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Abstract

We show here that a crude extract of green tea as well as two of its main constituents, epigallocatechin-3-gallate (EGCG) and epicatechin gallate (ECG), strongly inhibit Plasmodium falciparum growth in vitro. Both these catechins are found to potentiate the antimalarial effects of artemisinin without interfering with the folate pathway. The importance of these findings and their mechanistic implications are discussed in view of future therapeutic strategies.

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... Flavonoids such as acacetin, apigenin, baicalein, chrysin, genistein, kaempferol, luteolin, among many others have been identified to possess antimalarial activity (Lehane and Saliba 2008). Additionally, compounds from the catechin family have been involved in antimalarial action (Sannella et al. 2007). ...
... Several studies describe how catechin-related compounds such as epigallocatechin-3-gallate (EGCG) and epicatechin gallate (ECG) show moderate antiplasmodial effects. In a study by Sannella et al. (2007), a crude extract, as well as EGCG and ECG from green tea leaves, were found to strongly inhibit the growth of P. falciparum parasites in vitro. Additionally, they found that these catechins were able to potentiate the effect of artemisinin when used in combination against malaria parasites (Sannella et al. 2007). ...
... In a study by Sannella et al. (2007), a crude extract, as well as EGCG and ECG from green tea leaves, were found to strongly inhibit the growth of P. falciparum parasites in vitro. Additionally, they found that these catechins were able to potentiate the effect of artemisinin when used in combination against malaria parasites (Sannella et al. 2007). ...
Article
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Plasmodium falciparum (P. falciparum) malaria presents serious public health problems worldwide. The parasite´s resistance to antimalarial drugs has proven to be a significant hurdle in the search for effective treatments against the disease. For this reason, the study of natural products to find new antimalarials remains a crucial step in the fight against malaria. In this study, we aimed to study the in vivo performance of the decoction of C. nucifera leaves in P. berghei-infected mice. We analyzed the effectiveness of different routes of administration and the acute toxicity of the extract. Additionally, we determined the suppressive, curative and prophylactic activity of the extract. The results showed that the decoction of leaves of C. nucifera is most effective when administered intramuscularly to mice in comparison to intraperitoneal, subcutaneous and intragastric methods. We also found that organ signs of acute toxicity appear at 2000 mg/kg/day as evidenced by necropsy examination. Additionally, we found that the prophylactic effect of the extract is of 48% inhibition, however, there is no curative effect. Finally, in a 4-day suppressive assay, we found that the extract can inhibit the growth of the parasite by up to 54% at sub-toxic doses when administered intramuscularly.
... About forty related structures were investigated and several compounds were found to have very good activity against all three enzymes. The flavones and flavonols exhibiting a simple substitution pattern (that is, no hydroxy groups on ring B and one or two hydroxy groups on rings A/C) show moderate inhibition effects toward FabG The same finding was also confirmed by another recent investigation [107]. Within this study two P. falciparum strains were investigated, namely 3D7, a chloroquine-sensitive one, and F9CR-1/FVO, a chloroquine-resistant one. ...
... Another important aspect, not yet developed, is the search for molecules with little or no antiplasmodial activity which can synergistically act with known antimalarial drugs against Plasmodium. Thus, it is known that several flavonoids of A. annua can promote and enhance the antiplasmodic activity of artemisinin [133,134], and recently it has been demonstrated that epigallocatechin gallate, epicatechin gallate and green tea extract not only have moderate antiplasmodial activity but also produce synergism in the presence of sublethal doses of artemisinin [107]. Also these molecules could have an important role in fighting malaria. ...
... 30 μM for 3D7 and 20 μM for F9CR-1/FVO), and (-)epicatechin gallate (61, IC 50 7 μM for 3D7 and 5 μM for F9CRsynergism was observed between artemisinin and these two derivatives on the 3D7 drug-sensitive parasite strain using sublethal doses of artemisinin, ranging from 1 to 10 nM, both of them in the presence (and in the absence) of 15 μM (-) epigallocatechin gallate (60) or of 5 μM (-) epicatechin gallate (61)[107]. ...
Article
The paper is a compilation of the studies reported in the literature concerning non-nitrogenous natural constituents that have shown antiplasmodial activity and aims to provide a basis for further in vivo studies as well as for clinical trials to develop new antimalarial agents. Due to the increasingly unsatisfactory outcomes for N-heterocyclic drugs, coupled with the rising incidence of the deadly falciparum malaria, the advent of non-nitrogenous lead compounds is timely, signaling a new era of antimalarial chemotherapy. Currently a few non-nitrogenous molecules are used in therapy, but many promising molecules of plant origin are under study, such as peroxide sesquiterpenes, quinoid triterpenes, quassinoids, gallic acid derivatives, lignans, flavonoids and biflavonoids, xanthones, naphthoquinones and phenylanthraquinones. Many of these constituents are isolated from plants used traditionally to treat malaria and fever. Ethnopharmacology can still be considered as a rich source of lead molecules.
... However, it was also toxic to A2780 ovarian cancer and HEK293 cells [131]. Another antiplasmodial germacranolide, 15-O-methylgoyazensolide (206), was isolated from the leaf and twig extract of Piptocoma antillana (Asteraceae). It was equally active against the Dd2 strain and A2780 human ovarian cancer cells, indicating a non-selective antiplasmodial activity [132]. ...
... A previous study had shown that EGCG did not interfere with the parasite folate pathway. Moreover, the antiplasmodial activity of green tea and 334 was demonstrated previously, and EGCG was shown to have an additive effect in combination with artemisinin [206]. However, a higher IC 50 value (37.2 µM) for EGCG against 3D7 parasites was reported in that study, even though comparable assay methods were used to evaluate the activity. ...
... However, a higher IC 50 value (37.2 µM) for EGCG against 3D7 parasites was reported in that study, even though comparable assay methods were used to evaluate the activity. The availability, low cost, and lack of toxicity of green tea coupled with the potentiating effect on the antiplasmodial activity of artemisinin could be exploited to design new artemisinin combination therapies [206]. ...
Article
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Background: Malaria remains a significant public health challenge in regions of the world where it is endemic. An unprecedented decline in malaria incidences was recorded during the last decade due to the availability of effective control interventions, such as the deployment of artemisinin-based combination therapy and insecticide-treated nets. However, according to the World Health Organization, malaria is staging a comeback, in part due to the development of drug resistance. Therefore, there is an urgent need to discover new anti-malarial drugs. This article reviews the literature on natural products with antiplasmodial activity that was reported between 2010 and 2017. Methods: Relevant literature was sourced by searching the major scientific databases, including Web of Science, ScienceDirect, Scopus, SciFinder, Pubmed, and Google Scholar, using appropriate keyword combinations. Results and discussion: A total of 1524 compounds from 397 relevant references, assayed against at least one strain of Plasmodium, were reported in the period under review. Out of these, 39% were described as new natural products, and 29% of the compounds had IC50 ≤ 3.0 µM against at least one strain of Plasmodium. Several of these compounds have the potential to be developed into viable anti-malarial drugs. Also, some of these compounds could play a role in malaria eradication by targeting gametocytes. However, the research into natural products with potential for blocking the transmission of malaria is still in its infancy stage and needs to be vigorously pursued.
... Phenolic compounds have many biological activities and their presence in foods has been associated with health promoting properties. One bioactive property of the kombucha that has not yet been explored is its antimalarial activity, though some studies have demonstrated the antiplasmodic effect of phenolic compounds (Carmo et al., 2020;Lima et al., 2015;Sannella et al., 2007). Carmo et al. (2020) demonstrated the promising effects of flavonoids present in extracts of camu-camu (Myrciaria dubia) in the fight against malaria. ...
... Taking these data into account, the reduction on Plasmodium falciparum viability observed herein may be attributed to these phenolic compounds of BTK. In this sense, Sannella et al. (2007) observed that green tea crude extracts, rich in catechins as is the BTK, exerted antimalarial activity in both sensitive (3D7, IC 50 = 30.76 µM) and resistant (W2, IC 50 = 28.61 ...
Article
This study shows the changes in physicochemical and microbiological composition, and in the phenolic profile of black tea kombucha during fermentation. In addition, the antimalarial potential of the kombucha was evaluated. Ultra-performance liquid chromatography-mass spectrometry multiplex analysis (UPLC-MSE) results revealed a 1.7 log2 fold-change increase in phenolics with the fermentation time, with emphasis on the increase of phenolic acids (0.3 log2 fold-change). Over time there was degradation of flavonoids such as nepetin, hesperidin and catechin 5-O-gallate, to the detriment of the increase in phenolic acids such as gallic acid and cinnamic acid. In addition, black tea kombucha presented antiplasmodic activity against the 3D7 (sensitive chloroquine) and W2 (resistant to chloroquine) strains. Therefore, important changes in the black tea kombucha phenolic profile take place during fermentation, which may help in the development of kombuchas with higher bioactive potential and contribute to a better understanding of the kombucha fermentation process.
... Flavonoids are its important constituents that belong to a group of natural substances with variable phenolic structures found in fruits, vegetables, grains, flowers, tea and wine. Moreover, flavonoids have been described to increase phagocytic activity and exerted antimalarial effect in vitro against P. falciparum [19][20][21]. Although biological and therapeutic efficacies of N. nucifera have been reported to a certain extent, the studies on the antimalarial activity and phagocytosis during malaria infection have not yet been performed. ...
... It has been reported the antioxidant potential was related to antimalarial activity in several plant extracts. Moreover, flavonoids, quercetin and kaempferol have been reported to have potent antimalarial activity against P. berghei infected mice [19,30,31]. Hence, these compounds in N. nucifera stamen extract, and its potent antioxidant activity might play a central role to inhibit PbANKA growth in vivo. ...
