Therapeutic Potential of Neoechinulins and Their Derivatives: An Overview of the Molecular Mechanisms Behind Pharmacological Activities
Open accessAbstract
Neoechinulins are diketopiperazine type indole alkaloids that demonstrate radical scavenging, anti-inflammatory, antiviral, anti-neurodegenerative, neurotrophic factor-like, anticancer, pro-apoptotic, and anti-apoptotic properties. An array of neoechinulins such as neoechinulins A-E, isoechinulins A-C, cryptoechunilin have been isolated from various fungal sources like Aspergillus sp., Xylaria euglossa, Eurotium cristatum, Microsporum sp., etc. Besides, neoechinulin derivatives or stereoisomers were also obtained from diverse non-fungal sources viz. Tinospora sagittata, Opuntia dillenii, Cyrtomium fortunei, Cannabis sativa , and so on. The main purpose of this review is to provide update information on neoechinulins and their analogues about the molecular mechanisms of the pharmacological action and possible future research. The recent data from this review can be used to create a basis for the discovery of new neoechinulin-based drugs and their analogues in the near future. The online databases PubMed, Science and Google scholar were researched for the selection and collection of data from the available literature on neoechinulins, their natural sources and their pharmacological properties. The published books on this topic were also analysed. In vitro and in vivo assays have established the potential of neoechinulin A as a promising anticancer and anti-neuroinflammatory lead molecule. Neoechinulin B was also identified as a potential antiviral drug against hepatitis C virus. Toxicological and clinical trials are needed in the future to improve the phyto-pharmacological profile of neoquinolines. From the analysis of the literature, we found that neoechinulins and their derivatives have special biological potential. Although some modern pharmacological analyzes have highlighted the molecular mechanisms of action and some signalling pathways, the correlation between these phytoconstituents and pharmacological activities must be validated in the future by preclinical toxicological and clinical studies.
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Many naturally occurring substances such as resveratrol, neoechinulins, genistein or diosgenin provide antioxidant, anti-inflammatory, chelating, and/or scavenger activity.
“Many naturally occurring substances such as resveratrol, neoechinulins, genistein or diosgenin provided antioxidant, anti-inflammatory, chelating, and/or scavenger activity [115,200,224,225].”
From Multi-Target Mechanisms of Phytochemicals in Alzheimer’s Disease: Effects on Oxidative Stress, Neuroinflammation and Protein Aggregation (2022) · cites this paper as [224]
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Cites
Chronic Parkinsonism in Humans Due to a Product of Meperidine-Analog Synthesis
Langston, J. W., Ballard, P., Tetrud, J. W., & Irwin, I. (1983) · Science · doi:10.1126/science.6823561 · Cited by 4,914 · see citing works
Emerging roles of caspase-3 in apoptosis
Porter, A. G., & Jänicke, R. U. (1999) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4400476 · Cited by 3,870 · see citing works
Sharifi-Rad, M., Anil Kumar, N. V., Zucca, P., Varoni, E. M., Dini, L., Panzarini, E., Rajkovic, J., Tsouh Fokou, P. V., Azzini, E., Peluso, I., et al. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.00694 · Cited by 1,971 · see citing works
Self-citationMolecular Pathways of Neurodegeneration in Parkinson's Disease
Dawson, T. M., & Dawson, V. L. (2003) · Science · doi:10.1126/science.1087753 · Cited by 1,659 · see citing works
Widespread Peroxynitrite-Mediated Damage in Alzheimer’s Disease
Smith, M. A., Richey Harris, P. L., Sayre, L. M., Beckman, J. S., & Perry, G. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-08-02653.1997 · Cited by 1,239 · see citing works
The Alkaloids, Chemistry and Pharmacology
(1992) · European Journal of Medicinal Chemistry · doi:10.1016/0223-5234(92)90195-7 · Cited by 913 · see citing works
Kinetics of superoxide dismutase- and iron-catalyzed nitration of phenolics by peroxynitrite
Beckman, J. S., Ischiropoulos, H., Zhu, L., van der Woerd, M., Smith, C. D. L., Chen, J., Harrison, J. G., Martin, J. C., & Tsai, M. (1992) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(92)90432-v · Cited by 765 · see citing works
Protein Nitration in Parkinsonʼs Disease
Good, P. F., Hsu, A., Werner, P., Perl, D. P., & Olanow, C. W. (1998) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199804000-00006 · Cited by 540 · see citing works
Neuronal cell death in neurodegenerative diseases: recurring themes around protein handling
Gorman, A. M. (2008) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2008.00402.x · Cited by 362 · see citing works
Sharifi‐Rad, J., Rodrigues, C. F., Sharopov, F. S., Docea, A. O., Karaça, A. C., Sharifi‐Rad, M., Kahveci, D., Gülseren, G., Şenol, E., Demircan, E., et al. (2020) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph17072326 · Cited by 295 · cited 1× · see citing works
“Anti-inflammatory Inflammation is an important defence mechanism of the body during acute inflammatory responses, maintaining tissue homeostasis (22, 23).”
