potential for applications in oral healthcare formulations and localized antimicrobial therapies, though further validation of ROS mechanisms and cytotoxicity is recommended.
Downloads
References
1. Zhu Y, Wang Y, Zhang S, Li J, Li X, Ying Y, et al. Association of polymicrobial interactions with dental caries development and prevention. Front Microbiol. 2023;14:1162380. doi: 10.3389/ fmicb.2023.1162380, PMID: 37275173
2. Durand R, Roufegarinejad A, Chandad F, Rompré PH, Voyer R, Michalowicz BS, et al. Dental caries are positively associated with periodontal disease severity. Clin Oral Investig. 2019;23(10):3811-9. doi: 10.1007/s00784-019-02810-6, PMID: 30693397
3. Li Y, Xiang Y, Ren H, Zhang C, Hu Z, Leng W, et al. Association between periodontitis and dental caries: A systematic review and meta-analysis. Clin Oral Investig. 2024;28(6):306. doi: 10.1007/s00784-024- 05687-2, PMID: 38727727
4. Loesche WJ. Microbiology of dental decay and periodontal disease. In: Baron S, editor. Medical Microbiology. 4th ed. Galveston, TX: University of Texas Medical Branch at Galveston; 1996. Available from: https://www.ncbi.nlm.nih.gov/books/NBK8259
5. Zhang JS, Chu CH, Yu OY. Oral microbiome and dental caries development. Dent J (Basel). 2022;10(10):184. doi: 10.3390/ dj10100184, PMID: 36285994
6. Vajjiravelu R, Palani B, Shanmugam R, Jayakodi S. Bioinspired nanoparticles mediated from bioactive plants and their therapeutic application in liver cancer. Biomed Mater Devices. 2025; 191:1-6. doi: 10.1007/s44174-025-00062-5
7. Giedraitienė A, Ružauskas M, Šiugždinienė R, Tučkutė S, Grigonis K, Milčius D. Development of antibacterial cotton textiles by deposition of Fe2O3 nanoparticles using low-temperature plasma sputtering. Nanomaterials (Basel). 2023;13(24):3106. doi: 10.3390/nano13243106, PMID: 38133003
8. Mohamed AT, Hameed RA, El-Moslamy SH, Fareid M, Othman M, Loutfy SA, et al. Facile synthesis of Fe2O3, Fe2O3@CuO and WO3 nanoparticles: Characterization, structure determination and evaluation of their biological activity. Sci Rep. 2024;14(1):6081. doi: 10.1038/ s41598-024-55319-8, PMID: 38480834
9. Gudkov SV, Burmistrov DE, Serov DA, Rebezov MB, Semenova AA, Lisitsyn AB. Do iron oxide nanoparticles have significant antibacterial properties? Antibiotics (Basel). 2021;10(7):884. doi: 10.3390/ antibiotics10070884, PMID: 34356805
10. Preeth DR, Shairam M, Suganya N, Hootan R, Kartik R, Pierre K, et al. Green synthesis of copper oxide nanoparticles using sinapic acid:An underpinning step towards antiangiogenic therapy for breast cancer. J Biol Inorg Chem. 2019;24(5):633-45. doi: 1007/s00775-019-10 01676- z, PMID: 31230130
11. Raj Preeth D, Shairam M, Suganya N, Hootan R, Kartik R, Pierre K, et al. Green synthesis of copper oxide nanoparticles using sinapic acid: An underpinning step towards antiangiogenic therapy for breast cancer. J Biol Inorg Chem. 2019;24(5):633-45. doi: 10.1007/s00775-019- 01676-z, PMID: 31230130
12. Torrisi C, Morgante A, Malfa G, Acquaviva R, Castelli F, Pignatello R, et al. Sinapic acid release at the cell level by incorporation into nanoparticles: Experimental evidence using biomembrane models. Micro. 2021;1(1):120-8. doi: 10.3390/micro1010009
