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Bioactive Compounds Derived from Plants and Their Medicinal Potential

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

Deadline for manuscript submissions: 25 February 2025 | Viewed by 9495

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Special Issue Editors

Dr. Maria de Lourdes Pereira

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CICECO-Aveiro Institute of Materials and Department of Medical Sciences, University of Aveiro, 3810-193 Aveiro, Portugal
Interests: chromium compounds; food supplements; obesogenic; natural compounds
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Dr. Veeranoot Nissapatorn

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School of Allied Health Sciences, Southeast Asia Water Team, World Union for Herbal Drug Discovery, and Research Excellence Center for Innovation and Health Products, Walailak University, Nakhon Si Thammarat, Thailand
Interests: parasitology; waterborne parasites; tropical diseases; Acanthamoeba; infectious disease epidemiology; natural products
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Prof. Dr. Ana Paula Girol

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Pro-Rector of Research and Post-Graduation UNIFIPA, Catanduva, SP, Brazil
Interests: herbal medicines and biomaterials in inflammatory and tumor processes; mast cells; annexin A1 protein
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Dr. Sónia M. R. Oliveira

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Faculty of Dental Medicine, Catholic University of Portugal, 3504-505 Viseu, Portugal
Interests: neurophysiology; cancer biology; reproductive biology; cellular biology; biomimetic systems; rare diseases; eHealth; histology; molecular biology; biomedicine; infections; public health
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Special Issue Information

Dear Colleagues,

Medicinal plants offer a rich source of pharmaceutical compounds with demonstrated potential to improve and address human and animal diseases, offering important avenues for drug discovery. These bioactive compounds have diverse properties, such as antimicrobial, larvicidal, antioxidant, anticancer, and immunomodulatory activities. Advancements in experimental methodologies, ranging from experimental models and culture systems to microfluidic platforms, have facilitated the study of the bioactivity and pharmacology of these compounds with greater precision and efficiency.

As there have been advances in different technologies, such as data science and machine learning, that have begun to transform evidence-based medicine, particularly at the diagnostics level, we gain a ‘glimpse’ of what next-generation medicine and pharmacy can offer. Despite these advances, in both basic science and technology, clinical translations remain scarce or lagging.

This Special Issue aims to comprehensively gather reports on the bioactivity of several medicinal plants through rigorous experimentation (e.g., in vitro, ex vivo, and in vivo) and advance the development of evidence-based pharmaceutical interventions. The reports can explore various aspects of natural product pharmacology, including the identification of novel compounds, mechanistic studies, synergistic effects, formulation development, and clinical trials. In this collection, we would like to promote some positive paradigm shifts towards more natural and patient-centric therapeutics. Original research and review articles are welcome.

Dr. Maria de Lourdes Pereira
Dr. Veeranoot Nissapatorn
Prof. Dr. Ana Paula Girol
Dr. Sónia M. R. Oliveira
Guest Editors

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

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Keywords

phytopharmaceutical drugs
activity screening (antimicrobial, antioxidant, anticancer, and immunomodulatory activity)
experimental models (in vitro, ex vivo, in vivo, etc.)
microfluidic systems

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Published Papers (10 papers)

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Research

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28 pages, 12654 KiB

Open AccessArticle

Investigating the Antibacterial, Antioxidant, and Anti-Inflammatory Properties of a Lycopene Selenium Nano-Formulation: An In Vitro and In Vivo Study

by Reem Binsuwaidan, Thanaa A. El-Masry, Maysa M. F. El-Nagar, Enas I. El Zahaby, Mohamed M. S. Gaballa and Maisra M. El-Bouseary

Pharmaceuticals 2024, 17(12), 1600; https://doi.org/10.3390/ph17121600 (registering DOI) - 27 Nov 2024

