Dong-Seon Kim

Standardized interpretation of analytical responses in multi-herb formulations remains difficult: constituent measurements, composition ratios, and extraction conditions are rarely integrated quantitatively. Effect Factor (EF) provides a dimensionless, endpoint-aware index for matched-condition referencing, but constituent-level EF descriptors do not directly yield formulation-level expectations. Using an EF-indexed resource comprising 271 herbal materials and 22 multi-herb formulations with paired water and 30% ethanol extracts, we developed an EF-guided quantitative herbal medicine composition–activity relationship (QHMCAR) framework. Additive theoretical formulation EFs for 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), total phenolic content (TPC), and total flavonoid content (TFC) were derived from constituent EFs, composition ratios, and solvent-matched extraction yields. Analyses included predictor screening, least-squares calibration, additive-deviation analysis, diagnostics, fixed-form refitting, nested leave-one-prescription-identity-out (LOPO), and solvent sensitivity. Retained full-data models showed apparent R² of 0.748–0.830; fully nested grouped LOPO yielded Q² of 0.543–0.809. Against a grouped-LOPO untransformed linear baseline, transformation screening modestly improved DPPH prediction, matched ABTS, and yielded lower Q² for TPC and TFC. Positive additive deviations were endpoint-dependent, most pronounced for ABTS; solvent-sensitivity analysis identified limited additional variation except for an ABTS-specific intercept shift. QHMCAR enables transparent formulation-level expectation, calibration, and internal validation without implying pharmacological synergy, therapeutic efficacy, or external predictive validity.

Background Angelica gigas Nakai is a medicinal plant rich in pyranocoumarins with well-documented anti-inflammatory and neuroprotective properties. However, the pharmacological potential of residues remaining after conventional aqueous extraction remains largely unexplored. This study investigated the phytochemical composition and anti-neuroinflammatory activity of residue-derived extracts of A. gigas, focusing on the regulation of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome. Methods and Results A water extract (PO6W), an ethanol extract (PO6E), and a residue-derived ethanol extract (PO6RE) were chemically characterized and evaluated in lipopolysaccharide-stimulated BV2 microglial cells and an LPS-induced mouse model. Molecular docking, surface plasmon resonance, and MCC950 intervention were used to investigate the association between decursin and NLRP3 signaling. Despite prior aqueous extraction, the residual biomass retained substantial amounts of pyranocoumarins, and subsequent ethanol extraction yielded PO6RE with the highest levels of decursin and decursinol angelate. PO6RE significantly suppressed the expression levels of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain, cleaved caspase-1, and interleukin-1β in BV2 cells and reduced microglial activation in vivo. Decursin showed measurable binding to NLRP3 and reduced NLRP3 expression and interleukin-1β production. Conclusions A. gigas biomass remaining after aqueous extraction retains bioactive pyranocoumarins that can be recovered by subsequent ethanol extraction. The resulting residue-derived extract exhibited anti-neuroinflammatory activity associated with NLRP3 inflammasome signaling, highlighting extraction residues as an underutilized and potentially sustainable source of bioactive phytochemicals.

Background/Objectives: Reflux esophagitis (RE) is a chronic inflammatory disorder caused by reflux of gastric contents into the esophagus, leading to mucosal injury and epithelial barrier dysfunction. Although proton pump inhibitors are widely used, persistent inflammation and oxidative stress remain important therapeutic challenges. Yeokwisan (YWS) is prescribed for gastroesophageal reflux disease and functional dyspepsia; however, its protective mechanisms against RE remain unclear. This study investigated the protective and anti-inflammatory effects of YWS. Methods: We integrated network pharmacology analysis, mechanistic studies in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, and efficacy evaluation in a rat model of acute RE induced by pyloric and forestomach ligation. Results: Network pharmacology identified 174 common targets between YWS and RE and 23 hub genes through protein–protein interaction network and topological analyses, implicating PI3K/Akt, MAPK, Ras, HIF-1, chemokine, and other inflammation-related signaling pathways. In LPS-stimulated RAW264.7 macrophages, YWS significantly reduced intracellular reactive oxygen species, nitric oxide, TNF-α, and IL-6 production without inducing cytotoxicity and suppressed MAPK, PI3K/Akt, and NF-κB activation. In vivo, YWS attenuated acute reflux-induced esophageal mucosal injury and histopathological alterations, restored esophageal superoxide dismutase activity, reduced malondialdehyde levels, and lowered serum TNF-α, IL-6, and IL-1β levels. YWS also suppressed NF-κB/IκB activation and COX-2 expression in esophageal tissue. Conclusions: YWS exerted protective effects against acute reflux-induced esophageal injury and anti-inflammatory effects in activated macrophages, accompanied by attenuation of oxidative stress and inflammation-associated signaling. These findings support further investigation of YWS for reflux-associated esophageal inflammation.

