Antidepressant-like effects of aqueous extracts of miswak (Salvadora persica) and date palm (Phoenix dactylifera) on depression-like behaviors using CUMS model in male rats
Basma Youssef
Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt
Contribution: Conceptualization, Data curation, Methodology
Search for more papers by this authorKholoud S. Ramadan
Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt
Contribution: Conceptualization, Supervision
Search for more papers by this authorShaimaa ElShebiney
Department of Narcotics, Poisons and Ergogenic Aids, National Research Centre, Cairo, Egypt
Contribution: Conceptualization, Data curation, Formal analysis, Supervision
Search for more papers by this authorCorresponding Author
Ehab A. Ibrahim
Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt
Correspondence
Ehab A. Ibrahim, Biochemistry Department, Faculty of Science, Ain Shams University, El-Khalifa El-mamoun st., 11566 Abbassia, Cairo, Egypt.
Email: [email protected], [email protected]
Contribution: Conceptualization, Supervision, Writing - original draft, Writing - review & editing
Search for more papers by this authorBasma Youssef
Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt
Contribution: Conceptualization, Data curation, Methodology
Search for more papers by this authorKholoud S. Ramadan
Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt
Contribution: Conceptualization, Supervision
Search for more papers by this authorShaimaa ElShebiney
Department of Narcotics, Poisons and Ergogenic Aids, National Research Centre, Cairo, Egypt
Contribution: Conceptualization, Data curation, Formal analysis, Supervision
Search for more papers by this authorCorresponding Author
Ehab A. Ibrahim
Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt
Correspondence
Ehab A. Ibrahim, Biochemistry Department, Faculty of Science, Ain Shams University, El-Khalifa El-mamoun st., 11566 Abbassia, Cairo, Egypt.
Email: [email protected], [email protected]
Contribution: Conceptualization, Supervision, Writing - original draft, Writing - review & editing
Search for more papers by this authorFunding information
The author(s) did not receive any funding for this research, authorship, or publication of this paper.
Abstract
This study aimed to evaluate the antidepressant-like effects of aqueous extracts of miswak (Salvadora persica) and date palm (Phoenix dactylifera) and their combination on depression-like behaviors using a chronic unpredictable mild stress (CUMS) rat model of depression and to investigate the underlying possible mechanisms. Results showed that CUMS induced depression-like behaviors and anxiety in male rats, as determined by behavioral tests (FST, EPM, and OFT). CUMS significantly increased the levels of plasma malondialdehyde (MDA), cortisol, and pro-inflammatory cytokines (TNF-α and IL-6), in addition to enhancing acetylcholinesterase (ACHE) activity while plasma total antioxidant capacity and serotonin level were reduced. In the prefrontal cortex, CUMS decreased the expression of CREB and BDNF mRNA. However, aqueous extracts of miswak and date palm and their combination effectively ameliorated depressive-like behaviors, body weight loss, and oxidative stress induced by CUMS and restored serotonin and cortisol secretion to normal levels. Furthermore, the studied extracts improved the levels of plasma pro-inflammatory cytokines and CREB and BDNF mRNA expression in the prefrontal cortex. In conclusion, aqueous extracts of miswak and date palm have significant antidepressant-like effects on depression-like behaviors in CUMS model in rats. Moreover, their combination has higher antidepressant-like effects than either extract alone, suggesting that it may be an effective treatment for stress-induced depression-like behaviors acting through modulating pro-inflammatory cytokines and CREB/BDNF signaling pathway in the prefrontal cortex.
Practical applications
Chronic stress is a major contributor to the development of depression. In recent years, there has been a significant increase in the use of herbal remedies for the treatment of a variety of diseases, particularly mood disorders. Because of the side effects encountered by antidepressant drugs such as anxiety, sexual dysfunction, loss of appetite, and inadequate response or developing tolerance to these medications, there is a need for more efficient and convenient antidepressant treatments. According to this study, aqueous extracts of miswak and date palm are effective treatments for stress-induced depression-like behaviors.
CONFLICT OF INTEREST
The author(s) of this article have declared that they have no potential conflicts of interest related to the research, writing, or publication of this article.
REFERENCES
- Abdelhamid, Z. S., Serry, Z. M., Elnahas, N. M., & Ammar, N. M. (2016). Serum serotonin response to aerobic exercise versus phoenix. International Journal of PharmTech Research., 9, 108–114.
