Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2024

Open Access 01-12-2024 | Antimalaria | Research

In vivo antimalarial effect of 1-hydroxy-5,6,7-trimethoxyxanthone isolated from Mammea siamensis T. Anders. flowers: pharmacokinetic and acute toxicity studies

Authors: Prapaporn Chaniad, Arnon Chukaew, Prasit Na-ek, Gorawit Yusakul, Litavadee Chuaboon, Arisara Phuwajaroanpong, Walaiporn Plirat, Atthaphon Konyanee, Abdi Wira Septama, Chuchard Punsawad

Published in: BMC Complementary Medicine and Therapies | Issue 1/2024

Login to get access

Abstract

Background

The potent antiplasmodial activity of 1-hydroxy-5,6,7-trimethoxyxanthone (HTX), isolated from Mammea siamensis T. Anders. flowers, has previously been demonstrated in vitro. However, its in vivo activity has not been reported. Therefore, this study aimed to investigate the antimalarial activity and acute toxicity of HTX in a mouse model and to evaluate the pharmacokinetic profile of HTX following a single intraperitoneal administration.

Methods

The in vivo antimalarial activity of HTX was evaluated using a 4-day suppressive test. Mice were intraperitoneally injected with Plasmodium berghei ANKA strain and given HTX daily for 4 days. To detect acute toxicity, mice received a single dose of HTX and were observed for 14 days. Additionally, the biochemical parameters of the liver and kidney functions as well as the histopathology of liver and kidney tissues were examined. HTX pharmacokinetics after intraperitoneal administration was also investigated in a mouse model. Liquid chromatography triple quadrupole mass spectrometry was used to quantify plasma HTX and calculate pharmacokinetic parameters with the PKSolver software.

Results

HTX at 10 mg/kg body weight significantly suppressed parasitemia in malaria-infected mice by 74.26%. Mice treated with 3 mg/kg HTX showed 46.88% suppression, whereas mice treated with 1 mg/kg displayed 34.56% suppression. Additionally, no symptoms of acute toxicity were observed in the HTX-treated groups. There were no significant alterations in the biochemical parameters of the liver and kidney functions and no histological changes in liver or kidney tissues. Following intraperitoneal HTX administration, the pharmacokinetic profile exhibited a maximum concentration (Cmax) of 94.02 ng/mL, time to attain Cmax (Tmax) of 0.5 h, mean resident time of 14.80 h, and elimination half-life of 13.88 h.

