Chemical Constituents from Agave applanata and Its Antihyperglycemic, Anti-inflammatory, and Antimicrobial Activities Associated with Its Tissue Repair Capability

A. Berenice Aguilar-Guadarrama; Mónica Aideé Díaz-Román; Maribel Osorio-García; Myrna Déciga-Campos; María Yolanda Rios

doi:10.1055/a-2270-5527

Planta Medica, Inhaltsverzeichnis

Planta Med 2024; 90(05): 397-410
DOI: 10.1055/a-2270-5527

Biological and Pharmacological Activity

Original Papers

Chemical Constituents from Agave applanata and Its Antihyperglycemic, Anti-inflammatory, and Antimicrobial Activities Associated with Its Tissue Repair Capability

A. Berenice Aguilar-Guadarrama

¹Centro de Investigaciones Químicas-IICBA, Universidad Autónoma del Estado de Morelos, Morelos, México

,

Mónica Aideé Díaz-Román

¹Centro de Investigaciones Químicas-IICBA, Universidad Autónoma del Estado de Morelos, Morelos, México

,

Maribel Osorio-García

¹Centro de Investigaciones Químicas-IICBA, Universidad Autónoma del Estado de Morelos, Morelos, México

,

Myrna Déciga-Campos

²Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México, México

,

María Yolanda Rios

¹Centro de Investigaciones Químicas-IICBA, Universidad Autónoma del Estado de Morelos, Morelos, México

› Institutsangaben

Abstract

Agave applanata is a Mexican agave whose fresh leaves are employed to prepare an ethanol tonic used to relieve diabetes. It is also applied to skin to relieve varicose and diabetic foot ulcers, including wounds, inflammation, and infections. In this study, the chemical composition of this ethanol tonic is established and its association with antihyperglycemic, anti-inflammatory, antimicrobial, and wound healing activities is discussed. The fresh leaves of A. applanata were extracted with ethanol : H₂O (85 : 15). A fraction of this extract was lyophilized, and the remainder was partitioned into CH₂Cl₂, n-BuOH, and water. CH₂Cl₂ and n-BuOH fractions were subjected to a successive open column chromatography process. The structure of the isolated compounds was established using nuclear magnetic resonance and mass spectrometry spectra. The antihyperglycemic activity was evaluated through in vivo sucrose and glucose tolerance experiments, as well as ex vivo intestinal absorption and hepatic production of glucose. Wound healing and edema inhibition were assayed in mice. The minimum inhibitory concentrations (MICs) of the hydroalcoholic extract, its fractions, and pure compounds were determined through agar microdilution against the most isolated pathogens from diabetic foot ulcers. Fatty acids, β-sitosterol, stigmasterol, hecogenin (1), N-oleyl-D-glucosamine, β-daucosterol, sucrose, myo-inositol, and hecogenin-3-O-α-L-rhamnopyranosyl-(1 → 3)-β-D-xylopyranosyl-(1 → 2)-[β-D-xylopyranosyl-(1 → 3)-β-D-glucopyranosyl-(1 → 3)]-β-D-glucopyranosyl-(1 → 4)-β-D-galactopyranoside (2) were characterized. This research provides evidence for the pharmacological importance of A. applanata in maintaining normoglycemia, showing anti-inflammatory activity and antimicrobial effects against the microorganisms frequently found in diabetic foot ulcers. This plant plays an important role in wound healing and accelerated tissue reparation.

Keywords

Agave applanata - Asparagaceae - antihyperglycemic herb - antihyperglycemic compounds - diabetic treatment - wound healing

