Antimalarial activity of Toona ciliata MJ Roem aqueous methanolic leaf extract and its antioxidant and phytochemical properties

10.1016/j.jtcme.2023.05.004

Nalini Singh；Aditi Chatterjee；Wahengbam Kabita Chanu；Pradeep Mini Vaishalli；Chingakham Brajakishor Singh；Viswanathan Arun Nagaraj

Medicinal plants ； Antiplasmodial ； Hemolytic ； Cytotoxicity ； Acute toxicity

Journal of Traditional and Complementary Medicine

13卷6期（2023 / 11 / 01）

550 - 560

英文

Background and aim: Malaria is a global health issue causing substantial morbidity and mortality. Screening of various traditionally important medicinal plants is a key source for the discovery of new antimalarials. We evaluated the antimalarial and antioxidant activities, and performed detailed phytochemical analyses of Toona ciliata MJ Roem aqueous methanolic leaf extract (TcMLE). Experimental procedures: In vitro antiplasmodial studies in Plasmodium falciparum (Pƒ) 3D7 and PƒCam3.I^(R539T) strains were performed by [^3H]-hypoxanthine uptake assays. In vitro cytotoxicity in HeLa and HEK293T cell lines was evaluated using MTT assays. Hemolysis assay was performed using RBCs. Phytochemical analysis by GC-MS and in vitro antioxidant studies by DPPH and ABTS assays were performed. In vivo antimalarial studies in Pb-infected mice were carried out using Rane's test and Peters' 4- day test. Results and conclusions: TcMLE showed significant in vitro antioxidant activity and had phytochemicals reported for antimalarial activity. In vitro studies showed prominent antiplasmodial activity against Pf3D7 strain (IC_(50) ~22 μg/ml) and PfCam3.I^(R539T) strain (IC_(50) value ~43 μg/ml). In vitro cytotoxicity studies, in vitro hemolytic assays, and in vivo acute toxicity studies further suggested that TcMLE is nontoxic. In vivo antimalarial studies using Rane's test showed a significant decrease in parasitemia by ~70% at 1200 mg/kg doses and delayed the mortality of mice by ~10-14 days. Peters' 4-day test also showed a similar pattern. The present study demonstrated the antimalarial potential of TcMLE. These findings deliver a platform for further studies to identify the active components of TcMLE and discover new antimalarials.