Conclusions

HTX has in vivo antimalarial properties against P. berghei infection. Acute toxicity studies of HTX did not show behavioral changes or mortality. The median lethal dose was greater than 50 mg/kg body weight. Pharmacokinetic studies showed that HTX has a long elimination half-life; hence, shortening the duration of malaria treatment may be required to minimize toxicity.
Literature
1.
Alehegn AA, Yesuf JS, Birru EM. Antimalarial activity of crude extract and solvent fractions of the leaves of Bersama Abyssinica Fresen. (Melianthaceae) against Plasmodium berghei infection in Swiss albino mice. Evid Based Complement Alternat Med. 2020;2020:9467359.CrossRefPubMedPubMedCentral
2.
Muhaimin M, Madyawati L, Riski Dwimalida P, Anis Yohana C, Andreas Yoga A, Normalita Eka P et al. Antiplasmodial activity of methanolic leaf extract of mangrove plants against Plasmodium berghei. Pharmacogn J. 2019;11(5).
3.
WHO. World malaria report 2022. Geneva: World Health Organization; 2022.
4.
Pan WH, Xu XY, Shi N, Tsang SW, Zhang HJ. Antimalarial activity of plant metabolites. Int J Mol Sci. 2018;19(5).
5.
Koehne E, Kreidenweiss A, Adegbite BR, Manego RZ, McCall MBB, Mombo-Ngoma G, et al. In vitro activity of eravacycline, a novel synthetic halogenated tetracycline, against the malaria parasite Plasmodium Falciparum. J Glob Antimicrob Resist. 2021;24:93–7.CrossRefPubMed
6.
Fenta M, Kahaliw W. Evaluation of antimalarial activity of hydromethanolic crude extract and solvent fractions of the leaves of Nuxia congesta R. Br. Ex Fresen (Buddlejaceae) in Plasmodium Berghei infected mice. J Exp Pharmacol. 2019;11:121–34.CrossRefPubMedPubMedCentral
7.
Cui L, Mharakurwa S, Ndiaye D, Rathod PK, Rosenthal PJ. Antimalarial drug resistance: literature review and activities and findings of the ICEMR network. Am J Trop Med Hyg. 2015;93(3 Suppl):57–68.CrossRefPubMedPubMedCentral
8.
Bekono BD, Ntie-Kang F, Onguéné PA, Lifongo LL, Sippl W, Fester K, et al. The potential of anti-malarial compounds derived from African medicinal plants: a review of pharmacological evaluations from 2013 to 2019. Malar J. 2020;19(1):183.CrossRefPubMedPubMedCentral
9.
10.
Kweyamba PA, Zofou D, Efange N, Assob J-CN, Kitau J, Nyindo M. In vitro and in vivo studies on anti-malarial activity of Commiphora africana and Dichrostachys cinerea used by the Maasai in Arusha region, Tanzania. Malar J. 2019;18(1):119.
11.
Waluyo D, Prabandari EE, Pramisandi A, Hidayati DN, Chrisnayanti E, Puspitasari DJ, et al. Exploring natural microbial resources for the discovery of anti-malarial compounds. Parasitol Int. 2021;85:102432.CrossRefPubMed
12.
Achan J, Talisuna AO, Erhart A, Yeka A, Tibenderana JK, Baliraine FN, et al. Quinine, an old anti-malarial drug in a modern world: role in the treatment of malaria. Malar J. 2011;10:144.CrossRefPubMedPubMedCentral
13.
14.
Sangkaruk R, Rungrojsakul M, Tima S, Anuchapreeda S. Effect of Thai saraphi flower extracts on WT1 and Bcr/Abl protein expression in leukemic cell lines. Afr J Tradit Complement Altern Med. 2017;14(2):16–24.CrossRefPubMedPubMedCentral
15.
Ninomiya K, Shibatani K, Sueyoshi M, Chaipech S, Pongpiriyadacha Y, Hayakawa T, et al. Aromatase inhibitory activity of geranylated coumarins, mammeasins C and D, isolated from the flowers of Mammea siamensis. Chem Pharm Bull. 2016;64(7):880–5.CrossRef
16.
Tung NH, Uto T, Sakamoto A, Hayashida Y, Hidaka Y, Morinaga O, et al. Antiproliferative and apoptotic effects of compounds from the flower of Mammea siamensis (miq.) T. Anders. On human cancer cell lines. Bioorg Med Chem Lett. 2013;23(1):158–62.CrossRefPubMed
17.
Luo F, Sugita H, Muraki K, Saeki S, Chaipech S, Pongpiriyadacha Y, et al. Anti-proliferative activities of coumarins from the Thai medicinal plant Mammea siamensis (miq.) T. Anders. Against human digestive tract carcinoma cell lines. Fitoterapia. 2021;148:104780.CrossRefPubMed
18.
Morikawa T, Sueyoshi M, Chaipech S, Matsuda H, Nomura Y, Yabe M, et al. Suppressive effects of coumarins from Mammea siamensis on inducible nitric oxide synthase expression in RAW264.7 cells. Bioorg Med Chem. 2012;20(16):4968–77.CrossRefPubMed