Abstract

Background: The potent antioxidant lycopene has attracted a large amount of research attention given its potential health benefits. We aimed to assess the antimicrobial, anti-inflammatory, and antioxidant properties of lycopene (Lyc), selenium nanoparticles (Se-NPs), and lycopene selenium nanoparticles (Lyc-Se-NPs). Methods: FTIR, polydispersity index, and zeta potential evaluations provided a complete characterization of the synthesized Lyc-Se-NPs. The broth dilution method and a crystal violet microtiter plate assay were employed to assess the antibacterial and antibiofilm activity, respectively. The rat wound infection model was performed to study the anti-inflammatory effect. Findings: The Lyc-Se-NPs had a zeta potential range of −16.93 to −31.04 mV and a mean particle size of 126.6 ± 3.12 nm. All peaks’ percentage transmittance decreased, according to the FTIR analysis of the Lyc-Se-NPs, with the exception of one peak at 2924.22 cm⁻¹, which is suggestive of C-H stretching. The mean scavenging concentrations for Lyc-Se-NPs in the DPPH and ABTS radical scavenging experiments were 3.85 ± 0.65 and 4.26 ± 0.7 µg/mL, respectively. For S. aureus, the Lyc-Se-NPs’ MIC values varied from 64 to 1024 µg/mL. CLSM verified that S. aureus treated with sub-MICs of Lyc-Se-NPs showed a significant reduction in biofilm formation. Furthermore, the group treated with 50 mg of Lyc-Se-NPs showed the quickest rate of wound healing. They demonstrated a notable elevation of the HO⁻¹ content in skin tissues, together with the greatest downregulation of TNF-α, IL-1β, and COX-2. Conclusions: The distinguishing features of Lyc-Se-NPs reveal that this unique compound is a promising antibacterial, antioxidant, and anti-inflammatory agent. Full article

(This article belongs to the Special Issue Bioactive Compounds Derived from Plants and Their Medicinal Potential)

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17 pages, 2032 KiB

Open AccessArticle

Analgesic and Anti-Arthritic Potential of Methanolic Extract and Palmatine Obtained from Annona squamosa Leaves

by Caren Naomi Aguero Ito, Elisangela dos Santos Procopio, Natália de Matos Balsalobre, Lucas Luiz Machado, Saulo Euclides Silva-Filho, Taíse Fonseca Pedroso, Caroline Caramano de Lourenço, Rodrigo Juliano Oliveira, Arielle Cristina Arena, Marcos José Salvador and Cândida Aparecida Leite Kassuya

Pharmaceuticals 2024, 17(10), 1331; https://doi.org/10.3390/ph17101331 - 5 Oct 2024

Viewed by 911

Abstract

Background/Objectives: Annona squamosa is used in folk medicine to treat pain and arthritis. Palmatine is an alkaloid isolated from several plants, including A. squamosa leaves. The aim of the present study was to investigate the analgesic, anti-arthritic, and anti-inflammatory potential of the methanolic extract of A. squamosa (EMAS) and palmatine. Methods: The chemical profile of EMAS was evaluated by ultra high-performance liquid chromatography with electrospray ionization coupled to mass spectrometry (UHPLC-ESI/MS). EMAS and palmatine were evaluated in carrageenan-induced pleurisy, zymosan-induced joint inflammation, formalin-induced nociception, and tumor necrosis factor (TNF)-induced mechanical hyperalgesia in experimental models in mice. A cytotoxicity test of EMAS and palmatine was performed using a methylthiazolidiphenyl-tetrazolium (MTT) bromide assay. Results: The analysis of the chemical profile of the extract showed the presence of palmatine, liriodenine, and anonaine. Oral administration of EMAS and palmatine significantly reduced leukocyte migration and oxide nitric production in the carrageenan-induced pleurisy model. EMAS and palmatine reduced mechanical hyperalgesia, leukocyte migration, and edema formation in the joint inflammation induced by zymosan. In the formalin test, palmatine was effective against the second-phase nociceptive response, mechanical hyperalgesia, and cold allodynia. In addition, palmatine reduced mechanical hyperalgesia induced by TNF. EMAS and palmatine did not demonstrate cytotoxicity. Conclusions: The present study showed that A. squamosa and palmatine are analgesic and anti-inflammatory agents, and that the anti-hyperalgesic properties of palmatine may involve the TNF pathway. Palmatine may be one of the compounds responsible for the anti-hyperalgesic and/or anti-arthritic properties of this medicinal plant. Full article

(This article belongs to the Special Issue Bioactive Compounds Derived from Plants and Their Medicinal Potential)

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13 pages, 1878 KiB

Open AccessArticle

The Anti-Arthritic Potential of the Ethanolic Extract of Salvia Lachnostachys Benth. Leaves and Icetexane Dinor-Diterpenoid Fruticuline B

by Natália de M. Balsalobre, Elisangela dos Santos-Procopio, Cristhian S. Oliveira, Silvia C. Neves, Maria H. Verdan, Saulo E. Silva-Filho, Rodrigo J. Oliveira, Maria É. A. Stefanello and Cândida A. L. Kassuya

