Mineral contents, antimicrobial profile, acute and chronic toxicity of the aqueous extract of Moroccan Thymus vulgaris in rodents

Abstract

Moroccan flora is rich in plants used in traditional medicine, but the further scientific investigation is necessary. The aim of the research was to evaluate the nutritional content and antimicrobial activity of Moroccan Thymus vulgaris, as well as its possible acute and chronic toxicological effects on rodents. Inductively coupled plasma atomic emission spectroscopy (ICP-AES) was used to determine the mineral content. The antimicrobial activity was determined using a well-diffusion test, a minimum inhibitory concentration (MIC), and a minimum bactericidal/fungicidal concentration (MBC/MFC) assay. Acute and chronic toxicity studies were conducted in vivo on mice and rats, respectively. Following that, haematological, serum-biochemistry, and histological investigations were performed. Moroccan Thyme was shown to be a source of numerous minerals which are necessary for health promotion. All antimicrobial testing, disc diffusion, MIC, and MBC tests revealed that thyme had potent antibacterial activity against all microorganisms tested. Staphylococcus aureus was the most susceptible bacterium, followed by Salmonella enterica and Escherichia coli. Additionally, thyme exhibited great antifungal efficacy against Candida albicans. The acute toxicity results indicated that the aqueous extract of T. vulgaris is almost non-toxic when taken orally. According to the chronic toxicity study, the extract is generally safe when taken orally over an extended period of time. The biochemical and haematological characteristics of the serum and blood were within acceptable limits, and histological examination revealed no abnormalities. In conclusion, the findings of this investigation, confirm the antimicrobial efficacy of the aqueous extract of Moroccan T. vulgaris and its safety for experimental animals.

Keywords

• Thymus vulgaris
• Mineral analysis
• Toxicity
• Antimicrobial
• Rodents

References

1. Abdallah, E.M. (2011). Plants: An alternative source for antimicrobials. Journal of Applied Pharmaceutical Science, 1(6), 16–20.
2. Abdallah, E.M. (2016). Antibacterial activity of Hibiscus sabdariffa L. calyces against hospital isolates of multidrug resistant Acinetobacter baumannii. Journal of Acute Disease, 5(6), 512–516. https://doi.org/10.1016/j.joad.2016.08.024
3. Abdallah, E.M., Mujawah, A.A.H., & Al-Mijalli, S.H. (2021). GC-MS and Antibacterial potential of methanolic extract hyphaene Thebaica L. Fruit pulp against antibiotics-resistant pathogens. Journal of Pure and Applied Microbiology, 15(3), 1655–1664. https://doi.org/10.22207/jpam.15.3.62
4. Abdulkarimi, R., Daneshyar, M., & Aghazadeh, A. (2011). Thyme (Thymus vulgaris) extract consumption darkens liver, lowers blood cholesterol, proportional liver and abdominal fat weights in broiler chickens. Italian Journal of Animal Science, 10(2), e20. https://doi.org/10.4081/ijas.2011.e20
5. Abuga, I., Sulaiman, S.F., Wahab, R.A., Ooi, K.L., & Rasad, M.S.B.A. (2020). In vitro antibacterial effect of the leaf extract of Murraya koenigii on cell membrane destruction against pathogenic bacteria and phenolic compounds identification. European Journal of Integrative Medicine, 33, 101010.
6. Al Kaabi, S.K.S., Senthilkumar, A., Kizhakkayil, J., Alyafei, M.A.M., Kurup, S.S., Al Dhaheri, A.S., & Jaleel, A. (2022). Anticancer activity of Moringa peregrina (Forssk.) Fiori.: A Native plant in traditional herbal medicine of the United Arab Emirates. Horticulturae, 8(1), 37.
7. Al-Bayati, F.A. (2008). Synergistic antibacterial activity between Thymus vulgaris and Pimpinella anisum essential oils and methanol extracts. Journal of Ethnopharmacology, 116(3), 403–406.
8. Anand, U., Jacobo-Herrera, N., Altemimi, A., & Lakhssassi, N. (2019). A comprehensive review on medicinal plants as antimicrobial therapeutics: Potential avenues of biocompatible drug discovery. Metabolites, 9(11), 258.

9. Benourad, F., Kahvecioglu, Z., Youcef-Benkada, M., & Colet, J.-M. (2014). Prospective evaluation of potential toxicity of repeated doses of Thymus vulgaris L. extracts in rats by means of clinical chemistry, histopathology and NMR-based metabonomic approach. Drug Testing and Analysis, 6(10), 1069–1075.
