Abstract
Artabotrys hexapetalus (L.f.) Bhandari, Annonaceae, is one of Artabotrys species found in Asia, such as Sri Lanka, India, China, Malaysia, Indonesia, and other Southeast Asian countries. This plant is traditionally used as an herbal medicine. This research explored the potential of A. hexapetalus leaf and stem bark ethanol extract to treat type 2 diabetes by inhibiting the activity of α-glucosidase, including its relationship with the antioxidant activity, phenolic content, and flavonoid content. The analysis used α-glucosidase inhibition assay, 2,2-diphenyl-1-picrylhydrazyl free radical inhibition assay, ferric reducing antioxidant power assay, total phenolic content, total flavonoid content, liquid chromatography-tandem mass chromatography, and molecular docking analysis. Results showed that stem bark extract had a moderate α-glucosidase inhibitory activity with an IC50 value of 47.084 ppm. In contrast, the leaf extract had a weak α-glucosidase inhibitory activity with an IC50 value of 104.755 ppm. Random permutation in random forest simulation was used to predict the factors contributing to the α-glucosidase inhibition. For stem bark and leaf extracts, the α-glucosidase inhibition activity was predicted to be influenced by antioxidant activity and phenolic compounds. Comparisons between various analyses were shown to corroborate the random permutation results. Nevertheless, since the major identified active compound that likely played a role in α-glucosidase inhibition in stem bark was from terpene groups, it was predicted that some major compounds with high α-glucosidase inhibitory and antioxidant activities in stem bark were yet-to-be-identified.
Graphical Abstract
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data Availability
The data used in this research is available upon request to the authors.
References
Alara OR, Abdurahman NH, Obanijesu EO, Alara JA, Mudalip ASK (2020) Extract-rich in flavonoids from Hibiscus sabdariffa calyces: optimizing microwave-assisted extraction method and characterization through LC-Q-TOF-MS analysis. J Food Process Eng 43:e13339. https://doi.org/10.1111/jfpe.13339
Alqahtani AS, Hidayathulla S, Rehman MT, Elgamal AA, Al-Massarani S, Razmovski-Naumovski V, Alqahtani MS, El Dib RA, Alajmi MF (2020) Alpha-amylase and alpha-glucosidase enzyme inhibition and antioxidant potential of 3-oxolupenal and katononic acid isolated from Nuxia oppositifolia. Biomolecules 10:61. https://doi.org/10.3390/biom10010061
Andrew O, Yusuf S, Jangabe LM, Lawal BS, Adamu AA (2013) α-Glucosidase inhibitory potential of selected antidiabetic plants used in north-western Nigeria. J Med Plant Res 7:2010–2018. https://doi.org/10.5897/JMPR12.1005
Archana T, Soumya K, James J, Sudhakaran S (2021) Root extracts of Anacardium occidentale reduce hyperglycemia and oxidative stress in vitro. Clin Phytoscience 7:57. https://doi.org/10.1186/s40816-021-00293-1
Bailly C, Hénichart JP (2022) Advocacy for the medicinal plant Artabotrys hexapetalus (Yingzhao) and antimalarial Yingzhaosu endoperoxides. Molecules 27:6192. https://doi.org/10.3390/molecules27196192
Biau G, Scornet E (2016) A random forest guided tour. Test 25:197–227. https://doi.org/10.1007/s11749-016-0481-7
Boulmokh Y, Belguidoum K, Meddour F, Amira-Guebailia H (2021) Investigation of antioxidant activity of epigallocatechin gallate and epicatechin as compared to resveratrol and ascorbic acid: experimental and theoretical insights. Struct Chem 32:1907–1923. https://doi.org/10.1007/s11224-021-01763-5