Pharmaceuticals 2024, 17(9), 1226; https://doi.org/10.3390/ph17091226 - 18 Sep 2024

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Abstract

The decoction of Salvia lachnostachys Benth. leaves is used in Brazilian folk medicine for anti-spasmodic, antipyretic, and anxiolytic purposes. Some of the biological effects of an S. lachnostachys extract have been shown to be anti-inflammatory, anti-cancer, and antidepressant effects. In addition, this medicinal plant produces several compounds including icetexane diterpenoids, such as fruticuline A and fruticuline B. The aim of the present work was to evaluate the anti-hyperalgesic and anti-inflammatory properties of fruticuline B (FRUT B) and the ethanolic extract obtained from the leaves of S. lachnostachys (EESL) in experimental mouse models. EESL (30, 100, and 300 mg/kg) and FRUT B (1 mg/kg) were evaluated in articular inflammation-induced models in Swiss mice. In articular inflammation induced by Zymosan, EESL (300 mg/kg) and FRUT B (1 mg/kg) significantly reduced mechanical hyperalgesia (83.17% inhibition for EESL and 81.19% for FRUT B); edema (68.75% reduction for EESL and 33.66% for FRUT B); leukocyte migration (81.3% for EESSL and 92.2% for FRUT B), and nitric oxide production (88.3% for EESL and 74.4% for FRUT B). The exposure to fruticuline B significantly inhibited the edema (51.5%), mechanical (88.12%) and cold hyperalgesia (80.8%), and myeloperoxidase (MPO) (63.4%) activity 24 h after CFA injection. In the pleurisy model, FRUT B reduced 89.1% of leukocyte migration and 50.3% in nitric oxide production. Four hours after carrageenan injection, FRUT B (1 mg/kg) diminished 89.11% of mechanical hyperalgesia, 65.8% of paw edema, and 82.12% of the response to cold hyperalgesia. In the MTT test, EESL and fruticuline B caused no cytotoxicity. The present study revealed, for the first time, the anti-arthritic and anti-nociceptive effects of FRUT B, pointing out the therapeutic potential of the species to control inflammation and nociception. Future studies are needed to evaluate other biological properties of fruticuline B and to better understand its mechanism of action. Full article

(This article belongs to the Special Issue Bioactive Compounds Derived from Plants and Their Medicinal Potential)

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19 pages, 4126 KiB

Open AccessArticle

Thymol Protects against 5-Fluorouracil-Induced Hepatotoxicity via the Regulation of the Akt/GSK-3β Pathway in In Vivo and In Silico Experimental Models

by Yasmen F. Mahran, Amira M. Badr, Layla A. Al-Kharashi, Hanaa N. Alajami, Nouf T. Aldamry, Nervana Moustafa Bayoumy, Elshaymaa I. Elmongy and Sahar Soliman

Pharmaceuticals 2024, 17(8), 1094; https://doi.org/10.3390/ph17081094 - 21 Aug 2024

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Abstract

Background: 5-fluorouracil (5-FU) is a widely used, highly effective chemotherapeutic agent. However, its therapeutic efficacy is often limited by associated adverse effects, with hepatotoxicity being frequently reported with 5-FU therapy. Thymol is a monoterpene found in thyme (Thymus vulgaris L., Lamiaceae) and is known for its antioxidant, anti-apoptotic, and anticancer activities. This study aimed to explore the hepatoprotective activity of thymol against 5-FU-induced liver injury. Methods: Rats received two intraperitoneal doses of 5-FU (150 mg/kg) either alone or in combination with thymol at doses of 60 mg/kg or 120 mg/kg. Liver enzymes, oxidative stress, and apoptotic markers, in addition to histopathological changes, were assessed. Results: 5-FU induced marked liver injuries as evidenced by elevated liver enzymes and histopathological changes, in addition to abnormalities of oxidative and apoptotic markers. The administration of thymol ameliorated the 5-FU-induced oxidative damage through increasing hepatic antioxidants and lowering lipid peroxidation. Apoptotic response markers such as Bax, Bcl-2, Bax/Bcl-2 ratio, and PARP were also improved. Furthermore, Western blotting analysis showed that thymol modulated the 5-FU-induced changes in the expression of Akt/GSK-3β and p44/42 MAPK (ERK1/2) signaling pathways. Conclusions: Our research is the first to shed light on thymol’s potential protective effect against 5-FU- induced hepatotoxicity by inhibiting oxidative and apoptotic pathways and modulating the Akt/ GSK-3β as well as p44/42 MAPK (ERK1/2) signaling pathways. Full article

