Pharmacological Potential of Nigella sativa and Psidium guajava: Bioactive Compounds, Therapeutic Potential, and Challenges in Drug Development
DOI:
https://doi.org/10.47430/ujmr.25103.016Keywords:
Nigella sativa, Psidium guajava, antimicrobial resistance, phytochemicals, Bioactive compounds, pharmacological synergy, MIC meta-analysisAbstract
Study’s Excerpt:
- N. sativa and P. guajava show broad-spectrum antimicrobial potential.
- Thymoquinone pooled MIC was 6.83 μg/mL across studies.
- 24 studies reviewed; 12 included in quantitative meta-analysis.
- Key compounds include thymoquinone, carvacrol, and quercetin.
- Findings support plant-based alternatives for AMR management.
Full Abstract:
Antimicrobial resistance (AMR) is a growing global health crisis exacerbated by the slow pace of new drug development. This study systematically evaluated the pharmacological and antimicrobial properties of Nigella sativa and Psidium guajava, focusing on their bioactive constituents, clinical relevance, and therapeutic potential. A comprehensive search of eight databases covering the period 2015–2024 yielded 1,057 records, of which 111 full-text articles met the inclusion criteria. Ultimately, 24 studies were included in the qualitative synthesis, and 12 provided quantitative MIC data suitable for meta-analysis. Using a random-effects model, the pooled MIC estimate for thymoquinone was 6.83 μg/mL (95% CI: 4.85–8.82), indicating consistent broad-spectrum antimicrobial activity. Heatmaps and Venn diagrams highlighted compound-pathogen interactions and revealed overlapping and unique antibacterial spectra among thymoquinone, carvacrol, and quercetin-glycosides. The ROBINS-I tool revealed a low to moderate risk of bias in most domains, although the confounding and outcome measurement domains showed a serious risk in a few studies. Notably, publication bias was evident due to selective reporting of favorable MIC values. N. sativa and P. guajava exhibited significant antimicrobial, anti-inflammatory, and antitumor activities, mediated by compounds such as thymoquinone, carvacrol, tannins, and quercetin. These findings emphasize the potential of these plants as adjuncts or alternatives in antimicrobial therapy. However, challenges including standardization, bioavailability, and regulatory frameworks must be addressed through multidisciplinary research and sustainable bioproduction approaches.
Downloads
References
Abbas, M., Gururani, M. A., Ali, A., Bajwa, S., Hassan, R., Batool, S. W., ... & Wei, D. (2024). Antimicrobial properties and therapeutic potential of bioactive compounds in Nigella sativa: A review. Molecules, 29(20), 4914. https://doi.org/10.3390/molecules29204914
Abbasnezhad, A., Niazmand, S., Mahmoudabady, M., Rezaee, S. A., Soukhtanloo, M., Mosallanejad, R., & Hayatdavoudi, P. (2019). Nigella sativa L. seed regulated eNOS, VCAM-1 and LOX-1 genes expression and improved vasoreactivity in aorta of diabetic rat. Journal of Ethnopharmacology, 228, 142–147. https://doi.org/10.1016/j.jep.2018.09.021
Abdallah, H. M., El-Halawany, A. M., Darwish, K. M., Algandaby, M. M., Mohamed, G. A., Ibrahim, S. R., ... & Elfaky, M. A. (2022). Bio-guided isolation of SARS-CoV-2 main protease inhibitors from medicinal plants: In vitro assay and molecular dynamics. Plants, 11(15), 1914. https://doi.org/10.3390/plants11151914
Aftab, A., Yousaf, Z., & Rashid, M. (2023). Vegetative part of Nigella sativa L. potential antineoplastic sources against Hep2 and MCF7 human cancer cell lines. Journal of Taibah University for Science, 17. https://doi.org/10.1080/16583655.2022.2161294
Ahmad, S., & Beg, Z. H. (2016). Evaluation of therapeutic effect of omega-6 linoleic acid and thymoquinone enriched extracts from Nigella sativa oil in the mitigation of lipidemic oxidative stress in rats. Nutrition, 32(6), 649–655. https://doi.org/10.1016/j.nut.2015.12.003
Akansha, Kaushal, S., Arora, A., Heena, Sharma, P., & Jangra, R. (2023). Chemical composition and synergistic antifungal potential of Nigella sativa L. seeds and Syzygium aromaticum (L.) Merr. & L.M. Perry buds essential oils and their major compounds, and associated molecular docking studies. Journal of Essential Oil Bearing Plants, 26(3), 602–625. https://doi.org/10.1080/0972060X.2023.2220348
Al Dhaheri, Y., Wali, A. F., Akbar, I., Rasool, S., Razmpoor, M., Jabnoun, S., & Rashid, S. (2022). Nigella sativa, a cure for every disease: Phytochemistry, biological activities, and clinical trials. In Black Seeds (Nigella Sativa) (pp. 63–90). Elsevier. https://doi.org/10.1016/B978-0-12-824462-3.00011-1
Al Dosary, R. A. A. Q. (2023). Antibacterial and alteration of drug resistance activities of black cumin seed (Nigella sativa) extracts against urinary pathogens. Journal of Public Health Sciences, 2(03), 148–158. https://doi.org/10.56741/jphs.v2i03.389
Alamgir, A. N. M., & Alamgir, A. N. M. (2017). Cultivation of herbal drugs, biotechnology, and in vitro production of secondary metabolites, high-value medicinal plants, herbal wealth, and herbal trade. Therapeutic Use of Medicinal Plants and Their Extracts: Volume 1: Pharmacognosy, 379–452. https://doi.org/10.1007/978-3-319-63862-1_9
Alnour, T. M., Ahmed-Abakur, E. H., Elssaig, E. H., Abuduhier, F. M., & Ullah, M. F. (2022). Antimicrobial synergistic effects of dietary flavonoids rutin and quercetin in combination with antibiotics gentamicin and ceftriaxone against E. coli (MDR) and P. mirabilis (XDR) strains isolated from human infections: Implications for food-medicine interactions. Italian Journal of Food Science, 34(2), 34–42. https://doi.org/10.15586/ijfs.v34i2.2196
Alobaedi, O. H., Talib, W. H., & Basheti, I. A. (2017). Antitumor effect of thymoquinone combined with resveratrol on mice transplanted with breast cancer. Asian Pacific Journal of Tropical Medicine, 10(4), 400–408. https://doi.org/10.1016/j.apjtm.2017.03.026