BackgroundSalehi, B., Sharifi-Rad, J., Cappellini, F., Reiner, Ž., Zorzan, D., Imran, M., Sener, B., Kilic, M., El-Shazly, M., Fahmy, N. M., et al. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.01300 · Cited by 293 · cited 1× · see citing works
“Nuclear factor-kappa B (NF-κB) along with its inhibitory protein, IκB controls the transcription of pro-inflammatory mediators and cytokines such as NO (nitric oxide), iNOS (inducible isoform NO), COX-2 (ciclooxigenase 2), TNF-α (Tumour necrosis alfa), PGE2 (prostaglandin E2), and IL-1β (interleukin 1β) (30, 31) Besid…”
BackgroundWang, S., Li, X., Teuscher, F., Li, Diesel, A., Ebel, R., Proksch, P., & Wang, B. (2006) · Journal of Natural Products · doi:10.1021/np060248n · Cited by 278 · cited 1× · see citing works
“(2–5), ascomycete Xylaria euglossa (6), and some others (7, 8).”
BackgroundImpact of Natural Compounds on Neurodegenerative Disorders: From Preclinical to Pharmacotherapeutics
Sharifi‐Rad, M., Lankatillake, C., Dias, D. A., Docea, A. O., Mahomoodally, M. F., Lobine, D., Chazot, P. L., Kurt, B., Tumer, T. B., Moreira, A. C., et al. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9041061 · Cited by 260 · see citing works
Cucurbits Plants: A Key Emphasis to Its Pharmacological Potential
Salehi, B., Çapanoğlu, E., Adrar, N., Çatalkaya, G., Shaheen, S., Jaffer, M., Giri, L., Suyal, R., Jugran, A. K., Călina, D. C., et al. (2019) · Molecules · doi:10.3390/molecules24101854 · Cited by 160 · see citing works
Potential of marine natural products against drug-resistant fungal, viral, and parasitic infections
Abdelmohsen, U. R., Balasubramanian, S., Oelschlaeger, T. A., Grkovic, T., Pham, N. B., Quinn, R. J., & Hentschel, U. (2016) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(16)30323-1 · Cited by 154 · see citing works
Ficusplants: State of the art from a phytochemical, pharmacological, and toxicological perspective
Salehi, B., Mishra, A. P., Nigam, M., Karazhan, N., Shukla, I., Kiełtyka‐Dadasiewicz, A., SAWICKA, B. H., Głowacka, A., Abu-Darwish, M. S., Tarawneh, A. H., et al. (2020) · Phytotherapy Research · doi:10.1002/ptr.6884 · Cited by 128 · cited 5× · see citing works
“Besides, neoechinulin A induced reduction in the expression of iNOS catalyzes, COX-2 Frontiers in Nutrition | www.frontiersin.org 2 July 2021 | Volume 8 | Article 664197 and MAPK pathway dose-dependently resulted in a dosedependent decreased in the synthesis of nitric oxide (NO) and prostaglandin E2 (PGE2).”
BackgroundInfluentialOxidative Stress and Inflammation Interdependence in Multiple Sclerosis
Pădureanu, R., Albu, C. V., Mititelu, R. R., Bacanoiu, M. V., Docea, A. O., Călina, D. C., Pădureanu, V., Olaru, G., Sandu, R. E., Mălin, R. D., et al. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8111815 · Cited by 120 · see citing works
Chen, X., Si, L., Liu, D., Proksch, P., Zhang, L., Zhou, D., & Lin, W. (2015) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2015.02.006 · Cited by 116 · see citing works
Du, F., Li, X.-M., Li, C.-S., Shang, Z., & Wang, B. (2012) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2012.05.088 · Cited by 110 · cited 1× · see citing works
“(2–5), ascomycete Xylaria euglossa (6), and some others (7, 8).”
BackgroundInflammatory and Oxidative Stress Markers—Mirror Tools in Rheumatoid Arthritis
Mititelu, R. R., Pădureanu, R., Bacanoiu, M. V., Pădureanu, V., Docea, A. O., Călina, D. C., Bărbulescu, A. L., & Bugă, A. M. (2020) · Biomedicines · doi:10.3390/biomedicines8050125 · Cited by 110 · cited 1× · see citing works
“Nuclear factor-kappa B (NF-κB) along with its inhibitory protein, IκB controls the transcription of pro-inflammatory mediators and cytokines such as NO (nitric oxide), iNOS (inducible isoform NO), COX-2 (ciclooxigenase 2), TNF-α (Tumour necrosis alfa), PGE2 (prostaglandin E2), and IL-1β (interleukin 1β) (30, 31) Besid…”
BackgroundAvocado–Soybean Unsaponifiables: A Panoply of Potentialities to Be Exploited
Salehi, B., Rescigno, A., Dettori, T., Călina, D. C., Docea, A. O., Singh, L., Cebeci, F., Özçelik, B., Bhia, M., Beirami, A. D., et al. (2020) · Biomolecules · doi:10.3390/biom10010130 · Cited by 103 · cited 1× · see citing works
“NO, interleukin-1β (IL-1β), PGE2 etc (27).”
