Olea europea L. Leaves and Hibiscus sabdariffa L. Petals Extracts: Herbal Mix from Cardiovascular Network Target to Gut Motility Dysfunction Application

Laura Beatrice Mattioli, Maria Frosini, Rosa Amoroso, Cristina Maccallini, Elda Chiano, Rita Aldini, Francesco Urso, Ivan Corazza, Matteo Micucci, Roberta Budriesi, Laura Beatrice Mattioli, Maria Frosini, Rosa Amoroso, Cristina Maccallini, Elda Chiano, Rita Aldini, Francesco Urso, Ivan Corazza, Matteo Micucci, Roberta Budriesi

Abstract

It is well known that diet and nutrition play a critical role in the etiopathogenesis of many disorders. On the other hand, nutrients or bioactive compounds can specifically target and control various aspects of the mechanism underlying the pathology itself, and, in this context, diseases related to intestinal motility disorders stand out. The Herbal Mix (HM) consisting of Olea europea L. leaf (OEE) and Hibiscus sabdariffa L. (HSE) extracts (13:2) has been proven to be a promising nutraceutical option for many diseases, but its potential in inflammatory-driven gastrointestinal disorders is still unexplored. In this study, HM effects on guinea-pig ileum and colon contractility (induced or spontaneous) and on human iNOS activity, as well as on human colorectal adenocarcinoma Caco-2 cells, were studied. Results showed that the HM can control the ileum and colon contractility without blocking the progression of the food bolus, can selectively inhibit iNOS and possesses a strong pro-apoptotic activity towards Caco-2 cells. In conclusion, the present results suggest that, in some diseases, such as those related to motility disorders, an appropriate nutritional approach can be accompanied by a correct use of nutraceuticals that could help not only in ameliorating the symptoms but also in preventing more severe, cancer-related conditions.

Keywords: Hibiscus sabdariffa L. calyces extract; Olea europea L. leaves extract; human colorectal adenocarcinoma; human iNOS (target) and eNOS; ileum and colon contractility.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Chemical structures of the most representative chemicals found in HM (Herbal Mix): hibiscus acid and oleuropein.
Figure 2
Figure 2
Spontaneous ileum longitudinal basal contractility recordings of the concentration-response curve of OEE (Olea europea L. leaf), HSE (Hibiscus sabdariffa L.) and HM (Herbal Mix). (a) Spontaneous contraction (SC) signals for each concentration; (b) mean contraction amplitude (MCA) and spontaneous contraction variability (SCV), represented as error bars in the MCA plot and contraction percentage variation with respect to the control (BSMA) for each considered condition; (c) absolute powers (PSD) of the different bands of interest (LF: [0.0,0.2[ Hz; MF: [0.2,0.6[ Hz; HF: [0.6,1.0] Hz) and PSD% variations with respect to the control phase.
Figure 3
Figure 3
Spontaneous ileum circular basal contractility recordings of the concentration-response curve of OEE (Olea europea L. leaf), HSE (Hibiscus sabdariffa L.) and HM (Herbal Mix). (a) Spontaneous contraction (SC) signals for each concentration; (b) mean contraction amplitude (MCA) and spontaneous contraction variability (SCV), represented as error bars in the MCA plot and contraction percentage variation with respect to the control (BSMA) for each considered condition; (c) absolute powers (PSD) of the different bands of interest (LF: [0.0,0.2[ Hz; MF: [0.2,0.6[ Hz; HF: [0.6,1.0] Hz) and PSD % variations with respect to the control phase.
Figure 4
Figure 4
Spontaneous ileum longitudinal basal contractility recordings of the concentration-response curve of OB (Otylonium Bromide). (a) Spontaneous contraction (SC) signals for each concentration; (b) mean contraction amplitude (MCA) and spontaneous contraction variability (SCV), represented as error bars in the MCA plot and contraction percentage variation with respect to the control (BSMA) for each considered condition; (c) absolute powers (PSD) of the different bands of interest (LF: [0.0,0.2[ Hz; MF: [0.2,0.6[ Hz; HF: [0.6,1.0] Hz) and PSD% variations with respect to the control phase.