Antimalarial drug resistant malaria parasites are causing not only the spread of malaria to new areas but also its re-emergence in areas where it had previously been eradicated. In addition, malaria-associated impairment of phagocytosis has been reported during malaria parasite infection. The present study has been carried out to investigate the effect of Nelumbo nucifera stamen extract on phagocytosis and malaria parasite growth against Plasmodium berghei infected mice. Groups of ICR mice were treated orally by gavage with N. nucifera stamen extract (500, 1,000 and 2,000 mg/kg) after infection with P. berghei ANKA. Parasitemia, percent phagocytosis and phagocytic index were determined. At these doses, N. nucifera stamen extract inhibited parasitemia in dose-dependent manner, with similar level of antimalarial activity to chloroquine (5 mg/kg). In addition, increasing of phagocytosis and phagocytic index has also been observed in dose-dependent in infected mice treated with the extracts. In particularly, the highest activities of N. nucifera stamen extract were found at dose 2,000 mg/kg. These results indicated that aqueous crude extract of N. nucifera stamens have antimalarial and improve phagocytic activity against P. berghei ANKA infected mice.
... Different classes of compounds (alkaloids, flavonoids, quinones, xanthones and terpenes) with antiplasmodial activity have been isolated (Batista et al., 2009;Caniato and Puricelli, 2003;Nogueira and Lopes, 2011;Oliveira et al., 2009). Some of the compounds like galloylated catechins and procyanidins are reported to inhibit or reverse resistance of the most virulent malarial parasite Plasmodium falciparum (Park et al., 2010;Ramanandralbe et al., 2008;Sannella et al., 2007;Tasdemir et al., 2006). ...
... The mode of activity of such compounds is not known but is thought to be related to the unsaturated ketone moiety, which acts as a Michael acceptor . The antiplasmodial activity of epicatechin gallate (B12) against both chloroquine sensitive and resistant strains is consistent with that in the literature (Tasdemir et al., 2006;Sannella et al., 2007). This activity is associated with the galloyl ester substituent as catechin itself is not active. ...
Thesis
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Lannea plants belong to the family Anacardiaceae and are used in traditional medicine in the management of infectious diseases. Previous research on this genus focused on the biological activities of the plants. The Phytochemistry of most Lannea species is not reported. Lannea alata, Lannea rivae, Lannea schimperi and Lannea schweinfurthii were selected for this study. Previous studies illustrated antiplasmodial, cytotoxicity, antiviral, antioxidant and acetylcholinesterase inhibition of Lannea schweinfurthii extracts. Lannea schimperi extracts demonstrated antiulcer, antibacterial, cytotoxic and antifungal activities. However, no investigations were conducted to determine the compounds responsible for the observed activities. No prior work on Lannea alata and Lannea rivae has been reported. The present study aimed to isolate the biologically active phytochemicals occurring in the plants. This is the first phytochemical report of these Lannea species. In addition, pharmacological activities of the isolated compounds are discussed. From the four Lannea species seven known terpenes were isolated; sitosterol (A6), sitosterol glycoside (B6), taraxerol (B8) and taraxerone (B7), lupeol (A5), lupenone (D5) and lutein (B9). Two novel prenylated flavonoids, lanneaflavonol (A1) and dihydrolanneaflavonol (A2), together with eight known flavonoids, myricetin (B10), myricetin-3-O-αrhamnopyranoside (A3), myricetin-3-O-α-arabinofuranoside (A4), myricetin-3-O-βgalactopyranoside (B11), catechin (D7), epicatechin (D6), epicatechin gallate (B12) and rutin (D8) were also isolated.
... Finally, I should like to report some studies [85][86][87][88][89] with Artemisia annua L.. (Asteraceae, Figure 12) and artemisinin, a promising and potent antimalarial drug. These studies were carried out from the beginning in the framework of collaboration with a dear friend and colleague Prof. Luigi Messori of the Department of Analytical Chemistry of the University of Florence. ...
... Interesting results were also obtained using in the reaction hemoglobin instead of hemin [88]. Recent findings led to the discovery that green tea is also active against Plasmodium, and more importantly, its characteristic constituents, catechins, have a synergistic effect if administered with artemisinin [89]. Other studies on artemisinin and its extracts are also reported in this special issue. ...
Article
This paper presents an overview of Prof. Vincieri's accomplishments in his career as a researcher in the field of pharmacognosy (pharmaceutical biology), analytical phytochemistry and pharmaceutical technology applied to herbal drug preparations at the Department of Pharmaceutical Sciences of the University of Florence. This article is a recognition of his valuable contributions to these research fields, especially for his outstanding and innovative interdisciplinary studies on the quality control of herbal drugs, herbal drug preparations, herbal medicinal products, botanical food supplements, and some "special foods" such as grapes, wines, olives and olive oil.
... Flavonoids are known to have antibacterial activity, and some flavonoids have antimalarial activity [13]. Discovery and development of flavonoids as an antimalarial has been developed over the last few years [13,14]. ...
... Besides containing kaempferol 3-rhamnosyl-(1-3)-rhamnosyl-(1-6)glucoside, tea also contains a compound epigallocatechin 3,5,-di-Ogallate. Sannella et al. [14] stated in his study that the catechins content in tea, especially epigallocatechin-3-gallate and epicatechingallate, have inhibitory activity on the growth of P. falciparum in vitro. Another study states that tea catechin has the same potential as the binding of TCL with PfENR. ...
Article
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Objective: Malaria is a parasitic infection that causes worldwide health problems. The absence of an effective vaccine and Plasmodium strains that are resistant to antimalarial drugs emphasize the importance of developing new chemotherapeutic agents. The use of computers for in-silico screening, or virtual screening, is currently being developed as a method for discovering antimalarial drugs. One of the enzymes that can support the development of the malaria parasite is the Plasmodium falciparum enoyl-acyl carrier protein reductase (PfENR). Inhibition of these enzymes leads to Type II lipid biosynthesis inhibition on the parasite.Methods: This research investigates the use of virtual screening to find PfENR inhibitor candidates. A molecular docking method using GOLD software and the medicinal plants in Indonesia database will be used. This target has been optimized by the removal of residues and the addition of charge. Ligand is expected to be an inhibitor of PfENR.Results: In-silico screening, or virtual screening, found that the top five compounds with the highest GOLD score at trial are kaempferol 3-rhamnosyl- (1-3)-rhamnosyl-(1-6)-glucoside; cyanidin 3,5-di-(6-malonylglucoside); 8-hydroxyapigenin 8-(2’’, 4’’-disulfato glucuronide); epigallocatechin 3,5,-di- O-gallat; quercetin 3,4’-dimethyl ether 7-alpha-L-arabinofuranosyl-(1-6)-glucoside. They had GOLD scores of 94.73, 95.90, 86.46, 85.39, and 84.40, respectively.Conclusions: There are two candidate inhibitor compounds from tea (Camellia sinensis), which have potential for development as an antimalarial drug, which are kaempferol 3-rhamnosyl-(1-3)-rhamnosyl-(1-6)-glucoside and epigallocatechin 3,5,-di-O-gallate, with a GOLD score of 94.73 and 85.39, respectively.
... Within the framework of a large research project aimed at the discovery of antiplasmodial plant extracts and isolated constitu-ents having additive or synergistic activities with ARTs [18,19], we now report on the antiplasmodial properties of a decoction of papaya leaf in vitro against 3D7 P. falciparum strain, its synergistic effects with ART (1), and its activity in the Plasmodium berghei murine model alone or in combination with artesunate (ASN) (2) (▶ Fig. 1). ...
... Complete RPMI were changed daily and the parasitemia was followed using the thin blood smears. The tests were carried out as formerly reported [18,19]. Papaya dried extract and pure ART were prepared as stock solutions in 95 % EtOH and then diluted in complete RPMI medium to the required concentrations. ...
Article
Malaria treatment and control have become increasingly difficult because of the spread of drug-resistant strains of Plasmodium falciparum and Plasmodium vivax. Thus, there is a continuous need to develop new combination therapies such as artemisinin-based combination therapies (ACTs) to contrast the emergence of resistant Plasmodium strains. Despite ACT has been recommended by the World Health Organization since 2001, its overall deployment in poor endemic areas is very slow, principally due to its high cost. In the malaria endemic areas, plant remedies are still widely used mostly without assurance of their efficacy and/or safety. A variety of widespread herbal drugs or natural products were already reported for their possible plasmodicidal activities, but the studies concerning their activity in combination with artemisinins are very scarce. The antimalarial activity of papaya is mostly anecdotal, and the present study is aimed at investigating the antiplasmodial activity of a decoction obtained by traditional recipe from the mature leaves of Carica papaya. The decoction was analyzed by HPLC-DAD-MS (high performance liquid chromatography coupled with diodoarray detector and mass spectrometry) showing the presence of caffeoyl derivatives and di- and triglycosides of flavonols. The extract was found to be active against P. falciparum 3D7 strains with a synergism in the presence of artemisinin. In vivo activity against the murine malaria model of Plasmodium berghei was disclosed both for the dried extract alone (250, 500, and 750 mg/kg/d) and for its combination with artesunate (250 mg/kg/d papaya plus 10 mg/kg/d artesunate). This combination displayed the greatest antimalarial activity in terms of reduction of parasitemia and prevention of recrudescence in animals recovered from the infection.
... The mode of activity of such compounds is not known but is thought to be related to the unsaturated ketone moiety, which acts as a Michael acceptor (Roumy et al., 2009). The antiplasmodial activity of epicatechin gallate (14) against both chloroquine-sensitive and chloroquine-resistant strains was consistent with that in the literature (Tasdemir et al., 2006;Sannella et al., 2007). This activity is asso-ciated with the galloyl ester substituent as catechin itself is not active. ...
