Four new compounds, acacetin 8-C-[β-D-apiofuranosyl-(1 → 2)-β-D-glucopyranoside] (1), 7-methoxyacacetin 8-C-[β-D-apiofuranosyl-(1 → 3)-β-D-glucopyranoside] (2), 7-methoxyacacetin 8-C-[β-D-glucopyranosyl-(1 → 2)-β-D-glucopyranoside] (3), and 4‴-O-acetylacacetin 8-C-[α-L-rhamnopyranosyl-(1 → 2)-β-D-glucopyranoside] (4), along with ten known compounds (5–14), were isolated from Piper aduncum leaves. The effects of these compounds on lipopolysaccharide-induced expression of the proinflammatory cytokines IL-12 p40, IL-6, and TNF-α in bone marrow-derived dendritic cells were evaluated. Compounds 2, 3, 6, 8, 9, and 11–13 inhibited the production of both IL-12 p40 and IL-6, with IC₅₀ values ranging from 0.35 ± 0.01 to 1.40 ± 0.04 µM and 1.22 ± 0.02 to 3.79 ± 0.10 µM, respectively. Compounds 5 and 10 only showed strong inhibition effects on the production of IL-12 p40, with IC₅₀ values of 2.76 ± 0.08 and 0.39 ± 0.05 µM, respectively. However, all compounds showed weak activity or no activity on TNF-α production at the tested concentrations. ^* These authors contributed equally to this work.

The Fabaceae family, particularly genus Erythrina, is renowned for significant medicinal properties. These plants have been used as natural remedies to address various health issues and are rich in flavonoids. Therefore, this review aimed to provide a comprehensive overview of antibacterial activity, structure-activity relationship, especially against drug-resistance Staphylococcus aureus, and mode of action for flavonoids isolated from Erythrina. Data were collected from reputable electronic scholarly resources focusing on publications from 2000 to 2022. The results showed that the evaluated flavonoids include 31 % pterocarpans, 22 % flavanones, 20 % isoflavanones, 18 % isoflavones, 4 % isoflavans, 3 % isoflav-3-enes, 1 % 3-arylcoumarins, and 1 % coumestans. Most of these compounds in Erythrina plants were extracted from the roots and stem bark. Among these group of flavonoids, pterocarpan stands out as the most active class against S. aureus. Structure-activity relationship study emphasized pivotal contribution of the prenyl functional group to enhance antibacterial activity of flavonoids. Increasing the number of prenyl groups enhanced antibacterial effectiveness while modifying the group reduced this activity. The proposed antibacterial mechanisms of these flavonoids include the suppression of nucleic acid synthesis, disruption of cytoplasmic membrane function, and modulation of energy metabolism. Among the potent antibacterial flavonoids from genus Erythrina, compound 3,9-dihyroxy-10-γ,γ-dimethylallyl-6a,11a-dehydropterocarpan was found as the most potent against Methicillin-Resistant Staphylococcus aureus (MRSA) through the inhibition of nucleic acid synthesis. Other common flavonoids such as genistein, daidzein, apigenin, and luteolin exert antibacterial activity through the inhibition of ATP synthase.

Flavonoids are a secondary metabolite group with various bioactivities, such as antioxidants. They are rich in the genus Erythrina, such as Erythrina crista-galli. This research aims to isolate and characterize flavonoids from the twigs of E. crista-galli and determine their antioxidant properties through in silico and in vitro assays. The ethyl acetate extract of E. crista-galli twigs were separated by column chromatography and characterized using spectroscopic methods. Density functional theory (DFT) calculations were performed on the isolated flavonoids and the reference compounds (ascorbic acid and quercetin) to obtain global descriptive parameters and a donor–acceptor map (DAM). We successfully isolated lupinifolin (1) and citflavanone (2) for the first time from E. crista-galli, along with lonchocarpol A (3), which has been discovered previously. The DAM suggests that these flavanones are good antiradicals with effective electron donors. However, they tend to be electron acceptors in methanol. The frontier molecular orbital analysis implies that lupinifolin (1) is a better antiradical than the other flavanones. The DPPH assays show that lupinifolin (1) has the highest antioxidant (antiradical) activity, with an IC₅₀ value of 128.64 ppm. The in silico studies showed similar trends to the in vitro assays using the DPPH method.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the coronavirus disease 2019 (COVID-19) pandemic with more than 6 million deaths worldwide. Flavonoids from the genus Erythrina may inhibit SARS-CoV-2, targeting 3C-like protease (3CLpro), an enzyme essential in the virus’s growth. Hence, this study aimed to screen 378 flavonoids from Erythrina against 3CLpro, using molecular docking, Lipinski’s rule of five, and in silico absorption, distribution, metabolism, excretion, and toxicity. These virtual screening campaigns suggest that 108 flavonoids have stronger binding energy values (−13.23 to −10.20 kcal/mol) than the N3 inhibitor (−10.14 kcal/mol) as the reference ligand. Some 33 of these flavonoids may be hepatoxicity- and mutagenicity-free. They are also non-hERG I and II inhibitors. Two of them, orientanol E (171) and erycaffra F (57), have binding energy values in the top 10 hits and good absorption profiles, despite their poor distribution properties. They may have a high bioavailability in the body and be excreted from the body through feces. Conducted molecular dynamics simulations also support orientanol E (171) and erycaffra F (57) as 3CLpro inhibitor candidates. Our study suggests that flavonoids from Erythrina have the potential as 3CLpro inhibitors, which help guide further in vitro and in vivo experiments in COVID-19 drug development.

Two new dammarane-type triterpenoid fatty acid ester derivatives, 3β-oleate-20S-hydroxydammar-24-en (1) and 3β-oleate-20S,24S-epoxy-25-hydroxydammarane (2) with a known dammarane-type triterpenoid compound, such as 20S-hydroxydammar-24-en-3-on (3), were isolated from the stem bark of Aglaiaelliptica (C.DC.) Blume. The chemical structures were determined by spectroscopic methods, including FTIR, NMR (one and two-dimensional), and HRESITOF-MS analysis, as well as chemical derivatization and comparison with previous literature. Furthermore, the synthetic analog resulting from transesterification of 1 and 2 also obtained 3β,20S-dihydroxy-dammar-24-en (4) and 20S,24S-epoxy-3β,25-dihydroxydammarane (5), respectively. The cytotoxic effect of all isolated and synthetic analog compounds was evaluated using PrestoBlue reagent against MCF-7 breast cancer cell and B16-F10 melanoma cell lines. The 20S-hydroxydammar-24-en-3-on (3) showed the strongest activity against MCF-7 breast cancer and B16-F10 melanoma cell, indicating that the ketone group at C-3 in 3 plays an essential role in the cytotoxicity of dammarane-type triterpenoid. On the other hand, compounds 1 and 2 had very weak cytotoxic activity against the two cell lines, indicating the presence of fatty acid, significantly decreasing cytotoxic activity. This showed the significance of the discovery to investigate the essential structural feature in dammarane-type triterpenoid, specifically for the future development of anticancer drugs.