Eight undescribed metabolites (1-8), including three sesquiterpenoids (1-3) and five 2-(2-phenylethyl)chromones (4-8), and 28 known compounds (8-35) were isolated by bioassay-guided fractionation of A. sinensis extract. Their structures were elucidated by analyses of NMR and MS data, as well as single-crystal X-ray diffraction and ECD calculations. All the isolated compounds were systematically evaluated cytotoxic and anti-inflammatory activity. Four compounds including one eudesmane-type sesquiterpenoid (-)-(5R,7R,10R)-12,15-dioxo-α-selinene (9) and three 5,6:7,8-diepoxy-2-(2-phenylethyl)-5,6,7,8-tetrahydrochromones, namely (5R,6R,7R,8R)-oxidoagarochromone A (11), (5S,6S,7S,8S)-oxidoagarochromone B (12), and (5S,6S,7S,8S)-oxidoagarochromone C (13), were the most cytotoxic against eleven cancer cell lines (HL-60, K562, A549, MDA-MB-231, SW480, HepG2, HCT116, Caco2, SK-OV-3, MG-63, and U251), with IC50 values of 0.18-6.35 μM. Moreover, compounds 9 (IC50 = 0.19 μM), 11 (IC50 = 0.60 μM), and 12 (IC50 = 1.01 μM), and (5R,6S,7S,8S)-7,8-dihydroxy-5,6-epoxy-2-[2-(4-methoxyphenyl)ethyl]-5,6,7,8-tetrahydrochrome (16; IC50 = 3.55 μM) exhibited the strongest inhibition of the NO production. The absolute configurations of compounds 11-13 were determined by X-ray diffraction for the first time. These dual anticancer/anti-inflammatory compounds (9, 11, and 12) may serve as promising candidates for future mechanistic and in vivo studies.

Gastrodia elata (Orchidaceae) is a material used for medicine, food, and cosmetics in China. Two new alkaloids, 1,7-bis(4-hydroxybenzyl)-1,7-dihydro-6H-purin-6-one (1) and 1,9-bis(4-hydroxybenzyl)-1,9-dihydro-6H-purin-6-one (2), five known alkaloids, (–)-(R)-4-(2-hydroxy-2-quinolin-4-ylethyl)phenol ((–)-3), (+)-(S)-4-(2-hydroxy-2-quinolin-4-ylethyl)phenol ((+)-3), 1-(4-hydroxyphenyl)-β-carboline (4), p-topolin riboside (5), and cannabisin F (6), and nine other compounds (7–15), were isolated from the rhizomes, peduncles, and inflorescences of Gastrodia elata, a waste collected after seed harvesting. The chemical structures of these new compounds were determined by MS and NMR spectroscopic data. These isolated alkaloids were evaluated for their cholinesterase inhibitory activity and collagen I secretion-promoting activity. Compound 2 inhibited acetylcholinesterase (AChE) with an IC50 value of 19.8 ± 1.8 μM, whereas compound 4 exhibited an inhibitory effect on AChE with an IC50 value of 24.7 ± 3.2 μM, and on butyrylcholinesterase (BuChE) with an IC50 value of 0.84 ± 0.06 μM. At a concentration of 0.1 μM, compounds (–)-3, (+)-3, and 5 exhibited significant collagen I secretion-promoting activity in human dermal fibroblast adults (HDFa). These active compounds have potential for the development of neuroprotective drugs or antiaging cosmetics.

