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Pharmaceuticals
Special Issues
Natural Products for Treatment of Parasitic Diseases
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Natural Products for Treatment of Parasitic Diseases

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Natural Products".

Deadline for manuscript submissions: closed (25 August 2024) | Viewed by 18863

Special Issue Editors

Dr. Luiz Felipe Domingues Passero

E-Mail Website
Guest Editor
Institute for Advanced Studies of Ocean, São Paulo State University (UNESP), São Vicente 11350-011, Brazil
Interests: neglected tropical diseases; parasite; bacteria; virus; fungus; oral and local treatment; formulations; dermatological cream; liposome; nanoparticles; immunity
Special Issues, Collections and Topics in MDPI journals
Dr. João Henrique Ghilardi Lago

E-Mail Website
Guest Editor
Center of Natural Sciences and Humanities, Federal University of ABC, Santo André 09210-580, Brazil
Interests: natural products; alkaloids; terpenoids; lignoids; biological activity; parasitic diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Infectious diseases caused by parasites have been considered neglected because they affect predominantly vulnerable people living in poor areas of tropical countries, and in strict contact with parasite vectors, soil, water, or food contaminated with eggs or larval phases of helminths. Regarding protozoal diseases, epidemiological data provide astonishing information about the lethality rates, and malaria accounted for 627,000 deaths during 2020 alone. Helminthic infections are also responsible for millions of deaths; this class of diseases is treatable and, in general, the drugs used in therapy are affordable; however, 3,000 to 60,000 deaths are recorded every year due to Ascaris lumbricoides, which is not acceptable. Therefore, it becomes clear that conventional drugs used to treat parasitic diseases are outdated, are not effective in all clinical cases, and, more importantly, most of them induce severe side effects, such as pentavalent antimonial, a drug used to treat leishmaniasis, which is nephrotoxic and cardiotoxic. Side effects induced by first-line drugs used to treat parasitic diseases negatively correlate with patient compliance with treatment, which in turn has an important impact on the emergence of resistant strains.

Taking into account all these concerns, it is urgent to develop new drugs and therapeutic approaches to overcome the situation of neglected diseases, providing a better quality of life for affected people. In this sense, natural resources from fauna, flora, and microbes have been considered to exhibit huge molecular diversity that can be investigated to provide important classes of antiparasitic molecules, such as flavonoids, terpenes, alkaloids, and lignans, etc. This Special Issue seeks works on the discovery and characterization of alternative treatments for parasitic diseases based on natural products, as well as on the elucidation of the molecular structure of new molecules, analysis of the action mechanisms of molecules on parasites, evaluation of therapeutic potential in experimental models (in vivo), and special, but not limited, drugs formulated to be employed by the topic and oral routes. Studies on derivatives are encouraged and reviews are also welcome.

Dr. Luiz Felipe Domingues Passero
Dr. João Henrique Ghilardi Lago
Guest Editors

Manuscript Submission Information

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Keywords

  • natural products
  • parasitic diseases
  • medicinal chemistry
  • secondary metabolites
  • drug discovery
  • action mechanism
  • in vivo studies

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Published Papers (7 papers)

