scholarly journals Antileishmanial compounds from Connarus suberosus: Metabolomics, isolation and mechanism of action

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0241855
Author(s):  
Lais S. Morais ◽  
Renata G. Dusi ◽  
Daniel P. Demarque ◽  
Raquel L. Silva ◽  
Lorena C. Albernaz ◽  
...  
Keyword(s):  
Natural Products ◽  
Lipid Body ◽  
Peritoneal Macrophages ◽  
Positive Control ◽  
Antileishmanial Activity ◽  
Parasite Resistance ◽  
Prototype Development ◽  
Transmission Electron ◽  
High Incidence ◽  
Plasma Membrane Permeabilization

Leishmaniasis is a disease impacting public health worldwide due to its high incidence, morbidity and mortality. Available treatments are costly, lengthy and toxic, not to mention the problem of parasite resistance. The development of alternative treatments is warranted and natural products demonstrate promising activity. This study investigated the activity of Connarus suberosus extracts and compounds against Leishmania species. Several C. suberosus extracts were tested against L. amazonensis promastigotes. Active and inactive extracts were analyzed by UHPLC-MS and data evaluated using a metabolomics platform, revealing an unknown neoflavonoid (connarin, 3), isolated together with the pterocarpans: hemileiocarpin (1) and leiocarpin (2). The aforementioned compounds (1–3), together with the benzoquinones: rapanone (4), embelin (5) and suberonone (6) previously isolated by our group from the same species, were tested against: (i) L. amazonensis and L. infantum promastigotes, and (ii) L. amazonensis intracellular amastigotes, with the most active compound (3) also tested against L. infantum amastigotes. Cytotoxicity against murine peritoneal macrophages was also investigated. Compounds 2 and 3 presented an IC50 33.8 μM and 11.4 μM for L. amazonensis promastigotes; and 44.3 μM and 13.3 μM for L. infantum promastigotes, respectively. For L. amazonensis amastigotes, the IC50 of 2 was 20.4 μM with a selectivity index (SI) of 5.7, while the IC50 of 3 was 2.9 μM with an SI of 6.3. For L. infantum amastigotes, the IC50 of 3 was 7.7 μM. Compounds 2 and 3 presented activity comparable with the miltefosine positive control, with compound 3 found to be 2–4 times more active than the positive control, depending on the Leishmania species and form. The extracts and isolated compounds showed moderate toxicity against macrophages. Compounds 2 and 3 altered the mitochondrial membrane potential (ΔΨm) and neutral lipid body accumulation, while 2 also impacted plasma membrane permeabilization, culminating in cellular disorder and parasite death. Transmission electron microscopy of L. amazonensis promastigotes treated with compound 3 confirmed the presence of lipid bodies. Leiocarpin (2) and connarin (3) demonstrated antileishmanial activity. This study provides knowledge of natural products with antileishmanial activity, paving the way for prototype development to fight this neglected tropical disease.

Anti-Inflammatory Properties of Plant Derived Natural Products – A Systematic Review

2019 ◽  
Vol 26 (24) ◽  
pp. 4506-4536 ◽  
Author(s):  
Iris E. Allijn ◽  
René P. Brinkhuis ◽  
Gert Storm ◽  
Raymond M. Schiffelers
Keyword(s):  
Systematic Review ◽  
Natural Products ◽  
Positive Control ◽  
Therapeutic Effects ◽  
Reference Compound ◽  
Individual Molecular Species ◽  
The Past ◽  
Anti Inflammatory ◽  
The Individual ◽  
Natural Medicines

