Antiglycation and antitumoral activity of Tribulus terrestris dry extract

Document Type : Original Research Article

Authors

1 São Paulo State University (UNESP), Institute of Chemistry, Araraquara, São Paulo, Brazil

2 Fundação Educacional do Município de Assis (FEMA), Assis, São Paulo, Brazil

3 University of Campinas (UNICAMP), Faculty of Pharmaceutical Sciences, Campinas, São Paulo, Brazil

4 São Paulo State University (UNESP), School of Sciences, Humanities and Languages, Department of Biotechnology, Laboratory of Herbal Medicine and Natural Products, Assis, São Paulo, Brazil

Abstract

Objective: Investigation of the antiglycation and antitumoral potential of standardized and saponins-enriched extracts of Tribulus terrestris herbal medicine.
Materials and Methods: The procedures for the evaluation of the antiglycation activity of the standardized (TtSE) and saponins-enriched (TtEE) extracts of T. terrestris were: determination of relative mobility in electrophoresis (RME), free amino groups using OPA method and advanced glycation end-products (AGEs) fluorescence. Antioxidant activity was determined by DPPH radical scavenging test. In vitro antitumor activity of TtSE and TtEE was evaluated in human tumor cell lines.
Results: The results were obtained by antiglycation tests (RME, OPA method and AGEs fluorescence determination), using BSA as protein and ribose as glycation agent, and antioxidant assay (DPPH test); it was verified that both extracts of T. terrestris have antiglycation and antioxidant activity. In addition, the extracts were able to induce death of more than 50% of human tumor cell lines.
Conclusion: The present study showed that standardized and saponins-enriched extracts of T. terrestris herbal medicine present antiglycation and antioxidant and antiproliferative action in human tumor cells lines. The saponins-enriched extract proved a greater antiglycation and antioxidant activity in comparison to the standardized type.

