Plants of the Phytolaccaceae family with antimicrobial activity: A systematic review.

Phytolaccaceae is a plant family of the order Caryophyllales, which includes species used in traditional medicine to treat diseases. The purpose of this study was to investigate Phytolaccaceae family plants with potential antimicrobial action, through a systematic review. The study was conducted following the criteria of PRISMA protocol. The search was performed in the electronic databases PubMed, Web of Science, Scopus, and LILACS, in March 2021. The search strategy used free descriptors and terms, limiting articles to the English language, regardless of publication year. The risk of bias and the quality of publications were based on the CONSORT checklist, modified for in vitro studies and SYRCLE's RoB tool for in vivo study. Five independent judges performed quality assessments of publications and risk of bias analysis. Ninety-five publications were retrieved from the databases and, after screening and eligibility criteria, 22 articles remained, from 1998 to 2019. In the selected studies, the plants were obtained from eight countries. In vivo and in vitro studies of extracts from the Phytolaccaceae family plants, evaluating antibacterial (8 publications), antifungal (8), anti-Trypanosoma (2), anti-Leishmania (2), antiviral (1), and antiamoebic (1) activities, are included. The plant species identified belong to genera Petiveria, Phytolacca, Gallesia, Trichostigma, and Seguieria. The risk of bias in the 22 publications both in vitro and in vitro was suboptimal. The evidence obtained showed that the Phytolaccaceae family, a source of plants with antimicrobial action, can serve as a basis for the creation of new herbal medicines, expanding the possibility of treatment for infectious diseases and stimulating their preservation and biodiversity. However, more high-quality studies are needed to establish the clinical efficacy of the plant.

A standardized intraperitoneal Glucantime™ for experimental treatment of cutaneous leishmaniasis caused by Leishmania amazonensis in BALB/c mice.

Glucantime™ is the pentavalent antimony (Sb+5) recommended as the first choice for treating cutaneous leishmaniasis (CL). It has been used as treatment control in animal studies to investigate new anti-Leishmania compounds. However, these studies have a range of Glucantime™ doses, different treatment times and routes of administration, and differing results. Our goal was to standardize intraperitoneal Glucantime™ treatment for CL in BALB/c mice infected with L. amazonensis. BALB/c mice were divided into six groups, with eight animals per group. The animals were infected with L. amazonensis and intraperitoneally treated with different doses of Sb+5 (20, 100 and 200 mg/kg/day) for 30 consecutive days. Healthy animals were used as negative infection and treatment control. Infected and untreated animals were used as positive infection control. Animals infected and treated with Ampho B were used as treatment control. Biochemical and histological analysis was performed to assess renal and liver toxicity. The parasite load in the popliteal lymph node, spleen and liver was determined by limiting dilution. Histological and collagen fiber analyses were performed on the lesions. Animals treated with Sb+5 100 and 200 mg/kg/day showed a decreased paw measurements, associated with a reduction in the parasite load, with a clinical cure rate of 50% and 37.5%, respectively. These groups of animals also showed tissue regeneration and reduced inflammation. Animals treated with 100 mg/kg/day had collagen fiber parameters similar to those of the negative infection control. There were no biochemical signs of renal or liver toxicity in any of the groups. We found that Sb+5 100 mg/kg/day was the lowest dose that showed effectiveness in treating CL in mice, and it may be a good model of treatment control in studies evaluating new treatments for CL in BALB/c mice.

The anti-Leishmania potential of bioactive compounds derived from naphthoquinones and their possible applications. A systematic review of animal studies.

