In vitro evaluation of (−)α-bisabolol as a promising agent against Leishmania amazonensis

Rottini, Mariana Margatto; Amaral, Ana Cláudia F.; Ferreira, José Luiz P.; Silva, Jefferson Rocha de Andrade; Taniwaki, Noemi Nosomi; Souza, Celeste da Silva Freitas de; d’Escoffier, Luiz Ney; Almeida-Souza, Fernando; Hardoim, Daiana de Jesús; Costa, Salvatore; Calabrese, Kátia da Silva

doi:10.1016/j.exppara.2014.10.001

Cited by 38 publications

(23 citation statements)

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“…Due to severe adverse and toxic profile of synthetic molecules, there is an essential requirement of new, safer and active principles from nature (Sundar et al, 2000). Hence natural products once again got the attention and several groups are working on the development of natural product based new anti-leishmanial agents (Barata et al, 2000; Rocha et al, 2005; Sharma et al, 2013; Islamuddin et al, 2014a,b; Jameel et al, 2014; Rottini et al, 2015). Over the years several antifungal and anticancer agents were screened for their anti-leishmanial potentials.…”

Section: Discussionmentioning

confidence: 99%

β-Nitrostyrenes as Potential Anti-leishmanial Agents

et al. 2016

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Development of new therapeutic approach to treat leishmaniasis has become a priority. In the present study, the antileishmanial effect of β-nitrostyrenes was investigated against in vitro promastigotes and amastigotes. A series of β-nitrostyrenes have been synthesized by using Henry reaction and were evaluated for their antimicrobial activities by broth microdilution assay and in vitro antileishmanial activities against Leishmania donovani promastigotes by following standard guidelines. The most active compounds were futher evaluated for their in vitro antileishmanial activities against intracellular amastigotes. Among the tested β-nitrostyrenes, compounds 7, 8, 9, 12, and 17 exhibited potential activities (MICs range, 0.25–8 μg/mL) against clinically significant human pathogenic fungi. However, the microbactericidal concentrations (MBCs) and the microfungicidal concentrations (MFCs) were found to be either similar or only two-fold greater than the MICs. Anti-leishmanial results demonstrated that compounds 9, 12, 14, and 18 were found to be most active among the tested samples and exhibited 50% inhibitory concentration (IC50) by 23.40 ± 0.71, 37.83 ± 3.74, 40.50 ± 1.47, 55.66 ± 2.84 nM against L. donovani promastigotes and 30.5 ± 3.42, 21.46 ± 0.96, 26.43 ± 2.71, and 61.63 ± 8.02 nM respectively against intracellular L. donovani promastigotes amastigotes respectively which are comparable with standard AmB (19.60 ± 1.71 nM against promastigotes and 27.83 ± 3.26 nM against amastigotes). Compounds 9, 12, 14, and 18 were found to have potent in vitro leishmanicidal activity against L. donovani and found to be non-toxic against mammalian macrophages even at a concentration of 25 μM. Nitric oxide (NO) estimation studies reveals that these compounds are moderately inducing NO levels.

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Section: Discussionmentioning

confidence: 99%

β-Nitrostyrenes as Potential Anti-leishmanial Agents

et al. 2016

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“…Nontreated parasites were used as negative control. After 2, 4, 8, 16, 24, and 48 h-incubation promastigotes were collected by centrifugation at 1500× g. Cells were washed, fixed, and embedded in Epon ® resin (Polysciences, Inc., Warrington, PA, USA) [30]. Ultrathin sections were stained with uranyl acetate and lead citrate.…”

Section: Transmission Electron Microscopymentioning

confidence: 99%

“…A total of 10,000 events were acquired in the region previously established as corresponding to the parasites. Fluorescence was quantified and histograms were designed [30].…”

Section: Flow Cytometric Analysis For Detection Of Mitochondrial Membmentioning

confidence: 99%

A Triazole Hybrid of Neolignans as a Potential Antileishmanial Agent by Triggering Mitochondrial Dysfunction