Al-Rabia, M. W., Asfour, H. Z., Alhakamy, N. A., Abdulaal, W. H., Ibrahim, T. S., Abbas, H. A., ... & Nazeih, S. I. (2024). Thymoquinone is a natural antibiofilm and pathogenicity attenuating agent in Pseudomonas aeruginosa. Frontiers in Cellular and Infection Microbiology, 14, 1382289. https://doi.org/10.3389/fcimb.2024.1382289
Arip, M., Selvaraja, M., Tan, L. F., Leong, M. Y., Tan, P. L., Yap, V. L., ... & Jubair, N. (2022). Review on plant-based management in combating antimicrobial resistance—Mechanistic perspective. Frontiers in Pharmacology, 13, 879495. https://doi.org/10.3389/fphar.2022.879495
Ashraf, A., Sarfraz, R. A., Rashid, M. A., Mahmood, A., Shahid, M., & Noor, N. (2016). Chemical composition, antioxidant, antitumor, anticancer and cytotoxic effects of Psidium guajava leaf extracts. Pharmaceutical Biology, 54(10), 1971–1981. https://doi.org/10.3109/13880209.2015.1137604
Aware, C. B., Patil, D. N., Suryawanshi, S. S., Mali, P. R., Rane, M. R., Gurav, R. G., & Jadhav, J. P. (2022). Natural bioactive products as promising therapeutics: A review of natural product-based drug development. South African Journal of Botany, 151, 512–528. https://doi.org/10.1016/j.sajb.2022.05.028
Babu, B., Rao, P., Suman, E., & Udayalaxmi, J. (2023). A study of antibacterial effect of Nigella sativa seed extracts on bacterial isolates from cases of wound infection. Infectious Disorders—Drug Targets (Formerly Current Drug Targets—Infectious Disorders), 23(5), 41–45. https://doi.org/10.2174/1871526523666230403095441
Bahramian, S., Bigdeli, M. R., Rasoulian, B., & Moridi, F. M. (2016). Antitumor and antiangiogenic effects of the crude oil of Nigella sativa L. in tumor tissues in BALB/c mice. Zahra Journal of Research in Medical Sciences, 18(1). https://doi.org/10.17795/zjrms.6667
Balouiri, M., Sadiki, M., & Ibnsouda, S. K. (2016). Methods for in vitro evaluating antimicrobial activity: A review. Journal of Pharmaceutical Analysis, 6(2), 71–79. https://doi.org/10.1016/j.jpha.2015.11.005
Bano, A., Gupta, A., Rai, S., Sharma, S., Upadhyay, T. K., Al-Keridis, L. A., ... & Saeed, M. (2023). Bioactive compounds, antioxidant, and antibacterial activity against MDR and food-borne pathogenic bacteria of Psidium guajava L. fruit during ripening. Molecular Biotechnology. https://doi.org/10.1007/s12033-023-00779-y
Bashir, A., Ado, A., & Alli, A. I. (2022). Determination of antibacterial activity of Psidium guajava leaf extract against bacteria isolated from mobile phones of Umaru Musa Yar'adua University, Katsina community. UMYU Journal of Microbiology Research, 6(1), 219–226. https://doi.org/10.47430/ujmr.2161.032
Bashir, K. M. I., Kim, J. K., Chun, Y. S., Choi, J. S., & Ku, S. K. (2023). In vitro assessment of anti-adipogenic and anti-inflammatory properties of black cumin (Nigella sativa L.) seeds extract on 3T3-L1 adipocytes and RAW264.7 macrophages. Medicina, 59(11), 2028. https://doi.org/10.3390/medicina59112028
Bhaduri, A. (2023). Communities as inventors: Rethinking positive protection of traditional knowledge through patents. The Journal of World Intellectual Property, 26(3), 414–435. https://doi.org/10.1111/jwip.12279
Brito, A. K. D. S., Lima, G. D. M., Farias, L. M. D., Rodrigues, L. A. R. L., Carvalho, V. B. L. D., Pereira, C. F. D. C., ... & Martins, M. D. C. D. C. E. (2019). Lycopene-rich extract from red guava (Psidium guajava L.) decreases plasma triglycerides and improves oxidative stress biomarkers on experimentally-induced dyslipidemia in hamsters. Nutrients, 11(2), 393. https://doi.org/10.3390/nu11020393
Buah, J. D., Musa, D. D., & Eberemu, N. C. (2023). Antibacterial activities of guava (Psidium guajava) and orange (Citrus sinensis) leaves extracts on Staphylococcus aureus and Escherichia coli. Sahel Journal of Life Sciences FUDMA, 1(1), 130–136. https://doi.org/10.33003/sajols-2023-0101-014
Bylappa, Y., Balasubramanian, B., Park, S., Joseph, K. S., Chacko, A. M., Sudheer, W. N., ... & Khaneghah, A. M. (2024). Three decades of advances in extraction and analytical techniques for guava (Psidium guajava L.): A review. Results in Chemistry, 101708. https://doi.org/10.1016/j.rechem.2024.101708
Chaachouay, N., & Zidane, L. (2024). Plant-derived natural products: A source for drug discovery and development. Drugs and Drug Candidates, 3(1), 184–207. https://doi.org/10.3390/ddc3010011
Chassagne, F., Samarakoon, T., Porras, G., Lyles, J. T., Dettweiler, M., Marquez, L., ... & Quave, C. L. (2021). A systematic review of plants with antibacterial activities: A taxonomic and phylogenetic perspective. Frontiers in Pharmacology, 11, 586548. https://doi.org/10.3389/fphar.2020.586548
Chidzwondo, F., & Mutapi, F. (2024). Challenge of diagnosing acute infections in poor resource settings in Africa. AAS Open Research, 4, 28. https://doi.org/10.12688/aasopenres.13234.2
Chintada, V., & Golla, N. (2025). Exploring the therapeutic potential of bioactive compounds from plant sources. In Biotechnological Intervention in Production of Bioactive Compounds: Biosynthesis, Characterization and Applications (pp. 229–247). Springer Nature Switzerland. https://doi.org/10.1007/978-3-031-76859-0_15
Chu, S., Zhang, F., Wang, H., Xie, L., Chen, Z., Zeng, W., & Hu, F. (2022). Aqueous extract of guava (Psidium guajava L.) leaf ameliorates hyperglycemia by promoting hepatic glycogen synthesis and modulating gut microbiota. Frontiers in Pharmacology, 13, 907702. https://doi.org/10.3389/fphar.2022.907702
Dar, R. A., Shahnawaz, M., Ahanger, M. A., & Majid, I. U. (2023). Exploring the diverse bioactive compounds from medicinal plants: A review. Journal of Phytopharmacology, 12(3), 189–195. https://doi.org/10.31254/phyto.2023.12307
Das, K. K. (2016). Hepatoprotective effect of Nigella sativa seed in streptozotocin-induced diabetic albino rats: Histological observations.