Keywords


Abraham J, Staffurth J. 2020. Hormonal
therapy for cancer. Medicine, 48: 103-107.
Akbal O, Vural T, Malekghasemi S, Bozdoğan
B, Denkbaş EB. 2018. Saponin loaded
montmorillonite-human serum albumin
nanocomposites as drug delivery system in
colorectal cancer therapy. Appl Clay Sci,
166: 214-222.
Angelova S, Gospodinova Z, Krasteva M,
Antov G, Lozanov V, Markov T, Bozhanov
S, Georgieva E, Mitev V. 2013. Antitumor
activity of Bulgarian herb Tribulus terrestris
L. on human breast cancer cells. J BioSci
Biotech, 2: 25-32.
Anis MA, Sreerama YN. 2020. Inhibition of
protein glycoxidation and advanced
glycation end-product formation by
barnyard millet (Echinochloa frumentacea)
phenolics. Food Chem, 315:126-265.
Bansode SB, Gacche RN. 2019. Glycationinduced modification of tissue-specific
ECM proteins: A pathophysiological
mechanism in degenerative diseases.
Biochim Biophys Acta, 1863: 129411.
Borran M, Minaiyan M, Zolfaghari B,
Mahzouni P. 2017. Protective effect of
Tribulus terrestris fruit extract on ceruleininduced acute pancreatitis in mice.
Avicenna J Phytomed, 7: 250-260.
Chhatre S, Nesari T, Somani G, Kanchan D,
Figueiredo et al.
AJP, Vol. 11, No. 3, May-Jun 2021 234
Sathaye S. 2014. Phytopharmacological
overview of Tribulus terrestris. Pharmacogn
Rev, 8: 45-51.
Chhipa AS, Borse SP, Baksi R, Lalotra S,
Nivsarkar M. 2019. Targeting receptors of
advanced glycation end-products (RAGE):
Preventing diabetes induced cancer and
diabetic complications. Pathol Res Pract,
215: 152643.
Combarieu E, Fuzzati N, Lovati M, Mercalli E.
2003. Furostanol saponins from Tribulus
terrestris. Fitoterapia, 74(6): 583-591.
Dil FA, Ranjkesh Z, Goodarzi MT. 2019. A
systematic review of antiglycation
medicinal plants. Diabetes Metab Syndr, 13:
1225-1229.
Dinchev D, Janda B, Evstatieva L, Oleszek W,
Aslani MR, Kostova I. 2008. Distribution of
steroidal saponins in Tribulus terrestris
from different geographical regions.
Phytochemistry, 69: 176-186.
Divya MK, Dharmapal S, Achuthan CR, Babu
TD. 2014. Cytotoxic and antitumor effects
of Tribulus terrestris L fruit methanolic
extract. J Pharmacogn Phytochem, 3: 1-4.
Doost AS, Camp JV, Dewettinck K, Van der
Meeren P. 2019. Production of thymol
nanoemulsions stabilized using Quillaja
Saponin as a biosurfactant: Antioxidant
activity enhancement. Food Chem, 292:
134-143.
Elekofehinti OO. 2015. Saponins: Anti-diabetic
principles from medicinal plants - A review.
Pathophysiology, 22: 95-103.
El-Shaibany A, Al-Habori M, Al-Tahami B,
Al-Massarani S. 2015. Anti-hyperglycaemic
Activity of Tribulus terrestris L aerial part
extract in glucose-loaded normal rabbits.
Trop J Pharm Res, 14: 2263-2268.
Escribano J, Cabanes J, Jiménez-Atiénzar M,
Ibañez-Tremolada M, Gómez-Pando LR,
García-Carmona F, Gandía-Herrero F. 2017.
Characterization of betalains, saponins and
antioxidant power in differently colored
quinoa (Chenopodium quinoa) varieties.
Food Chem, 234: 285-294.
Ezeabara CA, Okeke CU, Aziagba BO, Ilodibia
CV, Emeka AN. 2014. Determination of
saponin content of various parts of six Citrus
species. Int Res J Pure Appl Chem, 4: 137-
143.
Ezeonu CS, Ejikeme CM. 2016. Qualitative and
quantitative determination of phytochemical
contents of indigenous nigerian softwoods.
New J Sci, 5601327: 1-9.
Fayle SE, Healy JP, Brown PA, Reid EA,
Gerrard JA, Ames JM. 2001. Novel
approaches to the analysis of the Maillard
reaction of proteins. Electrophoresis, 22:
1518-1525.
Gilabert-Oriol R, Weng A, von Mallinckrodt B,
Stöshel A, Nissi L, Melzig MF, Fuchs H,
Thakur M. 2015. Electrophoretic mobility as