19.
Chaniad P, Techarang T, Phuwajaroanpong A, Horata N, Septama AW, Punsawad C. Exploring potential antimalarial candidate from medicinal plants of Kheaw Hom remedy. Trop Med Infect Dis. 2022;7(11).
20.
Chaniad P, Chukaew A, Payaka A, Phuwajaroanpong A, Techarang T, Plirat W, et al. Antimalarial potential of compounds isolated from Mammea Siamensis T. Anders. Flowers: in vitro and molecular docking studies. BMC Complement Med Ther. 2022;22(1):266.CrossRefPubMedPubMedCentral
21.
Plirat W, Chaniad P, Phuwajaroanpong A, Septama AW, Punsawad C. Phytochemical, antimalarial, and acute oral toxicity properties of selected crude extracts of Prabchompoothaweep remedy in Plasmodium berghei-infected mice. Trop Med Infect Dis. 2022;7(12):395.CrossRefPubMedPubMedCentral
22.
Chaniad P, Techarang T, Phuwajaroanpong A, Punsawad C. Antimalarial activity and toxicological assessment of Betula alnoides extract against Plasmodium berghei infections in mice. Evid Based Complement Altern Med. 2019;2019:2324679.CrossRef
23.
Peters W. The four-day suppressive in vivo antimalarial test. Ann Trop Med Parasitol. 1975;69:155–71.CrossRefPubMed
24.
OECD. Test No. 425: acute oral toxicity: up-and-down procedure2022.
25.
Wichapoon B, Punsawad C, Chaisri U, Viriyavejakul P. Glomerular changes and alterations of zonula occludens-1 in the kidneys of Plasmodium Falciparum malaria patients. Malar J. 2014;13(1):176.CrossRefPubMedPubMedCentral
26.
Viriyavejakul P, Khachonsaksumet V, Punsawad C. Liver changes in severe Plasmodium Falciparum malaria: histopathology, apoptosis and nuclear factor kappa B expression. Malar J. 2014;13(1):106.CrossRefPubMedPubMedCentral
27.
Patnaik MP, Sharma V, Parmar VS, Boll PM. Synthesis of new trioxygenated xanthones of Tovomita Excelsa. ChemInform. 1987;18.
28.
29.
Tovilovic Kovacevic G, Zogovic N, Krstić-Milošević D. Secondary metabolites from endangered Gentiana, Gentianella, Centaurium, and Swertia species (Gentianaceae): promising natural biotherapeutics. 2020. p. 335 – 84.
30.
Mina EC, Mina JF. Ethnobotanical survey of plants commonly used for diabetes in Tarlac of central Luzon Philippines. IIUM Med J Malays. 2017;16(1).
31.
Chatatikun M, Chiabchalard A. Thai plants with high antioxidant levels, free radical scavenging activity, anti-tyrosinase and anti-collagenase activity. BMC Complement Altern Med. 2017;17(1):487.CrossRefPubMedPubMedCentral
32.
Zhang H, Tan Y-p, Zhao L, Wang L, Fu N-j, Zheng S-p, et al. Anticancer activity of dietary xanthone α-mangostin against hepatocellular carcinoma by inhibition of STAT3 signaling via stabilization of SHP1. Cell Death Dis. 2020;11(1):63.CrossRefPubMedPubMedCentral
33.
Upegui Y, Robledo SM, Gil Romero JF, Quiñones W, Archbold R, Torres F, et al. In vivo antimalarial activity of α-mangostin and the new xanthone δ-mangostin. Phytother Res. 2015;29(8):1195–201.CrossRefPubMed
34.
Kelly JX, Winter R, Peyton DH, Hinrichs DJ, Riscoe M. Optimization of xanthones for antimalarial activity: the 3,6-bis-omega-diethylaminoalkoxyxanthone series. Antimicrob Agents Chemother. 2002;46(1):144–50.CrossRefPubMedPubMedCentral
35.
Thome R, Lopes S, Costa F, Verinaud L. Chloroquine: modes of action of an undervalued drug. Immunol Lett. 2013;153.
36.
Pillat MM, Krüger A, Guimarães LMF, Lameu C, de Souza EE, Wrenger C, et al. Insights in chloroquine action: perspectives and implications in Malaria and COVID-19. Cytometry Part A. 2020;97(9):872–81.CrossRef
37.
Nigatu TA, Afework M, Urga K, Ergete W, Makonnen E. Toxicological investigation of acute and chronic treatment with Gnidia Stenophylla Gilg root extract on some blood parameters and histopathology of spleen, liver and kidney in mice. BMC Res Notes. 2017;10(1):625.CrossRefPubMedPubMedCentral
38.
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 N. E. Brown in mice and rats. Heliyon. 2019;5(1):e01179.CrossRefPubMedPubMedCentral
39.
Turner PV, Brabb T, Pekow C, Vasbinder MA. Administration of substances to laboratory animals: routes of administration and factors to consider. J Am Assoc Lab Anim Sci. 2011;50(5):600–13.PubMedPubMedCentral
