Wei Li

Daphne genkwa is a deciduous shrub distributed throughout East Asia and has long been used in traditional medicine. Previous phytochemical investigations have shown that D. genkwa is a rich source of bioactive daphnane diterpenoids. In the present study, a comprehensive structural characterization of daphnane diterpenoids in the flowers of D. genkwa was carried out using an LC-MS/MS-based approach. This approach integrated automated annotation program, manual inspection of MS/MS fragmentation pathways, and phytochemical investigation. It led to the structural characterization of 37 daphnane diterpenoids, including nine previously undescribed compounds. These findings demonstrated that D. genkwa flowers contain structurally diverse daphnane diterpenoids, mainly daphnane orthoesters and polyhydroxy daphnanes. Moreover, the diagnostic MS/MS fragmentation and retention time features established in this study provide reliable LC-MS/MS-based criteria for discriminating closely related structural isomers of polyhydroxy daphnanes that differ in their B-ring structures and acylation patterns.

The first total synthesis of the revised structures of urupocidins A and B was achieved based on the Pd(II)-catalyzed cyclization-carbonylation-cyclization cascade of optically active propargyl guanidine. The absolute configurations of natural urupocidins A and B were revised to the (8R,10S,15S) configuration by total synthesis.

Prolonged exposure to ultraviolet (UV) radiation in sunlight is a major extrinsic factor that impairs skin function and accelerates photoaging. In this study, a murine model of ultraviolet B (UVB)-induced photoaging exhibited characteristic symptoms, including skin roughness, erythema, hyperpigmentation, and increased wrinkle formation. Epicatechin gallate (ECG), a natural flavonoid, has demonstrated potential skin-protective properties. However, its specific effects and mechanisms against UVB-induced photoaging are not fully understood. Here, we investigated the protective role and underlying mechanism of ECG against UVB-induced damage in human epidermal keratinocytes (HaCaT cells). Using network pharmacology, p38 mitogen-activated protein kinase (p38 MAPK), specifically the p38α isoform, was identified as a key potential target of ECG. Our experimental results confirmed that ECG significantly attenuated UVB-induced photoaging. Mechanistically, ECG treatment effectively suppressed UVB-triggered phosphorylation of p38α, promoted autophagic flux (as evidenced by increased LC3B conversion and decreased p62 levels), and substantially reduced intracellular reactive oxygen species (ROS) accumulation. Consequently, ECG mitigated mitochondrial dysfunction, restored normal cell cycle progression, and decreased the expression of senescence-associated markers (p53, p16, p21) and inflammatory cytokines (IL6, TNF-α). In summary, our findings demonstrate that ECG protects against UVB-induced photoaging primarily by inhibiting p38α activation, thereby enhancing autophagy and alleviating oxidative stress. This study positions ECG as a promising therapeutic candidate for preventing and treating skin photoaging.

This paper reviews the structure, biosynthesis, synthesis, and activity of corynanthe alkaloids with the aim of providing new perspectives and discoveries for researchers in this field.

Ultraviolet radiation B (UVB) radiation can induce oxidative stress, DNA damage, and inflammation, leading to skin wrinkling, impaired barrier function, and an increased risk of cancer. Addressing or preventing photoaging may provide a promising therapeutic avenue for these conditions. Hyperoside (HY), a compound abundantly found in medicinal plants including Hypericum perforatum and Crataegus, has been reported to have various pharmacological activities such as antioxidant, anti-inflammatory, cytoprotective, and antitumor effects; however, there are currently no studies systematically exploring the potential and mechanisms of HY in alleviating skin damage caused by ultraviolet (UV) rays. We investigated the inhibitory effects of HY on oxidative stress responses, reducing keratinocyte aging. HY can also exert these effects by mediating the PI3K/AKT/mTOR signaling pathway through miR-361-5p, maintaining mitochondrial dynamic stability, alleviating mitochondrial dysfunction, and enhancing mitophagy. Additionally, in vivo, HY was able to significantly improve skin wrinkles in mice while reducing changes in thickness and aging of the epidermis and dermis.

Daphne odora is an evergreen shrub belonging to the Thymelaeaceae family that is widely cultivated as an ornamental garden plant. Its roots, leaves, and flowers have traditionally been used in Chinese medicine to treat pain, skin diseases, and rheumatism. While previous phytochemical studies have reported the presence of phenols, coumarins, biflavonoids, lignans, and daphnane diterpenoids in D. odora, its flowers remain largely unexplored. In the present study, the first comprehensive investigation of daphnane diterpenoids contained in the flower buds and blooming flowers of D. odora was conducted using ultra-high-performance liquid chromatography coupled with Q-Exactive-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Exactive-Orbitrap MS). A total of 30 daphnane diterpenoids were identified, including 12 previously unreported compounds, through detailed analysis of their retention times and MS/MS fragmentation patterns. Comparative profiling revealed that flower buds contained a higher abundance and greater diversity of daphnane diterpenoids than flowers. Furthermore, LC–MS-guided isolation enabled the purification of a novel compound, daphneodorin I (16), and its structure was elucidated through extensive physicochemical and spectroscopic analyses. Compound 16 represents the first daphnane diterpenoid with a Z-configured phenolic acyl moiety isolated from plants of the Thymelaeaceae family.

Complex natural products (CNPs) feature polycyclic structures, multiple consecutive chiral centers, and nonrepetitive structural units. Given their complexity, the structural annotation of CNPs remains a major bottleneck. Here, we introduce the modular fragmentation–based structural assembly (MFSA) strategy for the target CNP structural annotation. The MFSA strategy disassembled the structure based on fragmentation patterns, recognized targets via a pseudo-library, and reassembled the structure using characteristic ions and neutral losses. As a proof of concept, we focused on daphnane-type diterpenoids, a kind of specific bioactive CNP from Thymelaeaceae plants. Furthermore, we present a user-friendly application named CNPs-MFSA coded in Python. Using an in-house daphnane library, CNPs-MFSA outperformed SIRIUS, MS-FINDER, and MetFrag in Top-1 annotation accuracy. By applying CNPs-MFSA to 56 Thymelaeaceae plants, 204 high-confidence daphnanes within 822 annotated results, including 105 previously unreported compounds were found. Aconitine, paclitaxel, and obakunone analogs were incorporated as additional target CNP classes to illustrate the extension workflow.

Cimicifuga heracleifolia is a perennial herb that belongs to the Ranunculaceae family. Its dried rhizomes are a source of Cimicifugae Rhizoma, a traditional Chinese medicine used for detoxification, the treatment of febrile diseases, and the prevention of pathogenic invasion. In the present study, a phytochemical investigation of the rhizomes of C. heracleifolia resulted in the isolation of three indole alkaloids (1–3) and seven phenolic amides (4–10), including three new compounds, 6-methoxy-3-(3-methyl-1-oxo-2-butenyl) 1H indole (1), (3R)-1-(β-d-glucopyranosyl)-3-hydroxy-3-(3-methylbutyl)-2-oxindole (3), and N-acetyldopamine-3-O-β-d-allopyranoside (4). Their structures were elucidated using extensive physicochemical and spectroscopic analyses. All the isolated compounds were evaluated for their inhibitory activity against soluble epoxide hydrolase (sEH). The results showed that cimicifugamide A (6) exhibited the most potent inhibitory activity, with an IC₅₀ value of 8.74 μM, followed by cimicifugamide (7), demethoxycimicifugamide (8), and N-trans-feruloyl tyramine (10), with IC₅₀ values ranging from 15.63 to 20.58 μM. Kinetic analysis revealed that compound 6 inhibited sEH through a non-competitive mechanism.