De Castro, R., De Souza, T., Bezerra, L., Ferreira, G., De Brito Costa, E., & Cavalcanti, A. (2015). Antifungal activity and mode of action of thymol and its synergism with nystatin against Candida species involved with infections in the oral cavity: An in vitro study. BMC Complementary and Alternative Medicine, 15. https://doi.org/10.1186/s12906-015-0947-2
De Souza, G. H. D. A., Dos Santos Radai, J. A., Mattos Vaz, M. S., Esther da Silva, K., Fraga, T. L., Barbosa, L. S., & Simionatto, S. (2021). In vitro and in vivo antibacterial activity assays of carvacrol: A candidate for development of innovative treatments against KPC-producing Klebsiella pneumoniae. PLoS ONE, 16(2), e0246003. https://doi.org/10.1371/journal.pone.0246003
Dera, A. A., Ahmad, I., Rajagopalan, P., Al Shahrani, M., Saif, A., Alshahrani, M. Y., ... & Alfhili, M. A. (2021). Synergistic efficacies of thymoquinone and standard antibiotics against multi-drug resistant isolates. Saudi Medical Journal, 42(2), 196. https://doi.org/10.15537/smj.2021.2.25706
Dhanasekaran, S. (2019). Alteration of multi-drug resistance activities by ethanolic extracts of Nigella sativa against urinary pathogens. International Journal of Pharmacology, 15(8), 962–969. https://doi.org/10.3923/ijp.2019.962.969
Díaz-de-Cerio, E., Verardo, V., Gómez-Caravaca, A. M., Fernández-Gutiérrez, A., & Segura-Carretero, A. (2017). Health effects of Psidium guajava L. leaves: An overview of the last decade. International Journal of Molecular Sciences, 18(4), 897. https://doi.org/10.3390/ijms18040897
Efe, E. E., Agabi, K. J., & Ozock, D. (2024). Exploring the socio-economic impact of herbal medicine practices in Ondo State, Nigeria.
El Rabey, H. A., Al-Seeni, M. N., & Bakhashwain, A. S. (2017). The antidiabetic activity of Nigella sativa and propolis on streptozotocin-induced diabetes and diabetic nephropathy in male rats. Evidence-Based Complementary and Alternative Medicine, 2017(1), 5439645. https://doi.org/10.1155/2017/5439645
Elango, A., Rao, L. N., Sugumar, P., & Radhakrishnan, A. (2022). Evaluation of clinical efficacy and safety of Nigella sativa seed oil added to standard treatment in uncomplicated respiratory infection—A randomised, open labelled, and parallel arm study. Journal of Communicable Diseases, 91–97. https://doi.org/10.24321/0019.5138.202214
Emamat, H., Mousavi, S. H., Kargar Shouraki, J., Hazrati, E., Mirghazanfari, S. M., Samizadeh, E., & Hadi, S. (2022). The effect of Nigella sativa oil on vascular dysfunction assessed by flow-mediated dilation and vascular-related biomarkers in subjects with cardiovascular disease risk factors: A randomized controlled trial. Phytotherapy Research, 36(5), 2236–2245. https://doi.org/10.1002/ptr.7441
Emeka, L. B., Emeka, P. M., & Khan, T. M. (2015). Antimicrobial activity of Nigella sativa L. seed oil against multi-drug resistant Staphylococcus aureus isolated from diabetic wounds. Pakistan Journal of Pharmaceutical Sciences, 28(6).
Ezeh, C. K., Eze, C. N., Dibua, M. E. U., Emencheta, S. C., & Ezeh, C. C. (2022). Synthesis of silver nanoparticles using Nigella sativa seed extract and its efficacy against some multidrug-resistant uropathogens. Biomedical and Biotechnology Research Journal (BBRJ), 6(3), 400–409. https://doi.org/10.4103/bbrj.bbrj_104_22
Farhadi, K., Rajabi, E., Varpaei, H. A., Iranzadasl, M., Khodaparast, S., & Salehi, M. (2024). Thymol and carvacrol against Klebsiella: Antibacterial, anti-biofilm, and synergistic activities a systematic review. Frontiers in Pharmacology, 15, 1487083. https://doi.org/10.3389/fphar.2024.1487083
Fayed, M. A. (2022). Nigella sativa L.: A golden remedy: Significance worldwide highlighting their possible use for COVID-19. Universal Journal of Pharmaceutical Research, 7(3). https://doi.org/10.22270/ujpr.v7i3.778
Feridoniy, M., Alizadeh, F., Kokhdan, P., & Khodavandi, A. (2020). Study of the antifungal potential of carvacrol on growth inhibition of Candida krusei in a systemic candidiasis. Advances in Traditional Medicine, 20, 591–598. https://doi.org/10.1007/s13596-020-00482-2
Fermiano, T. H., Perez de Souza, J. V., Murase, L. S., Salvaterra Pasquini, J. P., de Lima Scodro, R. B., Zanetti Campanerut-Sá, P. A., ... & Cardoso, R. F. (2024). Antimicrobial activity of carvacrol and its derivatives on Mycobacterium spp.: Systematic review of preclinical studies. Future Medicinal Chemistry, 16(7), 679–688. https://doi.org/10.4155/fmc-2023-0249
Gholamnezhad, Z., Havakhah, S., & Boskabady, M. H. (2016). Preclinical and clinical effects of Nigella sativa and its constituent, thymoquinone: A review. Journal of Ethnopharmacology, 190, 372–386. https://doi.org/10.1016/j.jep.2016.06.061
Goel, S., & Mishra, P. (2018). Thymoquinone inhibits biofilm formation and has selective antibacterial activity due to ROS generation. Applied Microbiology and Biotechnology, 102(4), 1955–1967. https://doi.org/10.1007/s00253-018-8736-8
Govindaraghavan, S., & Sucher, N. J. (2015). Quality assessment of medicinal herbs and their extracts: Criteria and prerequisites for consistent safety and efficacy of herbal medicines. Epilepsy & Behavior, 52, 363–371. https://doi.org/10.1016/j.yebeh.2015.03.004
Hackman, H. K., Annison, L., Arhin, R. E., Azumah, B. K., Boateng, D., Nwosu, B., & Appenteng, M. (2020). Antimicrobial activity of Psidium guajava (guava) leaves extract on extended-spectrum beta-lactamase-producing Klebsiella pneumoniae that cause multi-drug resistant urinary tract infections.
