Generic placeholder image

Recent Patents on Nanotechnology

Editor-in-Chief

ISSN (Print): 1872-2105
ISSN (Online): 2212-4020

Research Article

Preclinical Safety Assessment of Lepidium sativum L. Seed Extract and its Nanoparticles via Acute and Subacute Oral Administration

Author(s): Asad Ahmad, Anuradha Mishra*, Rabia Nabi and Iffat Zareen Ahmad

Volume 18, Issue 3, 2024

Published on: 06 June, 2023

Page: [350 - 360] Pages: 11

DOI: 10.2174/1872210517666230417103129

Price: $65

Abstract

Background: Lepidium sativum (LS) seed extract has various pharmacological properties, such as antioxidant, hepatoprotective, and anticancer activities. However, the translation of L. sativum seed extract to the clinical phase is still tedious due to its bioavailability and stability issues. This problem can be solved by encapsulating it in a nanodelivery system to improve its therapeutic potency.

Methods: In this study, we have determined and compared the in vivo toxicity of ethanolic extracts of L. sativum seeds (EELS) and solid lipid nanoparticles (SLNs). To conduct toxicity (acute and subacute toxicity) assessments, EELS and SLNs were orally administered to Swiss albino mice. Animal survival, body weight, the weight of vital organs in relation to body weight, haematological profile, biochemistry profile, and histopathological alterations were examined.

Results: Animals administered with 2000 mg/kg and 5000 mg/kg in an acute toxicity study exhibited no toxicological symptoms regarding behaviour, gross pathology, and body weight. As per a study on acute toxicity, the LD50 (lethal dose) for SLNs and EELS was over 400 mg/kg and over 5000 mg/kg, respectively. When animals were given SLNs (50 and 100 mg/kg, orally) and EELS (250, 500, and 1000 mg/kg, orally) for 28 days, subacute toxicity study did not exhibit any clinical changes. There were no differences in weight gain, haematological parameters, or biochemical parameters compared to the control groups (p > 0.05). The organs of the treated animals showed no abnormalities in the histological analysis (liver, heart, kidney, and spleen).

Conclusion: The result confirms ethanolic extracts of L. sativum seeds and their SLNs to not have harmful effects following acute and subacute administration to mice. For further studies, patents available on Lepidium may be referred for its preclinical and clinical applications.

