Abstract
Malaria is a major life-threatening tropical disease affecting about half of the world’s population. Due to the increasing resistance of Plasmodium falciparum against the marketed drugs, the non-endemic areas of malaria are also at risk which demands for continuous and a compelling need to investigate the bioactive natural products for their pharmacological activity against malaria parasite and undoubtedly satisfactory outcomes are being observed with less adverse events in such endeavours. Flavonoids have emerged as the most important bio-therapeutic class possessing anti-malarial activity. Flavonoids have also been reported to reverse anti-malarial drug resistance, thus exerting dual therapeutic benefit. The pharmacological outcome of these bioactive constituents essentially depends on their circulating levels reaching the target site of action thus, necessitating the quantification in bio-matrices which is required for personalized therapy. Furthermore, the estimation of drug level in biological system is crucial for therapeutic drug monitoring. The development and validation of high-throughput bio-analytical methods for estimation of phytochemicals in biological fluids is a preliminary requirement for establishing such PK–PD relationship. The present review intends to shed an insightful focus on the available bio-analytical methods for assessment of natural anti-malarial flavonoids which will be of immense help in their further exploration.
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References
Ader, P., et al.: Bioavailability and metabolism of the flavonol quercetin in the pig. Free Radic. Biol. Med. 28, 1056–1067 (2000)
Al-Ishaq, R.K., et al.: Flavonoids and their anti-diabetic effects: cellular mechanisms and effects to improve blood sugar levels. Biomolecules 9, 430 (2019)
Alayo, M., et al.: Larvicidal potential and mosquito repellent activity of Cassia mimosoides extracts. Southeast Asian J. Trop. Med. Public Health 46, 596 (2015)
Bai, Y., et al.: Pharmacokinetic of 5 components after oral administration of Fructus Forsythiae by HPLC-MS/MS and the effects of harvest time and administration times. J. Chromatogr. B 993, 36–46 (2015)
Baranowska, I., et al.: UHPLC method for the simultaneous determination of β-blockers, isoflavones, and flavonoids in human urine. J. Chromatogr. Sci. 49, 764–773 (2011)
Batista, R., et al.: Plant-derived antimalarial agents: new leads and efficient phytomedicines. Part II. Non-alkaloidal natural products. Molecules 14, 3037–3072 (2009)
Bian, Y., et al.: Progress in the pretreatment and analysis of flavonoids: an update since 2013. Sep. Purif. Rev.: 1–27 (2020)
Biasutto, L., et al.: Determination of quercetin and resveratrol in whole blood—implications for bioavailability studies. Molecules 15, 6570–6579 (2010)
Brahmachari, G.: Naturally occurring flavanones: an overview. Nat. Prod. Commun. 3, 1934578X0800300820 (2008)
Bringmann, G., et al.: 6-Hydroxyluteolin-7-O-(1″-α-rhamnoside) from Vriesea sanguinolenta Cogn. and Marchal (Bromeliaceae). Phytochemistry 53, 965–969 (2000)
Caboni, P., et al.: LC–MS–MS determination of rotenone, deguelin, and rotenolone in human serum. Chromatographia 68, 739–745 (2008)
Carabias-Martínez, R., et al.: Pressurized liquid extraction in the analysis of food and biological samples. J. Chromatogr. A 1089, 1–17 (2005)
Chanphen, R., et al.: Antimalarial principles from Artemisia indica. J. Nat. Prod. 61, 1146–1147 (1998)
Chen, I.-L., et al.: Lymphatic absorption of quercetin and rutin in rat and their pharmacokinetics in systemic plasma. J. Agric. Food Chem. 58, 546–551 (2009)
Chen, T., et al.: Absorption and excretion of luteolin and apigenin in rats after oral administration of Chrysanthemum morifolium extract. J. Agric. Food Chem. 55, 273–277 (2007)