(This article belongs to the Special Issue Bioactive Compounds Derived from Plants and Their Medicinal Potential)

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22 pages, 3434 KiB

Open AccessArticle

Antinociceptive and Anti-Inflammatory Activities of Acetonic Extract from Bougainvillea x buttiana (var. Rose)

by Gabriela Castañeda-Corral, Mayra Cedillo-Cortezano, Magdalena Aviles-Flores, Misael López-Castillo, Juan José Acevedo-Fernández and Vera L. Petricevich

Pharmaceuticals 2024, 17(8), 1037; https://doi.org/10.3390/ph17081037 - 6 Aug 2024

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Abstract

Background:Bougainvillea x buttiana is an ornamental plant with antioxidant, anti-inflammatory, and cytotoxic activities, which has been traditionally used to treat respiratory diseases. This study aimed to investigate whether the acetonic extract of Bougainvillea x buttiana var. Rose (BxbRAE-100%) has analgesic and anti-inflammatory properties and its potential action mechanisms. Methods: Analgesic and anti-inflammatory activities were evaluated using three murine pain models and two acute inflammation models. In vitro, the ability of the extract to inhibit proteolytic activity and the activities of the enzymes phospholipase A2 (PLA2) and cyclooxygenase (COX) were evaluated. In silico analysis was performed to predict the physicochemical and Absorption, distribution, metabolism, and excretion (ADME) profiles of the compounds previously identified in BxbRAE-100%. Results: In vivo BxbRAE-100% decreased the nociceptive behaviors in the writhing model, the tail immersion, and the formalin test, suggesting that the extract has the potential to relieve pain at peripheral and central levels. Additionally, topical or oral BxbRAE-100% treatment reduced dose-dependent 12-O-Tetradecanoylphorbol-13-acetate (TPA)-induced ear inflammation and carrageenan-induced paw edema, respectively. In vitro, BxbRAE-100% significantly inhibited proteolytic activity and PLA2, COX-1 and COX-2 activities. In silico, the compounds previously identified in BxbRAE-100% met Lipinski’s rule of five and showed adequate ADME properties. Conclusions: These results support the use of B. x buttiana in Traditional Mexican Medicine and highlight its potential for the development of new treatments for pain and inflammation. Full article

(This article belongs to the Special Issue Bioactive Compounds Derived from Plants and Their Medicinal Potential)

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19 pages, 11500 KiB

Open AccessArticle

Ethanolic Extracts of Cupressaceae Species Conifers Provide Rapid Protection against Barium Chloride-Induced Cardiac Arrhythmia

by Meng-Ting Zeng, Li-Yue Huang, Xiao-Hui Zheng, Yan-Qi Fu and Ching-Feng Weng

Pharmaceuticals 2024, 17(8), 1003; https://doi.org/10.3390/ph17081003 - 29 Jul 2024

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Abstract

Sudden cardiac death (SCD) is responsible for a high percentage of cardiovascular fatalities, with ventricular arrhythmias being the most common cause. Despite numerous clinically available antiarrhythmic drugs (AADs), AADs retain some undesirable arrhythmic effects, and their inappropriate use can lead to severe adverse reactions. The exploration of new therapeutic options against arrhythmias with fewer unreceptive effects is of utmost importance. The ethanolic extracts of seven Cupressaceae species, namely, Chamaecyparis obtusa, Juniperus chinensis (L.) Ant., Sabina chinensis (L.) Ant. cv. Kaizuca, Platycladus orientalis (L.) Franco, Juniperus sabina L., Fokienia hodginsii, and Juniperus chinensis ‘Pyramidalis’ were investigated for their pharmacological effects on barium chloride (BaCl₂)-induced arrhythmia using normal II lead electrocardiogram (ECG) measurements in a mouse model. According to the ECG profiles, pretreatment with C. obtusa, P. orientalis, and J. sabina extracts provoked dose-dependent protection against BaCl₂-induced arrhythmia, while pretreatment with the other four species and amiodarone did not exert cardioprotective effects. The treatment effects were confirmed using a rat model. The therapeutic effects of C. obtusa, P. orientalis, and J. sabina extracts on the M2 and M3 receptors but not the M1 receptor were mediated by the inhibition of the M2 receptor blocker (methoctramine tetrahydrochloride), M3 antagonist (4-DAMP), or M1 receptor blocker (pirenzepine dihydrochloride). This first-line evidence illustrates that certain Cupressaceae species possess active antiarrhythmic components. The first line of key findings revealed that active components of certain Cupressaceae species have cardioprotective effects, suggesting that these innovative phytochemicals have promising potential for preventing the occurrence of cardiac arrhythmia and reducing sudden cardiac death. Full article

