The ethanol extract of the Gentiana olivieri Griseb plant was subjected to an investigation to ascertain the presence of its iridoid constituents. By means of HPLC and TLC monitoring, a total of thirteen previously unreported seco-iridoid glucosides olivierisecoside A-M, as well as seven known seco-iridoid glycosides and one known iridoid glycoside were isolated. Their structures were elucidated by a comprehensive spectroscopic data analysis and ECD calculations. The absolute configuration of olivierisecoside D was further confirmed through single-crystal X-ray diffraction analysis. All the identified compounds were characterized as aromatic conjugated seco-iridoid glucosides, with olivierisecoside F-I representing a particularly rare subtype known as the morroniside type seco-iridoids. In vitro testing of the isolated compounds revealed their potential anti-inflammatory and hepatoprotective effects. The results showed olivieroside B and 6'-gentisoyl-8-epi-kingiside have good anti-inflammatory activities in LPS induced RAW264.7 cells. Additionally, olivierisecoside M exhibited some improvements in PA-induced L02 and HepG2 cells damage, known compound loganin showed slight hepatoprotective effect in PA-induced HepG2 cells damage.

Fifteen undescribed diterpenoid quinones salviamilthone A-O (1-15), together with three known diterpenoid quinones (16-18), were isolated from the roots of Salvia miltiorrhiza Bunge. Their structures were elucidated using 1D and 2D NMR data, while the relative and absolute configurations were confirmed by NOESY correlations and comparison between experimental and calculated ECD spectra. In the evaluation of bioactivities, salviamilthone J (10), salviamone (18) (10 μM) significantly increased cell viability and decreased the expression of IL-1β in lipopolysaccharide-induced BEAS-2B cells. These data provide the molecular justification for the usage of Salvia miltiorrhiza in treating acute lung injury.

Silymarin, a mixture of diastereomeric and regioisomeric flavonolignans from milk thistle (Silybum marianum (L.) Gaertn.) fruits, is known to possess a panel of pharmacological activities. However, due to low water solubility and extensive phase II metabolism, the oral bioavailability of the flavonolignans is limited. Since their interaction with gut microbiome is likely due to their predominantly fecal excretion route, the biotransformation of milk thistle flavonolignans by gut microorganisms was studied. A 1:1 mixture of the two main silymarin flavonolignans silybins A and B was incubated in human fecal suspension from one donor for 24 h under anoxic conditions. Purification of the incubate allowed to isolate and structurally elucidate the two main metabolites as (2R, 3R)-2-{4-[2-(3,4-dihydroxy-phenyl)-(1R)-1-hydroxymethyl-ethoxy]-3-hydroxy-phenyl}-3,5,7-trihydroxy-chroman-4-one (a product of demethylation and dioxane ring cleavage) and demethylsilybin B. Furthermore, silymarin was incubated with human fecal suspension, and its biotransformation was monitored by means of LC-HRMS metabolite profiling. Apart from the two isolated and structurally elucidated metabolites, several types of biotransformation products could be annotated, including demethylation products, reduction/ring cleavage products, products of demethylation plus reduction/ring cleavage, as well as several low molecular weight aromatic metabolites. The potential pharmacological activities of these gut microbial metabolites deserve closer examination in the future.

Six different furanocoumarins were isolated from the aerial parts of Ducrosia anethifolia and tested in vitro for plant cell elongation in etiolated wheat coleoptile. They were also tested for their ability to control three different weeds: ribwort plantain, annual ryegrass, and common purslane. These compounds exhibited strong inhibition of plant cell elongation. In the case of (+)-heraclenin, the IC50 was lower than 20 μM, indicating a better inhibition than the positive control Logran®. Computational experiments for docking and molecular dynamics revealed for the investigated furanocoumarins bearing an epoxide moiety an improved fitting and stronger interaction with the auxin-like TIR1 ubiquitin ligase. Furthermore, the formed inhibition complex remained also stable during dynamic evaluation. Bidental interaction at the active site, along with an extended hydrogen-bond lifetime, explained the enhanced activity of the epoxides. The in vitro weed bioassay results showed that Plantago lanceolata was the most affected weed for germination, root, and shoot development. In addition, (+)-heraclenin displayed better inhibition values than positive control even at 300 μM concentration.

Strigolactones are compounds produced by plant roots in response to nutrient deficiency, acting both as local and systemic signals to control development and nutrition. Strigolactones are exuded in the rhizosphere to positively influence interactions with beneficial microbes. LC-MS/MS analysis shows that two genetically distinct grapevine rootstocks exudate one or two non-canonical strigolactones when subjected to low nitrogen conditions. Gene expression profiles and orobanche seed germination assays confirm that the biosynthesis and exudation of non-canonical compounds is the preferred pathway. The first compound, corresponding to heliolactone or 6-epi-heliolactone, is only exuded by the rootstock showing lower shoot branching and a higher level of mycorrhization with arbuscular mycorrhizal fungi. The structure of the second compound exuded by both rootstocks was identified by NMR and LC-MS/MS analysis. It is a non-canonical strigolactone, which has never been identified in another species. This first identification of a natural compound with the potential to stimulate beneficial root-microbe interactions in grapevines opens new perspectives in viticulture.

