Antidepressant-like effects of seeds of Citrullus lanatus in the reserpine-induced depressed mouse model
DOI:
https://doi.org/10.34117/bjdv10n7-060Keywords:
behavioral parameters, depression, Citrullus lanatus seeds, corticosteroneAbstract
Depression is a mental health disorder that affects millions of people worldwide. Plants and their products are widely used in the treatments of various diseases including depression for their therapeutic effectiveness with least or no side effects. The present study has therefore been conducted to evaluate the antidepressant like effects of Citrullus lanatus seed extract (CLSE) in the reserpine-induced depressed mouse model by assessing the phytoconstituents of CLSE, body weight, behaviour, histopathology of the adrenal gland and level of plasma corticosterone. Twenty-four adult male mice of Swiss strain were distributed into four groups of six each (n=6). Group I served as control while groups II, III and IV received reserpine (RES: 0.75mg/kg/BW/day) for 14 days, CLSE (300mg/kg/BW/day) only, for 28 days, and RES+CLSE [RES treatment for 14 days followed by CLSE treatment for 28 days], respectively. Behavioural alterations were analysed by food consumption, sucrose preference, eight-arm radial maze, and forced swim tests during the treatment. RES-induced depression caused marked alterations in the body weight, all behavioural parameters, histopathology of the adrenal cortex, and in the level of plasma corticosterone, compared with the control. Administration of CLSE only, did not cause significant alterations in all the studied parameters, compared with the control. However, CLSE administration in RES-treated mice resulted in significant restoration in all the studied parameters, similar to the control. The findings therefore suggest the antidepressive activity of the seeds of C. lanatus, that may emerge as one of the potential sources among the natural therapies of depression disorder.
References
Abbasi, E., Nassiri-Asl, M., Sheikhi, M., Shafiee, M. Effects of vitexin on scopolamine-induced memory impairment in rats. Chin. J. Physiol. n. 56, p.184-189, 2013.
Adnaik, R. S., Gavarkar, P. S., Mohite, S. K., Magdum, C. S. Anti-depressant activity of ethanolic extract of Citrullus vulgaris seeds in experimentally induced depressed mice. RJPT, n. 7, p. 660-662, 2014.
Alka, G., Anamika, S., Ranu, P. A review on watermelon (Citrullus lanatus) medicinal seeds. J. Pharmacogn. Phytochem. n. 7, p. 2222-2225, 2018.
Bartos J, Pesez M. Colorimetric and fluorimetric determination of aldehydes and ketones. Pure Appl. Chem. n. 51, p. 1803-1814, 1979.
Beppe, G. J., Dongmo, A. B., Foyet, H. S., Dimo, T., Mihasan, M., Hritcu, L. The aqueous extract of Albizia adianthifolia leaves attenuates 6-hydroxydopamine-induced anxiety, depression and oxidative stress in rat amygdala. BMC Complement Altern. Med. n. 15, p. 1-13, 2015.
Burgess, N., Maguire, E. A., O'Keefe, J. The human hippocampus and spatial and episodic memory. Neuron. n. 35, p. 625-641, 2002.
Buzsáki, G., Moser, E. I. Memory, navigation and theta rhythm in the hippocampal-entorhinal system. Nat. Neurosci. n. 16, p. 130-138, 2013.
Carratalá-Ros, C., Martínez-Verdú, A., Olivares-García, R., Salamone, J. D., Correa, M. Effects of the dopamine depleting agent tetrabenazine in tests evaluating different components of depressive-like behavior in mice: sex-dependent response to antidepressant drugs with SERT and DAT blocker profiles. Psychopharmacol. n. 240, p. 1615-1628, 2023.
Chatterjee, M., Verma, P., Maurya, R., Palit, G. Evaluation of ethanol leaf extract of Ocimum sanctum in experimental models of anxiety and depression. Pharm. Biol. n. 49, p. 477-483, 2011.
Chen, N., Li, W., Wu, S., Zhu, Y. Fluorimetric detection of reserpine in mouse serum through online post-column electrochemical derivatization. R. Soc. Open Sci. n. 5, p. 171948, 2018.
Chowdhury, A. A., Gawali, N. B., Bulani, V. D., Kothavade, P. S., Mestry, S. N., Deshpande, P. S., Juvekar, A. R. In vitro antiglycating effect and in vivo neuroprotective activity of Trigonelline in d-galactose induced cognitive impairment. Pharmacol. Rep. n. 70, p. 372-377, 2018.