10. Borugă, O., Jianu, C., Mişcă, C., Goleţ, I., Gruia, A.T., & Horhat, F.G. (2014). Thymus vulgaris essential oil: Chemical composition and antimicrobial activity. Journal of Medicine and Life, 7(Spec Iss 3), 56–60.
11. Bouyahya, A., Dakka, N., Et-Touys, A., Abrini, J., & Bakri, Y. (2017a). Medicinal plant products targeting quorum sensing for combating bacterial infections. Asian Pacific Journal of Tropical Medicine, 10(8), 729–743. https://doi.org/10.1016/j.apjtm.2017.07.021
12. Bouyahya, A., Et-Touys, A., Bakri, Y., Talbaui, A., Fellah, H., Abrini, J., & Dakka, N. (2017b). Chemical composition of Mentha pulegium and Rosmarinus officinalis essential oils and their antileishmanial, antibacterial and antioxidant activities. Microbial Pathogenesis, 111, 41–49.
13. Bouyahya, A., Dakka, N., Talbaoui, A., Et-Touys, A., El-Boury, H., Abrini, J., & Bakri, Y. (2017c). Correlation between phenological changes, chemical composition and biological activities of the essential oil from Moroccan endemic Oregano (Origanum compactum Benth). Industrial Crops and Products, 108, 729 737. https://doi.org/10.1016/j.indcrop.2017.07.033
14. Bouyahya, A., Abrini, J., Dakka, N., & Bakri, Y. (2019). Essential oils of Origanum compactum increase membrane permeability, disturb cell membrane integrity, and suppress quorum-sensing phenotype in bacteria. Journal of Pharmaceutical Analysis, 9(5), 301 311. https://doi.org/10.1016/j.jpha.2019.03.001
15. Bouyahya, A., El Omari, N., Elmenyiy, N., Guaouguaou, F.-E., Balahbib, A., El-Shazly, M., & Chamkhi, I. (2020a). Ethnomedicinal use, phytochemistry, pharmacology, and toxicology of Ajuga iva (L.,) Schreb. Journal of Ethnopharmacology, 258, 112875.
16. Bouyahya, A., Belmehdi, O., Benjouad, A., El Hassani, R. A., Amzazi, S., Dakka, N., & Bakri, Y. (2020b). Pharmacological properties and mechanism insights of Moroccan anticancer medicinal plants: What are the next steps? Industrial Crops and Products, 147, 112198.
17. Bouyahya, A., Chamkhi, I., Guaouguaou, F.-E., Benali, T., Balahbib, A., El Omari, N., Taha, D., El-Shazly, M., & El Menyiy, N. (2020c). Ethnomedicinal use, phytochemistry, pharmacology, and food benefits of Thymus capitatus. Journal of Ethnopharmacology, 259, 112925. https://doi.org/10.1016/j.jep.2020.112925
18. Bouyahya, A., El Menyiy, N., Oumeslakht, L., El Allam, A., Balahbib, A., Rauf, A., Muhammad, N., Kuznetsova, E., Derkho, M., & Thiruvengadam, M. (2021a). Preclinical and clinical antioxidant effects of natural compounds against oxidative stress-induced epigenetic instability in tumor cells. Antioxidants, 10(10), 1553.
19. Bouyahya, A., El Omari, N., Elmenyiy, N., Guaouguaou, F.-E., Balahbib, A., Belmehdi, O., Salhi, N., Imtara, H., Mrabti, H. N., & El-Shazly, M. (2021b). Moroccan antidiabetic medicinal plants: Ethnobotanical studies, phytochemical bioactive compounds, preclinical investigations, toxicological validations and clinical evidences; challenges, guidance and perspectives for future management of diabetes worldwide. Trends in Food Science & Technology, 115, 147–254.
20. Bouyahya, A., Guaouguaou, F.-E., El Omari, N., El Menyiy, N., Balahbib, A., El-Shazly, M., & Bakri, Y. (2021c). Anti-inflammatory and analgesic properties of moroccan medicinal plants: Phytochemistry, in vitro and in vivo investigations, mechanism insights, clinical evidences and perspectives. Journal of Pharmaceutical Analysis, 12, 35–37.