(This article belongs to the Special Issue Bioactive Compounds Derived from Plants and Their Medicinal Potential)

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22 pages, 7552 KiB

Open AccessArticle

Evaluation of Crocetin as a Protective Agent in High Altitude Hypoxia-Induced Organ Damage

by Jun Yang, Kai Luo, Ziliang Guo, Renjie Wang, Qingyuan Qian, Shuhe Ma, Maoxing Li and Yue Gao

Pharmaceuticals 2024, 17(8), 985; https://doi.org/10.3390/ph17080985 - 25 Jul 2024

Viewed by 881

Abstract

Crocetin is an aglycone of crocin naturally occurring in saffron and has been proved to have antioxidant, anti-inflammatory, and antibacterial activities. In this experiment, the protective effect of crocetin on vital organs in high-altitude hypoxia rats was studied. Crocetin was prepared from gardenia by the alkaline hydrolysis method, and its reducing ability and free radical scavenging ability were tested. The in vitro anti-hypoxia vitality was studied on PC₁₂ cells. The anti-hypoxic survival time of mice was determined in several models. The acute hypoxic injury rat model was established by simulating the hypoxic environment of 8000 m-high altitude for 24 h, and the anti-hypoxia effect of crocetin was evaluated by intraperitoneal injection with the doses of 10, 20, and 40 mg/kg. The water contents of the brain and lung were determined, and the pathological sections in the brain, lung, heart, liver, and kidney were observed by HE staining. The levels of oxidative stress (SOD, CAT, H₂O₂, GSH, GSH-Px, MDA) and inflammatory factors (IL-1β, IL-6, TNF-α, VEGF) in rat brain, lung, heart, liver, and kidney tissues were detected by ELISA. The results indicated that crocetin exhibited strong reducing ability and free radical scavenging ability and could improve the activity of PC₁₂ cells under hypoxia. After intraperitoneal injection with crocetin, the survival time of mice was prolonged, and the pathological damage, oxidative stress, and inflammation in rats’ tissue were ameliorated. The protective activity of crocetin on vital organs in high-altitude hypoxia rats may be related to reducing oxidative stress and inhibiting inflammatory response. Full article

(This article belongs to the Special Issue Bioactive Compounds Derived from Plants and Their Medicinal Potential)

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21 pages, 1438 KiB

Open AccessReview

Exploring the Comprehensive Neuroprotective and Anticancer Potential of Afzelin

by Mateusz Kciuk, Nitika Garg, Sanchit Dhankhar, Monika Saini, Somdutt Mujwar, Sushma Devi, Samrat Chauhan, Thakur Gurjeet Singh, Randhir Singh, Beata Marciniak, Adrianna Gielecińska and Renata Kontek

Pharmaceuticals 2024, 17(6), 701; https://doi.org/10.3390/ph17060701 - 28 May 2024

Cited by 3 | Viewed by 1302

Abstract

Neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and others) and cancer, seemingly disparate in their etiology and manifestation, exhibit intriguing associations in certain cellular and molecular processes. Both cancer and neurodegenerative diseases involve the deregulation of cellular processes such as apoptosis, proliferation, and DNA repair and pose a significant global health challenge. Afzelin (kaempferol 3-O-rhamnoside) is a flavonoid compound abundant in various plant sources. Afzelin exhibits a diverse range of biological activities, offering promising prospects for the treatment of diseases hallmarked by oxidative stress and deregulation of cell death pathways. Its protective potential against oxidative stress is also promising for alleviating the side effects of chemotherapy. This review explores the potential therapeutic implications of afzelin, including its capacity to mitigate oxidative stress, modulate inflammation, and promote cellular regeneration in neurodegenerative and cancer diseases. Full article