Chowdhury, A. A., Gawali, N. B., Munshi, R., Juvekar, A. R. Trigonelline insulates against oxidative stress, proinflammatory cytokines and restores BDNF levels in lipopolysaccharide induced cognitive impairment in adult mice. Metab. Brain Dis. n. 33, p. 681-691, 2018.
Cline, B. H., Costa-Nunes, J. P., Cespuglio, R., Markova, N., Santos, A. I., Bukhman, Y. V., Kubatiev, A., Steinbusch, H.W.M., Klaus-Peter Lesch, Strekalova, T. Dicholine succinate, the neuronal insulin sensitizer, normalizes behavior, REM sleep, hippocampal pGSK3 beta and mRNAs of NMDA receptor subunits in mouse models of depression. Front. Behav. Neurosci. n. 9, p. 37, 2015.
Cryan, J. F., Leonard, B. E. 5‐HT1A and beyond: the role of serotonin and its receptors in depression and the antidepressant response. Human Hum. Psychopharmacol. Clin. Exp. n. 15, p. 113-135, 2000.
Culig, L., Surget, A., Bourdey, M., Khemissi, W., Le Guisquet, A. M., Vogel, E., Belzung, C. Increasing adult hippocampal neurogenesis in mice after exposure to unpredictable chronic mild stress may counteract some of the effects of stress. Neuropharmacology, n. 126, p. 179-189, 2017.
De Freitas, C. M., Busanello, A., Schaffer, L. F., Peroza, L. R., Krum, B. N., Leal, C. Q., Fachinetto, R. Behavioral and neurochemical effects induced by reserpine in mice. Psychopharmacol., n. 233, p. 457-467, 2016.
Dhingra, D., Goyal, P. K. Evidences for the involvement of monoaminergic and GABAergic systems in antidepressant-like activity of Tinospora cordifolia in mice. Indian J. Pharm. Sci, n. 70, p. 761, 2008.
Dudau, L. E., Moisa, E., Sevastre-Berghian, A., Moldovan, R., Decea, R., Donosa, M., Stancu, B. The effect of curcumin on reserpine-induced depression-like behaviour in rats. Psychiatry Res. Neuroimaging, n. 334, p. 111682, 2023.
Erhirhie, E. O., Ekene, N. E. Medicinal values on Citrullus lanatus (watermelon): pharmacological review. Int. J. Res. Pharmaceut. Biomed. Sci., n. 4, p. 1305-1312, 2013.
Fleck, C., Appenroth, D., Fang, L., Schott, Y., Lehmann, J., Decker, M. Investigation into the in vivo effects of five novel tacrine/ferulic acid and β-carboline derivatives on scopolamine-induced cognitive impairment in rats using radial maze paradigm. Arzneimittelforschung, n. 60, p. 299-306, 2010.
Frank, P., Batty, G. D., Pentti, J., Jokela, M., Poole, L., Ervasti, J., Kivimäki, M. Association Between Depression and Physical Conditions Requiring Hospitalization. JAMA psychiatry. n. 80, p. 690–699, 2023.
Gao S., Cui Y.L., Yu C.Q., Wang Q.S., Zhang, Y. Tetrandrine exerts antidepressant-like effects in animal models: Role of brain-derived neurotrophic factor. Behav. Brain Res. n. 238, p. 79-85, 2013.
Gao, Z. Y., Yang, P., Huang, Q. J., Xu, H. Y. The influence of dizocilpine on the reserpine-induced behavioral and neurobiological changes in rats. Neurosci. Lett. n. 614, p. 89-94, 2016.
Gautam, K., Kumar, S., Srivastava, S., Singh, P. Pharmacological Properties of Citrullus lanatus. Perspective of Recent Adv. Med. Res. n. 6, p. 10-30, 2023.
Ge, J. B., Jiang, B., Shi, T. S., Li, W. Y., Chen, W. J., Zhu, B. L., Qin, Z. H. Cucurbitacin B exerts significant antidepressant-like effects in a chronic unpredictable mild stress model of depression: Involvement of the hippocampal BDNF-TrkB system. Int. J. Neuropsychopharmacol. n. 26, p. 680-691, 2023.