Chen, X., et al.: Pharmacokinetics of luteolin and tetra-acetyl-luteolin assayed by HPLC in rats after oral administration. Biomed. Chromatogr. 24, 826–832 (2010)
Chen, Z., et al.: Role of catechol-O-methyltransferase in the disposition of luteolin in rats. Drug Metab. Dispos. Biol. Fate Chem. 39, 667–674 (2011)
Chen, Z., et al.: Pharmacokinetic study of luteolin, apigenin, chrysoeriol and diosmetin after oral administration of Flos Chrysanthemi extract in rats. Fitoterapia 83, 1616–1622 (2012)
Chu, K., et al.: Uptake and distribution of catechins in fetal organs following in utero exposure in rats. Hum. Reprod. 22, 280–287 (2007)
Cushnie, T.T., Lamb, A.J.: Antimicrobial activity of flavonoids. Int. J. Antimicrob. Agents 26, 343–356 (2005)
Dai, B., et al.: Simultaneous determination of six flavonoids from Paulownia tomentosa flower extract in rat plasma by LC–MS/MS and its application to a pharmacokinetic study. J. Chromatogr. B 978, 54–61 (2015)
Daigle, D., Conkerton, E.: Analysis of flavonoids by HPLC: an update. J. Liq. Chromatogr. 11, 309–325 (1988)
Duan, K., et al.: LC–MS/MS determination and pharmacokinetic study of five flavone components after solvent extraction/acid hydrolysis in rat plasma after oral administration of Verbena officinalis L. extract. J. Ethnopharmacol. 135, 201–208 (2011)
Fan, L.-H., et al.: Determination of acacetin in rat plasma by UPLC-MS/MS and its application to a pharmacokinetic study. J. Chromatogr. B 986, 18–22 (2015)
Feng, D., et al.: Oral pharmacokinetic comparison of different genistein tablets in beagle dogs. J. Chromatogr. Sci. 51, 335–340 (2013)
Fu, T., et al.: Simultaneous determination of the major active components of tea polyphenols in rat plasma by a simple and specific HPLC assay. J. Chromatogr. B 875, 363–367 (2008)
Gerdin, B., Svensjö, E.: Inhibitory effect of the flavonoid O-(beta-hydroxyethyl)-rutoside on increased microvascular permeability induced by various agents in rat skin. Int. J. Microcirc. Clin. Exp. 2, 39–46 (1983)
Grotewold, E.: The science of flavonoids. Springer, New York (2006)
Guan, H., et al.: Interactions of pharmacokinetic profile of different parts from Ginkgo biloba extract in rats. J. Ethnopharmacol. 155(1), 758–768 (2014)
Guan, H., et al.: Comparative intestinal bacteria-associated pharmacokinetics of 16 components of Shengjiang Xiexin decoction between normal rats and rats with irinotecan hydrochloride (CPT-11)-induced gastrointestinal toxicity in vitro using salting-out sample preparation and LC-MS/MS. RSC Adv. 7, 43621–43635 (2017)
Hand, C.C., Meshnick, S.R.: Is chloroquine making a comeback? J. Infect. Dis. 203, 11–12 (2011)
He, J., et al.: A sensitive LC–MS/MS method for simultaneous determination of six flavonoids in rat plasma: application to a pharmacokinetic study of total flavonoids from mulberry leaves. J. Pharm. Biomed. Anal. 84, 189–195 (2013)
Hritcu, L., et al.: Antidepressant flavonoids and their relationship with oxidative stress. Oxid. Med. Cell. Longev. (2017). https://doi.org/10.1155/2017/5762172
Huck, C.W., Bonn, G.K.: Evaluation of detection methods for the reversed-phase HPLC determination of 3′, 4′, 5′-trimethoxyflavone in different phytopharmaceutical products and in human serum. Phytochem. Anal. 12, 104–109 (2001)
James, K.D., et al.: Dietary pretreatment with green tea polyphenol,(−)-epigallocatechin-3-gallate reduces the bioavailability and hepatotoxicity of subsequent oral bolus doses of (−)-epigallocatechin-3-gallate. Food Chem. Toxicol. 76, 103–108 (2015)
Jenett-Siems, K., et al.: Sipandinolide: a butenolide including a novel type of carbon skeleton from Siparuna andina. Planta Med. 66, 384–385 (2000)