Traditionally, natural medicines have been administered as plant extracts, which are composed of a mixture of molecules. The individual molecular species in this mixture may or may not contribute to the overall medicinal effects and some may even oppose the beneficial activity of others. To better control therapeutic effects, studies that characterized specific molecules and describe their individual activity that have been performed over the past decades. These studies appear to underline that natural products are particularly effective as antioxidants and anti-inflammatory agents. In this systematic review we aimed to identify potent anti-inflammatory natural products and relate their efficacy to their chemical structure and physicochemical properties. To identify these compounds, we performed a comprehensive literature search to find those studies, in which a dose-response description and a positive control reference compound was used to benchmark the observed activity. Of the analyzed papers, 7% of initially selected studies met these requirements and were subjected to further analysis. This analysis revealed that most selected natural products indeed appeared to possess anti-inflammatory activities, in particular anti-oxidative properties. In addition, 14% of the natural products outperformed the remaining natural products in all tested assays and are attractive candidates as new anti-inflammatory agents.

scholarly journals Screening of natural product extracts for fly repellent and larvicide

2021 ◽  
Vol 20 (1) ◽  
pp. 25-40
Author(s):  
Kanokwan Bootyothee ◽  
◽  
Surasit Aunpromma ◽  
Atchara Artchayasawat ◽  
Opal Pitaksakulrat ◽  
...  
Keyword(s):  
Natural Products ◽  
Mortality Rate ◽  
Crude Extract ◽  
Rural Areas ◽  
Inorganic Compounds ◽  
Food Contamination ◽  
Positive Control ◽  
Positive Control Group ◽  
Control Group ◽  
Significant Difference

Fly is one of the vectors of foodborne pathogenic vectors and causes myiasis in humans and animals. To prevent the contamination of food and myiasis, various chemical products are commonly used. However, eco-friendly is now a trend all over the world so natural products are the alternative ways to reduce the chemical residue in the environment. The present study was screened the 12 natural products in 4 groups; the essential oil plants, the alkaloid plants, the cyanogenic plant, and the inorganic compounds which use a simple extraction on the fly repelling and larvicide. The fly repelling efficacy with 2 criteria consist of the time of the first swarm and percent repelling (PR) in the first 15 min. The larvicidal efficacy was determined by the mortality rate within 24 h. The Kaffir lime peels aqueous crude extract exhibited the best result on fly repelling from both criteria with no significant difference. The bamboo shoots aqueous crude extract gave the best result on larvicide with significantly different from other groups (P < 0.001) which was faster than the positive control group (Coumaphos & Propoxur). Moreover, the high mortality rate reached 73.33 ± 15.28% within 24 h, higher than the positive control group. The present study indicates the power of common natural products on fly repellent and larvicide that may apply for fly repellant to reduce the food contamination especially fresh materials and prevention or treatment of animal and human myiasis in rural areas

Dipetalonema viteae: ultrastructural study on the in vitro interaction between rat macrophages and microfilariae in the presence of IgE antibody

Parasitology ◽  
1981 ◽  
Vol 82 (1) ◽  
pp. 55-62 ◽  
Author(s):  
M. A. Ouaissi ◽  
A. Haque ◽  
A. Capron
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Ultrastructural Study ◽  
Peritoneal Macrophages ◽  
Immune Serum ◽  
Sequence Of Events ◽  
Transmission Electron ◽  
Dipetalonema Viteae ◽  
In Vitro Interaction

SUMMARYThe in vitro interaction between rat peritoneal macrophages and Dipetalonema viteae microfilariae in the presence of amicrofilaraemic rat immune serum was studied by transmission electron microscopy. The probable sequence of events leading to the killing of D. viteae microfilaria by macrophages is as follows. (a) Rat peritoneal macrophages in the presence of amicrofilaraemic rat immune serum adhere to the parasite surface, (b) the macrophages extend their pseudopodia around the parasite, (c) the ‘lysosome-like’ granules discharge their contents on to the parasite surface, (d) the lytic activity of these products begins at the parasite surface and (e) subsequent breaking of the microfilarial cuticle occurs, exposing the parasite intracellular material.

