Affiliation:
1. Phenikaa University Nano Institute (PHENA), Phenikaa University, Yen Nghia, Ha Dong, Hanoi 12116, Vietnam
2. School of Medicine & Pharmacy, The University of Danang, Hoa Quy, Ngu Hanh Son, Da Nang City 550000, Vietnam
3. Institute of Chemistry, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Cau Giay, Hanoi 122100, Vietnam
4. Tay Nguyen University, 567 Le Duan, Buon Ma Thuot, Dak Lak 630000, Vietnam
Abstract
Objective: The Knema genus contains various naturally occurring secondary metabolites with pharmacological potential, including antitumor, neuroprotective, antidiabetic, and hepatoprotective activities. This study focuses on identifying nitric oxide production inhibitors from Vietnamese Knema globularia. Methods: The secondary metabolites were isolated using several chromatographic techniques. Their chemical structures were determined using nuclear magnetic resonance (NMR) spectroscopy and compared with published literature. The anti-inflammatory effect was evaluated using the Griess assay, and protein interactions were investigated through docking studies. Results: Based on their anti-inflammatory activity, six compounds (1-6) were isolated from Vietnamese K. globularia. These compounds were identified as lupeol (1), formononetin (2), isoliquiritigenin (3), 2-[4-(3-hydroxypropyl)-2-methoxyphenoxy]propane-1,3-diol (4), (+)-catechin (5), and (−)- epicatechin (6). For the first time, compounds 1, 3, and 4 were reported from Vietnamese K. globularia. All isolated compounds were tested against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in macrophage RAW264.7 cells to assess their anti-inflammatory potential. Compound 5 exhibited the highest inhibitory activity, with an IC50 value of 5.61 μM, followed by compounds 3 and 6, with IC50 values of 6.76 and 11.52 μM, respectively. However, compounds 1, 2, and 4 showed inactivity with IC50 values exceeding 30 μM. Molecular docking was then employed to investigate the affinity and interactions between compounds 3, 5, and 6 and proteins involved in inflammation, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and interleukin-8 (IL-8), along with ADMET (absorption, distribution, metabolism, excretion, and toxicity) predictions. Conclusion: These findings suggest that the active constituents derived from Vietnamese K. globularia have the potential as anti-inflammatory agents worthy of further exploration and development.