Enzyme Kinetics and Molecular Docking Investigation of Acetylcholinesterase and Butyrylcholinesterase Inhibitors from the Marine Alga Ecklonia cava

Ecklonia cava Kjellman (Laminareaceae) grows along the coast of Jeju Island, Korea, and is wellknown in Korea for its use as a food ingredient, animal feed, and medicine. This seaweed contains phlorotannins, polymerized units of phloroglucinol, a term derived from phloroglucinol, the building block of these complex molecules, which is also the common name for these compounds. Phlorotannins are secondary metabolites that hold significance for human health due to their various beneficial properties, including antioxidant, anti-cancer, anti-allergy, and anti-HIV activities. In this study, 10 phlorotannins (1–10) were isolated from an 80% EtOH extract of E. cava. The structures of these compounds were determined through spectroscopic analysis and comparison with the literature. The inhibitory effects of compounds 1–10 on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) were investigated. In an AChE inhibition assay, compounds 1, 2, 4, and 6–10 had IC50 values ranging from 0.9 ± 0.8 to 66.5 ± 0.4 µM; compounds 4, 6, and 9 had potent BuChE inhibitory effects, with IC50 values ranging from 1.4 ± 3.8 to 25.2 ± 0.1 µM. Furthermore, enzyme kinetics and molecular docking simulations were conducted to gain insights into the inhibition mode, binding mechanism, and crucial interactions between these active compounds and the target enzyme. This indicates that E. cava is a potentially valuable natural source of AChE and BuChE inhibitors.

Chemicals from Cimicifuga dahurica and Their Inhibitory Effects on Pro-inflammatory Cytokine Production by LPS-stimulated Bone Marrow-derived Dendritic Cells

Inflammation is a biological response caused by overactivation of the immune system and is controlled by immune cells via a variety of cytokines. The overproduction of pro-inflammatory cytokines enhances abnormal host immunity, resulting in diseases such as rheumatoid arthritis, cardiovascular disease, Alzheimer's disease, and cancer. Inhibiting the production of pro-inflammatory cytokines such as interleukin (IL)-12p40, IL-6, and tumor necrosis factor (TNF)-α might be one way to treat these conditions. Here, we investigated the anti-inflammatory activity of compounds isolated from Cimicifuga dahurica (Turcz.) Maxim., which is traditionally used as an antipyretic and analgesic in Korea. In primary cell culture assays, 12 compounds were found to inhibit the production of pro-inflammatory cytokines (IL-12p40, IL-6, and TNF-α) in vitro in bone marrow-derived dendritic cells stimulated with LPS.

Chemical Components from the Stems of Pueraria lobata and Their Tyrosinase Inhibitory Activity

Phytochemical investigation of the stems of Pueraria lobata (Wild) Ohwi (Leguminosae), led to the isolation of eighteen known compounds: β-amyrone (1), (+)-pinoresinol (2), (+)-syringaresinol (3) (+)-syringaresinol-O-β-D-glucoside (4), (+)-lariciresinol (5), (-)-tuberosin (6), naringenin (7), liquiritigenin (8), isoliquiritigenin (9) genistein (10), daidzein (11) daidzin (12) daidzein 4',7-diglucoside (13) 2,4,4'-trihydroxy deoxybenzoin (14), S-(+)-1-hydroxy-3-(4-hydroxyphenyl)-1-(4-hydroxy-2-methoxy-phenyl)propan-2-one (15), methyl 2-O-β-D-glucopyranosylbenzoate (16), pyromeconic acid 3-O-β-D-glucopyranoside 6'-(O-4''-hydroxy-3-methoxybenzoate) (17), and allantion (18). The chemical structures of these compounds were elucidated from spectroscopic data and by comparison of those data with previously published results. The effects of isolated compounds on mushroom tyrosinase enzymatic activity were screened. The results indicated that, chloroform extract of P. lobata stems turned out to be having tyrosinase inhibitory effect, and only compounds 5, 8, 9, and 11 showed enzyme inhibitory activity, with IC₅₀ values of 21.49 ± 4.44, 25.24 ± 6.79, 4.85 ± 2.29, and 17.50 ± 1.29 µM, respectively, in comparison with these of positive control, kojic acid (IC₅₀ 12.28 ± 2.72 µM). The results suggest that P. lobata stems extract as well as its chemical components may represent as potential candidates for tyrosinase inhibitors.