13. Balagangadharan K, Trivedi R, Vairamani M, Selvamurugan N. Sinapic
acid-loaded chitosan nanoparticles in polycaprolactone electrospun fibers for bone regeneration in vitro and in vivo. Carbohydr Polym. 2019;216:1-16. doi: 10.1016/j.carbpol.2019.04.002, PMID: 31047045
14. Al-Zahrani FA, Salem SS, Al-Ghamdi HA, Nhari LM, Lin L, El-Shishtawy RM. Green synthesis and antibacterial activity of Ag/Fe2O3 nanocomposite using Buddleja lindleyana extract. Bioengineering (Basel). 2022;9(9):452. doi: 10.3390/bioengineering9090452, PMID: 36134998
15. Vihodceva S, Šutka A, Sihtmäe M, Rosenberg M, Otsus M, Kurvet I, et al. Antibacterial activity of positively and negatively charged hematite (α-Fe2O3) nanoparticles to Escherichia coli, Staphylococcus aureus and Vibrio fischeri. Nanomaterials (Basel). 2021;11(3):652. doi: 10.3390/nano11030652, PMID: 33800165
16. Shanmugam R, Tharani M, Abullais SS, Patil SR, Karobari MI. Black seed assisted synthesis, characterization, free radical scavenging, antimicrobial and anti-inflammatory activity of iron oxide nanoparticles. BMC Complement Med Ther. 2024;24(1):241. doi: 10.1186/s12906- 024-04552-9, PMID: 38902620
17. Poyraz FŞ, Akbaş G, Duranoğlu D, Acar S, Mansuroğlu B, Ersöz M. Sinapic-acid-loaded nanoparticles optimized via experimental design methods: Cytotoxic, antiapoptotoic, antiproliferative, and antioxidant activity. ACS Omega. 2024;9(39):40329-45. doi: 10.1021/ acsomega.4c00216, PMID: 39371991
18. Russo S, Greco G, Sarpietro MG. Assessment of pharmaco-technological parameters of solid lipid nanoparticles as carriers for sinapic acid. Micro. 2023;3(2):510-20. doi: 10.3390/micro3020034
19. Ge X, Cao Z, Chu L. The antioxidant effect of the metal and metal-oxide nanoparticles. Antioxidants (Basel). 2022;11(4):791. doi: 10.3390/ antiox11040791, PMID: 35453476
20. Tharani M, Rajeshkumar S, Al-Ghanim KA, Nicoletti M, Sachivkina N, Govindarajan M. Terminalia chebula-assisted silver nanoparticles: Biological potential, synthesis, characterization, and ecotoxicity. Biomedicines. 2023;11(5):1472. doi: 10.3390/biomedicines11051472, PMID: 37239143
21. Menichetti A, Mavridi-Printezi A, Mordini D, Montalti M. Effect of size, shape and surface functionalization on the antibacterial activity of silver nanoparticles. J Funct Biomater. 2023;14(5):244. doi: 10.3390/ jfb14050244, PMID: 37233354
22. Pallela PN, Ummey S, Ruddaraju LK, Gadi S, Cherukuri CS, Barla S, et al. Antibacterial efficacy of green synthesized α-Fe2O3 nanoparticles using Sida cordifolia plant extract. Heliyon. 2019;5(11):e02765. doi: 10.1016/j.heliyon.2019.e02765, PMID: 31799458
23. Zúñiga-Miranda J, Guerra J, Mueller A, Mayorga-Ramos A, Carrera- Pacheco SE, Barba-Ostria C, et al. Iron oxide nanoparticles: Green synthesis and their antimicrobial activity. Nanomaterials (Basel). 2023;13(22):2919. doi: 10.3390/nano13222919, PMID: 37999273
24. Parthasarathy PR, Varshan EI, Shanmugam R. In vitro anti-diabetic activity of pomegranate peel extract-mediated strontium nanoparticles. Cureus. 2023;15(12):e51356. doi: 10.7759/cureus.51356
