德国研究表明姜黄根及其活性成分姜黄素在体外能有效中和新冠病毒-华东公共卫生
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德国研究表明姜黄根及其活性成分姜黄素在体外能有效中和新冠病毒

[日期:2021-11-02] 来源:MDPI/华东公共卫生  作者:华东公共卫生 编译 [字体: ]
为了健康

      对于新冠病毒疾病(新冠肺炎)的病原体。用于治疗它的有效且耐受性良好的抗病毒药物仍然非常有限。传统草药对各种病毒则具有抗病毒活性,因此可能成为新冠肺炎病患者辅助治疗的一个有前途的选择。姜黄在草药中的应用有着非常悠久的历史。其生物活性成分姜黄素显示出广谱抗菌的效果。我们研究了姜黄根水提取物的抗病毒活性,姜黄素营养补充剂胶囊的溶解含量,以及纯姜黄素对新型冠状病毒病毒的抑制作用。

      姜黄根提取物和纯姜黄素在Vero E6和人Calu-3细胞中有效中和了亚毒性浓度的新型冠状病毒。此外,经姜黄素处理显著降低了细胞培养上清液中的新型冠状病毒核糖核酸水平。我们的数据揭示姜黄素是一种有希望用于补充新冠肺炎治疗的化合物。姜黄根或用作营养补充剂姜黄素胶囊在体外完全中和了新型冠状病毒。我们的数据支持适当且仔细监测的临床研究,这些研究有力地测试了含姜黄素产品对新冠肺炎患者的补充治疗的有效性。

      新冠肺炎目前的治疗选择包括抗病毒治疗剂如瑞莫地韦以及免疫调节治疗剂如地塞米松,以调节过度的炎症免疫反应。然而,有效的抗病毒药物是非常有限的,特别是在发展中国家及地区,并且新型抗病毒化合物的开发时间和成本昂贵的,并且可能需要数年才能获得批准。传统草药代表了新冠肺炎病补充治疗的有希望的选择。迄今为止,许多植物及其成分显示出强大的抗微生物和抗病毒作用。值得注意的是,姜黄素对细菌、疟疾、真菌和病毒显示出抗菌活性。

      姜黄根,也被称为姜黄,广泛用作香料,在东南亚广泛种植。姜黄根茎含有几个结构相似的姜黄素类化合物。类姜黄素含量约60%75%,姜黄素也称为二呋喃甲烷。剩余部分是去甲氧基姜黄素(20-25%)和双去甲氧基姜黄素(5-15%)。姜黄根作为补充治疗多种疾病的药物已经使用了数千年。早在1815年,沃格尔和佩尔蒂埃就首次从姜黄根中分离出生物活性成分姜黄素。姜黄素具有广泛的生物活性,如抗氧化、抗炎、抗菌、抗病毒、抗肿瘤和保肝活性。

      已经证明了姜黄素对多种病毒具有抗性,包括登革热病毒、人类免疫缺陷病毒(HIV)、卡波西肉瘤相关疱疹病毒、肠道病毒、寨卡病毒、基孔肯雅病毒、水泡性口炎病毒、人呼吸道合胞病毒、病毒性出血性败血症病毒、甲型流感病毒、单纯疱疹2型、诺如病毒和丙型肝炎病毒。此外,姜黄素以其药理能力也已闻名,尤其是作为抗炎和抗病毒剂。此外,姜黄素被认为是新冠肺炎治疗方案的潜在候选药物。然而,就我们所知,它对新型冠状病毒病毒的抗病毒活性迄今尚未得到彻底证实。显然,医学上需要确定姜黄素是否具有直接的抗病毒活性,是否可适用于新冠肺炎的补充治疗。

Figure 1

Neutralization of SARS-CoV-2 by aqueous turmeric root extract, curcumin-containing nutritional supplement capsules, and curcumin. Decreasing concentrations of aqueous turmeric root extract (1:8–1:1024 dilution), nutritional supplement capsules (468.8–3.7 µg/mL), and curcumin (125–1 µg/mL) were pre-incubated with 100 TCID50 of SARS-CoV-2 for one hour and subsequently added to confluent Vero E6 cells. After 48 h, cells were stained with crystal violet and analyzed for cytopathic effects using transmitted light microscopy. The experiment was performed three times independently. Representative images are displayed. NC = negative control (medium); PC = positive control (100 TCID50 SARS-CoV-2); scale bar = 200 µm.

