Natural Products as Outstanding Alternatives in Diabetes Mellitus: A Patent Review.

Diabetes mellitus (DM) is a metabolic syndrome that can be considered a growing health problem in the world. High blood glucose levels are one of the most notable clinical signs. Currently, new therapeutic alternatives have been tackled from clinicians' and scientists' points of view. Natural products are considered a promising source, due to the huge diversity of metabolites with pharmaceutical applications. Therefore, this review aimed to uncover the latest advances in this field as a potential alternative to the current therapeutic strategies for the treatment of DM. This purpose is achieved after a patent review, using the Espacenet database of the European Patent Office (EPO) (2016-2022). Final screening allowed us to investigate 19 patents, their components, and several technology strategies in DM. Plants, seaweeds, fungi, and minerals were used as raw materials in the patents. Additionally, metabolites such as tannins, organic acids, polyphenols, terpenes, and flavonoids were found to be related to the potential activity in DM. Moreover, the cellular transportation of active ingredients and solid forms with special drug delivery profiles is also considered a pharmaceutical technology strategy that can improve their safety and efficacy. From this perspective, natural products can be a promissory source to obtain new drugs for DM therapy.

Antitumor effectiveness of a combined therapy with a new cucurbitacin B derivative and paclitaxel on a human lung cancer xenograft model.

Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors, with a high mortality rate due to the elevated risk of resistance. Natural cucurbitacins and their derivatives are recognized as promising antitumor compounds for several types of cancer, including NSCLC. In a recent study published by our research group, DACE (2-deoxy-2-amine-cucurbitacin E), which is a semisynthetic derivative of cucurbitacin B, showed potential in vitro synergistic antiproliferative effects combined with paclitaxel (PTX) in A549 cells. In sequence, the purpose of this study was to evaluate the in vivo antitumor efficacy of this combined therapy as well as with these drugs individually, using a human NSCLC xenograft model. Some indicators of sub chronic toxicity that could be affected by treatments were also assessed. The results obtained in vivo with the combined treatment (1mg/kg+PTX 10mg/kg) showed the most effective reduction of the relative tumor volume and the highest inhibition of tumor growth and proliferation, when compared with those of the single treatments. Furthermore, scintigraphic images, obtained before and after the treatments, showed that the most effective protocol able to reduce the residual viable tumor mass was the combined treatment. All treatment regimens were well tolerated without significant changes in body weight and no histological and functional damage to liver and kidney tissues. These results corroborate our previous in vitro synergistic effects published. Taken together, these insights are novel and highlight the therapeutic potential of DACE and PTX combination scheme for NSCLC.

Cosmetovigilancia: un estudio de alcance / Cosmetovigilance: a scoping study

Los cosméticos son productos de venta libre y de uso diario para los consumidores, quienes restan importancia a las implicaciones de salud que pueden experimentar a causa de los mismos. Es necesario monitorear la postcomercialización de estos productos, ya que en los años recientes se han visto asociados a reacciones adversas; de esta manera nace el concepto de cosmetovigilancia y la necesidad de implementar sistemas para llevarla a cabo. Esta revisión sistemática encontró un limitado número de publicaciones que informen del estado actual y de las tendencias de la cosmetovigilancia, aunque fue posible definir el concepto e identificar los países que lo han desarrollado e implementado, siendo la Unión Europea quien lidera estos aspectos, contando con la participación de distribuidores, industrias, profesionales de la salud y consumidores. La cosmetovigilancia es un campo de la vigilancia sanitaria que se encuentra aún en desarrollo y por lo tanto, es importante continuar con la indagación al respecto, hasta lograr un mecanismo de vigilancia eficiente y útil tanto para los países miembros de la Unión Europea, como para aquellos que aún se encuentran en vías de desarrollo, como Colombia.

Cosmetics are free sale products that are used daily by consumers who usually not concerned about the possible health implications by the use of these products. It is necessary to perform a post-sale monitoring for these products, since in recent years they have been associated with adverse reactions. For this reason was built the cosmetovigilance concept as well as the need to implement a system to perform this task. This systematic review found a limited number of publications about the current cosmetovigilance status and tendencies at world level. Nevertheless, it was possible to define the concept and identify the countries that have developed and implemented this system. European Union is the leader in this topic, with investigations, regulations, development and implementation of an harmonized cosmetovigilance system. These activities include the participation of distributors, manufacturing industries, health professionals and consumers. Cosmetovigilance is a sanitary vigilance area that is still under development and therefore it is important to keep on investigating about this topic until achieve an efficient and useful system, for both European Union members and developing countries such as Colombia.