a tool to separate immune adjuvant saponins
from Quillaja saponaria Molina. Int J
Pharm, 487: 39-48.
Gugliucci A, Bastos DHM, Schulze J, Souza
MFF. 2009. Caffeic and chlorogenic acids in
Ilex paraguariensis extracts are the main
inhibitors of AGE generation by
methylglyoxal in model proteins.
Fitoterapia, 80: 339–344.
Hammoda HM, Ghazy NM, Harraz FM,
Radwan MM, ElSohly MA, Abdallah II.
2013. Chemical constituents from Tribulus
terrestris and screening of their antioxidant
activity. Phytochemistry, 92: 153–159.
Ivanova A, Lazarova I, Mechkarova P,
Tchorbanov B. 2010. HPLC Method for
Screening of Steroidal Saponins and Rutin
as Biologically Active Compounds in
Tribulus terrestris L. Biotechnol Biotechnol
Equip, 24: 129-133.
Jud P, Sourij H. 2019. Therapeutic options to
reduce advanced glycation end products in
patients with diabetes mellitus: A review.
Diabetes Res Clin Pract, 148: 54-63.
Khan M, Liu H, Wang J, Sun B. 2020.
Inhibitory effect of phenolic compounds and
plant extracts on the formation of advance
glycation end products: A comprehensive
review. Food Res Int, 130: 108933.
Kim HJ, Kim JC, Min JS, Kim M-J, Kim JA,
Kor MH, Yoo HS, Ahn JK. 2011. Aqueous
extract of Tribulus terrestris Linn induces
cell growth arrest and apoptosis by downregulating NF-қB signaling in liver cancer
cells. J Ethnopharmacol, 136: 197-203.
Koomson DA, Kwakye BD, Darkwah WK,
Odum B, Asante M, Aidoo G. 2018.
Phytochemical Constituents, Total
Saponins, Alkaloids, Flavonoids and
Vitamin C Contents of Ethanol Extracts of
five Solanum torvum Fruits. Pharmacogn J,
10: 946-950.
Kouidrat Y, Amad A, Arai M, Miyashita M,
Lalau J-D, Loas G, Itokawa M. 2015.
Advanced glycation end products and
schizophrenia: A systematic review. J
Psychiatr Res, 66-67: 112-117.
Antiglycation and antitumoral activity of T. terrestris
AJP, Vol. 11, No. 3, May-Jun 2021 235
Krishna RN, Anitha R, Ezhilarasan D. 2020.
Aqueous extract of Tamarindus indica fruit
pulp exhibits antihyperglycaemic activity.
Avicenna J Phytomed, 10: 440-447.
Lamba HS, Bhargava CS, Thakur M, Bhargava
S. 2011. α-Gluosidase and aldose reductase
inhibitory activity in vitro and anti-diabetic
activity in vivo of Tribulus terrestris L.
(DUNAL). Int J Pharm Pharm Sci, 3: 270-
272.
Li M, Guan Y, Liu J, Zhai F, Zhang X, Guan L.
2013. Cellular and molecular mechanisms in
vascular smooth muscle cells by which total
saponin extracted from Tribulus terrestris
protects against artherosclerosis. Cell
Physiol Biochem, 32: 1299-1308.
Majidinia M, Bishayee A, Yousefi B. 2019.
Polyphenols: Major regulators of key
components of DNA damage response in
cancer. DNA Repair (Amst), 82: 102679.
Mishra NK, Biswal GS, Chowdary KA, Mishra
G. 2013. Anti-arthritic activity of Tribulus
terrestris studied in Freund’s Adjuvant
induced arthritic rats. J Pharm Educ Res, 4:
41-46.
Miura S, Watanabe J, Tomita T, Sano M,
Tomita I. 1994. The inhibitory of tea
polyphenols (flavan-3-ol derivatives) on
Cu2+ mediated oxidative modification of low
density lipoprotein. Biol Pharm Bull, 17:
1567-1572.
Mohd J, Akhtar AJ, Abuzer A, Javed A, Ali M,
Ennus T. 2012. Pharmacological scientific
evidence for the promise of Tribulus
terrestris. Int Res J Pharm, 3: 403-406.
Monks A, Scudeiro D, Skehan P, Shoemaker R,
Paull K, Vistica D, Hose C, Langley J,
Cronise P, Vaigro-Wolff A, Gray-Goodrich
M, Campbell H, Mayo J, Boyd M. 1991.
Feasibility of a high-flux anticancer drug
screen using a diverse panel of cultured
human tumor cell lines. J Natl Cancer Inst,
83: 757-766.
Mulinacci M, Vignolini P, La Marca G,
