Water Extract from Inflorescences of Industrial Hemp Futura 75 Variety as a Source of Anti-Inflammatory, Anti-Proliferative and Antimycotic Agents: Results from In Silico, In Vitro and Ex Vivo Studies
Abstract
:1. Introduction
2. Materials and Methods
2.1. Hemp Sample, Reagents and Standard Solutions
2.2. Extract Preparation
2.3. Phytochemical Analysis
2.4. Cell Culture
2.5. Ex Vivo Model of LPS-Induced Toxicity in Isolated Rat and Liver Tissues
2.6. Antifungal Activity of the Extract
2.7. Bioinformatics and Docking Studies
2.8. Docking Calculations
2.9. Statistical Analysis
3. Results and Discussion
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Montserrat-de la Paz, S.; Marín-Aguilar, F.; García-Gimenez, M.D.; Fernández-Arche, M. Hemp (Cannabis sativa L.) seed oil: Analytical and phytochemical characterization of the unsaponifiable fraction. J. Agric. Food Chem. 2014, 62, 1105–1110. [Google Scholar] [CrossRef] [PubMed]
- Vonapartis, E.; Aubin, M.-P.; Seguin, P.; Mustafa, A.F.; Charron, J.-B. Seed composition of ten industrial hemp cultivars approved for production in Canada. J. Food Compos. Anal. 2015, 39, 8–12. [Google Scholar] [CrossRef]
- Kiralan, M.; Gül, V.; Kara, S.M. Fatty acid composition of hempseed oils from different locations in Turkey. Span. J. Agric. Res. 2010, 8, 385–390. [Google Scholar] [CrossRef]
- De Backer, B.; Maebe, K.; Verstraete, A.G.; Charlier, C. Evolution of the content of THC and other major cannabinoids in drug-type cannabis cuttings and seedlings during growth of plants. J. Forensic Sci. 2012, 57, 918–922. [Google Scholar] [CrossRef]
- Amaducci, S.; Scordia, D.; Liu, F.; Zhang, Q.; Guo, H.; Testa, G.; Cosentino, S. Key cultivation techniques for hemp in Europe and China. Ind. Crop Prod. 2015, 68, 2–16. [Google Scholar] [CrossRef]
- Benelli, G.; Pavela, R.; Lupidi, G.; Nabissi, M.; Petrelli, R.; Kamte, S.L.N.; Cappellacci, L.; Fiorini, D.; Sut, S.; Dall’Acqua, S. The crop-residue of fiber hemp cv. Futura 75: From a waste product to a source of botanical insecticides. Environ. Sci. Pollut. R. 2018, 25, 10515–10525. [Google Scholar] [CrossRef]
- Smeriglio, A.; Trombetta, D.; Cornara, L.; Valussi, M.; De Feo, V.; Caputo, L. Characterization and phytotoxicity assessment of essential oils from plant byproducts. Molecules 2019, 24, 2941. [Google Scholar] [CrossRef] [Green Version]
- Zengin, G.; Menghini, L.; Di Sotto, A.; Mancinelli, R.; Sisto, F.; Carradori, S.; Cesa, S.; Fraschetti, C.; Filippi, A.; Angiolella, L. Chromatographic analyses, in vitro biological activities, and cytotoxicity of cannabis sativa l. Essential oil: A multidisciplinary study. Molecules 2018, 23, 3266. [Google Scholar] [CrossRef] [Green Version]
- Bertoli, A.; Tozzi, S.; Pistelli, L.; Angelini, L.G. Fibre hemp inflorescences: From crop-residues to essential oil production. Ind. Crop Prod. 2010, 32, 329–337. [Google Scholar] [CrossRef]
- Ferrante, C.; Recinella, L.; Ronci, M.; Menghini, L.; Brunetti, L.; Chiavaroli, A.; Leone, S.; Di Iorio, L.; Carradori, S.; Tirillini, B.; et al. Multiple pharmacognostic characterization on hemp commercial cultivars: Focus on inflorescence water extract activity. Food Chem. Toxicol. 2019, 125, 452–461. [Google Scholar] [CrossRef]