Cytotoxic effects of natural and semisynthetic cucurbitacins on lung cancer cell line A549.

Cucurbitacins and their derivatives are triterpenoids that are found in various plant families, and are known for their pharmacological and biological activities, including anti-cancer effects. Lung cancer represents a major public health problem, with non-small-cell lung cancer (NSCLC) being the most frequent and aggressive type of lung cancer. The objective of this work was to evaluate four cucurbitacins (CUCs) for their cytotoxic activity, effects on apoptosis induction, cell cycle progression, anti-migratory, and anti-invasive effects on the human NSCLC cell line (A549 cells). Our findings showed that these CUCs could suppress human NSCLC cell growth in vitro through their effects on the PI3Kinase and MAPK pathways, which lead to programmed cell death induction, as well as inhibition of cell migration and cell invasion. Additionally, these effects culminate in apoptosis induction and G2/M cell cycle arrest by modulating cyclin B1 expression, and in the mitigation of strategic steps of lung cancer metastasis, including migration and invasion of A549 cells. These results suggest that two natural (DDCB and CB) and two novel semisynthetic derivatives of cucurbitacin B (ACB and DBCB) could be considered as promising compounds with antitumor potential.

Synergistic Antiproliferative Effects of a New Cucurbitacin B Derivative and Chemotherapy Drugs on Lung Cancer Cell Line A549.

Nonsmall cell lung cancer (NSCLC) represents an important cause of mortality worldwide due to its aggressiveness and growing resistance to currently available therapy. Cucurbitacins have emerged as novel potential anticancer agents showing strong antiproliferative effects and can be promising candidates for combined treatments with clinically used anticancer agents. This study investigates the synergistic antiproliferative effects of a new semisynthetic derivative of cucurbitacin B (DACE) with three chemotherapy drugs: cisplatin (CIS), irinotecan (IRI), and paclitaxel (PAC) on A549 cells. The most effective combinations were selected for studies of the mechanism of action. Using an in silico tool, DACE seems to act by a different mechanism of action when compared with that of different classes of drugs already used in clinical settings. DACE also showed potent synergic effects with drugs, and the most potent combinations induced G2/M cell cycle arrest by modulating survivin and p53 expression, disruption of F-actin cytoskeleton, and cell death by apoptosis. These treatments completely inhibited the clonogenic potential and did not reduce the proliferation of nontumoral lung cells (MRC-5). DACE also showed relevant antimigratory and anti-invasive effects, and combined treatments modulated cell migration signaling pathways evolved with metastasis progression. The effects of DACE associated with drugs was potentiated by the oxidant agent l-buthionine-sulfoximine (BSO), and attenuated by N-acetilcysteine (NAC), an antioxidant agent. The antiproliferative effects induced by combined treatments were attenuated by a pan-caspase inhibitor, indicating that the effects of these treatments are dependent on caspase activity. Our data highlight the therapeutic potential of DACE used in combination with known chemotherapy drugs and offer important insights for the development of more effective and selective therapies against lung cancer.

Chemical modification produces species-specific changes in cucurbitacin antifeedant effect.

Cucurbitacins are secondary metabolites that mediate insect plant interactions not only as allomones against generalists but also as kairomones for specialist herbivores. This study was undertaken to identify the potential of cucurbitacin derivatives as insect antifeedant agents. The antifeedant capacity against a Cucurbitaceae specialist [ Epilachna paenulata (Coleoptera: Coccinellidae)] and a polyphagous insect [ Pseudaletia adultera (Lepidoptera: Noctuidae)] was evaluated in preference tests in which the insects were given a choice between food plants either treated with the cucurbitacin derivatives or treated with the solvent. The activity was found not to be related to the basic cucurbitacin skeleton, as only 15 of the 28 tested cucurbitacin derivatives were active. Only one of the tested compounds was phagostimulant to the specialist insect (the hemissuccinate of 16-oxo-dihydrocucurbitacin B derivative), while all other active derivatives were deterrent against one of the insects (13 compounds) or both of them (3 compounds). Changes in ring A of the cucurbitacins, as well as in the side chain, modified the activity. As a general trend, when chemical modifications of the basic structure produced a change in activity, the response was opposite in both insects used as biodetectors, indicating that a selective variation in the activity may be achieved by chemical modifications of the cucurbitacin skeleton.

