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Chemotherapeutic resistance can limit breast cancer outcomes; therefore, the exploration of novel therapeutic options is warranted. Isolated compounds found in cannabis have previously been shown to exhibit anti-cancer effects, but little is known about their effects in resistant breast cancer. Our study aimed to evaluate the effects of terpenes found in cannabis in in vitro chemotherapy-resistant model of breast cancer. We aimed to identify whether five terpenes found in cannabis produced anti-cancer effects, and whether their effects were improved upon co-treatment with cannabinoids and flavonoids also found in cannabis. Nerolidol and [beta]-caryophyllene produced the greatest cytotoxic effects, activated the apoptotic cascade, and reduced cellular invasion. Combinations with the flavonoid kaempferol potentiated the cytotoxic effects of ocimene, terpinolene, and [beta]-myrcene. Combinations of nerolidol and [DELTA]9-tetrahydrocannabinol or cannabidiol produced variable responses ranging from antagonism and additivity to synergy, depending on concentrations used. Our results indicate that cannabis terpenes, alone or combined with cannabinoids and flavonoids, produced anti-cancer effects in chemotherapy-resistant breast cancer cell lines. This study is a first step in the identification of compounds that could have therapeutic potential in the treatment of resistant breast cancer. Key words: breast cancer, terpenes, chemotherapeutic resistance, cannabis, apoptosis, synergy La resistance a la chimiotherapie peut constituer une entrave au traitement du cancer du sein; par consequent, l'exploration de nouvelles options therapeutiques est necessaire. On a montre precedemment que des composes isoles du cannabis peuvent afficher des effets anticancereux, mais on connait peu leurs effets dans le cancer du sein resistant. Notre etude vise a evaluer les effets de terpenes retrouves dans le cannabis dans un modele in vitro de cancer du sein resistant a la chimiotherapie. Nous avons cherche a etablir si cinq terpenes retrouves dans le cannabis entrainaient des effets anticancereux, et si leurs effets s'amelioraient avec un traitement concomitant a l'aide de cannabinoides et de flavonoides, qui se retrouvent aussi dans le cannabis. Le nerolidol et le [beta]-caryophyllene entrainaient les effets cytotoxiques les plus importants, l'activation de la cascade apoptotique et une diminution du caractere invasif des cellules. Les associations avec le kaempferol, un flavonoide, potentialisaient les effets cytotoxiques de l'ocimene, du terpinolene et du [beta]-myrcene. Les associations avec le nerolidol et le [DELTA]9-tetrahydrocannabinol ou le cannabidiol entrainaient des effets variables allant de l'antagonisme et de l'addition a la synergie, tout dependant des concentrations utilisees. Nos resultats montrent que les terpenes du cannabis en monotherapie ou en association avec des cannabinoides et des flavonoides, entrainaient des effets anticancereux dans des lignees cellulaires de cancer du sein resistant a la chimiotherapie. Cette etude constitue une premiere etape dans l'identification de composes qui pourraient avoir des effets eventuels dans le traitement du cancer du sein resistant. [Traduit par la Redaction] Mots-cles : cancer du sein, terpenes, resistance a la chimiotherapie, cannabis, apoptose, synergie, Introduction Breast cancer is the most commonly diagnosed cancer in females in the world accounting for 24.5% of all cancer diagnoses, and it is the leading cause of cancer mortality [...]

