1.Secondary Metabolites of Hemerocallis fulva var. kwanso Regel and Their PTP1B Inhibitory Potential
Thi Thanh LE ; Manh Tuan HA ; Trong Trieu TRAN ; Seung Eui MIN ; Kang-Hyun HAN ; Jungmoo HUH ; Jeong Ah KIM ; Byung Sun MIN
Natural Product Sciences 2026;32(1):76-83
A phytochemical study of the root extract of Hemerocallis fulva var. kwanso Regel resulted in the isolation and structural characterization of four lignans (1‒4), three flavanones (5, 6, and 8), one chalcone (9), and two monoterpenes (7 and 10). Enzyme inhibition assays revealed that two flavanone glucosides (5 and 6) showed significant inhibitory effect against protein tyrosine phosphatase 1B (PTP1B), with IC50 values of 31.38 µM and 51.46 µM, respectively. Further enzyme kinetic studies demonstrated that these two compounds acted as noncompetitive PTP1B inhibitors, with Ki values of 30.88 µM and 50.38 µM, respectively.
2.A New Methoxyflavonoid Rutinoside and PTP1B-Inhibitory Phenolic Compounds from the Water Extract of Areca catechu L.
Manh Tuan HA ; Trong Trieu TRAN ; Thu Huong TRAN ; Seung Eui MIN ; Sang-Jin PARK ; Kang-Hyun HAN ; Jungmoo HUH ; Jeong Ah KIM ; Byung Sun MIN
Natural Product Sciences 2026;32(1):50-55
Phytochemical investigation of the water extract and alkaloid fraction of Areca catechu L. led to theisolation of one new methoxyflavonoid rutinoside (1), together with eleven known compounds (2−12), five of which (8−12) belong to the pyridine alkaloid class. The structure of the new compound was elucidated through extensive spectroscopic analyses, including 1D and 2D NMR experiments and high-resolution mass spectrometry.Notably, rhamnazin-3-O-rutinoside (2) is reported here for the first time from this species. The isolated compounds were evaluated for their inhibitory activity against protein tyrosine phosphatase 1B (PTP1B) using a p-nitrophenyl phosphate assay. Flavonoids (3 and 4) and stilbene (5) exhibited notable inhibitory activity, with IC50 values of 13.30 ± 0.71, 13.44 ± 0.84, and 8.68 ± 0.12 μM, respectively. In contrast, methoxyflavonoid rutinosides (1 and 2) and pyridine alkaloids (8−12) did not show significant inhibitory activity against PTP1B.These findings provide additional chemical insights into A. catechu and its constituents in relation to PTP1B inhibition.
3.Combination Therapy with Betulinic Acid and TRAIL Increases ROS-Dependent Cytotoxicity and Inhibits PI3K/Akt Signaling in Human Bladder Cancer Cells
Cheol PARK ; Hee-Jae CHA ; Su Hyun HONG ; Heui-Soo KIM ; Sun-Hee LEEM ; Jung-Hyun SHIM ; Gi-Young KIM ; Kyoung Ah KANG ; Jin Won HYUN ; Yung Hyun CHOI
Biomolecules & Therapeutics 2026;34(3):641-651
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine that selectively targets cancer cells and induces apoptosis. However, many cancers, including bladder cancer, develop resistance to TRAIL, limiting the efficacy of TRAIL-based therapies. This study investigated whether betulinic acid (BA), a pentacyclic triterpenoid with anticancer and chemosensitizing properties, increases TRAIL-mediated apoptosis in TRAIL-resistant human bladder cancer cells. Combination treatment with BA and TRAIL significantly increased cytotoxicity and apoptosis compared to either treatment alone. This combination treatment also increased reactive oxygen species (ROS) production, increased Bax expression and Bid cleavage (tBid formation), and downregulated Bcl-2 levels. These effects were accompanied by caspase activation via extrinsic and intrinsic pathways, leading to cytochrome c release via mitochondrial membrane destabilization, thereby contributing to increased apoptosis. Furthermore, the combination treatment inhibited phosphoinositide 3-kinase (PI3K) and Akt phosphorylation; this effect was amplified by a PI3K inhibitor but abrogated by ROS inhibition. Collectively, our results suggest that BA sensitizes bladder cancer cells to TRAILinduced apoptosis via ROS-dependent activation of the apoptotic pathway and inhibition of PI3K/Akt signaling. Therefore, the BA and TRAIL combination exhibits potential to overcome TRAIL resistance in human bladder cancer.
4.Clinical Efficacy of Real-Time Artificial Intelligence-Assisted Colonoscopy in Colorectal Polyp Detection: A Prospective Multicenter Randomized Controlled Trial
Han Jo JEON ; Bora KEUM ; Eui Sun JEONG ; Seong-Eun KIM ; Chang Mo MOON ; Bomee LEE ; Sanghyun KIM ; Hyuk Soon CHOI ; Jae Min LEE ; Eun Sun KIM ; Yoon Tae JEEN
Gut and Liver 2026;20(1):97-106
Background/Aims:
Early detection and removal of colon polyps are critical for preventing colorectal cancer. Computer-aided detection (CADe) systems have been introduced to increase the polyp detection rate (PDR) during colonoscopy, potentially enhancing its effectiveness. This study aimed to evaluate the efficacy of a CADe system in colorectal neoplasm detection.
