Acute Oral Toxicity Studies and Evaluation of Central Analgesic Activity of Various extracts of Leaves of Rhizophora apiculata
Authors
-
Department of Pharmaceutical Chemistry, KL College of Pharmacy, Koneru Lakshmaiah Education Foundation, Vaddeswaram, Guntur - 522502, Andhra Pradesh ,IN
Annie Mande -
Department of Pharmaceutical Chemistry, KL College of Pharmacy, Koneru Lakshmaiah Education Foundation, Vaddeswaram, Guntur - 522502, Andhra Pradesh ,INNarender Malothu
-
Department of Pharmaceutical Chemistry, KL College of Pharmacy, Koneru Lakshmaiah Education Foundation, Vaddeswaram, Guntur - 522502, Andhra Pradesh ,INNagaraju Banadaru
-
Department of Pharmacology, Bapatla College of Pharmacy, S.N.P. Agraharam, Bapatla, Andhra Pradesh - 522101 ,INT. E. G. K. Murthy
DOI:
https://doi.org/10.18311/ti/2022/v29i2/29161Keywords:
Acute Oral Toxicity, Analgesic Activity, Histopathology, Tail Immersion Method, R. apiculataAbstract
The present study aimed to determine the acute toxicity and screening of central analgesic activity of various extracts of Rhizophora apiculata leaves. The animals (Mice) were divided into control (no drug) and extract-treated groups (n=5), which were treated with diethyl ether, ethyl alcohol, and aqueous extract of R. apiculata leaves in various doses for specific regulatory needs. The groups which were given the highest safe doses were observed for 14 days. Then, blood samples were collected from high dose treated live mice through the retro-orbital route and were analysed for haematological, biochemical, and histopathological study. Evaluation of central analgesic activity was carried out by using tail immersion and hot plate methods. No considerable alterations were observed in body weight and organ-to-body weight index with the administration of extracts. An increase in albumin, globulin, total protein content and high-density lipoproteins, white blood cells, mean corpuscular volume, and eosinophils were observed. And a decrease in low-density lipoproteins, very low-density lipoproteins, triglycerides, and red blood cells were observed. Lymphocyte and monocyte levels were also reduced. The results also showed that the ethyl alcohol and aqueous extracts have elevated the time taken to flick response in the tail immersion test, and reduced the number of jumps, paw lick responses in the hot plate method. It was concluded that the diethyl ether and ethanolic extracts were found to be safe, which falls under non-toxic chemicals (LD50>2000 smg/kg) whereas the aqueous extract was found safe up to 550 mg/kg beyond which, it was shown mortality. Ethyl alcohol and aqueous extracts were also proved to have analgesic activity.
Downloads
Published
How to Cite
Issue
Section
Accepted 2022-01-22
Published 2022-07-15
References
Ai S, Tang W, Guo RL, Li JQ, Yang W, He ZG. Research progress on Chinese herbal medicine fermentation and profile of active substances derived. Zhongguo Zhongyao zazhi China Journal of Chinese Materia Medica. 2019; 44(6):1110-8.
Rastogi S, Pandey MM, Rawat AKS. Traditional herbs: A remedy for cardiovascular disorders. Phytomedicine. 2016; 23(11):1082-9. https://doi.org/10.1016/j.phymed. 2015.10.012. PMid:26656228
Amro MS, Teoh SL, Norzana AG, Srijit D. The potential role of herbal products in the treatment of Parkinson’s disease. Clin Ter. 2018; 169(1).