Slack, G. J., Puniani, E., Frisvad, J. C., Samson, R. A., & Miller, J. D. (2009) · Mycological Research · doi:10.1016/j.mycres.2008.12.002 · Cited by 96 · see citing works
Epibatidine: A Promising Natural Alkaloid in Health
Salehi, B., Sestito, S., Rapposelli, S., Peron, G., Calina, D., Sharifi-Rad, M., Sharopov, F., Martins, N., & Sharifi-Rad, J. (2018) · Biomolecules · doi:10.3390/biom9010006 · Cited by 91 · cited 1× · see citing works
“These pro-inflammatory mediators and cytokines are induced by different enzymes like cyclooxygenase-2 (COX-2), iNOS (28, 29).”
BackgroundVeronica Plants—Drifting from Farm to Traditional Healing, Food Application, and Phytopharmacology
Salehi, B., Shetty, M. S., Kumar, N. V. A., Živković, J., Călina, D. C., Docea, A. O., Yazdi, S. E., Kılıç, C. S., Goloshvili, T., Nicola, S., et al. (2019) · Molecules · doi:10.3390/molecules24132454 · Cited by 91 · cited 1× · see citing works
“These pro-inflammatory mediators and cytokines are induced by different enzymes like cyclooxygenase-2 (COX-2), iNOS (28, 29).”
BackgroundA Review of Anti-Inflammatory Compounds from Marine Fungi, 2000–2018
Xu, J., Yi, M., Ding, L., & He, S. (2019) · Marine Drugs · doi:10.3390/md17110636 · Cited by 91 · see citing works
Kim, K.-S., Cui, X., Lee, D., Sohn, J., Yim, J. H., Kim, Y., & Oh, H. (2013) · Molecules · doi:10.3390/molecules181113245 · Cited by 86 · see citing works
Sharifi‐Rad, J., Kamiloğlu, S., Yeskaliyeva, B. K., Beyatlı, A., Alfred, M. A., Salehi, B., Călina, D. C., Docea, A. O., Imran, M., Kumar, N. V. A., et al. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.571459 · Cited by 80 · cited 5× · see citing works
“Besides, neoechinulin A induced reduction in the expression of iNOS catalyzes, COX-2 Frontiers in Nutrition | www.frontiersin.org 2 July 2021 | Volume 8 | Article 664197 and MAPK pathway dose-dependently resulted in a dosedependent decreased in the synthesis of nitric oxide (NO) and prostaglandin E2 (PGE2).”
BackgroundInfluentialBovio, E., Garzoli, L., Poli, A., Luganini, A., Villa, P., Musumeci, R., McCormack, G. P., Cocuzza, C. E., Gribaudo, G., Mehiri, M., et al. (2019) · Marine Drugs · doi:10.3390/md17040220 · Cited by 74 · see citing works
Marchelli, R., Dossena, A., Pochini, A., & Dradi, E. (1977) · Journal of the Chemical Society Perkin Transactions 1 · doi:10.1039/p19770000713 · Cited by 69 · see citing works
Calina, D., Buga, A. M., Mitroi, M., Buha, A., Caruntu, C., Scheau, C., Bouyahya, A., El Omari, N., El Menyiy, N., & Docea, A. O. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9082395 · Cited by 65 · see citing works
Marine-Derived Natural Compounds for the Treatment of Parkinson’s Disease
Huang, C., Zhang, Z., & Cui, W. (2019) · Marine Drugs · doi:10.3390/md17040221 · Cited by 62 · see citing works
Pettit, G. R., Hogan, F., Xu, J., Tan, R., Nogawa, T., Cichacz, Z. A., Pettit, R. K., Du, J., Ye, Q.-H., Cragg, G. M. L., et al. (2008) · Journal of Natural Products · doi:10.1021/np700738k · Cited by 54 · see citing works
Dewapriya, P., Li, Y.-X., Himaya, S. W. A., Pangestuti, R., & Kim, S. (2012) · NeuroToxicology · doi:10.1016/j.neuro.2012.12.004 · Cited by 52 · see citing works
Li, Y., Li, X., Kang, J. S., Choi, H. D., & Son, B. W. (2004) · The Journal of Antibiotics · doi:10.7164/antibiotics.57.337 · Cited by 52 · see citing works
New metabolites of Aspergillus amstelodami related to the biogenesis of neoechinulin