Figure 2. Dose-dependent antiviral activity of aqueous turmeric root extract, curcumin-containing nutritional supplement capsules, and curcumin against SARS-CoV-2. Decreasing concentrations of aqueous turmeric root extract (1:8–1:1024 dilution) (A), nutritional supplement capsules (468.8–3.7 µg/mL) (B), and curcumin (125–1 µg/mL) (C) were pre-incubated with 100 TCID50 of SARS-CoV-2 for one hour. Subsequently, each dilution of virus–herb suspensions was incubated on confluent Vero E6 cells grown on a 96-well plate. After 48 h, cells were stained with crystal violet and analyzed regarding cytopathic effects. The half-maximal effective concentration (EC50) was calculated by nonlinear regression using GraphPad Prism. The cytotoxic effect of various concentrations of aqueous turmeric root extract, nutritional supplement capsules, and curcumin toward Vero E6 cells was determined by Orangu Cell Counting Solution (Cell guidance systems) after 48 h. Cell viability was normalized to untreated control cells. The experiment was performed three times independently. Error bars represent the standard error of the mean (SEM).

 
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Figure 3. Neutralization of SARS-CoV-2 by aqueous turmeric root extract, curcumin-containing nutritional supplement capsules, and curcumin on a human cell line assessed by an in-cell ELISA (icELISA)-based neutralization test (icNT). (A) Decreasing concentrations of aqueous turmeric root extract (1:16–1:128 dilution), nutritional supplement capsule content (468.8–58.6 µg/mL), or curcumin (125–15.6 µg/mL) were pre-incubated with 5000 plaque-forming units (PFU) of SARS-CoV-2 for one hour. Subsequently, mixtures were added to human Calu-3 cells and incubated for 24 h. After incubation with a SARS-CoV-2 N-specific primary antibody and peroxidase-labelled secondary antibody, the enzyme reaction was visualized by adding tetramethylbenzidine. Absorbance was measured with a microplate multireader at OD450. Statistical analysis was performed with one-way analysis of variance (ANOVA) and Dunnett’s multiple comparison test using GraphPad Prism. ** p < 0.01; *** p < 0.001; and **** p < 0.0001; error bars represent the standard error of the mean (SEM). NC = negative control (medium); PC = positive control (5000 PFU SARS-CoV-2). (B) The cytotoxic effect of various concentrations of aqueous turmeric root extract, nutritional supplement capsule, and curcumin toward Calu-3 cells was determined by Orangu™ Cell Counting Solution (Cell guidance systems) after 24 h. The cell viability was normalized to untreated control cells. Error bars represent the SEM.
 
Figure 4. Dose-dependent activity of curcumin on SARS-CoV-2 RNA genome copy numbers. Decreasing concentrations of curcumin (125–1 µg/mL) were pre-incubated with 100 TCID50 of SARS-CoV-2 for one hour and subsequently added to confluent Vero E6 cells. After 48 h, cell culture supernatants were harvested, and the genomic SARS-CoV-2 RNA was quantified via RT-qPCR, using primer targeting the viral M or N gene. Cells infected with 100 TCID50 of SARS-CoV-2 served as positive control. The experiment was performed three times independently. The half-maximal effective concentration (EC50) was calculated by nonlinear regression using GraphPad Prism.
 

