The corms of Hypoxis argentea are widely used as a traditional remedy for diabetes mellitus in South Africa. In this study, we investigated the effects of non-toxic concentrations (12.5-100 μg mL-1) of the aqueous extract of H. argentea (HAA) corms on glucose uptake, pancreatic beta cell proliferation, and adipocyte differentiation. HAA stimulated glucose uptake in HepG2 cells up to 19.6 % and 17.0 % in L6 myotubes. Live-cell imaging microscopy revealed significant increases (p < 0.001) in total INS-1 cell numbers exposed to HAA, although no effect was observed on adipogenesis in 3T3-L1 pre-adipocytes. HAA produced weak to moderate inhibition of porcine pancreatic α-amylase, α-glucosidase, porcine pancreatic lipase, dipeptidyl peptidase IV (DPP IV) activities, as well as protein glycation. Our results suggest that the acclaimed anti-diabetic effects of H. argentea could be mediated by its promotion of glucose utilization and preservation of pancreatic beta cell populations while preventing fat accumulation in adipocytes.
1. World Health Organization, The Burden of Chronic Diseases in the African Region, Preventing Chronic Diseases, A Vital Investment, World Diabetes Foundation Summit, WHO global report, Geneva 2007.
2. A. A. Motala, M. A. K. Omar and F. J. Pirie, Epidemiology of Diabetes in Africa, in The Epidemiology of Diabetes Mellitus (Eds. J. M. Ekoe, M. Rewers, R. Williams and P. Zimmet), 2nd ed., Wiley, Chichester 2008, pp. 133-146.
3. N. S. Levitt, Diabetes in Africa: epidemiology, management and health-care challenges, Heart 4 (2008) 1376-1382; https://doi.org/10.1136/hrt.2008.147306
4. C. N. He, C. L. Wang and S. X. Guo, Study on chemical constituents in herbs of Anoectochilus roxburghii II, China, J. Chin. Mat. Med. 30 (2005) 761-776.
5. M. Jung, M. Park, H. C. Lee, Y. Kang, E. S. Kang and S. K. Kim, Antidiabetic agents from medicinal plants, Curr. Med. Chem. 13 (2006) 1203-1218; https://doi.org/10.2174/092986706776360860
6. S. O. Oyedemi, M. T. Yakubu and A. J. Afolayan, Antidiabetic activities of aqueous leaves extract of Leonotis leonurus in streptozotocin induced diabetic rats, J. Med. Plants Res. 5 (2011) 119-125.
7. N. Meliani, M. El Amine Dib, H. Allali and B. Tabti, Hypoglycaemic effect of Berberis vulgaris L. in normal and streptozotocin-induced diabetic rats, Asian Pac. J. Trop. Biomed. 1 ( 2011) 4 68-471; https://doi.org/10.1016/S2221-1691(11)60102-0
8. S. O. Oyedemi, G. Bradley and A. J. Afolayan, Ethno-botanical survey of medicinal plants used for the management of diabetes mellitus in the Nkonkobe municipality of South Africa, J. Med. Plants Res. 3 (2009) 1040-1044.
9. V. D. P. Nair and I. Kanfer, A capillary zone electrophoresis method for the quantitative determination of hypoxoside in commercial formulations of African potato (Hypoxis hemerocallidea), Phytochem. Anal. 18 (2007) 475-483; https://doi.org/10.1002/pca.1003
10. S. E. Drewes, E. Elliot, F. Khan, J. T. B. Dhlamini and M. S. S. Gcumisa, Hypoxis hemerocallidea -not merely a cure for benign prostate hyperplasia, J. Ethnopharmacol. 119 (2008) 593-598; https:// doi.org/10.1016/j.jep.2008.05.027
11. J. A. O. Ojewole, Anti-nociceptive, anti-inflammatory and anti-diabetic properties of Hypoxis hermerocallidea Fisch. & C.A. Mey (Hypoxidaceae) corm [‘African Potato’] aqueous extract in mice and rats, J. Ethnopharmacol. 103 (2006) 126-134; https://doi.org/10.1016/j.jep.2005.07.012
12. A. Vetere, A. Choudhary, S. M. Burns and B. K. Wagner, Targeting the pancreatic β-cell to treat diabetes, Nat. Rev. 13 (2014) 278-289; https://doi.org/10.1038/nrd4231
13. M. Feoktistova, P. Geserick and M. Leverkus, Crystal violet assay for determining the viability of cultured cells, Cold Spring Harb. Protoc. 2016; https://doi.org/ 1101/pdb.prot 087379
14. M. S. Deutschlander, M. Van de Venter, S. Roux, J. Louw and N. Lall, Hypoglycemic activity of four plant extracts traditionally used in South Africa in diabetes, J. Ethnopharmacol. 124 (2009) 619-624; https://doi.org/ 10.1016/j.jep.2009.04.052
15. J. L. Ramirez-Zacarias, F. Castro-Mufiozledo and W. Kuri-Harcuch, Quantitation of adipose conversion and triglycerides by staining intracytoplasmic lipids with oil red O, Histochemistry 97 (1997) 493-497.