Breiman L (2001) Random forests. Mach Learn 45:5–32. https://doi.org/10.1023/A:1010933404324
Cassia Ortiz A, Fideles SOM, Reis CHB, Bellini MZ, Souza Bastos Mazuqueli Pereira A, Pilon JPG, Marchi MA, Detregiachi CRP, Flato UAP, Moraes Trazzi BF, Pagani BT, Ponce JB, Gardizani TP, Souza Veronez F, Buchaim DV, Buchaim RL (2022) Therapeutic effects of citrus flavonoids neo hesperidin, hesperidin and its aglycone, hesperetin on bone health. Biomolecules 12:626. https://doi.org/10.3390/biom12050626
Chang CC, Yang MH, Wen HM, Chern JC (2002) Estimation of total flavonoid content in propolis by two complementary colorimetric methods. J Food Drug Anal 10:178–182. https://doi.org/10.38212/2224-6614.2748
Chavan JJ, Gaikwad NB, Kshirsagar R, Dixit GB (2013) Total phenolics, flavonoids and antioxidant properties of three Ceropegia species from Western Ghats of India. S Afr J Bot 88:273–277. https://doi.org/10.1016/j.sajb.2013.08.007
Dej-adisai S, Sakulkeo O, Wattanapiromsakul C, Pitakbut T (2022) Flavonoid constituents and alpha-glucosidase inhibition of Solanum stramonifolium Jacq. inflorescence with in vitro and in silico studies. Molecules 29:8189. https://doi.org/10.3390/molecules27238189
Dewi RT, Tachibana S, Darmawan A (2014) Effect on α-glucosidase inhibition and antioxidant activities of butyrolactone derivatives from Aspergillus terreus MC751. Med Chem Res 23:454–460. https://doi.org/10.1007/s00044-013-0659-4
Ding HY, Lin HC, Teng CM, Wu YC (2000) Phytochemical and pharmacological studies on Chinese Paeonia species. J Chin Chem Soc 47:381–388. https://doi.org/10.1002/jccs.200000051
Dirir AM, Daou M, Yousef AF, Yousef LF (2021) A review of alpha-glucosidase inhibitors from plants as potential candidates for the treatment of type-2 diabetes. Phytochem Rev 21:1049–1079. https://doi.org/10.1007/s11101-021-09773-1
Eberhardt J, Santos-Martins D, Tillack AF, Forli S (2021) AutoDock Vina 1.2.0: new docking methods, expanded force field, and python bindings. J Chem Inf Model 61:3891–3898. https://doi.org/10.1021/acs.jcim.1c00203
González-Palma I, Escalona-Buendía HB, Ponce-Alquicira E, Téllez-Téllez M, Gupta VK, Díaz-Godínez G, Soriano-Santos J (2016) Evaluation of the antioxidant activity of aqueous and methanol extracts of Pleurotus ostreatus in different growth stages. Front Microbiol 7:1099. https://doi.org/10.3389/fmicb.2016.01099
He ZD, But PPH, Chan TWD, Dong H, Xu HX, Lau CP, Sun HD (2001) Antioxidative glucosides from the fruits of Ligustrum lucidum. Chem Pharm Bull 49:780–784. https://doi.org/10.1248/cpb.49.780
Itam A, Wati MS, Agustin V, Sabri N, Jumanah RA, Efdi M (2021) Comparative study of phytochemical, antioxidant, and cytotoxic activities and phenolic content of Syzygium aqueum (Burm fAlston f) extracts growing in west Sumatera Indonesia. Sci. World J 2021:5537597. https://doi.org/10.1155/2021/5537597
Jiang Z, Gao W, Huang L (2019) Tanshinones, critical pharmacological components in Salvia miltiorrhiza. Front Pharmacol 10:202. https://doi.org/10.3389/fphar.2019.00202
Jingguang Y, Tongmei L, Lan S, Xiuzhen L, Wei D, Deyu L (2002) Neo-lignans and hemiterpenoid from the seeds of Artabotrys hexapetalus (Annonaceae). J Chin Pharm Sci 11:4–10