Chemical investigation of the EtOAc extract of the leaves of Pittosporum lenticellatum led to the isolation of twenty-five previously undescribed eudesmane sesquiterpenoid glycosides, pitlencosides A－Y (1-25); their structures were elucidated by extensive spectroscopic analysis, including 1D and 2D NMR, HR-ESI-MS, ECD spectra, and X-ray crystallographic analysis. Among them, compounds 4, 5, 7, 8, 15 and 16 exhibited significant inhibitory effects on the production of nitric oxide in lipopolysaccharide-induced BV-2 microglial cells by suppressing the expression of inducible nitric oxide synthase and cyclooxygenase-2, with IC50 values ranging from 7.95 to 25.88 μM, which showed stereo-chemical and substituent dependents. Western blot analysis and molecular docking simulation confirmed the anti-inflammatory activity of compounds 4, 5, 7, 8, 15 and 16.

An unprecedented dimeric abietane, succipenoid A (1), and two previously undescribed nor-abietane diterpenoids featuring a rarely occurring naphthalene ring or with a large conjugated system, succipenoids B and C (2 and 3), along with seven known diterpenoids (4-10) were isolated from the CH2Cl2 extract of succinum. The structures of these compounds, including their absolute configurations, were elucidated using spectroscopic and computational techniques. Notably, compounds 1-4 and 6-10 were isolated from succinum for the first time. In order to evaluate their anti-inflammatory potential, in vitro tests were conducted. The results demonstrated that compounds 1, 2, 4, and 6-10 exhibite dose-dependent inhibition of iNOS expression in lipopolysaccharide-induced RAW 264.7 cells.

Autophagy is a crucial process for maintaining cellular homeostasis by degrading and recycling unnecessary or damaged cellular components. In the process of exploring autophagy regulators in plants, unique nine oligomeric flavonoids linked by the bonding of C-3 and C-4, consisting of three pairs of biflavonoids, linderanidins A-C [(+)-1/(-)-1, (+)-2/(-)-2, and (+)-3/(-)-3], and three trimeric A-type proanthocyanidins, linderanidins D-F (4-6), were isolated from the roots of Lindera erythrocarpa. The structures and absolute configurations of these compounds were determined using various techniques, such as 1D and 2D NMR, mass spectrometry, X-ray crystallography, and electronic circular dichroism. All isolates were evaluated for their ability to regulate autophagy, and compounds (±)-1-(±)-3, (-)-1-(-)-3, (+)-1-(+)-3 and 4 were found to inhibit autophagy by blocking the fusion process between autophagosome and lysosome in HEK293 cells. This study suggests that unique oligomeric flavonoids possessing a C-3-C-4 linkage derived from the roots of L. erythrocarpa are potent autophagy inhibitors.

Six undescribed compounds, including three phenolic glycosides (1-3) and three indole alkaloids (4-6), together with ten known alkaloids (7-16) and three known phenolic glycosides (17-19), were isolated from 70% EtOH aqueous extracts of the roots and rhizomes of Clematis chinensis Osbeck. The structures were elucidated by NMR, HRESIMS and X-ray diffraction spectroscopies. The anti-inflammatory activity of these compounds was evaluated, and twelve compounds showed significant inhibitory activity against TNF-α with an inhibition ratio from 47.87% to 94.70% at a dose of 10 μM. Compound 7 exhibited significant inhibitory activity against TNF-α and IL-6 with IC50 values of 3.99 μM and 2.24 μM, respectively. Compound 8 displayed potent anti-inflammatory activity against mouse ear edema induced by croton oil. A mechanistic study suggested that compounds 7 and 8 decreased the activation of the NF-κB signaling pathway to reduce the secretion of inflammatory factors in LPS-induced RAW 264.7 cells.

The fern plant Woodsia ilvensis (L.) R. Br. belongs to the Woodsiaceae family and its leaves are used to treat diarrhea, soft-tissue injuries, and external injuries. Investigations of the compounds obtained from the plasmin-inhibitory-active extracts of W. ilvensis led to the isolation of two undescribed maleimide N-glycosides, an undescribed stilbenoid glycoside, and five undescribed acetylated flavonol bisdesmosides, together with 19 known compounds. The chemical structures of the isolated compounds were determined using spectroscopy. The absolute configurations of the sugar moieties were determined via HPLC after acid hydrolysis. Among the isolated compounds, some flavonoids and stilbenoid glycosides exhibited plasmin-inhibitory activity.

Delphinium kamaonense Huth is a sort of folkloric plant resource which is cultivated and planted with great ornamental and medicinal values. In this work, seven undescribed lycaconitine-type C19-diterpenoid alkaloids, especially a rare skeleton with -CH=N and N-oxide moieties, along with ten known compounds, were isolated from D. kamaonense, of which the structures were determined by various spectroscopic data, combined with calculated electronic circular dichroism (ECD) and single-crystal X-ray diffraction analysis. In vitro nitric oxide inhibitory activities assay of these compounds indicated that lycaconitine-type C19-diterpenoid alkaloids had significant anti-inflammatory inhibitory activities, with kamaonensine E being the most potent (0.9 ± 0.2 μM) stronger than positive (9.0 ± 1.3 μM). In the network pharmacology studies, binding three key targets mitogen-activated protein kinase 8 (MAPK8), mitogen-activated protein kinase 14 (MAPK14), and heat shock protein HSP 90-alpha (HSP90α), the anti-inflammatory mechanism might be related to MAPK signaling pathways. Furthermore, the molecular docking results revealed that the uncommon amides and methylenedioxy groups might be the most two promising pharmacophores for lycaconitine-type C19-diterpenoid alkaloids.