21. Carolina, A., Santana, E.F. De, Marcos, A., Coutinho, F.N., Henrique, R., Castro, A. De, & Nelly, M. (2013). Which approach is more effective in the selection of drugs. Evidence-Based Complementary and Alternative Medicine, 2013, 2005–2010.
22. Chakotiya, A.S., Tanwar, A., Narula, A., & Sharma, R. K. (2017). Zingiber officinale: Its antibacterial activity on Pseudomonas aeruginosa and mode of action evaluated by flow cytometry. Microbial Pathogenesis, 107, 254–260.
23. Chamkhi, I., Benali, T., Aanniz, T., El Menyiy, N., Guaouguaou, F.-E., El Omari, N., El-Shazly, M., Zengin, G., & Bouyahya, A. (2021). Plant-microbial interaction: The mechanism and the application of microbial elicitor induced secondary metabolites biosynthesis in medicinal plants. Plant Physiology and Biochemistry, 167, 269–295.
24. Chamkhi, I., Charfi, S., Hachlafi, N.E., Mechchate, H., Guaouguaou, F.-E., El Omari, N., Bakrim, S., Balahbib, A., Zengin, G., & Bouyahya, A. (2022). Genetic diversity, antimicrobial, nutritional, and phytochemical properties of Chenopodium album: A comprehensive review. Food Research International, 154, 110979.
25. Cowan, M.M. (1999). Plant products as antimicrobial agents. Clinical Microbiology Reviews, 12(4), 564–582.
26. Eddouks, M., Maghrani, M., Lemhadri, A., Ouahidi, M.-L., & Jouad, H. (2002a). Ethnopharmacological survey of medicinal plants used for the treatment of diabetes mellitus, hypertension and cardiac diseases in the south-east region of Morocco (Tafilalet). Journal of Ethnopharmacology, 82(2), 97–103. https://doi.org/10.1016/S0378-8741(02)00164-2
27. Eddouks, M., Maghrani, M., Lemhadri, A., Ouahidi, M.-L., & Jouad, H. (2002b). Ethnopharmacological survey of medicinal plants used for the treatment of diabetes mellitus, hypertension and cardiac diseases in the south-east region of Morocco (Tafilalet). Journal of Ethnopharmacology, 82(2–3), 97–103.
28. El Kabbaoui, M., Chda, A., El-Akhal, J., Azdad, O., Mejrhit, N., Aarab, L., Bencheikh, R., & Tazi, A. (2017). Acute and sub-chronic toxicity studies of the aqueous extract from leaves of Cistus ladaniferus L. in mice and rats. Journal of Ethnopharmacology, 209(April), 147–156. https://doi.org/10.1016/j.jep.2017.07.029
29. Escobar, A., Pérez, M., Romanelli, G., & Blustein, G. (2020). Thymol bioactivity: A review focusing on practical applications. Arabian Journal of Chemistry, 13(12), 9243–9269. https://doi.org/10.1016/j.arabjc.2020.11.009
30. Fournomiti, M., Kimbaris, A., Mantzourani, I., Plessas, S., Theodoridou, I., Papaemmanouil, V., Kapsiotis, I., Panopoulou, M., Stavropoulou, E., Bezirtzoglou, E. E., & Alexopoulos, A. (2015). Antimicrobial activity of essential oils of cultivated oregano (Origanum vulgare), sage (Salvia officinalis), and thyme (Thymus vulgaris) against clinical isolates of Escherichia coli , Klebsiella oxytoca, and Klebsiella pneumoniae. Microbial Ecology in Health & Disease, 26(0). https://doi.org/10.3402/mehd.v26.23289
31. Guillén, M.D., & Manzanos, M.J. (1998). Study of the composition of the different parts of a Spanish thymus vulgaris L. plant. Food Chemistry, 63(3), 373 383. https://doi.org/10.1016/S0308-8146(98)00013-2
32. Gulluce, M., Aslan, A., Sokmen, M., Sahin, F., Adiguzel, A., Agar, G., & Sokmen, A. (2006). Screening the antioxidant and antimicrobial properties of the lichens Parmelia saxatilis, Platismatia glauca, Ramalina pollinaria, Ramalina polymorpha and Umbilicaria nylanderiana. Phytomedicine, 13(7), 515 521. https://doi.org/10.1016/j.phymed.2005.09.008
33. Gupta, E., & Mishra, P. (2020). Functional Food with Some Health Benefits, So Called Superfood: A Review. Current Nutrition & Food Science, 17(2), 144 166. https://doi.org/10.2174/1573401316999200717171048
34. Hajlaoui, H., Arraouadi, S., Noumi, E., Aouadi, K., Adnan, M., Khan, M.A., Kadri, A., & Snoussi, M. (2021). Antimicrobial, antioxidant, anti-acetylcholinesterase, antidiabetic, and pharmacokinetic properties of Carum carvi L. and Coriandrum sativum L. essential oils alone and in combination. Molecules, 26(12), 3625.
