Sin-Min Li

Malignant melanoma is one of the most aggressive forms of skin cancer. Despite advances in targeted therapy and immunotherapy, the emergence of drug resistance and limited therapeutic efficacy in advanced stages remain major clinical challenges. In this study, a series of novel flavonols were synthesized and evaluated for their cytotoxic activity against human malignant melanoma A375 cells. Among the tested compounds, compound 4j exhibited the most potent inhibitory effect, with an IC ₅₀ value of 25.07 ± 2.24 μM, outperforming 5‐fluorouracil (5‐FU) used as a positive control. Furthermore, Western blot analysis revealed that compound 4j modulated the expression of key apoptotic regulators: it downregulated the anti‐apoptotic protein Bcl‐2, upregulated the pro‐apoptotic protein Bax, and activated caspase‐3, indicating induction of apoptosis via a caspase‐dependent mitochondrial pathway. Molecular docking analysis further showed that the halogenated derivatives exhibited distinct interaction patterns within the Bcl‐2 binding groove, supporting the observed positional structure–activity relationship. These findings demonstrate that compound 4j possesses promising anticancer activity against malignant melanoma cells. They support flavonols as valuable scaffolds for the development of new anti‐melanoma agents, with compound 4j emerging as a particularly compelling lead candidate.

This study investigated the extracts and bioactive constituents of the aerial parts of Polygonum aviculare L., a well-known traditional medicine for inflammation and diuresis, through bioactivity-guided investigation and molecular docking analysis. Solvent extracts demonstrated significant antioxidant, anti-α-glucosidase, and anti-inflammatory activities, supporting their value for further pharmacological investigation. Among the isolated compounds, gallic acid (1), quercetin (3), myricetin (4), avicularin (6), and isorhamnetin (7) exhibited excellent antioxidant activity in the DPPH assay (SC₅₀ ≤ 6.50 μM) and were stronger than the positive control BHT (SC₅₀ = 36.99 μM). Kaempferol (9) (IC₅₀ of 4.50 µM) demonstrated the highest α-glucosidase inhibition, surpassing that of the clinically used acarbose (IC₅₀ = 519.7 µM). Additionally, gallic acid and quercetin demonstrated significantly stronger NO inhibition than apigenin, while kaempferol showed comparable activity (IC₅₀ = 15.06 ± 1.50 μM vs. 16.08 ± 1.86 μM for apigenin). Molecular docking analyses supported favorable interactions between the active compounds and α-glucosidase and inducible nitric oxide synthase (iNOS). Kaempferol reduced the expression of iNOS and COX-2 in LPS-stimulated RAW 264.7 macrophages and was associated with increased KLF4 and Arg-1 expression and decreased phosphorylation of p38 MAPK and IκBα, suggesting a potential role in promoting an anti-inflammatory M2-like macrophage phenotype. Structure–activity relationship analysis indicated that flavonoid aglycones and specific hydroxylation patterns contribute to the observed biological activities. Collectively, these findings identify quercetin and kaempferol as highly active constituents of P. aviculare and support their potential for further pharmacological investigation.

Taraxacum mongolicum, a medicinal and edible plant of the Asteraceae family, is widely consumed in East Asia and contains diverse bioactive compounds. This study systematically evaluated the bioactivities of whole-plant extracts and their components and elucidated the underlying anti-inflammatory mechanisms. Among the extracts, the methanol fraction exhibited the strongest antioxidant activity, effective inhibition of nitric oxide (NO) production, and modulation of inflammation-related proteins. In addition, the extracts demonstrated α-glucosidase and acetylcholinesterase (AChE) inhibitory activities, indicating multifunctional bioactive potential. Activity-guided analysis identified luteolin (2) and apigenin (4) as key active compounds with strong NO inhibitory effects. Western blot analysis revealed that both compounds significantly downregulated NO-related protein expression. Mechanistically, luteolin attenuated inflammatory responses by inhibiting NF-κB signaling and modulating the MAPK pathway, whereas apigenin primarily exerted its effects through NF-κB suppression. Both compounds also promoted M2 macrophage marker expression, suggesting a role in immune regulation. Molecular docking analysis further confirmed stable binding interactions of luteolin and apigenin with iNOS and COX-2. Overall, these findings demonstrate that T. mongolicum possesses antioxidant, enzyme-inhibitory, and anti-inflammatory activities and supports its further investigation as a multifunctional bioactive resource.