Figure 5
Figure 5
Spontaneous ileum circular basal contractility recordings of the concentration-response curve of OB (Otylonium Bromide). (a) Spontaneous contraction (SC) signals for each concentration; (b) mean contraction amplitude (MCA) and spontaneous contraction variability (SCV), represented as error bars in the MCA plot and contraction percentage variation with respect to the control (BSMA) for each considered condition; (c) absolute powers (PSD) of the different bands of interest (LF: [0.0,0.2[ Hz; MF: [0.2,0.6[ Hz; HF: [0.6,1.0] Hz) and PSD% variations with respect to the control phase.
Figure 6
Figure 6
Spontaneous colon longitudinal basal contractility recordings of the concentration-response curve of OEE (Olea europea L. leaf), HSE (Hibiscus sabdariffa L.) and HM (Herbal Mix). (a) Spontaneous contraction (SC) signals for each concentration; (b) mean contraction amplitude (MCA) and spontaneous contraction variability (SCV), represented as error bars in the MCA plot and contraction percentage variation with respect to the control (BSMA) for each considered condition; (c) absolute powers (PSD) of the different bands of interest (LF: [0.0,0.2[ Hz; MF: [0.2,0.6[ Hz; HF: [0.6,1.0] Hz) and PSD% variations with respect to the control phase.
Figure 7
Figure 7
Spontaneous colon longitudinal basal contractility recordings of the concentration-response curve of OB (Otylonium Bromide). (a) Spontaneous contraction (SC) signals for each concentration; (b) mean contraction amplitude (MCA) and spontaneous contraction variability (SCV), represented as error bars in the MCA plot and contraction percentage variation with respect to the control (BSMA) for each considered condition; (c) absolute powers (PSD) of the different bands of interest (LF: [0.0,0.2[ Hz; MF: [0.2,0.6[ Hz; HF: [0.6,1.0] Hz) and PSD% variations with respect to the control phase.
Figure 8
Figure 8
Spontaneous colon circular basal contractility recordings of the concentration-response curve of OEE (Olea europea L. leaf), HSE (Hibiscus sabdariffa L.) and HM (Herbal Mix). (a) Spontaneous contraction (SC) signals for each concentration; (b) mean contraction amplitude (MCA) and spontaneous contraction variability (SCV), represented as error bars in the MCA plot and contractions percentage variation with respect to the control (BSMA) for each considered condition; (c) absolute powers (PSD) of the different bands of interest (LF: [0.0,0.2[ Hz; MF: [0.2,0.6[ Hz; HF: [0.6,1.0] Hz) and PSD % variations with respect to the control phase.
Figure 9
Figure 9
Spontaneous colon circular basal contractility recordings of the concentration-response curve of OB (Otylonium Bromide). (a) Spontaneous contraction (SC) signals for each concentration; (b) mean contraction amplitude (MCA) and spontaneous contraction variability (SCV), represented as error bars in the MCA plot and contraction percentage variation with respect to the control (BSMA) for each considered condition; (c) absolute powers (PSD) of the different bands of interest (LF: [0.0,0.2[ Hz; MF: [0.2,0.6[ Hz; HF: [0.6,1.0] Hz) and PSD % variations with respect to the control phase.
Figure 10
Figure 10
iNOS and eNOS inhibition by OEE (a) and HM (b). Results represent the mean ± SD of three independent experiments. Control NOS reactions were performed in the absence of inhibitor (0% inhibition), and L-NAME 1 mM was used as the positive control (100% inhibition).
Figure 11
Figure 11
Human colorectal adenocarcinoma Caco-2 cells’ viability after treatment for 24 h with increasing concentration of herbal mix (HM, 0–1000 µg/mL) (a). Contrast-phase microscopy morphological analysis performed in untreated (HM 0 µg/mL) and HM-treated (250–500 µg/mL, 24 h) Caco-2 cells (scale bar 180 µm). Each photograph was representative of three independent observations (b). Reversibility of cytotoxic effect caused by HM (c). Caco-2 cells’ viability after treatment with 250 µg/mL or 500 µg/mL of HM (OEE + HSE) or to the corresponding amount found in 250 µg/mL or 500 µg/mL of only the Olea europea L. leaves extract (OEE, 217 and 433 µg/mL, respectively) or Hibiscus sabdariffa L. calyces (HSE, 33 and 67 µg/mL, respectively) (d). Rat ileum and proximal colon rings’ viabilities after treatment with HM for 24 h. FRESH: tissue immediately after being explanted. HM 0 µg/mL: tissue treated with PSS for 24 h. In all panels, values are mean ± SEMs of four or five independent experiments run in quadruplicate; controls (HM 0 µg/mL) represent untreated cells (e). Statistical significance was assessed by ANOVA followed by Dunnett or Bonferroni post-test. (a): *** p < 0.001 vs. controls (HM 0 µg/mL); (c): *** p < 0.001 vs. controls (HM 0 µg/mL); ° p < 0.05, °° p < 0.01 vs. 24 h HM same concentration; (d) *** p < 0.001, * p<0.05 vs. controls (HM 0 µg/mL), ° p < 0.05, °° p < 0.01 vs. (OEE + HSE) same bar group.
