α-Phellandrene exhibits antinociceptive and tumor-reducing effects in a mouse model of oncologic pain

Pinheiro-Neto, Flaviano Ribeiro; Lopes, Everton Moraes; Timah, Boris; Gomes, Laércio da Silva; Dias, Willian Amorim; Filho, Antonio Carlos dos Reis; Leal, Bianca de Sousa; Rodrigues, Débora Caroline do Nascimento; Silva, Jurandy do Nascimento; Dittz, Dalton; Ferreira, Paulo Michel Pinheiro; Almeida, Fernanda Campos Sousa de

doi:10.1016/j.taap.2021.115497

Cited by 18 publications

(9 citation statements)

References 66 publications

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“…D-Limonene, constituting 19.823% of the mixture, exhibited gastrointestinal protective and antimicrobial effects [34] . Additionally, Pinene and Phellandrene were detected, the former noted for its antioxidant and antiviral properties [35] , and the latter for its analgesic activity [36] . Notably, the types and contents of the primary chemical components in this study were similar to previous research, although minor constituents showed considerable variation [37] , [38] .…”

Section: Resultsmentioning

confidence: 99%

Preparation of protein-stabilized Litsea cubeba essential oil nano-emulsion by ultrasonication: Bioactivity, stability, in vitro digestion, and safety evaluation

Peng,

Huang,

Liang

et al. 2024

Ultrasonics Sonochemistry

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Section: Resultsmentioning

confidence: 99%

Preparation of protein-stabilized Litsea cubeba essential oil nano-emulsion by ultrasonication: Bioactivity, stability, in vitro digestion, and safety evaluation

Peng,

Huang,

Liang

et al. 2024

Ultrasonics Sonochemistry

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“…They also provided important possible molecular mechanisms of how alpha-phellandrene affected gene expression and the possible signaling pathways in this line of tumor cells [ 60 , 61 ]. Finally, a recent study [ 62 ] demonstrated that alpha-phellandrene is not only antitumoral, but also exhibits antinociceptive effects. This molecule showed in vitro cytotoxic action on melanoma B-16/F-10 and Sarcoma 180, inhibition of in vivo tumor growth and decreased direct and indirect mechanical nociception in Sarcoma 180-bearing mice with early and advanced tumors, under acute or subacute conditions of treatment, especially at doses of 25.0 and 50.0 mg/kg.…”

Section: Resultsmentioning

confidence: 99%

Alpha-Phellandrene and Alpha-Phellandrene-Rich Essential Oils: A Systematic Review of Biological Activities, Pharmaceutical and Food Applications

Radice

Durofil

Buzzi

et al. 2022

Life

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Alpha-phellandrene is a very common cyclic monoterpene found in several EOs, which shows extensive biological activities. Therefore, the main focus of the present systematic review was to provide a comprehensive and critical analysis of the state of the art regarding its biological activities and pharmaceutical and food applications. In addition, the study identified essential oils rich in alpha-phellandrene and summarized their main biological activities as a preliminary screening to encourage subsequent studies on their single components. With this review, we selected and critically analyzed 99 papers, using the following bibliographic databases: PubMed, SciELO, Wiley and WOS, on 8 July, 2022. Data were independently extracted by four authors of this work, selecting those studies which reported the keyword “alpha-phellandrene” in the title and/or the abstract, and avoiding those in which there was not a clear correlation between the molecule and its biological activities and/or a specific concentration from its source. Duplication data were removed in the final article. Many essential oils have significant amounts of alpha-phellandrene, and the species Anethum graveolens and Foeniculum vulgare are frequently cited. Some studies on the above-mentioned species show high alpha-phellandrene amounts up to 82.1%. There were 12 studies on alpha-phellandrene as a pure molecule showed promising biological functions, including antitumoral, antinociceptive, larvicidal and insecticidal activities. There were 87 research works on EOs rich in alpha-phellandrene, which were summarized with a focus on additional data concerning potential biological activities. We believe this data is a useful starting point to start new research on the pure molecule, and, in particular, to distinguish between the synergistic effects of the different components of the OEs and those due to alpha-phellandrene itself. Toxicological data are still lacking, requiring further investigation on the threshold values to distinguish the boundary between beneficial and toxic effects, i.e., mutagenic, carcinogenic and allergenic. All these findings offer inspiration for potential applications of alpha-phellandrene as a new biopesticide, antimicrobial and antitumoral agent. In particular, we believe our work is of interest as a starting point for further studies on the food application of alpha-phellandrene.