Pieraccini G, Innocenti M, Vincieri FF.
2003. Food supplements of Tribulus
terrestris L.: An HPLC-ESI-MS method for
an estimation of the saponin content.
Chromatographia, 57: 581-592.
Nadjib RM, Amine G, Amine HM. 2018.
Glycated hemoglobin assay in a Tlemcen
population: Retrospective study. Diabetes
Metab Syndr, 12: 911-916.
Naz R, Ayub H, Nawaz S, Islam ZU, Yasmin
T, Bano A, Wakeel A, Zia S, Roberts TH.
2017. Antimicrobial activity, toxicity and
anti-inflammatory potential of methanolic
extracts of four ethnomedicinal plant species
from Punjab, Pakistan. BMC Complement
Altern Med, 17: 302.
Neha K, Haider MR, Pathak A, Yar MS. 2019.
Medicinal prospects of antioxidants: A
review. Eur J Med Chem, 178: 687-704.
NunesJHB, Bergamini FRG, Lustri WR, Paiva
PP, Ruiz ALTG, Carvalho JE, Corbi PP.
2017. Synthesis, characterization and in
vitro biological assays of a silver (I)
complex with 5-fluorouracil: A strategy to
overcome multidrug resistant tumor cells. J
Fluor Chem, 195: 93-101.
Oh JS, Baik SH, Ahn E-K, Jeong W, Hong SS.
2012. Antiinflammatory activity of Tribulus
terrestris in RAW264.7 Cells. J Immunol,
188: 54-62.
Pavin NF, Izaguirry AP, Soares MB, Spiazzi
CC, Mendes ASL, Leivas FG, Brum DS,
Cibin FWS. 2018. Tribulus terrestris
Protects against Male Reproductive Damage
Induced by Cyclophosphamide in Mice.
Oxid Med Cell Longev, 2018: 1-9.
Pokrywka A, Morawin B, Krzywański J,
Zembroń-Lacny A. 2017. An Overview on
Tribulus terrestris in Sports Nutrition and
Energy Regulation. In: Bagchi D (Ed),
Sustained Energy for Enhanced Human
Functions and Activity, pp. 155-165,
Cambridge, USA, Academic Press.
Pourali M, Yaghoobi MM, Sormaghi MHS.
2017. Cytotoxic, Anti-Proliferative and
Apoptotic Effects of Tribulus terrestris L.
Fruit Extract on Human Prostate Cancer
Lncap and Colon Cancer HT-29 Cell Lines.
Jundishapur J Nat Pharm Prod, 12: e33561.
Prasad C, Davis KE, Imrhan V, Juma S,
Vijayagopal P. 2019. Advanced Glycation
End Products and Risks for Chronic
Diseases: Intervening Through Lifestyle
Modification. Am J Lifestyle Med, 1: 384-
404.
Qureshi A, Naughton DP, Petroczi A. 2014. A
Systematic Review on the Herbal Extract
Tribulus terrestris and the Roots of its
Putative Aphrodisiac and Performance
Enhancing Effect. J Diet Suppl, 11: 64-79.
Rabbani G, Ahn SN. 2019. Structure,
enzymatic activities, glycation and
therapeutic potential of human serum
albumin: A natural cargo. Int J Biol
Macromol, 123: 979-990.
Ren Y, Chen Y, Hu B, Wu H, Lai F, Li X. 2015.
Figueiredo et al.
AJP, Vol. 11, No. 3, May-Jun 2021 236
Microwave-assisted extraction and a new
determination method for total steroid
saponins from Dioscorea zingiberensis C.H.
Wright. Steroids, 104: 145-152.
Rufino MSM, Alves RE, Brito ES, PérezJiménez J, Saura-Calixto F, Mancini-Filho
J. 2010. Bioactive compounds and
antioxidant capacities of 18 non-traditional
tropical fruits from Brazil. Food Chem, 121:
996-1002.
Sadowska-Bartosz I, Bartosz G. 2016. Effect of
glycation inhibitors on aging and age-related
diseases. Mech Ageing Dev, 160: 1-18.
Sajadimaj S, Bahramsoltani R, Iranpanah A,
Patra JK, Das G, Gouda S, Rahimi R,
Rezaeiamiri E, Cao H, Giampieri F, Battino
M, Tundis R, Campos MG, Farzaei MH,
Xiao J. 2020. Advances on Natural
Polyphenols as Anticancer Agents for Skin
Cancer. Pharmacol Res, 151: 104584.
Sanagoo S, Oskouei BS, Abdollahi NG, SalehiPourmehr H, Hazhir N, Farshbaf-Khalili A.
2019. Effect of Tribulus terrestris L. on
sperm parameters in men with idiopathic
infertility: A systematic review.
Complement Ther Med, 42: 95-103.