Kukreti N, Chitme HR, Varshney VK, Abdel-Wahab BA, Khateeb MM, Habeeb MS (2023) Antioxidant properties mediate nephroprotective and hepatoprotective activity of essential oil and hydro-alcoholic extract of the high-altitude plant Skimmia anquetilia. Antioxidants 12:1167. https://doi.org/10.3390/antiox12061167
Morris ASC, Denham AS, Bassett HH, Curby WT (2008) Differences between high- and low-affinity complexes of enzymes and nonenzymes. J Med Chem 51:6432–6441. https://doi.org/10.1021/jm8006504
Myles AJ, Feudale RN, Liu Y, Woody NA, Brown SD (2004) An introduction to decision tree modeling. J Chemom 18:275–285. https://doi.org/10.1002/cem.873
Patil P, Mandal S, Tomar SK, Anand S (2015) Food protein-derived bioactive peptides in management of type 2 diabetes. Eur J Nutr 54:863–880. https://doi.org/10.1007/s00394-015-0974-2
Piero MN, Nzaro GM, Njagi JM (2014) Diabetes mellitus – a devastating metabolic disorder. Asian J Biomed Pharm Sci 4:1–7. https://doi.org/10.15272/ajbps.v4i40
Pinzi L, Rastelli G (2019) Molecular docking: shifting paradigms in drug discovery. Int J Mol Sci 20:4331. https://doi.org/10.3390/ijms20184331
Rasheed A, Azeez RFA (2019) A review on natural antioxidants. Traditional and Complementary Medicine. IntechOpen. https://doi.org/10.5772/intechopen.82636
Ravindranath PA, Forli S, Goodsell DS, Olson AJ, Sanner MF (2015) Autodockfr: advances in protein-ligand docking with explicitly specified binding site flexibility. PLoS Comput Biol 11:1004586. https://doi.org/10.1371/journal.pcbi.1004586
Rosa D, Elya B, Hanafi M, Khatib A, Surya MI (2023) In vitro and in silico screening analysis of Artabotrys sumatranus leaf and twig extracts for α -glucosidase inhibition activity and its relationship with antioxidant activity. Sci Pharm 91:2. https://doi.org/10.3390/scipharm91010002
Rossi M, Wen K, Caruso F, Belli S (2020) Emodin scavenging of superoxide radical includes π–π interaction. X-ray crystal structure, hydrodynamic voltammetry and theoretical studies. Antioxidants 9:194. https://doi.org/10.3390/antiox9030194
Shukla R, Singh S, Singh A, Misra K (2021) Two pronged approach for prevention and therapy of COVID-19 (Sars-CoV-2) by a multi-targeted herbal drug, a component of ayurvedic decoction. Eur J Integr Med 43:101268. https://doi.org/10.1016/j.eujim.2020.101268
Sichaem J, Rojpitikul T, Sawasdee P, Lugsanangarm K, Tip-Pyang S (2015) Furoquinoline alkaloids from the leaves of Evodia lepta as potential cholinesterase inhibitors and their molecular docking. Nat Prod Comm 10:1359–1362. https://doi.org/10.1177/1934578x1501000811
Somanawat J, Talangsri N, Deepolngam S, Kaewamatawong R (2012) Flavonoid and megastigmane glycosides from Artabotrys hexapetalus leaves. Biochem Syst Ecol 44:124–127. https://doi.org/10.1016/j.bse.2012.04.023
Sun S, Zhao Y, Wang L, Tan Y, Shi Y, Sedjoah RCAA, Shao Y, Li L, Wang M, Wan J, Fan X, Guo R, Xin Z (2022) Ultrasound-assisted extraction of bound phenolic compounds from the residue of Apocynum venetum tea and their antioxidant activities. Food Biosc 47:101646. https://doi.org/10.1016/j.fbio.2022.101646
Tomasina F, Carabio C, Celano L, Thomson L (2012) Analysis of two methods to evaluate antioxidants. Biochem Mol Biol Educ 40:266–270. https://doi.org/10.1002/bmb.20617
Trott O, Olson AJ (2010) Autodock vina: improving the speed and accuracy of docking with a new scoring function efficient optimization and multithreading. J Comput Chem 31:455–461. https://doi.org/10.1002/jcc.21334