Article
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Six novel compounds, 3-nonadec-14′-(Z)-enyl phenol (1a); 4,5-dihydroxy-4,2′-epoxy-5-[16′-Z-18′-E-heneicosenyldiene]-cyclohex-2-enone (2), 2,4,5-trihydroxy-2-[16′-Z-heneicosenyl]-cyclohexanone (3); 4S,6R-dihydroxy-6-[12′-Z-heptadecenyl]-cyclohex-2-enone (4a); 4S,6R-dihydroxy-6-[14′-Z-nonadecenyl]-cyclohex-2-enone (4b); and 1,2,4-trihydroxy-4-[16′-Z-heneicosenyl]-cyclohexane (5) were identified from the roots and stems of Lannea rivae in addition to the known cardanols, 3-heptadec-12′-Z-enyl phenol (1b), 3-pentadec-10′-Z-enyl phenol (1c) and 3-pentadecyl phenol (1d), sitosterol (6), sitosterol glucoside (7), taraxerone (8), taraxerol (9), E-lutein (10), myricetin (11), myricetin-3-O-α-rhamnopyranoside (12), myricetin-3-O-β-galactopyranoside (13) and (-)-epicatechin-3-O-gallate (14). The ketones 4a and 4b were isolated as a mixture and were qualitatively separated and identified by GCMS. Myricetin (11) and epicatechin gallate (14) displayed over 90 % DPPH radical-scavenging activity at 50 μg mL−1, while its glycosides (12 and 13) showed percentages of over 70 % in the same assay. The same compounds 11 and 14 showed antibacterial activity similar to erythromycin and vancomycin against Gram-positive bacteria and were also active against Gram-negative bacteria, but not as much as the cefuroxime, ciprofloxacin and nalidixic acid standards. Compounds 1a–d, 4a–b and 5 were all relatively non-toxic, while 2 (the epoxy cyclohex-2-enone) and 3 (the trihydroxy cyclohexanone) showed more toxicity than the others. These two toxic compounds, 2 and 3 also showed antiplasmodial activity with IC50 values between 0.48 and 2.05 μg mL−1. The mixture of dihydroxy cyclohex-2-enones 4a and 4b, which was far less toxic than 2 and 3, also showed promising antiplasmodial activity and may be a possible lead for further investigation as an antiplasmodial drug.
... Jang et al. [9] studied the anticoccidial effects of green tea-based diets in chickens following oral infection with Eimeria maxima and found that the green teafed chicken produced significantly reduced fecal oocysts when compared to the E. maxima-infected group fed standard diet but it seems that the authors didn't check the sporulation rate of the shed oocysts. Sannella et al. [22] investigated the antimalarial properties of green tea and they found that crude extract of green tea and two of its constituents, epigallocatechin-3-gallate and epicatechin gallate, strongly inhibit Plasmodium falciparum growth in vitro. Recently, Molan et al. [15] studied the impact of water extracts from pine (Pinus radiata) bark on the sporulation of three species of avian coccidia and found that these extracts have the ability to decrease significantly the sporulation of the oocysts of these species under laboratory conditions. ...
... In vitro [75] Leaf extract Antibacterial In vitro [76,77] Leaf extract Antinociceptive activity In vivo [78] Leaf extract Antioxidant In vitro [79] Plant extract Anti-HIV In vitro [80] A. argyi Plant extract Anticancer In vitro [81] A. afra Plant extract Anticancer In vitro [82] A. biennis Plant Extract Anti-apoptosis In vitro [83] A. dracunculus Essential oil Antibacterial In vitro [84] A. arborescens, A. inculta Essential oil Antiradical In vitro [85] A. stricta Essential oil Antibacterial In vitro [86] A. ludoviciana Essential oil Antinociceptive activity In vivo [87] A. santonica Plant extract Antibacterial In vitro [88] A. keiskeana, A. selengensis Plant extract Anticancer In vitro [89] A. macrocephala Plant extract Antinociceptive In vivo [90] A. campestris Essential oil Antifungal In vitro [91] A. vulgaris Plant extract Antibacterial In vitro [92] A. vulgaris Leaf extract Anticancer In vitro [93] A. princeps Plant extract Antioxidant Anticancer In vitro [94] A. sieberi Plant extract Anticancer In vitro [95] A. judaica Essential oil Antibacterial In vitro [96] epigallocatechin gallate and catechin gallate, from a crude green tea extract showed strong antimalarial activity of their own and by enhancing the activity of artemisinin in in vitro studies. [113] Further, flavonoids have the potential to stimulate the anticancer effects of artemisinin by enhancing their bioavailability and serum half-life values, [114] inhibiting metabolic enzymes, [115] reduction of Fe 3þ and thus increasing the cellular Fe 2þ level [116] and by affecting key pro-apoptotic and antiapoptotic proteins in cancer cells. [117] Some of the major phytochemicals of medicinal interest found in Artemisia species are presented in Figure 1. ...
Article
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The genus Artemisia has been utilized worldwide due to its immense potential for protection against various diseases, especially malaria. Artemisia absinthium, previously renowned for its utilization in the popular beverage absinthe, is gaining resurgence due to its extensive pharmacological activities. Like A. annua, this species exhibits strong biological activities like antimalarial, anticancer and antioxidant. Although artemisinin was found to be the major metabolite for its antimalarial effects, several flavonoids and terpenoids are considered to possess biological activities when used alone and also to synergistically boost the bioavailability of artemisinin. However, due to the limited quantities of these metabolites in wild plants, in vitro cultures were established and strategies have been adopted to enhance medicinally important secondary metabolites in these cultures. This review elaborates on the traditional medicinal uses of Artemisia species and explains current trends to establish cell cultures of A. annua and A. absinthium for enhanced production of medicinally important secondary metabolites. Free full text: http://www.tandfonline.com/eprint/rTkxePCN6D9GxJwnjHgJ/full
... The recent reports have been described that black tea and green tea showed the effect to maintain and control blood glucose in diabetes patients [8]. Additionally, green tea extracts in malaria have been studied [9]. However, black tea extract in malaria researches and hypoglycemia protection during malaria infection have not yet been studied. ...
Hypoglycemia was found as one of all causes of death in malaria disease and urgently needed to fine new drugs to treat this condition. Hence, the present study was aimed to evaluate the effect of black tea extract on hypoglycemia induced by Plasmodium berghei infection in mice. Aqueous crude extract of black tea was freshly prepared using hot water method and used for efficacy test in vivo. For in vivo test, P. berghei ANKA infected mice were given orally by gavage with 500, 1000, and 2000 mg/kg of black tea extract for 4 consecutive days. Blood glucose levels were then measured. It was found that aqueous crude extract of black tea exerted dose-dependent anti-hypoglycemic activity, especially at a dose of 2000 mg/kg showed the highest activity. Although, pyrimethamine treated group showed significantly (p<0.01) decreasing of blood glucose levels, combination treatment with black tea extract could protect and maintain blood glucose to normal level. It can be concluded that aqueous crude extract of black tea presented anti-hypoglycemic activity against P. berghei infection in mice.
... Jang et al. [9] studied the anticoccidial effects of green tea-based diets in chickens following oral infection with Eimeria maxima and found that the green teafed chicken produced significantly reduced fecal oocysts when compared to the E. maxima-infected group fed standard diet but it seems that the authors didn't check the sporulation rate of the shed oocysts. Sannella et al. [22] investigated the antimalarial properties of green tea and they found that crude extract of green tea and two of its constituents, epigallocatechin-3-gallate and epicatechin gallate, strongly inhibit Plasmodium falciparum growth in vitro. Recently, Molan et al. [15] studied the impact of water extracts from pine (Pinus radiata) bark on the sporulation of three species of avian coccidia and found that these extracts have the ability to decrease significantly the sporulation of the oocysts of these species under laboratory conditions. ...
... Moreover, combination treatment of PYR and the extract also presented antimalarial activity. It has been reported the antioxidant potential was related to antimalarial activity in several plant extracts [18][19][20][21]. Hence, polyphenolic and sulfur compounds in shallot J Health Res  vol.29 no.x XXX 2015 extract, and its potent antioxidant activity might play a central role to inhibit PbANKA growth in vivo. ...
Article
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The present study has been carried out to investigate antimalarial and antihypoglycemic activities of aqueous crude extract of shallot (Allium ascalonicum) against Plasmodium berghei infected mice. Groups of ICR mice were treated orally with shallot extract (500, 1000, and 2000 mg/kg) after infection with P. berghei ANKA. Parasitemia and blood glucose levels were determined. At these doses, shallot extract inhibited parasitemia in dose-dependent manner, and could be used as combination treatment with pyrimethamine. In addition, antihypoglycemic activity has been observed in dose-dependent in infected mice treated with shallot extracts. In particularly, the highest activities of shallot extract were found at dose 2000 mg/kg. These results indicated that aqueous crude extract of shallot have antimalarial and antihypoglycemic activities against P. berghei ANKA infected mice.
... And acts as a hydrogen donor [22] . Furthermore, esterbonded gallate catechins from green tea, such as epigallocatechin-3-gallate (EGCG) and epicatechin-3-gallate (ECG), are potent in vitro inhibitors of several DHFRs at concentrations found in the serum and tissues of green tea drinkers (0.1-1.0 µM) [23] . ...
Article
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Methotrexate (MTX), a folic acid antagonist is widely used for the treatment of a variety of tumors. In the present study, the possible protective effect of aqueous green tea extract (AGTE) in methotrexate-induced haematotoxicity was investigated. Four main groups of white Albino rats were used: control group, (MTX) group, following a single dose of MTX (20 mg/kg, i.p.) saline was administered for 5 days. (AGTE) group, was treated with 1.25% concentration of AGTE only for 12 days and the (MTX+AGTE) group, in this group rats received different concentrations of AGTE (0.625, 1.25 and 2.5%), as their sole source of drinking water, 7days before and 5 days after MTX treatment. MTX induced significant decreases in RBC, Hb, Hct, WBC and platelets. Whereas increased MCV and MCH. Moreover, the concentrations of AGTE play a major role. The best protective effects of AGTE treatment were observed at the concentration 1.25% While 0.625% and 2.5% AGTE had no protective effects on haematological parameters.
... Moreover, some pyran and fused 4H-pyran derivatives have found application in clinical medicine. Zanamivir (III, Fig. 1) has been shown to be effective in treating influenza [23] and epicatechin (epigallocatechin) gallates IVa,b (Fig. 1) demonstrate strong effects against Plasmodium falciparum, the mosquito-borne organism responsible for malaria [24]. Due to the results *Address correspondence to this author at the Chemistry Department, Faculty of Science, Al-Azhar University, 11884, Nasr City, Cairo, Egypt; Tel: +201008199893; Fax: +20222629358; E-mail: ash_abdelwahab@hotmail.com mentioned above, we report here facile synthesis of the title compounds using benzylphthalazin-1-ylaminophenols as starting materials. ...
