Inhaled Litsea glaucescens K. (Lauraceae) leaves' essential oil has anxiolytic and antidepressant-like activity in mice by BDNF pathway activation.

ETHNOPHARMACOLOGICAL RELEVANCE: Litsea glaucescens K. (Lauraceae) is a small tree from the Mexican and Central American temperate forests, named as "Laurel". Its aromatic leaves are ordinarily consumed as condiments, but also are important in Mexican Traditional Medicine, and among the most important non wood forest products in this area. The leaves are currently used in a decoction for the relief of sadness by the Mazahua ethnic group. Interestingly, "Laurel" has a long history. It was named as "Ehecapahtli" (wind medicine) in pre-Columbian times and applied to heal maladies correlated to the Central Nervous System, among them depression, according to botanical texts written in the American Continent almost five centuries ago. AIM OF THE STUDY: Depression is the first cause of incapacity in the world, and society demands alternative treatments, including aromatherapy. We have previously demonstrated the antidepressant-like activity of L. glaucescens leaves' essential oil (LEO), as well as their monoterpenes linalool, and beta-pinene by intraperitoneal route in a mice behavioral model. Here we now examined if LEO and linalool exhibit this property and anxiolytic activity when administered to mice by inhalation. We also investigated if these effects occur by BDNF pathway activation in the brain. MATERIALS AND METHODS: The LEO was prepared by distillation with water steam and analyzed by gas chromatography-mass spectrometry (GC-MS). The monoterpenes linalool, eucalyptol and ß-pinene were identified and quantified. Antidepressant type properties were determined with the Forced Swim Test (FST) on mice previously exposed to LEO or linalool in an inhalation chamber. The spontaneous locomotor activity and the sedative effect were assessed with the Open Field Test (OFT), and the Exploratory Cylinder (EC), respectively. The anxiolytic properties were investigated with the Elevated Plus Maze Apparatus (EPM) and the Hole Board Test (HBT). All experiments were video documented. The mice were subjected to euthanasia, and the brain hippocampus and prefrontal cortex were dissected. RESULTS: The L. glaucescens essential oil (LEO) contains 31 compounds according to GC/MS, including eucalyptol, linalool and beta-pinene. The LEO has anxiolytic effect by inhalation in mice, as well as linalool, and ß-pinene, as indicated by OFT and EC tests. The LEO and imipramine have antidepressant like activity in mice as revealed by the FST; however, linalool and ketamine treatments didn't modify the time of immobility. The BDNF was increased in FST in mice treated with LEO in both areas of the brain as revealed by Western blot; but did not decrease the level of corticosterone in plasma. The OFT indicated that LEO and imipramine didn't reduce the spontaneous motor activity, while linalool and ketamine caused a significant decrease. CONCLUSION: Here we report by the first time that L. glaucescens leaves essential oil has anxiolytic effect by inhalation in mice, as well as linalool, and ß-pinene. This oil also maintains its antidepressant-like activity by this administration way, similarly to the previously determined intraperitoneally. Since inhalation is a common administration route for humans, our results suggest L. glaucescens essential oil deserve future investigation due to its potential application in aromatherapy.

Decoding signaling pathways involved in prolactin-induced neuroprotection: A review.

It has been well recognized that prolactin (PRL), a pleiotropic hormone, has many functions in the brain, such as maternal behavior, neurogenesis, and neuronal plasticity, among others. Recently, it has been reported to have a significant role in neuroprotection against excitotoxicity. Glutamate excitotoxicity is a common alteration in many neurological and neurodegenerative diseases, leading to neuronal death. In this sense, several efforts have been made to decrease the progression of these pathologies. Despite various reports of PRL's neuroprotective effect against excitotoxicity, the signaling pathways that underlie this mechanism remain unclear. This review aims to describe the most recent and relevant studies on the molecular signaling pathways, particularly, PI3K/AKT, NF-κB, and JAK2/STAT5, which are currently under investigation and might be implicated in the molecular mechanisms that explain the PRL effects against excitotoxicity and neuroprotection. Remarkable neuroprotective effects of PRL might be useful in the treatment of some neurological diseases.

Promising biomarkers of human aging: In search of a multi-omics panel to understand the aging process from a multidimensional perspective.