- Abuelgassim, A. O. (2020). Towards the utilization of date palm (Phoenix dactylifera) leaves as a rich source of antioxidants. Journal of Food & Nutrition Research, 8(11), 632–637. https://doi.org/10.12691/jfnr-8-11-3
- Ahmad, M., Imran, H., Yaqeen, Z., Rehman, Z., Rahman, A., Fatima, N., & Sohail, T. (2011). Pharmacological profile of Salvadora persica. Pakistan Journal of Pharmaceutical Sciences, 24(3), 323–330.
- AlFaris, N. A., AlTamimi, J. Z., AlGhamdi, F. A., Albaridi, N. A., Alzaheb, R. A., Aljabryn, D. H., Aljahani, A. H., & AlMousa, L. (2021). Total phenolic content in ripe date fruits (Phoenix dactylifera L.): A systematic review and meta-analysis. Saudi Journal of Biological Sciences, 28(6), 3566–3577. https://doi.org/10.1016/j.sjbs.2021.03.033
- Aljaloud, S., Colleran, H. L., & Ibrahim, S. A. (2020). Nutritional value of date fruits and potential use in nutritional bars for athletes. Food and Nutrition Sciences, 11(6), 463–480. https://doi.org/10.4236/fns.2020.116034
- Almahozi, A., Radhi, M., Alzayer, S., & Kamal, A. (2019). Effects of memantine in a mouse model of postoperative cognitive dysfunction. Behavioral Sciences, 9(3), 24. https://doi.org/10.3390/bs9030024
- Arosio, B., Guerini, F. R., Voshaar, R. C. O., & Aprahamian, I. (2021). Blood brain-derived neurotrophic factor (BDNF) and major depression: Do we have a translational perspective? Frontiers in Behavioral Neuroscience, 15, 626906. https://doi.org/10.3389/fnbeh.2021.626906
- Asrari, N., Yazdian-Robati, R., Abnous, K., Razavi, B. M., Rashednia, M., Hasani, F. V., & Hosseinzadeh, H. (2018). Antidepressant effects of aqueous extract of saffron and its effects on CREB, P-CREB, BDNF, and VGF proteins in rat cerebellum. Journal of Pharmacopuncture, 21(1), 35–40. https://doi.org/10.3831/KPI.2018.21.005
- Aumeeruddy, M. Z., Zengin, G., & Mahomoodally, M. F. (2018). A review of the traditional and modern uses of Salvadora persica L. (Miswak): Toothbrush tree of prophet Muhammad. Journal of Ethnopharmacology, 213, 409–444. https://doi.org/10.1016/j.jep.2017.11.030
- Bernhard, A., Mayer, J. S., Fann, N., & Freitag, C. M. (2021). Cortisol response to acute psychosocial stress in ADHD compared to conduct disorder and major depressive disorder: A systematic review. Neuroscience and Biobehavioral Reviews, 127, 899–916. https://doi.org/10.1016/j.neubiorev.2021.06.005
- Beutler, E., Duron, O., & Kelly, B. M. (1963). Improved method for the determination of blood glutathione. The Journal of Laboratory and Clinical Medicine, 61, 882–888.