Hackman, H. K., Arhin, R. E., Azumah, B. K., Boateng, D., Nwosu, B., & Apenteng, M. (2020). In vitro antibacterial activity of Psidium guajava (guava) leaves extract on carbapenem-resistant Klebsiella pneumoniae causing multi-drug resistant systemic infections.
Haitamy, M. N., Kariosentono, H., Prayitno, A., Setiamika, M., Nurwati, I., Riswiyanto, R. C. A., & Brahmadi, A. (2024). Exploring the anti-inflammatory effects of Nigella sativa on cyclooxygenase-2 through the nuclear factor-kappa B pathway in an Aspergillus niger-induced otitis externa mouse model. Journal of Advanced Pharmaceutical Technology & Research, 15(4), 341–345. https://doi.org/10.4103/JAPTR.JAPTR_110_24
Hashem, M. A., Mohamed, W. A., & Attia, E. S. (2018). Assessment of protective potential of Nigella sativa oil against carbendazim- and/or mancozeb-induced hematotoxicity, hepatotoxicity, and genotoxicity. Environmental Science and Pollution Research, 25, 1270–1282. https://doi.org/10.1007/s11356-017-0542-9
Hassan, E., Gendy, A., Abd-ElGawad, A., Elshamy, A., Farag, M., Alamery, S., & Omer, E. (2020). Comparative chemical profiles of the essential oils from different varieties of Psidium guajava L. Molecules, 26(1), 119. https://doi.org/10.3390/molecules26010119
Hassan, S. T., Šudomová, M., Mazurakova, A., & Kubatka, P. (2022). Insights into antiviral properties and molecular mechanisms of non-flavonoid polyphenols against human. International Journal of Molecular Sciences, 23(22), 13891. https://doi.org/10.3390/ijms232213891
Heinrich, M., Jalil, B., Abdel-Tawab, M., Echeverria, J., Kulić, Ž., McGaw, L. J., ... & Wang, J. B. (2022). Best practice in the chemical characterisation of extracts used in pharmacological and toxicological research—The ConPhyMP-guidelines. Frontiers in Pharmacology, 13, 953205. https://doi.org/10.3389/fphar.2022.953205
Hemananthan, E. (2020). In vitro studies to analyze the stability and bioavailability of thymoquinone encapsulated in the developed nanocarrier. Journal of Dispersion Science and Technology.
Herman, A., & Herman, A. P. (2023). Herbal products and their active constituents used alone and in combination with antibiotics against multidrug-resistant bacteria. Planta Medica, 89(2), 168–182. https://doi.org/10.1055/a-1890-5559
Hossain, C. M., Gera, M. E. E. T. A., & Ali, K. A. (2022). Current status and challenges of herbal drug development and regulatory aspect: A global perspective. Asian Journal of Pharmaceutical and Clinical Research, 15, 31–41. https://doi.org/10.22159/ajpcr.2022.v15i12.46134
Huynh, H. D., Nargotra, P., Wang, H. M. D., Shieh, C. J., Liu, Y. C., & Kuo, C. H. (2025). Bioactive compounds from guava leaves (Psidium guajava L.): Characterization, biological activity, synergistic effects, and technological applications. Molecules, 30(6), 1278. https://doi.org/10.3390/molecules30061278
Iduh, M. U., Imam, U. A., Muhammad, N. B., Enitan, S. S., & Hassan, Y. (2024). Mechanism of antimicrobial activities of medicinal plants extracts, from traditional knowledge to scientific insights. International Journal of Pathogen Research, 13(4), 72–86. https://doi.org/10.9734/ijpr/2024/v13i4300
Ilesanmi, F., Opeyemi, O., & Praise, O. (2020). Effect of different extraction solvents on the antimicrobial activity of Psidium guajava (guava) leaves against multi-drug resistant bacteria implicated in nosocomial infections. International Journal of Biotechnology, 9(1), 24–37. https://doi.org/10.18488/journal.57.2020.91.24.37
Imaduddin, M., Saba, N., Eman, A., Saba, K., & Kashfiya, A. (2022). Phytochemical screening and in vivo antileukemic activity of methanolic extract of seeds of Nigella sativa L. on benzene-induced leukemia in Wistar rats. Asian Pacific Journal of Health Sciences. https://doi.org/10.21276/apjhs.2022.9.2.39
Imam, A., Sulaimon, F. A., Sheu, M., Busari, M., Oyegbola, C., Okesina, A. A., ... & Ajao, M. S. (2022). Nigella sativa oil ingestion mitigates aluminum chloride induced cerebella oxidative, neurogenic damages and impaired motor functions in rats. Anatomy Journal of Africa, 11(1), 2109–2121. https://doi.org/10.4314/aja.v11i1.11
Innih, S., Osirike, P., Ubhenin, A., Ehi-Omosun, M., & Imafidon, E. (2016). Hepatoprotective effect of aqueous leaf extract of Psidium guajava in ketoconazole-treated adult male Wistar rats. Nigerian Journal of Life Sciences, 6(1), 218–224. https://doi.org/10.52417/njls.v6i1.302
Jankowski, G., Sawicki, R., Truszkiewicz, W., Wolan, N., Ziomek, M., Hryć, B., & Sieniawska, E. (2024). Molecular insight into thymoquinone mechanism of action against Mycobacterium tuberculosis. Frontiers in Microbiology, 15, 1353875. https://doi.org/10.3389/fmicb.2024.1353875
Kariawasam, K. W. J. C., Pathirana, R. N., Ratnasooriya, W. D., Handunnetti, S., & Abeysekera, W. P. K. M. (2017). Phytochemical profile and in vitro anti-inflammatory activity of aqueous leaf extract of Sri Lankan variety of Psidium guajava L. Journal of Pharmacognosy and Phytochemistry, 6(4), 22–26.