Methods:
This prospective, randomized controlled trial was conducted at two tertiary centers (May 2023 to April 2025). Patients were randomly assigned to CADe or conventional colonoscopy and underwent screening, surveillance, or diagnostic colonoscopy. The primary endpoint was the adenoma detection rate (ADR), while the secondary endpoints were the PDR, relative risk (RR) of polyp detection, adenomas per colonoscopy (APC), and factors influencing adenoma detection.
Results:
Of 1,004 enrolled patients, 998 were randomly allocated into CADe and conventional colonoscopy groups (497 CADe system and 501 conventional colonoscopy). The CADe group had greater polyp counts (2.2 per colonoscopy vs 1.4 per colonoscopy; p<0.001) and APC values (1.2 vs 0.8; p<0.001). The CADe group showed significantly higher PDRs (72.2% vs 54.5%;p<0.001; RR, 2.173; 95% confidence interval [CI], 1.669 to 2.828) and ADRs (52.3% vs 36.1%;p<0.001; RR, 1.940; 95% CI, 1.505 to 2.499). CADe also significantly increased the detection rate of hyperplastic polyps (p=0.007; RR, 1.474; 95% CI, 1.113 to 1.952) and increased the detection rates across all sizes and locations. In multivariable analysis, CADe use was the strongest independent predictor of adenoma detection (odds ratio, 1.914; 95% CI, 1.467 to 2.496), outweighing male sex, older age, diagnostic indication, and withdrawal time.
Conclusions
Real-time CADe-assisted colonoscopy significantly increased PDR and ADR and proved to be a strong independent predictor of adenoma detection (cris.nih.go.kr, KCT0009664).
5.Development of Korean Standardized Heart Failure Registry: Experience From Integration of KorAHF and KorHF III
Eui-Soon KIM ; Huijin LEE ; Jong-Chan YOUN ; Byung-Su YOO ; Hae-Young LEE ; Ju-Hee LEE ; Dong-Hyuk CHO ; Mi-Hyang JUNG ; Hye Sun LEE ; Hyun-Jai CHO
International Journal of Heart Failure 2026;8(1):1-11
Heart failure (HF) prevalence and associated socio-economic costs have risen rapidly in Korea, creating urgent demand for a national, standardized prospective registry to support quality monitoring, outcome comparison, and real-world evidence. Standardized data definitions are essential for valid comparisons across studies and healthcare settings. We created a unified national HF cohort by integrating the two largest Korean registries, KorAHF (2011–2014;n=5,625) and KorHF III (2018–2023; n=7,351), yielding 12,976 hospitalized HF patients. Because heterogeneous variable definitions impeded direct comparisons, we implemented a harmonization pipeline across demographic, clinical, imaging, biomarker, therapeutic, and outcome domains, aligned with international standards and reinforced by systematic data quality checks.A multidisciplinary panel then conducted a structured decision process to produce the Korean HF Standard Dataset, a tiered and interoperable variable set spanning six domains: demographics, presentation at admission, in-hospital events and comorbidities, discharge status, outpatient follow-up, and readmission events. This integrated platform and standardized variables enable precise identification of HF patient phenotypes and prognostic factors, establishing an evidence-based foundation for disease management. This supports an analysis of temporal changes in treatment patterns and outcomes, generates data to inform future clinical practice guidelines, and provides a practical basis for planning large, continuous, prospective HF registries. Furthermore, it also facilitates pragmatic, registry-based randomized clinical trials and unmet-needs assessments that can guide national health policy. Establishing a foundation for future linkage with national health databases, this platform will allow for enhanced accuracy, comparability, and representativeness, powering quality improvement initiatives and population-level monitoring of Korea’s growing HF burden.