Dental caries is a significant global oral health problem, primarily caused by Streptococcus mutans (S. mutans). Although previous studies have indicated that Caesalpinia sappan (CS) exhibits anti-caries properties, its specific anti-caries active compounds remain largely unidentified. This study aimed to identify the potential anti-caries components of CS through an integrated strategy involving bioassay-guided isolation targeting S. mutans, UPLC-MS/MS, network pharmacology, molecular docking, and molecular dynamics simulation. Bioassay-guided isolation led to the identification of 33 compounds in fraction 5 from CS, among which brazilin showed the highest content and effectively inhibited biofilm formation and acid production by S. mutans. Network pharmacology analysis predicted 11 active ingredients in CS, including brazilin, targeting 7 potential targets related to dental caries: AKT1, EGFR, BCL2, PTGS2, MMP9, ERBB2, and HSP90AA1, as well as two pathways—nitrogen metabolism and calcium signaling. Molecular docking revealed strong binding affinities of brazilin to PTGS2, EGFR, MMP9, GtfC, GtfD, and GbpC. Further, molecular dynamics simulation revealed strong stability between brazilin and PTGS2, GtfC. Together, these findings not only clarify the anti-caries chemical constituents of CS and their potential mechanisms of action, but also provide new insights into the bioactive components and mechanisms of natural plant-derived medicines for the prevention and treatment of dental caries.

Thirteen compounds (1–13), including two new amides, piperunnamides E (1) and F (2), were isolated from the aerial parts of Piper yunnanense collected from Myanmar. (7R,7′R,8R,8′R)-1 and (7S,7′S,8S,8′S)-1 were obtained by the chiral separation of 1 and their absolute configurations were determined by electronic circular dichroism (ECD) calculations. Sarmentomicine (5) and lutein A (13) significantly suppressed nitric oxide (NO) production (IC50 = 8.97 ± 0.38 μM and 30.48 ± 0.48 μM, respectively) in mouse monocyte RAW264.7 macrophages induced by lipopolysaccharide (LPS). This anti-inflammatory activity of sarmentomicine is being reported for the first time.

A pair of amide enantiomers, (+)-magenamide B [(+)-1] and (-)-magenamide B [(-)-1], and six undescribed alkaloids, magenamides CF (2-5), along with 2-nonyl-3,5-dioctylpyridine (6) and 3-decyl-2-nonyl-5-octylpyridine (7), together with 19 known compounds (8-26) were isolated from the stems of Piper magen (Piperaceae). The chemical structures of all the new compounds were elucidated using NMR and MS data. Magenamide C and 5,6-dihydro-1-[(2E)-3-(4-methoxyphenyl)-1-oxo-2-propen-1-yl]-2(1H)-pyridinone (15) strongly inhibited NO production, with IC50 values of 30.09 μM and 3.16 μM, respectively (positive control: L-NMMA, IC50 = 42.24 μM). Moreover, corydalisin C (24) showed DPPH radical scavenging activity, with an IC50 value of 26.10 μM (positive control: Trolox, IC50 = 21.38 μM). Compound 15 and magenamide A demonstrated protective effects against corticosterone-induced neuronal injury at a concentration of 2 μM (P < 0.001). 1-(m-Methoxycinnamoyl)pyrrolidine (16) exhibited BACE1 inhibitory activity, with an IC50 value of 8.73 μM (positive control: LY2886721, IC50 = 31.80 nM).

