Withaphysalin Derivatives from Iochroma arborescens Induce Antiproliferative and Antimigratory Activities in vitro.

Withanolides are steroidal lactones commonly found in plants of the Solanaceae family that have significant medicinal value. In this study, three withanolides extracted from Iochroma arborescens leaves were isolated and characterized. These included withaphysalin F (3: ) and two newly identified epimeric compounds: 18R- and 18S-O-methyl-withaphysalin F (1: and 2: ). Their structures were elucidated by NMR, IR, MS, CD, and X-ray diffraction analysis, and their potential against cell proliferation and migration was investigated. The cytotoxic assay revealed activity against different tumor and non-tumor cell lines. (18S)-O-methyl-withaphysalin F (2: ) presented cell death effects after at least 6 hours of exposure. MDA-MB-231 cells were exposed to 0.06 and 0.6 µM of (18S)-O-methyl-withaphysalin F (2: ), and reductions in cell adhesion, migration, and clonogenicity were observed. Morphological analysis revealed negative regulation in filopodia, salience, and roughness, as well as alterations in cellular microarchitecture. These results provide clues as to the effects of (18S)-O-methyl-withaphysalin F (2: ), allowing new molecular modifications to improve potency and selectivity and increase our antineoplastic arsenal.

Anxiolytic and Anticonvulsant Effects of Fisetin Isolated from Bauhinia pentandra on Adult Zebrafish (Danio rerio).

Anxiety and epilepsy are common worldwide and represent a primary global health concern. Fisetin, a flavonoid isolated from Bauhinia pentandra, has a wide range of biological activities may be a promising alternative to combat diseases related to the central nervous system (CNS). The present study aimed to investigate the anxiolytic and anticonvulsant effects of fisetin on adult zebrafish. Furthermore, molecular docking simulations were performed to improve the results. Fisetin did not present toxicity and caused anxiolytic behavior and delayed seizures in animals. This effect may occur through serotonin neurotransmission at 5-HT3A and/or 5-HT3B receptors. Molecular docking simulations showed that fisetin interacts with the orthosteric site of the 5-HT3A receptor with strong H-bond interactions with the Trp156 residue, with a strong contribution from the catechol ring, a behavior similar to that of the antagonist co-crystallized inhibitor granisetron (CWB). Fisetin may be a promising alternative to combat diseases related to the central nervous system. Keywords anxiety • Bauhinia pentandra • Danio rerio • epilepsy • fisetin.

Withanicandrin Isolated from Datura Ferox Promotes Antinociception by Modulating the Asics and TRPS Channels and Anti-Inflammation in Adult Zebrafish.

This is the first study to analyze the anti-inflammatory and antinociceptive effect of withanicandrin, isolated from Datura Ferox leaves, and the possible mechanism of action involved in adult zebrafish (ZFa). To this end, the animals were treated intraperitoneally (i. p.) with withanicandrin (4; 20 and 40 mg/kg; 20 µL) and subjected to locomotor activity and acute toxicity. Nociception tests were also carried out with chemical agents, in addition to tests to evaluate inflammatory processes induced by κ-Carrageenan 1.5 % and a Molecular Docking study. As a result, withanicandrin reduced nociceptive behavior by capsaicin at a dose of 40 mg/kg and by acid saline at doses of 4 and 40 mg/kg, through neuromodulation of TRPV1 channels and ASICs, identified through blocking the antinociceptive effect of withanicandrin by the antagonists capsazepine and naloxone. Furthermore, withanicandrin caused an anti-inflammatory effect through the reduction of abdominal edema, absence of leukocyte infiltrate in the liver tissue and reduction of ROS in thel liver tissue and presented better affinity energy compared to control morphine (TRPV1) and ibuprofen (COX-1 and COX-2).