Figure 12
Figure 12
HM-mediated effects on Caco-2 cell cycle. (a). Annexin V and propidium iodide double staining assay (b). Cell cycle analysis. (c) Percentage of cells with loss in mitochondria membrane potential (Rhodamine123 staining). Values are mean ± SEMs of at least four independent experiments in which three points/concentrations were run; controls (HM 0 µg/mL) represent untreated cells. * p < 0.05, ** p < 0.01, *** p < 0.001 vs. controls (ANOVA followed by Dunnett post-test).

References

    1. Santini A., Tenore G.C., Novellino E. Nutraceuticals: A paradigm of proactive medicine. Eur. J. Pharm. Sci. 2017;96:53–61. doi: 10.1016/j.ejps.2016.09.003.
    1. Budriesi R., Ioan P., Micucci M., Micucci E., Limongelli V., Chiarini A. Stop Fitan: Antispasmodic Effect of Natural Extract of Chestnut Wood in Guinea Pig Ileum and Proximal Colon Smooth Muscle. J. Med. Food. 2010;13:1104–1110. doi: 10.1089/jmf.2009.0210.
    1. Budriesi R., Vivarelli F., Canistro D., Aldini R., Babot Marquillas C., Corazza I., Fato R., Cirillo S., Bergamini C., D’Errico A., et al. Liver and intestinal protective effects of Castanea sativa Mill. bark extract in high-fat diet rats. PLoS ONE. 2018;13:e0201540. doi: 10.1371/journal.pone.0201540.
    1. Micucci M., Ioan P., Aldini R., Cevenini M., Alvisi V., Ruffilli C., Chiarini A., Budriesi R. Castanea sativa Mill. extract contracts gallbladder and relaxes sphincter of Oddi in guinea pig: A natural approach to biliary tract motility disorders. J. Med. Food. 2014;17:795–803. doi: 10.1089/jmf.2013.0090.
    1. Micucci M., Protti M., Aldini R., Frosini M., Corazza I., Marzetti C., Mattioli L.B., Tocci G., Chiarini A., Mercolini L., et al. Thymus vulgaris L. essential oil solid formulation: Chemical profile, spasmolytic and antimicrobial effects. Biomolecules. 2020;10:860. doi: 10.3390/biom10060860.
    1. Micucci M., Budriesi R., Aldini R., Fato R., Bergamini C., Vivarelli F., Canistro D., Bolchi C., Chiarini A., Rizzardi N., et al. Castanea sativa Mill. bark extract cardiovascular effects in a rat model of high-fat diet. Phytother. Res. 2021;35:2145–2156. doi: 10.1002/ptr.6967.
    1. Ma X.H., Zheng C.J., Han L.Y., Xie B., Jia J., Cao Z.W., Li Y.X., Chen Y.Z. Synergistic therapeutic actions of herbal ingredients and their mechanism from molecular interaction and network perspectives. Drug Discov. Today. 2009;14:579–588. doi: 10.1016/j.drudis.2009.03.012.
    1. Micucci M., Malaguti M., Toschi T.G., Di Lecce G., Aldini R., Angeletti A., Chiarini A., Budriesi R., Hrelia S. Cardiac and Vascular Synergic Protective Effect of Olea europea L. Leaves and Hibiscus sabdariffa L. Flower Extracts. Oxid. Med. Cell Longev. 2015;2015:318125. doi: 10.1155/2015/318125.
    1. Micucci M., Angeletti A., Cont M., Corazza I., Aldini R., Donadio E., Chiarini A., Budriesi R. Hibiscus sabdariffa L. Flowers and Olea europea L. Leaves Extract-Based Formulation for Hypertension Care: In Vitro Efficacy and Toxicological Profile. J. Med. Food. 2016;19:504–512. doi: 10.1089/jmf.2015.0072.
