Insight into the Interaction of Humulus lupulus L. Specialized Metabolites and Gastrointestinal Bitter Taste Receptors: In Vitro Study in STC-1 Cells and Molecular Docking.

Bitter taste receptors, also known as taste 2 receptors (T2R), are expressed throughout the body and are involved in regulating different physiological processes. T2R expression in the intestinal tract regulates orexigenic and anorexigenic peptide secretion, thus becoming potential a potential target for controlling food intake and the prevalence of obesity and overweight. The present study aims to investigate the implication of hop bitter compounds such as α-acids, ß-acids, and xanthohumol in the secretion of anorexigenic hormones and T2R expression in intestinal STC-1 cells. The tested bitter compounds induced the secretion of the anorexigenic hormones glucagon-like peptide 1 and cholecystokinin concurrently with a selective increase of murine Tas2r expression. Xanthohumol and α-acids selectively increase Tas2r138 and Tas2r130-Tas2r138 expression, respectively, in STC-1 cells, while ß-acids increased the expression of all bitter receptors studied, including Tas2r119, Tas2r105, Tas2r138, Tas2r120, and Tas2r130. Increased intracellular calcium levels confirmed this activity. As all investigated bitter molecules increased Tas2r138 expression, computational studies were performed on Tas2r138 and its human orthologue T2R38 for the first time. Molecular docking experiments showed that all molecules might be able to bind both bitter receptors, providing an excellent basis for applying hop bitter molecules as lead compounds to further design gastrointestinal-permeable T2R agonists.

Is a Low Dosage of Medical Cannabis Effective for Treating Pain Related to Fibromyalgia? A Pilot Study and Systematic Review.

Background and Objectives: Fibromyalgia is a multifaceted and frequently misunderstood chronic pain disease marked by widespread musculoskeletal pain and cognitive/somatic dysfunction. This trial aims to contribute to the existing knowledge on treating fibromyalgia (FM) with medical cannabis (Cannabis sativa L.) and explore a safer and more effective cannabis administration method. The goal is to provide evidence-based findings that can guide alternative treatment options for FM patients by assessing a pilot study. Materials and Methods: The trial was performed at the pain therapy unit of the San Carlo Hospital (Potenza, Italy) by administrating to 30 FM patients 100 mg/day of Bedrocan® (Bedrocan International, Veendam, The Netherlands) as a decoction. The Numerical Rating Scale (NRS) and SF-12 short-form health questionnaire were used to evaluate pain intensity and the quality of life at the beginning of the study and the 6th-month follow-up. A systematic review of all clinical studies investigating the use of cannabis to reduce FM was also undertaken to place this study in the context of the existing evidence base. Results: Pain intensity evaluated with the NRS lowered from a median of 8 [95% CI 7.66-8.54] at a baseline to a median of 4 (95% CI 3.28-4.79) after 6 months of follow-up (p-value < 0.001; t-test). Similarly, significant physical and mental state improvement, evaluated with the SF-12 questionnaire, was found in 96.67% and 82.33% of patients, respectively (95% CI 44.11-51.13 for the physical state, and 53.48-58.69 for mental state assessed after the 6th-month follow-up; p-value < 0.001; t-test). The systematic analysis of the literature identified 10 clinical trials concerning the treatment of fibromyalgia with cannabis. Conclusions: Considering results from the present pilot study and systematic review, it is possible to assume that medical cannabis may be considered an alternative therapy for FM patients who do not respond to conventional pharmacological therapy.

Withania somnifera (L.) Dunal, a Potential Source of Phytochemicals for Treating Neurodegenerative Diseases: A Systematic Review.

Withania somnifera (L.) Dunal is a medicinal plant belonging to the traditional Indian medical system, showing various therapeutic effects such as anti-cancer, anti-inflammatory, anti-microbial, anti-diabetic, and hepatoprotective activity. Of great interest is W. somnifera's potential beneficial effect against neurodegenerative diseases, since the authorized medicinal treatments can only delay disease progression and provide symptomatic relief and are not without side effects. A systematic search of PubMed and Scopus databases was performed to identify preclinical and clinical studies focusing on the applications of W. somnifera in preventing neurodegenerative diseases. Only English articles and those containing the keywords (Withania somnifera AND "neurodegenerative diseases", "neuroprotective effects", "Huntington", "Parkinson", "Alzheimer", "Amyotrophic Lateral Sclerosis", "neurological disorders") in the title or abstract were considered. Reviews, editorials, letters, meta-analyses, conference papers, short surveys, and book chapters were not considered. Selected articles were grouped by pathologies and summarized, considering the mechanism of action. The quality assessment and the risk of bias were performed using the Cochrane Handbook for Systematic Reviews of Interventions checklist. This review uses a systematic approach to summarize the results from 60 investigations to highlight the potential role of W. somnifera and its specialized metabolites in treating or preventing neurodegenerative diseases.

Harnessing Cyanobacteria's Bioactive Potential: A Sustainable Strategy for Antioxidant Production.

Unsaturated diacylglycerols are a class of antioxidant compounds with the potential to positively impact human health. Their ability to combat oxidative stress through radical scavenger activity underscores their significance in the context of preventive and therapeutic strategies. In this paper we highlight the role of Anabaena flos-aquae as a producer of unsaturated mono and diacylglycerols, and then demonstrate the antioxidant activity of its methanolic extract, which has as its main components a variety of acylglycerol analogues. This finding was revealed using a sustainable strategy in which the One Strain Many Compounds (OSMAC) cultivation in microscale was coupled with a bioinformatic approach to analyze a large dataset of mass spectrometry data using the molecular networking analyses. This strategy reduces time and costs, avoiding long and expensive steps of purification and obtaining informative data on the metabolic composition of the extracts. This study highlights the role of Anabaena as a sustainable and green source of novel bioactive compounds.

An Insight into Citrus medica Linn.: A Systematic Review on Phytochemical Profile and Biological Activities.

Plant species are a reservoir of natural compounds that can potentially be used to treat different diseases. Citrus medica Linn. belonging to the Rutaceae family, has been used for centuries in medicine for its antioxidant, anti-inflammatory, antimicrobial, antiviral, and antihyperglycemic properties. These activities are ascribable not only to the presence of health-promoting macronutrients and micronutrients, such as carbohydrates, minerals, amino acids, and vitamins, but also to specialized metabolites, such as flavonoids (apigenin, hesperetin, hesperidin, naringin, naringenin, rutin, quercetin, and diosmin), coumarins (citropten, scoparone, and bergapten), terpenes (limonene, γ-terpinene, limonin, and nomilin), and phenolic acids (p-coumaric acid, trans-ferulic acid, and chlorogenic acid). In recent years, particular attention has been focused on the antioxidant, anti-inflammatory, antimicrobial activity, antidiabetic, anticancer, and neuroprotective activity of C. medica. However, although many studies have reported this species' chemical and biological properties, the literature has never been analyzed via a systematic approach. For this reason, using PubMed and Scopus as databases, we performed a systematic review of C. medica's chemical composition and biological properties to inspire new research approaches and increase its curative application.