The larva of Allomyrina dichotoma (family Scarabaeidae) is an edible insect that is registered in the Korean Food Standards Codex as a food resource. The chemical study on the larvae of A. dichotoma resulted in the isolation of three new tetrahydroquinolines, allomyrinaines A–C (1–3), one new dopamine derivative, allomyrinamide A (4), and four known compounds (5–8). The structures were elucidated on the basis of 1D and 2D nuclear magnetic resonance (NMR) and MS spectroscopic data analysis. Allomyrinaines A–C (1–3) possessed three stereogenic centers at C-2, C-3, and C-4, whose relative configurations were determined by analyses of the coupling constants and the nuclear Overhauser enhancement spectroscopy (NOESY) data, as well as DP4+ calculation. The anti-inflammatory effects of compounds 1–4 were evaluated in human endothelial cells. Allomyrinaines A–C (1–3) could stabilize vascular barrier integrity on lipopolysaccharide (LPS)-induced vascular inflammation via inhibition of the nuclear factor-κB (NF-κB) pathway. The physiologically relevant concentration was confirmed by Q-TOF-MS-based quantitative analysis on allomyrinaines A–C in crude extract. This study suggests that allomyrinaines A–C (1–3) are bioactive constituents of A. dichotoma to treat vascular inflammatory disorder.

In our previous study, Hwang-Ryun-Hae-Dok-Tang, which contains berberine (BBR) as a main active ingredient, inhibited cytochrome P450 (CYP) 2D6 in a quasi-irreversible manner. However, no information is available on the detailed mechanism of BBR-induced CYP2D6 inhibition. Thus, the present study aimed to characterize the inhibition mode and kinetics of BBR and its analogues against CYP2D6 using pooled human liver microsomes (HLM). BBR exhibited selective quasi-irreversible inhibition of CYP2D6 with inactivation rate constant (k_inact) of 0.025 min⁻¹, inhibition constant (K_I) of 4.29 µM, and k_inact/K_I of 5.83 mL/min/µmol. In pooled HLM, BBR was metabolized to thalifendine (TFD), demethyleneberberine (DMB), M1 (proposed as demethylene-TFD), and to a lesser extent berberrubine (BRB), showing moderate metabolic stability with a half-life of 35.4 min and a microsomal intrinsic clearance of 7.82 µL/min/mg protein. However, unlike BBR, those metabolites (i.e., TFD, DMB, and BRB) were neither selective nor potent inhibitors of CYP2D6, based on comparison of half-maximal inhibitory concentration (IC₅₀). Notably, TFD, but not DMB, exhibited metabolism-dependent CYP2D6 inhibition as in the case of BBR, which suggests that methylenedioxybenzene moiety of BBR may play a critical role in the quasi-irreversible inhibition. Moreover, the metabolic clearance of nebivolol (β-blocker; CYP2D6 substrate) was reduced in the presence of BBR. The present results warrant further evaluation of BBR–drug interactions in clinical situations.

Insects are some of the most diverse organisms on the planet, and have potential value as food or medicine. Here, we investigated the photoprotective properties of insect extracts using hairless mice. The alleviating wrinkle formation effects of insect extracts were evaluated by histological skin analysis to determine epidermal thickness and identify collagen fiber damage. Moreover, we investigated the ability of the insect extracts to alleviate UVB-induced changes to matrix metalloproteinases (MMPs), oxidative damage, the mitogen-activated protein kinases (MAPKs) signaling pathway, and the expression of pro-inflammatory cytokines. Insect extracts reduced UVB-induced skin winkles, epidermal thickening, and collagen breakdown, and alleviated the epidermal barrier dysfunction induced by UVB, including the increased loss of transepidermal water. Moreover, the expression of skin hydration-related markers such as hyaluronic acid, transforming growth factor-beta (TGF-β), and procollagen was upregulated in the group treated with insect extracts compared to the vehicle-treated group after ultraviolet B (UVB) exposure. UVB irradiation also upregulated the expression of MMPs, the phosphorylation of MAPKs, and pro-inflammatory cytokines, which were all attenuated by the oral administration of insect extracts. These results indicate the photoaging protection effect of insect extracts and the underlying mechanism, demonstrating the potential for clinical development.

An ilimquinone (IQ) mixture isolated from Hippiospongia metachromia, consisting of IQ and epi-ilimaquinone (epi-IQ), exerts anti-HIV, anti-microbial, anti-inflammatory, and anti-cancer effects. An HPLC-MS/MS method was developed for simultaneous determination of the two epimers in rat plasma, separating them using a biphenyl column. Ascorbic acid is added during the sample preparation to ensure the stability of both isomers. The plasma concentrations of the isomers were monitored following intravenous and oral administration of the IQ mixture in rats as well as the individual epimers that were separately orally administered. Compare to IQ, epi-IQ was much more stable in rat plasma, likely due to its configurations of decalin. Both substances decayed in more than bi-exponential pattern, with an elimination rate constant of 1.2 h⁻¹ for IQ and 1.7 h⁻¹ for epi-IQ. The epi-IQ was distributed more widely than IQ by about two-fold. Consequently, the clearance of epi-IQ was greater than that of IQ by about three-fold. The oral absolute bioavailability for IQ was 38%, and, that for epi-IQ, was 13%. Although the systemic exposure of IQ was greater than that of epi-IQ by ~8.7-fold, the clearance of each isomer was similar when administered either orally or intravenously, when normalized for bioavailability. The stereo-specific behavior of the isomers appears to originate from differences in both their tissue distribution and gastrointestinal permeability.

With the recent development of chemical analysis technology, attention has been placed on natural light-sensitive compounds that exhibit photoreactivity to expand the structural diversity of natural product chemistry. Photochemical reactions that proceed via a free radical mechanism could be used to modulate the radical-scavenging ability of natural products as well as involve structural change. As the health benefits of radicals are also presented, there is a need for a controllable radical scavenging method for topical and selective application. In this study, we developed a novel acquisition and processing method to identify light-controlled radical scavengers in plant extracts and evaluate their antioxidant activity under light irradiation based on in situ UV-LED NMR spectroscopy. Using the developed method, licochalcones A and B, in which the trans and cis isomers undergo reversible photoisomerization, were selectively identified from licorice root extract, and their light-induced free radical scavenging activity was confirmed.

Sedum middendorffianum Maxim (SMM) is a Korean endemic plant belonging to the Crassulaceae family. This study aimed to investigate the antitumor effects of the SMM extract on human ovarian cancer cells. Among five endemic plants grown in Korea, the SMM extract showed the most potent cytotoxicity in ovarian cancer cells and had little effect on normal ovarian surface epithelial cells. Furthermore, we revealed that the SMM extract dose-dependently induced apoptosis in human ovarian cancer A2780 and SKOV3 cells. The SMM extract markedly stimulated the activation of caspase-3/8, while the broad-spectrum caspase inhibitor and caspase-8 selective inhibitor significantly reversed SMM extract-induced apoptosis. In addition, the SMM extract significantly inhibited cell invasion and the expression levels of matrix metalloproteinase (MMP)-2 and MMP-9 in ovarian cancer cells. Notably, the SMM extract increased the generation of intracellular ROS, and pretreatment with antioxidant N-acetyl-L-cysteine (NAC) significantly suppressed SMM-induced cytotoxicity and anti-invasive activity. Moreover, NAC treatment reversed the SMM-induced inhibition of MMP-2/9 expression. Taken together, these data suggest that the SMM extract induces caspase-dependent apoptotic cell death and inhibits MMP-dependent invasion via ROS regulation.