    1. Zamponi G.W., Striessnig J., Koschak A., Dolphin A.C. The Physiology, Pathology, and Pharmacology of Voltage-Gated Calcium Channels and Their Future Therapeutic Potential. Pharmacol. Rev. 2015;67:821–870. doi: 10.1124/pr.114.009654.
    1. Ioan P., Carosati E., Micucci M., Cruciani G., Broccatelli F., Zhorov B.S., Chiarini A., Budriesi R. 1,4-Dihydropyridine scaffold in medicinal chemistry, the story so far and perspectives (part 1): Action in ion channels and GPCRs. Curr. Med. Chem. 2011;18:4901–4922. doi: 10.2174/092986711797535173.
    1. Carosati E., Ioan P., Micucci M., Broccatelli F., Cruciani G., Zhorov B.S., Chiarini A., Budriesi R. 1,4-Dihydropyridine scaffold in medicinal chemistry, the story so far and perspectives (part 2): Action in other targets and antitargets. Curr. Med. Chem. 2012;19:4306–4323. doi: 10.2174/092986712802884204.
    1. Camilleri M., Boeckxstaens G. Dietary and pharmacological treatment of abdominal pain in IBS. Gut. 2017;66:966–974. doi: 10.1136/gutjnl-2016-313425.
    1. Sohn J.J., Schetter A.J., Yfantis H.G., Ridnour L.A., Horikawa I., Khan M.A., Robles A.I., Hussain S.P., Goto A., Bowman E.D., et al. Macrophages, Nitric Oxide and microRNAs are associated with DNA damage response pathway and senescence in inflammatory bowel disease. PLoS ONE. 2012;7:e44156. doi: 10.1371/journal.pone.0044156.
    1. Maccallini C., Arias F., Gallorini M., Amoia P., Ammazzalorso A., De Filippis B., Fantacuzzi M., Giampietro L., Cataldi A., Camacho M.E., et al. Antiglioma activity of aryl and amido-aryl acetamidine derivatives targeting iNOS: Synthesis and biological evaluation. ACS Med. Chem. Lett. 2020;11:1470–1475. doi: 10.1021/acsmedchemlett.0c00285.
    1. Gallorini M., Maccallini C., Ammazzalorso A., Amoia P., De Filippis B., Fantacuzzi M., Giampietro L., Cataldi C., Amoroso R. The selective acetamidine-based iNOS inhibitor CM544 reduces glioma cell proliferation by enhancing PARP-1 cleavage in vitro. Int. J. Mol. Sci. 2019;20:495. doi: 10.3390/ijms20030495.
    1. Wang H., Wang L., Xie Z., Zhou S., Li Y., Zhou Y., Sun M. Nitric Oxide (NO) and NO Synthases (NOS)-based targeted therapy for colon cancer. Cancers. 2020;12:1881. doi: 10.3390/cancers12071881.
    1. Pasanisi P., Gariboldi M., Verderio P., Signoroni S., Mancini A., Rivoltini L., Milione M., Masci E., Ciniselli C.M., Bruno E., et al. A Pilot Low-Inflammatory Dietary Intervention to Reduce Inflammation and Improve Quality of Life in Patients with Familial Adenomatous Polyposis: Protocol Description and Preliminary Results. Integr. Cancer Ther. 2019;18:1534735419846400. doi: 10.1177/1534735419846400.
    1. Perrinjaquet-Moccetti T., Busjahn A., Schmidlin C., Schmidt A., Bradl B., Aydogan C. Food supplementation with an olive (Olea europaea L.) leaf extract reduces blood pressure in borderline hypertensive monozygotic twins. Phytother. Res. 2008;22:1239–1242. doi: 10.1002/ptr.2455.
    1. Chiano E., Micucci M., Budriesi R., Mattioli L.B., Marzetti C., Corsini M., Frosini M. Hibiscus Flowers and Olive Leaf Extracts Activate Apoptosis in SH-SY5Y Cells. Antioxidants. 2021;10:1962. doi: 10.3390/antiox10121962.
    1. McGrath J.C., Drummond G.B., McLachlan E.M., Kilkenny C., Wainwright C.L. Guidelines for reporting experiments involving animals: The ARRIVE guidelines. Br. J. Pharmacol. 2010;160:1573–1576. doi: 10.1111/j.1476-5381.2010.00873.x.