16. L. G. Ranilla, Y. I. Kwon, E. Apostolidis and K. Shetty, Phenolic compounds, antioxidant activity and in vitro inhibitory potential against key enzymes relevant for hyperglycemia and hypertension of commonly used medicinal plants, herbs and spices in Latin America, Bioresour. Technol. 101 (2010) 4676-4689; https://doi.org/ 10.1016/j.biortech.2010.01.093
17. M. Al-Masri, M. K. Mohammad and M. O. Tahaa, Inhibition of dipeptidyl peptidase IV (DPP IV) is one of the mechanisms explaining the hypoglycemic effect of berberine, J. Enzyme Inhib. Med. Chem. 24 (2009) 1061-1066; https://doi.org/10.1080/14756360802610761
18. S. Schmidt, M. Jakab, S. Jav, D. Streif, A. Pitchmann, M. Zehl, S. Purevsuren, S. Glasl and M. Ritter, Extracts from Leonurus sibiricus L. increase insulin secretion and proliferation of rat INS-1E insulinoma cells, J. Ethnopharmacol. 150 (2013) 85-94; https://doi.org/10.1016/j.jep.2013.08.013
19. D. Liu, W. Zhen, Z. Yang, J. D. Carter, H. Si and K. A. Reynolds, Genistein acutely stimulates insulin secretion in pancreatic β cells through a cAMP-dependent protein kinase pathway, Diabetes 55 (2006) 1043-1050.
20. T. Lapidot, M. D. Walker and J. Kanner, Antioxidant and pro-oxidant effects of phenolics on pancreatic β-cells in vitro, J. Agric. Food Chem. 50 (2002) 7220-7225; https://doi.org/10.1021/jf020615a
21. M. Pinent, A. Castell, I. Baiges, G. Montagut, L. Arola and A. Ardevol, Bioactivity of flavonoids on insulin-secreting cells, Comp. Rev. Food Sci. Food Safety 7 (2008) 299-308; https://doi.org/10.1111/j. 1541-4337.2008.00048.x
22. E. M. Van Dam, R. Govers and D. E. James, Activation is required at a late stage of insulin-induced GLUT-4 translocation to the plasma membrane, Mol. Endocrinol. 19 (2005) 1067-1077; https://doi.org/10.1210/me.2004-0413
23. I. M. Mahomed and J. A. Ojewole, Hypoglycemic effect of Hypoxis hemerocallidea corm (African potato) aqueous extract in rats, Methods Find. Exp. Clin. Pharmacol. 25 (2003) 617-623; https://doi.org/10.1358/mf.2003.25.8.778082
24. S. Oyedemi, T. Koekemoer, G. Bradley, M. Van de Venter and A. Afolayan, In vitro anti-hyperglycemia properties of the aqueous stem bark extract from Strychnos henningsii (Gilg), Int. J. Diabetes Dev. C. 33 (2013) 120-127; https://doi.org/10.1007/s13410-013-0120-8
25. V. Rizzati, F. Boschi, M. Pedrotti, E. Zoico, A. Sharbati and M. Zamboni, Lipid droplets characterization in adipocyte differentiated 3T3-L1 cells: size and optical density distribution, Eur. J. Histochem. 57 (2013) 159-162; https://doi.org/10.4081/ejh.2013.e24
26. S.-J. Kim and S-Y. Choung, Inhibitory effects of Aster spathulifolius extract on adipogenesis and lipid accumulation in 3T3-L1 pre-adipocytes, J. Pharm. Pharmacol. 68 (2016) 107-118; https://doi.org/10.1111/jphp.12485
27. M. Lonn, K. Mehlig, C. Bengtsson and L. Lissner, Adipocyte size predicts incidence of type 2 diabetes in women, FASEB J. 24 (2010) 326-331; https://doi.org/10.1096/fj.09-133058
28. A. J. Alonso-Castro and L. A. Salazar-Olivo, The anti-diabetic properties of Gazuma ulmifolia Lam. are mediated by the stimulation of glucose uptake in normal and diabetic adipocytes without inducing adipogenesis, J. Ethnopharmacol. 118 (2008) 252-256; https://doi.org/10.1016/j.jep.2008.04.007
29. E. D. Abel, O. Peroni, J. A. Kim, Y. B. Kim, O. Boss, E. Hadro, T. Minnemann, G. I. Shulman and B. B. Kahn, Adipose-selective targeting of the GLUT 4 gene impairs insulin action in muscle and liver, Nature 409 (2001) 729-733; https://doi.org/10.1038/35055575
30. N. Fabre, I. Rustan, E. de Hoffmann and J. Quetin-Leclercq, Determination of flavone, flavonol and flavanone aglycones by negative ion liquid chromatography electrospray ion trap mass spectrometry. J. Am. Soc. Mass Spectrom. 12 (2001) 707-715; https://doi.org/10.1016/S1044-0305(01)00226-4
31. L. A. Abdulkhaleg, M. A. Assi, M. H. M Noor, R. Abdullah, M. Z. Saad and Y. H. Taufig-Yap, Therapeutic uses of epicatechin in diabetes and cancer, Vet World 10 (2017) 869-872; https://doi.org/10.14202/vetworld.2017.869-872
32. A. Arya, M. M. Al-Obaidi, N. Shahid, M. I. Bin Noordin, C. Y. Looi, W. F. Wong, S. L. Khaing and M. R. Mustafa, Synergistic effect of quercetin and quinic acid by alleviating structural degeneration in the liver, kidney and pancreas tissues of STZ-induced diabetic rats: a mechanistic study, Food Chem. Toxicol. 71 (2014) 183-196; https://doi.org/10.1016/j.fct.2014.06.010
33. C. Bucolo, K. W. Ward, E. Mazzon, S. Cuzzocrea and F. Drago, Protective effects of a coumarin derivative in diabetic rats, Invest. Ophthalmol. Vis. Sci. 50 (2009) 3846-3852; https://doi.org/10.1167/iovs.08-3328