25. Rajeshkumar S, Jayakodi S, Tharani M, Alharbi NS, Thiruvengadam M. Antimicrobial activity of probiotic bacteria-mediated cadmium oxide nanoparticles against fish pathogens. Microb Pathog. 2024;189:106602. doi: 10.1016/j.micpath.2024.106602, PMID: 38408546
26. Rajeshkumar S, Parameswari RP, Sandhiya D, Al-Ghanim KA, Nicoletti M, Govindarajan M. Green synthesis, characterization and bioactivity of Mangifera indica seed-wrapped zinc oxide nanoparticles. Molecules. 2023;28(6):2818. doi: 10.3390/molecules28062818, PMID: 36985789
27. Shanmugam R, Munusamy T, Nisha M A, Rajaselin A, Govindharaj S. Exploring the in vitro antidiabetic potential of metal oxide nanoparticles synthesized using lemongrass and mint formulation. Cureus. 2024;16(2):e53489. doi: 10.7759/cureus.53489, PMID: 38440044
28. Niazi F, Ali M, Haroon U, Farhana, Kamal A, Rashid T, et al. Effect of green Fe2O3 nanoparticles in controlling Fusarium fruit rot disease of loquat in Pakistan. Braz J Microbiol. 2023;54(3):1341-50. doi: 10.1007/ s42770-023-01050-x, PMID: 37400611
29. Mendes AR, Granadeiro CM, Leite A, Pereira E, Teixeira P, Poças F. Optimizing antimicrobial efficacy: Investigating the impact of zinc oxide nanoparticle shape and size. Nanomaterials (Basel). 2024;14(7):638. doi: 10.3390/nano14070638, PMID: 38607172
30. Precupas A, Popa VT. Impact of sinapic acid on bovine serum albumin thermal stability. Int J Mol Sci. 2024;25(2):936. doi: 10.3390/ ijms25020936, PMID: 38256010
31. Arif Muhammed R, Mohammed S, Visht S, Omar Yassen A. A review on development of colon targeted drug delivery system. Int J Appl Pharm. 2024;16(2):12-27. doi: 10.22159/ijap.2024v16i2
32. Franco D, Calabrese G, Guglielmino SP, Conoci S. Metal-based nanoparticles: Antibacterial mechanisms and biomedical application. Microorganisms. 2022;10(9):1778. doi: 10.3390/ microorganisms10091778, PMID: 36144380
33. Rajeshkumar S, Tharani M, Jeevitha M, Santhoshkumar J. Anticariogenic activity of fresh Aloe vera gel mediated copper oxide nanoparticles. Indian J Public Health Res Dev. 2019;10(11):3664. doi: 10.5958/0976-5506.2019.04158.5
34. Sasidharan I, Menon AN. Comparative chemical composition and antimicrobial activity of fresh and dry ginger oils (Zingiber officinale Roscoe). Int J Curr Pharm Res. 2010;2(4):40-3.
35. Rani AP, Archana N, Teja PS, Vikas. PM, Sekaran MS. Antimicrobial activity of medicinal plants. Int J Appl Pharm. 2010;2(3):15-21.
36. Palani B, Vajjiravelu R, Shanmugam R, Jayakodi S. A comprehensive review of traditional medicinal plants and their role in ovarian cancer treatment. S Afr J Bot. 2025;181:426-45. doi: 10.1016/j. sajb.2025.04.019
37. Kalaimathi J, Suresh K. Sinapic acid attenuates 7,12-dimethylbenz[a] anthracene-induced oral carcinogenesis by improving the apoptotic associated gene expression in hamsters. Asian J J Pathol Clin Res. 2015;8(6):134-138. ISSN 0974-2441.
Published
How to Cite
Issue
Section
Copyright (c) 2025 Kalaimathi Janakiraman, Revathi S, Suriya M, Deena Mol J, Karthika R, Suresh K, Rajeshkumar S
This work is licensed under a Creative Commons Attribution 4.0 International License.
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.