Girish, C., Oommen, S., Vishnu, R. Evidence for the involvement of the monoaminergic system in the antidepressant-like activity of methanolic extract of Bacopa monnieri in albino mice. Int. J. Basic. Clin. Pharmacol. n. 5, p. 914-922, 2016.
Glenn, M. J., Adams, R. S., McClurg, L. Supplemental dietary choline during development exerts antidepressant-like effects in adult female rats. Brain Res. n. 1443, p. 52-63, 2012.
Goodwin, G.M. Depression and associated physical diseases and symptoms. Dialogues Clin. Neurosci. n. 8, p. 259-265, 2022.
Gopal, M., Jain, S. K., Sudha, V. Evaluation of antidepressant activity of Polyherbal methanolic extract of leaves of Zingiber officinale, Azadirachta indica, Curcuma longa and Hibiscus rosasinesis. Asian J. Pharma. Res. n. 13, p. 233-236, 2023.
Govindarajulu et al. Reserpine-Induced Depression and Other Neurotoxicity: A Monoaminergic Hypothesis. Medicinal Herbs and Fungi: Neurotoxicity vs. Neuroprotection, p. 293-313, 2021.
Guo, Z., Liu, X., Huang, H. Kinetics and thermodynamics of reserpine adsorption onto strong acidic cationic exchange fiber. PloS one, n. 10, p. e0138619, 2015.
Hanff, T. C., Furst, S. J. Biochemical and anatomical substrates of depression and sickness behavior. Israel J. Psychiatry, n. 47, p. 64, 2010.
Hazra, S., Banerjee, R., Das, B. K., Ghosh, A. K., Banerjee, T. K., Hazra, U. S., Mondal, A. C. Evaluation of antidepressant activity of Bacopa monnieri in rat: a study in animal model of depression. Drug Discov. n. 2, p. 8-13, 2012.
Healy, D., Savage, M. Reserpine exhumed. BJPsych. n. 172, p. 376-378, 1998.
Hoffman, K. What can animal models tell us about depressive disorders? In: Modeling Neuropsychiatric Disorders in Laboratory Animals. p. 35–86, 2016.
Institute of Health Metrics and Evaluation. Global Health Data Exchange (GHDx). https://vizhub.healthdata.org/gbd-results/ (Accessed 4 March 2023).
Jaseela, K. P., Kumar, A., Babu, D., Swamy, V. B. Studies on Anti-depressant and Anti-inflammatory Activities of Curcuma aromatica Rhizome in Experimental Animal Models. Asian J Pharm. Res. n. 6, p. 79-86, 2016.
Jozuka, H., Jozuka, E., Takeuchi, S., Nishikaze, O. Comparison of immunological and endocrinological markers associated with major depression. J. Int. Med. Res. n. 31, p. 36-41, 2003.
Kabdy, H., Baslam, A., Baba, A. A., Laaradia, M. A., Aboufatima, R., Belbachir, A., Chait, A. Anxiolytic and antidepressant effects of the essential oil of Moroccan Cannabis sativa in mice exposed to unpredictable chronic mild stress: Behavioral and biochemical evidences. South African J. Bot. n. 165, p. 70-78, 2024.
Kamińska, K., Lenda, T., Konieczny, J., Czarnecka, A., Lorenc-Koci, E. Depressive-like neurochemical and behavioral markers of Parkinson’s disease after 6-OHDA administered unilaterally to the rat medial forebrain bundle. Pharmacol. Reports, n. 69, p. 985-994, 2017.
Kilari, E. K., Rao, L. S. N., Sreemanthula, S., Kola, P. K. Anti-stress and nootropic activity of aqueous extract of Piper longum fruit, estimated by non-invasive biomarkers and Y-maze test in rodents. Environ. Exp. Biol. n. 13, p. 25-31, 2015.
Kim, Y. R., Park, B. K., Seo, C. S., Kim, N. S., Lee, M. Y. Antidepressant and anxiolytic-like effects of the stem bark extract of Fraxinus rhynchophylla hance and its components in a mouse model of depressive-like disorder induced by reserpine administration. Frontiers in Behav. Neurosci. n. 15, p. 650833, 2021.
Kim, Y., Kim, J., He, M., Lee, A., Cho, E. Apigenin ameliorates scopolamine-induced cognitive dysfunction and neuronal damage in mice. Molecules, n. 26, p. 5192, 2021.