Graphical Abstract

[1]
Tiwari PN, Kulmi GS. Performance of Chandrasur (Lepidium sativum) under different levels of nitrogen and phosphorus. J Medicinal Aromat Plants 2004; 26(3): 479-81.
[2]
Ahmad A, Tabassum H, Nabi R, Mishra A, Ahmad IZ. Solid lipid nanoparticles of Lepidium sativum L seed extract: Formulation, optimisation and in vitro cytotoxicity studies. Drug Res 2022; 72(5): 284-93.
[http://dx.doi.org/10.1055/a-1800-5956] [PMID: 35504297]
[3]
Ms JM, Vanmathi JS, Chairman K. Phytochemical analysis of Lepidium sativum using UV-VIS and GC-MS. Int J Adv Res 2018; 6(9): 813-25.
[http://dx.doi.org/10.21474/IJAR01/7738]
[4]
Raish M, Ahmad A, Alkharfy KM, et al. Hepatoprotective] activity of Lepidium sativum seeds against D-galactosamine/] lipopolysaccharide induced hepatotoxicity in animal model. BMC Complement Altern Med 2016; 16(1): 501.
[http://dx.doi.org/10.1186/s12906-016-1483-4] [PMID: 27912738]
[5]
Malar J, Chairman K, Singh ARJ, Vanmathi JS, Balasubramanian A, Vasanthi K. Antioxidative activity of different parts of the plant Lepidium sativum Linn. Biotechnol Rep 2014; 3: 95-8.
[http://dx.doi.org/10.1016/j.btre.2014.05.006] [PMID: 28435800]
[6]
Patel U, Kulkarni M, Undale V, Bhosale A. Evaluation of diuretic activity of aqueous and methanol extracts of Lepidium sativum garden cress (cruciferae) in rats. Trop J Pharm Res 2009; 8(3) [Internet].
[http://dx.doi.org/10.4314/tjpr.v8i3.44536]
[7]
Al-Sheddi ES, Farshori NN, Al-Oqail MM, Musarrat J, Al-Khedhairy AA, Siddiqui MA. Protective effect of Lepidium sativum seed extract against hydrogen peroxide-induced cytotoxicity and oxidative stress in human liver cells (HepG2). Pharm Biol 2016; 54(2): 314-21.
[http://dx.doi.org/10.3109/13880209.2015.1035795] [PMID: 25885937]
[8]
Saleem U, Amin S, Ahmad B, Azeem H, Anwar F, Mary S. Acute oral toxicity evaluation of aqueous ethanolic extract of Saccharum munja Roxb. roots in albino mice as per OECD 425 TG. Toxicol Rep 2017; 1(1): 580-5.
[9]
Organisation for economic co‐operation and development. Test No. 407: Repeated dose 28‐day oral toxicity study in rodents. 2008.
[10]
Kumarnsit E, Keawpradub N, Nuankaew W. Acute and long-term effects of alkaloid extract of Mitragyna speciosa on food and water intake and body weight in rats. Fitoterapia 2006; 77(5): 339-45.
[http://dx.doi.org/10.1016/j.fitote.2006.04.006] [PMID: 16781828]
[11]
Chen HHC, Yu C, Ueng TH, et al. Acute and subacute toxicity study of water-soluble polyalkylsulfonated C60 in rats. Toxicol Pathol 1998; 26(1): 143-51.
[http://dx.doi.org/10.1177/019262339802600117] [PMID: 9502397]
[12]
Olaniyan JM, Muhammad HL, Makun HA, Busari MB, Abdullah AS. Acute and sub-acute toxicity studies of aqueous and methanol extracts of Nelsonia campestris in rats. J Acute Dis 2016; 5(1): 62-70.
[http://dx.doi.org/10.1016/j.joad.2015.08.006]
[13]
Hariri AT, Moallem SA, Mahmoudi M, Memar B, Razavi BM, Hosseinzadeh H. Effect of Crocus sativus L. stigma (saffron) against subacute effect of diazinon: Histopathological, hematological, biochemical and genotoxicity evaluations in rats. J Pharmacopuncture 2018; 21(2): 61-9.
[http://dx.doi.org/10.3831/KPI.2018.21.007] [PMID: 30151305]
[14]
Sultan Alvi S, Ansari IA, Khan I, Iqbal J, Khan MS. Potential role of lycopene in targeting proprotein convertase subtilisin/kexin type-9 to combat hypercholesterolemia. Free Radic Biol Med 2017; 108: 394-403.
[http://dx.doi.org/10.1016/j.freeradbiomed.2017.04.012] [PMID: 28412198]
[15]
Alvi SS, Ansari IA, Ahmad MK, Iqbal J, Khan MS. Lycopene amends LPS induced oxidative stress and hypertriglyceridemia via modulating PCSK-9 expression and Apo-CIII mediated lipoprotein lipase activity. Biomed Pharmacother 2017; 96: 1082-93.
[http://dx.doi.org/10.1016/j.biopha.2017.11.116] [PMID: 29174038]
[16]
Nabi R, Alvi S, Alouffi S, et al. Amelioration of neuropilin-1 and RAGE/matrix metalloproteinase-2 pathway-induced renal injury in diabetic rats by rosuvastatin. Arch Biol Sci 2021; 73(2): 265-78.
[http://dx.doi.org/10.2298/ABS210316021N]
[17]