Capsicum frutescens and Citrus limon: a new take on therapy against experimental trichinellosis

2021 ◽  
Vol 95 ◽  
Author(s):  
Marwa Ahmed Mohamed Salama ◽  
Nahed E. Mostafa ◽  
Naglaa Fathy Abd El-Aal ◽  
Eman M. Mostafa ◽  
Samar Kamel Hammad ◽  
...  
Keyword(s):  
Positive Control ◽  
Negative Control ◽  
Citrus Limon ◽  
Capsicum Frutescens ◽  
Histopathological Changes ◽  
Transmission Electron ◽  
Natural Remedies ◽  
Factor Α ◽  
Antiparasitic Agents ◽  
Necrosis Factor

Abstract Trichinellosis is a zoonotic disease that endangers human health and can lead to death. Restricted absorption and poor results of conventional therapies demand new effective natural remedies to treat both enteral and parenteral trichinellosis. This study assessed the antiparasitic and anti-inflammatory effects of Citrus limon and Capsicum frutescens on murine trichinellosis and compared them with those of albendazole and prednisolone, which are conventionally used to treat trichinellosis. Overall, 50 Swiss albino male mice were divided into five groups, with ten mice in each group: negative control, positive control, albendazole combined with prednisolone, C. limon, and C. frutescens. Mice were sacrificed 7 and 35 days after infection, for intestinal and muscular phase analyses. Drug efficacies were parasitologically, biochemically, histopathologically and ultrastructurally assessed. Our results demonstrated the efficacy of C. frutescens and C. limon extracts as antiparasitic agents, showing a substantial decrease in adult and larval counts. Moreover, both extracts had the ability to decrease serum tumour necrosis factor-α levels during the intestinal and muscular phases. In addition to the improved histopathological changes in the small intestine and muscles, the destructive effects on adults and larvae were ultrastructurally evident on transmission electron microscopy. In conclusion, C. frutescens and C. limon extracts are promising remedies for the treatment of experimental trichinellosis, particularly, the C. frutescens extract.

Zinc-clotrimazole complexes are effective against Trichomonas vaginalis

Parasitology ◽  
2019 ◽  
Vol 146 (9) ◽  
pp. 1206-1216 ◽  
Author(s):  
Victor Midlej ◽  
Felipe Rubim ◽  
Wilmer Villarreal ◽  
Érica S. Martins-Duarte ◽  
Maribel Navarro ◽  
...  
Keyword(s):  
Trichomonas Vaginalis ◽  
Transmitted Disease ◽  
Protozoan Parasite ◽  
Parasite Resistance ◽  
Zinc Compounds ◽  
Sexually Transmitted ◽  
Transmission Electron ◽  
Zinc Salts ◽  
Imidazole Compounds

AbstractTrichomonas vaginalis is a protozoan parasite that causes trichomoniasis in humans, the most prevalent non-viral sexually transmitted disease (STD). Imidazole compounds are used for the treatment of trichomoniasis, and metronidazole is the most commonly prescribed. However, these compounds can lead to parasite resistance and unwanted side effects. Therefore, there is a need for an alternative treatment for this disease. Here, we explored the potential of clotrimazole (CTZ) and zinc compounds, as well as CTZ complexed with zinc salts ([1] acetate [Zn(CTZ)2(Ac)2] and [2] a chloride [Zn(CTZ)2Cl2] complexes) against T. vaginalis. We synthesized the zinc complexed CTZ compounds and determined their concentration values that inhibited parasite growth by 50% (IC50). We used scanning and transmission electron microscopy to visualize the ultrastructural alterations induced by CTZ and their zinc complexes. The incubation of the parasites with [Zn(CTZ)2(Ac)2] complex inhibited their growth, yielding an IC50 of 4.9 µm. Moreover, there were changes in the shape of treated parasites, including the formation of surface projections that subsequently detached from the cell, in addition to changes in the hydrogenosomes, endoplasmic reticulum and Golgi complex. We found [Zn(CTZ)2(Ac)2] to be a highly effective compound against T. vaginalis in vitro, suggesting its potential utility as an alternative chemotherapy for trichomoniasis.