Santos CHC, Talpo TC, Motta BP, Kaga AK,
Baviera AM, Castro RN, Silva VC, SousaJunior PT, Wessjohann L, Carvalho MG.
2019. New compounds of Siolmatra
brasiliensis and inhibition of in vitro protein
glycation damage. Fitoterapia, 133: 109-
119.
Shamah-Levy T, Villalpando-Hernández S,
Rivera-Dommarco J. 2006. Manual de
procedimientos para proyectos de nutrición,
pp. 1-148, Cuernavaca, México, Instituto
Nacional de Salud Pública.
Siddiqui MA, Rasheed S, Saquib Q, AlKhedhairy AA, Al-Said MS, Musarrat J,
Choudhary MI. 2016. In Vitro dual
inhibition of protein glycation, and
oxidation by some Arabian plants. BMC
Complement Altern Med, 16: 276-2085.
Singh D, Chaudhuri PK. 2018. Structural
characteristics, bioavailability and
cardioprotective potential of saponins.
Integr Med Res, 7: 33-43.
Sisto M, Lisi S. 2019. Saponins from Tribulus
terrestris Linn Plant - Potentials and
Challenges for Prevention of Solar
Ultraviolet Radiation-Induced Damages and
Malignant Transformation. Biomed J Sci &
Tech Res, 16: 12345-12352.
Siva B, Venkanna A, Poornima B, Reddy SD,
Boustie J, Bastien S, Jain N, Rani PU, Babu
KS. 2017. New seco-limonoids from
Cipadessa baccifera: Isolation, structure
determination, synthesis and their
antiproliferative activities. Fitoterapia, 117:
34-40.
Sivapalan SR. 2016. Biological and
pharmacological studies of Tribulus
terrestris Linn: A review. Int J Multidiscip
Res Dev, 3: 257-265.
Sobolewska D, Galanty A, Grabowska K,
Makowska-Was J, Wróbel-Biedrawa D,
Podolak Irma. 2020. Saponins as cytotoxic
agents: an update (2010–2018). Part Isteroidal saponins. Phytochem Rev, 19: 139-
189.
Soleimanpour S, Sedighinia FS, Afshar AS,
Zarif R, Ghazvini K. 2015. Antibacterial
activity of Tribulus terrestris and its
synergistic effect with Capsella bursapastoris and Glycyrrhiza glabra against oral
pathogens: an in-vitro study. Avicenna J
Phytomed, 5: 210-217.
Sousa EO, Miranda CMBA, Nobre CB,
Boligon AA, Athayde ML, Costa JGM.
2015. Phytochemical analysis and
antioxidant activities of Lantana camara
and Lantana montevidensis extracts. Ind
Crop Prod, 70: 7-15.
Su L, Chen G, Feng S-G, Wang W, Li Z-F,
Chen H, Liu Y-X, Pei Y-H. 2009. Steroiral
saponins from Tribulus terrestris. Steroids,
74: 399-403.
Tian C, Chang Y, Zhang Z, Wang H, Xiao S,
Cui C, Liu M. 2019. Extraction technology,
component analysis, antioxidant,
antibacterial,analgesic and antiinflammatory activities of flavonoids
fraction from Tribulus terrestris L. leaves.
Heliyon, 5: 22-34.
Wang Q, Wu X, Shi F, Liu Y. 2019.
Comparison of antidiabetic effects of
saponins and polysaccharides from
Momordica charantia L. in STZ-induced
type 2 diabetic mice. Biomed Pharmacother,
109: 744-750.
Wei Y, Chen L, Chen J, Ge L, He RQ. 2009.
Rapid glycation with D-ribose induces
globular amyloid-like aggregations of BSA
with high cytotoxicity to SH-SY5Y cells.
BMC Cell Biol, 10: 10.
Younus H, Anwar S. 2016. Prevention of nonenzymatic glycosylation (glycation):
Implication in the treatment of diabetic
complication. Int J Health Sci (Qassim), 10:
Antiglycation and antitumoral activity of T. terrestris
AJP, Vol. 11, No. 3, May-Jun 2021 237
261-277.
Zendjabil M. 2020. Glycated albumin. Clin
Chim Acta, 502: 240-244.
Zeng C, Li Y, Ma J, Niu L, Tay FR. 2019.
Clinical/Translational Aspects of Advanced
Glycation End-Products. Trends Endocrinol
Metab, 30: 959-973.
Zhao Y-Z, Zhang Y-Y, Han H, Fan R-P, Hu Y,
Zhong L, Kou J-P, Yu B-Y. 2018. Advances
in the antitumor activities and mechanisms
of action of steroidal saponins. Chin J Nat
Medicines, 16: 732-748.