Tungmunnithum D, Thongboonyou A, Pholboon A, Yangsabai A (2018) Flavonoids and other phenolic compounds from medicinal plants for pharmaceutical and medical aspects: an overview. Medicines 5:93. https://doi.org/10.3390/medicines5030093
Wang X, Moris- Natschke SL, Lee KH (2006) New developments in the chemistry and biology of the bioactive constituents of tanshen. Med Res Rev 27:133–148. https://doi.org/10.1002/med.20077
Weng XC, Gordon MH (1992) Antioxidant activity of quinones extracted from tanshen (Salvia miltiorrhiza Bunge). J Agric Food Chem. 40:1331–1336. https://doi.org/10.1021/jf00020a007
Wiliantari S, Iswandana R, Elya B (2022) Total polyphenols total flavonoids antioxidant activity and inhibition of tyrosinase enzymes from extract and fraction of Passiflora ligularis Juss. Pharmacogn J 14:672–680. https://doi.org/10.5530/pj.2022.14.86
Xi FM, Liu YB, Qu J, Li Y, Tang ZH, Li L, Li YH, Chen XG, Ma SG, Yu SS (2017) Bioactive sesquiterpenoids from the roots of Artabotrys hexapetalus. Tetrahedron 73:571–582. https://doi.org/10.1016/j.tet.2016.12.043
Yang X, Xia H, Li Y, Cheng Y, Wang Y, Xia Y, Yue Y, Cheng X, Chu Z (2022) In vitro and ex vivo antioxidant activity and sustained release properties of sinomenine-loaded liposomes-in-hydrogel biomaterials simulating cells-in-extracellular matrix. Nat Prod Comm 17:1–11. https://doi.org/10.1177/1934578X221130699
Yeo JY, Hwang KW, Park SY (2020) Anti-inflammatory effect of neo-lignan isoamericanin A via suppression of NF-κB in liposaccharide-stimulated RAW 264.7 cells. Trop J Pharm Res 19:1857–1862. https://doi.org/10.4314/tjpr.v19i9.9
Zhou Q, Fu YH, Li XB, Chen GY, Wu SY, Song XP, Liu YP, Han CR (2015) Bioactive benzylisoquinoline alkaloids from Artabotrys hexapetalus. Phytochem Lett 11:296–300. https://doi.org/10.1016/j.phytol.2015.01.017
Acknowledgements
The authors would like to thank Bogor Botanical Garden for providing the samples for this research, as well as the Advanced Characterization Laboratories Serpong at National Research and Innovation Institutes and the Pharmaceutical Biology Laboratory and Food Quality Control Laboratory at Pelita Harapan University for providing facilities and technical support for this research.
Funding
This research was financially supported by PUTI Q2 2023 University of Indonesia No. NKB-589/ UN2.RST/HKP.05.00/2023, Pelita Harapan University through internal grant number P-29-FIKes/VIII/2022, and the National Research and Innovation Agency through Degree by Research Scholarship study funding.
Author information
Authors and Affiliations
Contributions
DR performed the experiments and drafted the manuscript; BE designed the experiments and reviewed the article; MH collected the samples and performed LC-MS/MS analyses; YH, MIS, and AK reviewed and did a critical reading of the manuscript. All the authors have read and agreed with the final version of the manuscript.
Corresponding author
Ethics declarations
Ethics Approval
Not applicable
Informed Consent
Not applicable
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Rosa, D., Elya, B., Hanafi, M. et al. Analysis of Artabotrys hexapetalus Stem Bark and Leaf Ethanol Extracts as α-Glucosidase Inhibitors: In Vitro Analysis, LC-MS/MS, Machine Learning, and Molecular Docking. Rev. Bras. Farmacogn. 34, 386–396 (2024). https://doi.org/10.1007/s43450-023-00494-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s43450-023-00494-4