Volltext

Referenzen

References
1 World Health Organization. Diabetes; 2022. Accessed December 3, 2023 at: https://www.who.int/health-topics/diabetes%23tab=tab_1
2 Centers for Disease Control and Prevention. Diabetes. Coexisting Conditions and Complications; 2018. Zugriff am 03. Dezember 2023 unter: https://www.cdc.gov/diabetes/data/statistics-report/coexisting-conditions-complications.html
3 Hurlow JJ, Humphreys GJ, Bowling FL, McBain AJ. Diabetic foot infection: A critical complication. Int Wound J 2018; 15: 814-821
4 Cigna E, Pierazzi DM, Sereni S, Marcasciano M, Losco L, Bolletta A. Lymphatico-venous anastomosis in chronic ulcer with venous insufficiency: A case report. Microsurgery 2021; 41: 574-578
5 Xie T, Ye J, Rerkasem K, Mani R. The venous ulcer continues to be a clinical challenge: An update. Burns Trauma 2018; 6: 18
6 Bonkemayer Millan S, Gan R, Townsend PE. Venous ulcers: Diagnosis and treatment. Am Fam Physician 2019; 100: 298-305
7 Richard JL, Lavigne JP, Got I, Hartemann A, Malgrange D, Tsirtsikolou D, Baleydier A, Senneville E. Management of patients hospitalized for diabetic foot infection: Results of the French OPIDIA study. Diabetes Metab 2011; 37: 208-215
8 Zubair M, Abida M, Jamal A. Incidence, risk factors for amputation among patients with diabetic foot ulcer in a North Indian tertiary hospital. Foot (Edinb) 2012; 22: 24-30
9 Saba N, Rizwan UK, Jamal A. Understanding diabetic foot infection and its management. Diabetes Metab Syndr 2017; 11: 149-156
10 Kandregula S, Behura A, Behera CR, Pattnaik D, Mishra A, Panda B, Mohanty S. A clinical significance of fungal infections in diabetic foot ulcers. Cureus 2022; 14: e26872
11 Kew Science. Asparagaceae Juss. Plants of the world online; 2021. Zugriff am 03. Dezember 2023 unter: http://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:30275682-2
12 Jiménez-Barron O, García-Sandoval R, Magallón S, García-Mendoza A, Nieto-Sotelo J, Aguirre-Planter E, Eguiarte LE. Phylogeny, diversification rate, and divergence time of Agave sensu lato (Asparagaceae), a group of recent origin in the process of diversification. Front Plant Sci 2020; 11: 536135
13 Kew Science. Agave L.; Plants of the world online 2021. Accessed December 3, 2023 at: http://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:325900-2
14 Puente-Garza CA, Espinosa-Leal CA, García-Lara S. Steroidal saponin and flavonol content and antioxidant activity during sporophyte development of maguey (Agave salmiana). Plant Foods Hum Nutr 2018; 73: 287-294
15 Simmons-Boyce JL, Tinto WF. Steroidal saponins and sapogenins from the Agavaceae family. Nat Prod Commun 2007; 2: 99-114
16 Sidana J, Singh B, Sharma P. Saponins of Agave: Chemistry and bioactivity. Phytochemistry 2016; 130: 22-46
17 Espinosa-Andrews H, Urías-Silvas JE, Morales-Hernandez N. The role of agave fructans in health and food applications: A review. Trends Food Sci Technol 2021; 114: 585-598
18 Cortés J, Sánchez-Mendoza E, Zamilpa A, González-Cortazar M, Herrera-Ruiz M, Almanza-Pérez JC, Terán-Cabanillas E, Condé R, Domínguez-Ramírez L, Montiel Arcos E, Jiménez-Ferrer JE. Steroidal saponin from Agave marmorata Roezl modulates inflammatory response by inhibiting NF-κB and AP-1. Nat Prod Res 2020; 36: 1123-1128
19 Pereira GM, Ribeiro MG, da Silva BP, Parente JP. Structural characterization of a new steroidal saponin from Agave angustifolia var. Marginata and a preliminary investigation of its in vivo antiulcerogenic activity and in vitro membrane permeability property. Bioorg Med Chem Lett 2017; 27: 4345-4349