6.Erratum to "Morroniside Protects C2C12 Myoblasts from Oxidative Damage Caused by ROS-mediated Mitochondrial Damage and Induction of Endoplasmic Reticulum Stress" Biomol Ther 32(3), 349-360 (2024)
Hyun HWANGBO ; Cheol PARK ; EunJin BANG ; Hyuk Soon KIM ; Sung-Jin BAE ; Eunjeong KIM ; Youngmi JUNG ; Sun-Hee LEEM ; Young Rok SEO ; Su Hyun HONG ; Gi-Young KIM ; Jin Won HYUN ; Yung Hyun CHOI
Biomolecules & Therapeutics 2025;33(3):555-555
7.Erratum to "Morroniside Protects C2C12 Myoblasts from Oxidative Damage Caused by ROS-mediated Mitochondrial Damage and Induction of Endoplasmic Reticulum Stress" Biomol Ther 32(3), 349-360 (2024)
Hyun HWANGBO ; Cheol PARK ; EunJin BANG ; Hyuk Soon KIM ; Sung-Jin BAE ; Eunjeong KIM ; Youngmi JUNG ; Sun-Hee LEEM ; Young Rok SEO ; Su Hyun HONG ; Gi-Young KIM ; Jin Won HYUN ; Yung Hyun CHOI
Biomolecules & Therapeutics 2025;33(3):555-555
8.Erratum to "Morroniside Protects C2C12 Myoblasts from Oxidative Damage Caused by ROS-mediated Mitochondrial Damage and Induction of Endoplasmic Reticulum Stress" Biomol Ther 32(3), 349-360 (2024)
Hyun HWANGBO ; Cheol PARK ; EunJin BANG ; Hyuk Soon KIM ; Sung-Jin BAE ; Eunjeong KIM ; Youngmi JUNG ; Sun-Hee LEEM ; Young Rok SEO ; Su Hyun HONG ; Gi-Young KIM ; Jin Won HYUN ; Yung Hyun CHOI
Biomolecules & Therapeutics 2025;33(3):555-555
9.Areca catechu L.: A Comprehensive and Updated Review of its Phytochemical and Pharmacological Properties
Manh Tuan HA ; Thu Huong TRAN ; Jungmoo HUH ; Seung Eui MIN ; Kang-Hyun HAN ; Yong-Bum KIM ; Jeong Ah KIM ; Byung Sun MIN
Natural Product Sciences 2025;31(4):236-250
Areca catechu L., the primary source of areca alkaloids, has long been considered the only species inthe genus containing these compounds. However, a recent study detected the same pyridine alkaloids in A. triandra, suggesting that alkaloid biosynthesis may also occur in other species of Areca. The immature fruit or pericarp of A. catechu is the principal component of betel quid, a masticatory deeply rooted in ancient oriental culture and consumed by over 600 million people globally. Its longstanding medicinal applications have attracted extensive modern research into its chemical composition, biological activities, and toxicity. This review provides a comprehensive update on the major chemical constituents of A. catechu, including alkaloids, flavonoids, tannins, other phenolic compounds, triterpenoids and phytosterols, fatty acids, glycerides, and polysaccharides, and their reported pharmacological activities, such as antioxidant, anti-inflammatory, analgesic and antinociceptive, cytotoxic, antibacterial and antifungal, hypoglycemic, lipid-regulating, antiparasitic, immunomodulatory, neuroprotective, digestive, antiviral, cardiovascular, anti-allergic, and other effects. Information was systematically collected from PubMed, Google Scholar, ACS, Web of Science, and ScienceDirect to provide an up-to-date summary of its phytochemistry and bioactivity.
10.Treatment Response With Potassium-competitive Acid Blockers Based on Clinical Phenotypes of Gastroesophageal Reflux Disease: A Systematic Literature Review and Meta-analysis
Seungyeon SEO ; Hye-Kyung JUNG ; C Prakash GYAWALI ; Hye Ah LEE ; Hyung Seok LIM ; Eui Sun JEONG ; Seong Eun KIM ; Chang Mo MOON
Journal of Neurogastroenterology and Motility 2024;30(3):259-271
Background/Aims:
Gastroesophageal reflux disease (GERD) is typically managed based on the clinical phenotype. We evaluated the efficacy and safety of potassium-competitive acid blockers (PCABs) in patients with various clinical GERD phenotypes.
Methods:
Core databases were searched for studies comparing PCABs and proton pump inhibitors (PPIs) in clinical GERD phenotypes of erosive reflux disease (ERD), non-erosive reflux disease (NERD), PPI-resistant GERD and night-time heartburn. Additional analysis was performed based on disease severity and drug dosage, and pooled efficacy was calculated.
Results:
In 9 randomized controlled trials (RCTs) evaluating the initial treatment of ERD, the risk ratio for healing with PCABs versus PPIs was 1.09 (95% CI, 1.04-1.13) at 2 weeks and 1.03 (95% CI, 1.00-1.07) at 8 weeks, respectively. PCABs exhibited a significant increase in both initial and sustained healing of ERD compared to PPIs in RCTs, driven particularly in severe ERD (Los Angeles grade C/D).In 3 NERD RCTs, PCAB was superior to placebo in proportion of days without heartburn. Observational studies on PPI-resistant symptomatic GERD reported symptom frequency improvement in 86.3% of patients, while 90.7% showed improvement in PPIresistant ERD across 5 observational studies. Two RCTs for night-time heartburn had different endpoints, limiting meta-analysis. Pronounced hypergastrinemia was observed in patients treated with PCABs.
Conclusions
Compared to PPIs, PCABs have superior efficacy and faster therapeutic effect in the initial and maintenance therapy of ERD, particularly severe ERD. While PCABs may be an alternative treatment option in NERD and PPI-resistant GERD, findings were inconclusive in patients with night-time heartburn.

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