(This article belongs to the Special Issue Bioactive Compounds Derived from Plants and Their Medicinal Potential)

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15 pages, 2548 KiB

Open AccessSystematic Review

Unveiling the Neuroprotective Potential of Date Palm (Phoenix dactylifera): A Systematic Review

by Syed Mohammed Basheeruddin Asdaq, Abdulaziz Ali Almutiri, Abdullah Alenzi, Maheen Shaikh, Mujeeb Ahmed Shaik, Sultan Alshehri and Syed Imam Rabbani

Pharmaceuticals 2024, 17(9), 1221; https://doi.org/10.3390/ph17091221 - 17 Sep 2024

Viewed by 1119

Abstract

Background: Neurodegenerative diseases primarily afflict the elderly and are characterized by a progressive loss of neurons. Oxidative stress is intricately linked to the advancement of these conditions. This study focuses on Phoenix dactylifera (P. dactylifera; Family: Arecaceae), commonly known as “Ajwa,” a globally cultivated herbal plant renowned for its potent antioxidant properties and reported neuroprotective effects in pharmacological studies. Method: This comprehensive systematic review delves into the antioxidant properties of plant extracts and their phytochemical components, with a particular emphasis on P. dactylifera and its potential neuroprotective benefits. Preferred reporting items for systemic reviews and meta-analysis (PRISMA) were employed to review the articles. Results: The study includes 269 articles published in the literature and 17 were selected after qualitative analysis. The growing body of research underscores the critical role of polyphenolic compounds found in P. dactylifera, which significantly contribute to its neuroprotective effects through antioxidant mechanisms. Despite emerging insights into the antioxidant actions of P. dactylifera, further investigation is essential to fully elucidate the specific pathways through which it confers neuroprotection. Conclusions: Like many other plant-based supplements, P. dactylifera’s antioxidant effects are likely mediated by synergistic interactions among its diverse bioactive compounds, rather than by any single constituent alone. Therefore, additional preclinical and clinical studies are necessary to explore P. dactylifera’s therapeutic potential comprehensively, especially in terms of its targeted antioxidant activities aimed at mitigating neurodegenerative processes. Such research holds promise for advancing our understanding and potentially harnessing the therapeutic benefits of P. dactylifera in neuroprotection. Full article

(This article belongs to the Special Issue Bioactive Compounds Derived from Plants and Their Medicinal Potential)

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8 pages, 648 KiB

Open AccessBrief Report

In Vitro Evaluation of the Combinatorial Effect of Naringenin and Miltefosine against Leishmania amazonensis

by Vinícius Lopes Lessa, Gustavo Gonçalves, Beatriz Santos, Victoria Cruz Cavalari, Rafael Felipe da Costa Vieira and Fabiano Borges Figueiredo

Pharmaceuticals 2024, 17(8), 1014; https://doi.org/10.3390/ph17081014 - 1 Aug 2024

Viewed by 710

Abstract

Leishmania amazonensis causes a clinical form called diffuse cutaneous leishmaniasis (DCL) with challenges to treatment, like low efficiency and drug toxicity. Therefore, it is necessary to investigate new therapies using less toxic leishmanicidal compounds, such as flavonoids like naringenin, and their combination with conventional drugs, such as miltefosine. Antileishmanial dose/response activity, isobologram, calculation of dose reduction index (DRI), and fractional inhibitory concentration index (FICI) tests were performed on in vitro assays using reference promastigote forms of L. amazonensis (IFLA/BR/67/PH8) to assess the combinatorial effect between naringenin and miltefosine. The in vitro results of isobologram, DRI, and FICI calculations showed that the combination of the compounds had an additive effect and was able to reduce the half maximal inhibitory concentration (IC₅₀) of miltefosine in the promastigote forms of the parasite compared to the treatment of the drug alone. This study demonstrated in vitro the viability of a combination action of the flavonoid with the treatment with miltefosine, opening space for further investigations on the association of natural compounds with the drugs used for the treatment of L. amazonensis. Full article

(This article belongs to the Special Issue Bioactive Compounds Derived from Plants and Their Medicinal Potential)

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