Josai University

Two new glycosides, named 3-methoxy-5-methylphenol-6-O-β-glucopyranosyl-(1→6)-β-glucopyranoside (compound 1) and 1-O-feruloyl-α-arabinofuranosyl-(1→6)-β-glucopyranoside (compound 2), were isolated from Asiasarum root, together with eight known compounds. Asiasarum root (crude drug name in Latin: ASIASARI RADIX) is well known for its anti-inflammation and antitussive properties and is commonly found in Kampo formula in Japan. The structures of new compounds 1 and 2 were characterized using one- and two-dimensional (1D and 2D) NMR spectroscopy and MS. In addition, the anti-glycation activity of the isolates was evaluated. Glycation is particularly advanced in patients with diabetes and is suspected to be associated with diabetic complications such as nephropathy, osteoporosis, and Alzheimer's disease. The inhibition of this reaction is thought to be linked to the prevention and treatment of these diseases. Compounds 2 (79.4%), 4 (82.4%), 5 (79.8%), 6 (86.5%), 7 (90.1%), 9 (61.4%), and 10 (82.2%) showed activities comparable to that of aminoguanidine (45.3%) used as a positive control.

Spices and herbs, which are derived from natural botanical sources, contain many bioactive compounds and play an important role in human health. The general and specific health benefits of these spices and herbs include anti-inflammatory, antioxidant, and anti-tumorigenic activities. Previously, we showed that cathepsin G, which is a neutrophil-derived serine protease localized in human breast cancer tissues, promotes cancer metastasis via induction of platelet-activating factor acetylhydrolase 1B2 (PAFAH1B2) expression in MCF-7 human breast cancer cells. Therefore, although regulation of cathepsin G activity is thought to be important in human breast cancer progression, no compounds that inhibit the activity have been identified for therapeutic purposes. In this study, we screened 50 spice and herb extracts. Peppermint, clove, Sichuan pepper, and fenugreek exhibited strong inhibitory effects on cathepsin G activity and suppressed cathepsin G-induced MCF-7 cell aggregation.; importantly, fenugreek suppressed the increase in PAFAH1B2 expression. The IC₅₀ of 37.38 μg/mL of fenugreek extract that showed inhibitory effect on cathepsin G-induced malignant progression was 5.87 times lower than the concentration that exerted cytotoxic effect. Interestingly, quercetin and trigonelline contained in fenugreek inhibited cathepsin G activity and suppressed the induction of cell aggregation and PAFAH1B2 expression in human breast cancer cells. These results suggest that quercetin and trigonelline are partly responsible for the inhibitory effect of fenugreek on cathepsin G-induced malignant progression of human breast cancer cells. Our findings provide a new breast cancer treatment strategy targeting cathepsin G, and fenugreek may have synergistic effects when combined with therapeutic drugs.

Insomnia is a significant global health issue associated with substantial economic costs. International guidelines recommend cognitive behavioural therapy for insomnia (CBT-I) as the first-line treatment for chronic insomnia; however, pharmacotherapy remains more common in clinical practice. Maintaining the effectiveness while reducing the time and frequency of CBT-I is essential for its implementation. We conducted a randomised controlled trial (RCT) to evaluate the effectiveness of a brief behavioural treatment for insomnia (BBTI) that focuses on sleep restriction and stimulus control (SC)—both established as effective standalone interventions. This article presents the study protocol to examine whether adding BBTI to treatment as usual improves outcomes in patients with chronic insomnia.

We will conduct a multicentre RCT. We will randomly assign patients with chronic insomnia to two groups (BBTI vs sleep hygiene) in a 1:1 ratio. The BBTI consists of three 15 min sessions over 4 weeks delivered by healthcare professionals following a detailed manual. The primary outcome is the Insomnia Severity Index at 8 weeks. Secondary outcomes include sleep latency, wake after sleep onset, total sleep time, sleep efficiency, Generalized Anxiety Disorder-7, Patient Health Questionnaire-9 and EuroQol-5D-5L. We will conduct the assessment at weeks 0 (baseline), 4 (end of intervention), 8 (post-intervention, primary endpoint) and 12 (follow-up). We will assess each sleep variable from the sleep diary at weeks 0 and 8. The analysis will be performed on an intention-to-treat basis.

This study has been approved by the Ethics Committee for Clinical and Epidemiological Research of Toyama University (approval no. R2023152).

UMIN000052911; pre-results.