Khalid, A., & Ahmad, S. S. (2024). Antibacterial activity of Nigella sativa against multi-drug resistant bacteria. International Journal of Pathology, 22(2), 45–95. https://doi.org/10.59736/IJP.22.02.899
Khalil, H., Abd El Maksoud, A. I., Roshdey, T., & El-Masry, S. (2019). Guava flavonoid glycosides prevent influenza A virus infection via rescue of P53 activity. Journal of Medical Virology, 91(1), 45–55. https://doi.org/10.1002/jmv.25295
Khan, M. S. A., & Ahmad, I. (2019). Herbal medicine: Current trends and future prospects. In New Look to Phytomedicine (pp. 3–13). Academic Press. https://doi.org/10.1016/B978-0-12-814619-4.00001-X
Krishnaswamy, S. (2024). Phytopharmaceutical biotechnology: Integration of botany, pharmacology and plant biotechnology to deliver the best therapeutic potential of herbs. In Concepts in pharmaceutical biotechnology and drug development (pp. 437–464). Springer Nature Singapore. https://doi.org/10.1007/978-981-97-1148-2_20
Kumar, M., Tomar, M., Amarowicz, R., Saurabh, V., Nair, M. S., Maheshwari, C., ... & Satankar, V. (2021). Guava (Psidium guajava L.) leaves: Nutritional composition, phytochemical profile, and health-promoting bioactivities. Foods, 10(4), 752. https://doi.org/10.3390/foods10040752
Kumari, R., Deepali, B., & Bhatnagar, S. (2021). Biodiversity loss: Threats and conservation strategies. International Journal of Pharmaceutical Sciences Review and Research, 68(1), 242–254. https://doi.org/10.47583/ijpsrr.2021.v68i01.037
Lallemand, E. A., Lacroix, M. Z., Toutain, P. L., Boullier, S., Ferran, A. A., & Bousquet-Melou, A. (2016). In vitro degradation of antimicrobials during use of broth microdilution method can increase the measured minimal inhibitory and minimal bactericidal concentrations. Frontiers in Microbiology, 7, 2051. https://doi.org/10.3389/fmicb.2016.02051
Liebelt, D. J., Jordan, J. T., & Doherty, C. J. (2019). Only a matter of time: The impact of daily and seasonal rhythms on phytochemicals. Phytochemistry Reviews, 18, 1409–1433. https://doi.org/10.1007/s11101-019-09617-z
Mahomoodally, M. F., Aumeeruddy, M. Z., Legoabe, L. J., Montesano, D., & Zengin, G. (2022). Nigella sativa L. and its active compound thymoquinone in the clinical management of diabetes: A systematic review. International Journal of Molecular Sciences, 23(20), 12111. https://doi.org/10.3390/ijms232012111
Majdalawieh, A. F., & Fayyad, M. W. (2016). Recent advances on the anti-cancer properties of Nigella sativa, a widely used food additive. Journal of Ayurveda and Integrative Medicine, 7(3), 173–180. https://doi.org/10.1016/j.jaim.2016.07.004
Maryam, A. J., Fatimah, A. A., Ebtesam, A. K., Abdulrahman, A. S., & Ineta, B. E. (2016). In-vitro studies on the effect of Nigella sativa Linn. seed oil extract on multidrug-resistant Gram-positive and Gram-negative bacteria. Journal of Medicinal Plants, 4(2), 195–199.
Masri, M., Muthiadin, C., Masita, M., Cahyanto, T., Lianah, L., Rusny, R., & Tridesianti, S. (2021). Black cumin (Nigella sativa) against Mycobacterium tuberculosis strain H37RV and MDR-TB. Elkawnie: Journal of Islamic Science and Technology, 7(1), 182–196. https://doi.org/10.22373/ekw.v7i1.9335
Memar, M. Y., Raei, P., Alizadeh, N., Aghdam, M. A., & Kafil, H. S. (2017). Carvacrol and thymol: Strong antimicrobial agents against resistant isolates. Reviews and Research in Medical Microbiology, 28(2), 63–68. https://doi.org/10.1097/MRM.0000000000000100
Mir, T. A., Jan, M., Khare, R. K., & Bhat, M. H. (2021). Medicinal plant resources: Threat to its biodiversity and conservation strategies. In Medicinal and aromatic plants: Healthcare and industrial applications (pp. 717–739). Springer. https://doi.org/10.1007/978-3-030-58975-2_28
Moses, A. S., Singh, S. N., Pratap, D., & Salam, S. (2019). Determination and comparison of antimicrobial activity of Psidium guajava and Emblica officinalis against MDR bacteria. Journal of Pharmacognosy and Phytochemistry, 8(1), 2169–2172.