scholarly journals In Vitro Schistosomicidal Activity of the Alkaloid-Rich Fraction from Ruta graveolens L. (Rutaceae) and Its Characterization by UPLC-QTOF-MS

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Lara Soares Aleixo de Carvalho ◽  
Lucas Sales Queiroz ◽  
Ismael José Alves Junior ◽  
Ayla das Chagas Almeida ◽  
Elaine Soares Coimbra ◽  
...  
Keyword(s):  
Folk Medicine ◽  
Peritoneal Macrophages ◽  
Antileishmanial Activity ◽  
Parasitic Infections ◽  
Leishmania Braziliensis ◽  
Ruta Graveolens ◽  
Active Fraction ◽  
Ms Analysis ◽  
First Time

Schistosomiasis is a neglected tropical disease that affects million people worldwide, mostly in developing countries. Ruta graveolens (Rutaceae) is a plant used in folk medicine to treat several diseases, including parasitic infections. In this study, we reported the in vitro schistosomicidal activity of the R. graveolens extract (Rg) and its active fraction (Rg-FAE). Also, the characterization of Rg-FAE by UPLC-ESI-QTOF-MS analysis and its in vitro antileishmanial activity against Leishmania braziliensis were also performed. In vitro schistosomicidal assays were assessed against adult worms of S. mansoni, while cell viability against peritoneal macrophages was measured by MTT assay. Rg (100 μg/mL) exhibited noticeable schistosomicidal activity, causing 100% mortality and decreasing motor activity of all adult male and female schistosomes, but with low activity against L. braziliensis. After chromatographic fractionation of Rg, fraction Rg-FAE was obtained, showing high activity against adult schistosomes. UPLC-ESI-QTOF-MS analysis of Rg-FAE revealed the presence of eleven alkaloids and one furanocoumarin. No significant antileishmanial activity was found for Rg, while Rg-FAE exhibited activity against L. braziliensis promastigotes. We demonstrated, for the first time, that the R. graveolens extract (Rg) and its alkaloid-rich fraction (Rg-FAE) are active against adult worms of S. mansoni, with no significant cytotoxicity on macrophages. Our findings open the route to further antiparasitic studies with the active fraction of R. graveolens and its identified compounds, especially alkaloids.

scholarly journals Cartilage Trauma Induces Necroptotic Chondrocyte Death and Expulsion of Cellular Contents

2020 ◽  
Vol 21 (12) ◽  
pp. 4204
Author(s):  
Josef Stolberg-Stolberg ◽  
Meike Sambale ◽  
Uwe Hansen ◽  
Alexandra Schäfer ◽  
Michael Raschke ◽  
...  
Keyword(s):  
Significant Loss ◽  
Caspase Inhibitor ◽  
Akt Inhibitor ◽  
Chondrocyte Death ◽  
Transmission Electron ◽  
High Prevalence ◽  
Post Traumatic ◽  
Plasma Membrane Permeabilization ◽  
Traumatic Arthritis

Necroptotic cell death is characterized by an activation of RIPK3 and MLKL that leads to plasma membrane permeabilization and the release of immunostimulatory cellular contents. High levels of chondrocyte death occur following intra-articular trauma, which frequently leads to post-traumatic osteoarthritis development. The aim of this study is to assess necroptosis levels in cartilage post-trauma and to examine whether chondrocyte necroptotic mechanisms may be investigated and modified in vitro. Fractured human and murine cartilage, analysed immunohistochemically for necroptosis marker expression, demonstrated significantly higher levels of RIPK3 and phospho-MLKL than uninjured controls. Primary murine chondrocytes stimulated in vitro with the TNFα and AKT-inhibitor alongside the pan-caspase inhibitor Z-VAD-fmk exhibited a significant loss of metabolic activity and viability, accompanied by an increase in MLKL phosphorylation, which was rescued by further treatment of chondrocytes with necrostatin-1. Transmission electron microscopy demonstrated morphological features of necroptosis in chondrocytes following TNFα and Z-VAD-fmk treatment. Release of dsDNA from necroptotic chondrocytes was found to be significantly increased compared to controls. This study demonstrates that cartilage trauma leads to a high prevalence of necroptotic chondrocyte death, which can be induced and inhibited in vitro, indicating that both necroptosis and its consequential release of immunostimulatory cellular contents are potential therapeutic targets in post-traumatic arthritis treatment.