- Bhatt, S., Nagappa, A. N., & Patil, C. R. (2020). Role of oxidative stress in depression. Drug Discovery Today, 25(7), 1270–1276. https://doi.org/10.1016/j.drudis.2020.05.001
- Budni, J., Moretti, M., Freitas, A. E., Neis, V. B., Ribeiro, C. M., de Oliveira Balen, G., Rieger, D. K., Leal, R. B., & Rodrigues, A. L. S. (2021). Behavioral and neurochemical effects of folic acid in a mouse model of depression induced by TNF-α. Behavioural Brain Research, 414, 113512. https://doi.org/10.1016/j.bbr.2021.113512
- Chen, T., Liu, S., Zheng, M., Li, Y., & He, L. (2021). The effect of geniposide on chronic unpredictable mild stress-induced depressive mice through BTK/TLR4/NF-κB and BDNF/TrkB signaling pathways. Phytotherapy Research, 35(2), 932–945. https://doi.org/10.1002/ptr.6846
- Costache, A., Riza, A. L., Ioana, M., Glavan, D. G., Dinca, M. E., Vladu, I. M., Popescu, M., & Udristoiu, I. (2020). Circulating cortisol in a cohort of depressive patients. Current Health Sciences Journal, 46(1), 11–15. https://doi.org/10.12865/CHSJ.46.01.02
- Cryan, J. F., & Holmes, A. (2005). The ascent of mouse: Advances in modelling human depression and anxiety. Nature Reviews Drug Discovery, 4(9), 775–790. https://doi.org/10.1038/nrd1825
- Ekeanyanwu, R. C., Nkwocha, C. C., & Ekeanyanwu, C. L. (2021). Behavioural and biochemical indications of the antidepressant activities of essential oils from Monodora myristica (Gaertn) seed and Xylopia aethiopica (Dunal) fruit in rats. IBRO Neuroscience Reports, 10, 66–74. https://doi.org/10.1016/j.ibneur.2021.01.001
- El Hawary, S. S., Saad, S., El Halawany, A. M., Ali, Z. Y., & El Bishbishy, M. (2016). Phenolic content and anti-hyperglycemic activity of pecan cultivars from Egypt. Pharmaceutical Biology, 54(5), 788–798. https://doi.org/10.3109/13880209.2015.1080732
- El-Bali, M. A., Abdulhakim, A., Mohamed, R. T., El-Malky, M. A., Bakri, R. A., & Al-Harthi, S. A. (2020). Antiprotozoal potential of Salvadora persica against three virulent subtypes of Blastocystis sp. Journal of Parasitic Diseases, 44(4), 694–701. https://doi.org/10.1007/s12639-020-01247-z
- Ellman, G. L., Courtney, K. D., Andres, V., Jr., & Featherstone, R. M. (1961). A new and rapid colorimetric determination of acetylcholinesterase activity. Biochemical Pharmacology, 7, 88–95. https://doi.org/10.1016/0006-2952(61)90145-9
- El-Mousalamy, M. D. A., Hussein, A. A. M., Mahmoud, S. A., Abdelaziz, A., & Shaker, G. (2016). Aqueous and methanolic extracts of palm date seeds and fruits (Phoenix dactylifera) protects against diabetic nephropathy in type II diabetic rats. Biochemistry & Physiology, 5(2), 1–9. https://doi.org/10.4172/2168-9652.1000205
10.4172/2168?9652.1000205 Google Scholar
- Farag, M., Abdel-Mageed, W. M., El Gamal, A. A., & Basudan, O. A. (2021). Salvadora persica L.: Toothbrush tree with health benefits and industrial applications—An updated evidence-based review. Saudi Pharmaceutical Journal, 29(7), 751–763. https://doi.org/10.1016/j.jsps.2021.05.007
- Gill, H., Gill, B., El-Halabi, S., Chen-Li, D., Lipsitz, O., Rosenblat, J. D., van Rheenen, T., Rodrigues, N. B., Mansur, R. B., Majeed, A., Lui, L. M. W., Nasri, F., Lee, Y., & Mcintyre, R. S. (2020). Antidepressant medications and weight change: A narrative review. Obesity, 28(11), 2064–2072. https://doi.org/10.1002/oby.22969
- Himanshu, D., & Deepa, S. N. (2020). A review of behavioral tests to evaluate different types of anxiety and anti-anxiety effects. Clinical Psychopharmacology and Neuroscience, 18(3), 341–351. https://doi.org/10.9758/cpn.2020.18.3.341