Dossena, A., Marchelli, R., & Pochini, A. (1974) · Journal of the Chemical Society Chemical Communications · doi:10.1039/c39740000771 · Cited by 45 · see citing works
Wijesekara, I., Li, Y.-X., Vo, T., Ta, Q. V., Ngo, D., & Kim, S. (2012) · Process Biochemistry · doi:10.1016/j.procbio.2012.11.012 · Cited by 45 · see citing works
Isolation of an Antioxidative Substance Produced byAspergillus repens
Ryuta, Y. A. G. I., & Doi, M. (1999) · Bioscience Biotechnology and Biochemistry · doi:10.1271/bbb.63.932 · Cited by 45 · see citing works
Kimoto, K., Aoki, T., Shibata, Y., Kamisuki, S., Sugawara, F., Kuramochi, K., Nakazaki, A., Kobayashi, S. S., Kuroiwa, K., Watanabe, N., et al. (2007) · The Journal of Antibiotics · doi:10.1038/ja.2007.79 · Cited by 44 · see citing works
Xylactam, a New Nitrogen-containing Compound from the Fruiting Bodies of Ascomycete Xylaria euglossa
Wang, X.-N., Tan, R. X., & Liu, J. (2005) · The Journal of Antibiotics · doi:10.1038/ja.2005.31 · Cited by 42 · cited 1× · see citing works
“(2–5), ascomycete Xylaria euglossa (6), and some others (7, 8).”
BackgroundTwo new alkaloids from Portulaca oleracea L. and their bioactivities
Zhao, C., Zhang, C., He, F., Zhang, W., Leng, A., & Ying, X. (2019) · Fitoterapia · doi:10.1016/j.fitote.2019.05.005 · Cited by 37 · see citing works
Protective Properties of Neoechinulin A against SIN-1-Induced Neuronal Cell Death
Maruyama, K. (2004) · The Journal of Biochemistry · doi:10.1093/jb/mvh103 · Cited by 35 · see citing works
Kuramochi, K., Ohnishi, K., Fujieda, S., Nakajima, M., Saitoh, Y., Watanabe, N., Takeuchi, T., Nakazaki, A., Sugawara, F., Arai, T., et al. (2008) · Chemical and Pharmaceutical Bulletin · doi:10.1248/cpb.56.1738 · Cited by 30 · see citing works
Neoechinulin A Impedes the Progression of Rotenone-Induced Cytotoxicity in PC12 Cells
Akashi, S., Kimura, T., Takeuchi, T., Kuramochi, K., Kobayashi, S. S., Sugawara, F., Watanabe, N., & Arai, T. (2011) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.34.243 · Cited by 30 · see citing works
Neoechinulin A Protects PC12 Cells against MPP+-induced Cytotoxicity
Kajimura, Y., Aoki, T., Kuramochi, K., Kobayashi, S. S., Sugawara, F., Watanabe, N., & Arai, T. (2008) · The Journal of Antibiotics · doi:10.1038/ja.2008.48 · Cited by 29 · see citing works
Nakajima, S., Watashi, K., Ohashi, H., Kamisuki, S., Izaguirre-Carbonell, J., Kwon, A. T.-J., Suzuki, H., Kataoka, M., Tsukuda, S., Okada, M., et al. (2016) · Journal of Virology · doi:10.1128/jvi.00856-16 · Cited by 29 · see citing works
Ito, T., Noritake, K., Sugiura, H., Kamiya, Y., Tomita, H., Ito, Y., Sugiura, H., Ochi, N., & Yoshihashi, Y. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm9010028 · Cited by 29 · see citing works
Neoechinulin A induced memory improvements and antidepressant-like effects in mice
Sasaki‐Hamada, S., Hoshi, M., Niwa, Y., Ueda, Y., Kokaji, A., Kamisuki, S., Kuramochi, K., Sugawara, F., & Oka, J. (2016) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2016.08.002 · Cited by 21 · see citing works
Diketopiperazine indole alkaloids from hemp seed
Yan, X., Zhou, Y., Tang, J., Ji, M., Lou, H., & Fan, P. (2016) · Phytochemistry Letters · doi:10.1016/j.phytol.2016.09.001 · Cited by 21 · cited 1× · see citing works
“Stereoisomers of diketopiperazine indole alkaloids namely (12S, 22R)Dihydroxyisoechinulin A, (12S, 22S)-Dihydroxyisoechinulin A, (12R)-Neoechinulin A, and (12S)-Neoechinulin A were isolated from hemp seed (10).”
BackgroundZhu, Y., Yu, G., Wang, Y., Xu, J.-H., Xu, F., Fu, H., Zhao, Y.-H., & Wu, J. (2019) · Chemistry of Natural Compounds · doi:10.1007/s10600-019-02651-5 · Cited by 10 · see citing works
Identification of proteins that bind to the neuroprotective agent neoechinulin A
Kamisuki, S., Himeno, N., Tsurukawa, Y., Kusayanagi, T., Takeno, M., Kamakura, T., Kuramochi, K., & Sugawara, F. (2018) · Bioscience Biotechnology and Biochemistry · doi:10.1080/09168451.2018.1433018 · Cited by 9 · see citing works
Synthesis and Neuroprotective Action of Optically Pure Neoechinulin A and Its Analogs
Aoki, T., Ohnishi, K., Kimoto, M., Fujieda, S., Kuramochi, K., Takeuchi, T., Nakazaki, A., Watanabe, N., Sugawara, F., Arai, T., et al. (2010) · Pharmaceuticals · doi:10.3390/ph3041063 · Cited by 8 · see citing works
Chemical constituents of Cyrtomium fortumei (J.) Smith
Yang, S., Liu, M., Liang, N., Xiang, H., & Yang, S. (2013) · Natural Product Research · doi:10.1080/14786419.2013.824442 · Cited by 7 · cited 1× · see citing works
“Their presence in different plant sources including Tinosporae Radix (the roots of Tinospora sagittata) (11), Opuntia dillenii (12), Cyrtomium fortunei (13) etc.”
BackgroundIsolation and identification of the chemical constituents of Opuntia dillenii Haw.
Li, Z. (2013) · Zhongguo yaowu huaxue zazhi · Cited by 7 · see citing works
Chapter 4 Alkaloidal Substances from Aspergillus Species
Yamamoto, Y., & Arai, K. (1986) · The Alkaloids. Chemistry and physiology · doi:10.1016/s0099-9598(08)60249-7
Flagged first, then by citations
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Sorted by citations
Dhyani, P., Quispe, C., Sharma, E., Bahukhandi, A., Sati, P., Attri, D. C., Szopa, A., Sharifi-Rad, J., Docea, A. O., Mardare, I., et al. (2022) · Cancer Cell International · doi:10.1186/s12935-022-02624-9 · Cited by 483 · see citing works
Paclitaxel: Application in Modern Oncology and Nanomedicine‐Based Cancer Therapy
Sharifi‐Rad, J., Quispe, C., Patra, J. K., Singh, Y. D., Panda, M. K., Das, G., Adetunji, C. O., Michael, O. S., Sytar, O., Polito, L., et al. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/3687700 · Cited by 316 · see citing works
“frequently than normal cells, and for this reason, they can be more affected than healthy tissues [16].”
BackgroundPotential mechanisms of quercetin in cancer prevention: focus on cellular and molecular targets
Asgharian, P., Tazehkand, A. P., Hosseini, K., Forouhandeh, H., Ghasemnejad, T., Ranjbar, M., Hasan, M., Kumar, M., Beirami, S. M., Tarhriz, V., et al. (2022) · Cancer Cell International · doi:10.1186/s12935-022-02677-w · Cited by 281 · see citing works
“Chemopreventive properties of natural bioactive substances have been increasingly important to researchers in the field of medicine in recent years [5, 6].”
BackgroundSharifi-Rad, J., Rapposelli, S., Sestito, S., Herrera-Bravo, J., Arancibia-Diaz, A., Salazar, L. A., Yeskaliyeva, B., Beyatli, A., Leyva-Gómez, G., González-Contreras, C., et al. (2022) · Journal of Personalized Medicine · doi:10.3390/jpm12091515 · Cited by 125 · see citing works
Urtica dioica-Derived Phytochemicals for Pharmacological and Therapeutic Applications
Taheri, Y., Quispe, C., Herrera‐Bravo, J., Sharifi‐Rad, J., Ezzat, S. M., Merghany, R. M., Shaheen, S., Azmi, L., Mishra, A. P., Şener, B., et al. (2022) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2022/4024331 · Cited by 133 · see citing works
Ijaz, S., Iqbal, J., Abbasi, B. A., Ullah, Z., Yaseen, T., Kanwal, S., Mahmood, T., Sydykbayeva, S., Ydyrys, A., Almarhoon, Z. M., et al. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.114687 · Cited by 121 · see citing works
RetractedPhenolic compounds as Nrf2 inhibitors: potential applications in cancer therapy
Sharifi‐Rad, J., Seidel, V., Izabela, M., Monserrat-Mesquida, M., Sureda, A., Ormazábal, V., Zuñiga, F. A., Shetty, M. S., Pezzani, R., Ydyrys, A., et al. (2023) · Cell Communication and Signaling · doi:10.1186/s12964-023-01109-0 · Cited by 105 · see citing works
“Especially considering that conventional anticancer therapies generate cytotoxicity dependent on the efficient accumulation of ROS [14, 15].”
BackgroundArtemisia spp.: An Update on Its Chemical Composition, Pharmacological and Toxicological Profiles
Sharifi‐Rad, J., Herrera‐Bravo, J., Semwal, P., Painuli, S., Badoni, H., Ezzat, S. M., Farid, M. M., Merghany, R. M., Aborehab, N. M., Salem, M. A., et al. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/5628601 · Cited by 101 · see citing works
Tobacco Smoking and Liver Cancer Risk: Potential Avenues for Carcinogenesis
Jain, D., Chaudhary, P., Varshney, N., Razzak, K. S. B., Verma, D., Zahra, T. R. K., Janmeda, P., Sharifi‐Rad, J., Daştan, S. D., Mahmud, S., et al. (2021) · Journal of Oncology · doi:10.1155/2021/5905357 · Cited by 96 · see citing works
“*ese genetic variations cause uncontrolled cell proliferation and suppress natural processes that normally limit atypical cell growth, leading to cancer [48].”
BackgroundRecent updates on anticancer mechanisms of polyphenols
Sharma, E., Attri, D. C., Sati, P., Dhyani, P., Szopa, A., Sharifi‐Rad, J., Hano, C., Călina, D. C., & Cho, W. C. S. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.1005910 · Cited by 96 · see citing works
Nutraceutical Profiling, Bioactive Composition, and Biological Applications of Lepidium sativum L.
Painuli, S., Quispe, C., Herrera‐Bravo, J., Semwal, P., Martorell, M., Almarhoon, Z. M., Seilkhan, A., Ydyrys, A., Sharifi‐Rad, J., Alshehri, M. M., et al. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/2910411 · Cited by 77 · see citing works
Dhyani, P., Sati, P., Sharma, E., Attri, D. C., Bahukhandi, A., Tynybekov, B., Szopa, A., Sharifi‐Rad, J., Călina, D. C., Suleria, H. A. R., et al. (2022) · Cancer Cell International · doi:10.1186/s12935-022-02721-9 · Cited by 76 · see citing works
Sharifi‐Rad, J., Quispe, C., Herrera‐Bravo, J., Akram, M., Abbaass, W., Semwal, P., Painuli, S., Коновалов, Д. А., Alfred, M. A., Kumar, N. V. A., et al. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/6584693 · Cited by 63 · see citing works
“Medicinal plants and herbs have been used worldwide in the management of different diseases [1, 2].”
BackgroundRetractedChaudhary, P., Mitra, D., MOHAPATRA, P. K. D., Docea, A. O., Myo, E. M., Janmeda, P., Martorell, M., Iriti, M., Ibrayeva, M., Sharifi‐Rad, J., et al. (2023) · Arabian Journal of Chemistry · doi:10.1016/j.arabjc.2023.104680 · Cited by 60 · see citing works
Anticancer properties of bromelain: State-of-the-art and recent trends
Pezzani, R., Jiménez-Garcia, M., Capó, X., Gürer, E. S., Sharopov, F. S., Rachel, T. Y. L., Ntieche, D. W., Rescigno, A., Peddio, S., Zucca, P., et al. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2022.1068778 · Cited by 59 · see citing works
Mitra, S., Anand, U., Sanyal, R., Jha, N. K., Behl, T., Mundhra, A., Ghosh, A., Radha, Kumar, M., Proćków, J., et al. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.112378 · Cited by 52 · see citing works
Ali, E. S., Akter, S., Ramproshad, S., Mondal, B., Riaz, T. A., Islam, M. T., Khan, I. N., Docea, A. O., Călina, D. C., Sharifi‐Rad, J., et al. (2022) · Cancer Cell International · doi:10.1186/s12935-022-02666-z · Cited by 48 · see citing works
Lasia spinosa Chemical Composition and Therapeutic Potential: A Literature‐Based Review
Hossain, R., Quispe, C., Herrera‐Bravo, J., Islam, M. S., Sarkar, C. K., Islam, M. T., Martorell, M., Martins, N. A., Al‐Harrasi, A., Al-Rawahi, A. N., et al. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/1602437 · Cited by 42 · see citing works
“This cytotoxicity is done in different ways: some bioactive compounds can affect the genetic material of cells, and others act by blocking the access of malignant cells to the nutrients needed for division and multiplication [58, 59].”
BackgroundTherapeutic potentials of ononin with mechanistic insights: A comprehensive review
Bhuia, M. S., Aktar, A., Chowdhury, R., Ferdous, J., Rahman, M. A., Hasan, M. S. A., & Islam, M. T. (2023) · Food Bioscience · doi:10.1016/j.fbio.2023.103302 · Cited by 38 · see citing works
Sharifi-Rad, J., Quispe, C., Turgumbayeva, A., Mertdinç, Z., Tütüncü, S., Aydar, E. F., Özçelik, B., Anna, S.-W., Mariola, S., Koziróg, A., et al. (2023) · Zeitschrift für Naturforschung C · doi:10.1515/znc-2022-0076 · Cited by 39 · see citing works
Natural essential oils as a new therapeutic tool in colorectal cancer
Garzoli, S., Alarcón, P., Seitimova, G. A., Alarcón-Zapata, B., Martorell, M., Sharopov, F. S., Fokou, P. V. T., Dize, D., Yamthé, L. R. T., Les, F., et al. (2022) · Cancer Cell International · doi:10.1186/s12935-022-02806-5 · Cited by 38 · see citing works
“After a decline in the pharmaceutical industry’s search for natural products from the 1990s onwards due to technical barriers to screening, isolation, characterization and optimization, in recent years, technological and scientific development has revitalized the interest in them [27, 28].”
BackgroundApoptosis evasion via long non-coding RNAs in colorectal cancer
Irfan, M., Javed, Z., Khan, K., Khan, N., Docea, A. O., Călina, D. C., Sharifi‐Rad, J., & Cho, W. C. S. (2022) · Cancer Cell International · doi:10.1186/s12935-022-02695-8 · Cited by 35 · see citing works
“It is an important protein that regulates the cell cycle and controls programmed cell death [52, 53].”
BackgroundIslam, M. T., Martorell, M., González-Contreras, C., Villagrán, M., Mardones, L., Tynybekov, B., Docea, A. O., Razis, A. F. A., Modu, B., Călina, D. C., et al. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1099380 · Cited by 28 · see citing works
Neurobiological Promises of the Bitter Diterpene Lactone Andrographolide
Hossain, R., Quispe, C., Herrera‐Bravo, J., Beltrán, J. F., Islam, M. T., Shaheen, S., Martins, N. A., Martorell, M., Kumar, M., Sharifi‐Rad, J., et al. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/3079577 · Cited by 29 · see citing works
Secondary Metabolites from Coral-Associated Fungi: Source, Chemistry and Bioactivities
Chen, Y., Pang, X., He, Y., Lin, X., Zhou, X., Liu, Y., & Yang, B. (2022) · Journal of Fungi · doi:10.3390/jof8101043 · Cited by 27 · see citing works
“Moreover, compound 40 also displayed strong cytotoxic activity against human cervical carcinoma HeLa cells and exerted anti-inflammatory, antiviral, and neuroprotective activity [40,41].”
BackgroundAtoki, A. V., Aja, P. M., Ondari, E. N., & Shinkafi, T. S. (2023) · International Journal of Food Properties · doi:10.1080/10942912.2023.2243050 · Cited by 19 · see citing works
Use of Albumin for Drug Delivery as a Diagnostic and Therapeutic Tool
Karami, E., Moghaddam, M. M., & Kazemi‐Lomedasht, F. (2023) · Current Pharmaceutical Biotechnology · doi:10.2174/1389201024666230807161200 · Cited by 12 · see citing works
Omer, G. A., & Mohammed, L. Y. (2023) · Baghdad Science Journal · doi:10.21123/bsj.2023.8658 · Cited by 12 · see citing works
El‐Kashef, D. H., Obidake, D. D., Schiedlauske, K., Deipenbrock, A., Scharf, S. A., Wang, H., Naumann, D., Friedrich, D., Miljanovic, S., Sohi, T. H. H., et al. (2023) · Marine Drugs · doi:10.3390/md22010005 · Cited by 10 · see citing works
“Indole DKPs are not only characterized by the diversities in their chemical structures but are also reported to exhibit significant biological activities, such as anti-inflammatory, anticancer, antiviral, anti-neurogenerative, and antioxidant activities [9,14].”
BackgroundKhanfar, M. A., & Saleh, M. (2023) · Current Medicinal Chemistry · doi:10.2174/0109298673271674231109052709 · Cited by 6 · see citing works
Chemical Constituents and Bioactivities of the Plant-Derived Fungus Aspergillus fumigatus
Sang, Z., Zhang, Y., Qiu, K., Zheng, Y., Chen, C., Xu, L., Lai, J., Zou, Z., & Tan, H. (2024) · Molecules · doi:10.3390/molecules29030649 · Cited by 5 · see citing works
SAWICKA, B. H., Ziarati, P., Messaoudi, M., Agarpanah, J., Skiba, D., Bienia, B., Barbaś, P., Rebiai, A., Krochmal‐Marczak, B., & Yeganehpoor, F. (2022) · Advances in medical diagnosis, treatment, and care (AMDTC) book series · doi:10.4018/978-1-6684-5129-8.ch023 · Cited by 4 · see citing works
Forest fungi: Advancement of White biotechnology via forest fungi
Raturi, S., & Kumari, S. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-18870-1.00019-6 · Cited by 3 · see citing works
Ruiz, M. M., Cabanillas, B. J., Haddad, M., Díaz, A., Sauvain, M., & Castillo, D. (2025) · International Journal of Microbiology · doi:10.1155/ijm/8756981 · Cited by 4 · see citing works
“Maculosin has demonstrated antiviral potential against the Hepatitis C virus by inhibiting the NS3 protease ( IC 50 = 8 2 ± 1 7 μ g/mL) [24] alongside [42].”
Wei, R., Pan, X., Cai, D., & Pan, L. (2025) · Cell Biochemistry and Biophysics · doi:10.1007/s12013-024-01662-6 · Cited by 2 · see citing works
Shlyk, N. P., Yurchenko, E. A., Leshchenko, E. V., Chingizova, E. A., Chingizov, A. R., Chausova, V. E., Kirichuk, N. N., Khudyakova, Y. V., Викторович, П. М., Antonov, A. S., et al. (2025) · The Journal of Antibiotics · doi:10.1038/s41429-025-00811-0 · Cited by 1 · see citing works
“Moreover, 4 suppressed the liver X receptor (LXR) in a cell culture system of the hepatitis C virus (HCV) and affected H1N1 virus-infected in Madin-Darby canine kidney (MDCK) cells [72].”
Abraham, S., Lentaya, H. O., Isroni, M., Sativa, R. G., Monconegoro, D. A., Baruji, T., Tasia, W. R. N., Supriyono, A., Nuralih, N., Permadi, E. E., et al. (2025) · Preparative Biochemistry & Biotechnology · doi:10.1080/10826068.2025.2562464 · Cited by 1 · see citing works
“[42] A summary of the endophytic fungi and their secondary metabolites with anti-oxidant potentials is presented in Table 1.”
Evaluating of aqueous and Alcoholic extracts of (Urtica pilulifera L.) in the hypersensitivity
Abed, E. Y., & Khashan, K. T. (2024) · BIO Web of Conferences · doi:10.1051/bioconf/202413906028
A Review on Phytochemistry and Pharmacological Overview of Mentha ArvensisPreprint
Negi, P., Mehta, R., Negi, D., Gwasikoti, J., & Joshi, N. (2025) · SSRN Electronic Journal · doi:10.2139/ssrn.5088866
Dhyani, P., Quispe, C., Sharma, E., Bahukhandi, A., Sati, P., Attri, D. C., Szopa, A., Sharifi-Rad, J., Docea, A. O., Mardare, I., et al. (2022) · Figshare · doi:10.6084/m9.figshare.19980552
Ödemiş, Ö., Alan, Y., & Karakurt, E. M. (2026) · Research Square · doi:10.21203/rs.3.rs-10619266/v1
Zeleke, G. A., Emire, S. A., & de Wit, M. (2026) · Separation Science Plus · doi:10.1002/sscp.70303
Qi, J.-J., Zeng, H.-T., & Yuan, T. (2026) · Tetrahedron Letters · doi:10.1016/j.tetlet.2026.156278
- Authors
- Sharifi-Rad, J., Bahukhandi, A., Dhyani, P., Sati, P., Capanoglu, E., Docea, A. O., Al-Harrasi, A., Dey, A., & Calina, D.
- Affiliations
- G.B. Pant Institute of Himalayan Environment and Development (IN)
- Institute of Himalayan Bioresource Technology (IN)
- Graphic Era University (IN)
- University of Medicine and Pharmacy of Craiova (RO)
- Presidency University (IN)
- Venue
- Frontiers in Nutrition
- Publisher
- Frontiers Media SA
- Published
- 2021-07-16
- Volume
- 8
- Pages
- 664197-664197
- ISSN
- 2296-861X (ISSN-L)
- PMC
- PMC8322439
- OpenAlex
- W3186309197
- Cited by
- 43
- References
- 53
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 3 · 2023: 11 · 2022: 16 · 2021: 5
- FWCI
- 1.11
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Nutrition (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Istanbul Technical University Academic Open Archive (Istanbul Technical University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Microbial Natural Products and Biosynthesis
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Alkaloids: synthesis and pharmacology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Synthesis and bioactivity of alkaloids
- Keywords
- fungal natural products, Aspergillus, Eurotium cristatum, Microsporum, Opuntia dillenii, Cyrtomium fortunei, Cannabis sativa, anticancer activity, anti-neuroinflammatory activity, antiviral activity, hepatitis C virus, free radical scavenging, anti-inflammatory activity, neurotrophic factors, apoptosis, molecular mechanisms of action
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