Kammalla, A.K., et al.: Comparative pharmacokinetic interactions of quercetin and rutin in rats after oral administration of European patented formulation containing Hipphophae rhamnoides and co-administration of quercetin and rutin. Eur. J. Drug Metab. Pharmacokinet. 40, 277–284 (2015)
Kaur, K., et al.: Antimalarials from nature. Bioorg. Med. Chem. Lett. 17, 3229–3256 (2009)
Khaomek, P., et al.: In vitro antimalarial activity of prenylated flavonoids from Erythrina fusca. J. Nat. Med. 62, 217–220 (2008)
Kim, S.-B., et al.: Development and validation of a highly sensitive LC–MS/MS method for the determination of acacetin in human plasma and its application to a protein binding study. Arch. Pharm. Res.: 1–8 (2015)
Kraft, C., et al.: Antiplasmodial activity of isoflavones from Andira inermis. J. Ethnopharmacol. 73, 131–135 (2000)
Kraft, C., et al.: In vitro antiplasmodial evaluation of medicinal plants from Zimbabwe. Phytother. Res. 17, 123–128 (2003)
Kumar, S., Pandey, A.K.: Chemistry and biological activities of flavonoids: an overview. Sci. World J. (2013). https://doi.org/10.1155/2013/162750
Kunert, O., et al.: Antiplasmodial and leishmanicidal activity of biflavonoids from Indian Selaginella bryopteris. Phytochem. Lett. 1, 171–174 (2008)
Lan, K., et al.: Towards polypharmacokinetics: pharmacokinetics of multicomponent drugs and herbal medicines using a metabolomics approach. Evid.-Based Complement. Altern. Med. (2013). https://doi.org/10.1155/2013/819147
Li, L., et al.: Simultaneous determination of luteolin and apigenin in dog plasma by RP-HPLC. J. Pharm. Biomed. Anal. 37, 615–620 (2005)
Li, Q., et al.: A combined strategy of mass fragmentation, post-column cobalt complexation and shift in ultraviolet absorption spectra to determine the uridine 5′-diphospho-glucuronosyltransferase metabolism profiling of flavones after oral administration of a flavone mixture in rats. J. Chromatogr. A 1395, 116–128 (2015)
Lim, S.S., et al.: In vitro antimalarial activity of flavonoids and chalcones. Bull. Korean Chem. Soc. 28, 2495 (2007)
Limmatvapirat, C., et al.: Antitubercular and antiplasmodial constituents of Abrus precatorius. Planta Med. 70, 276–278 (2004)
Lin, L.-C., et al.: Isolation of luteolin and luteolin-7-O-glucoside from Dendranthema morifolium Ramat Tzvel and their pharmacokinetics in rats. J. Agric. Food Chem. 63, 7700–7706 (2015)
Liu, W., et al.: A novel benzo [d] imidazole derivate prevents the development of dextran sulfate sodium-induced murine experimental colitis via inhibition of NLRP3 inflammasome. Biochem. Pharmacol. 85, 1504–1512 (2013)
Lu, L., et al.: Abelmoschi Corolla non-flavonoid components altered the pharmacokinetic profile of its flavonoids in rat. J. Ethnopharmacol. 148, 804–811 (2013)
Mahomoodally, M.F.: Traditional medicines in Africa: an appraisal of ten potent African medicinal plants. Evid. Based Complement. Altern. Med. 2013, 617459 (2013)
Maione-Silva, L., et al.: Development and validation of a simple and rapid liquid chromatography method for the determination of genistein in skin permeation studies. Biol. Pharm. Bull. 35, 1986–1990 (2012)
Manach, C.: The use of HPLC with coulometric array detection in the analysis of flavonoids in complex matrixes. The Royal Society of Chemistry, Cambridge (2003)
Manach, C., et al.: Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am. J. Clin. Nutr. Title 81, 230S-242S (2005)
Misaka, S., et al.: Development of rapid and simultaneous quantitative method for green tea catechins on the bioanalytical study using UPLC/ESI-MS. Biomed. Chrom. 27, 1–6 (2013)
Mohanty, S., et al.: Flavonoids rich fraction of Citrus limetta fruit peels reduces proinflammatory cytokine production and attenuates malaria pathogenesis. Curr. Pharm. Biotechnol. 16, 544–552 (2015)
