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Cholinesterase (ChE) and monoamine oxidase (MAO) inhibitors have been attracted as candidate treatments for Alzheimer's disease (AD). Fifteen khellactone-type coumarins from the roots of Peucedanum japonicum Thunberg were tested for acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and MAO inhibitory activities. Compound 3′-angeloyl-4′-(2-methylbutyryl)khellactone ( PJ13 ) most potently inhibited AChE (IC 50  = 9.28 µM), followed by 3′-isovaleryl-4′-(2-methylbutyroyl)khellactone ( PJ15 ) (IC 50  = 10.0 μM). Compound senecioyl-4′-angeloyl-khellactone ( PJ5 ) most potently inhibited BChE (IC 50  = 7.22 μM) and had the highest selectivity index (> 5.54), followed by 3′-senecioyl-4′-(2-methylbutyryl)khellactone ( PJ10 ) and 3′,4′-disenecioylkhellactone ( PJ4 ) (IC 50  = 10.2 and 10.7 μM, respectively). Compounds PJ13 , PJ15 , and PJ5 showed reversible and mixed-types of inhibition with K i values of 5.98, 10.4 (for AChE), and 4.16 µM (for BChE), respectively. However, all 15 compounds weakly inhibited MAO-A and MAO-B. Molecular docking simulation revealed that PJ13 had a higher binding affinity (− 9.3 kcal/mol) with AChE than PJ15 (− 7.8 kcal/mol) or PJ5 (− 5.4 kcal/mol), due to the formation of a hydrogen bond with Tyr121 (distance: 2.52 Å). On the other hand, the binding affinity of PJ5 (− 10.0 kcal/mol) with BChE was higher than for PJ13 (− 7.7 kcal/mol) or PJ15 (− 8.1 kcal/mol), due to the formation of a hydrogen bond with Ser198 (distance: 2.05 Å). These results suggest that PJ13 and PJ5 are potential reversible selective inhibitors of AChE and BChE, respectively, for the treatment of AD.

Study Design Retrospective Cohort Study. Objectives This study aimed to examine the effect of state legislation on prescribing behavior after a commonly performed spinal procedure, posterior lumbar interbody fusion (PLIF). Methods Two cohorts of patients from the Pearl Diver Database were created based on patients who underwent PLIF surgery in 2014-15 and 2018-19. We compared opioid prescription rates and morphine-milli-equivalent (MME) between states with and without prescription legislation. Results We analyzed 50 958 PLIF patients from 2014-15 and 46 751 patients from 2018-19. Among them, 38 states passed opioid prescription laws in 2016-2017, while 12 states did not. The percentage of patients receiving opioid prescriptions within 365 days post-surgery remained similar in both time periods (49% in 2014-15 and 48% in 2018-2019). This trend was consistent across states with and without prescription legislation (50% vs 48% in 2014-2015, and similar in 2018-19). Opioid prescription quantity significantly decreased in all states between 2014-15 and 2018-19. In states with legislation, average MME dropped from 9198 ± 21 002 to 4932 ± 13 213 (46.4% decrease), and in states without legislation, it decreased from 9175 ± 21 032 to 4994 ± 11 687 (45.6% decrease). However, these differences were not statistically significant (P = .7985). Conclusion From 2014 to 2018, there was a significant decrease in the number of opioids prescribed after PLIF. However, this decrease occurred irrespective of state legislation on prescribing practices being passed. We believe the reduction in opioids prescribed was due to increased awareness surrounding the dangers of opioids among physicians.

Breast cancer is one of the most common cancers in women and is associated with a high mortality rate. The majority of deaths resulting from breast cancer are attributable to metastatic growth; in addition, chemoresistance is a major concern in the treatment of patients with breast cancer. However, limited drugs are available for the treatment of metastatic breast cancer. In this study, the chemoadjuvant effects of a methanolic extract from the leaves of Pseudolysimachion rotundum var. subintegrum (NC13) and an active component isolated from the plant, verminoside (Vms), were evaluated. Furthermore, their potent anti-metastatic activities were validated in vitro and in vivo in animal models. The anti-metastatic and chemosensitizing activities of NC13 and Vms on cisplatin treatment were found to be partly mediated by suppression of the epithelial–mesenchymal transition of cancer cells. Collectively, our results implied that NC13 and its bioactive component Vms could be developed as effective chemoadjuvants in combination with conventional therapeutics.