- Mazidi, M.; Taraghdari, S.B.; Rezaee, P.; Kamgar, M.; Jomezadeh, M.R.; Hasani, O.A.; Soukhtanloo, M.; Hosseini, M.; Gholamnezhad, Z.; Rakhshandeh, H. The effect of hydroalcoholic extract of Cannabis Sativa on appetite hormone in rat. J. Compl. Integr. Med. 2014, 11, 253–257. [Google Scholar] [CrossRef] [PubMed]
- El-Zawawy, N.A.; Ali, S.S. Pyocyanin as anti-tyrosinase and anti tinea corporis: A novel treatment study. Microg. Pathog. 2016, 100, 213–220. [Google Scholar] [CrossRef] [PubMed]
- Zengin, G.; Locatelli, M.; Stefanucci, A.; Macedonio, G.; Novellino, E.; Mirzaie, S.; Dvorácskó, S.; Carradori, S.; Brunetti, L.; Orlando, G.; et al. Chemical characterization, antioxidant properties, anti-inflammatory activity, and enzyme inhibition of Ipomoea batatas L. leaf extracts. Int. J. Food Prop. 2017, 20, 1907–1919. [Google Scholar] [CrossRef] [Green Version]
- Chiavaroli, A.; Recinella, L.; Ferrante, C.; Locatelli, M.; Macchione, N.; Zengin, G.; Leporini, L.; Leone, S.; Martinotti, S.; Brunetti, L.; et al. Crocus sativus, Serenoa repens and Pinus massoniana extracts modulate inflammatory response in isolated rat prostate challenged with LPS. J. Boil. Regul. Homeost. Agents 2017, 31, 531–541. [Google Scholar]
- Menghini, L.; Ferrante, C.; Leporini, L.; Recinella, L.; Chiavaroli, A.; Leone, S.; Pintore, G.; Vacca, M.; Orlando, G.; Brunetti, L. An hydroalcoholic chamomile extract modulates inflammatory and immune response in HT29 cells and isolated rat colon. Phytother. Res. 2016, 30, 1513–1518. [Google Scholar] [CrossRef]
- Brunetti, L.; Leone, S.; Orlando, G.; Ferrante, C.; Recinella, L.; Chiavaroli, A.; Di Nisio, C.; Shohreh, R.; Manippa, F.; Ricciuti, A.; et al. Hypotensive effects of omentin-1 related to increased adiponectin and decreased interleukin-6 in intra-thoracic pericardial adipose tissue. Pharmacol. Rep. 2014, 66, 991–995. [Google Scholar] [CrossRef]
- di Giacomo, V.; Chiavaroli, A.; Orlando, G.; Cataldi, A.; Rapino, M.; Di Valerio, V.; Leone, S.; Brunetti, L.; Menghini, L.; Recinella, L.; et al. Neuroprotective and Neuromodulatory Effects Induced by Cannabidiol and Cannabigerol in Rat Hypo-E22 cells and Isolated Hypothalamus. Antioxidants 2020, 9, 71. [Google Scholar] [CrossRef] [Green Version]
- CLSI. Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts. Approved Standard; Document M38; Clinical Laboratory Standards Institute: Wayne, PA, USA, 2018. [Google Scholar]
- Gu, L.; Lu, J.; Li, Q.; Wu, N.; Zhang, L.; Li, H.; Xing, W.; Zhang, X. A network-based analysis of key pharmacological pathways of Andrographis paniculata acting on Alzheimer’s disease and experimental validation. J. Ethnopharmacol. 2020, 251, 112488. [Google Scholar] [CrossRef]
- Pedretti, A.; Villa, L.; Vistoli, G. VEGA—An open platform to develop chemo-bio-informatics applications, using plug-in architecture and script programming. J. Comput. Aided Mol. Des. 2004, 18, 167–173. [Google Scholar] [CrossRef]
- The Molinspiration Database. Available online: http://www.molinspiration.com (accessed on 20 April 2020).