scholarly journals Novel Carbon Dots Derived from Puerariae lobatae Radix and Their Anti-Gout Effects

Molecules ◽  
2019 ◽  
Vol 24 (22) ◽  
pp. 4152
Author(s):  
Xiaoke Wang ◽  
Yue Zhang ◽  
Meiling Zhang ◽  
Hui Kong ◽  
Suna Wang ◽  
...  
Keyword(s):  
Carbon Dots ◽  
Gouty Arthritis ◽  
Current Treatment ◽  
Water Soluble ◽  
Cell Counting ◽  
Raw264.7 Cells ◽  
Transmission Electron ◽  
High Incidence ◽  
Good Biocompatibility

Gout is a disease with a high incidence and causing great harm, and the current treatment drugs are not satisfactory. In this study, novel water-soluble carbon dots (CDs) with anti-gout effect, named Puerariae lobatae Radix CDs (PLR-CDs), are reported. PLR-CDs were synthesized with an improved pyrolysis method at 300 °C, and their characterization was performed with multifaceted approaches, such as transmission electron microscopy (TEM) and ultraviolet–visible (UV–vis) and Fourier-transform infrared (FTIR) spectroscopy. In addition, the biocompatibility of PLR-CDs was studied using the cell counting kit (CCK)-8 in LO2 cells and RAW264.7 cells, and the anti-gout activity of PLR-CDs was examined on animal models of hyperuricemia and gouty arthritis. The characterization of PLR-CDs indicated that they were nearly spherical, with diameters ranging from 3.0 to 10.0 nm, and the lattice spacing was 0.283 nm. The toxicity experiment revealed that PLR-CDs were non-poisonous for LO2 cells and RAW264.7 cells at concentrations below 250 μg/mL. The results of pharmacodynamic experiments showed that PLR-CDs could lower the blood uric acid level in model rats by inhibiting the activity of xanthine oxidase and reduce the degree of swelling and pathological damage of gouty arthritis. Thus, PLR-CDs with anti-gout biological activity and good biocompatibility have the prospect of clinical application for the treatment of gout.

scholarly journals A cocktail of betulinic acid, parthenolide, honokiol and ginsenoside Rh2 in liposome systems for lung cancer treatment

Nanomedicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 41-54 ◽  
Author(s):  
Xin Jin ◽  
Qing Yang ◽  
Ning Cai ◽  
Zhenhai Zhang
Keyword(s):  
Lung Cancer ◽  
Natural Products ◽  
Betulinic Acid ◽  
Synergistic Action ◽  
Ginsenoside Rh2 ◽  
High Incidence ◽  
High Incidence Rate ◽  
Very High

Aim: Lung cancer has a very high incidence rate, and thus, there is an urgent need for novel and effective therapies. Materials & methods: In this study, we proposed a potential treatment option by combining four natural products in liposome systems. Results: In vitro studies indicated that the combination of betulinic acid, parthenolide, honokiol and ginsenoside Rh2 exhibited a synergistic action. When these four natural products were loaded into liposome systems, we observed an increased effect. The relative action was also observed in vivo. The cisplatin group presented obvious kidney damage, whereas both cocktail therapy and cocktail liposome therapy were safer. Conclusion: Therefore, we propose cocktail liposome systems may provide a more efficient and safer treatment for lung cancer.

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