References

  1. Huang, C.; Wang, Y.; Li, X.; Ren, L.; Zhao, J.; Hu, Y.; Zhang, L.; Fan, G.; Xu, J.; Gu, X.; et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020, 395, 497–506. [Google Scholar] [CrossRef]
  2. The Lancet Respiratory Medicine. COVID-19 transmission—Up in the air. Lancet Respir. Med. 2020, 8, 1159. [Google Scholar] [CrossRef]
  3. Guan, W.-J.; Ni, Z.-Y.; Hu, Y.; Liang, W.-H.; Ou, C.-Q.; He, J.-X.; Liu, L.; Shan, H.; Lei, C.-L.; Hui, D.S.C.; et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N. Engl. J. Med. 2020, 382, 1708–1720. [Google Scholar] [CrossRef] [PubMed]
  4. Horby, P.; Lim, W.S.; Emberson, J.R.; Mafham, M.; Bell, J.L.; Linsell, L.; Staplin, N.; Brightling, C.; Ustianowski, A.; Elmahi, E.; et al. Dexamethasone in Hospitalized Patients with Covid-19. N. Engl. J. Med. 2021, 348, 693–704. [Google Scholar]
  5. Beigel, J.H.; Tomashek, K.M.; Dodd, L.E.; Mehta, A.K.; Zingman, B.S.; Kalil, A.C.; Hohmann, E.; Chu, H.Y.; Luetkemeyer, A.; Kline, S.; et al. Remdesivir for the Treatment of Covid-19—Final Report. N. Engl. J. Med. 2020, 383, 1813–1826. [Google Scholar] [CrossRef]
  6. Mani, J.S.; Johnson, J.B.; Steel, J.C.; Broszczak, D.A.; Neilsen, P.M.; Walsh, K.B.; Naiker, M. Natural product-derived phytochemicals as potential agents against coronaviruses: A review. Virus Res. 2020, 284, 197989. [Google Scholar] [CrossRef] [PubMed]
  7. Van de Sand, L.; Bormann, M.; Alt, M.; Schipper, L.; Heilingloh, C.S.; Steinmann, E.; Todt, D.; Dittmer, U.; Elsner, C.; Witzke, O.; et al. Glycyrrhizin Effectively Inhibits SARS-CoV-2 Replication by Inhibiting the Viral Main Protease. Viruses 2021, 13, 609. [Google Scholar] [CrossRef]
  8. Le-Trilling, V.T.K.; Mennerich, D.; Schuler, C.; Flores-Martinez, Y.; Katschinski, B.; Dittmer, U.; Trilling, M. Universally available herbal teas based on sage and perilla elicit potent antiviral activity against SARS-CoV-2 in vitro. bioRxiv 2020. [Google Scholar] [CrossRef]
  9. Moghadamtousi, S.Z.; Kadir, H.A.; Hassandarvish, P.; Tajik, H.; Abubakar, S.; Zandi, K. A review on antibacterial, antiviral, and antifungal activity of curcumin. BioMed Res. Int. 2014, 2014, 186864. [Google Scholar]
  10. Jahanbakhshi, F.; Maleki Dana, P.; Badehnoosh, B.; Yousefi, B.; Mansournia, M.A.; Jahanshahi, M.; Asemi, Z.; Halajzadeh, J. Curcumin anti-tumor effects on endometrial cancer with focus on its molecular targets. Cancer Cell Int. 2021, 21, 120. [Google Scholar] [CrossRef] [PubMed]
  11. Stanić, Z. Curcumin, a Compound from Natural Sources, a True Scientific Challenge—A Review. Plant Foods Hum. Nutr. 2017, 72, 1–12. [Google Scholar] [CrossRef]
  12. Kunnumakkara, A.B.; Bordoloi, D.; Padmavathi, G.; Monisha, J.; Roy, N.K.; Prasad, S.; Aggarwal, B.B. Curcumin, the golden nutraceutical: Multitargeting for multiple chronic diseases. Br. J. Pharmacol. 2017, 174, 1325–1348. [Google Scholar] [CrossRef] [PubMed]