Mori, A., et al.: Antibacterial activity and mode of action of plant flavonoids against Proteus vulgaris and Staphylococcus aureus. Phytochemistry 26, 2231–2234 (1987)
Muiva, L.M., et al.: Antiplasmodial β-hydroxydihydrochalcone from seedpods of Tephrosia elata. Phytochem. Lett. 2, 99–102 (2009)
Naddaf, N., Haddad, S.: Apigenin effect against Leishmania tropica amastigotes in vitro. J. Parasit. Dis. 44, 574–578 (2020)
Nakagawa, K., Miyazawa, T.: Chemiluminescence–high-performance liquid chromatographic determination of tea catechin, (−)-epigallocatechin 3-gallate, at picomole levels in rat and human plasma. Anal. Biochem. 248, 41–49 (1997)
Nogueira, C.R., Lopes, L.M.: Antiplasmodial natural products. Molecules 16, 2146–2190 (2011)
Ntie-Kang, F., et al.: The potential of anti-malarial compounds derived from African medicinal plants, part II: a pharmacological evaluation of non-alkaloids and non-terpenoids. Malar. J. 13(10), 1186 (2014)
Ohemeng, K., et al.: DNA gyrase inhibitory and antibacterial activity of some flavones (1). Bioorg. Med. Chem. Lett. 3, 225–230 (1993)
Pal, D., Verma, P.: Flavonoids: a powerful and abundant source of antioxidants. Int. J. Pharm. Pharm. Sci. 5, 95–98 (2013)
Paulke, A., et al.: Isoquercitrin provides better bioavailability than quercetin: comparison of quercetin metabolites in body tissue and brain sections after six days administration of isoquercitrin and quercetin. Die Pharmazie Int. J. Pharm. Sci. 67, 991–996 (2012)
Pietta, P.-G.: Flavonoids as antioxidants. J. Nat. Prod. 63, 1035–1042 (2000)
Preedy, V.R.: Isoflavones: Chemistry, Analysis, Function and Effects. RSC Publishing, Cambridge (2012)
Qiu, F., et al.: HPLC-ESI-MS/MS analysis and pharmacokinetics of luteoloside, a potential anticarcinogenic component isolated from Lonicera japonica, in beagle dogs. Biomed. Chromatogr. 27, 311–317 (2013)
Reinboth, M., et al.: Oral bioavailability of quercetin from different quercetin glycosides in dogs. Br. J. Nutr. 104, 198–203 (2010)
Rudrapal, M., Chetia, D.: Plant flavonoids as potential source of future antimalarial leads. Syst. Rev. Pharm. 8, 13 (2017)
Shanmugam, R., et al.: Bioanalytical method development and validation for herbal quercetin in nano formulation by RPUFLC in rabbit plasma. J. Bioequiv. Bioavailab. 5, 191–196 (2013)
Sheet, W.F.: World Malaria Report 2015. World Health Organization, Geneva (2016)
Soleas, G., et al.: Ultrasensitive assay for three polyphenols (catechin, quercetin and resveratrol) and their conjugates in biological fluids utilizing gas chromatography with mass selective detection. J. Chromatogr. B Biomed. Sci. Appl. 757, 161–172 (2001)
Stefova, M., et al.: Encyclopedia of Chromatography. Taylor & Francis , Boca Raton (2003)
Sun, D., et al.: Simultaneous determination of four flavonoids and one phenolic acid in rat plasma by LC–MS/MS and its application to a pharmacokinetic study after oral administration of the Herba Desmodii Styracifolii extract. J. Chromatogr. B 932, 66–73 (2013)
Supko, J., Phillips, L.: High-performance liquid chromatographic assay for genistein in biological fluids. J. Chromatogr. B Biomed. Sci. Appl. 666, 157–167 (1995)
Tekel, J., et al.: Development of a simple method for the determination of genistein, daidzein, biochanin A, and formononetin (biochanin B) in human urine. J. Agric. Food Chem. 47, 3489–3494 (1999)
Teng, W.-C., et al.: Medicinal Plants and Malaria: Applications, Trends, and Prospects. CRC Press , Boca Raton (2016)
Trampuz, A., et al.: Clinical review: severe malaria. Crit. Care-Lond. 7, 315–323 (2003)
Udeani, G.O., et al.: Pharmacokinetics of deguelin, a cancer chemopreventive agent in rats. Cancer Chemother. Pharmacol. 47, 263–268 (2001)
Vogel, G.: New map illustrates risk from the ‘other’ malaria. Science 329, 618–618 (2010)