Leishmaniasis affects millions of people worldwide, and available treatments have severe limitations. Natural and derivative products are significant sources of innovative therapeutic agents. Naphthoquinones are natural or synthetic chemical compounds with broad biological activity. This systematic review aimed to evaluate the potential anti-Leishmania activity of bioactive compounds derived from naphthoquinones in animal models. Conducted in accordance with PRISMA guidelines, two blocks of MeSH terms were assembled: group I, Leishmania OR Leishmaniasis; group II, Atovaquone OR Lapachol OR Beta lapachone OR Naphthoquinones. The search was performed on PubMed, Web of Science, SCOPUS, EMBASE, and Lilacs databases. Twenty-four articles were retrieved and submitted for quality assessment using the SYRCLE critical appraisal tool. The in vivo anti-Leishmania potential of naphthoquinones was evaluated in visceral and cutaneous leishmaniasis using several measurement parameters. Analyzed compounds varied in structure, association with reference drugs, and encapsulation using a drug delivery system. The study design, including treatment protocol, differed between studies. The findings of the studies in this systematic review indicate the anti-Leishmania potential of naphthoquinones in vivo, with different treatment regimens directed against different Leishmania species. The employed drug delivery systems improve the results concerning selectivity, distribution, and required therapeutic dose. The immunomodulatory action was shown to be beneficial to the host, favoring an adequate immune response against infection by Leishmania parasites since it favored Th1 responses. All studies presented a moderate to high risk of bias. These findings suggest that more studies are needed to assess the overall effectiveness and safety of these treatments.

Successful combined therapy with Glucantime™ and pentoxifylline for the nasal mucosal lesion recently developed in a leishmaniasis patient having untreated cutaneous lesion for seven decades.

Leishmaniasis is a worldwide problem and has been neglected in a wide range of fields, from diagnosis to treatment. This report describes a case of mucosal leishmaniasis, which may developped after seven decades of an inadequately treated cutaneous lesion. A female patient, 79 years old, from the non-endemic area for leishmaniasis in northern Paraná, presenting mucosal lesion in the nose and throat, reported an "angry ulcer" treated inappropriately as a child when she lived in an endemic region of the state of São Paulo. Indirect immunofluorescence and direct parasite screening were positive. Polymerase chain reaction detected a parasite belonging to the subgenus Leishmania (Viannia) sp. Due to patients limitations, such as low weight and advanced age, the therapeutic model adopted was the combined small doses of Glucantime™ to pentoxifylline, which ensured treatment success.

Genetic variations in the human immune system influence susceptibility to tegumentary leishmaniasis: a systematic review and meta-analysis.

OBJECTIVES: The outcomes of tegumentary leishmaniasis (TL) rely on a complex interaction between the host immune system and the parasite. This study assessed the influence of polymorphisms in immune-related genes on TL. METHODS: Web of Science, Scopus, PubMed, and Embase databases were searched systemically. The meta-analysis used a retrospective model in examining alleles, heterozygotes, and homozygotes. A quality assessment and an analysis of cumulative evidence were performed. RESULTS: A total of 29 genes (encoding for cytokines, chemokines, and other immune receptors) and 84 polymorphisms were analyzed. The IL-1ß_rs16944 (OR = 1.341, p = 0.003), TNF-α_rs1800629 (OR = 3.804, p = 0.004), MIF_rs755622 (OR = 3.357, p = 0.001), and INF- γ_rs243056 (OR = 1.670, p = 0.028) polymorphisms were speculated as risk factor for TL. They decrease the expression of the corresponding genes crucial for TL control. The quality assessment score was approximately 50%, suggesting the need for a clear method and polymorphism characterization for further comparison. The relevant risk of bias and other considerations resulted in low and moderate cumulative evidence confidence. CONCLUSIONS: IL-1ß_rs16944, TNF-α_rs1800629, MIF_rs755622, and INF-γ_rs2430561 polymorphisms were speculated as risk factor for TL, corroborating that IL-1ß, TNF-α, INF-γ, and MIF are involved in the TL pathogenesis.

Potential of Pluronics® P-123 and F-127 as nanocarriers of anti-Leishmania chemotherapy.