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Research

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25 pages, 7591 KiB  
Article
Beta vulgaris Betalains Mitigate Parasitemia and Brain Oxidative Stress Induced by Plasmodium berghei in Mice
by Samar A. Khan, Muslimah N. Alsulami, Atif A. Alsehimi, Majed S. Alzahrani, Dina A. Mosule and Haleema H. Albohiri
Pharmaceuticals 2024, 17(8), 1064; https://doi.org/10.3390/ph17081064 - 13 Aug 2024
Cited by 2 | Viewed by 1100
Abstract
Although many drugs have been discovered to treat malaria infection, many of them face resistance from the host’s body with long-term use. Therefore, this study aimed to evaluate the activity of betalains (from Beta vulgaris) and chloroquine (a reference drug) against brain [...] Read more.
Although many drugs have been discovered to treat malaria infection, many of them face resistance from the host’s body with long-term use. Therefore, this study aimed to evaluate the activity of betalains (from Beta vulgaris) and chloroquine (a reference drug) against brain oxidative stress induced by Plasmodium berghei in male mice. Two protocols were applied in this study: the therapeutic and prophylactic protocols. The results of the therapeutic protocol revealed a significant decrease in the level of parasitemia caused by P. berghei. Additionally, the histopathological changes in various brain regions were markedly improved after treatment with betalains. Regarding the prophylactic protocol, betalains were able to protect the brain tissues from oxidative stress, inflammation, and disrupted neurotransmitters expected to occur as a result of infection by P. berghei. This was demonstrated by modulating the activities of brain antioxidants (SOD and GSH), inflammatory cytokines (IL-6, IL-10, IL-12, TNF-α, and INF-γ), and neurotransmitters (serotonin, epinephrine, and norepinephrine). This study has proven that using betalains as a treatment or as a preventive has a vital and effective role in confronting the brain histopathological, oxidative stress, and inflammatory changes induced by P. berghei infection. Full article
(This article belongs to the Special Issue Natural Products for Treatment of Parasitic Diseases)
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14 pages, 2675 KiB  
Article
1H-NMR Metabolomic Study of the Mushroom Pleurotus djamor for the Identification of Nematocidal Compounds
by Jesús Antonio Pineda-Alegría, Luis Manuel Peña-Rodríguez, Alexandre Cardoso-Taketa, José E. Sánchez, Juan Felipe de Jesús Torres-Acosta, Gloria Ivonne Hernández-Bolio, Anabel Ortiz-Caltempa, María Luisa Villarreal and Liliana Aguilar-Marcelino
Pharmaceuticals 2024, 17(5), 580; https://doi.org/10.3390/ph17050580 - 30 Apr 2024
Cited by 1 | Viewed by 1539
Abstract
Due to the increasing populations of anthelmintic-resistant gastrointestinal nematodes and as a consequence of the adverse effects of synthetic drugs, this study focuses on the search for secondary metabolites with nematocidal activity from the edible mushroom Pleurotus djamor using The proton nuclear magnetic [...] Read more.
Due to the increasing populations of anthelmintic-resistant gastrointestinal nematodes and as a consequence of the adverse effects of synthetic drugs, this study focuses on the search for secondary metabolites with nematocidal activity from the edible mushroom Pleurotus djamor using The proton nuclear magnetic resonance (1H-NMR) metabolomics. The highest activity was shown by the ethyl acetate fractions of mycelium (EC50 290.8 µg/mL) and basidiomes (EC50 282.7 µg/mL). Principal component analysis (PCA) and hierarchical data analysis (HCA) of the 1H-NMR metabolic profiles data showed that the ethanolic extracts, the ethyl acetate, butanol, and water fractions from mycelium have different metabolic profiles than those from basidiomes, while low polarity (hexane) fractions from both stages of fungal development show similar profiles. Orthogonal partial least squares discriminant analysis (OPLS-DA) allowed the identification of signals in the 1H-NMR metabolic profile associated with nematocidal activity. The signals yielded via OPLS-DA and bidimensional NMR analysis allowed the identification of uracil as a component in the ethyl acetate fraction from basidiomes, with an EC50 of 237.7 µg/mL. The results obtained showed that chemometric analyses of the 1H-NMR metabolic profiles represent a viable strategy for the identification of bioactive compounds from samples with complex chemical profiles. Full article
(This article belongs to the Special Issue Natural Products for Treatment of Parasitic Diseases)
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11 pages, 1007 KiB  
Article
Camellia sinensis Aqueous Extract: A Promising Candidate for Hepatic Eimeriosis Treatment in Rabbits
by Hanadi B. A. Baghdadi and Mohamed Abdo Rizk
Pharmaceuticals 2023, 16(11), 1598; https://doi.org/10.3390/ph16111598 - 13 Nov 2023
Viewed by 1316
Abstract
Eimeria stiedae (E. stiedae) is a common coccidian species that infects the liver and causes economic losses for the rabbit industry. This study aimed to determine the efficiency of green tea aqueous extract (GTE) as a natural treatment for eimeriosis caused [...] Read more.
Eimeria stiedae (E. stiedae) is a common coccidian species that infects the liver and causes economic losses for the rabbit industry. This study aimed to determine the efficiency of green tea aqueous extract (GTE) as a natural treatment for eimeriosis caused by E. stiedae. Male rabbits Cuniculus L. (Oryctolagus) of the New Zealand White rabbit strain (4–4.5 months) were used, as they are suitable for research and conducting experiments. Thirty rabbits were allocated into six groups, with five rabbits in each group; the G1 group (non-infected untreated) served as a negative control group; the G2 group was not infected and treated with 250 mg GTE; the G3 group was not infected and treated with 500 mg GTE; the G4 group was untreated and was infected with 3 × 104 Sporulated E. stiedae oocysts, which served as a positive control group; the G5 group was infected and treated with 250 mg GTE; and the G6 group was infected and treated with 500 mg GTE. The hematological and biochemical analyses of each group of rabbit sera were carried out. Phytochemical analysis was performed to evaluate the active components in GTE leaves using the following methods: IR spectroscopy, liquid chromatography–mass spectrometry (LC-MS), energy-dispersive X-ray spectroscopy (EDX), and scanning electron microscopy. The infected rabbit groups treated with GTE at both doses of 250 and 500 mg/kg exhibited a significant decrease in the extent of E. stiedae oocyst shedding compared with the infected untreated group at 14, 21, and 28 days post-infection. Also, treatment with green tea showed improvement in liver weight compared with the enlarged livers of infected, untreated rabbits. The disturbance in serum liver enzymes’ gamma-glutamyl transferase (GGT) and aspartate aminotransferase (AST/GOT) levels, as well as serum glucose, potassium, uric acid, cholesterol, and urea levels, were improved after the treatment of infected rabbit groups with green tea compared with the infected untreated group. Moreover, in this study, the images of the egg stages of the parasite were taken using a fluorescence microscope at 25 µm and 26 µm magnifications. This study provides promising results for the effective cell absorption of the aqueous extract of green tea, which was confirmed in the analyzed images using a scanning electron microscope at 5 µm and 20 µm magnifications. Full article
(This article belongs to the Special Issue Natural Products for Treatment of Parasitic Diseases)
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18 pages, 5451 KiB  
Article
High Selectivity of 8-Hydroxyquinoline on Leishmania (Leishmania) and Leishmania (Viannia) Species Correlates with a Potent Therapeutic Activity In Vivo
by Sarah Kymberly Santos de Lima, Jéssica Adriana Jesus, Cristiano Raminelli, Márcia Dalastra Laurenti and Luiz Felipe Domingues Passero
Pharmaceuticals 2023, 16(5), 707; https://doi.org/10.3390/ph16050707 - 7 May 2023
Cited by 2 | Viewed by 2244
Abstract
Leishmaniasis is a neglected disease caused by protozoa of the genus Leishmania, which causes different clinical manifestations. Drugs currently used in the treatment such as pentavalent antimonial and amphotericin B cause severe side effects in patients, and parasite resistance has been reported. [...] Read more.
Leishmaniasis is a neglected disease caused by protozoa of the genus Leishmania, which causes different clinical manifestations. Drugs currently used in the treatment such as pentavalent antimonial and amphotericin B cause severe side effects in patients, and parasite resistance has been reported. Thus, it is necessary and urgent to characterize new and effective alternative drugs to replace the current chemotherapy of leishmaniasis. In this regard, it has been experimentally demonstrated that quinoline derivatives present significative pharmacological and parasitic properties. Thus, the aim of this work was to demonstrate the leishmanicidal activity of 8-hydroxyquinoline (8-HQ) in vitro and in vivo. The leishmanicidal activity (in vitro) of 8-HQ was assayed on promastigote and intracellular amastigote forms of L. (L.) amazonensis, L. (L.) infantum chagasi, L. (V.) guyanensis L. (V.) naiffi, L. (V.) lainsoni, and L. (V.) shawi. Additionally, the levels of nitric oxide and hydrogen peroxide were analyzed. The therapeutic potential of 8-HQ was analyzed in BALB/c mice infected with a strain of L. (L.) amazonensis that causes anergic cutaneous diffuse leishmaniasis. In vitro data showed that at 24 and 72 h, 8-HQ eliminated promastigote and intracellular amastigote forms of all studied species and this effect may be potentialized by nitric oxide. Furthermore, 8-HQ was more selective than miltefosine. Infected animals treated with 8-HQ by the intralesional route dramatically reduced the number of tissue parasites in the skin, and it was associated with an increase in IFN-γ and decrease in IL-4, which correlated with a reduction in inflammatory reaction in the skin. These results strongly support the idea that 8-HQ is an alternative molecule that can be employed in the treatment of leishmaniasis, given its selectivity and multispectral action in parasites from the Leishmania genus. Full article
(This article belongs to the Special Issue Natural Products for Treatment of Parasitic Diseases)
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16 pages, 2534 KiB  
Article
Antidiarrheal Potential of Viola canescens: In Vivo and In Silico Approaches
by Imtiaz Ahmad, Bader S. Alotaibi, Nosheen Malak, Fayaz Asad, Barkat Ullah, Nasreen Nasreen, Adil Khan and Chien-Chin Chen
Pharmaceuticals 2023, 16(4), 489; https://doi.org/10.3390/ph16040489 - 25 Mar 2023
Cited by 1 | Viewed by 2350
Abstract
Viola canescens Wall. is an important medicinal plant with reported therapeutic benefits. The current work sought to investigate the antidiarrheal properties of V. canescens extracts both in vivo and in silico. This study applied molecular docking to unravel the molecular mechanism of V. [...] Read more.
Viola canescens Wall. is an important medicinal plant with reported therapeutic benefits. The current work sought to investigate the antidiarrheal properties of V. canescens extracts both in vivo and in silico. This study applied molecular docking to unravel the molecular mechanism of V. canescens and to find the most effective phytocompounds with antidiarrheal effects. The antidiarrheal activity of V. canescens was assessed utilizing the castor oil-induced diarrhea assay and the charcoal meal assay. Antidiarrheal characteristics were evaluated by measuring parameters such as intestinal motility, fecal score, and hypersecretion. The V. canescens extract had a dose-dependent and statistically significant impact in the charcoal meal assay and castor oil-induced diarrhea assay. In the castor oil-induced diarrhea assay, the ethyl acetate fraction (65.96%) showed the highest percentage of defecation inhibition at the highest dose (300 mg/kg (bw)), followed by the uncorrected crystalline compound (63.83%), crude alkaloids (63.83%), chloroform fraction (63.83%), and crude flavonoids (55.32%), while the aqueous fraction (40.43%) and n-Hexane fraction (42.55%) revealed the lowest antidiarrheal potential. In addition, the molecular docking investigation showed emetine, quercetin, and violanthin, isolated chemicals of V. canescens, to have the highest binding affinity to the target μ and δ opioid receptors with significant inhibitory capacity. These pharmacologically active metabolites in V. canescens were effective in treating diarrhea. This study lends credence to the traditional usage of V. canescens in treating gastrointestinal disorders. Full article
(This article belongs to the Special Issue Natural Products for Treatment of Parasitic Diseases)
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Review