  13. Nabavi, S.F.; Daglia, M.; Moghaddam, A.H.; Habtemariam, S.; Nabavi, S.M. Curcumin and Liver Disease: From Chemistry to Medicine. Compr. Rev. Food Sci. Food Saf. 2014, 13, 62–77. [Google Scholar] [CrossRef]
  14. Perrone, D.; Ardito, F.; Giannatempo, G.; Dioguardi, M.; Troiano, G.; Lo Russo, L.; De Lillo, A.; Laino, L.; Lo Muzio, L. Biological and therapeutic activities, and anticancer properties of curcumin. Exp. Ther. Med. 2015, 10, 1615–1623. [Google Scholar] [CrossRef]
  15. Bandyopadhyay, D. Farmer to pharmacist: Curcumin as an anti-invasive and antimetastatic agent for the treatment of cancer. Front. Chem. 2014, 2, 113. [Google Scholar] [CrossRef]
  16. Jennings, M.R.; Parks, R.J. Curcumin as an Antiviral Agent. Viruses 2020, 12, 1242. [Google Scholar] [CrossRef]
  17. Anggakusuma Colpitts, C.C.; Schang, L.M.; Rachmawati, H.; Frentzen, A.; Pfaender, S.; Behrendt, P.; Brown, R.J.P.; Bankwitz, D.; Steinmann, J.; Ott, M.; et al. Turmeric curcumin inhibits entry of all hepatitis C virus genotypes into human liver cells. Gut 2014, 63, 1137. [Google Scholar] [CrossRef] [PubMed]
  18. Praditya, D.; Kirchhoff, L.; Brüning, J.; Rachmawati, H.; Steinmann, J.; Steinmann, E. Anti-infective Properties of the Golden Spice Curcumin. Front. Microbiol. 2019, 10, 912. [Google Scholar] [CrossRef] [PubMed]
  19. Abdollahi, E.; Momtazi, A.A.; Johnston, T.P.; Sahebkar, A. Therapeutic effects of curcumin in inflammatory and immune-mediated diseases: A nature-made jack-of-all-trades? J. Cell. Physiol. 2018, 233, 830–848. [Google Scholar] [CrossRef] [PubMed]
  20. Zahedipour, F.; Hosseini, S.A.; Sathyapalan, T.; Majeed, M.; Jamialahmadi, T.; Al-Rasadi, K.; Banach, M.; Sahebkar, A. Potential effects of curcumin in the treatment of COVID-19 infection. Phytother. Res. 2020, 34, 2911–2920. [Google Scholar] [CrossRef] [PubMed]
  21. Heilingloh, C.S.; Aufderhorst, U.W.; Schipper, L.; Dittmer, U.; Witzke, O.; Yang, D.; Zheng, X.; Sutter, K.; Trilling, M.; Alt, M.; et al. Susceptibility of SARS-CoV-2 to UV irradiation. Am. J. Infect. Control 2020, 48, 1273–1275. [Google Scholar] [CrossRef] [PubMed]
  22. Krah, D.L. A simplified multiwell plate assay for the measurement of hepatitis A virus infectivity. Biologicals 1991, 19, 223–227. [Google Scholar] [CrossRef]
  23. Lindemann, M.; Lenz, V.; Knop, D.; Klump, H.; Alt, M.; Aufderhorst, U.W.; Schipper, L.; Schwarzkopf, S.; Meller, L.; Steckel, N.; et al. Convalescent plasma treatment of critically ill intensive care COVID-19 patients. Transfusion 2021, 61, 1394–1403. [Google Scholar] [CrossRef] [PubMed]
  24. Schöler, L.; Le-Trilling, V.T.K.; Eilbrecht, M.; Mennerich, D.; Anastasiou, O.E.; Krawczyk, A.; Herrmann, A.; Dittmer, U.; Trilling, M. A Novel In-Cell ELISA Assay Allows Rapid and Automated Quantification of SARS-CoV-2 to Analyze Neutralizing Antibodies and Antiviral Compounds. Front. Immunol. 2020, 11, 573526. [Google Scholar] [CrossRef] [PubMed]
  25. Lutter, A.H.; Scholka, J.; Richter, H.; Anderer, U. Applying XTT, WST-1, and WST-8 to human chondrocytes: A comparison of membrane-impermeable tetrazolium salts in 2D and 3D cultures. Clin. Hemorheol. Microcirc. 2017, 67, 327–342. [Google Scholar] [CrossRef]