Mohammadi S, Jafari B, Asgharian P, Martorell M, Sharifi?Rad J. Medicinal plants used in the treatment of Malaria: A key emphasis to artemisia, cinchona, cryptolepis, and tabebuia genera. Phytother Res. 2020; 34(7):1556-69. https://doi.org/10.1002/ptr.6628. PMid:32022345
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; 4:580-5. https:// doi.org/10.1016/j.toxrep.2017.10.005. PMid:29152463. PMCid:PMC5671618
Christapher PV, Parasuraman S, Asmawi MZ, Murugaiyah V. Acute and subchronic toxicity studies of methanol extract of Polygonum minus leaves in Sprague Dawley rats. Regul Toxicol Pharmacol. 2017; 86:33-41. https://doi.org/10.1016/j.yrtph.2017.02.005. PMid:28229903
Friess DA. Mangrove forests. Curr Biol. 2016; 26(16):R746-8. https://doi.org/10.1016/j. cub.2016.04.004. PMid:27554647
Sachithanandam V, Lalitha P, Parthiban A, Mageswaran T, Manmadhan K, Sridhar R. A review on antidiabetic properties of Indian mangrove plants with reference to island ecosystem. Evid Based Complementary Altern Med. 2019; 1-21. https://doi.org/10.1155/2019/4305148. PMid:31885647. PMCid:PMC6915161
Saddhe AA, Malvankar MR, Kumar K. Selection of reference genes for quantitative real-time PCR analysis in halophytic plant Rhizophora apiculata. Peer J. 2018; 6. https://doi.org/10.7717/peerj.5226. PMid:30013853. PMCid:PMC6046198
Selvaraj G, Kaliamurthi S, Thirugnasambandan R. Effect of glycosin alkaloid from Rhizophora apiculata in noninsulin dependent diabetic rats and its mechanism of action: in vivo and in silico studies. Phytomedicine. 2016; 23(6):632-40. https://doi.org/10.1016/j.phymed. 2016.03.004. PMid:27161404
Jaiswal SR, Sontakke SD. Experimental evaluation of analgesic and anti-inflammatory activity of simvastatin and atorvastatin. Indian J Pharmacol. 2012; 44(4):475-9. https://doi.org/10.4103/0253-7613.99311. PMid:23087508. PMCid:PMC3469950
Moulin DE, Clark AJ, Gilron I, Ware MA, Watson CPN, Sessle BJ, et al. Pharmacological management of chronic neuropathic pain-consensus statement and guidelines from the Canadian pain society. Pain Res Manag. 2007; 12(1):13-21. https://doi.org/10.1155/2007/730785. PMid:17372630. PMCid:PMC2670721
Guguloth SK, Malothu N, Kulandaivelu U, Rao KG, Areti AR, Noothi S. Phytochemical investigation and in vitro thrombolytic activity of Terminalia pallida Brandis leaves. Res J Pharm Technol. 2021; 14(2):879-82. https:// doi.org/10.5958/0974-360X.2021.00156.6
OECD. Test No. 425: Acute Oral Toxicity: Up-and- Down Procedure. OECD; 2008.
Ping KY, Darah I, Chen Y, Sreeramanan S, Sasidharan S. Acute and subchronic toxicity study of Euphorbia hirta L. methanol extract in rats. Biomed Res Int. 2013:1-14. https://doi.org/10.1155/2013/182064. PMid:24386634. PMCid:PMC3872372
Illuri R, Venkataramana SH, Daguet D, Kodimule S. Subacute and acute toxicity of Ferula asafoetida and Silybum marianum formulation and effect of the formulation on delaying gastric emptying. BMC Complement Med Ther. 2019; 19(1):2576-7. https://doi.org/10.1186/s12906-019- 2576-7. PMid:31277639. PMCid:PMC6612090
Upadhyay P, Shukla R, Mishra SK. Acute and subacute toxicity study of hydro-alcoholic leaves extract of Reinwardtia indica in rats. Biomed Pharmacother. 2019; 111: 36-41. https://doi.org/10.1016/j.biopha. 2018.12.056. PMid:30576932
Ezeja MI, Omeh YS, Ezeigbo II, Ekechukwu A. Evaluation of the analgesic activity of the methanolic stem bark extract of Dialium guineense (Wild). Ann Med Health Sci Res. 2011; 1(1):55-62.
Tilburt JC, Kaptchuk TJ. Herbal medicine research and global health: an ethical analysis. Bull World Health Organ. 2008; 86(8):594-9. https://doi.org/10.2471/ BLT.07.042820. PMid:18797616. PMCid:PMC2649468
Sen T, Samanta SK. Medicinal plants, human health and biodiversity: A broad review. J Biotechnol Biodivers. 2014:59-110. https://doi.org/10.1007/10_2014_273. PMid:25001990
Oecd Test No. 425: Acute oral toxicity: Up-anddown procedure. OECD Guidelines for the Testing of Chemicals, 2008; Section 4:1-27.