Objectives: This study aimed to assess the impact of traditional Korean medicine services (TKMS) on subsequent knee surgery and opioid use in patients diagnosed with knee osteoarthritis (KOA). Methods: This retrospective cohort study used National Health Insurance Review and Assessment Service claims data from 2015 to 2017 to identify patients treated for KOA (M17) in 2016. Patients with at least two Korean medicine (KM) clinic visits within 6 weeks of the initial diagnosis formed the TKMS group, while those without visits to KM clinics formed the n group. Propensity score matching (PSM) (1:1) was applied and the incidence of knee surgery and opioid use was followed up for one year. Kaplan–Meier survival curves and Cox proportional hazards models estimated time-to-event outcomes and hazard ratios (HRs). Sensitivity analyses were performed to verify the results across varied treatment windows of 4, 8, and 10 weeks. Results: After PSM, 247,168 patients were included in the analysis for each group. The TKMS group exhibited significantly lower HRs for knee surgery (HR = 0.69, 95% CI: 0.66–0.72), opioid use (HR = 0.66, 95% CI: 0.65–0.66), and their compound events (HR = 0.66, 95% CI: 0.65–0.67) compared with the Non-TKMS group. The results remained consistent across sensitivity analyses. Conclusions: Among patients with KOA, the utilization of TKMS may significantly reduce the incidence of knee surgery and opioid use. Thus, the utilization of TKMS may be associated with a reduced need for unnecessary surgical interventions and with lower reliance on high-risk medications.

Background Magnolin is a natural compound abundantly found in Magnolia flos, which has been traditionally used in oriental medicine to treat headaches, nasal congestion and anti-inflammatory reactions. Our recent results have demonstrated that magnolin targets the active pockets of ERK1 and ERK2, which are important signaling molecules in cancer cell metastasis. The aim of this study is to evaluate the effects of magnolin on cell migration and to further explore the molecular mechanisms involved. Methods Magnolin-mediated signaling inhibition was confirmed by Western blotting using RSK2 +/+ and RSK2 −/− MEFs, A549 and NCI-H1975 lung cancer cells, and by NF-κB and Cox-2 promoter luciferase reporter assays. Inhibition of cell migration by magnolin was examined by wound healing and/or Boyden Chamber assays using JB6 Cl41 and A549 human lung cancer cells. The molecular mechanisms involved in cell migration and epithelial-to-mesenchymal transition were determined by zymography, Western blotting, real-time PCR and immunocytofluorescence. Results Magnolin inhibited NF-κB transactivation activity by suppressing the ERKs/RSK2 signaling pathway. Moreover, magnolin abrogated the increase in EGF-induced COX-2 protein levels and wound healing. In human lung cancer cells such as A549 and NCI-H1975, which harbor constitutive active Ras and EGFR mutants, respectively, magnolin suppressed wound healing and cell invasion as seen by a Boyden chamber assay. In addition, it was observed that magnolin inhibited MMP-2 and −9 gene expression and activity. The knockdown or knockout of RSK2 in A549 lung cancer cells or MEFs revealed that magnolin targeting ERKs/RSK2 signaling suppressed epithelial-to-mesenchymal transition by modulating EMT marker proteins such as N-cadherin, E-cadherin, Snail, Vimentin and MMPs. Conclusions These results demonstrate that magnolin inhibits cell migration and invasion by targeting the ERKs/RSK2 signaling pathway.

Methyl lucidone (ML) from the dried fruit of Lindera erythrocarpa Makino (Lauraceae) exhibits cytotoxic effects in various cancer cell lines. However, its effects on ovarian cancer cells remain unknown. This study evaluates the mechanism of ML-induced apoptosis, cell cycle distribution in ovarian cells. The cytotoxic effect of ML (2.5-80 µM) on OVCAR-8 and SKOV-3 cells was evaluated by MTS assay for 24 and 48 h. Apoptosis and cell cycle arrest were analysed by flow cytometry. PCR, western blot analyses were performed to examine the related signalling pathways. ML induced significant cellular morphological changes and apoptosis in ovarian cancer cells, leading to an antiproliferative effect (IC 50  = 33.3-54.7 µM for OVCAR-8 and 48.8-60.7 µM for SKOV-3 cells). Treatment with ML induced cleavage of caspase-3/9 and PARP and release of cytochrome c from the mitochondria. Moreover, ML downregulated the expression of Bcl-2 and Bcl-xL and induced cell cycle arrest in the G 2 /M phase. Additionally, ML suppressed the expression of cyclin-A/B and promoted that of the cyclin-dependent kinase inhibitors p21 and p27. The expression of death receptors was not altered. Interestingly, ML also inhibited the activity of PI3K/Akt and NF-κB. ML caused G 2 /M phase arrest and apoptosis in ovarian cancer cells by activating intrinsic apoptotic pathways and suppressing the PI3K/Akt survival pathway. ML may be a potential anticancer agent to suppress ovarian cancer proliferation; thus, to improve the survival rate of cancer patients.

