Skip to main navigation menu Skip to main content Skip to site footer
Plant Science Today (PST)

Research Articles

Vol. 12 No. 4 (2025)

The acute toxicity, antioxidant and antihyperlipidemic activity of flavonoid glycosides from Ruta montana in female rats with hyperlipidemia induced by Triton WR-1339

DOI
https://doi.org/10.14719/pst.7863
Submitted
21 February 2025
Published
20-10-2025 — Updated on 30-10-2025
Versions

Abstract

This work aimed to evaluate the antihyperlipidemic activity of the aerial part of Ruta montana flavonoid- glycosides enriched extract (RMFEE) in Triton WR1339-induced hyperlipidemia in female rats, along with its antioxidant properties and acute toxicity. Female Wistar rats with Triton WR-1339-induced hyperlipidemia were used to assess RMFEE's antihyperlipidemic effects. The DPPH assay was used to determine antioxidant activity and acute toxicity was assessed via a single oral gavage of RMFEE at 600 and 2000 mg/kg body weight, following OECD 423 guidelines. Pretreatment with RMFEE at 150 and 400 mg/kg significantly reduced elevations in plasma levels of total cholesterol, triglycerides and non-HDL-C, while also significantly decreasing the atherogenic TG/HDL-C ratio in the hyperlipidemic rats. RMFEE also exhibited notable antioxidant activity in the DPPH assay. No mortality or signs of toxicity were observed within two weeks following a single oral administration of RMFEE at either 600 or 2000 mg/kg. Oral administration of RMFEE (150 and 400 mg/kg) prior to induction of hyperlipidemia by Triton WR-1339 demonstrated antihyperlipidemic activity in female rats. Specifically, the 400 mg/kg dose significantly prevented the increase in the TG/HDL ratio caused by Triton WR-1339. RMFEE also showed antioxidant activity with IC50=88.27 ± 3.12 µg/mL. The acute toxicity of the oral dose for RMFEE indicates very low toxicity, with an LD50 exceeding 2000 mg/kg.  

References

  1. 1. Ochani PC, D’Mello P. Antioxidant and antihyperlipidemic activity of Hibiscus sabdariffa Linn. leaves and calyces extracts in rats. Indian J Exp Biol. 2009;47(4):276-82.
  2. 2. Cicero AF, Colletti A. Combinations of phytomedicines with different lipid lowering activity for dyslipidemia management: the available clinical data. Phytomedicine. 2016;23(11):1113-8. https://doi.org/10.1016/j.phymed.2015.10.011
  3. 3. Sharma K, Kumar K, Mishra N. Nanoparticulate carrier system: A novel treatment approach for hyperlipidemia. Drug Deliv. 2016;23:684-99. https://doi.org/10.3109/10717544.2014.920937
  4. 4. Palabiyik E, Sulumer AN, Uguz H, Avci B, Askin S, Askin H. Walnut fruit diaphragm ethanol extract ameliorates damage due to Triton WR-1339-induced hyperlipidemia in rats. Eur J Lipid Sci Technol. 2024;126(1):2300105. https://doi.org/10.1002/ejlt.202300105
  5. 5. Duraipandiyan V, Al-Dhabi NA, Irudayaraj SS, Sunil C. Hypolipidemic activity of friedelin isolated from Azima tetracantha in hyperlipidemic rats. Rev Bras Farmacogn. 2016;26(1):89-93. https://doi.org/10.1016/j.bjp.2015.07.025
  6. 6. Hmidani A, Bourkhis B, Khouya T, Harnafi H, Filali-Zegzouti Y, Alem C. Effect of Phoenix dactylifera seeds extract in Triton WR-1339 and high fat diet induced hyperlipidaemia in rats: a comparison with simvastatin. J Ethnopharmacol. 2020;259:112961. https://doi.org/10.1016/j.jep.2020.112961
  7. 7. Kaliora AC, Dedoussis GVZ, Schmidt H. Dietary antioxidants in preventing atherogenesis. Atherosclerosis. 2006;187(1):1-17. https://doi.org/10.1016/j.atherosclerosis.2005.11.001
  8. 8. Rony KA, Ajith TA, Nima N, Janardhanan KK. Hypolipidemic activity of Phellinus rimosus against Triton WR-1339 and high cholesterol diet induced hyperlipidemic rats. Environ Toxicol Pharmacol. 2014;37(2):482-92. https://doi.org/10.1016/j.etap.2014.01.004
  9. 9. Yang X, Yang L, Zheng H. Hypolipidemic and antioxidant effects of mulberry (Morus alba L.) fruit in hyperlipidaemia rats. Food Chem Toxicol. 2010;48(8-9):2374-9. https://doi.org/10.1016/j.fct.2010.05.074
  10. 10. Wanga Q, Jiang C, Fang S, Wang J, Ji Y, Shang X, et al. Antihyperglycemic, antihyperlipidemic and antioxidant effects of ethanol and aqueous extracts of Cyclocarya paliurus leaves in type 2 diabetic rats. J Ethnopharmacol. 2013;150(3):1119-27. https://doi.org/10.1016/j.jep.2013.10.040
  11. 11. Adigun NS, Oladiji AT, Ajiboye TO. Antioxidant and anti-hyperlipidemic activity of hydroethanolic seed extract of Aframomum melegueta K. Schum in Triton X-100 induced hyperlipidemic rats. S Afr J Bot. 2016;105:324-32. https://doi.org/10.1016/j.sajb.2016.03.015
  12. 12. Wangb X, Li W, Xiao L, Liu C, Qi H, Zhang Z. In vivo antihyperlipidemic and antioxidant activity of porphyran in hyperlipidemic mice. Carbohydr Polym. 2017;174:417-20. https://doi.org/10.1016/j.carbpol.2017.06.040
  13. 13. Agbo MO, Uzor PF, Nneji UNA, Odurukwe CUE, Ogbatue UB, Mbaoji EC. Antioxidant, total phenolic and flavonoid content of selected Nigerian medicinal plants. Dhaka Univ J Pharm Sci. 2015;14(1):35-41. https://doi.org/10.3329/dujps.v14i1.23733
  14. 14. Merghem M, Dahamna S. In-vitro antioxidant activity and total phenolic content of Ruta montana L. J Drug Deliv Ther. 2020;10(2):69-75. https://doi.org/10.22270/jddt.v10i2.3919
  15. 15. Zeichen de Sa R, Rey A, Arganaraz E, Bindstein E. Perinatal toxicology of Ruta chalepensis (Rutaceae) in mice. J Ethnopharmacol. 2000;69:93. https://doi.org/10.1016/S0378-8741(98)00232-3
  16. 16. Raghav SK, Gupta B, Agrawal C, Goswami K, Das HR. Anti-inflammatory effect of Ruta graveolens L. in murine macrophage cells. J Ethnopharmacol. 2006;108:104-34. https://doi.org/10.1016/j.jep.2005.09.008
  17. 17. Farid O, Hebi M, Ajebli M, El Haidani A, Eddouks M. Antidiabetic effect of Ruta montana L. in streptozotocin-induced diabetic rats. J Basic Clin Physiol Pharmacol. 2017;28(3):275-82. https://doi.org/10.1515/jbcpp-2016-0030
  18. 18. Eddouks M, Maghrani M, Lemhadri A, Ouahidi ML, Jouad H. Ethnopharmacological survey of medicinal plants used for the treatment of diabetes mellitus, hypertension and cardiac diseases in the south-east region of Morocco (Tafilalet). J Ethnopharmacol. 2002;82(2-3):97-103. https://doi.org/10.1016/S0378-8741(02)00164-2
  19. 19. El-Ouady F, Eddouks M. Ruta montana evokes antihypertensive activity through an increase of prostaglandins release in L-NAME-induced hypertensive rats. Endocr Metab Immune Disord Drug Targets. 2021;21(2):305-14. https://doi.org/10.2174/1871530320666200628025430
  20. 20. Bouadid I, Amssayef A, Eddouks M. Study of the antihypertensive effect of Laurus nobilis in rats. Cardiovasc Hematol Agents Med Chem. 2023;21(1):42-54. https://doi.org/10.2174/1871525720666220512154041
  21. 21. Ajebli M, Eddouks M. Flavonoid-enriched extract from desert plant Warionia saharae improves glucose and cholesterol levels in diabetic rats. Cardiovasc Hematol Agents Med Chem. 2019;17:28-39. https://doi.org/10.2174/1871525717666190121143934
  22. 22. Evans WC. Trease and Evans pharmacognosy. 14th ed. Singapore: Harcourt Brace and Company Asia Pvt Ltd; 1997. p. 12-68.
  23. 23. Kim DO, Jeong SW, Lee CY. Antioxidant capacity of phenolic phytochemicals from various cultivars of plums. Food Chem. 2003;81(3):321-6. https://doi.org/10.1016/S0308-8146(02)00423-5
  24. 24. Rocha T, Speranc A, Nogueira CW, Zeni G. Hypolipidaemic activity of orally administered diphenyl diselenide in Triton WR-1339-induced hyperlipidaemia in mice. J Pharm Pharmacol. 2009;61(12):1673-9. https://doi.org/10.1211/jpp.61.12.0013
  25. 25. Borrayo G, Basurto L, González-Escudero E, Diaz A, Vázquez A, Sánchez L, et al. TG/HDL-C ratio as cardio-metabolic biomarker even in normal weight women. Acta Endocrinol. 2018;14(2):261. https://doi.org/10.4183/aeb.2018.261
  26. 26. Organization for Economic Cooperation and Development (OECD). Guideline 423: acute oral toxicity–acute toxic class method. 2001.
  27. 27. Ali R, Ali R, Jaimini A, Nishad DK, Mittal G, Chaurasia OP, et al. Acute and sub-acute toxicity and efficacy studies of Hippophae rhamnoides based herbal antioxidant supplement. Indian J Pharmacol. 2012;44:504-8. https://doi.org/10.4103/0253-7613.99329
  28. 28. Lobo VC, Phatak A, Chandra N. Acute toxicity studies of some Indian medicinal plants. Pharmacognosy Journal. 2012;2(8):207-10. https://doi.org/10.1016/S0975-3575(10)80094-X
  29. 29. Louli V, Ragoussis N, Magoulas K. Recovery of phenolic antioxidants from wine industry by-products. Bioresource technology. 2004;92(2):201-8. https://doi.org/10.1016/j.biortech.2003.06.002
  30. 30. Farid O, Eddouks M. Evaluation of the anti-hypercholesterolemic and antioxidant activity of Mentha pulegium aqueous extract in normal and streptozotocin-induced diabetic rats. The Natural Products Journal. 2019;9:1-8.
  31. 31. Zarzecki MS, Araujo SM, Bortolotto VC, de Paula MT, Jesse CR, Prigol M. Hypolipidemic action of chrysin on Triton WR-1339-induced hyperlipidemia in female C57BL/6 mice. Toxicology Reports. 2014;1:200-8. https://doi.org/10.1016/j.toxrep.2014.02.003