Koneru, A., Satyanarayana, S., Mukkanti, K., Khan, K. A. Antidepressant activity of The Unani formulation: Itrifal Kishneezi. Pharmacologyonline, n. 3, p. 671-676, 2010.
Krishnan, V; Nestler, E. J. Animal models of depression: molecular perspectives. Molecular And Functional Models in Neuropsychiatry, p. 121-147, 2011.
Kuypers, N. J., Hoane, M. R. Pyridoxine administration improves behavioral and anatomical outcome after unilateral contusion injury in the rat. J. Neurotrauma, n. 27, p. 1275-1282, 2010.
Lazzara, S., Napoli, E., Carrubba, A. Hypericum spp.: a resource from wild Mediterranean flora for the treatment of mild depression. Bioactive Phytochemicals—Perspectives for Modern Medicine, n. 3, p. 337-354, 2015.
Lee, S. A., Hong, S. S., Han, X. H., Hwang, J. S., Oh, G. J., Lee, K. S., Ro, J. S. Piperine from the fruits of Piper longum with inhibitory effect on monoamine oxidase and antidepressant-like activity. Chem. Pharm. Bull. n. 53, p. 832-835, 2005.
Lima, L. K. F., Pereira, S. K. S., Junior, R. D. S. S., Santos, F. P. D. S., Nascimento, A. D. S., Feitosa, C. M., Rai, M. A brief review on the neuroprotective mechanisms of vitexin. BioMed Res. Int. n. 2018, p. 4785089, 2018.
López-Muñoz, F., Bhatara, V. S., Alamo, C., Cuenca, E. Historical approach to reserpine discovery and its introduction in psychiatry. Actas Esp. Psiquiatr. n. 32, p. 387-395, 2004.
Maifitrianti, H. S; Suryadi, D. Steamed Watermelon (Citrullus lanatus Thunb.) Juice Improves Spatial Memory in Dementia Rat Model, n. 2018, p. 96-101, 2021.
Mao, Q. Q., Huang, Z., Zhong, X. M., Xian, Y. F., Ip, S. P. Piperine reverses chronic unpredictable mild stress-induced behavioral and biochemical alterations in rats. Cell. Mol. Neurobiol. n. 34, p. 403-408, 2014.
Mutalik, M; Mutalik, M. Tinospora cordifolia: Role in depression, cognition and memory. Australian J. Med. Herbal., n. 23, p. 168-173, 2011.
Nagakura Y, Oe T, Aoki T, Matsuoka N. Biogenic amine depletion causes chronic muscular pain and tactile allodynia accompanied by depression: A putative animal model of fibromyalgia.” PAIN. n. 146, p. 26-33, 2009.
Nagata, T., Yamamoto, S., Yaguchi, T., ISO, H., Tanaka, A., Nishizaki, T. The newly synthesized linoleic acid derivative DCP‐LA ameliorates memory deficits in animal models treated with amyloid‐β peptide and scopolamine. Psychogeriatr. n. 5, p. 122-126, 2005.
Naidu, P. S., Singh, A; Kulkarni, S. K. Reversal of reserpine-induced orofacial dyskinesia and cognitive dysfunction by quercetin. Pharmacol. n. 70, p. 59-67, 2004.
Olanrewaju, J. A., Owolabi, J. O., Awodein, I. P., Enya, J. I., Adelodun, S. T., Olatunji, S. Y., Fabiyi, S. O. Zingiber officinale ethanolic extract attenuated reserpine-induced depression-like condition and associated hippocampal aberrations in experimental Wistar rats. J. Exp. Pharmacol. n. 12, p. 439-446, 2020.
Oseni, O. A., Odesanmi, O. E., Oladele, F. C. Antioxidative and antidiabetic activities of watermelon (Citrullus lanatus) juice on oxidative stress in alloxan-induced diabetic male Wistar albino rats. Nigerian Med. J.: J. Nigeria Med. Associ. n. 56, p. 272, 2015.
Oyenihi, O. R., Afolabi, B. A., Oyenihi, A. B., Ogunmokun, O. J., Oguntibeju, O. O. Hepato-and neuro-protective effects of watermelon juice on acute ethanol-induced oxidative stress in rats. Toxicol. Reports, n. 3, p. 288-294, 2016.