Comparative interpretation of antioxidant activity across complex natural-product extracts and multi-component formulations is often limited by heterogeneous endpoints, assay-specific reporting, and incompatible units. In this study, we establish a dimensionless Effect Factor (EF) framework as a standardized comparative indexing system for matched-condition comparison of antioxidant-related readouts. EF maps four widely used antioxidant-related readouts—ABTS, DPPH, total phenolic content (TPC), and total flavonoid content (TFC)—into a common dimensionless index space while preserving endpoint meaning through two complementary tracks: potency-type EF and content-type EF. Using a standardized extraction and assay pipeline, we generated EF indices for 586 extracts prepared under water and 30% ethanol conditions and organized them into EF-indexed databases. EF is not intended as a predictive or biologically validated efficacy metric, but as a standardized comparative indexing framework that enables reproducible benchmarking, database-level referencing, and structured interpretation of heterogeneous antioxidant-related data under harmonized experimental conditions. These results establish the EF-indexed resource as a scalable and expandable comparative infrastructure for natural-product research.

Centella asiatica, a widely used medicinal herb in Oriental and increasingly Western medicine, is applied for wound healing, dermatological disorders, and gastrointestinal illness. We investigated the effects of fermented C. asiatica extract (FCAE), prepared with Lactobacillus, on airway inflammation in a murine model of chronic obstructive pulmonary disease (COPD) induced by cigarette smoke extract (CSE) and lipopolysaccharide (LPS). CSE/LPS stimulation caused marked immune cell infiltration in airways. FCAE (100 and 200 mg/kg) reduced neutrophils in the bronchoalveolar lavage fluid (BALF) by 26.03% and 70.11%, respectively, and decreased activated T cells and B cells in the lung, mediastinal lymph nodes, and Peyer’s patches, while inhibiting collagen fibrosis. FCAE significantly reduced IL-1α (32.51%), CXCL1 (47.63%), CXCL2 (45.37%), and TNF-α (39.51%) levels in the BALF compared with the control group. It also downregulated the expression of muc5ac (58.39%), CXCL1 (67.32%), CXCL2 (57.60%), and TNF-α (54.61%) and suppressed p-STAT3 activation by 50.22%. Furthermore, FCAE enhanced tracheal phenol red secretion by 229.62%, indicating expectorant activity. UPLC analysis identified nine components, which, together with FCAE, inhibited RANTES, TNF-α, and IL-6 in inflammation-induced BEAS-2B cells. Overall, FCAE attenuates immune activation and airway inflammation, supporting its potential as a candidate therapy or functional food for respiratory diseases.

Sarcopenia starts around age 40, with individuals losing more than 30% of muscle mass by age 70. Due to the absence of approved pharmacological treatments, current management primarily relies on exercise and protein supplementations. Schizonepeta tenuifolia is a medicinal plant commonly found in Korea, China, Japan and is traditionally used for headaches, colds and allergies. However, its preventive effect against sarcopenia have not yet been explored. This study to investigate whether the ethanol extract of Schizonepeta tenuifolia (DKB138) enhances muscle strength in a dexamethasone (DEX)-muscle atrophy mice model. The preventive effects of DKB138 against muscle atrophy were evaluated in DEX-induced models both in vitro and in vivo. In vitro, DEX-induced myotubes were assessed for cell viability to determine cytoprotective effects. In vivo, a DEX-induced muscle atrophy mouse model was used evaluate muscle strength and functional performance. Using UPLC and comparison with reference standards, seven components of DKB138 were identified. DKB138 effectively prevented DEX-induced death in C2C12 skeletal muscle cells. In vivo, mice treated with DKB138 exhibited 28.5% increase in grip strength (*** p < 0.001) and a threefold significant increase in running distance (** p < 0.01) compared to the DEX-induced mice. Additionally, DKB138 treatment resulted in downregulation of Murf-1 and Atrogin mRNA while upregulating of MyoD mRNA expression. These finding demonstrate that DKB138 protects against DEX-induced muscle atrophy by suppressing muscle degradation factors and enhancing muscle strength. These results suggest that DKB138 has potential as functional food against muscle dysfunction and atrophy. Graphical Abstract