This study focused on identifying and characterizing 1,3-diphenylpropane derivatives from flavonoids that inhibit human indoleamine 2,3-dioxygenase 1 (hIDO1) enzymes, which play a role in immune regulation and are associated with various diseases. A series of isolated metabolites (1–7) demonstrated modest to high inhibition of hIDO1, with binding degree values ranging from 26.31 to 72.17%. In particular, during a target-based screening of natural products using hIDO1, kazinol J (6, a 1,3-diphenylpropane derivative) was found to potently inhibit hIDO1, with a binding degree of 72.17% at 1 ppm. Kazinol J (6) showed concentration-dependent and mixed inhibition kinetics and achieved slow and time-dependent inhibition of hIDO1. Additionally, docking simulations were performed to evaluate the inhibitory potential and binding interactions of the compounds with hIDO1. These findings suggest that these 1,3-diphenylpropane derivatives can serve as therapeutic agents for conditions involving hIDO1 dysregulation, such as cancer, autoimmune disorders, and infectious diseases.

The untargeted metabolomics-based molecular networking approach combined with multivariate analysis, proves to be an effective strategy for distinguishing raw materials in herbal medicine according to specific criteria. It exhibits the correlations between chemical constituents and the geographical habitats of plants, providing a valuable tool for ensuring quality control in mass production within the industry. In this study, we conducted a comprehensive investigation of the chemical compositions of Epimedium koreanum Nakai and performed comparative analyses on four extracts collected from distinct regions in South Korea using untargeted metabolomics tools. Through the comprehensive use of UPLC-QTOF/MS analysis and advanced statistical techniques, we elucidated the chemical composition, leading to the identification of key chemical markers. Additionally, the molecular networking analysis revealed distinct clusters of flavonoids and phenolic acids, highlighting the influence of regional factors on the metabolite profiles. These findings offer a promising avenue for enhancing quality control and traceability in the herbal medicine industry, underscoring the important role of geographical variation in the chemical profiles of herbal products.

Study Design A retrospective cohort utilizing the PearlDiver Patient Claims Database. Objective Cervical disc arthroplasty (CDA) is accepted treatment for cervical radiculopathy; however, it may also be safe and effective in myelopathy. Thus, we compared clinical characteristics and outcomes in patients undergoing CDA and anterior cervical discectomy and fusion (ACDF) for degenerative cervical myelopathy (DCM) specifically. Methods Patients undergoing CDA or ACDF between 2015-2019 were identified with follow-up through 2021. Univariate and multivariable analyses were performed to identify factors associated with either procedure. Reoperation rates were compared using propensity-matched analysis. Results We identified n = 2391 CDA and n = 50 845 ACDF procedures for DCM. Factors favoring CDA included: female sex, younger age, lower CCI, lower incidence of obesity, osteoporosis, diabetes, or smoking (P ≤ .001); remaining significant after multivariable logistic regression except for sex (P = .06). Single-level surgery was more predictive for undergoing CDA. CDA patients had lower 90-day readmissions, complications, and lower opioid utilization. The overall reoperation rate was 5%. Predictors of reoperation included: male sex, younger age, greater CCI, obesity, osteoporosis, diabetes, smoking, and multi-level surgery; all remaining significant after multivariable analysis except for diabetes (P = .23) and CCI (P = .05). After propensity-matching CDA and ACDF patients (n = 2391), there was no difference in re-operation rates (P = .47). Conclusions CDA patients were healthier (less obesity, smoking, diabetes, better CCI) and represented 4.5% of anterior procedures for DCM. In univariate analysis, readmission rates, medical complications, and opioid use were lower in CDA patients, despite a similar reoperation rate. Considering these findings, CDA might be used very selectively for DCM.

YPL-001 is a drug substance of Pseudolysimachion rotundum var. subintegrum and has been reported to be a potent COPD inhibitor. For the first time, this study demonstrated a correlation among the iridoid constituents, antioxidants, and MUC5AC inhibition activities in P. rotundum during different growth stages (5 to 11 weeks). Single-factor extraction was used to optimize the plant extraction conditions to maximize the major iridoid constituents (70% ethanol, 40 °C, 1 h); isolated metabolites 1–6 were identified using nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS). The contents of each metabolite and antioxidant/MUC5AC inhibition effects were markedly changed according to the growth stages, especially for catalposide (2, 5.97 → 10.99 mg/g, 1.8-fold) and isovanillyl catapol (5, 4.42 → 20.00 mg/g, 4.5-fold), which were the predominant substances in August. Our results indicated that YPL-001 could potentially contribute to enhancing the P. rotundum value in accumulated iridoids at the growth stage and the biological effect aspects to develop industrial medicinal crops.