- Politi, M.; Zloh, M.; Pintado, M.E.; Castro, P.M.; Heinrich, M.; Prieto, J.M. Direct metabolic fingerprinting of commercial herbal tinctures by nuclear magnetic resonance spectroscopy and mass spectrometry. Phytochem. Analysis 2009, 20, 328–334. [Google Scholar] [CrossRef]
- Anastasiadi, M.; Zira, A.; Magiatis, P.; Haroutounian, S.A.; Skaltsounis, A.L.; Mikros, E. 1H NMR-based metabonomics for the classification of Greek wines according to variety, region, and vintage. Comparison with HPLC data. J. Agric. Food Chem. 2009, 57, 11067–11074. [Google Scholar] [CrossRef] [PubMed]
- Boffo, E.F.; Tavares, L.A.; Tobias, A.C.; Ferreira, M.M.; Ferreira, A.G. Identification of components of Brazilian honey by 1H NMR and classification of its botanical origin by chemometric methods. LWT 2012, 49, 55–63. [Google Scholar] [CrossRef] [Green Version]
- Sinan, K.I.; Zengin, G.; Zheleva-Dimitrova, D.; Etienne, O.K.; Fawzi Mahomoodally, M.; Bouyahya, A.; Lobine, D.; Chiavaroli, A.; Ferrante, C.; Menghini, L.; et al. Qualitative Phytochemical Fingerprint and Network Pharmacology Investigation of Achyranthes aspera Linn. Extracts. Molecules 2020, 25, 1973. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Patrignani, P.; Sacco, A.; Sostres, C.; Bruno, A.; Dovizio, M.; Piazuelo, E.; Di Francesco, L.; Contursi, A.; Zucchelli, M.; Schiavone, S. Low-dose aspirin acetylates cyclooxygenase-1 in human colorectal mucosa: Implications for the chemoprevention of colorectal cancer. Clin. Pharmacol. Ther. 2017, 102, 52–61. [Google Scholar] [CrossRef]
- Shamsi, F.; Hasan, P.; Queen, A.; Hussain, A.; Khan, P.; Zeya, B.; King, H.M.; Rana, S.; Garrison, J.; Alajmi, M.F. Synthesis and SAR studies of novel 1, 2, 4-oxadiazole-sulfonamide based compounds as potential anticancer agents for colorectal cancer therapy. Bioorg. Chem. 2020, 98, 103754. [Google Scholar] [CrossRef]
- Sinan, K.I.; Chiavaroli, A.; Orlando, G.; Bene, K.; Zengin, G.; Cziáky, Z.; Jekő, J.; Mahomoodally, M.F.; Picot-Allain, M.C.N.; Menghini, L.; et al. Biopotential of bersama abyssinica fresen stem bark extracts: UHPLC profiles, antioxidant, enzyme inhibitory, and antiproliferative propensities. Antioxidants 2020, 9, 163. [Google Scholar] [CrossRef] [Green Version]
- Salah, A.; Bouaziz, C.; Amara, I.; Abid-Essefi, S.; Bacha, H. Eugenol protects against citrinin-induced cytotoxicity and oxidative damages in cultured human colorectal HCT116 cells. Environ. Sci. Pollut. R. 2019, 26, 31374–31383. [Google Scholar] [CrossRef]
- Chen, W.; Jin, M.; Wu, W. Experimental study on inhibitory effect of rutin against platelet activation induced by platelet activating factor in rabbits. Zhongguo Zhong Xi Yi Jie He Za Zhi 2002, 22, 283–285. [Google Scholar]
- Borman, R.; Tilford, N.; Harmer, D.; Day, N.; Ellis, E.; Sheldrick, R.; Carey, J.; Coleman, R.; Baxter, G. 5-HT2B receptors play a key role in mediating the excitatory effects of 5-HT in human colon in vitro. Br. J. Pharmacol. 2002, 135, 1144–1151. [Google Scholar] [CrossRef] [Green Version]
- Dolivo, D.M.; Larson, S.A.; Dominko, T. Tryptophan metabolites kynurenine and serotonin regulate fibroblast activation and fibrosis. Cell. Mol. Life Sci. 2018, 75, 3663–3681. [Google Scholar] [CrossRef]
- Stavely, R.; Fraser, S.; Sharma, S.; Rahman, A.A.; Stojanovska, V.; Sakkal, S.; Apostolopoulos, V.; Bertrand, P.; Nurgali, K. The onset and progression of chronic colitis parallels increased mucosal serotonin release via enterochromaffin cell hyperplasia and downregulation of the serotonin reuptake transporter. Inflamm. Bowel Dis. 2018, 24, 1021–1034. [Google Scholar] [CrossRef] [PubMed]