40.
Yudhani R, Pesik R, Azzahro S, Anisa A, Hendriyani R. Renal function parameter on acute toxicity test of kapulaga (Amomum cardamom) seed extract in rat. IOP Conf Series: Mater Sci Eng. 2019;578:012053.CrossRef
41.
Rivadeneyra-Domínguez E, Becerra-Contreras Y, Vázquez-Luna A, Díaz-Sobac R, Rodríguez-Landa JF. Alterations of blood chemistry, hepatic and renal function, and blood cytometry in acrylamide-treated rats. Toxicol Rep. 2018;5:1124–8.CrossRefPubMedPubMedCentral
42.
Auletta CS. RAC M. Acute, subchronic, and chronic toxicology. Handb Toxicol. 1995:51–162.
43.
Hussain K, Ismail Z, Sadikun A, Ibrahim P. Bioactive markers based pharmacokinetic evaluation of extracts of a traditional medicinal plant, Piper Sarmentosum. Evid Based Complement Alternat Med. 2011;2011:980760.CrossRefPubMedPubMedCentral
44.
Okada K, Sato A, Hiramoto A, Isogawa R, Kurosaki Y, Higaki K, et al. Pharmacokinetic analysis of new synthetic antimalarial N-251. Trop Med Int Health. 2019;47(1):40.CrossRef
45.
Al Shoyaib A, Archie SR, Karamyan VT. Intraperitoneal route of drug administration: should it be used in experimental animal studies? Pharm Res. 2019;37(1):12.CrossRefPubMedPubMedCentral
46.
Morris CA, Duparc S, Borghini-Fuhrer I, Jung D, Shin C-S, Fleckenstein L. Review of the clinical pharmacokinetics of artesunate and its active metabolite dihydroartemisinin following intravenous, intramuscular, oral or rectal administration. Malar J. 2011;10(1):263.CrossRefPubMedPubMedCentral
47.
Tarning J, Rijken MJ, McGready R, Phyo AP, Hanpithakpong W, Day NP, et al. Population pharmacokinetics of dihydroartemisinin and piperaquine in pregnant and nonpregnant women with uncomplicated malaria. Antimicrob Agents Chemother. 2012;56(4):1997–2007.CrossRefPubMedPubMedCentral
48.
Hong X, Liu C-h, Huang X-t, Huang T-l, Ye S-m, Ou W-p, et al. Pharmacokinetics of dihydroartemisinin in Artekin tablets for single and repeated dosing in Chinese healthy volunteers. Biopharm Drug Dispos. 2008;29(4):237–44.CrossRefPubMed
49.
Gautam A, Ahmed T, Sharma P, Varshney B, Kothari M, Saha N, et al. Pharmacokinetics and pharmacodynamics of arterolane maleate following multiple oral doses in adult patients with P. Falciparum malaria. J Clin Pharmacol. 2011;51(11):1519–28.CrossRefPubMed
50.
Tanner L, Haynes RK, Wiesner L. An in vitro ADME and in vivo pharmacokinetic study of novel TB-active decoquinate derivatives. Front Pharmacol. 2019;10.
51.
Bassat Q, Maïga-Ascofaré O, May J, Clain J, Mombo-Ngoma G, Groger M, et al. Challenges in the clinical development pathway for triple and multiple drug combinations in the treatment of uncomplicated falciparum malaria. Malar J. 2022;21(1):61.CrossRefPubMedPubMedCentral
Metadata
Title
In vivo antimalarial effect of 1-hydroxy-5,6,7-trimethoxyxanthone isolated from Mammea siamensis T. Anders. flowers: pharmacokinetic and acute toxicity studies
Authors
Prapaporn Chaniad
Arnon Chukaew
Prasit Na-ek
Gorawit Yusakul
Litavadee Chuaboon
Arisara Phuwajaroanpong
Walaiporn Plirat
Atthaphon Konyanee
Abdi Wira Septama
Chuchard Punsawad
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2024
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-024-04427-z

Other articles of this Issue 1/2024

BMC Complementary Medicine and Therapies 1/2024 Go to the issue

Research

Ginsenoside compound K induces ferroptosis via the FOXO pathway in liver cancer cells

Research

Ethnobotanical assessment of antidiabetic medicinal plants in District Karak, Pakistan

Research

Views of healthcare professionals on complementary and alternative medicine use by patients with diabetes: a qualitative study

Research

Molecular mechanism of resveratrol promoting differentiation of preosteoblastic MC3T3-E1 cells based on network pharmacology and experimental validation

Research

Development and characterization of a topical gel, containing lavender (Lavandula angustifolia) oil loaded solid lipid nanoparticles

Research

Study on the differential hepatotoxicity of raw polygonum multiflorum and polygonum multiflorum praeparata and its mechanism