Ramadan MF, Oraby HF. Lepidium sativum seeds: therapeutic significance and health-promoting potential. Nuts and seeds in health and disease prevention. Cambridge: Academic Press 2020; pp. 273-89.
[http://dx.doi.org/10.1016/B978-0-12-818553-7.00020-6]
[18]
Abdulmalek S, Eldala A, Awad D, Balbaa M. Ameliorative effect of curcumin and zinc oxide nanoparticles on multiple mechanisms in obese rats with induced type 2 diabetes. Sci Rep 2021; 11(1): 20677.
[http://dx.doi.org/10.1038/s41598-021-00108-w] [PMID: 34667196]
[19]
Benrahou K, Mrabti HN, Assaggaf HM, et al. Acute and subacute toxicity studies of Erodium guttatum extracts by oral administration in rodents. Toxins 2022; 14(11): 735.
[http://dx.doi.org/10.3390/toxins14110735] [PMID: 36355985]
[20]
Al-Yahya MA, Mossa JS, Ageel AM, Rafatullah S. Pharmacological and safety evaluation studies on Lepidium sativum L., Seeds. Phytomedicine 1994; 1(2): 155-9.
[http://dx.doi.org/10.1016/S0944-7113(11)80035-8] [PMID: 23195890]
[21]
Datta PK, Diwakar BT, Viswanatha S, Murthy KN, Naidu KA. Original Report Safety evaluation studies on Garden cress (Lepidium sativum L.) seeds in Wistar rats. Int J Appl Res Nat Prod 2011; 4(1)
[22]
Yang M, Wu Z, Wang Y, et al. Acute and subacute toxicity evaluation of ethanol extract from aerial parts of Epigynum auritum in mice. Food Chem Toxicol 2019; 131(110534): 110534.
[http://dx.doi.org/10.1016/j.fct.2019.05.042] [PMID: 31150781]
[23]
Adam SEI. Effects of various levels of dietary Lepidium sativum L. seeds in rats. Am J Chin Med 1999; 27(03n04): 397-405.
[http://dx.doi.org/10.1142/S0192415X99000458] [PMID: 10592849]
[24]
Li X, Luo Y, Wang L, et al. Acute and subacute toxicity of ethanol extracts from Salvia przewalskii Maxim in rodents. J Ethnopharmacol 2010; 131(1): 110-5.
[http://dx.doi.org/10.1016/j.jep.2010.06.012] [PMID: 20561576]
[25]
Kamani M, Mhabadi JA, Atlasi MA, Seyedi F, Kamani E, Nikzad H. Protective effect of alcoholic extract of garden cress seeds on the histopathological changes of the ventral prostate in streptozotocin diabetic rats. Int J Morphol 2017; 35(3): 1178-84.
[http://dx.doi.org/10.4067/S0717-95022017000300057]
[26]
Burow M, Bergner A, Gershenzon J, Wittstock U. Glucosinolate hydrolysis in Lepidium sativum––identification of the thiocyanate-forming protein. Plant Mol Biol 2006; 63(1): 49-61.
[http://dx.doi.org/10.1007/s11103-006-9071-5] [PMID: 17139450]
[27]
Virtanen AI, Saarivirta M. The formation of benzyl thiocyanate in the seeds of Lepidium sativum. S Kemistilehti B 1962; 35: 102-4.
[28]
Munday R, Munday CM. Induction of phase II detoxification enzymes in rats by plant-derived isothiocyanates: Comparison of allyl isothiocyanate with sulforaphane and related compounds. J Agric Food Chem 2004; 52(7): 1867-71.
[http://dx.doi.org/10.1021/jf030549s] [PMID: 15053522]
[29]
Shah AH, Qureshi S, Tariq M, Ageel AM. Toxicity studies on six plants used in the traditional Arab system of medicine. Phytother Res 1989; 3(1): 25-9.
[http://dx.doi.org/10.1002/ptr.2650030107]
[30]
Zhang C, Li J, Xiao M, et al. Oral colon-targeted mucoadhesive micelles with enzyme-responsive controlled release of curcumin for ulcerative colitis therapy. Chin Chem Lett 2022; 33(11): 4924-9.
[http://dx.doi.org/10.1016/j.cclet.2022.03.110]
[31]
Chen H, Wang Q. Regulatory mechanisms of lipid biosynthesis in microalgae. Biol Rev Camb Philos Soc 2021; 96(5): 2373-91.
[http://dx.doi.org/10.1111/brv.12759] [PMID: 34101323]
[32]
Yau AA, Sani SK, Datta A. Potential of curcumin loaded nanoparticles in antimicrobial photodyanamic therapy. Int J Pharmacy Res Technol 2021; 11(2)
[33]
Neerati P, Palle S. Resveratrol nanoparticle pretreatment improved the oral bioavailability of bromocriptine: Involvement of liver and intestinal CYP3A enzyme inhibition. J Nat Sci Biol Med 2019; 10(2): 209.
[http://dx.doi.org/10.4103/jnsbm.JNSBM_126_19]
[34]
Avachat MK, Dhamne AG. Oral controlled release drug delivery system with husk powder from Lepidium sativum seeds. WO2002100438A1, 2003.
[35]
Avachat MK, Dhamne AG. Method of manufacturing husk from Lepidium sativum seeds. The patent cooperation treaty. WO2002102856A1, 2002.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy