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White jute (Corchorus capsularis L.) leaf extract has potent leishmanicidal activity against Leishmania donovani
Abstract
In pursuit of effective, safe and affordable antileishmanial drugs, the current study was designed to explore Corchorus capsularis L. leaf extract (CCEx) as an effective leishmanicidal substitute against Leishmania donovani. The leaf extract displays potent antileishmanial activity against L. donovani promastigotes with an IC 50 value of 79.00 ± 0.3 μg/ml. CCEx also significantly induces intracellular reactive oxygen species (ROS) with a concomitant decrease in the level of non-protein thiols in virulent parasites. Additionally, CCEx treatment induces substantial morphological alterations in parasites. Moreover, reagent-based phytochemical analysis of the extract revealed the presence of various phytochemical constituents. Further study is underway to identify the bioactive component(s) or fraction(s) of CCEx through bioassay-guided fractionation.
... There are no previous reports on the effect of the clinically important amastigote phase of the parasite L. donovani. A few reports of the anti-leishmanial properties of plant-based materials such as extracts of Embilica officinalis [38], Putranjiva roxburghii [39], and Corchorus capsularis [40] were based on the inhibition of the promastigotes form of L. donovani. The IC 50 values of the extracts in these reports range from 21.6 µgmL −1 to 79.0 µgmL −1 . ...
... The LEUP IC 50 for the promastigotes stage was determined to be 47.90 µgmL −1 . Embilica officinalis, Putranjiva roxburghii, and Corchorus capsularis extracts checked the promastigote's growth with IC 50 values of 21.6, 25.6, and 79.0 µgmL −1 , respectively [38][39][40]. The LEUP-AgNPs IC 50 value for promastigotes was 6.72 µgmL −1 which was considerably (P < 0.001) less than the LEUP IC 50 value. ...
Uraria picta is used as a folk medicine to cure various ailments. Regardless of ethnobotanical application, a therapeutic study of the plant parts has yet to be reported. Aqueous leaf extract was enriched with secondary metabolites like phenols, alkaloids, and terpenoids. Total phenol (60.97 mgG⁻¹ GAE), total flavonoid (52.36 mgG⁻¹ RE), and antioxidant activity (IC50 2666.95 µgmL⁻¹) of the extract were measured. Bio-based silver nanoparticles (LEUP-AgNPs) were fabricated using a secondary metabolite-enriched leaf extract of U. picta (LEUP), and characterization of LEUP-AgNPs was done. The LEUP-AgNPs were crystalline, circular (13.04 ± 5.97 nm), monodisperse (pdi 0.205), and stable (-17.8 mV). The LEUP-AgNPs surface was composed of carbon, nitrogen, oxygen, and silver. A comparative study was performed to evaluate the potential of LEUP and LEUP-AgNPs against promastigotes and intra-RAW264.7 macrophage amastigotes of Leishmania donovani. A high dose of LEUP and LEUP-AgNPs significantly inhibited the growth of promastigotes up to 53% and 68%, with an IC50 value of 47.90 µgmL⁻¹ and 6.79 µgmL⁻¹, respectively. LEUP and LEUP-AgNPs higher doses also inhibited intracellular amastigotes up to 53% and 80% with an IC50 value of 6.72 µgmL⁻¹ and 1.16 µgmL⁻¹, respectively. The microscopic examination revealed that LEUP-AgNPs lead to size reduction and aggregations of promastigotes. The LEUP-AgNPs efficiently declined the number of amastigotes per RAW 264.7 macrophages compared to LEUP. LEUP-AgNPs had no cytotoxic effects on RAW 264.7 macrophages based on the CC50 value. Findings showed LEUP-AgNPs were more efficient than LEUP in controlling L. donovani, which induces visceral leishmaniasis.
... The first two ranked compounds, corosolic acid (1) and jacoumaric acid (2) were more active than guajadial B (5) and medicagenic acid (6), with an IC50 of 1.32 ± 0.59 µg/mL for jacoumaric acid and 1.01 ± 0.06 µg/mL for corosolic acid ( Table 2). Since most antileishmanial drugs act by the production of reactive oxygen species (ROS) that lead to the death of parasites [23,24], we measured the production of ROS induced by jacoumaric acid and corosolic acid at the IC50 (1.32 µg/mL and 1.06 µg/mL, respectively) and IC90 (1.90 µg/mL and 1.43 µg/mL, respectively) using H2DCFDA (2′,7′-dichlorodihydrofluorescein diacetate). The corresponding graph presented in Figure 4A clearly demonstrates that jacoumaric acid and corosolic Table 1 for details). ...
... The first two ranked compounds, corosolic acid (1) and jacoumaric acid (2) were more active than guajadial B (5) and medicagenic acid (6), with an IC 50 of 1.32 ± 0.59 µg/mL for jacoumaric acid and 1.01 ± 0.06 µg/mL for corosolic acid ( Table 2). Since most antileishmanial drugs act by the production of reactive oxygen species (ROS) that lead to the death of parasites [23,24], we measured the production of ROS induced by jacoumaric acid and corosolic acid at the IC 50 (1.32 µg/mL and 1.06 µg/mL, respectively) and IC 90 (1.90 µg/mL and 1.43 µg/mL, respectively) using H 2 DCFDA (2 ,7 -dichlorodihydrofluorescein diacetate). ...
With an estimated annual incidence of one million cases, leishmaniasis is one of the top five vector-borne diseases. Currently available medical treatments involve side effects, including toxicity, non-specific targeting, and resistance development. Thus, new antileishmanial chemical entities are of the utmost interest to fight against this disease. The aim of this study was to obtain potential antileishmanial natural products from Psidium guajava leaves using a metabolomic workflow. Several crude extracts from P. guajava leaves harvested from different locations in the Lao People's Democratic Republic (Lao PDR) were profiled by liquid chromatography coupled to high-resolution mass spectrometry, and subsequently evaluated for their antileishmanial activities. The putative active compounds were highlighted by multivariate correlation analysis between the antileishmanial response and chromatographic profiles of P. guajava mixtures. The results showed that the pooled apolar fractions from P. guajava were the most active (IC50 = 1.96 ± 0.47 µg/mL). Multivariate data analysis of the apolar fractions highlighted a family of triterpenoid compounds, including jacoumaric acid (IC50 = 1.318 ± 0.59 µg/mL) and corosolic acid (IC50 = 1.01 ± 0.06 µg/mL). Our approach allowed the identification of antileishmanial compounds from the crude extracts in only a small number of steps and can be easily adapted for use in the discovery workflows of several other natural products.
... In 2019 P.K. Pramanik, et al conducted a research on Corchorus capsularis L. leaf extract (CCEx) as a replacement leishmanicide for Leishmania donovani. The widespread plant Corchorus capsularis L., also known as white jute, has a variety of therapeutic benefits [41]. The leaves of C. capsularis L. have strong antimicrobial, anti-inflammatory and antinociceptive effects [65] [66]. ...
Leishmaniasis is considered one of the different neglected tropical diseases by the World Health Organization. Over the past few decades to tackle leishmaniasis, effective and novel drugs have progressed. But few are expensive some other medication shows poor effects and few drugs with long treatment lead to cause resistance. But it is very important to start a better medication against leishmania so researchers came to the front of the utilization of natural products which are considered a better option. Finding active compounds in medicinal plants is another alternative to currently accessible medications. Materials and methods: This study examined and reported the far more potential natural products used to treat disease caused by Leishmania spp. Leishmaniasis, plant metabolites, in vivo, in vitro, and treatment against leishmaniasis have been used as search terms in the Google Scholar, PubMed, and Science Direct databases, and only papers published between 2015 and 2021 have been chosen for further analysis. Results: The use of novel natural compounds with leishmanicidal action as well as the leishmanicidal activity of natural compounds against promastigote, axenic, and intracellular amastigote forms were included in roughly 20 research papers that were reviewed.Conclusion: Due to their capacity to selectively target parasites without harming host cell viability, herbal plants are a possible source of new anti-leishmanial medication. Future leishmaniasis treatments will draw on the isolated compounds as a source, completing those already offered in clinics.
... [84] Antileishmanial activity C. capsularis Leaf Chloroform Showed potent antileishmanial activity against L. donovani promastigotes with an IC50 value of 79 μg/mL and exhibited very specific apoptotic features by targeting LdTryR. [80,167] Antibacterial activity C. capsularis C. olitorius Leaf Lipophilic extracts ...
Plant bioactive compounds have gained global significance in terms of both medicinal and economic ramifications due to being easily accessible and are believed to be effective with fewer side effects. Growing relevant clinical and scientific evidence has become an important criterion for accepting traditional health claims of medicinal plants and also supports the traditional uses of Corchorus as folk medicine. C. capsularis and C. olitorius have broad applications ranging from textile to biocomposite, and young leaves and shoots are used as healthy vegetables and have long been used as traditional remedies for fever, ascites, algesia, liver disorders, piles, and tumors in many cultures. This review systematically summarized and emphasized the nutritional attributes, mostly available bioactive compounds, and biological and potential pharmaceutical properties of C. capsularis and C. olitorius, disclosed to users and non-users. Results suggest that various phytochemicals such as cardiac glycosides, phenols, flavonoids, sterols, lipids, and fatty acids were found or analytically identified in different plant parts (leaf, stem, seed, and root), and many of them are responsible for pharmacological properties and their antitumor, anticancer, antioxidant, antinociceptive, anti-inflammatory, analgesic, antipyretic, antiviral, antibacterial, anticonvulsant, antidiabetic and antiobesity, and cardiovascular properties help to prevent and cure many chronic diseases. In addition to their use in traditional food and medicine, their leaves have also been developed for skin care products, and some other possible uses are described. From this review, it is clear that the isolated compounds of both species have great potential to prevent and treat various diseases and be used as functional foods. In conclusion, this comprehensive review establishes a significant reference base for future research into various medical and functional food applications.
... Antipromastigote activity and cytotoxicity assay of β-sitosterol CCL and commercial β-sitosterol. To check the inhibitory effect of commercial β-sitosterol on the growth of L. donovani promastigotes, an MTT assay was performed as described previously 9 . Promastigotes (1 × 10 7 /well) were treated individually with β-sitosterol CCL and commercial β-sitosterol (Abcam, USA) (0-200 µg/ml) for 48 h. ...
Leishmaniasis, a major neglected tropical disease, affects millions of individuals worldwide. Among the various clinical forms, visceral leishmaniasis (VL) is the deadliest. Current antileishmanial drugs exhibit toxicity- and resistance-related issues. Therefore, advanced chemotherapeutic alternatives are in demand, and currently, plant sources are considered preferable choices. Our previous report has shown that the chloroform extract of Corchorus capsularis L. leaves exhibits a significant effect against Leishmania donovani promastigotes. In the current study, bioassay-guided fractionation results for Corchorus capsularis L. leaf-derived β-sitosterol (β-sitosterolCCL) were observed by spectroscopic analysis (FTIR, ¹H NMR, ¹³C NMR and GC–MS). The inhibitory efficacy of this β-sitosterolCCL against L. donovani promastigotes was measured (IC50 = 17.7 ± 0.43 µg/ml). β-SitosterolCCL significantly disrupts the redox balance via intracellular ROS production, which triggers various apoptotic events, such as structural alteration, increased storage of lipid bodies, mitochondrial membrane depolarization, externalization of phosphatidylserine and non-protein thiol depletion, in promastigotes. Additionally, the antileishmanial activity of β-sitosterolCCL was validated by enzyme inhibition and an in silico study in which β-sitosterolCCL was found to inhibit Leishmania donovani trypanothione reductase (LdTryR). Overall, β-sitosterolCCL appears to be a novel inhibitor of LdTryR and might represent a successful approach for treatment of VL in the future.
Malaria disease is an infectious disease, endemic to tropical and sub‐tropical regions causing half a million people’s deaths every year. Bioactive compounds derived from medicinal plants are used to treat malaria disease. H. cannabinus and C. capsularisare two edible medicinal plants abundant in distribution in the Assam region, India. In this study, in‐vitro and in‐silico investigations were performed to explore the anti‐malarial activity of the plant extracts against Plasmodium falciparum with its validation of hemocompatibility on human RBC. We report H. cannabinus and C. capsularis extracts possess highly potent antimalarial activity against Plasmodium falciparum with IC50 values of 3.80 ± 0.3 μg/mL and 7.90 ± 0.8 μg/mL, respectively. The plant extracts showed growth inhibition of A549 lung adenocarcinoma cells, no toxicity on noncancerous Vero cells, and no hemolytic activity on human RBCs. The GC‐MS analysis detected bioactive compounds 2‐pyrazoline‐3‐carboxylic acid; 5‐hydroxy‐1‐(4‐methyl benzoyl)‐5‐phen 5‐oxo‐1‐phenyl‐4H‐pyrazole‐3‐carboxylic acid; 9‐oximino‐2,7‐diethoxyfluorene; and nonane‐diamide, n, n'‐di‐benzoyloxy in H. cannabinus; and, (+)‐sesamin; tetrahydropyran‐4‐carboxylic acid, 4‐phenyl‐, (3‐chloro‐4‐methylphenyl; and safrole in C. capsularis. In the in‐silico study, antimalarial compounds in the extracts were predicted with good binding affinities of docking score < ‐7.5 kcal/mol on Falcipain‐2, and Cyt C2 proteins that help the growth and invasion of P. falciparum.
Leishmaniasis is a deadly tropical disease that is neglected in many countries. World Health Organization, along with a few other countries, has been working together to protect against these parasites. Many novel drugs from the past few years have been discovered and subjected against leishmaniasis, which have been effective but they are quite expensive for lower-class people. Some drugs showed no effect on the patients, and the longer use of these medicines has made resistance against these deadly parasites. Researchers have been working for better medication by using natural products from medicinal plants (oils, secondary metabo-lites, plant extracts) and other alternatives to find active compounds as an alternative to the current synthetic drugs.
Materials and Methods
To find more potential natural products to treat Leishmania spp, a study has been conducted and reported many plant metabolites and other natural alternatives from plants and their extracts. Selected research papers with few term words such as natural products, plant metabolites, Leishmaniasis, in vivo, in vitro, and treatment against leishmania-sis; in the Google Scholar, PubMed, and Science Direct databases with selected research papers published between 2015 and 2021 have been chosen for further analysis has been included in this report which has examined either in vivo or in vitro analysis.
Results
This paper reported more than 20 novel natural compounds in 20 research papers that have been identified which report a leishmanicidal activity and shows an action against pro-mastigote, axenic, and intracellular amastigote forms.
Conclusion
Medicinal plants, along with a few plant parts and extracts, have been reported as a possible novel anti-leishmanial medication. These medicinal plants are considered nontoxic to Host cells. Leishmaniasis treatments will draw on the isolated compounds as a source further and these compounds compete with those already offered in clinics.
The present study was implemented to synthesize green silver nanoparticles from aqueous leaf extract of Nyctanthes arbor-tristis (AgNPNAs) and to analyze their physicochemical properties in evaluating their antileishmanial activity. Formation of AgNPNAs from leaf extract (LE) was evidenced by the change of peak intensity in the fluorescence spectrum. The particles were nearly monodispersed (PDI = 0.134) with hydrodynamic diameter of 67.83 nm and appeared quite stable (zeta potential = −19.1 mV). FESEM study demonstrated nearly spherical shape of AgNPNAs and apparently smooth surface area was identified by AFM. The diameter of AgNPNAs (~ 21 nm) was measured by HRTEM. The amorphous crystal nature, polycrystallinity and low grain size of AgNPNAs were comprehended by the XRD. The crystalline nature was supported from SAED profile. The EDX spectra identified the constituents of AgNPNAs whereas the XPS spectra unraveled the Ag2O state. The FTIR analysis implemented the phytofabricating agent(s) to be attached to the Ag0 via carboxyl group. The leishmanicidal activity of AgNPNAs on Leishmania donovani (MHOM/IN/1983/AG83) was compared with commercial silver nanoparticles (AgNPCOs), AgNO3, miltefosine and leaf extract (LE). The AgNO3 (IC50 = 0.469 ± 0.116 μg/ml), AgNPCOs (IC50 = 4.74 ± 0.221 μg/ml), miltefosine (IC50 = 0.87 ± 0.038 μg/ml) proved their better leishmanicidal efficacy than AgNPNAs (IC50 = 11.46 ± 0.120 μg/ml) and LE was found to be incompetent as parasiticidal. However, AgNPNAs showed greater safety level (IC50 = 136.33 ± 0.881 μg/ml) in normal macrophages (Raw 264.7) than AgNO3 (IC50 = 1.81 ± 0.133 μg/ml), AgNPCOs (IC50 = 10.06 ± 0.719 μg/ml) and miltefosine (IC50 = 18.73 ± 0.9 μg/ml). Altogether, this study revealed the physicochemical properties of AgNPNAs and their biocompatibility in killing L. donovani promastigotes indicating their new identity as potential antileishmanial agent.
Leishmania infection causes a group of tropical diseases and has remained neglected for decades. It spreads by sandfly vector and is one of the most fatal protozoan diseases after malaria. Leishmaniases are a group of diseases caused by the infection of different Leishmania species and display clinically different forms like “Visceral leishmaniasis” (VL), “mucocutaneous leishmaniasis” and “cutaneous leishmaniasis” (CL). Approximately one billion people living in an endemic area are at high risk. Three hundred thousand cases of VL are reported annually and around twenty thousand people die every year, proving it as one of the most lethal forms of leishmaniasis. Until now, no effective vaccine could be made. There is an increase in drug resistance in the case of conventional drugs. New synthetic drugs are either too costly or have side effects. Requirements of new drugs are of utmost importance to control this situation. Plants provide a source of unlimited chemical diversity, which can be screened for antileishmanial activities. Moreover, their low cost and less or no side effects make them idle candidates in the search of new antileishmanial drugs.
Looming drug resistance cases of leishmaniasis infection are an undeniably serious danger to worldwide public health, also jeopardize the efficacy of available drugs. Besides this, no successful vaccine is available till date. Since the ancient era, many plants and their parts have been used as medicines against various ailments. Hence, the importance of drug development for new molecules against Leishmania infection is significant that is a cost-effective and safer drug preferably from the natural herbal resources. We evaluated the GC–MS screening and efficacy of Putranjiva roxburghii (PR) against the sensitive and resistant promastigotes of L. donovani. GC–MS profiling revealed that the extract was rich in myo-inositol-4-C-methyl, azulene and desulphosinigrin. Quantitative investigation of phytoconstituents confirmed that PR was rich in phenols, flavonoids and terpenoids. We found an IC50 25.61 ± 0.57 µg/mL and 29.02 ± 1.21 µg/mL of PR against sodium stibogluconate sensitive and resistant strain respectively. It was found to be safer in cytotoxicity assay and generated ROS mediated oxidative stress in the parasitic cells which was evidenced by the increased and decreased levels of superoxide radicals, lipid peroxidation products, lipid bodies and levels of thiol, plasma membrane integrity respectively. Therefore, our results support the importance of P. roxburghii as a medicinal plant against L. donovani and showed potential for exploration as an antileishmanial agent.
To overcome the drug toxicity and frequent resistance of parasites against the conventional drugs for the healing of human visceral leishmaniasis, innovative plant derived antileishmanial components are very imperative. Fuelled by the complications of clinically available antileishmanial drugs, a novel potato serine protease inhibitor was identified with its efficacy on experimental visceral leishmaniasis (VL). The serine protease inhibitors from potato tuber extract (PTEx) bearing molecular mass of 39 kDa (PTF1), 23 kDa (PTF2) and 17 kDa (PTF3) were purified and identified. Among them, PTF3 was selected as the most active inhibitor (IC50 143.5 ± 2.4 µg/ml) regarding its antileishmanial property. Again, intracellular amastigote load was reduced upto 83.1 ± 1.7% in pre-treated parasite and 88.5 ± 0.5% in in vivo model with effective dose of PTF3. Protective immune response by PTF3 was noted with increased production of antimicrobial substances and up-regulation of pro-inflammatory cytokines. Therapeutic potency of PTF3 is also followed by 80% survival in infected hamster. The peptide mass fingerprint (MALDI-TOF) results showed similarity of PTF3 with serine protease inhibitors database. Altogether, these results strongly propose the effectiveness of PTF3 as potent immunomodulatory therapeutics for controlling VL.
The aim of this study is to describe the major evolutionary historical events among Leishmania, sandflies, and the associated animal reservoirs in detail, in accordance with the geographical evolution of the Earth, which has not been previously discussed on a large scale.Leishmania and sandfly classification has always been a controversial matter, and the increasing number of species currently described further complicates this issue. Despite several hypotheses on the origin, evolution, and distribution of Leishmania and sandflies in the Old and New World, no consistent agreement exists regarding dissemination of the actors that play roles in leishmaniasis. For this purpose, we present here three centuries of research on sandflies and Leishmania descriptions, as well as a complete description of Leishmania and sandfly fossils and the emergence date of each Leishmania and sandfly group during different geographical periods, from 550 million years ago until now. We discuss critically the different approaches that were used for Leishmana and sandfly classification and their synonymies, proposing an updated classification for each species of Leishmania and sandfly. We update information on the current distribution and dispersion of different species of Leishmania (53), sandflies (more than 800 at genus or subgenus level), and animal reservoirs in each of the following geographical ecozones: Palearctic, Nearctic, Neotropic, Afrotropical, Oriental, Malagasy, and Australian. We propose an updated list of the potential and proven sandfly vectors for each Leishmania species in the Old and New World. Finally, we address a classical question about digenetic Leishmania evolution: which was the first host, a vertebrate or an invertebrate?We propose an updated view of events that have played important roles in the geographical dispersion of sandflies, in relation to both the Leishmania species they transmit and the animal reservoirs of the parasites.
Plants produce a wide diversity of secondary metabolites (SM) which serve them as defense compounds against herbivores, and other plants and microbes, but also as signal compounds. In general, SM exhibit a wide array of biological and pharmacological properties. Because of this, some plants or products isolated from them have been and are still used to treat infections, health disorders or diseases. This review provides evidence that many SM have a broad spectrum of bioactivities. They often interact with the main targets in cells, such as proteins, biomembranes or nucleic acids. Whereas some SM appear to have been optimized on a few molecular targets, such as alkaloids on receptors of neurotransmitters, others (such as phenolics and terpenoids) are less specific and attack a multitude of proteins by building hydrogen, hydrophobic and ionic bonds, thus modulating their 3D structures and in consequence their bioactivities. The main modes of action are described for the major groups of common plant secondary metabolites. The multitarget activities of many SM can explain the medical application of complex extracts from medicinal plants for more health disorders which involve several targets. Herbal medicine is not a placebo medicine but a rational medicine, and for several of them clinical trials have shown efficacy.
The aim of the present study is to synthesize silver (Ag) and titanium dioxide (TiO2) nanoparticles (NPs) using green synthesis from aqueous leaves extract of Euphorbia prostrata as antileishmanial agents and to explore the underlying molecular mechanism of induced cell death. In vitro antileishmanial activity of synthesized NPs was tested against promastigotes of Leishmania donovani by alamarBlue® and propidium iodide uptake assay. Antileishmanial activity of synthesized NPs on intracellular amastigotes was assessed by Giemsa staining. The leishmanicidal effect of synthesized Ag NPs was further confirmed by DNA fragmentation assay; cell cycle progression and transmission electron microscopy (TEM) of the treated parasites. TEM analysis of the synthesized Ag NPs showed spherical shape with an average size of 12.82 ± 2.50 nm and in comparison to synthesized TiO2 NPs, synthesized Ag NPs were found to be most active against Leishmania parasites after 24 h exposure with IC50 value of 14.94 μg/ml and 3.89 μg/ml in promastigotes and intracellular amastigotes respectively. A significant increase in G0/G1 phase of the cell cycle with subsequent decrease in S (synthesis) and G2/M phases when compared to control was observed. The growth inhibitory effect of synthesized Ag NPs was attributed to increased length of S phase. Decreased reactive oxygen species level was also observed which could be responsible for caspase independent shift from apoptosis (G0/G1 arrest) to massive necrosis. High molecular weight DNA fragmentation as a positive consequence of necrotic cell death was also visualized. We also report that the unique trypanothione/trypanothione reductase (TR) system of Leishmania cells was significantly inhibited by synthesized Ag NPs. The green synthesized Ag NPs may provide promising leads for the development of cost effective and safer alternative treatment against visceral leishmaniasis.
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Using a suite of morphological traits and neutral molecular markers, we have reevaluated the origins of the two cultivated jute species. The nine Corchorus species, which are restricted to both Africa and Asia, were phenotyped for bast fibre yield- and quality-linked traits, morphophenetically classified based on those traits’ similarities, genotyped by nuclear microsatellites and haplotyped by chloroplast microsatellites. The two cultivated jute species
contain ~70% of the neutral genetic diversity present in their wild relatives. Phylogenetic analyses using 38 highly polymorphic nuclear microsatellites identified C. aestuans as the
common ancestor to both the cultivated jute species. C. urticifolius is the nuclear progenitor of C. olitorius (dark jute), but no close nuclear progenitor of C. capsularis (white jute) could
be identified. Although either C. aestuans or C. pseudoolitorius or both appear to be the possible cytoplasmic progenitors of white jute, the matrilineal ancestry of dark jute remains obscure. However, the presence of a single, unique chloroplast haplotype in each of the two cultivated species indicates the involvement of other unknown wild relatives. Taken together with archaeobotanical evidence, our results suggest that dark jute had its origin in equatorial region of east Africa, but was domesticated in India. We could not support an Indo-Myanmar origin of white jute, and possibly it also originated in Africa, but was domesticated in Asia.
This review summarizes human infections caused by endoparasites, including protozoa, nematodes, trematodes, and cestodes, which affect more than 30% of the human population, and medicinal plants of potential use in their treatment. Because vaccinations do not work in most instances and the parasites have sometimes become resistant to the available synthetic therapeutics, it is important to search for alternative sources of anti-parasitic drugs. Plants produce a high diversity of secondary metabolites with interesting biological activities, such as cytotoxic, anti-parasitic and anti-microbial properties. These drugs often interfere with central targets in parasites, such as DNA (intercalation, alkylation), membrane integrity, microtubules and neuronal signal transduction. Plant extracts and isolated secondary metabolites which can inhibit protozoan parasites, such as Plasmodium, Trypanosoma, Leishmania, Trichomonas and intestinal worms are discussed. The identified plants and compounds offer a chance to develop new drugs against parasitic diseases. Most of them need to be tested in more detail, especially in animal models and if successful, in clinical trials.
Four medicinal plants (Chrozophora hierosolymitana Spreng, Chrysanthemum leucanthemum L., Ephedra gerardiana Wall. ex Stapf, and Quercus dilatata L.) used by indigenous healers to treat various infectious diseases were selected for the present study. The major objective of the present study was isolation and characterization of antimicrobial components from the crude plant extracts using bioassay guided fractionation.
Seven methanolic extracts of the four plants were screened to identify any antimicrobial agents present in them. The active crude plant extract was fractionated first by solvent partitioning and then by HPLC. Characterization of the active fractions was done by using spectrophotometer.
All the seven methanolic extracts showed low antifungal activity, however, when these extracts were tested for antibacterial activity, significant activity was exhibited by two extracts. The extract of aerial parts of Q. dilatata was most active and therefore, was selected for further analysis. Initially fractionation was done by solvent-solvent partitioning and out of six partitioned fractions, ethanol fraction was selected on the basis of results of antibacterial activity and phytochemical analysis. Further, fractionation was carried out by RP-HPLC and purified active subfractions were characterized by comparing their absorption spectra with that of the known natural products isolated from the plants of Quercus genus.
The results suggest that this is the first report of the isolated antibacterial compounds from this genus.
Leishmaniasis, a parasitic disease caused by protozoa of the genus Leishmania, affects more than 12 million people worldwide. Quercetin has generated considerable interest as a pharmaceutical compound with a wide range of therapeutic activities. One such activity is exhibited against the bloodstream parasite Trypanosoma brucei and amastigotes of Leishmania donovani. However, the mechanism of protozoan action of quercetin has not been studied.
In the present study, we report here the mechanism for the antileishmanial activity of quercetin against Leishmania amazonensis promastigotes. Quercetin inhibited L. amazonensis promastigote growth in a dose- and time- dependent manner beginning at 48 hours of treatment and with maximum growth inhibition observed at 96 hours. The IC(50) for quercetin at 48 hours was 31.4 µM. Quercetin increased ROS generation in a dose-dependent manner after 48 hours of treatment. The antioxidant GSH and NAC each significantly reduced quercetin-induced cell death. In addition, quercetin caused mitochondrial dysfunction due to collapse of mitochondrial membrane potential.
The effects of several drugs that interfere directly with mitochondrial physiology in parasites such as Leishmania have been described. The unique mitochondrial features of Leishmania make this organelle an ideal drug target while minimizing toxicity. Quercetin has been described as a pro-oxidant, generating ROS which are responsible for cell death in some cancer cells. Mitochondrial membrane potential loss can be brought about by ROS added directly in vitro or induced by chemical agents. Taken together, our results demonstrate that quercetin eventually exerts its antileishmanial effect on L. amazonensis promastigotes due to the generation of ROS and disrupted parasite mitochondrial function.
Leishmania parasites lack catalase and therefore, their anti-oxidant system hinges primarily upon non-protein thiols; accordingly, depletion of thiols could potentially serve as an effective drug target. We have developed a flow cytometry based assay using 5-chloromethyl fluorescein diacetate based upon its selective staining of non-protein thiols. Its specificity was confirmed using buthionine sulphoximine (a gamma-glutamyl cysteine synthetase inhibitor), diamide (an oxidizing agent of intracellular thiols) and N-ethylmaleimide (a covalent modifier of cysteine residues) as evidenced by reduction in fluorescence; furthermore, restoration of fluorescence by N-acetyl cysteine corroborated specificity of 5-chloromethyl fluorescein diacetate to measure non-protein thiols. Differences in basal level of thiols in antimony sensitive and antimony resistant Leishmania field isolates were detected. The depletion of non-protein thiols by conventional anti-leishmanial drugs e.g. antimony and miltefosine was demonstrated. Furthermore, fluorescence was unaffected by depletion of ATP in majority of the strains studied, indicating that 5-chloromethyl fluorescein diacetate is not a substrate for the pump operative in most Leishmania donovani strains. Taken together, measurement of 5-chloromethyl fluorescein diacetate fluorescence is an effective method for monitoring non-protein thiols in Leishmania promastigotes.
The mechanisms by which Leishmaniaparasites survive exposure to highly reactive oxygen (ROS) and nitrogen (RNS) species within phagosomes of macrophages are
not well known. Recently it has been shown that RNS alone is sufficient and necessary to control Leishmania donovani infection in mice (Murray, H. W., and Nathan, C. F. (1999) J. Exp. Med. 189, 741–746). No enzymatic defense against RNS has been discovered inLeishmania to date. We have previously isolated two peroxidoxins (LcPxn1 and LcPxn2) from Leishmania chagasiand showed that recombinant LcPxn1 protein was capable of detoxifying hydrogen peroxide, hydroperoxide, and hydroxyl radicals
(Barr, S. D., and Gedamu, L. (2001) J. Biol. Chem. 276, 34279–34287). In further characterizing the physiological role of peroxidoxins in Leishmania survival, we show here that recombinant LcPxn1 protein can detoxify RNS in addition to ROS, whereas recombinant LcPxn2 protein
can only detoxify hydrogen peroxide. LcPxn1 and LcPxn2 are localized to the cytoplasm, and overexpression of LcPxn1 in L. chagasi parasites enhanced survival when exposed to exogenous ROS and RNS and enhanced survival within U937 macrophage cells. Site-directed
mutagenesis studies revealed that the conserved Cys-52 residue is essential for detoxifying hydrogen peroxide, t-butyl hydroperoxide, and hydroxyl radicals, whereas the conserved Cys-173 residue is essential for detoxifying t-butyl hydroperoxide and peroxynitrite. This is the first report of an enzymatic defense against RNS in Leishmania.
The biochemical changes consequent to respiratory chain inhibition and their relationship to cell death in Leishmania spp. remain elusive. Inhibitors of respiratory chain complexes I, II, and III were able to induce apoptotic death of the bloodstream form of Leishmania donovani. Complex I inhibition resulted in mitochondrial hyperpolarization that was preceded by increased superoxide production. Limitation of electron transport by thenoyltrifluoroacetone and antimycin A, inhibitors of complexes II and III, respectively, resulted in dissipation of mitochondrial membrane potential that was sensitive to cyclosporin A, a blocker of mitochondrial permeability transition pore. Further studies conducted with thenoyltrifluoroacetone showed maximal generation of hydrogen peroxide with a moderate elevation of superoxide levels. Complex III inhibition provoked superoxide generation only. Interference with complex II but not complexes I and III increased intracellular Ca(2+). A tight link between Ca(2+) and reactive oxygen species was demonstrated by antioxidant-induced diminution of the Ca(2+) increase. However, chelation of extracellular Ca(2+) could not abrogate the early increase of reactive oxygen species, providing evidence that Ca(2+) elevation was downstream to reactive oxygen species generation. Ca(2+) influx occurred through nonselective cation and L-type channels and Na(+)/Ca(2+) exchanger-like pathways. Antioxidants such as glutathione and Ca(2+) channel blockers reduced apoptotic death. This study provides a new possibility that concurrent inhibition of respiratory chain complex II with pentamidine administration increases cytotoxicity of the drug. This increased cytotoxicity was connected to a 4-fold elevation in intracellular Ca(2+) that was pooled only from intracellular sources. Therefore, inhibition of complexes I, II, and III leads to apoptosis and complex II inhibition in parallel with pentamidine administration-enhanced drug efficacy.
The antinociceptive and anti-inflammatory properties of Corchorus capsularis leaves chloroform extract were investigated in experimental animal models. The antinociceptive activity was measured using the writhing, hot plate and formalin tests, while the anti-inflammatory activity was measured using the carrageenan-induced paw edema test. The extract, obtained after 72 h soaking of the air-dried leaves in chloroform followed by in vacuo evaporation to dryness, was weighed and prepared by serial dilution in DMSO in the doses of 20, 100 and 200 mg/kg. The extract was administered (s.c.) 30 min prior to subjection to the respective assays. The extract was found to exhibit significant (p < 0.05) antinociceptive and anti-inflammatory activities. As a conclusion, the present study confirmed the traditional claims of using C. capsularis to treat various ailments related to inflammation and pain.
Visceral leishmaniasis (VL) is a systemic protozoan disease that is transmitted by phlebotomine sandflies. Poor and neglected populations in East Africa and the Indian sub-continent are particularly affected. Early and accurate diagnosis and treatment remain key components of VL control. In addition to improved diagnostic tests, accurate and simple tests are needed to identify treatment failures. Miltefosine, paromomycin and liposomal amphotericin B are gradually replacing pentavalent antimonials and conventional amphotericin B as the preferred treatments in some regions, but in other areas these drugs are still being evaluated in both mono- and combination therapies. New diagnostic tools and new treatment strategies will only have an impact if they are made widely available to patients.
A curcumin analog dibenzalacetone (DBA) Apoptosis A B S T R A C T Curcumin is the major phenolic compound found in turmeric, a dry powder of rhizomes and roots of the plant, Curcuma longa L., which is widely used as spice and food colorant around the world, and in herbal medicinal practice in Asian countries. The present study reports the leishmanicidal activity of trans-dibenzalacetone (DBA), a synthetic monoketone analog of curcumin, against Leishmania donovani parasites. We for the first time report the antiproliferative effect of a curcumin analog (DBA) on the intracellular amastigotes of L. donovani, the clinically more relevant stage of the parasite than its promastigotes stage. The leishmanicidal effect of DBA was further confirmed by scanning and transmission electron microscopies. Cell growth was arrested in G0/G1 phase with increased concentration of cytosolic calcium and dissipation of mitochondrial membrane potential. Further, the unique trypanothione/trypanothione reductase (TR) system of Leishmania cells was significantly inhibited by DBA. This economically synthesizable simple monoketone analog of curcumin has the potential for field use against visceral leishmaniasis which is currently widespread in tropical and subtropical developing countries of the world. In conclusion, we have identified an analog of curcumin for potential applications against leishma-niasis, based on its strong antiparasitic activity and low toxicity. This curcumin analog compares favorably, at least in vitro, with the existing medication miltefosine.
The increasing number of drug resistance issue of Leishmania donovani strain to common drugs compels to develop new therapeutics against leishmaniasis with minimal toxicity. In this regard, bioactive phytocomponents may lead to the discovery of new medicines with appropriate efficiency. The important roles of Leishmania proteases in the virulence of Leishmania parasite make them very hopeful targets for the improvement of current remedial of leishmaniasis. As part of a hunt for new drugs, we have evaluated in vivo anti-leishmanial activity of serine protease inhibitor rich fraction (PTEx), isolated by sodium bisulfite extraction from potato tuber. The amastigote load of 25mg/kg body weight/day treated BALB/c mice showed 86.9% decrease in liver and 88.7% in case of spleen. This anti-leishmanial effect was also supported by PTEx induced immunomodulatory activity like acute formation of ROS and prolonged NO generation. The Th1/Th2 cytokine balance in splenocytes of PTEx treated animals was estimated and evaluated by ELISA assay as well as by mRNA expression using RT-PCR. Furthermore, significant survival rate (80%) was observed in PTEx treated hamsters. Thus, from the present observations we could accentuate the potential of PTEx to be employed as a new therapeutics from natural source against L. donovani. This might also provide a novel perception of natural serine protease inhibitor from potato tuber as an alternate approach for the treatment of visceral leishmaniasis.
Leishmaniasis is a major public health problem, and the alarming spread of parasite resistance underlines the importance of discovering new therapeutic products. The present study aims to investigate the in vitro leishmanicidal activity of an Agaricus blazei Murill mushroom extract as compared to different Leishmania species and stages. The water extract proved to be effective against promastigote and amastigote-like stages of Leishmania amazonensis, L. chagasi, and L. major, with IC(50) (50% inhibitory concentration) values of 67.5, 65.8, and 56.8 μg/mL for promastigotes, and 115.4, 112.3, and 108.4 μg/mL for amastigotes-like respectively. The infectivity of the three Leishmania species before and after treatment with the water extract was analyzed, and it could be observed that 82%, 57%, and 73% of the macrophages were infected with L. amazonensis, L. major, and L. chagasi, respectively. However, when parasites were pre-incubated with the water extract, and later used to infect macrophages, they were able to infect only 12.7%, 24.5%, and 19.7% of the phagocytic cells for L. amazonensis, L. chagasi, and L. major, respectively. In other experiments, macrophages were infected with L. amazonensis, L. chagasi, or L. major, and later treated with the aforementioned extract, presented reductions of 84.4%, 79.6%, and 85.3% in the parasite burden after treatment. A confocal microscopy revealed the loss of the viability of the parasites within the infected macrophages after treatment with the water extract. The applied extract presented a low cytotoxicity in murine macrophages and a null hemolytic activity in type O(+) human red blood cells. No nitric oxide (NO) production, nor inducible nitric oxide syntase expression, could be observed in macrophages after stimulation with the water extract, suggesting that biological activity may be due to direct mechanisms other than macrophage activation by means of NO production. In conclusion, the results demonstrate that the A. blazei Murill water extract can potentially be used as a therapeutic alternative on its own, or in association with other drugs, to treat Visceral and Cutaneous Leishmaniasis.
There is growing evidence that metalloid-induced cell death in protozoan parasites is due to oxidative injury; however, the biochemical changes related to this event are not fully understood. Leishmania spp. demonstrated cross-resistance to two related metalloids, arsenic and antimony, and both metalloids induced cell death accompanied by cell shrinkage and DNA fragmentation that was preceded by an increase in reactive oxygen species. Both drugs caused mitochondrial dysfunction in terms of loss of membrane potential and a drop in ATP levels. Arsenic treatment resulted in an elevation of intracellular Ca2+ levels that did not occur with antimony exposure. Cellular glutathione level was reduced after antimony treatment but arsenic did not affect glutathione. Inhibition of Ca2+ influx during arsenic treatment reduced cell death, whereas supplementation of glutathione during antimony treatment rescued cell loss. Under iron-depleted conditions, the cytotoxic effects of arsenic and antimony did not occur and cell survival increased; in contrast, the presence of excess iron resulted in higher cell death. Therefore, this study provides a new possibility that iron can potentiate parasite death induced by metalloids like arsenic and antimony. In addition, an important observation is that the two similar metalloids produce toxicity by very different mechanisms.
Leishmaniases remain a major public health problem today despite the vast amount of research conducted on Leishmania pathogens. The biological model is genetically and ecologically complex. This paper explores the advances in Leishmania genetics and reviews population structure, taxonomy, epidemiology and pathogenicity. Current knowledge of Leishmania genetics is placed in the context of natural populations. Various studies have described a clonal structure for Leishmania but recombination, pseudo-recombination and other genetic processes have also been reported. The impact of these different models on epidemiology and the medical aspects of leishmaniases is considered from an evolutionary point of view. The role of these parasites in the expression of pathogenicity in humans is also explored. It is important to ascertain whether genetic variability of the parasites is related to the different clinical expressions of leishmaniasis. The review aims to put current knowledge of Leishmania and the leishmaniases in perspective and to underline priority questions which 'leishmaniacs' must answer in various domains: epidemiology, population genetics, taxonomy and pathogenicity. It concludes by presenting a number of feasible ways of responding to these questions.