35. Harvey, A.L. (2008). Natural products drug discovery. Drug Discovery Today, 13(19–20), 894–901. https://doi.org/10.1016/j.drudis.2008.07.004
36. Imelouane, B., Amhamdi, H., Whathelet, J., Ankit, M., Khedid, K., & EL Bachiri, A. (2011). Chemical composition and antimicrobial activity of essential oil of Thymus vulgaris from Yemen. Turkish Journal of Biochemistry, 36(4), 342–349.
37. Jafari, B., Fatemi, S., Pashazadeh, M., Al-Snafi, A.E., & Shariat, A. (2020). Antibacterial effects of Thymus vulgaris, Mentha pulegium, Crocus sativus and Salvia officinalis on pathogenic bacteria: A brief review study based on gram-positive and gram-negative bacteria. Jorjani Biomedicine Journal, 8(3), 58–74.
38. Jones, K.E., Patel, N.G., Levy, M.A., Storeygard, A., Balk, D., Gittleman, J.L., & Daszak, P. (2008). Global trends in emerging infectious diseases. Nature, 451(7181), 990–993.
39. Joshi, T., Jain, T., Mahar, R., Singh, S.K., Srivastava, P., Shukla, S.K., Mishra, D.K., Bhatta, R.S., Banerjee, D., & Kanojiya, S. (2018). Pyranocarbazoles from Murraya koenigii (L.) Spreng. As antimicrobial agents. Natural Product Research, 32(4), 430–434.
40. Khalfaoui, A., Noumi, E., Belaabed, S., Aouadi, K., Lamjed, B., Adnan, M., Defant, A., Kadri, A., Snoussi, M., & Khan, M.A. (2021). LC-ESI/MS-Phytochemical Profiling with antioxidant, antibacterial, antifungal, antiviral and in silico pharmacological properties of Algerian Asphodelus tenuifolius (Cav.) organic extracts. Antioxidants, 10(4), 628.
41. Major, R.H. (1954). A history of medicine. In A history of medicine (pp. 563–563).
42. Mann, C.M., Cox, S.D., & Markham, J.L. (2000). The outer membrane of Pseudomonas aeruginosa NCTC 6749 contributes to its tolerance to the essential oil of Melaleuca alternifolia (tea tree oil). Letters in Applied Microbiology, 30(4), 294–297.
43. Matasyoh, J.C., Maiyo, Z.C., Ngure, R.M., & Chepkorir, R. (2009). Chemical composition and antimicrobial activity of the essential oil of Coriandrum sativum. Food Chemistry, 113(2), 526–529.
44. Mendelson, M., & Matsoso, M. P. (2015). The World Health Organization global action plan for antimicrobial resistance. SAMJ: South African Medical Journal, 105(5), 325–325.
45. Miraj, S., & Kiani, S. (2016). A review study of therapeutic effects of Salvia officinalis L‏. Der Pharmacia Lettre, 8(6), 299-303.
46. Mrabti, H.N., Bouyahya, A., Ed-Dra, A., Kachmar, M.R., Mrabti, N.N., Benali, T., Shariati, M.A., Ouahbi, A., Doudach, L., & Faouzi, M.E.A. (2021). Polyphenolic profile and biological properties of Arbutus unedo root extracts. European Journal of Integrative Medicine, 42(September 2020), 101266. https://doi.org/10.1016/j.eujim.2020.101266
47. Mrabti, H.N., Jaradat, N., Fichtali, I., Ouedrhiri, W., Jodeh, S., Ayesh, S., Cherrah, Y., & Faouzi, M.E.A. (2018). Separation, identification, and antidiabetic activity of catechin isolated from Arbutus unedo L. Plant roots. Plants, 7(2), 31. https://doi.org/10.3390/plants7020031
48. Mseddi, K., Alimi, F., Noumi, E., Veettil, V.N., Deshpande, S., Adnan, M., Hamdi, A., Elkahoui, S., Alghamdi, A., & Kadri, A. (2020). Thymus musilii Velen. as a promising source of potent bioactive compounds with its pharmacological properties: In vitro and in silico analysis. Arabian Journal of Chemistry, 13(8), 6782–6801.