1. Ahmed, MA,Ameyaw, EO,Ackah-Armah, F(2022).In vitro and in vivo antimalarial activities of Avicennia africana P. Beauv.(Avicenniaceae) ethanolic leaf extract.J Tradit Complementary Med,12(4),391-401.
   連結：
2. (2019).Malaria.Intech Open.
3. Arrey Tarkang, P,Nwakiban Atchan, AP,Kuiate, JR,Okalebo, FA,Guantai, AN,Agbor, GA(2013).Antioxidant potential of a polyherbal antimalarial as an indicator of its therapeutic value.Adv Pharmacol Sci,678,458.
4. Banzouzi, JT,Prado, R,Menan, H(2002).In vitro antiplasmodial activity of extracts of Alchornea cordifolia and identification of an active constituent: ellagic acid.J Ethnopharmacol,81(3),399-401.
5. Baumann, E,Stoya, G,Volkner, A,Richter, W,Lemke, C,Linss, W(2000).Hemolysis of human erythrocytes with saponin affects the membrane structure.Acta Histochem,102(1),21-35.
6. Ben, Cao ZB(1999).Editorial Committee of the Administration Bureau of Traditional Chinese Medicine3.Shanghai, China:Chinese Materia Medica (Zhonghua Benchao).
7. Bhalodia, NR,Nariya, PB,Acharya, RN,Shukla, VJ(2013).In vitro antioxidant activity of hydro alcoholic extract from the fruit pulp of Cassia fistula Linn.Int J Ayurveda Res,34(2),209.
8. Bibi, Y,Nisa, S,Chaudhary, FM,Zia, M(2011).Antibacterial activity of some selected medicinal plants of Pakistan.BMC Compl Alternative Med,11(1),1-7.
9. Bickii, J,Njifutie, N,Foyere, JA,Basco, LK,Ringwald, P(2000).In vitro antimalarial activity of limonoids from Khaya grandifoliola CDC (Meliaceae).J Ethnopharmacol,69(1),27-33.
10. Bokhari, NA,Siddiqui, I,Perveen, K,Siddique, I,Soliman, DW(2015).Mycocidal ability of Toona ciliata against Rhizoctonia solani.JAPS,25(5)
11. Chandana, M,Anand, A,Ghosh, S(2022).Malaria parasite heme biosynthesis promotes and griseofulvin protects against cerebral malaria in mice.Nat Commun,13(1),1-22.
12. Chandra, S,Khan, S,Avula, B(2014).Assessment of total phenolic and flavonoid content, antioxidant properties, and yield of aeroponically and conventionally grown leafy vegetables and fruit crops: a comparative study.Evid based Complement Altern Med,2014,253875.
13. Charturvedi, P.,Raseroka, B.H.,Ntshebe, O..Evaluation of antimalarial activity of Melia azedarach.J Appl Zool Res,17(1),109-113.
14. Chatterjee, A,Singh, N,Chanu, WK,Singh, CB,Nagaraj, VA(2022).Phytochemical screening, cytotoxicity assessment and evaluation of in vitro antiplasmodial and in vivo antimalarial activities of Mentha spicata L. methanolic leaf extract.J Ethnopharmacol,298,115636.
15. Chowdhury, R,Hasan, CM,Rashid, MA(2003).Bioactivity from Toona ciliata stem bark.Pharm Biol,41(4),281-283.
16. Desjardins, RE,Canfield, CJ,Haynes, JD,Chulay, JD(1979).Quantitative assessment of antimalarial activity in vitro by a semiautomated microdilution technique.Antimicrob Agents Chemother,16(6),710.
17. Divakar, D,Parminder, R(2017).Phytopharmacology of Toona ciliata: a review.Int Res J Pharm,8(5),30-35.
18. Gopalakrishnan, G,Pradeep Singh, ND,Kasinath, V,Malathi, R,Rajan, SS(2000).Photo-oxidation of cedrelone, a tetranortriterpenoid from Toona ciliata.Photochem Photobiol,72(4),464466.
19. Gupta, M,Kumar, S,Kumar, R(2021).Inhibition of heme detoxification pathway in malaria parasite by 3-hydroxy-11-keto-b-boswellic acid isolated from Boswellia serrata.Biomed Pharmacother,144,112302.
20. Hartmann, T(1996).Diversity and variability of plant secondary metabolism: a mechanistic view.Proceedings of the 9 Th International Symposium on Insect-Plant Relationships,Dordrecht:
21. Hossain, H,Akbar, PN,Rahman, SE,Khan, TA,Rahman, MM,Jahan, IA(2014).In-vivo anti-inflammatory and in-vitro antioxidant activities of Toona ciliata leaves native to Bangladesh.Global J Med Res,14(7),17-26.
22. Hua, P,Edmonds, JM(2008).Toona (endlicher) M. Roemer. Fam Nat Syn Monogr 1: 131.Flora of China,11,112-115.
23. Hussein, RA,El-Anssary, AA(2019).Plants secondary metabolites: the key drivers of the pharmacological actions of medicinal plants.Herb Med,1(3)
24. Isah, AB,Ibrahim, YKE,Iwalewa, EO(2003).Evaluation of the antimalarial properties and standardization of tablets of Azadirachta indica (Meliaceae) in mice.Phytother Res,17(7),807-810.
25. Isah, MB,Tajuddeen, N,Umar, MI,Alhafiz, ZA,Mohammed, A,Ibrahim, MA(2018).Terpenoids as emerging therapeutic agents: cellular targets and mechanisms of action against protozoan parasites.Stud Nat Prod Chem,59,227-250.
26. Iwu, MM(1993).African Medicinal Plants.Maryland:CRC Press.
27. Karra, AG,Tziortziou, M,Kylindri, P(2020).Boswellic acids and their derivatives as potent regulators of glucocorticoid receptor actions.Arch Biochem Biophys,695,108656.
28. Kirtikar, KR,Basu, BD(1995).Indian Medicinal Plants.India:Deharadun.
29. Krugliak, M,Deharo, E,Shalmiev, G,Sauvain, M,Moretti, C,Ginsburg, H(1995).Antimalarial effects of C18 fatty acids on Plasmodium falciparum in culture and on Plasmodium vinckei petteri and Plasmodium yoelii nigeriensis in vivo.Exp Parasitol,81(1),97-105.