Hyperuricemia, characterized by elevated serum uric acid levels, is a major risk factor for gout and kidney disease. This study evaluated the antihyperuricemic effects of Cornus officinalis extract (COE) using urate transporter 1 (URAT1)-expressing oocytes and a hyperuricemia rat model. COE effectively inhibited uric acid absorption by modulating URAT1, with an IC₅₀ value of 3.24 µg/mL. In the hyperuricemia model, COE administration (100 and 200 mg/kg) significantly reduced serum uric acid levels and increased urinary uric acid excretion. The primary constituents of COE, morroniside (MO) and loganin (LO) exerted similar effects, with MO exhibiting potent inhibition of uric acid absorption even at low concentrations. Kidney tissue analysis revealed a reduction in blood urea nitrogen (BUN) levels, indicating improved renal function. Liver function parameters (ALT, AST, and LDH) remained unchanged, suggesting an absence of hepatotoxicity. Ultra-high-performance liquid chromatography with charged aerosol detection (UHPLC-CAD) analysis identified MO (17.8 mg/g), LO (9.8 mg/g), and cornin (1.4 mg/g) as the principal components of COE. These findings suggest that COE enhances uric acid excretion via URAT1 regulation and exerts renoprotective effects, highlighting its potential as an antihyperuricemic agent. Furthermore, MO and LO were identified as the primary active constituents, and COE appears to be a promising therapeutic candidate with a favorable safety profile.

Wild soybean (Glycine soja, GS) is a traditional medicine used to treat inflammation. In this study, the anti-atopic properties of GS leaf and stem extract on skin inflammation were evaluated in the Dermatophagoides farinae-extract-induced mouse model and keratinocytes. Oral administration of the GS extract reduced scratching, dermatitis score, transepidermal water loss, thickness of epidermis, inflammatory cell accumulation, and serum concentrations of thymic stromal lymphopoietin and immunoglobulin E. GS downregulated the expression of inflammatory gene markers of atopic dermatitis (AD), including interleukin (IL)-6; regulated on activation, normal T cell expressed and secreted (RANTES); thymus- and activation-regulated chemokine (TARC); and macrophage-derived chemokine (MDC) and upregulated the expression of filaggrin, a keratinocyte differentiation marker, in skin tissue. GS downregulated Janus kinase 1, signal transducer and activation of transcription (STAT) 1, and STAT3 pathways. Using ultra-performance liquid chromatography, we identified seven flavonoids in GS extract, including apigenin, epicatechin, genistein, genistin, daidzin, daidzein, and soyasaponin Bb. GS, apigenin, and genistein reduced the expression of IL-6, MDC, TARC, and RANTES and increased filaggrin via the downregulation of STAT3 phosphorylation in interferon-γ/tumor necrosis factor-α-stimulated keratinocytes. Our results suggest that GS leaf and stem extract ameliorates AD-like skin inflammation by regulating the immune response and restoring skin barrier function.

WDJ-S4, a standardized herbal formula, has been prescribed for refractory functional dyspepsia (FD) in Korea, but the detailed mechanisms are lacking. The present study investigates the acceleration of gastrointestinal (GI) motility by WDJ-S4 and its potential mechanisms. For five days, WDJ-S4 (50, 100 and 200 mg/kg) or mosapride (3 mg/kg) was orally given to BALB/c mice. After 20 h of fasting, loperamide (10 mg/kg, i.p.) was given to the mice except for normal group. To assess gastric emptying or intestinal propulsion, 500 μL of 0.05% phenol red or 200 μL of 5% charcoal diet was given once orally. Loperamide delayed gastric emptying and intestinal propulsion, while WDJ-S4 ameliorated peristaltic dysfunction, evidenced by reductions of remaining phenol red in the stomach and a marked increase of charcoal propulsion in the intestine. WDJ-S4 also normalized levels of acetylcholine and acetylcholine-related enzymes, including choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), in the gastric antrum and jejunum. C-kit level and smooth muscle contraction-related genes were elevated by WDJ-S4 in both the gastric antrum and jejunum. Overall, WDJ-S4 can effectively promote GI motility. The efficacy is associated with modulation of acetylcholine pathway and the interstitial cells of Cajal (ICCs) activation. All the results provide scientific evidence supporting the clinical usage of WDJ-S4 for FD.