  32. 32. Cífková R, Krajčoviechová A. Dyslipidemia and cardiovascular disease in women. Curr Cardiol Rep. 2015;17:52. https://doi.org/10.1007/s11886-015-0609-5
  33. 33. Rajai N, Welty FK. Dyslipidemia in women: etiology and management. Stroke Revisited: Dyslipidemia in Stroke. 2021:173-202. https://doi.org/10.1007/978-981-16-3923-4_16
  34. 34. Bisht A, Madhav NS, Upadhyaya K. A huge updated review on dyslipidemia etiology with various approaches for its treatment. Pharmacophore. 2012;3(5):244-64.
  35. 35. Levine S, Saltzman A. A procedure for inducing sustained hyperlipemia in rats by administration of a surfactant. Journal of Pharmacological and Toxicological Methods. 2007;55:224-6. https://doi.org/10.1016/j.vascn.2006.05.009
  36. 36. Harnafi M, Bekkouch O, Touiss I, Mokhtari I, Milenkovic D, Harnafi H, et al. Phenolic-rich extract from almond (Prunus dulcis) hulls improves lipid metabolism in Triton WR-1339 and high-fat diet-induced hyperlipidemic mice and prevents lipoprotein oxidation: a comparison with fenofibrate and butylated hydroxyanisole. Preventive nutrition and food science. 2020;25(3):254. https://doi.org/10.3746/pnf.2020.25.3.254
  37. 37. Chan PT, Fong WP, Cheung YL, Huang Y, Ho WK, Chen ZY. Jasmine green tea epicatechins are hypolipidemic in hamsters (Mesocricetus auratus) fed a high fat diet. J Nutr. 1999;129(6):1094-101. https://doi.org/10.1093/jn/129.6.1094
  38. 38. Anila L, Vijayalakshmi NR. Flavonoids from Emblica officinalis and Mangifera indica effectiveness for dyslipidemia. J Ethnopharmacol. 2002;79(1):81-7. https://doi.org/10.1016/S0378-8741(01)00361-0
  39. 39. Baharvand-Ahmadi B, Rafieian-Kopaei M, Zarshenas MM, Bahmani M, Bahmani M. Contrasting actions of various antioxidants on hyperlipidemia: a review and new concepts. Der Pharmacia Lettre. 2015;7(12):81-8.
  40. 40. Chung TH, Shim JY, Kwon YJ, Lee YJ. High triglyceride to high-density lipoprotein cholesterol ratio and arterial stiffness in postmenopausal Korean women. The Journal of Clinical Hypertension. 2019;21(3):399-404. https://doi.org/10.1111/jch.13484
  41. 41. Kampmann U, Knorr S, Fuglsang J, Ovesen P. Determinants of maternal insulin resistance during pregnancy: an updated overview. Journal of diabetes research. 2019;2019:5320156. https://doi.org/10.1155/2019/5320156
  42. 42. Baneu P, Văcărescu C, Drăgan SR, Cirin L, Lazăr-Höcher AI, Cozgarea A, et al. The triglyceride/HDL ratio as a surrogate biomarker for insulin resistance. Biomedicines. 2024;12:1493. https://doi.org/10.3390/biomedicines12071493
  43. 43. Haidara M, Mikhailidis DP, Yassin HZ, Dobutovic B, Smiljanic KT, Soskic S, et al. Evaluation of the possible contribution of antioxidants administration in metabolic syndrome. Curr Pharm Des. 2011;17(33):3699-712. https://doi.org/10.2174/138161211798220882
  44. 44. Rajani GP, Ashok P. In vitro antioxidant and antihyperlipidemic activities of Bauhinia variegata Linn. Indian journal of pharmacology. 2009;41(5):227-32. https://doi.org/10.4103/0253-7613.58513
  45. 45. Ibrahim MB, Sowemimo AA, Sofidiya MO, Badmos KB, Fageyinbo MS, Abdulkareem FB, et al. Sub-acute and chronic toxicity profiles of Markhamia tomentosa ethanolic leaf extract in rats. J Ethnopharmacol. 2016;193:68-75. https://doi.org/10.1016/j.jep.2016.07.036
  46. 46. Ugwah-Oguejiofor CJ, Okoli CO, Ugwah MO, Umaru ML, Ogbulie CS, Mshelia HE, et al. Acute and sub-acute toxicity of aqueous extract of aerial parts of Caralluma dalzielii NE Brown in mice and rats. Heliyon. 2019;5(1). https://doi.org/10.1016/j.heliyon.2019.e01179

Downloads

Download data is not yet available.