30. Kumar, S,Rana, M,Kumar, D,Kashyap, D,Rana, M(2012).A mini review on the phytochemistry and pharmacological activities of the plant Toona ciliate (Meliaceae).Int J Phytothearpy Res,2(1),8-18.
31. Leicach, SR,Chludil, HD(2014).Plant secondary metabolites: structureeactivity relationships in human health prevention and treatment of common diseases.Stud Nat Prod Chem,42,267-304.
32. Liu, JQ,Wang, CF,Li, Y,Chen, JC,Zhou, L,Qiu, MH(2012).Limonoids from the leaves of Toona ciliata var.Yunnanensis Phytochem,76,141-149.
33. Malairajan, P,Gopalakrishnan, G,Narasimhan, S,Veni, KJK(2006).Analgesic activity of some Indian medicinal plants.J Ethnopharmacol,106(3),425-428.
34. Malairajan, P,Gopalakrishnan, G,Narasimhan, S,Veni, KJK,Kavimani, S(2007).Antiulcer activity of crude alcoholic extract of Toona ciliata Roemer (heart wood).J Ethnopharmacol,110(2),348-351.
35. Manandhar, NP(2002).Plants and People of Nepal.Timber press.
36. Nair, AB,Jacob, S(2016).A simple practice guide for dose conversion between animals and human.J Basic Clin Pharm,7(2),27.
37. Nardella, F,Dobrescu, I,Hassan, H(2023).Hemisynthetic alkaloids derived from trilobine are antimalarials with sustained activity in multidrug-resistant Plasmodium falciparum.iScience,26(2)
38. Peters, W(1975).The four-day suppressive in vivo antimalarial test.Ann Trop Med Parasitol,69,155-171.
39. Rahman, M,Islam, M,Biswas, M,Khurshid Alam, AHM(2015).In vitro antioxidant and free radical scavenging activity of different parts of Tabebuia pallida growing in Bangladesh.BMC Res Notes,8(1),1-9.
40. Rockville, M(2005).Guidance for Industry: Estimating the Maximum Safe Starting Dose in Adult Healthy Volunteer.MD, USA:USFDA: Silver Spring.
41. Rodrigues, Goulart H,Kimura, EA,Peres, VJ,Couto, AS,Aquino, Duarte FA,Katzin, AM(2004).Terpenes arrest parasite development and inhibit biosynthesis of isoprenoids in Plasmodium falciparum.Antimicrob Agents Chemother,48(7),2502-2509.
42. Rudrapal, M,Chetia, D(2017).Plant flavonoids as potential source of future antimalarial leads.Sys Rev Pharm,8(1),13.
43. Ryley, JF,Peters, W(1995).The antimalarial activity of some quinoline esters.Ann Trop Med Parasitol,84,209-222.
44. Shaikh, JR,Patil, MK(2020).Qualitative tests for preliminary phytochemical screening: anoverview.Int J Chem Stud,8(2),603-608.
45. Sharma, V,Saini, P,Sheikh, I(2017).Role of plant secondary metabolites as potential antimalarial drugs.Sys Rev Pharm,8(1),13-18.
46. Shi, QQ,Zhang, XJ,Wang, TT(2021).Toonaones A I, limonoids with NLRP3 inflammasome inhibitory activity from Toona ciliata.M Roem Phytochem,184,112661.
47. Singh, SV,Manhas, A,Kumar, Y(2017).Antimalarial activity and safety assessment of Flueggea virosa leaves and its major constituent with special emphasis on their mode of action.Biomed Pharmacother,89,761-771.
48. Sinha, S,Batovska, DI,Medhi, B(2019).In vitro anti-malarial efficacy of chalcones: cytotoxicity profile, mechanism of action and their effect on erythrocytes.Malar J,18(1),1-11.
49. Tasdemir, D,Sanabria, D,Lauinger, IL(2010).2-Hexadecynoic acid inhibits plasmodial FAS-II enzymes and arrests erythrocytic and liver stage Plasmodium infections.Bioorg Med Chem,18(21),7475-7485.
50. The Organization of Economic Co-operation and Development=OECD(2008).The OECD Guidelines for Testing of Chemicals.
51. Trager, W,Jensen, JB(1976).Human malaria parasites in continuous culture.Science,193(4254),673-675.
52. Uphof, JCT(1959).Dictionary of Economic Plants.Weinheim:H. R. Engelmann (J. Cramer).
53. Vinodhini, V,Lokeswari, TS(2014).Antioxidant activity of the isolated compounds, methanolic and hexane extracts of Toona ciliata leaves.Int J Eng Technol,4(3)
54. Warrier, PK(1993).Indian Medicinal Plants: A Compendium of 500 Species.Orient Blackswan.
55. World Health Organization(2022).World Malaria Report. 2022.
56. Yadav, R,Pednekar, A,Avalaskar, A,Rathi, M,Rewachandani, Y(2015).A comprehensive review on Meliaceaefamily.World J Pharm Res,2015,1572-1577.
57. Yang, W,Chen, X,Li, Y,Guo, S,Wang, Z,Yu, X(2020).Advances in pharmacological activities of terpenoids.Nat Prod Res,15(3)
58. Yusuf, H(2011).The antimalarial activity of the extract of the neem leaves (Azadir-achta indica, A. Juss) on Plasmodium falciparum in vitro Chapter.Proceedings of Annu. Int. Conf. 1
59. Zhang, F,Wang, JS,Gu, YC,Kong, LY(2012).Cytotoxic and anti-inflammatory triterpenoids from Toona ciliata.J Nat Prod,75(4),538-546.
60. Zhang, PP,Bu, YG,Xue, S(2021).Four new limonoids from the barks of Toona ciliata.Nat Prod Bioprospecting,11,81-86.
61. Zheleva-Dimitrova, D,Nedialkov, P,Kitanov, G(2010).Radical scavenging and antioxidant activities of methanolic extracts from Hypericum species growing in Bulgaria.Phcog Mag,6(22),74.