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A series of (4-benzylphthalazin-1-ylamino)phenols 4-6 were prepared. Bromination of (4-benzylphthalazin-1- ylamino)phenol (1) with bromine afforded the bromophenol derivative 7, while condensation of the isomeric (4- benzylphthalazin-1-ylamino)phenol (2) or 7-(4-benzylphthalazin-1-ylamino) naphthalene-2-ol (3) with arylidenemalononitriles 8a-c in ethanol/piperidine solution afforded chromene derivatives 9a-c and 10a,b. Treatment of 7-(4- benzylphthalazin-1-ylamino)-4-(p-methoxyphenyl)-4H-chromene-3-carbonitrile (9a) with triethyl orthoformate/Ac2O afforded ethoxymethyleneamino derivative 11. Condensation of 9a with DMFDMA/xylene gave chromenopyrimidine derivative 13, while treatment of 9a with Ac2O afforded the N-acetylimino derivative 14. The structures of the newly synthesized derivatives were confirmed by their elemental analysis and spectral data. The antimicrobial activities of some selected compounds were also studied and some of them were found to exhibit promising effects against Gram-positive and Gram-negative bacteria and fungi.
... Interestingly, EGCG, (−)-epicatechin 3gallate, caffeoylquinic acid and rosmarinic acid from green tea potentiated anti-P. falciparum activity of artemisinin but did not interfere with the folate pathway [36,37] . Digitonin synergistically increases toxicity of EGCG on survival of plasmodium sporozoites [38]. ...
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Objective: To examine the efficacy of 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one (CM1) iron chelator and green tea extract (GTE) as anti-malarial activity in Plasmodium berghei (P. berghei) infected mice. Methods: The CM1 (0–100 mg/kg/day) and GTE (0–100 mg (−)-epigallocatechin 3-gallate equivalent/kg/day) were orally administered to P. berghei infected mice for consecutive 4 days. Parasitized red blood cells (PRBC) were enumerated by using Giemsa staining microscopic method. Results: CM1 lowered percentage of PRBC in dose-dependent manner with an ED50 value of 56.91 mg/kg, when compared with pyrimethamine (PYR) (ED50 = 0.76 mg/kg). GTE treatment did not show any inhibition of the malaria parasite growth. In combined treatment, CM1 along with 0.6 mg/kg PYR significantly inhibited the growth of P. berghei in mice while GTE did not enhance the PYR anti-malarial activity. Conclusions: CM1 would be effective per se and synergize with PYR in inhibiting growth of murine malaria parasites, possibly by limiting iron supply from plasma transferrin and host PRBC cytoplasm, and chelating catalytic iron cstitutive in parasites’ mitochondrial cytochromes and cytoplasmic ribonucleotide reductase. CM1 would be a promising adjuvant to enhance PYR anti-malarial activity and minimize the drug resistance.
... Moreover, combination treatment of PYR and the extract also presented antimalarial activity. It has been reported the antioxidant potential was related to antimalarial activity in several plant extracts [18][19][20][21]. Hence, polyphenolic and sulfur compounds in shallot J Health Res  vol.29 no.1 February 2015 extract, and its potent antioxidant activity might play a central role to inhibit PbANKA growth in vivo. ...
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The present study investigated antimalarial and antihypoglycemic activities of aqueous crude extract of shallot (Allium ascalonicum) in Plasmodium berghei infected mice. Groups of ICR mice were treated orally with shallot extract (500, 1000, and 2000 mg/kg) after infection with P. berghei ANKA. Parasitemia and blood glucose levels were determined. At these doses, shallot extract inhibited parasitemia in dose-dependent manner, and could be used as combination treatment with pyrimethamine. In addition, antihypoglycemic activity was observed in dose-dependent fashion in infected mice treated with shallot extracts. In particular, the highest activities of shallot extract were found at dose 2000 mg/kg. These results indicated that aqueous crude extract of shallot has antimalarial and antihypoglycemic activities in P. berghei ANKA infected mice.
... The standard drug, CQ caused chemosuppression, which was higher than those of the extract treated groups. It has been reported that the antioxidant potential was related to antimalarial activity in several plant extracts [21][22][23][24]. Hence, flavonoids and polyphenolic compounds in Siamese neem tree, and its potent antioxidant activity might play a role to inhibit PbANKA growth in vivo. ...
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The present study has been carried out to investigate antimalarial and anti-hypoglycemic activities of leaf aqueous crude extract of Siamese neem tree (Azadirachta indica) against Plasmodium berghei infected mice. Groups of ICR mice were treated orally with Siamese neem tree extract (500, 1000, and 2000 mg/kg) after infection with P. berghei ANKA. Parasitemia and blood glucose levels were determined. At these doses, Siamese neem tree extract inhibited parasitemia in dose-dependent manner with significance (P < 0.05). In addition, anti-hypoglycemic activity has been observed in infected mice treated with Siamese neem tree extracts. In particularly, the highest activities of Siamese neem tree extract were found at dose 2000 mg/kg. These results indicated that leaf aqueous crude extract of Siamese neem tree have antimalarial and anti-hypoglycemic activities against P. berghei ANKA infected mice.
... The previous study reported that EGCG and ECG were able to inhibit the growth of P. falciparum (strains NF54, K1 and 3D7) with IC 50 value was 10 µM-40 µM, while the ungallated catechins had less potent anti-malarial activity with IC 50 values in excess of 100-300 µM. The anti-malarial mechanisms of catechins were not yet able to be explained [35,36]. ...
... Combinations of two different PIs showed either synergistic or additive effects. Similar effects have been recorded previously for other antimalarial compounds and PIs [50][51][52]. DtTCI and AeTI complimented each other better than their respective combinations with STI. This may possibly be due to the fact that there is a slightly low (∼42%) sequence homogeneity between AeTI and DtTCI as compared to a high sequence homogeneity between AeTI and STI (∼47.4%) as well as DtTCI and STI (∼53%). ...
... Tea is rich in polyphenols associated with numerous pharmacological properties such as; antimicrobial [5], anti-inflammatory [6], anti-aging [7,8] antimalarial [9] and antioxidant activity [1,3,10]. Cancer, accelerated aging and other chronic disease associated with free radical induced oxidative damage [4] can be ameliorated by phytochemicals in tea since antioxidants in tea have been shown to protect DNA from damage induced by free radicals and slow or halt initiation and progression of cancerous tumor growth [12]. ...
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Background Tea (Camellia sinensis) infusions are widely consumed beverages with numerous health benefits. However, physiological and molecular responses mediating these activities are poorly understood. Method Three replicates of 4TI cancer cell suspension (2.0 × 105 cells/ml) were challenged in vitro with various concentrations of green, black and purple tea infusions to asseses their cytoxicity and associated differentially expressed genes in the cells. Inhibitory activity was tested by using serial dilutions of respective tea infusions in a 96 well ELISA plate. ResultsGreen tea had the highest inhibition on 4TI cells proliferation at a concentration of IC50 = 13.12 μg/ml. Further analysis of the 4TI cancer cell line treated with tea using 454 pyrosequencing generated 425,696 reads with an input mean length of 286.54. Trimmed sequences were imported on a CLC genomic workbench v7.03 and annotated on a reference mouse genome (Mus musculus strain C57BL/6 J). Results revealed a differential expression of apoptosis related genes in the transcriptome. Casp8, Casp9, Casp3, Casp6, Casp8AP2, Aifm1, Aifm2 and Apopt1 genes were significantly upregulated indicating the process of apoptosis was initiated and executed. Conclusion These findings on caspases offer valuable information on the mechanism of tea as an anticancer agent and will contribute to further research in future novel treatments.
... In addition, hundreds of volatile compounds contribute to aromatic properties of tea (Yang 2005). In vitro and animal studies provide strong evidence that the bioactivity of tea polyphenolic catechins are able to affect the pathogenesis of several chronic diseases, including cancers, cardiovascular diseases, diabetes, obesity, and other bacterial and viral diseases (Khan and Mukhtar 2007;Sannella et al. 2007;Yang et al. 2009;Peng et al. 2014). Clinical studies further support the role of tea in human health (Howes and Simmonds 2014). ...
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Organic tea production has increased in China over the past decade because of the perceived higher quality of the tea as well as the benefits for environmental and human wellbeing. The present study compared the functional quality components of tea harvested from organic and conventional management systems in adjacent fields within the same farms at six sites in eastern China. Findings demonstrated that water extracts of organic tea had significantly higher concentrations of key catechins linked to tea quality, including epigallocatechin gallate (EGCG), epigallocatechin (EGC), epicatechin gallate (ECG) and epicatechin (EC), compared to that of conventional tea. Concentrations of proline and γ-aminobutyric acid were also statistically higher in organic tea from some sites. However, most of free amino acids, particularly theanine, were lower in organic tea. The findings indicated that the tea in organic systems were under greater environmental stress than the tea in the conventional system, as accumulation of catechins and proline in plants is associated with environmental stress. The lower concentrations of amino acids in organic tea indicated potential nitrogen deficiencies and the need for managing soil nitrogen to increase overall amino acid levels while still managing for high levels of polyphenols. The higher concentrations of antioxidant compounds in organic tea suggested potentially greater health benefits, as these compounds are linked to disease mitigation and health promotion in human consumers. Overall, this study showed improved quality characteristics of organically produced tea whilst also highlighting agro-ecosystem techniques to further enhance the functional quality characteristics of organic tea on the basis of amino acid profiles.
... Ce composé a la capacité d'inhiber les réponses pro-inflammatoires en bloquant l'activation du facteur de transcription NFkB (Rodrigues de Araújo et al., 2019).En outre, parmi les composés chimiques différents, l'epigallocatechin gallate (EGCG), identifié uniquement dans l'extrait de Terminalia d'origine Dubréka, est largement étudié pour sa bioactivité polyvalente. En plus de son activité antiplasmodiale(Tasdemir et al., 2006) et de son effet potentialisateur de l'artémisinine(Sannella et al., 2007), l'EGCG inhibe trois enzymes importantes (FabG, FabZ et FabI) impliquées dans la biosynthèse des acides gras de P. ...
Thesis
Le paludisme demeure la première préoccupation médicale de bien des pays africains dont la Guinée où la quasi-totalité de la population est exposée au risque d'infection avec une prévalence estimée à 15% chez les enfants de moins de 5 ans. En dehors de la médecine conventionnelle, la pharmacopée et la médecine traditionnelle guinéennes constituent des recours fréquents dans la gestion du paludisme par les familles. A cet égard, des enquêtes ethnobotaniques ont permis de recenser et de collecter de nombreuses plantes médicinales parmi lesquelles Terminalia albida, Desmodium velutinum et Rourea minor. Dans le cadre d'une validation des usages traditionnels, ces plantes ont été évaluées in vitro avec la souche chloroquino-résistante PfK1 et in vivo dans deux modèles murins à Plasmodium chabaudi chabaudi pour le paludisme simple, et à Plasmodium berghei ANKA pour le neuropaludisme. Les résultats obtenus ont permis de mettre en évidence le potentiel antipaludique de T.albida. En outre, la comparaison de deux extraits de T. albida issus de deux régions différentes de Guinée, a permis de mettre en évidence des efficacités in vitro et in vivo différentes selon la provenance de la plante. Afin de comprendre les mécanismes d'action de T. albida dans le modèle de neuropaludisme, les capacités anti-inflammatoires et anti-oxydantes de la plante ont été étudiées in vivo et in vitro dans des conditions inflammatoires. In vivo, l'administration de l'extrait de T.albida a permis de limiter le recrutement des lymphocytes T et l'expression des marqueurs pro-inflammatoires dans le cerveau des souris traitées. Ces propriétés ont été confirmées in vitro dans un modèle inflammatoire non palustre. In vitro, T.albida a également démontré une remarquable activité dose-dépendante de neutralisation des espèces réactives de l'oxygène. Ainsi, les propriétés anti-inflammatoires et anti-oxydantes de T.albida participent à la résolution du neuropaludisme dans le modèle d'infection à P. berghei ANKA. Des investigations phytochimiques ont permis d'identifier trente-huit composés dans l'écorce de la tige de T. albida. Parmi elles, plusieurs molécules déjà identifiées peuvent être responsables des différentes activités biologiques observées, notamment les tanins et les triterpénoïdes. Enfin, des investigations botaniques ont permis de fournir des éléments caractéristiques permettant de déterminer la provenance de T. albida et de mettre en évidence l'influence de l'écosystème sur la production des métabolites secondaires dans les espèces de Terminalia récoltées à différents endroits. Ces résultats confirment l'effet antipaludique de T. albida et valident son usage traditionnel. Cependant, des études complémentaires sont nécessaires pour identifier plus précisément les molécules actives. Les activités anti-inflammatoires et anti-oxydantes de T. albida démontrées dans ce travail présentent également un intérêt pour la prise en charge de nombreuses pathologies, autres que le paludisme.
... And acts as a hydrogen donor [22] . Furthermore, esterbonded gallate catechins from green tea, such as epigallocatechin-3-gallate (EGCG) and epicatechin-3-gallate (ECG), are potent in vitro inhibitors of several DHFRs at concentrations found in the serum and tissues of green tea drinkers (0.1-1.0 µM) [23] . ...
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Methotrexate (MTX), a folic acid antagonist is widely used for the treatment of a variety of tumors. In the present study, the possible protective effect of aqueous green tea extract (AGTE) in methotrexate-induced haematotoxicity was investigated. Four main groups of white Albino rats were used: control group, (MTX) group, following a single dose of MTX (20 mg/kg, i.p.) saline was administered for 5 days. (AGTE) group, was treated with 1.25% concentration of AGTE only for 12 days and the (MTX+AGTE) group, in this group rats received different concentrations of AGTE (0.625, 1.25 and 2.5%), as their sole source of drinking water, 7days before and 5 days after MTX treatment. MTX induced significant decreases in RBC, Hb, Hct, WBC and platelets. Whereas increased MCV and MCH. Moreover, the concentrations of AGTE play a major role. The best protective effects of AGTE treatment were observed at the concentration 1.25% While 0.625% and 2.5% AGTE had no protective effects on haematological parameters.
... Previous studies have presented data on the anti-microbial effects of C. sinensis and its components against Gram positive and Gram negative multi-drug resistant pathogens (Parvez et al., 2019). In regard to parasites, C. sinensis potentiated the antimalarial effect of artemisinin without interfering with the folate pathway (Sannella et al., 2007;Thipubon et al., 2015). Also, C. sinensis reduced the Haemonchus contortus worm burden (Zhong et al., 2014), inhibited promastigote and amastigote forms of Leishmania braziliensis (Inacio et al., 2014), and inhibited Leishmania amazonensis (dos Reis et al., 2013;Inacio et al., 2013). ...
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The effect of Camellia sinensis (green tea) on the growth of Acanthamoeba castellanii trophozoites was examined using a microplate based-Sulforhodamine B (SRB) assay. C. sinensis hot and cold brews at 75% and 100% concentrations significantly inhibited the growth of trophozoites. We also examined the structural alterations in C. sinensis-treated trophozoites using transmission electron microscopy (TEM) and scanning electron microscopy (SEM). This analysis showed that C. sinensis compromised the cell membrane integrity and caused progressive destruction of trophozoites. C. sinensis also significantly inhibited the parasite's ability to form cysts in a dose-dependent manner and reduced the rate of excystation from cysts to trophozoites. C. sinensis exhibited low cytotoxic effects on primary corneal stromal cells. However, cytotoxicity was more pronounced in SV40-immortalized corneal epithelial cells. Chromatographic analysis showed that both hot and cold C. sinensis brews contained the same number and type of chemical compounds. This work demonstrated that C. sinensis has acanthamoebicidal activity against trophozoite and cystic forms of A. castellanii. Further studies are warranted to identify the exact substances in C. sinensis that have the most potent anti-acanthamoebic effect.
... Methanolic extracts of S. aromaticum and C. sinensis exhibited growth-inhibitory effects against Babesia and Theileria parasites. Several reports documented the inhibitory effect of S. aromaticum and C. sinensis methanolic extracts against the growth of other apicomplexan parasites including Plasmodium which is closely related to Babesia and Theileria (Bagavan et al., 2011;Sannella et al., 2007). Santoro et al. (2007) reported that S. aromaticum eugenol has strong trypanocidal activity. ...
Article
Currently, chemotherapeutics against piroplasmosis are also associated with toxicity and the emergence of drug-resistant parasites. Therefore, the discovery of new drug compounds is necessary for the effective control of bovine and equine piroplasms. Syzygium aromaticum (clove) and Camellia sinensis (green tea) have several documented medicinal properties. In the present study, the growth-inhibiting effects of S. aromaticum and C. sinensis methanolic extracts were evaluated in vitro and in vivo. The half-maximal inhibitory concentration (IC 50 ) values for methanolic S. aromaticum against Babesia bovis, B. bigemina, B. divergens, B. caballi, and Theileria equi were 109.8 ± 3.8, 8.7 ± 0.09, 76.4 ± 4.5, 19.6 ± 2.2, and 60 ± 7.3 μg/ml, respectively. Methanolic C. sinensis exhibited IC 50 values of 114 ± 6.1, 71.3 ± 3.7, 35.9 ± 6.8, 32.7 ± 20.3, and 60.8 ± 7.9 μg/ml against B. bovis, B. bigemina, B. divergens, B. caballi, and T. equi, respectively. The toxicity assay on Madin–Darby bovine kidney (MDBK), mouse embryonic fibroblast (NIH/3T3), and human foreskin fibroblast (HFF) cell lines showed that methanolic S. aromaticum and methanolic C. sinensis affected only the viability of the MDBK cell line with half-maximal effective concentrations (EC 50 ) of 894.7 ± 4.9 and 473.7 ± 7.4 μg/ml, respectively, while the viability of NIH/3T3 and HFF cell lines was not affected even at 1000 μg/ml. In the in vivo experiment, methanolic S. aromaticum and methanolic C. sinensis oral treatments at 150 mg/kg inhibited the growth of Babesia microti in mice by 69.2% and 42.4%, respectively. These findings suggest that methanolic S. aromaticum and methanolic C. sinensis extracts have the potential as alternative remedies for treating piroplasmosis.
... Also the ingestion of cocoa powder by mice revealed the same anti-malarial effects of epicatechin [70], as well as the intake of green tea, where the IC50 values measured sufficient to inhibit the malarial activity were > 300 µM for (-)-epigallocatechin and > 500 µM for epicatechin. This property presented by epicatechin is possibly due to its ability to interfere with some biochemical pathways, for example with the inhibition of dihydrofolate reductase, one of the typical mechanism of action for a few clinically established antimalarial drugs [71]. ...
Chapter
Phenolic compounds are phytochemicals extensively distributed by fruits, vegetables and other food products. Recently, they have been gaining great scientific interest due to their great antioxidant capacity. According to their chemical structure, they can be divided into phenolic acids, stilbenes and flavonoids like as anthocyanins, flavonols, flavanones, flavanonols, flavones, isoflavones and flavan-3-ols. These last ones are the most structurally complex subclass of flavonoids, ranging from simple monomers (+)-catechin and its isomers (-)-epicatechin, to complex structures, as oligomeric and polymeric proanthocyanidins (condensed tannins). (+)-Catechin and (-)-epicatechin are present in several vegetables and fruits, being (-)-epicatechin widely present in chocolates, red wine, green and black teas, broad beans, pears, apples, black grapes, apricots, and in raspberry, blackberry, cherry and bilberry fruits, and are responsible for the astringent taste and the bitter note. As like the others flavonoids, (-)-epicatechin shows the C6-C3-C6 structure, which is the major responsible for their displayed health benefits. Recent studies reported that (-)-epicatechin is very effective against free radical scavenging and lipid peroxidation, possess anti-hemorrhagic properties, and proved to have metabolic and physiologic effects in protection against worldwide pandemic pathologies, like cancer, diabetes, osteoporosis, cardiovascular and neurodegenerative diseases. Thus, this chapter will be focused in principal sources and health benefits associated with food consumption rich in (-)-epicatechin, highlighting their chemical structure, bioavailability, biological potential and health benefits currently described.
... Antimalarial activities of many local Thai plants have been reported, for example the Siamese neem tree, green tea extracts, Garcinia mangostana Linn., Phyllanthus emblica, Annona squamosa, Centella asiatica and Ipomoea pes-caprae. [8][9][10][11] The objective of this study was to determine the antimalarial activity against the P. falciparum strain TM267 of ethanol crude extracts from 20 local Thai herbs, Azadirachta indica A., Saccharu mofficinarum L., Curcuma longa L., Curcuma xanthorrhiza Roxb., Zingiber montanum, Citrus hystrix DC., Hibiscus sabdariffa L., Ocimum sanctum L., Ocimum basilicum L., Allium sativum L., Quercus infectoria, Myristica fragrans Houtt., Strychnos nux-vomica L., Salacia chinensis L., Maclura cochinchinensis Lour., Pentace burmanica Kurz., Mammea siamensis Kosterm., Vitex trifolia Linn., Plumbago indica L. and Dracaena loureiri. Interestingly, this study also examined potential antimalarial drug prediction from PfDHFR docking. ...
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Objective: To determine the antimalarial activity of ethanol crude extracts from 20 Thai herbs against Plasmodium falciparum (P. falciparum) chloroquine-resistant strain TM267. Molecular docking of the active compounds from the selected Thaiherbs were analyzed with Plasmodium falciparum dihydrofolate reductase (PfDHFR). Material and Method: An in vitro study of antimalarial activity against P. falciparum TM267 was done using a parasite lactate dehydrogenese assay, and the cytotoxic effects of extracts were tested against Vero cells using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The 50% inhibitory concentration (IC50) and 50% cytotoxicity concentration were calculated from the dose-response curves. Molecular docking and post-docking were analyzed with the x-ray crystal structure of PfDHFR-thymidylate synthase complexed with pyrimethamine, nicotinamide adenine dinucleotide phosphate and deoxyuridylate. Results: Of these, the Plumbago indica L. root extract showed high antimalarial activity, with an IC50 value of 3.7 μg/ml and less cytotoxicity when tested against Vero cells, followed by the Citrus hystrix DC. fruit extract, Vitex trifolia Linn. root extract, Ocimum sanctum L. leave extract, of Allium sativum L. bulb extract and Salacia chinensis L. stem extract, respectively. All 7 active compounds reported from these herbal extracts had high docking scores against PfDHFR. The Citrusoside C from Citrus hystrix DC. had the highest docking score. Conclusion: It could be purposed that there were active compounds in Plumbago indica L., Vitex trifolia Linn. and Citrus hystrix DC. which are potential inhibitors against malaria that could bind to the active site of PfDHFR. However, the active Citrusosides from Citrus hystrix DC. should be further investigated for their effectiveness against malaria.
... Significant cooperation between NF-kB members and the Nrf2 signaling pathway was observed in various physiological disturbances. Additionally, it has been exposed that the Keap1 (Ahmad, Cheng, & Mukhtar, 2000;Babu & Liu, 2008;Bao & Peng, 2016;Bernatoniene & Kopustinskiene, 2018;Farkhondeh et al., 2020;Farkhondeh, Yazdi, & Samarghandian, 2018;Khan, Afaq, Saleem, Ahmad, & Mukhtar, 2006;Mak, 2012;Saeed et al., 2017;Samarghandian, Azimi Nezhad, & Farkhondeh, 2017;Sannella et al., 2007;Sinija & Mishra, 2008;Song & Seong, 2007;Thielecke & Boschmann, 2009;Yamagata, 2020). Green tea catechins are also used as flavoring and coloring agents in foods. ...
Chapter
Circular RNAs (cirRNAs) are long, noncoding endogenous RNA molecules and covalently closed continuous loop without 5′–3′ polarity and polyadenylated tail which are largely concentrated in the nucleus. CirRNA regulates gene expression by modulating microRNAs and functions as potential biomarker. CirRNAs can translate in vivo to link between their expression and disease. They are resistant to RNA exonuclease and can convert to the linear RNA by microRNA which can then act as competitor to endogenous RNA. This chapter summarizes the evolutionary conservation and expression of cirRNAs, their identification, highlighting various computational approaches on cirRNA, and translation with a focus on the breakthroughs and the challenges in this new field.
... Catechin, (−)-epicatechin, epigallocatechin-3-gallate, epigallocatechin, and (−)-epicatechin gallate, are flavanols or polyphenols. (−)-Epicatechin is a sort of polyphenolic flavonoids which has identified and isolated from variety of medicinal plants such as Ricinus communis (Zahir et al. 2011), Theobroma cacao (Erlejman et al. 2008), Rubus coriifolius (Alanís et al. 2003), Camellia sinensis (Sannella et al. 2007), Crataegus laevigata (Kirakosyan et al. 2003) and Carapa guianensis (Qi et al. 2003). It is as essential phytoconstituents which is having wide spectrum of biological activities against certain globally challenged diseases and their related disorders as well. ...
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Gaucher disease is one of the common lysosomal storage diseases widespread all over the world. It is divided into three types such as type 1 (non-neuropathic), type 2 (acute infantile neuropathic) and type 3 (chronic neuropathic). This is caused by the deficiency of glucocerebrosidases from the midpoint nervous system. Recent years, computational tools are very important and play a vital role in identifying new leads for disease treatment. This study was performed to screen the effective bioactive molecules against glucocerebrosidases. In this study, Molecular docking and ADME profiles of bioactive molecules were found with the help of Schrödinger software. Results showed that, (−)-epicatechin are having best docking score and good binding affinity than other ligands. Hence, we concluded that the (−)-epicatechin may be a better drug candidate for gaucher disease which can be explored further.
... Catechin, (−)-epicatechin, epigallocatechin-3-gallate, epigallocatechin, and (−)-epicatechin gallate, are flavanols or polyphenols. (−)-Epicatechin is a sort of polyphenolic flavonoids which has identified and isolated from variety of medicinal plants such as Ricinus communis (Zahir et al. 2011), Theobroma cacao (Erlejman et al. 2008), Rubus coriifolius (Alanís et al. 2003), Camellia sinensis (Sannella et al. 2007), Crataegus laevigata (Kirakosyan et al. 2003) and Carapa guianensis (Qi et al. 2003). It is as essential phytoconstituents which is having wide spectrum of biological activities against certain globally challenged diseases and their related disorders as well. ...
... Antiplasmodial activity of some gallic acid derived from green tea was also tested by Sannela et al., and the result showed that both epigallocatechingallate and epigallocatechin have potential antiplasmodial activity. [16] Oxidative stress through the generation of reactive oxygen species plays important role in the pathogenesis of malaria infection that causes hemoglobin degradation. [17] As phenolic compounds, gallic acid, methyl gallate, and kempferol-3-O-rhamnoside have antioxidant properties that may be responsible for antiplasmodial activity. ...
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Background: Alectryon serratus was selected from a screening program devoted to search naturally occurring antimalarial compound from plants in Alas Purwo National Park, Banyuwangi, East Java, Indonesia. The previous studies showed that ethanol extract of A. serratus leaves contains some polyphenol compounds. Objective: This study was designed to isolate and investigate antiplasmodial activity of polyphenol compounds. Material and methods: The ethanol extract of A. serratus leaves was fractioned using liquid-liquid fractionation and column chromatography. Isolated compounds were identified using High-performance liquid chromatography, ultraviolet-visible, nuclear magnetic resonance, and compared with references. The isolates were tested in vitro for antiplasmodial activity against chloroquine-sensitive 3D7 strain of Plasmodium falciparum. Thin blood smears were used to assess the levels of parasitemia and growth inhibition of the isolates. Result: Half maximal Inhibitory concentration of Gallic acid (1), methyl gallate (2), and kempferol-3-O-rhamnoside (3) were 0.0722 μM, 0.0128 μM, and 3.4595 μM, respectively. Conclusion: The results suggest that gallic acid, methyl gallate, and kempferol-3-O-rhamnoside isolated from A. serratus leaves have antiplasmodial activity and are potential to be developed as antimalarial drugs. Summary: The ethanol extract of Alectryon serratus leaves was successively fractionated in CH2Cl2, EtOAc, and n-butanol. EtOAc fraction was fractionated using column chromatography and purified using preparative thin-layer chromatography (TLC). Isolates were studied for their antiplasmodial activity on parasites culture of chloroquine-sensitive 3D7 strain of Plasmodium falciparum. Parasitemia percentages, growth percentages, and inhibition percentages of each group were calculated. The half maximal inhibitory concentration (IC50) values that represent the concentration required to inhibit 50% of Plasmodium growth were calculated from a calibration curve using linear regression. The results suggest that isolates have antiplasmodial activity and are responsible in the antimalarial activity of Alectryon serratus leaves. Abbreviations Used: S.F: Subfraction, EGCG: Epigallocatechingallate, EGC: Epigallocatechin.
... EGCG inhibited 50% of parasite growth (IC 50 ) at a concentration of 2.9 µM. This finding further suggests that EGCG is a potent antiplasmodial agent, as previously suggested [21]. Figure 6. ...
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Heat shock proteins (Hsps), amongst them, Hsp70 and Hsp90 families, serve mainly as facilitators of protein folding (molecular chaperones) of the cell. The Hsp70 family of proteins represents one of the most important molecular chaperones in the cell. Plasmodium falciparum, the main agent of malaria, expresses six Hsp70 isoforms. Two (PfHsp70-1 and PfHsp70-z) of these localize to the parasite cytosol. PHsp70-1 is known to occur in a functional complex with another chaperone, PfHsp90 via a co-chaperone, P. falciparum Hsp70-Hsp90 organising protein (PfHop). (−)-Epigallocatechin-3-gallate (EGCG) is a green tea constituent that is thought to possess antiplasmodial activity. However, the mechanism by which EGCG exhibits antiplasmodial activity is not fully understood. A previous study proposed that EGCG binds to the N-terminal ATPase domain of Hsp70. In the current study, we overexpressed and purified recombinant forms of two P. falciparum cytosol localized Hsp70s (PfHsp70-1 and PfHsp70-z), and PfHop, a co-chaperone of PfHsp70-1. Using the surface plasmon resonance approach, we demonstrated that EGCG directly binds to the two Hsp70s. We further observed that binding of EGCG to the two proteins resulted in secondary and tertiary conformational changes. In addition, EGCG inhibited the ATPase and chaperone function of the two proteins. Furthermore, EGCG abrogated association of the two Hsp70s with their functional partners. Using parasites cultured in vitro at the blood stages, we observed that 2.9 µM EGCG suppressed 50% P. falciparum parasite growth (IC50). Our findings demonstrate that EGCG directly binds to PfHsp70-1 and PfHsp70-z to inhibit both the ATPase and chaperone functions of the proteins. Our study constitutes the first direct evidence suggesting that the antiplasmodial activity of EGCG is at least in part accounted for by its inhibition of Hsp70 function.
