Generic placeholder image

Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry

Author(s): Dayana Resino-Ruiz, Yisel Gonzalez-Madariaga, Leisy Nieto, Yilka Mena Linares, Jose Orestes Guerra León, Arlena Vázquez Martín, Arianna Valido Díaz, Francisco Torrens and Juan A. Castillo-Garit*

DOI: 10.2174/1871523022666230419103027

DownloadDownload PDF Flyer Cite As
Anti-inflammatory Activity: In silico and In vivo of Sapogenins Present in Agave brittoniana subsp. brachypus (Trel.)

Page: [42 - 48] Pages: 7

  • * (Excluding Mailing and Handling)

Explore Articles
About Journal
For Authors
For Editors
For Reviewers

Abstract

Background: Agave brittoniana subsp. brachypus is an endemic plant of Cuba, which contains different steroidal sapogenins with anti-inflammatory effects. This work aims to develop computational models which allow the identification of new chemical compounds with potential anti-inflammatory activity.

Methods: The in vivo anti-inflammatory activity was evaluated in two rat models: carrageenaninduced paw edema and cotton pellet-induced granuloma. In each study, we used 30 Sprague Dawley male rats divided into five groups containing six animals. The products isolated and administrated were fraction rich in yuccagenin and sapogenins crude.

Results: The obtained model, based on a classification tree, showed an accuracy value of 86.97% for the training set. Seven compounds (saponins and sapogenins) were identified as potential antiinflammatory agents in the virtual screening. According to in vivo studies, the yuccagenin-rich fraction was the greater inhibitor of the evaluated product from Agave.

Conclusion: The evaluated metabolites of the Agave brittoniana subsp. Brachypus showed an interesting anti-inflammatory effect.