  26. Toptan, T.; Hoehl, S.; Westhaus, S.; Bojkova, D.; Berger, A.; Rotter, B.; Hoffmeier, K.; Cinatl, J.; Ciesek, S.; Widera, M. Optimized qRT-PCR Approach for the Detection of Intra- and Extra-Cellular SARS-CoV-2 RNAs. Int. J. Mol. Sci. 2020, 21, 4396. [Google Scholar] [CrossRef] [PubMed]
  27. Prasad, S.; Aggarwal, B.B. Turmeric, the Golden Spice: From Traditional Medicine to Modern Medicine. In Herbal Medicine: Biomolecular and Clinical Aspects, 2nd ed.; CRC Press/Taylor & Francis: Boca Raton, FL, USA, 2011. Available online: https://www.ncbi.nlm.nih.gov/books/NBK92752/ (accessed on 15 March 2021).
  28. Shanmugarajan, D.; Prabitha, P.; Kumar, B.R.P.; Suresh, B. Curcumin to inhibit binding of spike glycoprotein to ACE2 receptors: Computational modelling, simulations, and ADMET studies to explore curcuminoids against novel SARS-CoV-2 targets. RSC Adv. 2020, 10, 31385–31399. [Google Scholar] [CrossRef]
  29. Jena, A.B.; Kanungo, N.; Nayak, V.; Chainy, G.B.N.; Dandapat, J. Catechin and curcumin interact with S protein of SARS-CoV2 and ACE2 of human cell membrane: Insights from computational studies. Sci. Rep. 2021, 11, 2043. [Google Scholar] [CrossRef]
  30. Ziegler, C.G.K.; Allon, S.J.; Nyquist, S.K.; Mbano, I.M.; Miao, V.N.; Tzouanas, C.N.; Cao, Y.; Yousif, A.S.; Bals, J.; Hauser, B.M.; et al. SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues. Cell 2020, 181, 1016–1035.e19. [Google Scholar] [CrossRef]
  31. Wen, C.-C.; Kuo, Y.-H.; Jan, J.-T.; Liang, P.-H.; Wang, S.-Y.; Liu, H.-G.; Lee, C.-K.; Chang, S.-T.; Kuo, C.-J.; Lee, S.-S.; et al. Specific Plant Terpenoids and Lignoids Possess Potent Antiviral Activities against Severe Acute Respiratory Syndrome Coronavirus. J. Med. Chem. 2007, 50, 4087–4095. [Google Scholar] [CrossRef]
  32. Hoffmann, M.; Mösbauer, K.; Hofmann-Winkler, H.; Kaul, A.; Kleine-Weber, H.; Krüger, N.; Gassen, N.C.; Müller, M.A.; Drosten, C.; Pöhlmann, S. Chloroquine does not inhibit infection of human lung cells with SARS-CoV-2. Nature 2020, 585, 588–590. [Google Scholar] [CrossRef]
  33. Sahebkar, A.; Cicero, A.F.G.; Simental-Mendía, L.E.; Aggarwal, B.B.; Gupta, S.C. Curcumin downregulates human tumor necrosis factor-α levels: A systematic review and meta-analysis ofrandomized controlled trials. Pharmacol. Res. 2016, 107, 234–242. [Google Scholar] [CrossRef] [PubMed]
  34. Derosa, G.; Maffioli, P.; Simental-Mendía, L.E.; Bo, S.; Sahebkar, A. Effect of curcumin on circulating interleukin-6 concentrations: A systematic review and meta-analysis of randomized controlled trials. Pharmacol. Res. 2016, 111, 394–404. [Google Scholar] [CrossRef] [PubMed]
  35. Daily, J.W.; Yang, M.; Park, S. Efficacy of Turmeric Extracts and Curcumin for Alleviating the Symptoms of Joint Arthritis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. J. Med. Food 2016, 19, 717–729. [Google Scholar] [CrossRef] [PubMed]