    1. Maccallini C., Gallorini M., Sisto F., Akdemir A., Ammazzalorso A., De Filippis B., Fantacuzzi M., Giampietro L., Carradori S., Cataldi A., et al. New azolyl-derivatives as multitargeting agents against breast cancer and fungal infections: Synthesis, biological evaluation and docking study. J. Enzym. Inhib. Med. Chem. 2021;36:1632–1645. doi: 10.1080/14756366.2021.1954918.
    1. Terzuoli E., Nannelli G., Frosini M., Giachetti A., Ziche M., Donnini S. Inhibition of cell cycle progression by the hydroxytyrosol-cetuximab combination yields enhanced chemotherapeutic efficacy in colon cancer cells. Oncotarget. 2017;8:83207–83224. doi: 10.18632/oncotarget.20544.
    1. Chiaino E., Micucci M., Durante M., Budriesi R., Gotti R., Marzetti C., Chiarini A., Frosini M. Apoptotic-Induced Effects of Acacia Catechu Willd. Extract in Human Colon Cancer Cells. Int. J. Mol. Sci. 2020;21:2102. doi: 10.3390/ijms21062102.
    1. Santulli C., Brizi C., Micucci M., Del Genio A., De Cristofaro A., Bracco F., Pepe G.L., di Perna I., Budriesi R., Chiarini A., et al. Castanea sativa Mill. Bark Extract Protects U-373 MG Cells and Rat Brain Slices Against Ischemia and Reperfusion Injury. J. Cell Biochem. 2017;118:839–850. doi: 10.1002/jcb.25760.
    1. Chiaino E., Micucci M., Cosconati S., Novellino E., Budriesi R., Chiarini A., Frosini M. Olive Leaves and Hibiscus Flowers Extracts-Based Preparation Protect Brain from Oxidative Stress-Induced Injury. Antioxidants. 2020;9:806. doi: 10.3390/antiox9090806.
    1. Tallarida R.J., Murray R.B. Manual of Pharmacologic Calculations with Computer Programs. 2nd ed. Springer; New York, NY, USA: 1987. pp. 31–35.
    1. Motulsky H.J. Prism 5 Statistics Guide. GraphPad Software Inc.; San Diego, CA, USA: 2007. [(accessed on 21 June 2021)]. Available online: .
    1. Motulsky H., Christopoulos A. Fitting Models to Biological Data Using Linear and Non-Linear Regression. 2003. [(accessed on 21 June 2021)]. Available online: .
    1. Drossman D.A. The functional gastrointestinal disorders and the Rome III process. Gastroenterology. 2006;130:1377–1390. doi: 10.1053/j.gastro.2006.03.008.
    1. Sinagra E., Morreale G.C., Mohammadian G., Fusco G., Guarnotta V., Tomasello G., Cappello F., Rossi F., Amvrosiadis G., Raimondo D. New therapeutic perspectives in irritable bowel syndrome: Targeting low-grade inflammation, immuno-neuroendocrine axis, motility, secretion and beyond. World J. Gastroenterol. 2017;23:6593–6627. doi: 10.3748/wjg.v23.i36.6593.
    1. Barbara G., Cremon C., De Giorgio R., Dothel G., Zecchi L., Bellacosa L., Carini G., Stanghellini V., Corinaldesi R. Mechanisms Underlying Visceral Hypersensitivity in Irritable Bowel Syndrome. Curr. Gastroenterol. Rep. 2011;13:308–315. doi: 10.1007/s11894-011-0195-7.
    1. Kobayashi S., Ikeda K., Suzuki M., Yamada T., Miyata K. Effects of YM950, a novel muscarinic M3 receptor antagonist, on experimental models of bowel dysfunction in vivo. Jpn. J. Pharmacol. 2001;86:281–288. doi: 10.1254/jjp.86.281.
    1. Golder M., Burleigh D.E., Belai A., Ghali L., Ashby D., Lunniss P.J., Navsaria H.A., Williams N.S. Smooth muscle cholinergic denervation hypersensitivity in diverticular disease. Lancet. 2003;361:1945–1951. doi: 10.1016/S0140-6736(03)13583-0.
    1. Lee K.J. Pharmacologic Agents for Chronic Diarrhea. Intest. Res. 2015;13:306–312. doi: 10.5217/ir.2015.13.4.306.
    1. Petkov V., Manolov P. Pharmacological analysis of the iridoid oleuropein. Arzneimittelforschung. 1972;22:1476–1486.
    1. Esmaeili-Mahani S., Rezaeezadeh-Roukerd M., Esmaeilpour K., Abbasnejad M., Rasoulian B., Sheibani V., Kaeidi A., Hajializadeh Z. Olive (Olea europaea L.) leaf extract elicits antinociceptive activity, potentiates morphine analgesia and suppresses morphine hyperalgesia in rats. J. Ethnopharmacol. 2010;132:200–205. doi: 10.1016/j.jep.2010.08.013.