Leishmaniasis is a neglected disease and drugs approved for its treatment often lead to abandonment, failure of therapy and even death. Photodynamic therapy (PDT) has been shown to be a promising, non-invasive and selective for a target region without requiring high-cost technology. Usually, it is employed a photosensitizing agent (PS) incorporated into nanoparticles (NP). Pluronics® P-123 and F-127 micelles are very interesting aqueous NP promoting efficient and selective delivery and less adverse effects. This study aimed to detect the activity of Pluronics® P-123 and F-127 themselves since there is a scarcity of data on these NP activities without drugs incorporation. This study evaluated, in vitro, the activity of Pluronics® against promastigotes and amastigotes of Leishmania amazonensis and also their cytotoxicities. Additionally, the determination of the mitochondria membrane potential in promastigotes, internalization of these Pluronics® in the parasite membrane and macrophages and its stability in the culture medium was evaluated. Results showed that Pluronics® did not cause significant damage to human red cells and promastigotes. The P-123 and F-127 inhibited the survival rate of L. amazonensis amastigotes, and also presented loss of mitochondrial membrane potential on promastigotes. The Pluronics® showed low cytotoxic activity on J774A.1 macrophages, while only P-123 showed moderate cytotoxicity for BALB/c macrophages. The stability of P-123 and F-127 in culture medium was maintained for ten days. In conclusion, the NP studied can be used for incorporating potent leishmanicidal chemotherapy, due to their selectivity towards macrophages, being a promising system for the treatment of cutaneous leishmaniasis.

6,7-Dehydroroyleanone diterpene derived from Tetradenia riparia essential oil modulates IL-4/IL-12 release by macrophages that are infected with Leishmania amazonensis.

The treatment of cutaneous leishmaniasis in associated with several adverse effects and therapeutic failure, resulting in patients' abandonment of treatment. Research on new drugs with leishmanicidal potential from medicinal plants is essential. The anti-Leishmania activity of Tetradenia riparia essential oil (TrEO) and its derivatives, such as the diterpene 6,7-dehydroroyleanone (TrROY), and the immunomodulatory effects of TrEO have been reported. However, few studies have investigated the effects of TrROY. The present study evaluated the modulation of cytokine production by murine macrophages that were infected with Leishmania amazonensis (6 parasites/macrophage) and treated with TrROY (0.1, 1, and 100 µg/ml). Cytokine levels were measured by flow cytometry. The results were analyzed using Student's t test at a 95% confidence interval. Microscopic counting was performed to evaluate the inhibitory effects of TrROY on intracellular infection. TrROY modulated the production of cytokines that are essential for the immune defense response to Leishmania, with a decrease in interleukin-4 (IL-4) levels and an increase in IL-12 levels. A TrROY concentration of 0.1 µg/ml was chosen for the subsequent experiments. This dose was chosen because it modulated IL-4/IL-12 release by murine macrophages that were infected with Leishmania and because it presented no cytotoxic effects. TrROY (0.1 µg/ml) induced a 31% reduction of the rate of infection in murine macrophages compared with untreated cells. TrROY may be a promising leishmanicidal agent. Further in vitro and in vivo studies should be conducted to evaluate the anti-Leishmania and immunomodulatory activity of TrROY.

American tegumentary leishmaniasis: diagnostic and treatment challenges in a clinical case.

This clinical case presents a patient with a raised and ulcerative lesion with erythematous edges in the mouth, on the lower lip that was unsuccessfully treated as herpes labialis. Clinical data and laboratory tests (Montenegro skin test, indirect immunofluorescence, direct parasite search and polymerase chain reaction) led to the diagnosis of American tegumentary leishmaniasis caused by Leishmania (Viannia) sp. Treatment with pentavalent antimonial (Glucantime®) for 120 days was not effective and administration of amphotericin B for 30 days resulted in wound healing. Glucantime® treatment protocol was longer than the recommended by the Brazilian Ministry of Health in the handbook of mucosal leishmaniasis. This suggests that amphotericin B should have been administered earlier, preventing the psychological and social problems faced by the patient. This study reports a rare clinical case of primary mucosal leishmaniasis on the lip that had a delayed diagnosis, highlighting the precariousness in the management of disease and showing that, despite the importance of leishmaniasis in Brazil, it is still neglected by health professionals.