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“…Antioxidant and Investigations in vitro and in vivo have already pointed out the anti-inflammatory action of different preparations of C. sylvestris (alcoholic/aqueous extracts or essential oils), and they have demonstrated inhibition of edema activity, leukocyte migration, myeloperoxidase activity, nitrogen-derived free radical compounds [22][23][24]26,27,[54][55][56], phospholipase A 2 , and tissue proteases [81]. Certainly, the involvement of inflammatory mediators, such as prostaglandins, leukotrienes, cytokines, and biogenic amines, activates and sensibilizes C fiber-related polymodal nociceptors, which play an important role in cutaneous hyperalgesia triggered by mechanical and/or thermal stimuli [15]. This may explain, at least in part, how inhibition of production and/or action of inflammatory mediators are related to the antinociceptive mechanism of FC.…”

Section: Analgesic In Vivo Effectsmentioning

confidence: 99%

“…In this context, natural products have been used as a source of novel anticancer [12][13][14] and antinociceptive [15] agents. Among them, Casearia (Salicaceae) comprises about 180 species distributed in sub-tropical and tropical regions [16] and has promising anticancer effects [17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Promising Effects of Casearins in Tumor-Bearing Mice and Antinociceptive Action against Oncologic Pain: Molecular Docking and In Vivo Findings

Silva,

Beserra Filho,

Acha

et al. 2024

Pharmaceuticals

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Safer analgesic drugs remain a hard challenge because of cardiovascular and/or gastrointestinal toxicity, mainly. So, this study evaluated in vivo the antiproliferative actions of a fraction with casearins (FC) from Casearia sylvestris leaves against human colorectal carcinomas and antihyperalgesic effects on inflammatory- or opiate-based pain relief and oncologic pain in Sarcoma 180 (S180)-bearing mice. Moreover, docking investigations evaluated the binding among Casearin X and NMDA(N-methyl-D-aspartate)-type glutamate receptors. HCT-116 colorectal carcinoma-xenografted mice were treated with FC for 15 days. Antinociceptive assays included chemically induced algesia and investigated mechanisms by pharmacological blockade. Intraplantar region S180-bearing animals received a single dose of FC and were examined for mechanical allodynia and behavior alterations. AutoDock Vina determined molecular interactions among Cas X and NMDA receptor subunits. FC reduced tumor growth at i.p. (5 and 10 mg/kg) and oral (25 mg/kg/day) doses (31.12–39.27%). FC reduced abdominal pain, as confirmed by formalin and glutamate protocols, whose antinociception activity was blocked by naloxone and L-NAME (neurogenic phase) and naloxone, atropine, and flumazenil (inflammatory phase). Meanwhile, glibenclamide potentiated the FC analgesic effects. FC increased the paw withdrawal threshold without producing changes in exploratory parameters or motor coordination. Cas X generated a more stable complex with active sites of the NMDA receptor GluN2B subunits. FC is a promising antitumor agent against colorectal carcinomas, has peripheral analgesic effects by desensitizing secondary afferent neurons, and inhibits glutamate release from presynaptic neurons and/or their action on cognate receptors. These findings emphasize the use of clerodane diterpenes against cancer-related pain conditions.

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α-Phellandrene exhibits antinociceptive and tumor-reducing effects in a mouse model of oncologic pain

Cited by 18 publications

References 66 publications

Preparation of protein-stabilized Litsea cubeba essential oil nano-emulsion by ultrasonication: Bioactivity, stability, in vitro digestion, and safety evaluation

Preparation of protein-stabilized Litsea cubeba essential oil nano-emulsion by ultrasonication: Bioactivity, stability, in vitro digestion, and safety evaluation

Alpha-Phellandrene and Alpha-Phellandrene-Rich Essential Oils: A Systematic Review of Biological Activities, Pharmaceutical and Food Applications

Promising Effects of Casearins in Tumor-Bearing Mice and Antinociceptive Action against Oncologic Pain: Molecular Docking and In Vivo Findings

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