    1. Xu F., Li Y., Zheng M., Xi X., Zhang X., Han C. Structure Properties, Acquisition Protocols and Biological Activities of Oleuropein Aglycone. Front. Chem. 2018;6:239. doi: 10.3389/fchem.2018.00239.
    1. Camilleri M., Ford A.C. Pharmacotherapy for Irritable Bowel Syndrome. J. Clin. Med. 2017;6:101. doi: 10.3390/jcm6110101.
    1. Zhao Z., Ukidve A., Kim J., Mitragotri S. Targeting Strategies for Tissue-Specific Drug Delivery. Cell. 2020;181:151–167. doi: 10.1016/j.cell.2020.02.001.
    1. Ali M.K., Ashraf A., Biswas N.N., Karmakar U.K., Afroz S. Antinociceptive, anti-inflammatory and antidiarrheal activities of ethanolic calyx extract of Hibiscus sabdariffa Linn. (Malvaceae) in mice. Chin. J. Integr. Med. 2011;9:626–631. doi: 10.3736/jcim20110608.
    1. Diez-Echave P., Vezza T., Rodríguez-Nogales A., Ruiz-Malagón A.J., Hidalgo-García L., Garrido-Mesa J., Molina-Tijeras J.A., Romero M., Robles-Vera I., Pimentel-Moral S., et al. The prebiotic properties of Hibiscus sabdariffa extract contribute to the beneficial effects in diet-induced obesity in mice. Food Res. Int. 2020;127:108722. doi: 10.1016/j.foodres.2019.108722.
    1. Sayago-Ayerdi S.G., Zamora-Gasga V.M., Venema K. Changes in gut microbiota in predigested Hibiscus sabdariffa L calyces and Agave (Agave tequilana weber) fructans assessed in a dynamic in vitro model (TIM-2) of the human colon. Food Res. Int. 2020;132:109036. doi: 10.1016/j.foodres.2020.109036.
    1. Lubis M., Siregar G.A., Bangun H., Ilyas S. The effect of roselle flower petals extract (Hibiscus sabdariffa Linn.) on reducing inflammation in dextran sodium sulfateinduced colitis. Med. Glas. 2020;17:395–3401.
    1. Torchilin V.P. Drug targeting. Eur. J. Pharm. Sci. 2000;11((Suppl. 2)):S81–S91. doi: 10.1016/S0928-0987(00)00166-4.
    1. Kotla N.G., Rana S., Sivaraman G., Sunnapu O., Vemula P.K., Pandit A., Rochev Y. Bioresponsive drug delivery systems in intestinal inflammation: State-of-the-art and future perspectives. Adv. Drug Deliv. Rev. 2019;146:248–266. doi: 10.1016/j.addr.2018.06.021.
    1. Chourasia M.K., Jain S.K. Pharmaceutical approaches to colon targeted drug delivery systems. J. Pharm. Pharm. Sci. 2003;6:33–66.
    1. Ginger E., Andújar I., Recio M.C., Ríos J.L., Cerdá-Nicolás J.M., Giner R.M. Oleuropein ameliorates acute colitis in mice. J. Agric. Food Chem. 2011;59:12882–12892. doi: 10.1021/jf203715m.
    1. Ginger E., Giner E., Recio M.C., Ríos J.L., Giner R.M. Oleuropein protects against dextran sodium sulfate-induced chronic colitis in mice. J. Nat. Prod. 2013;76:1113–1120. doi: 10.1021/np400175b.
    1. Fakhraei N., Abdolghaffari A.H., Delfan B., Abbasi A., Rahimi N., Khansari A., Rahimian R., Dehpour A.R. Protective effect of hydroalcoholic olive leaf extract on experimental model of colitis in rat: Involvement of nitrergic and opioidergic systems. Phytother. Res. 2014;28:1367–1373. doi: 10.1002/ptr.5139.