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25 pages, 10387 KiB  
Review
Curcumin and Its Derivatives as Potential Antimalarial and Anti-Inflammatory Agents: A Review on Structure–Activity Relationship and Mechanism of Action
by Siti Nur Hidayah Jamil, Amatul Hamizah Ali, Shevin Rizal Feroz, Su Datt Lam, Hani Kartini Agustar, Mohd Ridzuan Mohd Abd Razak and Jalifah Latip
Pharmaceuticals 2023, 16(4), 609; https://doi.org/10.3390/ph16040609 - 18 Apr 2023
Cited by 13 | Viewed by 4907
Abstract
Curcumin, one of the major ingredients of turmeric (Curcuma longa), has been widely reported for its diverse bioactivities, including against malaria and inflammatory-related diseases. However, curcumin’s low bioavailability limits its potential as an antimalarial and anti-inflammatory agent. Therefore, research on the [...] Read more.
Curcumin, one of the major ingredients of turmeric (Curcuma longa), has been widely reported for its diverse bioactivities, including against malaria and inflammatory-related diseases. However, curcumin’s low bioavailability limits its potential as an antimalarial and anti-inflammatory agent. Therefore, research on the design and synthesis of novel curcumin derivatives is being actively pursued to improve the pharmacokinetic profile and efficacy of curcumin. This review discusses the antimalarial and anti-inflammatory activities and the structure–activity relationship (SAR), as well as the mechanisms of action of curcumin and its derivatives in malarial treatment. This review provides information on the identification of the methoxy phenyl group responsible for the antimalarial activity and the potential sites and functional groups of curcumin for structural modification to improve its antimalarial and anti-inflammatory actions, as well as potential molecular targets of curcumin derivatives in the context of malaria and inflammation. Full article
(This article belongs to the Special Issue Natural Products for Treatment of Parasitic Diseases)
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Other