Park, B. K., Kim, Y. R., Kim, Y. H., Yang, C., Seo, C. S., Jung, I. C., Lee, M. Y. Antidepressant‐Like Effects of Gyejibokryeong-hwan in a Mouse Model of Reserpine‐Induced Depression. BioMed Res. Int. n. 2018, p. 5845491, 2018.
Pawłowski, L. Effects of the Membrane-active Antidepressant Drugs, Selective 5-HT or NA Uptake Inhibitors, on p-Chloroamphetamine (PCA)-induced Hyperthermia in Heat-adapted Rats. Palgrave, London, In New Concepts in Depression, p. 204-210, 1988.
Pemminati, S., Gopalakrishna, H. N., Alva, A., Pai, M. R. S. M., Seema, Y., Raj, V., Pillai, D. Antidepressant activity of ethanolic extract of leaves of Ocimum sanctum in mice. J. Pharm. Res. n. 3, p. 624-626, 2010.
Penner, M. R; Mizumori, S. J. Age-associated changes in the hippocampal-ventral striatum-ventral tegmental loop that impact learning, prediction, and context discrimination. Front. Aging Neurosci. n. 4, p.1-12, 2012.
Porsolt, R.D., Anton, G., Blavet, N., Jalfre, M. Behavioural despair in rats: a new model sensitive to antidepressant treatment. Eur. J. Pharmacol. n. 47, p. 379-391, 1978.
Pu, F., Mishima, K., Egashira, N., Iwasaki, K., Kaneko, T., Uchida, T., Fujiwara, M. Protective effect of buckwheat polyphenols against long-lasting impairment of spatial memory associated with hippocampal neuronal damage in rats subjected to repeated cerebral ischemia. J. Pharmacol. Sci. n. 94, p. 393-402, 2004.
Qi, S., Li, Z., Bai, L., Yuan, K., Sun, S., Ye, J., Wang, M. Effect of Apigenin on Learning and Memory Ability of Senile Dementia Mice. Rev. Cient. Fac. Cienc. Vet. n. 30, p. 2573-2581, 2020.
Qiao, Y., Liu, S., Li, G., Lu, Y., Wu, Y., Ding, Y., Ke, C. Role of depressive symptoms in cardiometabolic diseases and subsequent transitions to all-cause mortality: an application of multistate models in a prospective cohort study. Stroke Vasc. Neurol. n. 6, p.511-518, 2021.
Rahman, H., Eswaraiah, M. C., Anoosha, T., Nagaveni, K., Manjula, K. Evaluation for CNS activities of hexane extract of Citrullus lanatus seeds. Res. J. Pharm. Technol. n. 6, p. 878-884, 2013.
Sadek, M. T., El-Abd, S. S., Ibrahim, M. A. Effect of Chronic Unpredictable Mild Stress on Adrenal Cortex of Adult Rat and The Possible Protective Role of Licorice Extract: A Histological and Immunohistochemical Study. EJH. n. 44, p. 887-901, 2021.
Saghaei, E., Nasiri Boroujeni, S., Safavi, P., Borjian Boroujeni, Z., Bijad, E. Diosmetin mitigates cognitive and memory impairment provoked by chronic unpredictable mild stress in mice. eCAM. n. 2020, p. 1-10, 2020.
Samad, N., Manzoor, N., Muneer, Z., Bhatti, S. A., Imran, I. Reserpine-induced altered neuro-behavioral, biochemical and histopathological assessments prevent by enhanced antioxidant defence system of thymoquinone in mice. Metab. Brain Dis. n. 36, p. 2535-2552, 2021.
Sandhya, R., Haritha, P., Swathi, B. Antidepressant activity of aqueous extract of Citrullus lanatus. JGTPS. n. 11, p. 8300-8307, 2021.
Savici, J., Boldura, O. M., Balta, C., Muselin, F., Mederle, N., Cristina, R. T., Brezovan, D. Effects of Aronia melanocarpa and Hypericum perforatum aqueous extracts on hexavalent chromium induced toxicity in rat’s thyrocytes. J. Trace Elem. Med. Biol. n. 78, p. 127151, 2023.