Tyramine exerts hypolipidemic and anti-obesity effects in vivo

Abstract Obesity and dyslipidemia are conditions often associated with cardiovascular risk, inflammation, oxidative stress, and death. Thus, a new approach has been highlighted to promote research and development of pharmacological tools derived from natural sources. Among the most widely studied groups of substances, polyphenols such as tyramine stand out. This study investigated hypolipidemic and anti-obesity properties of tyramine. Oral toxicity evaluation, models of dyslipidemia and obesity were used. To induce dyslipidemia, Poloxamer-407 (P-407) was administered intraperitoneally. In the hypercholesterolemic and obesity model, specific diet and oral tyramine were provided. After 24h of P-407 administration, tyramine 2 mg/kg (T2) decreased triglycerides (TG) (2057.0 ± 158.5 mg/dL vs. 2838 ± 168.3 mg/dL). After 48h, TG were decreased by T2 (453.0 ± 35.47 vs. 760.2 ± 41.86 mg/dL) and 4 mg/kg (T4) (605.8 ± 26.61 760.2 ± 41.86 mg/dL). T2 reduced total cholesterol (TC) after 24h (309.0 ± 11.17 mg/dL vs. 399.7 ± 15.7 mg/dL); After 48h, 1 mg/kg (T1) (220.5 ± 12.78 mg/dL), T2 (205.8 ± 7.1 mg/dL) and T4 (216.8 ± 12.79 mg/dL), compared to P-407 (275.5 ± 12.1 mg/dL). The treatment decreased thiobarbituric acid reactive substances and nitrite in liver, increased superoxide dismutase, reduced the diet-induced dyslipidemia, decreasing TC around 15%. Tyramine reduced body mass, glucose, and TC after hypercaloric feed. Treatment with 5 mg/L (0.46 ± 0.04 ng/dL) and 10 mg/L (0.44 ± 0.02 ng/dL) reduced plasma insulin (1.18 ± 0.23 ng/dL). Tyramine increased adiponectin at 5 mg/L (1.02 ± 0.02 vs. 0.83 ± 0.02 ng/mL) and 10mg/L (0.96 ± 0.04 ng/mL). In conclusion, tyramine has low toxicity in rodents, has antioxidant effect, reduces plasma triglycerides and cholesterol levels. However, further studies should be conducted in rodents and non-rodents to better understand the pharmacodynamic and pharmacokinetic properties of tyramine

Reports on in vivo and in vitro contribution of medicinal plants to improve the female reproductive function / Relatos sobre a contribuição in vivo e in vitro de plantas medicinais na melhora da função reprodutiva feminina

Medicinal plants are known as a prolific source of secondary metabolites which have important function both in vivo and in vitro during the ovarian folliculogenesis and steroidogenesis in many animal species. Some secondary metabolites can act as antioxidants generally through their ability to scavenge reactive oxygen species (ROS) or can regulate ovarian hormonal production. In general, these properties are responsible for the medicinal functions to treat woman infertility disorder. Some plants are constituted of biological actives substances which have been used to treat reproductive dysfunction. However, until recently, little was known about the implication of plants and/or their secondary metabolites on in vitro folliculogenesis and steroidogenesis. With the development of the technology, there is an increase implication of those substances in assisted reproductive technology (ART). The present review highlights some medicinal plants used in the treatment of woman disorders related to infertility. In addition, it provides an in vivo and in vitro overview of herbs and their active compounds with claims for improvement of ovarian activity thus showing their implication in female reproductive health care.(AU)

Sabe-se que as plantas medicinais são uma fonte abundante de metabólitos secundários que têm função importante tanto in vivo quanto in vitro durante a foliculogênese e a esteroidogênese ovarianas em muitas espécies animais. Alguns metabólitos secundários podem atuar como antioxidantes, geralmente através de sua capacidade de eliminar espécies reativas de oxigênio (ROS) ou podem regular a produção hormonal ovariana. Em geral, essas propriedades são responsáveis pelas funções medicinais usadas para tratar distúrbios da infertilidade feminina. Algumas plantas contêm substâncias biológicas ativas que têm sido utilizadas para tratar a disfunção reprodutiva. No entanto, até recentemente, pouco se sabia sobre o efeito das plantas e/ou seus metabólitos secundários na foliculogênese e na esteroidogênese in vitro. Com o desenvolvimento da tecnologia, há uma implicação crescente dessas substâncias na tecnologia de reprodução assistida (TRA). A presente revisão destaca algumas plantas medicinais utilizadas no tratamento de distúrbios femininos relacionados à infertilidade. Além disso, fornece uma visão in vivo e in vitro de ervas e seus compostos ativos com alegações de melhora da atividade ovariana, mostrando assim seu envolvimento nos cuidados de saúde reprodutiva feminina.(AU)