Ylang-ylang (Cananga odorata (Lam.) Hook. f. & Thomson) essential oil reduced neuropathic-pain and associated anxiety symptoms in mice

Ethnopharmacological relevance: Ylang-ylang essential oil (YEO), obtained from the flowers of the tropical tree Cananga odorata (Lam.) Hook. f. & Thomson (family Annonaceae), has been largely used in the traditional medicine with many uses, including anxiety and altered neuronal states. Neuropathic pain is a chronic pain condition with a high incidence of comorbidities, such as anxiety, depression, and other mood disorders, that drastically affect the patient''s quality of life. The currently available drugs used for the management of neuropathic pain are inadequate due to poor efficacy and tolerability, highlighting the medicinal need of a better pharmacotherapy. Several clinical studies have reported that massage or inhalation with selected essentials oils reduces symptoms associated to pain and anxiety. Aim of the study: The aim of this study was to investigate the analgesic properties of YEO and its efficacy in reducing neuropathy-associated mood alterations. Materials and methods: The analgesic properties were tested in the spared nerve injury (SNI) model using male mice. Anxiolytic, antidepressant, and locomotor properties were also evaluated using behavioural tests. Finally, the YEO mechanism of action was investigated in the spinal cord and hippocampus of neuropathic mice. Results: Oral administration of YEO (30 mg/kg) reduced SNI-induced neuropathic pain and ameliorates pain-related anxiety symptoms that appeared 28 days after surgery. YEO reduced the expression of MAPKs, NOS2, p-p65, markers of neuroinflammation, and promoted normalizing effect on neurotrophin levels (BDNF). Conclusions: YEO induced neuropathic pain relief and ameliorated pain-associated anxiety, representing an interesting candidate for the management of neuropathic pain conditions and pain-related comorbidities. © 2022 The Author

Attenuation of anxiety-like behavior by helichrysum stoechas (L.) moench methanolic extract through up-regulation of erk signaling pathways in noradrenergic neurons

The long-term use of anxiolytic and antidepressant drugs can cause a plethora of side effects and the use of complementary and alternative medicine, which is generally considered safer than conventional medicine, is consistently increasing. Helichrysum stoechas (L.) Moench methanolic extract (HSE) has shown MAO-A inhibitory properties in previous studies. With the aim of obtaining innovative and safer therapies for mood disorders, this study investigated the potential activity of HSE in the management of anxiety-and depression-related symptoms. HSE showed dose-dependent (30–100 mg/kg p.o.) anxiolytic-like activity in the light dark box and marble burying tests, without any antidepressant-like activity, as shown by the results of the tail suspension test. Additionally, HSE did not have any effect on the modulation of pain, which highlights its selectivity in the control of anxiety-related behavior. At active doses, HSE did not produce any sedative effect or result in impaired motor coordination and memory functions. Western blotting experiments showed the ability of HSE to counteract the reduction in the phosphorylation of ERK44/42, to restore brain-derived neurotrophic factor (BDNF) expression and to return cyclic AMP response element binding (CREB) levels to basal levels in noradrenergic hippocampal neurons of mice exposed to an anxiety-related environment, which indicates a protective role against anxiety behavior. These results suggest that oral administration of HSE might represent an interesting opportunity for the management of anxiety disorders

Targeting the rna-binding protein hur as potential thera-peutic approach for neurological disorders: Focus on amyo-trophic lateral sclerosis (als), spinal muscle atrophy (sma) and multiple sclerosis

The importance of precise co- and post-transcriptional processing of RNA in the regulation of gene expression has become increasingly clear. RNA-binding proteins (RBPs) are a class of proteins that bind single- or double-chain RNA, with different affinities and selectivity, thus regulating the various functions of RNA and the fate of the cells themselves. ELAV (embryonic lethal/abnormal visual system)/Hu proteins represent an important family of RBPs and play a key role in the fate of newly transcribed mRNA. ELAV proteins bind AU-rich element (ARE)-containing transcripts, which are usually present on the mRNA of proteins such as cytokines, growth factors, and other proteins involved in neuronal differentiation and maintenance. In this review, we focused on a member of ELAV/Hu proteins, HuR, and its role in the development of neurodegenerative disorders, with a particular focus on demyelinating diseases

A fixed combination of probiotics and herbal extracts attenuates intestinal barrier dysfunction from inflammatory stress in an in vitro model using Caco-2 cells.