... Significant cooperation between NF-kB members and the Nrf2 signaling pathway was observed in various physiological disturbances. Additionally, it has been exposed that the Keap1 (Ahmad, Cheng, & Mukhtar, 2000;Babu & Liu, 2008;Bao & Peng, 2016;Bernatoniene & Kopustinskiene, 2018;Farkhondeh et al., 2020;Farkhondeh, Yazdi, & Samarghandian, 2018;Khan, Afaq, Saleem, Ahmad, & Mukhtar, 2006;Mak, 2012;Saeed et al., 2017;Samarghandian, Azimi Nezhad, & Farkhondeh, 2017;Sannella et al., 2007;Sinija & Mishra, 2008;Song & Seong, 2007;Thielecke & Boschmann, 2009;Yamagata, 2020). Green tea catechins are also used as flavoring and coloring agents in foods. ...
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The direct antiplasmodial effects of five structurally-related flavonoids, namely quercetin, rutin, eriodictyol, eriodictyolchalcone and catechin, were analyzed in vitro on P. falciparum. Notably, all these flavonoids, with the only exception of rutin, caused relevant inhibition of P. falciparum growth when given at 1 mM concentration. In addition, they were found to affect greatly the potent antiplasmodial activity of artemisinin, leading to significant additive and even synergistic effects. In particular, quercetin induced a pronounced synergistic effect. The observed synergisms might be conveniently exploited to design new and/or more effective combination therapies.
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Human beings have been affl icted with malaria since antiquity (WHO 1986). The disease is caused by a protozoan of the genus Plasmodium and is transmitted through bites by female mosquitoes belonging to the genus Anopheles. Four sub-species of Plasmodium can cause malaria in humans; the sub-species are Plasmodium falciparum, P. vivax, P. malariae, and P. ovale. Ninety per cent of known human deaths are caused by P. falciparum. When the parasites enter the blood stream through mosquito bites, they infect and destroy red blood cells leading to fever and other symptoms such as chills, muscle ache, headache, nausea, vomiting, diarrhea and a feeling of tiredness. In cases of uncomplicated malaria the symptoms are present but there are no signs of severity or vital organ dysfunction. Severe malaria, which is only caused by P. falciparum can lead to coma, severe respiratory problems, and severe anemia and can ultimately lead to death. It is estimated that 300-500 million malaria infections occur on an annual basis and 90% of these infections happen in sub-Saharan Africa (Bodeker 2004). About 58% of malaria deaths occur in the poorest 20% of the population (Barat 2002).
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Malaria is one of the severe infectious diseases that has victimized about half a civilization billion people each year worldwide. The application of long-lasting insecticides is the main strategy to control malaria; however, a surge in antimalarial drug development is also taking a leading role to break off the infections. Although, recurring drug resistance can compromise the efficiency of both conventional and novel antimalarial medicines. The eradication of malaria is significantly contingent on discovering novel potent agents that are low cost and easy to administer. In this context, plant metabolites inhibit malaria infection progression and might potentially be utilized as an alternative treatment for malaria, such as artemisinin. Advances in genetic engineering technology, especially the advent of molecular farming, have made plants more versatile in producing protein drugs (PDs) to treat infectious diseases, including malaria. These recent developments in genetic modifications have enabled the production of native pharmaceutically active compounds and the accumulation of diverse heterologous proteins such as human antibodies, booster vaccines, and many PDs to treat infectious diseases and genetic disorders. This review will discuss the pivotal role of a plant-based production system that expresses natural antimalarial agents or host protein drugs to cure malaria infections. The potential of these natural and induced compounds will support modern healthcare systems in treating malaria infections, especially in developing countries to mitigate human fatalities.
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Adhesion of Plasmodium falciparum-infected erythrocytes (IE) to host endothelium has been associated with pathology in malaria. Although the interaction with endothelial cells can be complex due to the relatively large number of host receptors available for binding, specific proteins have been identified that are more commonly used than others. For example, binding to intercellular adhesion molecule 1 (ICAM 1) is found frequently in parasites from pediatric cases of malaria. The binding site for P. falciparum-infected erythrocytes on ICAM 1 has been mapped in some detail and is distinct from the site for lymphocyte function-associated antigen 1 (LFA-1). Part of the ICAM 1 binding site for P. falciparum-infected erythrocytes (the DE loop) was used to screen a library of compounds based on its structure (derived from the crystal structure of human ICAM 1). This resulted in the identification of 36 structural mimeotopes as potential competitive inhibitors of binding. One of these compounds, (+)-epigalloyl-catechin-gallate [(+)-EGCG], was found to inhibit IE adhesion to ICAM 1 in a dose-dependent manner with two variant ICAM 1-binding parasite lines, providing the first example of a potential mimeotope-based anticytoadherence inhibitor for Plasmodium falciparum.
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Plasmodium falciparum can now be maintained in continuous culture in human erythrocytes incubated at 38 degrees C in RPMI 1640 medium with human serum under an atmosphere with 7 percent carbon dioxide and low oxygen (1 or 5 percent). The original parasite material, derived from an infected Aotus trivirgatus monkey, was diluted more than 100 million times by the addition of human erythrocytes at 3- or 4-day intervals. The parasites continued to reproduce in their normal asexual cycle of approximately 48 hours but were no longer highly synchronous. The have remained infective to Aotus.
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By converting methotrexate (MTX) into poly-gamma-glutamyl derivatives, cultured human fibroblasts accumulated high intracellular levels of drug. Once polyglutamates had been formed, DNA synthesis and cell growth remained suppressed even after MTX had been removed from the culture medium. Co-cultivation of cells with MTX and folinic acid reversed the effect of MTX on polyglutamate formation, DNA synthesis, and cell growth. However, if folinic acid was added to the culture medium following a preincubation in methotrexate, DNA synthesis initially remained inhibited and cell growth was only gradually restored. Co-cultivation of cells with 0.67 mM glycine, 37.5 micrometers adenosine, and 41.3 micrometers thymidine (GAT) and MTX did not prevent polyglutamate formation but allowed cells to grow. If GAT was removed from the culture medium along with MTX, cell growth and DNA synthesis were inhibited. If GAT was added to the culture medium following growth in MTX, cell growth recovered. These studies differentiate the effects of GAT and folinic acid treatment. Folinic acid prevented MTX polyglutamate accumulation and reversed the effects of MTX on cell growth when present along with MTX in the cultures. Folinic acid was only partially effective in circumventing the MTX-induced block in folate metabolism when added after pretreatment with MTX. In contrast, GAT allowed growth of cells both in the presence of MTX and after a preincubation in MTX. In contrast, GAT allowed growth of cells both in the presence of MTX and after a preincubation in MTX. However, co-incubation in MTX plus GAT resulted in the accumulation of polyglutamates and a sustained inhibition of cell growth and DNA synthesis upon removal of both MTX and GAT from the culture medium.
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This report compares the use of the lactate dehydrogenase (pLDH) assay with 3H-hypoxanthine incorporation and Giemsa microscopy for the evaluation of anti-malaria drug inhibition of the growth of P. falciparum in vitro. The inhibition profiles and IC50 determinations of the pLDH assay were directly comparable to those determined by the radioactive uptake and microscopic methods. Furthermore, the pLDH culture sensitivity assay is reproducible, easily interpreted, rapid and inexpensive to perform, suggesting field applicability.
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To the editor−The recent press, both popular and scientific, has given wide coverage of the beneficial properties of green tea, most commonly used in Asian countries. Consumption has been associated with prevention of cancer development and metastasis1. The main flavonol of green tea, epigallocatechin-3-gallate (EGCG), inhibits urokinase2, one of the hydrolases implicated in tumor invasion. Moreover, green tea consumption by mice significantly limits angiogenesis3, crucial for the growth of all solid tumors.
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The role of antioxidants in the neurotoxicity of the antimalarial endoperoxides artemether and dihydroartemisinin was studied in vitro by quantitative image analysis of neurite outgrowth in the neuroblastoma cell line NB2a. Intracellular glutathione concentrations were measured by high performance liquid chromatography with fluorescence detection. Both dihydroartemisinin (1 microM) and a combination of artemether (0.3 microM) plus haemin (2 microM) significantly inhibited neurite outgrowth from differentiating NB2a cells to 11.5 +/- 11.0% (SD) and 19.6 +/- 15.2% of controls, respectively. The inhibition by artemether/haemin was prevented by the antioxidants superoxide dismutase (109.7 +/- 47.8% of control), catalase (107.0 +/- 29.3%) glutathione (123.8 +/- 12.4%), L-cysteine (88.0 +/- 6.3%), N-acetyl-L-cysteine (107.8 +/- 14.9%), and ascorbic acid (104.3 +/- 12.7%). Dihydroartemisinin-induced neurotoxicity was completely or partially prevented by L-cysteine (99.5 +/- 17.7% of control), glutathione (57.9 +/- 23.4% of control), and N-acetyl-L-cysteine (57.3 +/- 9.5%), but was not prevented by superoxide dismutase, catalase, or ascorbic acid. Buthionine sulphoximine, an inhibitor of gamma-glutamylcysteine synthetase, significantly increased the neurotoxic effect of non-toxic concentrations of artemether/haemin (0.1 microM/2 microM) and dihydroartemisinin (0.2 microM), suggesting that endogenous glutathione participates in the prevention of the neurotoxicity of artemether/haemin and dihydroartemisinin. Artemether/haemin completely depleted intracellular glutathione levels, whereas dihydroartemisinin had no effect. We conclude that although glutathione status is an important determinant in the neurotoxicity of endoperoxides, depletion of glutathione is not a prerequisite for their toxicity. This is consistent with their mechanisms of toxicity being free radical-mediated damage to redox-sensitive proteins essential for neurite outgrowth, or alteration of a redox-sensitive signalling system which regulates neurite outgrowth.