Mangosteen (Garcinia mangostana L.) has long been used in traditional Southeast Asian medicine to treat inflammatory-related conditions. In this study, three new compounds, including garcimangone A (1), garcimangone B (2), and the S-form of garcimangone C (3), and 18 known compounds were isolated and investigated for their anti-inflammatory properties and effects on M1- and M2-associated markers. Among the isolated components, γ-mangostin (5), garcinone D (6), morusignin J (15), and fuscaxanthone C (16) showed the most potent NO-inhibitory effects in LPS-stimulated RAW264.7 cells. SAR study revealed that chromeno moiety at C-3,4, oxygen substituents at C-1,3,6,7, and isoprenyl groups at C-2,8 are key structural features that promoted anti-inflammatory activity. Cytokine analysis results indicated that morusignin J (15) and fuscaxanthone C (16) could modulate the production of pro-inflammatory cytokines, such as TNF-α and IL-6, while modulating the anti-inflammatory cytokine IL-10. Western blot results demonstrated that morusignin J (15) modulated the inflammatory response through NF-κB and MAPK signaling and increased the expression of M2-associated markers KLF4 and arginase-1 in LPS-induced RAW264.7 macrophages. Further molecular docking analysis confirmed the high binding affinity of morusignin J (15) with key iNOS residues, such as Gln257, Pro344, Glu371, and Hem901, and the in silico prediction supported its potent oral bioavailability and drug-likeness. These in vitro and in silico findings highlight that pericarps of G. mangostana possess potential as promising natural sources for functional extracts and bioactive constituents for the development of antioxidative and anti-inflammatory candidates, and warrant further in vivo investigation in the future.

Oxidative stress is a key driver of chronic inflammatory diseases. Anodendron affine is a native Formosan plant species in Taiwan that remains largely underexplored phytochemically and bioactivity. To reveal the bioactive constituents and assess its potential as a source of anti-inflammatory antioxidants, we performed bioactivity-guided fractionation and evaluated the inhibition of superoxide anion (O₂^•−) generation in formyl-L-methionyl-L-leucyl-L-phenylalanine-stimulated human neutrophils. Molecular docking simulations were employed to model interactions with Formyl peptide receptor 1 (FPR1) and the Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex, including neutrophil cytosol factor 1 (p47phox) and NADPH oxidase 2 (NOX2), to propose a theoretical mechanism of action. Phytochemical investigation led to the isolation of two new compounds, methyl 4,5-O-diferuloyl-3-methoxyquinate (1) and 16-pregnen-3,12,20-trione (2), together with four known compounds. Notably, 4-hydroxy-3-prenylbenzoic acid (5) exhibited potent inhibitory activity (IC₅₀ = 17.65 ± 0.97 μM), surpassing the activity of the positive control, ibuprofen (IC₅₀ = 27.85 ± 3.56 μM). Docking studies suggested that anodendrosin H (4) and 4-hydroxy-3-prenylbenzoic acid (5) exhibit high predicted binding affinity to p47phox and NOX2. Based on these results, compounds 1, 4, and 5 from A. affine were identified as potential lead candidates for the development of novel anti-inflammatory therapeutics.

Leaves of Eriobotrya japonica have long been utilized in traditional Chinese medicine (TCM) for treating pulmonary inflammation and stomach disorders. This study extends their pharmacological applications by evaluating the antioxidant, anti-α-glucosidase, anti-acetylcholinesterase (AChE), and anti-inflammatory activities of solvent extracts and isolated bioactive components through an integrative approach combining extraction, bioassays, and molecular docking. Solvent extracts prepared with varying polarities exhibited distinct bioactivities, with the 100 °C water and methanol extracts displaying the strongest antioxidant potential. The ethyl acetate extract exhibited potent α-glucosidase inhibition, whereas the n-hexane extract demonstrated significant AChE inhibitory activity. Among the isolated compounds, epicatechin (5) (SC₅₀ = 7.83 ± 0.34 μM) and rutin (6) (SC₅₀ = 6.69 ± 0.25 μM) showed superior ABTS and superoxide scavenging activities, respectively, compared to the positive controls (BHT and cynaroside). Ursolic acid (2) exhibited stronger α-glucosidase inhibition (IC₅₀ = 10.68 ± 0.76 μM) than acarbose (IC₅₀ = 419.93 ± 29.15 μM), while tormentic acid (4) demonstrated superior AChE inhibition compared to chlorogenic acid. Ursolic acid (2) also displayed NO inhibition (IC₅₀ = 20.18 ± 1.46 μM) comparable to quercetin (IC₅₀ = 17.05 ± 1.63 μM), with Western blot analysis confirming its potent iNOS inhibitory activity. Molecular docking further supported these findings, revealing that ursolic acid (2) exhibited stronger binding affinity to α-glucosidase (−8.7 kcal/mol) than acarbose (−5.1 kcal/mol), tormentic acid (4) displayed higher binding energy to AChE (−8.8 kcal/mol) compared to chlorogenic acid (−7.8 kcal/mol), and ursolic acid (2) (−7.5 kcal/mol) showed a binding affinity to iNOS similar to that of quercetin (−7.7 kcal/mol). These results highlight the strong potential of E. japonica leaf extracts and bioactive compounds as natural antioxidants, enzyme inhibitors, and anti-inflammatory agents, supporting their development as dietary supplements or therapeutic candidates for managing oxidative stress, hyperglycemia, neurodegenerative diseases, and inflammatory disorders.