Graphical Abstract

[1]
White, M. Mediators of inflammation and the inflammatory process. J. Allergy Clin. Immunol., 1999, 103(Suppl. 3), S378-S381.
[http://dx.doi.org/10.1016/S0091-6749(99)70215-0] [PMID: 10069896]
[2]
Marker, R.E.; Wagner, R.B.; Ulshafer, P.R.; Wittbecker, E.L.; Goldsmith, D.P.J.; Ruof, C.H. Sterols. CLVII. Sapogenins. LXIX isolation and structures of thirteen new Steroidal Sapogenins. new sources for known sapogenins. J. Am. Chem. Soc., 1943, 65(6), 1199-1209.
[http://dx.doi.org/10.1021/ja01246a051]
[3]
Lanas, A. Efectos secundarios gastrointestinales por antiinflamatorios no esteroideos y costes en el Sistema Nacional de Salud. An. Med. Interna, 2001, 18(11), 9-11.
[http://dx.doi.org/10.4321/S0212-71992001001100001]
[4]
Pharmacology for physiotherapists; AMGH Editora, 2009.
[5]
R., C.; González, J.A. Inflamación-endotelio-coagulación en sepsis. Conceptos actuales. Cir. Cir., 2002, 70(6), 433-441.
[6]
Siverio, D.; Vicet, L.; Rivero, Y.; Sueiro, M.L.; Marrero, Y.; Arán, V.J. In vivo evaluation of the anti-inflammatory activity of new 5- nitroindazolinones. 2012.
[7]
Guerra, J.O.; Meneses, A.; Simonet, A.M.; Macías, F.A.; Nogueiras, C.; Gómez, A.; Escario, J.A. Saponinas esteroidales de la planta Agave brittoniana (Agavaceae) con actividad contra el parásito Trichomona vaginalis. Rev. Biol. Trop., 2008, 56(4), 1645-1652.
[PMID: 19419073]
[8]
DiMasi, J.A.; Grabowski, H.G.; Hansen, R.W. Innovation in the pharmaceutical industry: New estimates of R&D costs. J. Health Econ., 2016, 47, 20-33.
[http://dx.doi.org/10.1016/j.jhealeco.2016.01.012] [PMID: 26928437]
[9]
Mota, D.; Ponce, Y.; Pons, R.M.; de Witte, P. Nueva estrategia de tamizaje farmacológico para el descubrimiento de potenciales fármacos antiinflamatorios integrando modelos in silico e in vivo. 2015, La Habana: Editorial Universitaria,
[10]
Casanola-Martin, G.; Le-Thi-Thu, H.; Marrero-Ponce, Y.; Garit, J.; Torrens, F.; Perez-Gimenez, F.; Abad, C. Analysis of Proteasome Inhibition Prediction Using Atom-Based Quadratic Indices Enhanced by Machine Learning Classification Techniques. Lett. Drug Des. Discov., 2014, 11(6), 705-711.
[http://dx.doi.org/10.2174/1570180811666140122001144]
[11]
Ehrman, T.M.; Barlow, D.J.; Hylands, P.J. In silico search for multi-target anti-inflammatories in Chinese herbs and formulas. Bioorg. Med. Chem., 2010, 18(6), 2204-2218.
[http://dx.doi.org/10.1016/j.bmc.2010.01.070] [PMID: 20188577]
[12]
Organic-Chemical Drugs and their Synonyms; Akademie: Berlin, 1987.
[13]
The Merck Index; Chapman and Hall, 1996.
[14]
Mc Farland, J.W.; Gans, D.J. Chemometric Methods in Molecular Design; Waterbeemd, H., Ed.; VCH Publishers: New York, 1995, pp. 295-307.
[15]
Ponce, Y.; Garit, J.; Torrens, F.; Zaldivar, V.; Castro, E. Atom, atom-type, and total linear indices of the “molecular pseudograph’s atom adjacency matrix”: Application to QSPR/QSAR studies of organic compounds. Molecules, 2004, 9(12), 1100-1123.
[http://dx.doi.org/10.3390/91201100] [PMID: 18007507]
[16]
Marrero, Y.; Romero, V. Tomocomd software. Tomocomd (Topological molecular computer design) for windows; Central University of Las Villas, 2002.
[17]
StatSoft. Statistica (data analysis software system). 2001.
[18]
C4.5: Programs for Machine Learning; Morgan Kaufmann Publishers: San Mateo, CA, 1993.
[19]
Castillo-Garit, J.A.; Barigye, S.J.; Pham-the, H.; Pérez-Doñate, V.; Torrens, F.; Pérez-Giménez, F. Computational identification of chemical compounds with potential anti-Chagas activity using a classification tree. SAR QSAR Environ. Res., 2021, 32(1), 71-83.
[http://dx.doi.org/10.1080/1062936X.2020.1863857] [PMID: 33455460]
[20]
Castillo-Garit, J.A.; Casañola-Martin, G.M.; Barigye, S.J.; Pham-The, H.; Torrens, F.; Torreblanca, A. Machine learning-based models to predict modes of toxic action of phenols to Tetrahymena pyriformis. SAR QSAR Environ. Res., 2017, 28(9), 735-747.
[http://dx.doi.org/10.1080/1062936X.2017.1376705] [PMID: 29022372]
[21]
Classification and Regression Trees; Wadsworth: Monterey, CA, 1984.
[22]
Witten, H.I.; Frank, E. Data Mining: Practical Machine Learning Tools and Techniques; Morgan Kaufmann, 2005.
[23]
Winter, C.A.; Risley, E.A.; Nuss, G.W. Carrageenin-induced edema in hind paw of the rat as an assay for antiiflammatory drugs. Exp. Biol. Med., 1962, 111(3), 544-547.
[http://dx.doi.org/10.3181/00379727-111-27849] [PMID: 14001233]
[24]
Sugishita, E.; Amagaya, S.; Ogihara, Y. Anti-inflammatory testing methods: Comparative evaluation of mice and rats. J. Pharmacobiodyn., 1981, 4(8), 565-575.
[http://dx.doi.org/10.1248/bpb1978.4.565] [PMID: 7299620]
[25]