- Hussain, S. M., & Taha, M. (2015). A laboratory quest on use of date fruit (Phoenix Dactylifera, L.) extract in prevention of chemically induced memory deficit models in mice. Asian Journal of Biomedical and Pharmaceutical Sciences, 5(49), 5. https://doi.org/10.15272/ajbps.v5i49.739
- Ibrahim, E. A., Moawed, F. S. M., & Moustafa, E. M. (2020). Suppression of inflammatory cascades via novel cinnamic acid nanoparticles in acute hepatitis rat model. Archives of Biochemistry and Biophysics, 696, 108658. https://doi.org/10.1016/j.abb.2020.108658
- Jia, Z., Yang, J., Cao, Z., Zhao, J., Zhang, J., Lu, Y., Chu, L., Zhang, S., Chen, Y., & Pei, L. (2021). Baicalin ameliorates chronic unpredictable mild stress-induced depression through the BDNF/ERK/CREB signaling pathway. Behavioural Brain Research, 414, 113463. https://doi.org/10.1016/j.bbr.2021.113463
- Kawabata, K., Kawai, Y., & Terao, J. (2010). Suppressive effect of quercetin on acute stress-induced hypothalamic-pituitary-adrenal axis response in Wistar rats. The Journal of Nutritional Biochemistry, 21(5), 374–380. https://doi.org/10.1016/j.jnutbio.2009.01.008
- Khadrawy, Y. A., Sawie, H. G., Abdel-Salam, O. M. E., & Hosny, E. N. (2017). Cannabis exacerbates depressive symptoms in rat model induced by reserpine. Behavioural Brain Research, 324, 41–50. https://doi.org/10.1016/j.bbr.2017.02.015
- Kim, Y. R., Park, B. K., Kim, Y. H., Shim, I., Kang, I. C., & Lee, M. Y. (2018). Antidepressant effect of Fraxinus rhynchophylla hance extract in a mouse model of chronic stress-induced depression. BioMed Research International, 2018, 8249563. https://doi.org/10.1155/2018/8249563
- Koracevic, D., Koracevic, G., Djordjevic, V., Andrejevic, S., & Cosic, V. (2001). Method for the measurement of antioxidant activity in human fluids. Journal of Clinical Pathology, 54(5), 356–361. https://doi.org/10.1136/jcp.54.5.356
- Krishnaiah, D., Devi, T., Bono, A., & Sarbatly, R. (2009). Studies on phytochemical constituents of six Malaysian medicinal plants. Journal of Medicinal Plants Research, 3(2), 67–72. https://doi.org/10.5897/JMPR.9001153
10.5897/JMPR.9001153 Google Scholar
- Kumar, D., & Sharma, P. K. (2021). Traditional use, phytochemicals and pharmacological activity of Salvadora persica: A Review. Current Nutrition & Food Science, 17(3), 302–309. https://doi.org/10.2174/1573401316999200807205224
- Lages, Y. V. M., Rossi, A. D., Krahe, T. E., & Landeira-Fernandez, J. (2021). Effect of chronic unpredictable mild stress on the expression profile of serotonin receptors in rats and mice: a meta-analysis. Neuroscience and Biobehavioral Reviews, 124, 78–88. https://doi.org/10.1016/j.neubiorev.2021.01.020
- Li, H., Li, Y., Zhang, X., Ren, G., Wang, L., Li, J., Wang, M., Ren, T., Zhao, Y., Yang, M., & Huang, X. (2021). The combination of Aquilaria sinensis (Lour.) Gilg and Aucklandia costus Falc. volatile oils exerts antidepressant effects in a CUMS-induced rat model by regulating the HPA Axis and levels of neurotransmitters. Frontiers in Pharmacology, 11, 614413. https://doi.org/10.3389/fphar.2020.614413
- Li, Y., Wu, L., Chen, C., Wang, L., Guo, C., Zhao, X., Zhao, T., Wang, X., Liu, A., & Yan, Z. (2020). Serum metabolic profiling reveals the antidepressive effects of the total iridoids of Valeriana jatamansi jones on chronic unpredictable mild stress mice. Frontiers in Pharmacology, 11, 338. https://doi.org/10.3389/fphar.2020.00338