Mouwakeh, A., Kincses, A., Nové, M., Mosolygó, T., Mohácsi-Farkas, C., Kiskó, G., & Spengler, G. (2019). Nigella sativa essential oil and its bioactive compounds as resistance modifiers against Staphylococcus aureus. Phytotherapy Research, 33(4), 1010–1018. https://doi.org/10.1002/ptr.6294
Mouwakeh, A., Telbisz, A., Spengler, G., Mohacsi-Farkas, C., & Kiskó, G. (2018). Antibacterial and resistance modifying activities of Nigella sativa essential oil and its active compounds against Listeria monocytogenes. In Vivo, 32(4), 737–743. https://doi.org/10.21873/invivo.11302
Mushtaq, A., Aslam, B., Faisal, M. N., Hussain, A., Shamim, S., Kousar, S., ... & Umer, A. (2024). Nigella sativa L. attenuates oxidative stress, inflammation and apoptosis in Concanavalin A-induced acute immunological liver damage in mice. Brazilian Archives of Biology and Technology, 67, e24230554. https://doi.org/10.1590/1678-4324-2024230554
Mustafa, G., Arif, R., Atta, A., Sharif, S., & Jamil, A. (2017). Bioactive compounds from medicinal plants and their importance in drug discovery in Pakistan. Matrix Science Pharma, 1(1), 17–26. https://doi.org/10.26480/msp.01.2017.17.26
Nagy, A. M., Abdelhameed, M. F., Elkarim, A. S. A., Sarker, T. C., Abd-ElGawad, A. M., Elshamy, A. I., & Hammam, A. M. (2024). Enhancement of female rat fertility via ethanolic extract from Nigella sativa L. (black cumin) seeds assessed via HPLC-ESI-MS/MS and molecular docking. Molecules, 29(3), 735. https://doi.org/10.3390/molecules29030735
Najmi, A., Javed, S. A., Al Bratty, M., & Alhazmi, H. A. (2022). Modern approaches in the discovery and development of plant-based natural products and their analogues as potential therapeutic agents. Molecules, 27(2), 349. https://doi.org/10.3390/molecules27020349
Naseer, S., Hussain, S., Naeem, N., Pervaiz, M., & Rahman, M. (2018). The phytochemistry and medicinal value of Psidium guajava (guava). Clinical Phytoscience, 4(1), 1–8. https://doi.org/10.1186/s40816-018-0093-8
Nasim, N., Sandeep, I. S., & Mohanty, S. (2022). Plant-derived natural products for drug discovery: Current approaches and prospects. The Nucleus, 65(3), 399–411. https://doi.org/10.1007/s13237-022-00405-3
Neumann, N., Honke, M., Povydysh, M., Guenther, S., & Schulze, C. (2022). Evaluating tannins and flavonoids from traditionally used medicinal plants with biofilm inhibitory effects against MRGN E. coli. Molecules, 27(7), 2284. https://doi.org/10.3390/molecules27072284
Nguyen, T. L. A., & Bhattacharya, D. (2022). Antimicrobial activity of quercetin: An approach to its mechanistic principle. Molecules, 27(8), 2494. https://doi.org/10.3390/molecules27082494
Odieka, A. E., Obuzor, G. U., Oyedeji, O. O., Gondwe, M., Hosu, Y. S., & Oyedeji, A. O. (2022). The medicinal natural products of Cannabis sativa Linn.: A review. Molecules, 27(5), 1689. https://doi.org/10.3390/molecules27051689
Ojueromi, O. O., Oboh, G., & Ademosun, A. O. (2022). Effect of black seeds (Nigella sativa) on inflammatory and immunomodulatory markers in Plasmodium berghei‐infected mice. Journal of Food Biochemistry, 46(11), e14300. https://doi.org/10.1111/jfbc.14300
Ojueromi, O. O., Oboh, G., & Ademosun, A. O. (2024). Nigella sativa-fortified cookies ameliorate oxidative stress, inflammatory and immune dysfunction in Plasmodium berghei-infected murine model. Journal of Medicinal Food, 27(6), 552–562. https://doi.org/10.1089/jmf.2023.0181
Patyra, A., Kołtun-Jasion, M., Jakubiak, O., & Kiss, A. K. (2022). Extraction techniques and analytical methods for isolation and characterization of lignans. Plants, 11(17), 2323. https://doi.org/10.3390/plants11172323
Pelegrin, S., Galtier, F., Chalançon, A., Gagnol, J. P., Barbanel, A. M., Pélissier, Y., ... & Chevassus, H. (2019). Effects of Nigella sativa seeds (black cumin) on insulin secretion and lipid profile: A pilot study in healthy volunteers. British Journal of Clinical Pharmacology, 85(7), 1607–1611. https://doi.org/10.1111/bcp.13922
Pereira, G. A., Chaves, D. S. D. A., Silva, T. M. E., Motta, R. E. D. A., Silva, A. B. R. D., Patricio, T. C. D. C., ... & Karpiński, T. M. (2023). Antimicrobial activity of Psidium guajava aqueous extract against sensitive and resistant bacterial strains. Microorganisms, 11(7), 1784. https://doi.org/10.3390/microorganisms11071784
Pognan, F., Beilmann, M., Boonen, H. C., Czich, A., Dear, G., Hewitt, P., ... & Newham, P. (2023). The evolving role of investigative toxicology in the pharmaceutical industry. Nature Reviews Drug Discovery, 22(4), 317–335. https://doi.org/10.1038/s41573-022-00633-x
Polinati, R. M., Teodoro, A. J., Correa, M. G., Casanova, F. A., Passos, C. L. A., Silva, J. L., & Fialho, E. (2022). Effects of lycopene from guava (Psidium guajava L.) derived products on breast cancer cells. Natural Product Research, 36(5), 1405–1408. https://doi.org/10.1080/14786419.2021.1880402
Proença, C. E. B., Tuler, A. C., Lucas, E. J., Vasconcelos, T. N. D. C., de Faria, J. E. Q., Staggemeier, V. G., ... & da Costa, I. R. (2022). Diversity, phylogeny and evolution of the rapidly evolving genus Psidium L. (Myrtaceae, Myrteae). Annals of Botany, 129(4), 367–388. https://doi.org/10.1093/aob/mcac005
Qin, X. J., Yu, Q., Yan, H., Khan, A., Feng, M. Y., Li, P. P., ... & Liu, H. Y. (2017). Meroterpenoids with antitumor activities from guava (Psidium guajava). Journal of Agricultural and Food Chemistry, 65(24), 4993–4999. https://doi.org/10.1021/acs.jafc.7b01762
Qu, S., Dai, C., Shen, Z., Tang, Q., Wang, H., Zhai, B., ... & Hao, Z. (2019). Mechanism of synergy between tetracycline and quercetin against antibiotic resistant Escherichia coli. Frontiers in Microbiology, 10, 2536. https://doi.org/10.3389/fmicb.2019.02536
Rafati, M., Ghasemi, A., Saeedi, M., Habibi, E., Salehifar, E., Mosazadeh, M., & Maham, M. (2019). Nigella sativa L. for prevention of acute radiation dermatitis in breast cancer: A randomized, double-blind, placebo-controlled, clinical trial. Complementary Therapies in Medicine, 47, 102205. https://doi.org/10.1016/j.ctim.2019.102205
Razmpoosh, E., Safi, S., Nadjarzadeh, A., Fallahzadeh, H., Abdollahi, N., Mazaheri, M., ... & Salehi-Abargouei, A. (2021). The effect of Nigella sativa supplementation on cardiovascular risk factors in obese and overweight women: A crossover, double-blind, placebo-controlled randomized clinical trial. European Journal of Nutrition, 60, 1863–1874. https://doi.org/10.1007/s00394-020-02374-2
Reyes-Jurado, F., Franco-Vega, A., Ramírez-Corona, N., Palou, E., & López-Malo, A. (2015). Essential oils: Antimicrobial activities, extraction methods, and their modeling. Food Engineering Reviews, 7, 275–297. https://doi.org/10.1007/s12393-014-9099-2
Said, S. A., Abdulbaset, A., El-Kholy, A. A., Besckales, O., & Sabri, N. A. (2022). The effect of Nigella sativa and vitamin D3 supplementation on the clinical outcome in COVID-19 patients: A randomized controlled clinical trial. Frontiers in Pharmacology, 13, 1011522. https://doi.org/10.3389/fphar.2022.1011522
Seghatoleslam, M., Alipour, F., Shafieian, R., Hassanzadeh, Z., Edalatmanesh, M. A., Sadeghnia, H. R., & Hosseini, M. (2016). The effects of Nigella sativa on neural damage after pentylenetetrazole induced seizures in rats. Journal of Traditional and Complementary Medicine, 6(3), 262–268. https://doi.org/10.1016/j.jtcme.2015.06.003
Selvakumar, P., Seenivasan, S., Deshmukh, S. M., Ponnapalli, H., & Das, A. (2025). Environmental protection and policies. In Renewable Energy and the Economic Welfare of Society (pp. 71–102). IGI Global. https://doi.org/10.4018/979-8-3693-7580-8.ch004
Shabbir, A., Butt, H. I., Shahzad, M., Arshad, H. M., & Waheed, I. (2016). Immunostimulatory effect of methanolic leaves extract of Psidium guajava (guava) on humoral and cell-mediated immunity in mice. JAPS: Journal of Animal & Plant Sciences, 26(5).