Shahyad, S., Sahraei, H., Mousallo, K., Jahromi, G. P., Mohammadi, M. T. Effect of Papaver rhoeas hydroalcoholic extract on blood corticosterone and psychosocial behaviors in the mice model of predator exposure-induced post-traumatic stress disorder. Heliyon, n. 9, p. e18084, 2023.
Slattery, D. A., Markou, A., Cryan, J. F. Evaluation of reward processes in an animal model of depression. Psychopharmacol. n. 190, p. 555-568, 2007.
Strawbridge, R., Javed, R. R., Cave, J., Jauhar, S., Young, A. H. The effects of reserpine on depression: A systematic review. J. Psychopharmacol. n. 37, p.248-260, 2023.
Suh, J., Foster, D. J., Davoudi, H., Wilson, M. A., Tonegawa, S. Impaired hippocampal ripple-associated replay in a mouse model of schizophrenia. Neuron. n. 80, p. 484-493, 2013.
Tabassum, I., Siddiqui, Z. N., Rizvi, S. J. Effects of Ocimum sanctum and Camellia sinensis on stress-induced anxiety and depression in male albino Rattus norvegicus. Indian J. Pharmacol. n. 42, p. 283-288, 2010.
Tang, M., Ai, Y., Zhu, S., Song, N., Xu, X., Liang, L., He, T. Antidepressant-like effect of essential oils from Citrus reticulata in reserpine-induced depressive mouse. Nat. Prod. Commun. n. 17, p. 1-12, 2022.
Teegarden, S. Behavioral phenotyping in rats and mice. Materials and Methods, n. 2, p. 122, 2012.
Tseng, H. C., Wang, M. H., Soung, H. S., Chang, Y., Chang, K. C. (−) Epigallocatechin-3-gallate prevents the reserpine-induced impairment of short-term social memory in rats. Behav. Pharmacol. n. 26, p. 741-747, 2015.
van Onselen, R; Downing, T. G. Neonatal reserpine administration produces widespread neuronal losses and⍺-Synuclein inclusions in a rat model. Neurotox. Res. n. 39, p. 1762-1770, 2021.
Várkonyi, D., Török, B., Sipos, E., Fazekas, C. L., Bánrévi, K., Correia, P., Zelena, D. Investigation of anxiety-and depressive-like symptoms in 4-and 8-Month-Old Male Triple Transgenic Mouse Models of Alzheimer’s Disease. Int. J. Mol. Sci. n. 23, p. 1-22, 2022.
Veselinovic, T., Schorn, H., Vernaleken, I. B., Schiffl, K., Klomp, M., Gründer, G. Impact of different antidopaminergic mechanisms on the dopaminergic control of prolactin secretion. J. Clin. Psychopharmacol. n. 31, p. 214-220, 2011.
Wahid, S., Alqahtani, A., Khan, R. A. Nootropic Effects of C. melo and C. lanatus seed extracts. BioMed Res. Int. n. 2020, p.1-7, 2020.
Wang, X. L., Miao, C., Su, Y., Zhang, C., Meng, X. MAD2B Blunts Chronic Unpredictable Stress and Corticosterone Stimulation–Induced Depression-Like Behaviors in Mice. Int. J. Neuropsychopharmacol. n. 26, p. 137-148, 2023.
Whitlock, J. R., Heynen, A. J., Shuler, M. G., Bear, M. F. Learning induces long-term potentiation in the hippocampus. Sci. n. 313, p. 1093-1097, 2006.
Yoo, D. Y., Choi, J. H., Kim, W., Nam, S. M., Jung, H. Y., Kim, J. H., Hwang, I. K. Effects of luteolin on spatial memory, cell proliferation, and neuroblast differentiation in the hippocampal dentate gyrus in a scopolamine-induced amnesia model. Neurolog. Res. n. 35, p. 813-820, 2013.
Zaki, S. M., Abdelgawad, F. A., El-Shaarawy, E. A. A., Radwan, R. A. K., Aboul-Hoda, B. E. Stress-induced changes in the aged-rat adrenal cortex. Histological and histomorphometric study. Folia Morphol. n. 77, p. 629-641, 2018.
Zhu, G. H., Sun, X. P., Li, J., Pi, L., Tang, H. Q., Gao, H. Q., Hua, Q. No association between low-dose reserpine use and depression in older hypertensive patient: result of a multicenter, cross-sectional study. J.Geriatr. Cardiol. n. 16, p. 608-613, 2019.