Synthesis and cytotoxic activity evaluation of dihydrocucurbitacin B and cucurbitacin B derivatives.

Two cucurbitacins, dihydrocucurbitacin B (1) and cucurbitacin B (2), which can be obtained in large amounts from the roots of Wilbrandia ebracteata and from the fruits of Luffa operculata, respectively, were used as starting materials for the preparation of a library of 29 semi-synthetic derivatives. The structural changes that were performed include the removal, modification or permutation of functional groups in rings A and B as well as in the side chain. All new semisynthetic compounds, as well as 1 and 2, were tested in vitro for their cytotoxic effects on non-small-cell lung cancer cells (A549 cells). Some of these compound displayed potent to moderate activity against A549 tumor cells, especially those cucurbitacin B derivatives which were modified at ring A.

Investigação das atividades alelopática e antimicrobiana de Mikania laevigata (Asteraceae) obtida de cultivos hidropônico e tradicional / Investigation of the allelopathic and antimicrobial activities of Mikania laevigata (Asteraceae) obtained in hydroponic and traditional cultivars

Os extratos etanólicos de folhas de guaco (Mikania laevigata) cultivado tradicionalmente no solo ou por hidroponia foram avaliados quanto às atividades alelopática e antimicrobiana. Para a atividade alelopática foi utilizado o ensaio de inibição da germinação de sementes de alface (Lactuca sativa), enquanto que para a atividade antimicrobiana utilizouse a técnica de difusão em disco. Observou-se um notável efeito alelopático dos extratos de ambos os cultivos, em especial do extrato etanólico do guaco tradicional, que mesmo na menor concentração testada inibiu completamente a germinação das sementes. Nenhum dos extratos etanólicos do guaco apresentou atividade antibacteriana significativa para as linhagens de Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis e Enterococcus faecium.

The ethanolic extract of "guaco" (Mikania laevigata) traditionally cultivated in the soil or in a hydroponic system were tested for allelopathic and antimicrobial activities. Allelopathic activity was evaluated by the inhibition of germination assay using lettuce seeds, and antimicrobial activity by the disc diffusion assay. A notable allelopathic effect was observed for both extracts, although a more expressive activity of traditional "guaco" was verified, since the inhibition of seeds germination was 100% even in the lower concentration. None ethanolic extract of "guaco" presented significant antimicrobial activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis and Enterococcus faecium.

Anti-inflammatory evaluation of Solidago chilensis Meyen in a murine model of pleurisy.

UNLABELLED: The aim of this study was to investigate the anti-inflammatory effects and the mechanism of action of the aqueous extracts obtained from rhizomes, leaves and inflorescences of Solidago chilensis in the mouse model of pleurisy. The extracts were prepared by infusion and were lyophilized. RESULTS: The aqueous extracts of rhizomes, leaves or inflorescences inhibited leukocytes, neutrophils and exudation (P<0.05) in the inflammation induced by carrageenan. The rhizomes aqueous extract, butanolic and aqueous residual fractions inhibited leukocytes, neutrophils, myeloperoxidase, adenosine-deaminase, and tumor necrosis factor alpha levels in the inflammation induced by carrageenan (P<0.05). The rhizome aqueous extract and butanolic fraction also inhibited exudation, nitric oxide, and interleukin-1 beta levels (P<0.05). The rhizomes aqueous extract and its two derived fractions reduced leukocytes and mononuclears in the pleurisy induced by bradykinin, histamine, or substance P (P<0.05) and neutrophils in the pleurisy induced by histamine or substance P (P<0.05). Only aqueous residual fraction inhibited neutrophils induced by bradykinin (P<0.05). CONCLUSION: Solidago chilensis aqueous extracts from leaves, inflorescences and rhizomes demonstrated an important anti-inflammatory effect, inhibiting cells in the inflammation caused by carrageenan. In addition, the rhizomes aqueous extract and its derived fractions also decreased pro-inflammatory mediators release into the site of the inflammatory process. The rhizomes aqueous extract and the butanolic fraction showed more evident anti-inflammatory actions.