Shafodino, F. S., Lusilao, J. M., & Mwapagha, L. M. (2022). Phytochemical characterization and antimicrobial activity of Nigella sativa seeds. PLoS ONE, 17(8), e0272457. https://doi.org/10.1371/journal.pone.0272457
Shetty, Y. S., Shankarapillai, R., Vivekanandan, G., Shetty, R. M., Reddy, C. S., Reddy, H., & Mangalekar, S. B. (2018). Evaluation of the efficacy of guava extract as an antimicrobial agent on periodontal pathogens. Journal of Contemporary Dental Practice, 19(6), 690–697. https://doi.org/10.5005/jp-journals-10024-2321
Sousa Silveira, Z. D., Macêdo, N. S., Sampaio dos Santos, J. F., Sampaio de Freitas, T., Rodrigues dos Santos Barbosa, C., Júnior, D. L. D. S., ... & Martins, N. (2020). Evaluation of the antibacterial activity and efflux pump reversal of thymol and carvacrol against Staphylococcus aureus and their toxicity in Drosophila melanogaster. Molecules, 25(9), 2103. https://doi.org/10.3390/molecules25092103
Srivastava, R., Dubey, N. K., Sharma, M., Kharkwal, H., Bajpai, R., & Srivastava, R. (2025). Boosting the human antiviral response in conjunction with natural plant products. Frontiers in Natural Products, 3, 1470639. https://doi.org/10.3389/fntpr.2024.1470639
Stielow, M., Witczyńska, A., Kubryń, N., Fijałkowski, Ł., Nowaczyk, J., & Nowaczyk, A. (2023). The bioavailability of drugs—The current state of knowledge. Molecules, 28(24), 8038. https://doi.org/10.3390/molecules28248038
Streicher, L. M. (2021). Exploring the future of infectious disease treatment in a post-antibiotic era: A comparative review of alternative therapeutics. Journal of Global Antimicrobial Resistance, 24, 285–295. https://doi.org/10.1016/j.jgar.2020.12.025
Tan, Y., Lin, Q., Yao, J., Zhang, G., Peng, X., & Tian, J. (2023). In vitro outcomes of quercetin on Candida albicans planktonic and biofilm cells and in vivo effects on vulvovaginal candidiasis: Evidences of its mechanisms of action. Phytomedicine, 114, 154800. https://doi.org/10.1016/j.phymed.2023.154800
Tella, T., Masola, B., & Mukaratirwa, S. (2019). The effect of Psidium guajava aqueous leaf extract on liver glycogen enzymes, hormone sensitive lipase and serum lipid profile in diabetic rats. Biomedicine & Pharmacotherapy, 109, 2441–2446. https://doi.org/10.1016/j.biopha.2018.11.137
Thomford, N. E., Dzobo, K., Chopera, D., Wonkam, A., Skelton, M., Blackhurst, D., ... & Dandara, C. (2015). Pharmacogenomics implications of using herbal medicinal plants on African populations in health transition. Pharmaceuticals, 8(3), 637–663. https://doi.org/10.3390/ph8030637
Tian, L., Wang, X., Liu, R., Zhang, D., Wang, X., Sun, R., ... & Gong, G. (2021). Antibacterial mechanism of thymol against Enterobacter sakazakii. Food Control, 123, 107716. https://doi.org/10.1016/j.foodcont.2020.107716
Tiotsop, R. S., Mbaveng, A. T., Seukep, A. J., Matieta, V. Y., Nayim, P., Wamba, B. E., ... & Kuete, V. (2023). Psidium guajava (Myrtaceae) re-sensitizes multidrug-resistant Pseudomonas aeruginosa over-expressing MexAB-OprM efflux pumps to commonly prescribed antibiotics. Investigational Medicinal Chemistry and Pharmacology, 6(2), 80. https://doi.org/10.31183/imcp.2023.00080
Ugbogu, E. A., Emmanuel, O., Uche, M. E., Dike, E. D., Okoro, B. C., Ibe, C., ... & Ugbogu, O. C. (2022). The ethnobotanical, phytochemistry and pharmacological activities of Psidium guajava L. Arabian Journal of Chemistry, 15(5), 103759. https://doi.org/10.1016/j.arabjc.2022.103759
Ullah, F., Ayaz, M., Sadiq, A., Ullah, F., Hussain, I., Shahid, M., ... & Devkota, H. P. (2020). Potential role of plant extracts and phytochemicals against foodborne pathogens. Applied Sciences, 10(13), 4597. https://doi.org/10.3390/app10134597
Upadhyay, S. K., & Singh, S. P. (Eds.). (2023). Plants as bioreactors for industrial molecules. John Wiley & Sons. https://doi.org/10.1002/9781119875116
Uzzan, S., Rostevanov, I. S., Rubin, E., Benguigui, O., Marazka, S., Kaplanski, J., ... & Azab, A. N. (2024). Chronic treatment with Nigella sativa oil exerts antimanic properties and reduces brain inflammation in rats. International Journal of Molecular Sciences, 25(3), 1823. https://doi.org/10.3390/ijms25031823
Vaou, N., Stavropoulou, E., Voidarou, C., Tsakris, Z., Rozos, G., Tsigalou, C., & Bezirtzoglou, E. (2022). Interactions between medical plant-derived bioactive compounds: Focus on antimicrobial combination effects. Antibiotics, 11(8), 1014. https://doi.org/10.3390/antibiotics11081014
Vasconcelos, A. G., das GN Amorim, A., Dos Santos, R. C., Souza, J. M. T., de Souza, L. K. M., de SL Araújo, T., ... & de SA Leite, J. R. (2017). Lycopene rich extract from red guava (Psidium guajava L.) displays anti-inflammatory and antioxidant profile by reducing suggestive hallmarks of acute inflammatory response in mice. Food Research International, 99, 959–968. https://doi.org/10.1016/j.foodres.2017.01.017
Vermaak, C. (2020). The effect of Psidium guajava L. (herbal extract, mother tincture and 3cH) on multi-drug resistant Pseudomonas aeruginosa, in vitro [Doctoral dissertation, University of Johannesburg].