et al. 2019

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In the search for new compounds with antileishmanial activity, we synthesized a triazole hybrid analogue of the neolignans grandisin and machilin G (LASQUIM 25), which was previously found highly active against both promastigotes and intracellular amastigote forms of Leishmania amazonensis. In this work, we investigated the leishmanicidal effects of LASQUIM 25 to identify the mechanisms involved in the cell death of L. amazonensis promastigotes. Transmission electron microscopy (TEM) analysis showed marked effects of LASQUIM 25 (IC50 = 7.2 µM) on the morphology of promastigote forms, notably on mitochondria. The direct action of the triazole derivative on the parasite was noticed over time from 2 h to 48 h, and cells displayed several ultrastructural alterations characteristic of apoptotic cells. Also, flow cytometric analysis (FACS) after TMRE staining detected changes in mitochondrial membrane potential after LASQUIM 25 treatment (64.83% labeling versus 83.38% labeling in nontreated cells). On the other hand, FACS after PI staining in 24 h-treatment showed a slight alteration in the integrity of the cell membrane, a necrotic event (16.76% necrotic cells versus 3.19% staining in live parasites). An abnormal secretion of lipids was observed, suggesting an exocytic activity. Another striking finding was the presence of autophagy-related lysosome-like vacuoles, suggesting an autophagic cell death that may arise as consequence of mitochondrial stress. Taken together, these results suggest that LASQUIM 25 leishmanicidal mechanisms involve some degree of mitochondrial dysregulation, already evidenced by the treatment with the IC50 of this compound. This effect may be due to the presence of a methylenedioxy group originated from machilin G, whose toxicity has been associated with the capacity to generate electrophilic intermediates.

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“…9,10 α-bisabolol (α-bis) is a small, plant-derived, oily sesquiterpene alcohol found as the major constituent of the essential oil from German chamomile (Chamomilla recutita (L.) Rauschert), a plant used for centuries for its medicinal properties. 11,12 α-bis has shown anti-inflammatory, 13 antimicrobial, antifungal, larvicidal, 14 leishmanicidal, 15 and antitumor properties. 16,17 Despite these protective effects, the therapeutic potential of α-bis in inflammatory lung diseases has not yet been investigated.…”

Section: Introductionmentioning

confidence: 99%

α-bisabolol-loaded lipid-core nanocapsules reduce lipopolysaccharide-induced pulmonary inflammation in mice

D'Almeida¹,

Oliveira²,

Souza³

et al. 2017

IJN

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Acute respiratory distress syndrome (ARDS) is a severe clinical condition of respiratory failure due to an intense inflammatory response with different etiologies. Despite all efforts, therapy remains limited, and ARDS is still associated with high mortality and morbidity. Plants can provide a vast source of active natural products for the discovery of new drugs. α-bisabolol (α-bis), a constituent of the essential oil from chamomile, has elicited pharmacological interest. However, the molecule has some limitations to its biological application. This study was conducted to develop a drug delivery system using lipid-core nanocapsules (LNCs) to improve the anti-inflammatory effects of orally administered α-bis. α-bis-loaded LNCs (α-bis-LNCs) were prepared by interfacial deposition of poly(ε-caprolactone) and orally administered in a mouse model of ARDS triggered by an intranasal administration of lipopolysaccharide (LPS). We found that α-bis-LNCs (30, 50, and 100 mg kg −1 ) significantly reduced airway hyperreactivity (AHR), neutrophil infiltration, myeloperoxidase activity, chemokine levels (KC and MIP-2), and tissue lung injury 18 hours after the LPS challenge. By contrast, free α-bis failed to modify AHR and neutrophil accumulation in the bronchoalveolar lavage effluent and lung parenchyma and inhibited elevation in the myeloperoxidase and MIP-2 levels only at the highest dose. Furthermore, only α-bis-LNCs reduced LPS-induced changes in mitogen-activated protein kinase signaling, as observed by a significant reduction in phosphorylation levels of ERK1/2, JNK, and p38 proteins. Taken together, our results clearly show that by using LNCs, α-bis was able to decrease LPS-induced inflammation. These findings may be explained by the robust increase of α-bis concentration in the lung tissue that was achieved by the LNCs. Altogether, these results indicate that α-bis-LNCs should further be investigated as a potential alternative for the treatment of ARDS.

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In vitro evaluation of (−)α-bisabolol as a promising agent against Leishmania amazonensis

Cited by 38 publications

References 20 publications

β-Nitrostyrenes as Potential Anti-leishmanial Agents

β-Nitrostyrenes as Potential Anti-leishmanial Agents

A Triazole Hybrid of Neolignans as a Potential Antileishmanial Agent by Triggering Mitochondrial Dysfunction

α-bisabolol-loaded lipid-core nanocapsules reduce lipopolysaccharide-induced pulmonary inflammation in mice

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In vitro evaluation of (−)α-bisabolol as a promising agent against Leishmania amazonensis

Cited by 38 publications

References 20 publications

β-Nitrostyrenes as Potential Anti-leishmanial Agents

β-Nitrostyrenes as Potential Anti-leishmanial Agents

A Triazole Hybrid of Neolignans as a Potential Antileishmanial Agent by Triggering Mitochondrial Dysfunction

&alpha;-bisabolol-loaded lipid-core nanocapsules reduce lipopolysaccharide-induced pulmonary inflammation in mice

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α-bisabolol-loaded lipid-core nanocapsules reduce lipopolysaccharide-induced pulmonary inflammation in mice