The enzyme tyrosinase plays a key role in the early stages of melanin biosynthesis. This study evaluated the inhibitory activity of anthocyanidin (1) and anthocyanins (2–6) on the catalytic reaction. Of the six derivatives examined, 1–3 showed inhibitory activity with IC50 values of 3.7 ± 0.1, 10.3 ± 1.0, and 41.3 ± 3.2 μM, respectively. Based on enzyme kinetics, 1–3 were confirmed to be competitive inhibitors with Ki values of 2.8, 9.0, and 51.9 μM, respectively. Molecular docking analysis revealed the formation of a binary encounter complex between 1–3 and the tyrosinase catalytic site. Luteolinidin (1) and petunidin 3-O-glucoside (2) may serve as tyrosinase inhibitors to block melanin production.

Phloroglucinols—one of the major secondary metabolites in Dryopteris crassirhizoma—exhibit various pharmacological effects, such as antiviral, antioxidant, and antidiabetic activities. This study evaluated 30 phloroglucinols isolated from the rhizomes of D. crassirhizoma for their inhibitory activity on β-glucuronidase via in vitro assays. Among them, dimeric phloroglucinols 13–15 moderately inhibited β-glucuronidase, and trimeric phloroglucinols 26–28 showed strong inhibitory effects, with IC50 values ranging from 5.6 to 8.0 μM. Enzyme kinetic analysis confirmed all six active compounds to be in a competitive mode of inhibition. Molecular docking simulations revealed the key binding interactions with the active site of β-glucuronidase protein and the binding mechanisms of these active metabolites. Our results suggest that the rhizomes of D. crassirhizoma and trimeric compounds 26–28 may serve as potential candidates for discovering and developing new β-glucuronidase inhibitors.

Cinnamomum cassia L. is used as a spice and flavoring agent as well as a traditional medicine worldwide. Diterpenoids, a class of compounds present in C. cassia, have various pharmacological effects, such as anti-inflammatory, antitumor, and antibacterial activities; however, there are insufficient studies on the metabolism of diterpenoids. In this study, the metabolism of seven diterpenoids, namely, anhydrocinnzeylanol, anhydrocinnzeylanine (AHC), cinncassiol A, cinncassiol B, cinnzeylanol, cinnzeylanone, and cinnzeylanine, obtained from the bark of C. cassia was studied in human liver microsomes (HLMs). All studied diterpenoids, except for AHC, exhibited strong metabolic stability; however, AHC was rapidly metabolized to 3% in HLMs in the presence of β-NADPH. Using a high-resolution quadrupole-orbitrap mass spectrometer, 20 metabolites were identified as dehydrogenated metabolites (M1–M3), dehydrogenated and oxidated metabolites (M4–M10), mono-oxidated metabolites (M11–M13), or dioxidated metabolites (M14–M20). In addition, CYP isoforms involved in AHC metabolism were determined by profiling metabolites produced after incubation in 11 recombinant cDNA-expressed CYP isoforms. Thus, the diterpenoid compound AHC was identified in a metabolic pathway involving CYP3A4 in HLMs.

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Dryopteris crassirhizoma Nakai is a plant with significant medicinal properties, such as anticancer, antioxidant, and anti-inflammatory activities, making it an attractive research target. Our study describes the isolation of major metabolites from D. crassirhizoma, and their inhibitory activities on α-glucosidase were evaluated for the first time. The results revealed that nortrisflavaspidic acid ABB (2) is the most potent α-glucosidase inhibitor, with an IC50 of 34.0 ± 0.14 μM. In addition, artificial neural network (ANN) and response surface methodology (RSM) were used in this study to optimize the extraction conditions and evaluate the independent and interactive effects of ultrasonic-assisted extraction parameters. The optimal extraction conditions are extraction time of 103.03 min, sonication power of 342.69 W, and solvent-to-material ratio of 94.00 mL/g. The agreement between the predicted models of ANN and RSM and the experimental values was notably high, with a percentage of 97.51% and 97.15%, respectively, indicating that both models have the potential to be utilized for optimizing the industrial extraction process of active metabolites from D. crassirhizoma. Our results could provide relevant information for producing high-quality extracts from D. crassirhizoma for functional foods, nutraceuticals, and pharmaceutical industries.