49. Mustafa, S., Hina, S., Mahmood, S., Mueen-ud-din, G., & Alam, M.Q. (2020). Exploring phytochemical potential of nature’ s bliss Thymus vulgaris L. Mini review. International Journal of Botany Studies, 5(3), 493–496.
50. Naceiri Mrabti, H., Doudach, L., El Menyiy, N., Bourhia, M., Mohammad Salamatullah, A., Reda Kachmar, M., Belmehdi, O., El Moudden, H., Naceiri Mrabti, N., & Harhar, H. (2021). Phytochemistry and Pharmacology of Thymus broussonetii Boiss. Evidence-Based Complementary and Alternative Medicine, 2021, Article ID 6350035, 15 pages
51. Noumi, E., Snoussi, M., Anouar, E.H., Alreshidi, M., Veettil, V.N., Elkahoui, S., Adnan, M., Patel, M., Kadri, A., & Aouadi, K. (2020). HR-LCMS-based metabolite profiling, antioxidant, and anticancer properties of Teucrium polium L. methanolic extract: Computational and in vitro study. Antioxidants, 9(11), 1089.
52. OECD (2001). Acute Oral Toxicity – Fixed Dose Procedure (chptr). In Guidelines for the Testing of Chemicals (pp. 1–14).
53. Oliviero, M., Romilde, I., Beatrice, M.M., Matteo, V., Giovanna, N., Consuelo, A., Claudio, C., Giorgio, S., Maggi, F., & Massimo, N. (2016). Evaluations of thyme extract effects in human normal bronchial and tracheal epithelial cell lines and in human lung cancer cell line. Chemico-Biological Interactions, 256, 125–133. https://doi.org/10.1016/j.cbi.2016.06.024
54. Ouknin, M., Romane, A., Arjouni, M.Y., & Majidi, L. (2018). Mineral composition, multivariate analysis of some oligo-elements and heavy metals in some species of genus Thymus. Journal of Materials and Environmental Science, 9(3), 980–985.
55. Özcan, M. (2004). Mineral contents of some plants used as condiments in Turkey. Food Chemistry, 84(3), 437–440.
56. Pieracci, Y., Ciccarelli, D., Giovanelli, S., Pistelli, L., Flamini, G., Cervelli, C., Mancianti, F., Nardoni, S., Bertelloni, F., & Ebani, V.V. (2021). Antimicrobial activity and composition of five Rosmarinus (Now Salvia spp. and varieties) essential oils. Antibiotics, 10(9), 1090. https://doi.org/10.3390/antibiotics10091090
57. Prasanth, R., Kandisa, R.V., Varsha, P., & Satyam, S. (2014). Review on Thymus vulgaris traditional ues and pharmacological properties. Medicinal & Aromatic Plants, 03(04), 3–5. https://doi.org/10.4172/2167-0412.1000167
58. Qiao, M., Ying, G.-G., Singer, A.C., & Zhu, Y.-G. (2018). Review of antibiotic resistance in China and its environment. Environment International, 110, 160–172.
59. Randhawa, M.A., Alenazy, A.K., Alrowaili, M.G., & Basha, J. (2017). An active principle of Nigella sativa L., thymoquinone, showing significant antimicrobial activity against anaerobic bacteria. Journal of Intercultural Ethnopharmacology, 6(1), 97-101. https://doi.org/10.5455/jice.20161018021238
60. Reddy, M.N., Adnan, M., Alreshidi, M.M., Saeed, M., & Patel, M. (2020). Evaluation of anticancer, antibacterial and antioxidant properties of a medicinally treasured fern Tectaria coadunata with its phytoconstituents analysis by HR-LCMS. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents), 20(15), 1845–1856.
61. Rojas-Armas, J., Arroyo-Acevedo, J., Ortiz-Sánchez, M., Palomino-Pacheco, M., Castro-Luna, A., Ramos-Cevallos, N., Justil-Guerrero, H., Hilario-Vargas, J., & Herrera-Calderón, O. (2019). Acute and repeated 28-day oral dose toxicity studies of Thymus vulgaris L. essential oil in rats. Toxicological Research, 35(3), 225–232.
