Planta Med 2019; 85(04): 274-281
DOI: 10.1055/a-0762-0885
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

PPARα and γ Activation Effects of New Nor-triterpenoidal Saponins from the Aerial Parts of Anabasis articulata

Riham Salah El Dine
1   Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo, Egypt
,
Hossam M. Abdallah
1   Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo, Egypt
2   Department of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia
,
Zeinab A. Kandil
1   Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo, Egypt
,
Ahmed A. Zaki
3   National Center for Natural Products Research, School of Pharmacy, University of Mississippi, Oxford, Mississippi, USA
4   Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt
,
Shabana I. Khan
3   National Center for Natural Products Research, School of Pharmacy, University of Mississippi, Oxford, Mississippi, USA
,
Ikhlas A. Khan
3   National Center for Natural Products Research, School of Pharmacy, University of Mississippi, Oxford, Mississippi, USA
› Author Affiliations
Further Information

Publication History

received 01 June 2018
revised 05 October 2018

accepted 14 October 2018

Publication Date:
25 October 2018 (online)

Abstract

Anabasis articulata, traditionally used to treat diabetes, is rich in saponin content. This study was performed to investigate the agonistic effect of its saponins on peroxisome proliferator-activated receptor-α and peroxisome proliferator-activated receptor-γ in human hepatoma (HepG2) cells to explore the possibility of the involvement of these nuclear receptors in the mechanism of the antidiabetic effect of the plant. Chemical investigation of the n-butanol fraction resulted in the isolation of three new and one known 30-noroleanane triterpenoid saponins. The structures of the new compounds were elucidated as 3β-hydroxy,23-aldehyde-30-norolean-12,20(29)-dien-28-oic acid-28-O-β-D-glucopyranosyl ester (1), 3β-O-D-galactopyranosyl-23-aldehyde-30-norolean-12,20(29)-dien-28-oic acid-28-O-β-D-glucopyranosyl ester (2), and 3β-O-D-xylopyranosyl-30-norolean-12,20(29)-dien-28-oic acid 28-O-β-D-glucopyranosyl ester (3), while the known 30-nortriterpenoidal saponin was identified as boussingoside E (4). Although, the isolated saponins (1 – 4) did not show > 1.5-fold activation of peroxisome proliferator-activated receptor-γ, but two of them (1 and 3) activated peroxisome proliferator-activated receptor-α to the higher extents of 2.25- and 1.86-fold, respectively. These results suggest that the reported antidiabetic action of the isolated saponins may not solely involve the activation of peroxisome proliferator-activated receptor-γ. However, the agonistic activity of the n-butanol fraction of A. articulata (1.71-fold induction) and two of its saponins (1 and 3) towards peroxisome proliferator-activated receptor-α may be beneficial in the cardiovascular condition that is closely associated with diabetes and other metabolic disorders.