The aging process has been linked to the occurrence of chronic diseases and functional impairments, including cancer, sarcopenia, frailty, metabolic, cardiovascular, and neurodegenerative diseases. Nonetheless, aging is highly variable and heterogeneous and represents a challenge for its characterization. In this sense, intrinsic capacity (IC) stands as a novel perspective by the World Health Organization, which integrates the individual wellbeing, environment, and risk factors to understand aging. However, there is a lack of quantitative and qualitative attributes to define it objectively. Therefore, in this review we attempt to summarize the most relevant and promising biomarkers described in clinical studies at date over different molecular levels, including epigenomics, transcriptomics, proteomics, metabolomics, and the microbiome. To aid gerontologists, geriatricians, and biomedical researchers to understand the aging process through the IC. Aging biomarkers reflect the physiological state of individuals and the underlying mechanisms related to homeostatic changes throughout an individual lifespan; they demonstrated that aging could be measured independently of time (that may explain its heterogeneity) and to be helpful to predict age-related syndromes and mortality. In summary, we highlight the areas of opportunity and gaps of knowledge that must be addressed to fully integrate biomedical findings into clinically useful tools and interventions.

Prolactin prevents mitochondrial dysfunction induced by glutamate excitotoxicity in hippocampal neurons.

Prolactin (PRL) is a pleiotropic hormone secreted by several cells and tissues in the body, such as mammary glands, T-lymphocytes, hypothalamus, among others. This hormone possess neuroprotective properties against glutamate-excitotoxicity through the activation of NF-kB, suggesting it could exert an antioxidant action. However, the role of PRL on the antioxidant defense during glutamate-induced excitotoxicity is not clear to date. Therefore, in the present study, we have evaluated the effect of PRL on SOD activity and protein content of both of its isoforms (Mn2+-SOD and Cu2+/Zn2+-SOD), as well as, its action on mitochondrial activity in primary culture of hippocampal neurons of rats. Additionally, we have evaluated the possible antioxidant effect of PRL through the determination of lipid peroxidation products (LPO), measured as malondialdehyde (MDA). Results show that PRL enhances the activity and the protein content of Mn2+-SOD and Cu2+/Zn2+-SOD in neurons exposed to glutamate-induced excitotoxicity. Moreover, our results demonstrate that PRL prevents mitochondrial dysfunction induced by glutamate and significantly decreases the levels of LPO products. To our knowledge, this is the first time that a potential antioxidant effect of PRL has been described in hippocampal neurons exposed to glutamate excitotoxicity, opening questions of its potentiality for therapeutics.

The RNA world of human ageing.

Ageing is one of the most complex processes in nature; how could we prevent the associated biological changes and chronic diseases that string along with this process, is a challenge in healthcare around the world. Recent advances in next-generation sequencing have reached a stage where it is possible to know from a specific tissue the most abundant transcripts, alternative splicing process and, non-coding RNA molecules (microRNA's, long non-coding RNA's, and circular RNAs). Moreover, our knowledge of several biological processes related to ageing such as senescence and autophagy have dramatically increased in the last years. In the present review, we attempt to summarise the latest scientific advances from the most critical studies performed in human clinical samples, specific to the RNA studies about ageing. Overall, human transcriptomics research indicates that although there are common alterations of the regular expression patterns of the energetic and oxidative metabolism, extracellular matrix regulation and inflammation pathways, ageing seems to be gender and tissue-specific in general. Additionally, there is an age-related implication in several numbers of impaired events on the normal alternative splicing process. On the other hand, there is a direct relation of several non-coding RNA molecules with age-related changes which indicates its possible use as biomarkers for diagnostics and therapeutically purposes. Together, these findings highlight the importance to continue focusing research on RNA studies to improve our knowledge in the pathophysiology of age-related diseases.

Toxicogenomic analysis of pharmacological active coumarins isolated from Calophyllum brasiliense.

Calophyllum brasiliense (Calophyllaceae) is a tropical rain forest tree, mainly distributed in South and Central America. It is an important source of bioactive natural products like, for instance soulatrolide, and mammea type coumarins. Soulatrolide is a tetracyclic dipyranocoumarins and a potent inhibitor of HIV-1 reverse transcriptase and Mycobacterium tuberculosis. Mammea A/BA and A/BB coumarins, pure or as a mixture, are highly active against several leukemia cell lines, Trypanosoma cruzi and Leishmania amazonensis. In the present work, a toxicogenomic analysis of Soulatrolide and Mammea A/BA + A/BB (3:1) mixture was performed in order to validate the toxicological potential of this type of compounds. Soulatrolide or mixture of mammea A/BA + A/BB (3:1) was administered orally to male mice (CD-1) at dose of 100 mg/kg/daily, for 1 week. After this time, mice were sacrificed, and RNA extracted from the liver of treated animals. Transcriptomic analysis was performed using Affymetrix Mouse Gene 1.0 ST Array. Robust microarray analysis (RMA) and two way ANOVA test revealed for mammea mixture treatment 46 genes upregulated and 72 downregulated genes; meanwhile, for soulatrolide 665 were upregulated and 1077 downregulated genes. Enrichment analysis for such genes revealed that in both type of treatments genetic expression were mainly involved in drug metabolism. Overall results indicate a safety profile. The microarray data complies with MIAME guidelines and are deposited in GEO under accession number GSE72755.