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10 pages, 582 KiB  
Brief Report
A Dietary Plant Extract Formulation Helps Reduce Flea Populations in Cats: A Double-Blind Randomized Study
by Damien Banuls, Jessie Brun, Jean-Louis Blua and Marie Christine Cadiergues
Pharmaceuticals 2023, 16(2), 195; https://doi.org/10.3390/ph16020195 - 28 Jan 2023
Cited by 2 | Viewed by 4103
Abstract
There is a growing demand for natural products to be used to control fleas in pets. A prospective, double-blind, randomized, placebo-controlled study evaluated the efficacy of the biological plant-based food supplement Bioticks® (thyme, rosemary, lemon balm, fenugreek, wormwood, and lemongrass extracts) as [...] Read more.
There is a growing demand for natural products to be used to control fleas in pets. A prospective, double-blind, randomized, placebo-controlled study evaluated the efficacy of the biological plant-based food supplement Bioticks® (thyme, rosemary, lemon balm, fenugreek, wormwood, and lemongrass extracts) as a flea control product in naturally flea-infested cats with an indoor–outdoor lifestyle. Ten cats were used as placebo controls (group A). Ten other cats were fed the same daily diet but supplemented with Bioticks® (group B). Fleas were counted by combing at D0 and D0 + 14 days, then one, two, three, four, and five months after the start of this study. No flea treatment was administered, and no environmental changes were made for six months prior to the start and throughout this study. The product was well-tolerated. The mean flea population in group B progressively and steadily decreased to reach 3.3 ± 2.1 at month five. At the same time and under similar maintenance conditions, the average flea population in group A remained stable (14.3 ± 2.5) until the fifth month. The percentages of efficacy (Abbott formula) in group B compared to group A was 27%, 20%, 52%, 66%, and 77%, respectively, at one, two, three, four, and five months after the start of this study. Full article
(This article belongs to the Special Issue Natural Products for Treatment of Parasitic Diseases)
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