[beta]-elemene (Bel) is a sesquiterpene compound that has shown potential in the antinociceptive treatment. This study focused on the function of Bel in neuropathic pain relief in mice. A murine model with spared nerve injury (SNI) was established and treated with Bel. The paw withdrawal thresholds in response to mechanical and thermal stimulations were examined using von Frey filaments. The L4-L6 spinal dorsal horn tissue samples were collected for histological examination. Bel treatment reduced the sensitivities of model mice to mechanical and thermal stimulations, and it inhibited activation of microglia and the secretion of inflammatory cytokines including tumor necrosis factor-[alpha] (TNF-[alpha]), interleukin-1[beta] (IL-1[beta]), and IL-6 in tissues. Bel treatment reduced the expression of nociceptor excitatory N-methyl-D-aspartate receptor (NMDAR), whereas it enhanced the expression of nociceptor inhibitory gamma-aminobutyric acid A (GABAA) receptor to relieve the nociception of mice. The C-X-C motif chemokine receptor 3 (CXCR3) is a downstream molecule mediated by Bel. Either overexpression of CXCR3 or downregulation of GABAA receptor in the tissues aggravated the neuropathic pain in SNI mice which was initially relieved by Bel. In conclusion, this study suggested that Bel might serve as a drug for nociception management by inhibiting CXCR3 and upregulating GABAA receptor. This study may offer novel insights into the field of neuropathic pain relief. Key words: [beta]-elemene, spared nerve injury, neuropathic pain relief, CXCR3, GABAA receptor. Le [beta]-elemene (Bel) est un compose sesquiterpene dont on a montre le potentiel antinociceptif. Cette etude etait centree sur le fonctionnement du Bel dans le soulagement de la douleur neuropathique chez la souris. Nous avons etabli un modele murin de nerf epargne (ou SNI pour << spared nerve injury >>) et administre du Bel. A l'aide de filaments de von Frey, nous avons examine les seuils de retrait de la patte en reaction a des stimulations mecaniques et thermiques. Nous avons preleve des echantillons tissulaires de corne dorsale de moelle epiniere en L4 a L6 en vue d'un examen histologique. L'administration de Bel permettait de faire diminuer la sensibilite des souris a des stimulations mecaniques et thermiques, ainsi que d'inhiber l'activation de la microglie et la secretion de cytokines inflammatoires dans les tissus, y compris le facteur de necrose tumorale (TNF)-[alpha] et les interleukines (IL)-1[beta] et IL-6. L'administration de Bel entrainait une diminution de l'expression des recepteurs NMDA (nocirecepteurs excitateurs), mais une augmentation de l'expression des recepteurs GABAA (nocirecepteurs inhibiteurs) pour soulager les souris de la nociception. Le CXCR3 etait une molecule en aval de la modulation par le Bel. La surexpression du CXCR3 comme la regulation a la baisse des recepteurs GABAA dans les tissus entrainaient une aggravation de la douleur neuropathique qui etait soulagee initialement par le Bel chez les souris SNI. En conclusion, cette etude laisse entendre que le Bel pourrait servir de medicament dans la prise en charge de la nociception en entrainant une inhibition de CXCR3 et une regulation a la hausse des recepteurs GABAA. Cette etude pourrait permettre d'obtenir de nouvelles connaissances dans le domaine du soulagement de la douleur neuropathique. [Traduit par la Redaction] Mots-cles : [beta]-elemene, nerf epargne, soulagement de la douleur neuropathique, CXCR3, recepteurs GABAA., Introduction Lesions or diseases involving the somatosensory nervous system may not only result in a functional impairment but also in elevated pain sensitivity and spontaneous pain (Scholz et al. 2019). [...]

The metabolic disturbance of obesity is one of the most common risk factors of atherosclerosis. Resistin, an obesity- induced adipokine, can induce the expression of cell adhesion molecules and the attachment of monocytes to endothelial cells, which play an important role in the development of atherosclerosis. Ursolic acid, a pentacyclic triterpenoid found in fruits and many herbs, exhibits an array of biological effects such as anti-inflammatory and antioxidative properties. The aim of this study was to investigate the potential underlying mechanisms of the effect of ursolic acid on resistin-induced adhesion of U937 cells to human umbilical vein endothelial cells (HUVECs). Our data indicated that ursolic acid suppressed the adhesion of U937 to HUVECs and downregulated the expression of adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1), intracellular cell adhesion molecule-1 (ICAM-1), and E-selectin, in resistin-induced HUVECs by decreasing the production of intracellular reaction oxygen species (ROS) and attenuating the nuclear translocation of NFκB. Ursolic acid appeared to inhibit