Background: Inflammatory Bowel Diseases (IBD), are considered a growing global disease, with about ten million people being affected worldwide. Maintenance of intestinal barrier integrity is crucial for preventing IBD onset and exacerbations. Some recent patents regarding oily formulations containing probiotics (WO2010122107A1 and WO2010103374A9) and the use of probiotics for gastrointestinal complaints (US20110110905A1 and US9057112B2) exist, or are pending application. Objective: In this work, we studied the effect of a fixed combination of registered Lactobacillus reuteri and Lactobacillus acidophilus strains and herbal extracts in an in vitro inflammation experimental model. Methods: Caco-2 cell monolayer was exposed to INF-\u3b3+TNF-\u3b1 or to LPS; Trans Epithelial Electrical Resistance (TEER) and paracellular permeability were investigated. ZO-1 and occludin Tight Junctions (TJs) were also investigated by mean of immunofluorescence. Results: Pre-treatment with the fixed combination of probiotics and herbal extracts prevented the inflammation-induced TEER decrease, paracellular permeability increase and TJs translocation. Conclusions: In summary, the fixed combination of probiotics and herbal extracts investigated in this research was found to be an interesting candidate for targeting the re-establishment of intestinal barrier function in IBD conditions

A Novel Perilla frutescens (L.) Britton Cell-Derived Phytocomplex Regulates Keratinocytes Inflammatory Cascade and Barrier Function and Preserves Vaginal Mucosal Integrity In Vivo

: In the last years, the medicinal plant Perilla frutescens (L.) Britton has gained scientific interest because leaf extracts, due to the presence of rosmarinic acid and other polyphenols, have shown anti-allergic and skin protective potential in pre-clinical studies. Nevertheless, the lack of standardized extracts has limited clinical applications to date. In this work, for the first time, a standardized phytocomplex of P. frutescens, enriched in rosmarinic acid and total polyphenols, was produced through innovative in vitro cell culture biotechnology and tested. The activity of perilla was evaluated in an in vitro inflammatory model of human keratinocytes (HaCaT) by monitoring tight junctions, filaggrin, and loricrin protein levels, the release of pro-inflammatory cytokines and JNK MAPK signaling. In a practical health care application, the perilla biotechnological phytocomplex was tested in a multilayer model of vaginal mucosa, and then, in a preliminary clinical observation to explore its capacity to preserve vaginal mucosal integrity in women in peri-menopause. In keratinocytes cells, perilla phytocomplex demonstrated to exert a marked activity in epidermis barrier maintenance and anti-inflammatory effects, preserving tight junction expression and downregulating cytokines release through targeting JNK activation. Furthermore, perilla showed positive effects in retaining vaginal mucosal integrity in the reconstructed vaginal mucosa model and in vivo tests. Overall, our data suggest that the biotechnological P. frutescens phytocomplex could represent an innovative ingredient for dermatological applications

Cannabidiol-enriched Cannabis sativa L. extract modulates inflammatory-induced human peripheral mononuclear cells response

Recent studies propose non-psychotropic Cannabis sativa L. as a candidate drug having a role in the pathogenic mechanisms involved in inflammation [1]. In order to evaluate the biological effect of a chemically standardized extract of C. sativa var. carmagnola dried female inflorescences (CSE) and its main constituents, the purpose of this study was to investigate the modulation of cannabinoid receptors (CBr) and pro-inflammatory cytokines in an acute inflammatory stress in vitro model. CSE was chemically characterized by HPLC-DAD and GC. The CSE biological effect was investigated on human peripheral blood mononuclear cells (PBMC) firstly exposed to the endotoxin LPS (2, 6, 24 hours) in order to evaluate CBr and cytokines regulation. Then, cells were pre-treated with CSE and its main components at the concentration of 1 μg/ml, followed by a 2 hours stimulation with the endotoxin LPS. CSE was found to contain cannabidiol (CBD) >20%, THC <0.6% and β-caryophyllene as principal sesquiterpene; flavonoids were found only <0.1%. Short term exposure to LPS significantly downregulated CB1r and CB2r gene expression and induced IL-1β, IL-6 and TNF-α release. CBr transcription resulted attenuat by pre-treatment with CSE, and more with CBD. Moreover, the LPS-induced release of the pro-inflammatory cytokine IL-6 was attenuated by CSE and CBD treatment. C. sativa extract and its main constituent CBD were able to regulate the LPS-induced inflammatory PBMC response through the modulation of CBr expression. These results contribute to support the role of the non-psychotropic cannabis compounds in the management of the inflammatory mechanisms