- Tashita, C.; Hoshi, M.; Hirata, A.; Nakamoto, K.; Ando, T.; Hattori, T.; Yamamoto, Y.; Tezuka, H.; Tomita, H.; Hara, A. Kynurenine plays an immunosuppressive role in 2, 4, 6-trinitrobenzene sulfate-induced colitis in mice. World J. Gastroenterol. 2020, 26, 918. [Google Scholar] [CrossRef] [PubMed]
- Maddison, D.C.; Giorgini, F. The kynurenine pathway and neurodegenerative disease. In Seminars in Cell & Developmental Biology; Elsevier: Amsterdam, The Netherlands, 2015; pp. 134–141. [Google Scholar]
- Jiang, X.; Xu, L.; Tang, L.; Liu, F.; Chen, Z.; Zhang, J.; Chen, L.; Pang, C.; Yu, X. Role of the indoleamine-2, 3-dioxygenase/kynurenine pathway of tryptophan metabolism in behavioral alterations in a hepatic encephalopathy rat model. J. Neuroinflammion 2018, 15, 3. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lee, J.; Chang, C.; Liu, I.; Chi, T.; Yu, H.; Cheng, J. Changes in endogenous monoamines in aged rats. Clin. Exp. Pharmacol. Physiol. 2001, 28, 285–289. [Google Scholar] [CrossRef] [PubMed]
- Zara, C.; Severino, A.; Flego, D.; Ruggio, A.; Pedicino, D.; Giglio, A.F.; Trotta, F.; Lucci, C.; D’Amario, D.; Vinci, R. Indoleamine 2, 3-dioxygenase (IDO) enzyme links innate immunity and altered T-cell differentiation in non-ST segment elevation acute coronary syndrome. Int. J. Mol. Sci. 2018, 19, 63. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Walczak, K.; Turski, W.A.; Rajtar, G. Kynurenic acid inhibits colon cancer proliferation in vitro: Effects on signaling pathways. Amino Acids 2014, 46, 2393–2401. [Google Scholar] [CrossRef] [Green Version]
- Mahomoodally, M.F.; Sinan, K.I.; Bene, K.; Zengin, G.; Orlando, G.; Menghini, L.; Veschi, S.; Chiavaroli, A.; Recinella, L.; Brunetti, L.; et al. Bridelia speciosa Müll. Arg. Stem bark Extracts as a Potential Biomedicine: From Tropical Western Africa to the Pharmacy Shelf. Antioxidants 2020, 9, 128. [Google Scholar] [CrossRef] [Green Version]
- Zhou, H.; Tang, L.; Yang, Y.; Lin, L.; Dai, J.; Ge, P.; Ai, Q.; Jiang, R.; Zhang, L. Dopamine alleviated acute liver injury induced by lipopolysaccharide/D-galactosamine in mice. Int. Immunopharmacol. 2018, 61, 249–255. [Google Scholar] [CrossRef]
- Eisenhofer, G.; Åneman, A.; Friberg, P.; Hooper, D.; Fåndriks, L.; Lonroth, H.; Hunyady, B.I.; Mezey, E. Substantial production of dopamine in the human gastrointestinal tract. J. Clin. Endocrinol. Metab. 1997, 82, 3864–3871. [Google Scholar] [CrossRef]
- Xue, R.; Zhang, H.; Pan, J.; Du, Z.; Zhou, W.; Zhang, Z.; Tian, Z.; Zhou, R.; Bai, L. Peripheral dopamine controlled by gut microbes inhibits invariant natural killer T cell-mediated hepatitis. Front. Immunol. 2018, 9, 2398. [Google Scholar] [CrossRef] [Green Version]
- Isa-Isa, R.; Arenas, R.; Isa, M. Inflammatory tinea capitis: Kerion, dermatophytic granuloma, and mycetoma. Clin. Dermatol. 2010, 28, 133–136. [Google Scholar] [CrossRef] [PubMed]
- Zhang, M.; Jiang, L.; Li, F.; Xu, Y.; Lv, S.; Wang, B. Simultaneous dermatophytosis and keratomycosis caused by Trichophyton interdigitale infection: A case report and literature review. BMC Infect. Dis. 2019, 19, 1–8. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kolbe, L.; Mann, T.; Gerwat, W.; Batzer, J.; Ahlheit, S.; Scherner, C.; Wenck, H.; Stäb, F. 4-n-butylresorcinol, a highly effective tyrosinase inhibitor for the topical treatment of hyperpigmentation. J. Eur. Acad. Dermatol. 2013, 27, 19–23. [Google Scholar] [CrossRef] [PubMed]
- Bottari, N.B.; Lopes, L.Q.S.; Pizzuti, K.; dos Santos Alves, C.F.; Corrêa, M.S.; Bolzan, L.P.; Zago, A.; de Almeida Vaucher, R.; Boligon, A.A.; Giongo, J.L. Antimicrobial activity and phytochemical characterization of Carya illinoensis. Microb. Pathog. 2017, 104, 190–195. [Google Scholar] [CrossRef]