20 Argueta A, Cano L, Rodarte M. Atlas de las plantas de la medicina tradicional mexicana. 1st ed.. ed. México City, México: Instituto Nacional Indigenista; 1994
21 Ahmad F, Ali M, Alam P. New phytoconstituents from the stem bark of Tinospora cordifolia Miers. Nat Prod Res 2010; 24: 926-934
22 Forgo P, Kövér KE. Gradient enhanced selective experiments in the ¹H NMR chemical shift assignment of the skeleton and side-chain resonances of stigmasterol, a phytosterol derivative. Steroids 2004; 69: 43-50
23 Agrawal PK, Jain RK, Gupta RK, Thakur RS. Carbon-13 NMR spectroscopy of steroidal sapogenins and steroidal saponins. Phytochemistry 1985; 24: 2479-2496
24 Pettit GR, Moser BR, Herald DL, Knight JC, Chapuis JC, Zheng X. The Cephalostatins. 23. Conversion of hecogenin to a steroidal 1, 6-dioxaspiro[5.5]nonane analogue for cephalostatin. J Nat Prod 2015; 78: 1067-1072
25 García-Álvarez I, Corrales G, Doncel-Pérez E, Muñoz A, Nieto-Sampedro M, Fernández-Mayoralas A. Design and synthesis of glycoside inhibitors of glioma and melanoma growth. J Med Chem 2007; 50: 364-373
26 Chen PY, Chen CH, Kuo CC, Lee TH, Kuo YH, Lee CK. Cytotoxic steroidal saponins from Agave sisalana . Planta Med 2011; 77: 929-933
27 Cong PV, Anh HLT, Vinh LB, Han YK, Trung NQ, Minh BQ, Duc NV, Ngoc TM, Hien NTT, Manh HD, Lien LT, Lee KY. Alpha-glucosidase inhibitory activity of saponins isolated from Vernonia gratiosa Hance. J Microbiol Biotechnol 2023; 33: 797-805
28 Kumar S, Narwal S, Kumar V, Prakash O. α-glucosidase inhibitors from plants: A natural approach to treat diabetes. Pharmacogn Rev 2011; 5: 19-29
29 Sharabi K, Tavares CD, Rines AK, Puigserver P. Molecular pathophysiology of hepatic glucose production. Mol Aspects Med 2015; 46: 21-33
30 Hu X, Wang S, Xu J, Wang DB, Chen Y, Yang GZ. Triterpenoid saponins from Stauntonia chinensis ameliorate insulin resistance via the AMP-activated protein kinase and IR/IRS-1/PI3K/Akt pathways in insulin-resistant HepG2 cells. Int J Mol Sci 2014; 15: 10446-10458
31 Xu J, Wang S, Feng T, Chen Y, Yang G. Hypoglycemic and hypolipidemic effects of total saponins from Stauntonia chinensis in diabetic db/db mice. J Cell Mol Med 2018; 22: 6026-6038
32 Elekofehinti OO, Ejelonu OC, Kamdem JP, Akinlosotu OB, Adanlawo IG. Saponins as adipokines modulator: A possible therapeutic intervention for type 2 diabetes. World J Diabetes 2017; 8: 337-345
33 Spampinato SF, Caruso GI, De Pasquele R, Sortino MA, Merlo S. The treatment of impaired wound healing in diabetes: Looking among old drugs. Pharmaceuticals (Basel) 2020; 13: 60
34 Baltzis D, Eleftheriadou I, Veves A. Pathogenesis and treatment of impaired wound healing in diabetes mellitus: New insights. Adv Ther 2014; 31: 817-836
35 Jang KJ, Kim HK, Han MH, Oh YN, Yoon HM, Chung YH, Kim GY, Hwang HJ, Kim BW, Choi YH. Anti-inflammatory effects of saponins derived from the roots of Platycodon grandiflorus in lipopolysaccharide-stimulated BV2 microglial cells. Int J Mol Med 2013; 31: 1357-1366
36 Razika L, Thanina AC, Nadjiba CM, Narimen B, Mahdi DM, Karim A. Antioxidant and wound healing potential of saponins extracted from the leaves of Algerian Urtica dioica L. Pak J Pharm Sci 2017; 30: 1023-1029
37 Kim YS, Cho IH, Jeong MJ, Jeong SJ, Nah SY, Cho YS, Kim SH, Go A, Kim SE, Kang SS, Moon CJ, Kim JC, Kim SH, Bae CS. Therapeutic effect of total ginseng saponin on skin wound healing. J Ginseng Res 2011; 35: 360-367