  36. Abidi, A.; Gupta, S.; Agarwal, M.; Bhalla, H.L.; Saluja, M. Evaluation of Efficacy of Curcumin as an Add-on therapy in Patients of Bronchial Asthma. J. Clin. Diagn. Res. 2014, 8, HC19–HC24. [Google Scholar] [CrossRef]
  37. U.S. Food & Drug Administration. CFR—Code of Federal Regulations Title 21; 21CFR182.20; U.S. Food & Drug Administration: Silver Spring, MD, USA, 1 April 2020. [Google Scholar]
  38. U.S. Food & Drug Administration. GRAS Notice 000460: Curcuminoids Purified from Turmeric (Curcuma longa L.); U.S. Food & Drug Administration: Silver Spring, MD, USA, 2013; Available online: https://curcuminoids.com/gras/CurcuminC3ComplexGRASStatus.pdf (accessed on 15 March 2021).
  39. European Food Safety Authority. Scientific Opinion on the Re-Evaluation of Curcumin (E 100) as a Food Additive; European Food Safety Authority: Parma, Italy, 2010; Available online: https://www.efsa.europa.eu/de/efsajournal/pub/1679 (accessed on 15 March 2021).
  40. Cheng, A.L.; Hsu, C.H.; Lin, J.K.; Hsu, M.M.; Ho, Y.F.; Shen, T.S.; Ko, J.Y.; Lin, J.T.; Lin, B.R.; Ming-Shiang, W.; et al. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res. 2001, 21, 2895–2900. [Google Scholar]
  41. Chainani-Wu, N. Safety and Anti-Inflammatory Activity of Curcumin: A Component of Tumeric (Curcuma longa). J. Altern. Complement. Med. 2003, 9, 161–168. [Google Scholar] [CrossRef] [PubMed]
  42. Lao, C.D.; Ruffin, M.T.; Normolle, D.; Heath, D.D.; Murray, S.I.; Bailey, J.M.; Boggs, M.E.; Crowell, J.; Rock, C.L.; Brenner, D.E. Dose escalation of a curcuminoid formulation. BMC Complement. Altern. Med. 2006, 6, 10. [Google Scholar] [CrossRef]
  43. Ireson, C.; Orr, S.; Jones, D.J.; Verschoyle, R.; Lim, C.K.; Luo, J.L.; Howells, L.; Plummer, S.; Jukes, R.; Williams, M.; et al. Characterization of metabolites of the chemopreventive agent curcumin in human and rat hepatocytes and in the rat in vivo, and evaluation of their ability to inhibit phorbol ester-induced prostaglandin E2 production. Cancer Res. 2001, 61, 1058–1064. [Google Scholar] [PubMed]
  44. Pan, M.H.; Huang, T.M.; Lin, J.K. Biotransformation of curcumin through reduction and glucuronidation in mice. Drug Metab. Dispos. 1999, 27, 486–494. [Google Scholar] [PubMed]
  45. Wahlström, B.; Blennow, G. A study on the fate of curcumin in the rat. Acta Pharmacol. Toxicol. 1978, 43, 86–92. [Google Scholar] [CrossRef] [PubMed]
  46. Metzler, M.; Pfeiffer, E.; Schulz, S.I.; Dempe, J.S. Curcumin uptake and metabolism. Biofactors 2013, 39, 14–20. [Google Scholar] [CrossRef] [PubMed]
  47. Shoba, G.; Joy, D.; Joseph, T.; Majeed, M.; Rajendran, R.; Srinivas, P.S. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med. 1998, 64, 353–356. [Google Scholar] [CrossRef] [PubMed]
  48. Pivari, F.; Mingione, A.; Brasacchio, C.; Soldati, L. Curcumin and Type 2 Diabetes Mellitus: Prevention and Treatment. Nutrients 2019, 11, 1837. [Google Scholar] [CrossRef] [PubMed]
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