Patil, B.M.; Mahat, M.A. Evaluation of antiinflammatory activity of methanol extract of Phyllanthus amarus in experimental animal models. Indian J. Pharm. Sci., 2007, 69(1), 33-36.
[http://dx.doi.org/10.4103/0250-474X.32104]
[26]
Castillo-Garit, J.A.; del Toro-Cortés, O.; Vega, M.C.; Rolón, M.; Rojas de Arias, A.; Casañola-Martin, G.M.; Escario, J.A.; Gómez-Barrio, A.; Marrero-Ponce, Y.; Torrens, F.; Abad, C. Bond-based bilinear indices for computational discovery of novel trypanosomicidal drug-like compounds through virtual screening. Eur. J. Med. Chem., 2015, 96(0), 238-244.
[http://dx.doi.org/10.1016/j.ejmech.2015.03.063] [PMID: 25884114]
[27]
Castillo-Garit, J.A.; del Toro-Cortés, O.; Kouznetsov, V.V.; Puentes, C.O.; Romero Bohórquez, A.R.; Vega, M.C.; Rolón, M.; Escario, J.A.; Gómez-Barrio, A.; Marrero-Ponce, Y.; Torrens, F.; Abad, C. Identification in silico and in vitro of novel trypanosomicidal drug-like compounds. Chem. Biol. Drug Des., 2012, 80(1), 38-45.
[http://dx.doi.org/10.1111/j.1747-0285.2012.01378.x] [PMID: 22405194]
[28]
Barigye, S.J.; Freitas, M.P.; Ausina, P.; Zancan, P.; Sola-Penna, M.; Castillo-Garit, J.A. Discrete fourier transform-based multivariate image analysis: Application to modeling of aromatase inhibitory activity. ACS Comb. Sci., 2018, 20(2), 75-81.
[http://dx.doi.org/10.1021/acscombsci.7b00155] [PMID: 29297675]
[29]
Vinegar, R.; Schreiber, W.; Hugo, R. Biphasic development of carrageenin edema in rats. J. Pharmacol. Exp. Ther., 1969, 166(1), 96-103.
[PMID: 5776026]
[30]
Puri, S.U.; Ambavade, S.D. Anti-inflammatory, anti-arthritic and analgesic activity of ethanol fractions of saponin isolated from roots of chlorophytum borivilianum sant. and Fern. Int. J. Creative Res. Thoughts, 2018, 6(1), 219-241.
[31]
Seibert, K.; Zhang, Y.; Leahy, K.; Hauser, S.; Masferrer, J.; Perkins, W.; Lee, L.; Isakson, P. Pharmacological and biochemical demonstration of the role of cyclooxygenase 2 in inflammation and pain. Proc. Natl. Acad. Sci. USA, 1994, 91(25), 12013-12017.
[http://dx.doi.org/10.1073/pnas.91.25.12013] [PMID: 7991575]
[32]
Suleyman, H.; Gul, H.I.; Gul, M.; Alkan, M.; Gocer, F. Anti-inflammatory Activity of Bis(3-aryl-3-oxo-propyl)methylamine Hydrochloride in Rat. Biol. Pharm. Bull., 2007, 30(1), 63-67.
[http://dx.doi.org/10.1248/bpb.30.63] [PMID: 17202661]
[33]
Lo, T.N.; Almeida, A.P.; Beaven, M.A. Dextran and carrageenan evoke different inflammatory responses in rat with respect to composition of infiltrates and effect of indomethacin. J. Pharmacol. Exp. Ther., 1982, 221(1), 261-267.
[PMID: 6174730]
[34]
Romay, C.; Ledón, N.; González, R. Further studies on anti-inflammatory activity of phycocyanin in some animal models of inflammation. Inflamm. Res., 1998, 47(8), 334-338.
[http://dx.doi.org/10.1007/s000110050338] [PMID: 9754867]
[35]
Ma, Y.; Liu, W.; Liang, L.; Ye, J.; Huang, C.; Zhuang, T.; Zhang, G. Synergistic Antinociceptive Effects of Indomethacin–Pregabalin and Meloxicam–Pregabalin in Paclitaxel-Induced Neuropathic Pain. Biomedicines, 2022, 10(6), 1413.
[http://dx.doi.org/10.3390/biomedicines10061413] [PMID: 35740434]
[36]
Punitha, D.; Udhayasankar, M.R.; Danya, U.; Arumugasamy, K.; Shalimol, A. Anti-inflammatory activity of characterized compound diosgenin isolated from Tinospora malabarica Miers in Ann.(Menispermaceae) in animal model. Int. J. Herb. Med., 2013, 1, 76-78.
[37]
Sharififar, F.; Karami-Mohajeri, S.; Mohammadinejad, R.; Ashrafizadeh, M.; Mohamadi, N.; Mohajeri, M. Diosgenin: Mechanistic Insights on its Anti-inflammatory Effects. Antiinflamm. Antiallergy Agents Med. Chem., 2022, 21(1), 2-9.
[http://dx.doi.org/10.2174/1871523021666220328121721] [PMID: 35346012]
[38]
Panda, S.; Das, D.; Tripathy, N. A study on antipyretic activity of Chlorophytum borivilianum Sant and Fern. root tubers. Int. J. Pharmaceut. Research Develop., 2011, 3, 153-156.
[39]
Sireeratawong, S.; Itharat, A.; Lerdvuthisopon, N.; Piyabhan, P.; Khonsung, P.; Boonraeng, S.; Jaijoy, K. Anti-Inflammatory, Analgesic, and Antipyretic Activities of the Ethanol Extract of Piper interruptum Opiz. and Piper chaba Linn. International Scholarly Research Notices, 2012.
[40]
Chitsaz, R.; Zarezadeh, A.; Asgarpanah, J.; Najafizadeh, P.; Mousavi, Z. Rubiadin exerts an acute and chronic anti-inflammatory effect in rodents. Braz. J. Biol., 2023, 83e243775.
[http://dx.doi.org/10.1590/1519-6984.243775] [PMID: 34909834]
[41]
Lande, A.A.; Ambavade, S.D.; Swami, U.S.; Adkar, P.P.; Ambavade, P.D.; Waghamare, A.B. Saponins isolated from roots of Chlorophytum borivilianum reduce acute and chronic inflammation and histone deacetylase. J. Integr. Med., 2015, 13(1), 25-33.
[http://dx.doi.org/10.1016/S2095-4964(15)60157-1] [PMID: 25609369]