Panda SP, Panigrahy UP, Prasanth DS, Gorla US, Guntupalli C, Panda DP, Jena BR. A trimethoxy flavonoid isolated from stem extract of Tabebuia chrysantha suppresses angiogenesis in angiosarcoma. J Pharm Pharmacol. 2020; 72(7):990-9. https://doi.org/10.1111/ jphp.13272. PMid:32311118
Prabhu VV, Guruvayoorappan C. Protective effect of marine mangrove Rhizophora apiculata on acetic acid induced experimental colitis by regulating antioxidant enzymes, inflammatory mediators and nuclear factor-kappa B subunits. Int Immunopharmacol. 2014; 18(1):124-34. https://doi.org/10.1016/j. intimp.2013.11.007. PMid:24269623
Loo AY, Jain K, Darah I. Antioxidant activity of compounds isolated from the pyroligneous acid, Rhizophora apiculata. Food Chem. 2008; 107(3):1151-60. https:// doi.org/10.1016/j.foodchem.2007.09.044
Prabhu VV, Guruvayoorappan C. Evaluation of immunostimulant activity and chemoprotective effect of mangrove Rhizophora apiculata against cyclophosphamide induced toxicity in BALB/c mice. Immunopharmacol Immunotoxicol. 2012; 34(4): 608- 15. https://doi.org/10.3109/08923973.2011.642883. PMid:22211366
Saleem U, Ahmad B, Ahmad M, Erum A, Hussain K, Bukhari NI. Is folklore use of Euphorbia helioscopia devoid of toxic effects? Drug Chem Toxicol. 2016; 39(2):233-7. https://doi.org/10.3109/01480545.2015.109 2040. PMid:26453021
Mahesh S, Kumar KSP, Patgiri BJ. A review on Vatavidhvamsana rasa, An ayurvedic herbo-mineralo preparation. Int J Res Ayurveda Pharm. 2020; 11(4):143- 146. https://doi.org/10.7897/2277-4343.1104105
Alberga D, Trisciuzzi D, Mansouri K, Mangiatordi GF, Nicolotti O. Prediction of acute oral systemic toxicity using a multi fingerprint similarity approach. Toxicol Sci. 2019; 167(2):484-95. https://doi.org/10.1093/toxsci/ kfy255. PMid:30371864
Deye N, Vincent F, Michel P, Ehrmann S, Da Silva D, Piagnerelli M, et al. Changes in cardiac arrest patients’ temperature management after the 2013 “TTM” trial: Results from an international survey. Ann Intensive Care. 2016; 6(1):1-9. https://doi.org/10.1186/s13613- 015-0104-6. PMid:26753837. PMCid:PMC4709360
Sharma R, Kaur R, Mukesh M, Sharma VL. Assessment of hepatotoxicity of first-line anti-tuberculosis drugs on Wistar rats. Naunyn-Schmiedeberg’s Arch Pharmacol. 2018; 391(1):83-93. https://doi.org/10.1007/s00210-017- 1434-8. PMid:29124333
Padmanabhan N, Menelaou K, Gao J, Anderson A, Blake GE, Li T, et al. Abnormal folate metabolism causes age?, sex?and parent?of?origin?specific haematological defects in mice. J Physiol. 2018; 596(18):4341-60. https://doi.org/10.1113/JP276419. PMid:30024025. PMCid:PMC6138292
Travlos GS, Morris RW, Elwell MR, Duke A, Rosenblum S, Thompson MB. Frequency and relationships of clinical chemistry and liver and kidney histopathology findings in 13-week toxicity studies in rats. Toxicology. 1996; 107(1):17-29. https://doi.org/10.1016/0300- 483X(95)03197-N
Pundir CS, Jakhar S, Narwal V. Determination of urea with special emphasis on biosensors: A review. Biosens Bioelectron. 2019; 123:36-50. https://doi.org/10.1016/j. bios.2018.09.067. PMid:30308420
Manjunatha BK, Vidya SM, Dhiman P, Pallavi R, Mankani KL. Hepatoprotective activity of Leucas hirta against CCl4 induced hepatic damage in rats. Indian J Exp Biol. 2005; 43(8):722-7.
Ozer J, Ratner M, Shaw M, Bailey W, Schomaker S. The current state of serum biomarkers of hepatotoxicity. Toxicology. 2008; 245(3):194-205. https://doi. org/10.1016/j.tox.2007.11.021. PMid:18291570
Seida A, El-Hefnawy H, Abou-Hussein D, Mokhtar FA, Abdel-Naim A. Evaluation of Medicago sativa L. sprouts as antihyperlipidemic and antihyperglycemic agent. Pak J Pharm Sci. 2015; 28(6):2061-74.
Chunlaratthanaphorn S, Lertprasertsuke N, Srisawat U, Thuppia A, Ngamjariyawat A, Suwanlikhid N, et al. Acute and subchronic toxicity study of the water extract from root of Citrus aurantifolia (Christm. et Panz.) Swingle in rats. Songklanakarin J Sci Technol. 2007; 29(1):125-39.
Ramesh V, Rai R, Pai MM, Joy T, Jiji PJ, Blossom V. Therapeutic potential of pomegranate juice in Wistar rats against Aluminium Induced Neurotoxicity. Int J Toxicol. 2021; 28(4):357-62.
Mondal H, Saha S, Awang K, Hossain H, Ablat A, Islam MK, et al. Central-stimulating and analgesic activity of the ethanolic extract of Alternanthera sessilis in mice. BMC Complement Altern Med. 2014; 14(1):1-9. https:// doi.org/10.1186/1472-6882-14-398. PMid:25315440. PMCid:PMC4209046