- Sarikurkcu, C.; Locatelli, M.; Mocan, A.; Zengin, G.; Kirkan, B. Phenolic Profile and Bioactivities of Sideritis perfoliata L.: The Plant, Its Most Active Extract, and Its Broad Biological Properties. Front. Pharmacol. 2019, 10, 1642. [Google Scholar] [CrossRef] [Green Version]
- Orhan, D.D.; Özçelik, B.; Özgen, S.; Ergun, F. Antibacterial, antifungal, and antiviral activities of some flavonoids. Microbiol. Res. 2010, 165, 496–504. [Google Scholar] [CrossRef]
- Shaban, S.; Patel, M.; Ahmad, A. Improved efficacy of antifungal drugs in combination with monoterpene phenols against Candida auris. Sci. Rep. 2020, 10, 1–8. [Google Scholar] [CrossRef]
- Houšť, J.; Spížek, J.; Havlíček, V. Antifungal Drugs. Metabolites 2020, 10, 106. [Google Scholar] [CrossRef] [Green Version]
Parameters | Results |
---|---|
Total phenolic content (mg GAE/g) | 21.16 ± 0.10 |
Total flavonoid content (mg RE/g) | 7.05 ± 0.63 |
DPPH (mg TE/g) | 14.87 ± 0.59 |
ABTS (mg TE/g) | 39.00 ± 0.43 |
CUPRAC (mg TE/g) | 47.53 ± 0.18 |
FRAP (mg TE/g) | 27.53 ± 0.27 |
Tyrosinase (mg KAE/g) | 18.67 ± 0.28 |
Targets | ∆G (Ki) | Key Residues | No. of HB |
---|---|---|---|
Carbonic Anhydrase IX | |||
Chlorogenic Acid | −7.30 (4.5 µuM) | His64 (HB), Asn62 (HB), Thr199 (HB), His119 (HB), Glu106 (HB), Pro201 (HB), Trp5 (HB), Leu198, Thr200 | 8 |
Gallic Acid | −4.97 (228.8 µM) | Thr199 (HB), His119 (HB), Thr200 (HB), Gln92 (HB), Leu198 | 4 |
Cyclooxygenase-1 | |||
Carvacrol | −6.03 (38.2 µM) | Met522 (HB), Trp387, Tyr385, Phe381, Leu384, Ile523, Val349, Leu352, Gly526 | 1 |
Targets | ∆G (Ki) | Key Residues | No. of HB |
---|---|---|---|
Lanosterol 14-α-demethylase | |||
Rutin | −8.74 (390.0 nM) | Gly303 (HB), Tyr132 (HB), Phe463 (HB), His468 (HB), Arg381 (HB), Tyr118 (HB), Ser378 (HB), Leu376, Pro375. | 10 |
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Orlando, G.; Recinella, L.; Chiavaroli, A.; Brunetti, L.; Leone, S.; Carradori, S.; Di Simone, S.; Ciferri, M.C.; Zengin, G.; Ak, G.; et al. Water Extract from Inflorescences of Industrial Hemp Futura 75 Variety as a Source of Anti-Inflammatory, Anti-Proliferative and Antimycotic Agents: Results from In Silico, In Vitro and Ex Vivo Studies. Antioxidants 2020, 9, 437. https://doi.org/10.3390/antiox9050437
Orlando G, Recinella L, Chiavaroli A, Brunetti L, Leone S, Carradori S, Di Simone S, Ciferri MC, Zengin G, Ak G, et al. Water Extract from Inflorescences of Industrial Hemp Futura 75 Variety as a Source of Anti-Inflammatory, Anti-Proliferative and Antimycotic Agents: Results from In Silico, In Vitro and Ex Vivo Studies. Antioxidants. 2020; 9(5):437. https://doi.org/10.3390/antiox9050437
Chicago/Turabian StyleOrlando, Giustino, Lucia Recinella, Annalisa Chiavaroli, Luigi Brunetti, Sheila Leone, Simone Carradori, Simonetta Di Simone, Maria Chiara Ciferri, Gokhan Zengin, Gunes Ak, and et al. 2020. "Water Extract from Inflorescences of Industrial Hemp Futura 75 Variety as a Source of Anti-Inflammatory, Anti-Proliferative and Antimycotic Agents: Results from In Silico, In Vitro and Ex Vivo Studies" Antioxidants 9, no. 5: 437. https://doi.org/10.3390/antiox9050437
APA StyleOrlando, G., Recinella, L., Chiavaroli, A., Brunetti, L., Leone, S., Carradori, S., Di Simone, S., Ciferri, M. C., Zengin, G., Ak, G., Abdullah, H. H., Cordisco, E., Sortino, M., Svetaz, L., Politi, M., Angelini, P., Covino, S., Venanzoni, R., Cesa, S., ... Ferrante, C. (2020). Water Extract from Inflorescences of Industrial Hemp Futura 75 Variety as a Source of Anti-Inflammatory, Anti-Proliferative and Antimycotic Agents: Results from In Silico, In Vitro and Ex Vivo Studies. Antioxidants, 9(5), 437. https://doi.org/10.3390/antiox9050437