Supporting Information

 
  • References

  • 1 Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet 2005; 365: 1415-1428
  • 2 Nisoli E, Clementi E, Carruba MO, Moncada S. Defective mitochondrial biogenesis: a hallmark of the high cardiovascular risk in the metabolic syndrome?. Circ Res 2007; 100: 795-806
  • 3 Laudet V, Hänni C, Coll J, Catzeflis F, Stéhelin D. Evolution of the nuclear receptor gene superfamily. EMBO J 1992; 11: 1003-1013
  • 4 Dreyer C, Krey G, Keller H, Givel F, Helftenbein G, Wahli W. Control of the peroxisomal β-oxidation pathway by a novel family of nuclear hormone receptors. Cell 1992; 68: 879-887
  • 5 Evans RM, Barish GD, Wang YX. PPARs and the complex journey to obesity. Nat Med 2004; 10: 355-361
  • 6 Auboeuf D, Rieusset J, Fajas L, Vallier P, Frering V, Riou JP, Staels B, Auwerx J, Laville M, Vidal H. Tissue distribution and quantification of the expression of mRNAs of peroxisome proliferator-activated receptors and liver X receptor-α in humans: no alteration in adipose tissue of obese and NIDDM patients. Diabetes 1997; 46: 1319-1327
  • 7 Shen P, Liu MH, Ng TY, Chan YH, Yong E. Differential effects of isoflavones, from Astragalus membranaceus and Pueraria thomsonii, on the activation of PPARα, PPARγ, and adipocyte differentiation in vitro . J Nutr 2006; 136: 899-905
  • 8 Vidal-Puig AJ, Considine RV, Jimenez-Liñan M, Werman A, Pories WJ, Caro JF, Flier JS. Peroxisome proliferator-activated receptor gene expression in human tissues. Effects of obesity, weight loss, and regulation by insulin and glucocorticoids. J Clin Invest 1997; 99: 2416-2422
  • 9 Medina-Gomez G, Gray SL, Yetukuri L, Shimomura K, Virtue S, Campbell M, Curtis RK, Jimenez-Linan M, Blount M, Yeo GS. PPAR gamma 2 prevents lipotoxicity by controlling adipose tissue expandability and peripheral lipid metabolism. PLoS Genet 2007; 3: e64
  • 10 Indulekha K, Unnikrishnan R, Mohan V. Extending current Definitions of the metabolic Syndrome. In: Kurian M, Wolfe B, Ikramuddin S. eds. Metabolic Syndrome and Diabetes. New York: Springer; 2016: 19-30
  • 11 Roman-Ramos R, Flores-Saenz JL, Alarcon-Aguilar FJ. Anti-hyperglycemic effect of some edible plants. J Ethnopharmacol 1995; 48: 25-32
  • 12 Yang MH, Avula B, Smillie T, Khan IA, Khan SI. Screening of medicinal plants for PPARα and PPARγ activation and evaluation of their effects on glucose uptake and 3T3-L1 adipogenesis. Planta Med 2013; 79: 1084-1095
  • 13 Christensen KB, Minet A, Svenstrup H, Grevsen K, Zhang H, Schrader E, Rimbach G, Wein S, Wolffram S, Kristiansen K. Identification of plant extracts with potential antidiabetic properties: effect on human peroxisome proliferator-activated receptor (PPAR), adipocyte differentiation and insulin-stimulated glucose uptake. Phytother Res 2009; 23: 1316-1325
  • 14 Marles RJ, Farnsworth NR. Antidiabetic plants and their active constituents. Phytomedicine 1995; 2: 137-189
  • 15 Kambouche N, Merah B, Derdour A, Bellahouel S, Bouayed J, Dicko A, Younos C, Soulimani R. Hypoglycemic and antihyperglycemic effects of Anabasis articulata (Forssk) Moq (Chenopodiaceae), an Algerian medicinal plant. Afr J Biotechnol 2009; 8: 5589-5594
  • 16 Metwally NS, Mohamed AM, Elsharabasy FS. Chemical constituents of the Egyptian Plant Anabasis articulata (Forssk) Moq and its antidiabetic effects on rats with streptozotocin-induced diabetic hepatopathy. J App Pharm Sci 2012; 2: 54-65
  • 17 Abdallah HM, Abdel-Naim AB, Ashour OM, Shehata IA, Abdel-Sattar EA. Anti-inflammatory activity of selected plants from Saudi Arabia. Z Naturforsch C 2014; 69: 1-9
  • 18 Kambouche N, Merah B, Derdour A, Bellahouel S, Benziane M, Younos C, Firkioui M, Bedouhene S, Soulimani R. Étude de lʼeffet antidiabétique des saponines extraites d Anabasis articulata (Forssk) Moq, plante utilisée traditionnellement en Algérie. Phytothérapie 2009; 7: 197-201