62. Rota, M.C., Herrera, A., Martínez, R.M., Sotomayor, J.A., & Jordán, M.J. (2008). Antimicrobial activity and chemical composition of Thymus vulgaris, Thymus zygis and Thymus hyemalis essential oils. Food Control, 19(7), 681 687. https://doi.org/10.1016/j.foodcont.2007.07.007
63. Salehi, B., Quispe, C., Chamkhi, I., El Omari, N., Balahbib, A., Sharifi-Rad, J., Bouyahya, A., Akram, M, Iqbal, M., Docea, A.O., Caruntu, C., Leyva-Gómez, G., Dey, A, Martorell, M., Calina, D., López, V., & Les, F. (2021) Pharmacological Properties of Chalcones: A Review of Preclinical Including Molecular Mechanisms and Clinical Evidence. Frontiers in Pharmacology, 11, 592654. https://doi.org/10.3389/fphar.2020.592654
64. Salman, M.T., Khan, R.A., & Shukla, I. (2008). Antimicrobial activity of Nigella sativa Linn. Seed oilagainst multi-drug resistant bacteria from clinical isolates. Natural Product Radiance, 7(1), 10-14.
65. Savaroğlu, F., İşçen, C.F., Vatan, A.P., Kabadere, O., & Sİlhan, S. (2011). Determination of antimicrobial and antiproliferative activities of the aquatic moss Fontinalis antipyretica Hedw. Turkish Journal of Biology, 35(3), 361–369.
66. Sharifi-Rad, J., Dey, A., Koirala, N., Shaheen, S., El Omari, N., Salehi, B., Goloshvili, T., Silva, N.C.C., Bouyahya, A., & Vitalini, S. (2021). Cinnamomum species: Bridging phytochemistry knowledge, pharmacological properties and toxicological safety for health benefits. Frontiers in Pharmacology, 11(12), 1541. https://doi.org/10.3390/plants11121541
67. Soni, M.G., Thurmond, T.S., Miller III, E.R., Spriggs, T., Bendich, A., & Omaye, S.T. (2010). Safety of vitamins and minerals: Controversies and perspective. Toxicological Sciences, 118(2), 348–355.
68. Swayeh, N.H., Abu-Raghif, A.R., Qasim, B.J., & Sahib, H.B. (2014). The protective effects of Thymus Vulgaris aqueous extract against Methotrexate-induced hepatic toxicity in rabbits. International Journal of Pharmaceutical Sciences Review and Research, 29, 187–193.
69. Tuama, R.J. (2016). Effect of thyme (Thymus vulgaris L.) oil on some biochemical parameters of diabetic female rats. World Journal of Pharmaceutical Research, 4(6), 320–325. https://doi.org/10.13140/RG.2.2.24589.49122
70. Tural, S., & Turhan, S. (2017). antimicrobial and antioxidant properties of thyme (Thymus vulgaris L.), Rosemary (Rosmarinus officinalis L.) and laurel (Lauris nobilis L.) essential oils and their mixtures. The Journal of Food, 42(5), 588 596. https://doi.org/10.15237/gida.gd17030
71. Vannucci, L., Fossi, C., Quattrini, S., Guasti, L., Pampaloni, B., Gronchi, G., Giusti, F., Romagnoli, C., Cianferotti, L., Marcucci, G., & Brandi, M.L. (2018). Calcium Intake in bone health: A focus on calcium rich mineral waters. Nutrients, 10(12), 1 12. https://doi.org/10.3390/nu10121930
72. Zaazaa, L., Naceiri Mrabti, H., Ed-Dra, A., Bendahbia, K., Hami, H., Soulaymani, A., & Ibriz, M. (2021). Determination of Mineral Composition and Phenolic Content and Investigation of Antioxidant, Antidiabetic, and Antibacterial Activities of Crocus sativus L. Aqueous Stigmas Extracts. Advances in Pharmacological and Pharmaceutical Sciences, 2021, Article ID 7533938, 7 pages. https://doi.org/10.1155/2021/7533938
73. Zare-Shehneh, M., Askarfarashah, M., Ebrahimi, L., Kor, N.M., Zare-Zardini, H., Soltaninejad, H., Hashemian, Z., & Jabinian, F. (2014). Biological activities of a new antimicrobial peptide from Coriandrum sativum. International Journal of Biosciences, 4(6), 89–99.