Wang, F., et al.: Determination of quercetin and kaempferol in human urine after orally administrated tablet of ginkgo biloba extract by HPLC. J. Pharm. Biomed. Anal. 33, 317–321 (2003)
Wang, X., et al.: Pharmacokinetic interaction between the flavonoid luteolin and γ-hydroxybutyrate in rats: potential involvement of monocarboxylate transporters. AAPS J. 10, 47–55 (2008)
Weaver, C.M., et al.: Flavonoid intake and bone health. J. Nutr. Gerontol. Geriatr. 31, 239–253 (2012)
Wieling, J.: LC–MS–MS experiences with internal standards. Chromatographia 55, S107–S113 (2002)
Willcox, M.: Improved traditional phytomedicines in current use for the clinical treatment of malaria. Planta Med. 77, 662–671 (2011)
Wittemer, S., et al.: Bioavailability and pharmacokinetics of caffeoylquinic acids and flavonoids after oral administration of Artichoke leaf extracts in humans. Phytomedicine 12, 28–38 (2005)
Wittemer, S.M., Veit, M.: Validated method for the determination of six metabolites derived from artichoke leaf extract in human plasma by high-performance liquid chromatography–coulometric-array detection. J. Chromatogr. B. 793, 367–375 (2003)
Wittig, J., et al.: Identification of quercetin glucuronides in human plasma by high-performance liquid chromatography–tandem mass spectrometry. J. Chromatogr. B Biomed. Sci. Appl. 753, 237–243 (2001)
Yang, Z., et al.: Simultaneous determination of genistein and its four phase II metabolites in blood by a sensitive and robust UPLC–MS/MS method: application to an oral bioavailability study of genistein in mice. J. Pharm. Biomed. Anal. 53, 81–89 (2010)
Yao, X., et al.: A UPLC-MS/MS method for qualification of quercetin-3-O-β-D-glucopyranoside-(4® 1)-α-L-rhamnoside in rat plasma and application to pharmacokinetic studies. Molecules 18, 3050–3059 (2013)
Ye, G., et al.: Determination of calycosin-7-O-β-d-glucopyranoside in rat plasma and urine by HPLC. Biomed. Chromatogr. 21, 762–767 (2007)
Yin, R., et al.: UFLC–MS/MS method for simultaneous determination of luteolin-7-O-gentiobioside, luteolin-7-O-β-d-glucoside and luteolin-7-O-β-d-glucuronide in beagle dog plasma and its application to a pharmacokinetic study after administration of traditional Chinese medicinal preparation: Kudiezi injection. J. Pharm. Biomed. Anal. 72, 127–133 (2013)
Zeng, H.-J., et al.: Pharmacokinetic study of six flavones in rat plasma and tissues after oral administration of ‘JiangYaBiFeng’ using SPE-HPLC–DAD. J. Pharm. Biomed. Anal. 56, 815–819 (2011)
Zhang, A., et al.: Simultaneous determination of 14 phenolic compounds in grape canes by HPLC-DAD-UV using wavelength switching detection. Molecules 18(11), 14241–14257 (2013)
Zhang, Z., et al.: LC–MS/MS determination and pharmacokinetic study of seven flavonoids in rat plasma after oral administration of Cirsium japonicum DC. extract. J. Ethnopharmacol. 158, 66–75 (2014)
Zhao, W.O., et al.: LC-ESI-MS/MS analysis and pharmacokinetics of heterophyllin B, a cyclic octapeptide from Pseudostellaria heterophylla in rat plasma. Biomed. Chromatogr. 29, 1693–1699 (2015)
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The authors are thankful to Director, CDRI for his constant encouragement and support. We also acknowledge CSIR, India, for providing the research fellowship and Department of Science and Technology (DST) for providing funding under Project GAP0235. CDRI communication number for this article is 10291.
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Chaturvedi, S., Malik, M.Y., Sultana, N. et al. Chromatographic separation and estimation of natural antimalarial flavonoids in biological matrices. Proc.Indian Natl. Sci. Acad. 87, 446–468 (2021). https://doi.org/10.1007/s43538-021-00050-5
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DOI: https://doi.org/10.1007/s43538-021-00050-5