In vivo activity of ursolic and oleanolic acids during the acute phase of Trypanosoma cruzi infection

Ferreira, Daniele da Silva; Esperandim, Viviane Rodrigues; Toldo, Míriam Paula Alonso; Kuehn, C.; Júnior, José Clóvis do Prado; Cunha, Wilson Roberto; Silva, Márcio Luís Andrade e; Albuquerque, Sérgio de

doi:10.1016/j.exppara.2013.04.005

Cited by 29 publications

(18 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Triterpenoids are polycyclic compounds derived from the linear hydrocarbon squalene and comprise one of the most promising groups of phytochemicals due to its multifunctionality in the treatment of a broad range of diseases [16][17][18][19][20][21]. For instance, oleanolic acid administered at low doses has hepatoprotective properties, whereas high doses can result in cholestasis and hepatotoxicity [22].…”

Section: Introductionmentioning

confidence: 99%

“…Besides its antitumoral activity, UA possesses a wide variety of biological activities, such as antioxidant [26], hepatoprotective [22], hypoglycaemic [27], antibacterial [26], antiviral [28], antifungal [29] and antiprotozoal [18]. Its antiprotozoal efficacy has been tested in vitro against Trypanosoma cruzi [21], Plasmodium falciparum [22], and Leishmania spp [30].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Evaluating the Potential of Ursolic Acid as Bioproduct for Cutaneous and Visceral Leishmaniasis

et al. 2020

View full text Add to dashboard Cite

Leishmaniasis affects around 12 million people worldwide and is estimated to cause the ninth-largest disease burden. There are three main forms of the disease, visceral (VL), cutaneous (CL), and mucocutaneous (MCL), leading to more than one million new cases every year and several thousand deaths. Current treatments based on chemically synthesized molecules are far from ideal. In this study, we have tested the in vitro and in vivo efficacy of ursolic acid (UA), a multifunctional triterpenoid with well-known antitumoral, antioxidant, and antimicrobial effects on different Leishmania strains. The in vitro antileishmanial activity against the intracellular forms was six and three-fold higher compared to extracellular forms of L. amazonensis and L. infantum, respectively. UA also showed to be a potent antileishmanial drug against both VL and CL manifestations of the disease in experimental models. UA parenterally administered at 5 mg/kg for seven days significantly reduced the parasite burden in liver and spleen not only in murine acute infection but also in a chronic-infection model against L. infantum. In addition, UA ointment (0.2%) topically administered for four weeks diminished (50%) lesion size progression in a chronic infection model of CL caused by L. amazonensis, which was much greater than the effect of UA formulated as an O/W emulsion. UA played a key role in the immunological response modulating the Th1 response. The exposure of Leishmania-infected macrophages to UA led to a significant different production in the cytokine levels depending on the Leishmania strain causing the infection. In conclusion, UA can be a promising therapy against both CL and VL.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Evaluating the Potential of Ursolic Acid as Bioproduct for Cutaneous and Visceral Leishmaniasis

et al. 2020

View full text Add to dashboard Cite

show abstract

“…So far, > 20 000 individual triterpene structures, representing over 100 skeletal variations, are known from natural sources (Thimmappa et al, 2014;Ghosh, 2016). Pentacyclic triterpenes (PCTs) constitute a predominant triterpene class with diverse pharmaceutical activities (Laszczyk, 2009;Kong et al, 2013;da Silva Ferreira et al, 2013). Plant-origin PCTs are currently being marketed as dietary supplements as well as over-the-counter drugs and semi-synthetic PCT derivatives are undergoing clinical trials for the treatment of human diseases (Sheng & Sun, 2011;Moses et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Two CYP716A subfamily cytochrome P450 monooxygenases of sweet basil play similar but nonredundant roles in ursane‐ and oleanane‐type pentacyclic triterpene biosynthesis