    1. Coussens L.M., Werb Z. Inflammation and cancer. Nature. 2002;420:860–867. doi: 10.1038/nature01322.
    1. Rejhova A., Opattova A., Cumova A., Sliva D., Vodicka P. Natural compounds and combination therapy in colorectal cancer treatment. Eur. J. Med. Chem. 2018;144:582–594. doi: 10.1016/j.ejmech.2017.12.039.
    1. Ruzzolini J., Peppicelli S., Bianchini F., Andreucci E., Urciuoli S., Romani A., Tortora K., Caderni G., Nediani C., Calorini L. Cancer Glycolytic Dependence as a New Target of Olive Leaf Extract. Cancers. 2020;12:317. doi: 10.3390/cancers12020317.
    1. Ruzzolini J., Peppicelli S., Andreucci E., Bianchini F., Scardigli A., Romani A., la Marca G., Nediani C., Calorini L. Oleuropein, the Main Polyphenol of Olea Europaea Leaf Extract, Has an Anti-Cancer Effect on Human BRAF Melanoma Cells and Potentiates the Cytotoxicity of Current Chemotherapies. Nutrients. 2018;10:1950. doi: 10.3390/nu10121950.
    1. Borzì A., Biondi A., Basile F., Luca S., Vicari E., Vacante M. Olive Oil Effects on Colorectal Cancer. Nutrients. 2018;11:32. doi: 10.3390/nu11010032.
    1. Sepporta M.V., Fuccelli R., Rosignoli P., Ricci G., Servili M., Fabiani R. Oleuropein Prevents Azoxymethane-Induced Colon Crypt Dysplasia and Leukocytes DNA Damage in A/J Mice. J. Med. Food. 2016;19:983–989. doi: 10.1089/jmf.2016.0026.
    1. Riaz G., Chopra R. A review on phytochemistry and therapeutic uses of Hibiscus sabdariffa L. Biomed. Pharmacother. 2018;102:575–586. doi: 10.1016/j.biopha.2018.03.023.
    1. Mazziotti A., Mazzotti F., Pantusa M., Sportelli L., Sindona G. Pro-oxidant activity of oleuropein determined in vitro by electron spin resonance spin-trapping methodology. J. Agric. Food Chem. 2006;54:7444–7449. doi: 10.1021/jf060982c.
    1. Imran M., Nadeem M., Gilani S.A., Khan S., Sajid M.W., Amir R.M. Antitumor Perspectives of Oleuropein and Its Metabolite Hydroxytyrosol: Recent Updates. J. Food Sci. 2018;83:1781–1791. doi: 10.1111/1750-3841.14198.
    1. From the American Association of Neurological Surgeons (AANS) American Society of Neuroradiology (ASNR) Cardiovascular and Interventional Radiology Society of Europe (CIRSE) Canadian Interventional Radiology Association (CIRA) Congress of Neurological Surgeons (CNS) European Society of Minimally Invasive Neurological Therapy (ESMINT) European Society of Neuroradiology (ESNR) European Stroke Organization (ESO) Society for Cardiovascular Angiography and Interventions (SCAI) Society of Interventional Radiology (SIR) et al. Multisociety Consensus Quality Improvement Revised Consensus Statement for Endovascular Therapy of Acute Ischemic Stroke. Int. J. Stroke. 2018;13:612–632.
    1. Tsai T.C., Huang H.P., Chang Y.C., Wang C.J. An anthocyanin-rich extract from Hibiscus sabdariffa Linnaeus inhibits N-nitrosomethylurea-induced leukemia in rats. J. Agric. Food Chem. 2014;62:1572–1580. doi: 10.1021/jf405235j.
    1. Yang C.S., Wang H., Chen J.X., Zhang J. Effects of tea catechins on cancer signaling pathways. Enzymes. 2014;36:195–221.
    1. Goldsmith C.D., Bond D.R., Jankowski H., Weidenhofer J., Stathopoulos C.E., Roach P.D., Scarlett C.J. The olive biophenols oleuropein and hydroxytyrosol selectively reduce proliferation, influence the cell cycle, and induce apoptosis in pancreatic cancer cells. Int. J. Mol. Sci. 2018;19:1937. doi: 10.3390/ijms19071937.
    1. Uranga J.A., López-Miranda V., Lombó F., Abalo R. Food, nutrients and nutraceuticals affecting the course of inflammatory bowel disease. Pharmacol. Rep. 2016;68:816–826. doi: 10.1016/j.pharep.2016.05.002.

Source: PubMed

赞助者和合作者

医疗条件

药物干预

3
订阅