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Increasing interest in the health benefits of tea has led to the inclusion of tea extracts in dietary supplements and functional foods. However, epidemiologic evidence regarding the effects of tea consumption on cancer and cardiovascular disease risk is conflicting. While tea contains a number of bioactive chemicals, it is particularly rich in catechins, of which epigallocatechin gallate (EGCG) is the most abundant. Catechins and their derivatives are thought to contribute to the beneficial effects ascribed to tea. Tea catechins and polyphenols are effective scavengers of reactive oxygen species in vitro and may also function indirectly as antioxidants through their effects on transcription factors and enzyme activities. The fact that catechins are rapidly and extensively metabolized emphasizes the importance of demonstrating their antioxidant activity in vivo. In humans, modest transient increases in plasma antioxidant capacity have been demonstrated following the consumption of tea and green tea catechins. The effects of tea and green tea catechins on biomarkers of oxidative stress, especially oxidative DNA damage, appear very promising in animal models, but data on biomarkers of in vivo oxidative stress in humans are limited. Larger human studies examining the effects of tea and tea catechin intake on biomarkers of oxidative damage to lipids, proteins, and DNA are needed.
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Various growth factors such as the platelet derived growth factor (PDGF), insulin-like growth factor (IGF), epidermal growth factor (EGF), fibroblast growth factor (FGF), and vascular endothelial growth factor (VEGF) transduce their mitogenic signals through the activation of tyrosine kinase receptors (RTKs). Since enhanced RTK activity has been associated with the development of proliferative diseases such as atherosclerosis and cancer, there has been an increased interest recently in the development of small molecule RTK inhibitors for the prevention/treatment of the aforementioned diseases. Many cell culture and animal studies have shown that catechins, the main compounds of the green tea leaves, are potent natural inhibitors of several RTKs. In the present article we review the various molecular and cellular mechanisms through which catechins inhibit the growth factor-RTK-mediated signal transduction pathways and exert their antiproliferative/apoptotic effects.
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Parasitic apicomplexans are responsible for some of the most severe worldwide health problems, including malaria, toxoplasmosis and cryptosporidiosis. These parasites are characterized by a bifunctional enzyme, dihydrofolate reductase-thymidylate synthase (DHFR-TS), which has a crucial role in pyrimidine biosynthesis. Inhibitors of DHFR have been successful in the treatment of toxoplasmosis and malaria. However, there is currently no effective therapy for cryptosporidiosis, and despite early successes against malaria, resistance to DHFR inhibitors in malaria parasites has now become a global problem. Novel DHFR inhibitors, designed using the recently revealed crystal structures of the enzymes from two parasitic protozoa, are in development.
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The development in Plasmodium falciparum of the resistance to chloroquine (CQ) constitutes a public health priority, due to its direct influence in childhood mortality. The molecular basis for CQ resistance (CQR) is still unclear but, recently, a new relevant gene, named pfcrt, with several point mutations was identified in P. falciparum. Two mutations, K76T and A220S, have been considered crucial for CQR in further studies, making the pfcrt a good candidate as determinant for CQR in P. falciparum. To contribute to this topic, we have undertaken a molecular screening on 164 P. falciparum isolates from Africa: 120 isolates were Italian imported malaria cases, 27 and 17 isolates were from a school-children survey from Congo and Tanzania, respectively. In vitro tests (pLDH and WHO-Mark III tests) for CQ sensitivity have been also carried out on 28 plasmodial isolates and results compared to those obtained by molecular analysis in the same isolates. The SVIET pfcrt haplotype has been identified in the samples from Congo, and this is the first time that this haplotype is detected in Africa. Our results give further evidence to the reliability of the 76T (and the linked 74I-75E) pfcrt point mutation as molecular marker for CQR.
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Interactions between antimicrobial agents provide clues as to their mechanisms of action and influence the combinations chosen for therapy of infectious diseases. In the treatment of malaria, combinations of drugs, in many cases acting synergistically, are increasingly important in view of the frequency of resistance to single agents. The study of antimalarial drug interactions is therefore of great significance to both treatment and research. It is therefore worrying that the analysis of drug-interaction data is often inadequate, leading in some cases to dubious conclusions about synergism or antagonism. Furthermore, making mechanistic deductions from drug-interaction data is not straightforward and of the many reported instances of antimalarial synergism or antagonism, few have been fully explained biochemically. This review discusses recent findings on antimalarial drug interactions and some pitfalls in their analysis and interpretation. The conclusions are likely to have relevance to other antimicrobial agents.
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Can drinking several cups of green tea a day keep the doctor away? This certainly seems so, given the popularity of this practice in East Asian culture and the increased interest in green tea in the Western world. Several epidemiological studies have shown beneficial effects of green tea in cancer, cardiovascular, and neurological diseases. The health benefits associated with green tea consumption have also been corroborated in animal studies of cancer chemoprevention, hypercholesterolemia, artherosclerosis, Parkinson's disease, Alzheimer's disease, and other aging-related disorders. However, the use of green tea as a cancer chemopreventive or for other health benefits has been confounded by the low oral bioavailability of its active polyphenolic catechins, particularly epigallocatechin-3-gallate (EGCG), the most active catechin. This review summarizes the purported beneficial effects of green tea and EGCG in various animal models of human diseases. Dose-related differences in the effects of EGCG in cancer versus neurodegenerative and cardiovascular diseases, as well as discrepancies between doses used in in vitro studies and achievable plasma understanding of the in vivo effects of green tea catechins in humans, before the use of green tea is widely adopted as health-promoting measure.
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Dihydrofolate reductase (DHFR) plays an essential role in cellular biochemistry and has been a well-recognized drug target for over fifty years. Antifolate inhibitors of DHFR, including clinically used therapeutics such as methotrexate, trimethoprim, and pyrimethamine have been successful as anticancer, antibacterial, antifungal and antiparasitic agents. As resistant strains of these microorganisms evolve and as new disease threats arise, the need for new antifolates that are potent and specific for infectious organisms becomes more pressing. Several new antifolates have been reported over the past decade; many of these are potent against a particular species of DHFR, but achieving the goal of potency and selectivity has proven to be more difficult. This review will describe recent advances in attaining species selectivity in developing new antifolates. Specifically, advances in developing inhibitors against Pneumocystis jirovecii and Plasmodium falciparum, the causative agents in pneumocystis pneumonia and malaria, respectively, will be presented.
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Sulpha drugs act as competitive inhibitors of p-amino benzoic acid, an intermediate in the de novo folate pathway. Dihydropteroate synthase condenses sulpha drugs into sulpha-dihydropteroate (sulpha-DHP), which competes with dihydrofolate, the dihydrofolate reductase (DHFR) substrate. This designates DHFR as a possible target of sulpha-DHP. We suggest here that Plasmodium vivax DHFR is indeed the in vivo target of sulpha drugs. The wild-type DHFR expressed in Saccharomyces cerevisiae leads to cell growth inhibition, while sensitivity to the drug is exacerbated in the mutants. Contrary to what is observed with sulphanilamide, methotrexate is less effective on P. vivax-DHFR mutants than on wild-type mutant.
Article
After the discovery of a potent natural flavonoid glucoside as a potent inhibitor of FabI, a large flavonoid library was screened against three important enzymes (i.e., FabG, FabZ, and FabI) involved in the fatty acid biosynthesis of P. falciparum. Although flavones with a simple hydroxylation pattern (compounds 4-9) showed moderate inhibitory activity toward the enzymes tested (IC50 10-100 microM), the more complex flavonoids (12-16) exhibited strong activity toward all three enzymes (IC50 0.5-8 microM). Isoflavonoids 26-28 showed moderate (IC50 7-30 microM) but selective activity against FabZ. The most active compounds were C-3 gallic acid esters of catechins (32, 33, 37, 38), which are strong inhibitors of all three enzymes (IC50 0.2-1.1 microM). Kinetic analysis using luteolin (12) and (-)-catechin gallate (37) as model compounds revealed that FabG was inhibited in a noncompetitive manner. FabZ was inhibited competitively, whereas both compounds behaved as tight-binding noncompetitive inhibitors of FabI. In addition, these polyphenols showed in vitro activity against chloroquine-sensitive (NF54) and -resistant (K1) P. falciparum strains in the low to submicromolar range.
Article
Green tea is one of the most popular beverages worldwide. Its major components include (-)-epicatechin ((-)-EC), (-)-epicatechin-3-gallate (ECG) (-)-epigallocatechin (EGC) and (-)-epigallocatechin-3-gallate (EGCG). It has demonstrated strong antioxidative, anti-inflammatory and anti-cancerous properties and attracted a great deal of interest over last several years. However, there is some discrepancy between the results from human pidemiological studies and cultured cell and animal models. Two reasons for its limited in vivo activities have been considered: metabolism and bioavailability. Recent studies have demonstrated that green tea catechins undergo methylation, glucuronidation and sulfation in in vitro systems and in animals and in humans. It has been also found that efflux transporters Pgp, MRP1 and MRP2 play roles in the absorption and excretion of green tea catechins. Several processes including intestinal metabolism, microbial metabolism, hepatic metabolism and chemical degradation have been found to be involved in the fate of green tea, and to be responsible for its low availability in animals, and most likely also in humans. Pharmacokinetics, absorption, distribution, drug metabolism and excretion properties of green tea provide a better understanding for its in vivo activities. In this article, drug metabolism and microbial metabolism of green tea catechins in in vitro systems and in animals and in humans will be reviewed. It also covers the factors affecting their biotransformation and bioavailability: drug-drug inhibitory and inductive interactions of phase I and phase II enzymes, inhibition of non-drug-metabolizing enzymes, transporters, chemical instability, epimerization and interindividual variability.
  • C Severini
  • M Menegon
  • A R Sannella
  • M G Paglia
  • P Narciso
  • A Matteelli
  • M Gulletta
  • P Caramello
  • F Canta
  • M V Xayavong
  • I N S Moura
  • N J Pieniazek
  • D Taramelli
  • G Maiori
C. Severini, M. Menegon, A.R. Sannella, M.G. Paglia, P. Narciso, A. Matteelli, M. Gulletta, P. Caramello, F. Canta, M.V. Xayavong, I.N.S. Moura, N.J. Pieniazek, D. Taramelli, G. Maiori, Prevalence of pfcrt point mutations and level of cloroquine resistance in Plasmodium falciparum isolates from Africa, Infect. Genet. Evol. 6 (2006) 262-268.