- Liu, D., Xie, K., Yang, X., Gu, J., Ge, L., Wang, X., & Wang, Z. (2014). Resveratrol reverses the effects of chronic unpredictable mild stress on behavior, serum corticosterone levels and BDNF expression in rats. Behavioural Brain Research, 264, 9–16. https://doi.org/10.1016/j.bbr.2014.01.039
- Liu, H., Kaur, J., Dashtipour, K., Kinyamu, R., Ribak, C. E., & Friedman, L. K. (2003). Suppression of hippocampal neurogenesis is associated with developmental stage, number of perinatal seizure episodes, and glucocorticosteroid level. Experimental Neurology, 184(1), 196–213. https://doi.org/10.1016/s0014-4886(03)00207-3
- Livak, K. J., & Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta C(T)) Method. Methods, 25(4), 402–408. https://doi.org/10.1006/meth.2001.1262
- Ma, J. C., Zhang, H. L., Huang, H. P., Ma, Z. L., Chen, S. F., Qiu, Z. K., & Chen, J. S. (2021). Antidepressant-like effects of Z-ligustilide on chronic unpredictable mild stress-induced depression in rats. Experimental and Therapeutic Medicine, 22(1), 677. https://doi.org/10.3892/etm.2021.10109
- Mekhemar, M., Geib, M., Kumar, M., Radha, H. Y., & Dörfer, C. (2021). Salvadora persica: nature's gift for periodontal health. Antioxidants (Basel), 10(5), 712. https://doi.org/10.3390/antiox10050712
- Mihara, M., & Uchiyama, M. (1978). Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Analytical Biochemistry, 86(1), 271–278. https://doi.org/10.1016/0003-2697(78)90342-1
- Mishra, S. K., Hidau, M. K., & Rai, S. (2021). Memantine treatment exerts an antidepressant-like effect by preventing hippocampal mitochondrial dysfunction and memory impairment via upregulation of CREB/BDNF signaling in the rat model of chronic unpredictable stress-induced depression. Neurochemistry International, 142, 104932. https://doi.org/10.1016/j.neuint.2020.104932
- Monforte, M. T., Trovato, A., Rossitto, A., Forestieri, A. M., d'Aquino, A., Miceli, N., & Galati, E. M. (2002). Anticonvulsant and sedative effects of Salvadora persica L. stem extracts. Phytotherapy Research, 16(4), 395–397. https://doi.org/10.1002/ptr.977
- Moylan, S., Berk, M., Dean, O. M., Samuni, Y., Williams, L. J., O'Neil, A., Hayley, A. C., Pasco, J. A., Anderson, G., Jacka, F. N., & Maes, M. (2014). Oxidative & nitrosative stress in depression: Why so much stress? Neuroscience and Biobehavioral Reviews, 45, 46–62. https://doi.org/10.1016/j.neubiorev.2014.05.007
- Phillips, C. (2017). Brain-derived neurotrophic factor, depression, and physical activity: Making the neuroplastic connection. Neural Plasticity, 2017, 7260130. https://doi.org/10.1155/2017/7260130
- Rabbani, S. I. (2020). Ameliorative effect of Salvadora persica (Miswak) on cigarette smoke induced anxiety and depression in rats. International Journal of Pharmaceutical Investigation, 10(1), 32–36. https://doi.org/10.5530/ijpi.2020.1.6
- Ramadan, K. S., Farid, H. E. A., & Almarashi, R. M. M. (2016). Antidepressant-like effects of aqueous extract of Salvadora persica in rat model of depression. International Journal of Pharmaceutical Investigation, 7(8), 697. https://doi.org/10.4172/2155-6156.1000697
10.4172/2155?6156.1000697 Google Scholar
- Razavi, B. M., Sadeghi, M., Abnous, K., Vahdati Hasani, F., & Hosseinzadeh, H. (2017). Study of the role of CREB, BDNF, and VGF neuropeptide in long term antidepressant activity of crocin in the rat cerebellum. Iranian Journal of Pharmaceutical Research, 16(4), 1452–1462.
- Reddy, C. S., & Vardhaman, P. (2013). Evaluation of Phoenix dactylifera fruits for Antiurolithiatic activity. Hygeia Journal for Drug and Medicines, 5(1), 135–140.