resistin-induced atherosclerosis, suggesting that ursolic acid may play a protective role in obesity-induced cardiovascular diseases. Key words: ursolic acid, triterpenoid, obesity, adhesion molecule, resistin, reaction oxygen species, atherosclerosis, NFκB. Les perturbations metaboliques de l'obesite constituent un des facteurs de risque les plus frequents de l'atherosclerose. La resistine, une adipokine induite par l'obesite, peut induire l'expression de molecules d'adhesion cellulaire et l'attachement des monocytes aux cellules endotheliales, ce qui joue un role important dans le developpement de l'atherosclerose. L'acide ursolique, un triterpenoide pentacyclique trouve dans les fruits et plusieurs herbes, presente un spectre d'effets biologiques anti-inflammatoires et antioxydants. Le but de cette etude etait d'examiner les mecanismes potentiels qui sous-tendent l'effet de l'acide ursolique sur l'adhesion induite par la resistine des cellules U937 aux cellules endotheliales de cordon ombilical humaines (HUVEC). Les donnees des auteurs ont indique que l'acide ursolique supprimait l'adhesion des cellules U937 aux HUVEC et regulait a la baisse l'expression des molecules d'adhesion VCAM-1, ICAM-1 et E-selectine chez les HUVEC traitees a la resistine, en diminuant la production d'especes reactives d'oxygenes (ERO) intracellulaires et en diminuant la translocation cellulaire du NFκB. L'acide ursolique semblait inhiber l'atherosclerose induite par la resistine, suggerant qu'il pourrait jouer un role protecteur contre les maladies cardiovasculaires induites par l'obesite. [Traduit par la Redaction] Mots-cles : acide ursolique, triterpenoide, obesite, molecule d'adhesion, resistine, espece reactive d'oxygene, atherosclerose, NFκB., Introduction Obesity is associated with a number of chronic diseases, including cardiovascular diseases, diabetes mellitus, and cancer. Because the prevalence of obesity is on the rise worldwide (Flegal et al. [...]

Background: Leishmaniasis comprises several infectious diseases caused by protozoa parasites of Leishmania genus. In recent years, there has been a growing interest in the therapeutic use of natural products to treat parasitic diseases. Among them Croton cajucara Benth. (Euphorbiaceae) is a plant found in the Amazonian region with a history of safe use in folk medicine. Purpose: The purpose of this study was to investigate the effects of derodane diterpenes, trans dehydrocrotonin (DCTN), trans-crotonin (CTN) and acetylaleuritolic acid (AAA) obtained from powdered bark of C. cajucara against promastigotes, axenic and intracellular amastigotes of Leishmania amazonensis. Furthermore, the effects of DCTN and CTN on the trypanotiona reductase enzyme were also investigated. The extraction of the terpenes was carried out as previously reported (Maciel et al., 1998; 2003). Methods: The effect of the isolated compounds (DCTN, CTN and AAA) from the bark of C. cajucara was assessed in vitro against promastigotes, axenic amastigotes and intracellular amastigotes of L. amazonensis by counting of remaining parasites in a Neubauer chamber in comparison to pentamidine used as standard drug. The action of natural products on trypanothione reductase was assessed using soluble protein fraction of promastigotes. The assays were performed by incubation with HEPES, EDTA, NADPH and trypanothione disulfide to quantify the NAPH consumption by TryR. Results: The results showed very high efficacy, especially of the diterpene DCTN, against promastigotes (ICS0 = 6.30 ± 0.06 µg/ml) and axenic amastigotes ([IC.sub.50] = 19.98 ± 0.05 µg/ml) of L amazonenesis. The cytotoxic effect of the best active natural product was evaluated on mouse peritoneal infected macrophages ([IC.sub.50] = 0.47 [+ or -] 0.03 µg/ml in 24 h of culture), and the treatment revealed that DCTN never reaches toxic concentrations while reducing the infection and, most importantly, with no toxicity (>100 µg/ml with 0% of macrophage kill) when compared to pentamidine (37.5 µg/ml with 100% of macrophage kill). Furthermore, all of the natural products assayed on the trypanothione reductase enzyme inhibited the enzyme activity compared to the control. Conclusion: Clerodane diterpenes from C. cajucara showed promising in vitro antileishmanial effects against L amazonensis, specially the DCTN with no macrophage toxicity up to the assayed concentration. In addition, the action on trypanothione reductase enzyme revealed a possible mechanism of action. Keywords: Leishmania amazonensis Terpenes trans-Deydrocrotonin Croton cajucara Macrophage Antiprotozoal activity, Introduction Leishmaniasis comprises several diseases caused by protozoan parasites of the Leishmania genus, which are transmitted by sand-flies. This parasite has been endemic in 88 countries of four continents (Paloque [...]