Wang, L., Wang, D., Wu, X., Xu, R., & Li, Y. (2020). Antiviral mechanism of carvacrol on HSV-2 infectivity through inhibition of RIP3-mediated programmed cell necrosis pathway and ubiquitin-proteasome system in BSC-1 cells. BMC Infectious Diseases, 20. https://doi.org/10.1186/s12879-020-05556-9
Wang, M., Zhan, X., Ma, X., Wang, R., Guo, D., Zhang, Y., ... & Shi, C. (2022). Antibacterial activity of thymoquinone against Shigella flexneri and its effect on biofilm formation. Foodborne Pathogens and Disease, 19(11), 767–778. https://doi.org/10.1089/fpd.2022.0056
Wang, M., Zhang, S., Li, R., & Zhao, Q. (2024). Unraveling the specialized metabolic pathways in medicinal plant genomes: A review. Frontiers in Plant Science, 15, 1459533. https://doi.org/10.3389/fpls.2024.1459533
Wei, J., Wang, B., Chen, Y., Wang, Q., Ahmed, A. F., Zhang, Y., & Kang, W. (2022). The immunomodulatory effects of active ingredients from Nigella sativa in RAW264.7 cells through NF-κB/MAPK signaling pathways. Frontiers in Nutrition, 9, 899797. https://doi.org/10.3389/fnut.2022.899797
Wei, Y., Ji, X. J., & Cao, M. (Eds.). (2024). Engineering biology for microbial biosynthesis of plant-derived bioactive compounds. Elsevier.
Wijesundara, N. M., Lee, S. F., Cheng, Z., Davidson, R., & Rupasinghe, H. V. (2021). Carvacrol exhibits rapid bactericidal activity against Streptococcus pyogenes through cell membrane damage. Scientific Reports, 11(1), 1487. https://doi.org/10.1038/s41598-020-79713-0
Wijesundara, N. M., Lee, S. F., Cheng, Z., Davidson, R., Langelaan, D. N., & Rupasinghe, H. V. (2022). Bactericidal activity of carvacrol against Streptococcus pyogenes involves alteration of membrane fluidity and integrity through interaction with membrane phospholipids. Pharmaceutics, 14(10), 1992. https://doi.org/10.3390/pharmaceutics14101992
Wu, Y., Bai, J., Zhong, K., Huang, Y., Qi, H., Jiang, Y., & Gao, H. (2016). Antibacterial activity and membrane-disruptive mechanism of 3-p-trans-coumaroyl-2-hydroxyquinic acid, a novel phenolic compound from pine needles of Cedrus deodara, against Staphylococcus aureus. Molecules, 21(8), 1084. https://doi.org/10.3390/molecules21081084
Yin, L., Liang, C., Wei, W., Huang, S., Ren, Y., Geng, Y., ... & Ouyang, P. (2022). The antibacterial activity of thymol against drug-resistant Streptococcus iniae and its protective effect on channel catfish (Ictalurus punctatus). Frontiers in Microbiology, 13, 914868. https://doi.org/10.3389/fmicb.2022.914868
Yu, Q., Wang, C., Zhang, X., Chen, H., Wu, M. X., & Lu, M. (2024). Photochemical strategies toward precision targeting against multidrug-resistant bacterial infections. ACS Nano. https://doi.org/10.1021/acsnano.3c12714
Zhang, H., Zhang, J., Lang, Z., Botella, J. R., & Zhu, J. K. (2017). Genome editing—principles and applications for functional genomics research and crop improvement. Critical Reviews in Plant Sciences, 36(4), 291–309. https://doi.org/10.1080/07352689.2017.1402989
Zhang, W., Wang, J., Chen, Y., Zheng, H., Xie, B., & Sun, Z. (2018). Flavonoid compounds and antibacterial mechanisms of different parts of white guava (Psidium guajava L. cv. Pearl). Natural Product Research, 34, 1621–1625. https://doi.org/10.1080/14786419.2018.1522313
Zhu, C., Lei, M., Andargie, M., Zeng, J., & Li, J. (2019). Antifungal activity and mechanism of action of tannic acid against Penicillium digitatum. Physiological and Molecular Plant Pathology, 107, 46–50. https://doi.org/10.1016/j.pmpp.2019.04.009
Zhu, X., Ouyang, W., Pan, C., Gao, Z., Han, Y., Song, M., ... & Cao, Y. (2019). Identification of a new benzophenone from Psidium guajava L. leaves and its antineoplastic effects on human colon cancer cells. Food & Function, 10(7), 4189–4198. https://doi.org/10.1039/C9FO00569B
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Abdulmajid Bashir, Gambo Lawal Mukhtar, Affan Usman
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