38 Agius L. Role of glycogen phosphorylase in liver glycogen metabolism. Mol Aspects Med 2015; 46: 34-35
39 Hong F, Pan S, Guo Y, Xu P, Zhai Y. PPARs as nuclear receptors for nutrient and energy metabolism. Molecules 2019; 24: 2545
40 Yoon SY, Ahn D, Hwang JY, Kang MJ, Chung SJ. Linoleic acid exerts antidiabetic effects by inhibiting protein tyrosine phosphatases associated with insulin resistance. J Funct Foods 2021; 83: 104532
41 Arora A, Behl T, Sehgal A, Singh S, Sharma N, Chigurupati S, Kaur R, Bhatia S, Al-Harrasi A, Vargas-De-La-Cruz C, Bungau S. Free fatty acid receptor 1: A ray of hope in the therapy of type 2 diabetes mellitus. Inflammopharmacology 2021; 29: 1625-1639
42 Bartoszek A, Moo EV, Binienda A, Fabisiak A, Krajewska JB, Mosińska P, Niewinna K, Tarasiuk A, Martemyanov K, Salaga M, Fichna J. Free fatty acid receptors as new potential therapeutic target in inflammatory bowel diseases. Pharmacol Res 2020; 152: 104604
43 Hernandez-Quiles M, Broekema MF, Kalkhoven E. PPARgamma in metabolism, immunity, and cancer: Unified and diverse mechanisms of action. Front Endocrinol 2021; 12: 624112
44 Manosalva C, Alarcón P, González K, Soto J, Igor K, Peña F, Medina G, Burgos RA, Hidalgo MA. Free fatty acid receptor 1 signaling contributes to migration, MMP-9 activity, and expression of IL-8 induced by linoleic acid in HaCaT cells. Front Pharmacol 2020; 11: 595
45 Mirza RE, Fang MM, Novak ML, Urao N, Sui A, Ennis WJ, Koh TJ. Macrophage PPARγ and impaired wound healing in type 2 diabetes. J Pathol 2015; 236: 433-444
46 Ortiz-Andrade RR, Sánchez-Salgado JC, Navarrete-Vázquez G, Webster SP, Binnie M, García-Jiménez S, León-Rivera I, Cigarroa-Vázquez P, Villalobos-Molina R, Estrada-Soto S. Antidiabetic and toxicological evaluations of naringenin in normoglycaemic and NIIDDM rat models and its implications on extra-pancreatic glucose regulation. Diabetes Obes Metab 2008; 10: 1097-1104
47 Ibrahim MA, Islam MS. Butanol fraction of Khaya senegalensis root modulates β-cell function and ameliorates diabetes-related biochemical parameters in a type 2 diabetes rat model. J Ethnopharmacol 2014; 154: 832-838
48 Ramírez G, Zavala M, Pérez J, Zamilpa A. In vitro screening of medicinal plants used in Mexico as antidiabetics with glucosidase and lipase inhibitory activities. Evid Based Complement Alternat Med 2012; 2012: 701261
49 Adame-Miranda S, Granados-Guzmán G, Silva-Mares DA, Acevedo-Fernández JJ, Waksman-Minski N, Salazar-Aranda R. Evaluation of antihyperglycemic activity of plants in northeast Mexico. Cell Mol Biol 2021; 677: 212-218
50 Buettner R, Straub RH, Ottinger I, Woenckhaus M, Schölmerich J, Bollheimer LC. Efficient analysis of hepatic glucose output and insulin action using a liver slice culture system. Horm Metab Res 2005; 37: 127-132
51 García-Argáez AN, Ramírez-Apan TO, Parra-Delgado H, Velázquez G, Martínez-Vázquez M. Anti-inflammatory activity of coumarins from Decatropis bicolor on TPA ear edema mice model. Planta Med 2000; 66: 279-281
52 Gutiérrez SC, Castañón GC, Güitrón SA. Model for the quantitative evaluation of cicatrization. Pilot study with bee honey. Cir Gen 2005; 27: 114-119
53 Rios JL, Recio MC, Villar A. Screening methods for natural products with antimicrobial activity: A review of the literature. J Ethnopharmacol 1988; 23: 127-149

Zusatzmaterial

Ergänzendes Material