- Roshankhah, S., Abdolmaleki, A., & Salahshoor, M. R. (2020). Anti-inflammatory, anti-apoptotic, and antioxidant actions of Middle Eastern Phoenix dactylifera extract on mercury-induced hepatotoxicity in vivo. Molecular Biology Reports, 47(8), 6053–6065. https://doi.org/10.1007/s11033-020-05680-4
- Saeedi Borujeni, M. J., Esfandiary, E., Ghanadian, M., Valiani, A., Baradaran, A., & Yazdani, A. (2019). Alterations in lipid peroxidation, lipid profile, insulin sensitivity, and hepatic histopathological changes in diabetic rats following the treatment with Salvadora persica. Journal of Cellular Biochemistry, 120(3), 3696–3708. https://doi.org/10.1002/jcb.27649
- Sinha, A. K. (1972). Colorimetric assay of catalase. Analytical Biochemistry, 47(2), 389–394. https://doi.org/10.1016/0003-2697(72)90132-7
- Thakare, V. N., Lakade, S. H., Mahajan, M. P., Kulkarni, Y. P., Dhakane, V. D., Harde, M. T., & Patel, B. M. (2021). Protocatechuic acid attenuates chronic unpredictable mild stress induced-behavioral and biochemical alterations in mice. European Journal of Pharmacology, 898, 173992. https://doi.org/10.1016/j.ejphar.2021.173992
- Tiffin, P. A., Mediavilla, J. L., Close, H., Kasim, A. S., Welsh, P., Paton, L. W., & Mason, J. M. (2019). What were the impacts of the Committee on Safety of Medicines warning and publication of the NICE guidelines on trends in child and adolescent antidepressant prescribing in primary care? A population based study. BMJ Open, 9(8), e028201. https://doi.org/10.1136/bmjopen-2018-028201
- Wang, C., Guo, J., & Guo, R. (2017). Effect of XingPiJieYu decoction on spatial learning and memory and cAMP-PKA-CREB-BDNF pathway in rat model of depression through chronic unpredictable stress. BMC Complementary and Alternative Medicine, 17(1), 73. https://doi.org/10.1186/s12906-016-1543-9
- Xing, H., Zhang, K., Zhang, R., Shi, H., Bi, K., & Chen, X. (2015). Antidepressant-like effect of the water extract of the fixed combination of Gardenia jasminoides, Citrus aurantium and Magnolia officinalis in a rat model of chronic unpredictable mild stress. Phytomedicine, 22(13), 1178–1185. https://doi.org/10.1016/j.phymed.2015.09.004
- Younas, A., Naqvi, S. A., Khan, M. R., Shabbir, M. A., Jatoi, M. A., Anwar, F., Inam-Ur-Raheem, M., Saari, N., & Aadil, R. M. (2020). Functional food and nutra-pharmaceutical perspectives of date (Phoenix dactylifera L.) fruit. Journal of Food Biochemistry, 44(9), e13332. https://doi.org/10.1111/jfbc.13332
- Yu, M., Gouvinhas, I., Rocha, J., & AIRNA, B. (2021). Phytochemical and antioxidant analysis of medicinal and food plants towards bioactive food and pharmaceutical resources. Scientific Reports, 11(1), 10041. https://doi.org/10.1038/s41598-021-89437-4
- Zeni, A. L. B., Camargo, A., & Dalmagro, A. P. (2017). Ferulic acid reverses depression-like behavior and oxidative stress induced by chronic corticosterone treatment in mice. Steroids, 125, 131–136. https://doi.org/10.1016/j.steroids.2017.07.006
- Zhao, J., Niu, C., Wang, J., Yang, H., Du, Y., Wei, L., & Li, C. (2018). The depressive-like behaviors of chronic unpredictable mild stress-treated mice, ameliorated by Tibetan medicine Zuotai: involvement in the hypothalamic-pituitary-adrenal (HPA) axis pathway. Neuropsychiatric Disease and Treatment, 14, 129–141. https://doi.org/10.2147/NDT.S151107
- Zheng, X., Cheng, Y., Chen, Y., Yue, Y., Li, Y., Xia, S., Li, Y., Deng, H., Zhang, J., & Cao, Y. (2019). Ferulic acid improves depressive-like behavior in prenatally-stressed offspring rats via anti-inflammatory activity and HPA axis. International Journal of Molecular Sciences, 20(3), 493. https://doi.org/10.3390/ijms20030493
- Zhuo, J., Chen, B., Sun, C., Jiang, T., Chen, Z., Liu, Y., Nie, J., Yang, H., Zheng, J., Lai, X., & Su, Z. (2020). Patchouli alcohol protects against chronic unpredictable mild stress-induced depressant-like behavior through inhibiting excessive autophagy via activation of mTOR signaling pathway. Biomedicine & Pharmacotherapy, 127, 110115. https://doi.org/10.1016/j.biopha.2020.110115
- Zihad, S. M. N. K., Uddin, S. J., Sifat, N., Lovely, F., Rouf, R., Shilpi, J. A., Sheikh, B. Y., & Göransson, U. (2021). Antioxidant properties and phenolic profiling by UPLC-QTOF-MS of Ajwah, Safawy and Sukkari cultivars of date palm. Biochemistry and Biophysics Reports, 25, 100909. https://doi.org/10.1016/j.bbrep.2021.100909