Soluble Epoxide Hydrolase Inhibitory Activity from Euphorbia supina Rafin

In our search for natural soluble epoxide hydrolase (sEH) inhibitors from plants, an extract of the dried whole plants of Euphorbia supina Rafin was found to significantly inhibit sEH activity in vitro. Phytochemical investigation of E. supina resulted in isolation of 17 compounds (1 - 17), including triterpenes (1 - 4), phenolic compounds (5 - 8), and flavonoid derivatives (9 - 17). The structures of the isolated compounds were established mainly by extensive analysis of the 1D and 2D NMR, and MS data. All of the isolated compounds were evaluated for their sEH inhibitory activity. Among the isolated phenolic compounds, 8 was identified as a significant inhibitor of sEH, with an IC50 value of 15.4 +/- 1.3 microM. Additionally, a kinetic analysis of isolated compounds (2, 5, 8 - 11, 13, and 17) indicated that the inhibitory effects of flavonoid derivatives 10 and 11 were of mixed-type, with inhibitory constants (Ki) ranging from 3.6 +/- 0.8 to 21.8 +/- 1.0 microM, whereas compounds 2, 5, 8, 9, 13, and 17 were non-competitive inhibitors with inhibition Ki values ranging from 3.3 +/- 0.2 to 39.5 +/- 0.0 microM.

Anti-inflammatory Triterpenes and Glyceryl Glycosides from Kandelia candel (L.) Druce

Phytochemical investigation of Kandelia candel resulted in the isolation of six triterpenes (1 - 5) and two glyceryl glycosides (6 and 7) and their structures were determined by comparing the spectroscopic data with those of reported values. In present study, we described the inhibitory effects of fractions and isolated compounds from K. candel on pro-inflammatory cytokines (IL-12 p40, IL-6, and TNF-alpha) production in lipopolysaccharide (LPS) stimulated bone marrow-derived dendritic cells (BMDCs). Results indicated that compounds 3, 6, and 7 showed potent inhibition on IL-6 production (IC50 values at less than 0.5 microM, respectively). Meanwhile, compounds 6 and 7 exhibited strong inhibitory effects on the production of TNF-alpha (IC50 values of 1.7 +/- 0.1 and 5.5 +/- 0.2 microM). Compounds 1 and 3 were also showed the inhibitory effects on IL-12 p40 production (IC50 values of 8.9 +/- 0.4 and 3.3 +/- 0.1 microM, respectively).

A Case of Lymphedema Associated with Psoriasis / 대한내과학회지

Lymphedema is a rare but known complication of psoriatic arthritis and other inflammatory arthritides. Only a few cases associated with psoriatic arthritis have been reported, but none showed psoriasis was the sole factor. The precise etiology is, as yet, unknown, but many different mechanisms are likely to cause lymphedema in psoriatic arthritis, such as lymphatic vascular damage and perilymphatic accumulation of inflammatory material. Various immunosuppressive drugs have been assessed in treating this condition. Here, we report the case of an 85-year-old man with psoriasis presenting with a rare complication of bilateral lymphedema in the lower extremities. Lymphedema as well as psoriasis improved with cyclosporine.

A Case of Three Different Synchronous and Metachronous Primary Lung Cancers / 대한내과학회지

Multiple primary lung cancers are characterized as either synchronous (detected or resected simultaneously) or metachronous (defined by a time interval between the detection of a subsequent primary lesion). The diagnosis of multiple primary lung cancers requires the temporal, histologic, and anatomic classification of tumors or simultaneous detection of two tumors. The incidence of multiple primary lung cancers has been increasing recently due to the widespread use of imaging modalities and life extension. Here, we report a 65-year-old male patient with multiple primary lung cancers comprising three different cell types (adenocarcinoma, squamous cell carcinoma, and small cell carcinoma).