Dehydroabietic acid isolated from Pinus elliottii exerts in vitro antileishmanial action by pro-oxidant effect, inducing ROS production in promastigote and downregulating Nrf2/ferritin expression in amastigote forms of Leishmania amazonensis

Gonçalves, Manoela Daiele; Bortoleti, Bruna Taciane da Silva; Tomiotto-Pellissier, Fernanda; Miranda-Sapla, Milena Menegazzo; Assolini, João Paulo; Carloto, Amanda Cristina Machado; Carvalho, Priscila Pamela Trindade; Tudisco, Ellen Takasse; Urbano, Alexandre; Ambrósio, Sérgio Ricardo; Hirooka, Elisa Yoko; Simão, Andréa Name Colado; Costa, Idessânia Nazareth; Pavanelli, Wander Rogério; Conchon‐Costa, Ivete; Arakawa, Nilton Syogo

doi:10.1016/j.fitote.2018.05.027

Cited by 35 publications

(21 citation statements)

References 24 publications

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“…Mahanine inhibits JAK1 and Src which subsequently promotes the degradation of STAT3, an important transcription factor in macrophages that causes upregulation of IL-10 expression and suppression of Th1 responses ( Biswas et al, 2011 ; Lee et al, 2011 ; Das et al, 2014 ). While mahanine possesses its own unique immunomodulatory effects, several other natural compounds stimulate ROS and NO production in vitro including but not limited to, lupeol from Sterculia villosa , dehydroabietic acid from Pinus elliottii , and oil extracts from Nectandra species ( da Costa-Silva et al, 2015 ; Bosquiroli et al, 2017 ; Das et al, 2017 ; Goncalves et al, 2018 ). For example, Punica granatum , commonly known as pomegranate, has been shown to have antiparasitic and antioxidant properties ( Kaur et al, 2006 ).…”

Section: Host-targeted Therapeutics and Approaches For Treatment Of Lmentioning

confidence: 99%

Host-Directed Drug Therapies for Neglected Tropical Diseases Caused by Protozoan Parasites

et al. 2018

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The neglected tropical diseases (NTDs) caused by protozoan parasites are responsible for significant morbidity and mortality worldwide. Current treatments using anti-parasitic drugs are toxic and prolonged with poor patient compliance. In addition, emergence of drug-resistant parasites is increasing worldwide. Hence, there is a need for safer and better therapeutics for these infections. Host-directed therapy using drugs that target host pathways required for pathogen survival or its clearance is a promising approach for treating infections. This review will give a summary of the current status and advances of host-targeted therapies for treating NTDs caused by protozoa.

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Section: Host-targeted Therapeutics and Approaches For Treatment Of Lmentioning

confidence: 99%

Host-Directed Drug Therapies for Neglected Tropical Diseases Caused by Protozoan Parasites

et al. 2018

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“…Dehydroabietic acid is a naturally occurring compound in many coniferous plants [26] and has shown anti-leishmanial, antiaging, and antibacterial activities [19,27,28]. However, the anti-inflammatory mechanism of DAA has not been revealed.…”

Section: Discussionmentioning

confidence: 99%

“…Dehydroabietic acid (DAA) (Figure 1) is, along with abietic acid, a major compound of rosin derived from coniferous plants such as Pinus , Picea , Larix , and Abies [17,18,19]. Abietic acids are known to have biological activity including anti-inflammation or anti-allergy, and DAA has been studied as a peroxisome proliferator-activated receptor (PPAR) ligand in macrophages to suppress inflammation [19,20,21,22]. However, the detailed regulatory mechanism in inflammatory responses has not been deciphered.…”

Section: Introductionmentioning

confidence: 99%

Dehydroabietic Acid Suppresses Inflammatory Response Via Suppression of Src-, Syk-, and TAK1-Mediated Pathways

Kim

Kang

Lee

et al. 2019

IJMS

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Dehydroabietic acid (DAA) is a naturally occurring diterpene resin acid derived from coniferous plants such as Pinus and Picea. Various bioactive effects of DAA have been studied including antibacterial, antifungal, and anticancer activities. However, the anti-inflammatory mechanism of DAA remains unclear. We evaluated the anti-inflammatory effect of DAA in macrophage cell lines. Dehydroabietic acid clearly reduced nitric oxide (NO) production and inflammatory gene expression decreased according to RT-PCR results. Dehydroabietic acid displayed anti-inflammatory activity at the transcriptional level in results from NF-κB- or AP-1-mediated luciferase assays. To identify the DAA target protein, we investigated NF-κB and AP-1 pathways by Western blotting analysis. Dehydroabietic acid suppressed the activity of proto-oncogene tyrosine protein kinase (Src) and spleen tyrosine kinase (Syk) in the NF-κB cascade and transforming growth factor beta-activated kinase 1 (TAK1) in the AP-1 cascade. Using overexpression strategies, we confirmed that DAA targeted these kinases. Our findings demonstrate the anti-inflammatory effects and molecular mechanism of DAA. This suggests that DAA has potential as a drug or supplement to ameliorate inflammation.

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“…Dehydroabietic acid (DHA), isolated from Pinus elliottii, a conifer belonging to the family Pinaceae, also has in vitro antileishmanial action by downregulating Nrf2/Ferritin expression, thereby inducing a pro-oxidant effect and increasing the ROS levels in macrophages, which adversely affects the replication of L. amazonensis (Gonçalves et al, 2018).…”

Section: Nrf2 As a Possible Therapeutic Target In Leishmania Infectionmentioning

confidence: 99%

The Potential Role of Nrf2 Signaling in Leishmania Infection Outcomes

Vivarini

Lopes

2020

Front. Cell. Infect. Microbiol.

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Nrf2 [nuclear factor erythroid 2-related factor 2 (Nrf2)] regulates the expression of a plethora of genes involved in the response to oxidative stress due to inflammation, aging, and tissue damage, among other pathological conditions. Deregulation of this cytoprotective system may also interfere with innate and adaptive immune responses. Oxidative burst, one of the main microbicidal mechanisms, could be impaired during initial phagocytosis of parasites, which could lead to the successful establishment of infection and promote susceptibility to diseases. A wide diversity of infections, mainly those caused by intracellular pathogens such as viruses, bacteria, and protozoan parasites, modulate the activation of Nrf2 by interfering with post-translational modifications, interactions between different protein complexes and the immune response. Nrf2 may be induced by pathogens via distinct pathways such as those involving the engagement of Toll-like receptors, the activation of PI3K/Akt, and endoplasmic reticulum stress. Recent studies have revealed the importance of Nrf2 on leishmaniasis. This mini-review discusses relevant findings that reveal the connection between Leishmania-induced modifications of the host pathways and their relevance to the modulation of the Nrf2-dependent antioxidative response to the infection.

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Dehydroabietic acid isolated from Pinus elliottii exerts in vitro antileishmanial action by pro-oxidant effect, inducing ROS production in promastigote and downregulating Nrf2/ferritin expression in amastigote forms of Leishmania amazonensis

Cited by 35 publications

References 24 publications

Host-Directed Drug Therapies for Neglected Tropical Diseases Caused by Protozoan Parasites

Host-Directed Drug Therapies for Neglected Tropical Diseases Caused by Protozoan Parasites

Dehydroabietic Acid Suppresses Inflammatory Response Via Suppression of Src-, Syk-, and TAK1-Mediated Pathways

The Potential Role of Nrf2 Signaling in Leishmania Infection Outcomes

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