et al. 2017

View full text Add to dashboard Cite

SummaryThe medicinal plant sweet basil (Ocimum basilicum) accumulates bioactive ursane-and oleanane-type pentacyclic triterpenes (PCTs), ursolic acid and oleanolic acid, respectively, in a spatio-temporal manner; however, the biosynthetic enzymes and their contributions towards PCT biosynthesis remain to be elucidated.Two CYP716A subfamily cytochrome P450 monooxygenases (CYP716A252 and CYP716A253) are identified from a methyl jasmonate-responsive expression sequence tag collection and functionally characterized, employing yeast (Saccharomyces cerevisiae) expression platform and adapting virus-induced gene silencing (VIGS) in sweet basil.CYP716A252 and CYP716A253 catalyzed sequential three-step oxidation at the C-28 position of a-amyrin and b-amyrin to produce ursolic acid and oleanolic acid, respectively. Although CYP716A253 was more efficient than CYP716A252 for amyrin C-28 oxidation in yeast, VIGS revealed essential roles for both of these CYP716As in constitutive biosynthesis of ursolic acid and oleanolic acid in sweet basil leaves. However, CYP716A253 played a major role in elicitor-induced biosynthesis of ursolic acid and oleanolic acid.Overall, the results suggest similar as well as distinct roles of CYP716A252 and CYP716A253 for the spatio-temporal biosynthesis of PCTs. CYP716A252 and CYP716A253 might be useful for the alternative and sustainable production of PCTs in microbial host, besides increasing plant metabolite content through genetic modification.

show abstract

“…Ursane-type and oleanane-type pentacyclic triterpenes (C30 compounds) are known for a variety of pharmaceutical properties, including anti-inflammatory, hepatoprotective, antitumor, antihyperlipidemic, antiulcer, and antimicrobial benefits (Kunkel et al, 2011;Wilkinson et al, 2011;Kurek et al, 2012;da Silva Ferreira et al, 2013;Kong et al, 2013). However, there are limited data on the biosynthesis of these secondary metabolites in plants (Brendolise et al, 2011;Huang et al, 2012;Yu et al, 2013).…”

mentioning

confidence: 99%

Methyl Jasmonate-Elicited Transcriptional Responses and Pentacyclic Triterpene Biosynthesis in Sweet Basil

et al. 2013

View full text Add to dashboard Cite

Sweet basil (Ocimum basilicum) is well known for its diverse pharmacological properties and has been widely used in traditional medicine for the treatment of various ailments. Although a variety of secondary metabolites with potent biological activities are identified, our understanding of the biosynthetic pathways that produce them has remained largely incomplete. We studied transcriptional changes in sweet basil after methyl jasmonate (MeJA) treatment, which is considered an elicitor of secondary metabolites, and identified 388 candidate MeJA-responsive unique transcripts. Transcript analysis suggests that in addition to controlling its own biosynthesis and stress responses, MeJA up-regulates transcripts of the various secondary metabolic pathways, including terpenoids and phenylpropanoids/flavonoids. Furthermore, combined transcript and metabolite analysis revealed MeJA-induced biosynthesis of the medicinally important ursane-type and oleanane-type pentacyclic triterpenes. Two MeJAresponsive oxidosqualene cyclases (ObAS1 and ObAS2) that encode for 761-and 765-amino acid proteins, respectively, were identified and characterized. Functional expressions of ObAS1 and ObAS2 in Saccharomyces cerevisiae led to the production of b-amyrin and a-amyrin, the direct precursors of oleanane-type and ursane-type pentacyclic triterpenes, respectively. ObAS1 was identified as a b-amyrin synthase, whereas ObAS2 was a mixed amyrin synthase that produced both a-amyrin and b-amyrin but had a product preference for a-amyrin. Moreover, transcript and metabolite analysis shed light on the spatiotemporal regulation of pentacyclic triterpene biosynthesis in sweet basil. Taken together, these results will be helpful in elucidating the secondary metabolic pathways of sweet basil and developing metabolic engineering strategies for enhanced production of pentacyclic triterpenes.

show abstract

In vivo activity of ursolic and oleanolic acids during the acute phase of Trypanosoma cruzi infection

Cited by 29 publications

References 35 publications

Evaluating the Potential of Ursolic Acid as Bioproduct for Cutaneous and Visceral Leishmaniasis

Evaluating the Potential of Ursolic Acid as Bioproduct for Cutaneous and Visceral Leishmaniasis

Two CYP716A subfamily cytochrome P450 monooxygenases of sweet basil play similar but nonredundant roles in ursane‐ and oleanane‐type pentacyclic triterpene biosynthesis

Methyl Jasmonate-Elicited Transcriptional Responses and Pentacyclic Triterpene Biosynthesis in Sweet Basil

Contact Info

Product

Resources

About