  • 19 Abdallah HM, El-Bassossy H, Mohamed GA, El-Halawany AM, Alshali KZ, Banjar ZM. Phenolics from Garcinia mangostana inhibit advanced glycation endproducts formation: effect on Amadori products, cross-linked structures and protein thiols. Molecules 2016; 21: 251
  • 20 Abdallah HM, El-Bassossy HM, Mohamed GA, El-Halawany AM, Alshali KZ, Banjar ZM. Phenolics from Garcinia mangostana alleviate exaggerated vasoconstriction in metabolic syndrome through direct vasodilatation and nitric oxide generation. BMC Complement Altern Med 2016; 16: 359
  • 21 Abdallah HM, El-Bassossy HM, Mohamed GA, El-Halawany AM, Alshali KZ, Banjar ZM. Mangostanaxanthones III and IV: advanced glycation end-product inhibitors from the pericarp of Garcinia mangostana . J Nat Med 2017; 71: 216-226
  • 22 Espada A, Riguera R, Jiménez C. Boussingoside E, a new triterpenoid saponin from the tubers of Boussingaultia baselloides . J Nat Prod 1997; 60: 17-19
  • 23 Wang QZ, Liu XF, Shan Y, Guan FQ, Chen Y, Wang XY, Wang M, Feng X. Two new nortriterpenoid saponins from Salicornia bigelovii Torr. and their cytotoxic activity. Fitoterapia 2012; 83: 742-749
  • 24 Abdallah HM, Al-Abd AM, Asaad GF, Abdel-Naim AB, El-Halawany AM. Isolation of antiosteoporotic compounds from seeds of Sophora japonica . PLoS One 2014; 9: e98559
  • 25 Yoshikawa M, Murakami T, Kadoya M, Yamahara J, Matsuda H. Medicial foodstuffs. XV. Sugar beet. (2): Structures of betavulgarosides V, VI, VII, VIII, IX and X from the roots and leaves of sugar beet (Beta vulgaris L., Chenopodiaceae). Chem Pharm Bull 1998; 46: 1758-1763
  • 26 Jitsuno M, Mimaki Y. Triterpene glycosides from the aerial parts of Larrea tridentata . Phytochemistry 2010; 71: 2157-2167
  • 27 Cabrita L, Frøystein NÅ, Andersen ØM. Anthocyanin trisaccharides in blue berries of Vaccinium padifolium . Food Chem 2000; 69: 33-36
  • 28 Hamed AI, Springuel I, El-Emary NA, Mitome H, Miyaoka H, Yamada Y. Triterpenoidal saponin glycosides from Glinus lotoides var. dictamnoides . Phytochemistry 1996; 43: 183-188
  • 29 Zehring J, Reim V, Schröter D, Neugart S, Schreiner M, Rohn S, Maul R. Identification of novel saponins in vegetable amaranth and characterization of their hemolytic activity. Food Res Int 2015; 78: 361-368
  • 30 Wang J, Xu QL, Zheng MF, Ren H, Lei T, Wu P, Zhou ZY, Wei XY, Tan JW. Bioactive 30-noroleanane triterpenes from the pericarps of Akebia trifoliata . Molecules 2014; 19: 4301-4312
  • 31 Shan Y, Li H, Guan F, Chen Y, Yin M, Wang M, Feng X, Wang Q. Triterpenoids from the Herbs of Salicornia bigelovii . Molecules 2015; 20: 20334-20340
  • 32 Espada A, Rodriguez J, Villaverde MC, Riguera R. Hypoglucaemic triterpenoid saponins from Boussingaultia baselloides . Can J Chem 1990; 68: 2039-2044
  • 33 Burdi DK, Qureshi S, Ghanghro AB. An overview of available hypoglycemic triterpenoids and saponins to cure diabetes mellitus. ALS 2014; 1: 119-128
  • 34 Quang TH, Ngan NTT, Van Minh C, Van Kiem P, Thao NP, Tai BH, Nhiem NX, Song SB, Kim YH. Effect of triterpenes and triterpene saponins from the stem bark of Kalopanax pictus on the transactivational activities of three PPAR subtypes. Carbohydr Res 2011; 346: 2567-2575
  • 35 Wang L, Waltenberger B, Pferschy-Wenzig EM, Blunder M, Liu X, Malainer C, Blazevic T, Schwaiger S, Rollinger JM, Heiss EH. Natural product agonists of peroxisome proliferator-activated receptor gamma (PPARγ): a review. Biochem Pharmacol 2014; 92: 73-89
  • 36 Yang MH, Vasquez Y, Ali Z, Khan IA, Khan SI. Constituents from Terminalia species increase PPARα and PPARγ levels and stimulate glucose uptake without enhancing adipocyte differentiation. J Ethnopharmacol 2013; 149: 490-498