The stem bark of Aquilaria yunnanensis(Thymelaeaceae) is traditionally used to treat cough and asthma in folk medicine. However, its active components have not been reported. In the present study, the chemical constituents of A. yunnanensis stem bark were isolated and identified, and their inhibitory activities against nitric oxide(NO) production in RAW264.7 cells induced by lipopolysaccharide(LPS) were evaluated to clarify the anti-inflammatory components in the stem bark of A. yunnanensis. A total of 22 compounds, including a new norlignan [(±)-1], were isolated from the ethanolic extract of A. yunnanensis stem bark by column chromatography, high-performance liquid chromatography(HPLC), recrystallization, etc. Through chiral separation of(±)-1,(-)-1 and(+)-1 were obtained. Based on electronic circular dichroism(ECD) calculations, the absolute configurations of(-)-1 and(+)-1 were determined to be(-)-(7R,8S,8'S)-4-O-(1,3-dihydroxypropan-2-yl)zhebeiresinol and(+)-(7S,8R,8'R)-4-O-(1,3-dihydroxypropan-2-yl)zhebeiresinol. The known compounds included(±)-zhebeiresinol(2),(+)-syringaresinol(3),(+)-episyringaresinol(4), orcinol(5), orsellinic acid(6), methyl orsellinate(7), 3,4-dihydroxybenzoic acid(8), lecanoric acid(9), barbatic acid(10), 7β-hydroxy-β-sitosterol(11), β-sitosterol(12), stigmasterol(13), ergosterol peroxide(14), genkwanin(15), pilloin(16), 5-hydroxy-3',4',7-trimethoxyflavone(17),(-)-epicatechin(18),(-)-epicatechin gallate(19), tectorigenin 2-O-α-L-rhamnopyranoside(20), 2,3-dihydroxypropyl docosanoate(21), and 1-O-linolenoylglycerol(22). According to the bioassay testing results, compounds 4 and 22 which inhibited NO production with IC_(50) values of(32.82±1.04) and(18.50±0.95) μmol·L~(-1), respectively, exhibited anti-inflammatory activities.

Phytochemical investigation of Astragalus variabilis led to the isolation of three steroidal compounds, identified by spectroscopic analyses as variabilisterones A (1) and B (2), and Δ3,5-Pregnadien-20β-ol-7-one (3). Compounds 1 and 2 were new pregnane-type steroids, while compound 3 was obtained from this plant for the first time. In vitro assays demonstrated that, compared with COX-1, compounds 1-3 exhibited a degree of selectivity toward COX-2 and showed moderate COX-2 inhibitory activities, with IC50 values of 16.98 ± 2.25, 15.15 ± 0.70, and 15.16 ± 3.87 μM, respectively. To elucidate the potential mechanism, molecular docking, molecular dynamics simulations, and MM/GBSA calculations were performed for compounds 1-2, indicating stable binding within the COX-2 active site via predominantly hydrophobic interactions complemented by hydrogen bonding. Molecular dynamics results demonstrated overall structural stability of the complexes without significant perturbation of protein secondary structure, while DCCM analysis suggested minimal impact on global protein dynamics, and binding free energy calculations confirmed thermodynamically favorable interactions. ADMET predictions were further conducted to preliminarily evaluate pharmacokinetic properties. Collectively, these findings highlight the anti-inflammatory potential of pregnane-type steroids from A. variabilis and support their further investigation as potential COX-2 inhibitors.

Dental caries represents a major global oral health issue, primarily caused by Streptococcus mutans ( S. mutans ). While previous studies have indicated that Caesalpinia sappan ( CS ) possesses anti-caries activity, its specific anti-caries chemical constituents remain largely unexplored. This study aimed to identify the potential anti-caries constituents of CS using an integrated approach combining network pharmacology, ultra-Performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS), bioassay-guided isolation targeting S. mutans , and molecular docking. We identified a total of 35 active ingredients in CS , sharing 79 potential therapeutic targets associated with dental caries, including AKT1, EGFR, BCL2, PTGS2, MMP9, ERBB2, and HSP90AA1. Key pathways implicated included nitrogen metabolism and calcium signaling. Bioassay-guided isolation yielded 33 compounds in the fifth fraction from CS . However, only brazilin overlapped with the network pharmacology-predicted key ingredients. Brazilin effectively inhibited biofilm formation and acid production by S. mutans and demonstrated strong binding affinity to EGFR, BCL2, and MMP9 in molecular docking analysis, with docking scores all below -7 kcal/mol. Collectively, these findings not only elucidate the anti-caries chemical constituents of CS and their potential mechanisms of action but also provide novel insights into the bioactive constituents and mechanisms underlying natural plant-derived medicines for the prevention and treatment of dental caries.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, and its incidence rate and mortality are relatively high. Paclitaxel, a classic chemotherapy drug, has become one of the first-line drugs commonly used for patients with advanced NSCLC in clinical practice, but multidrug resistance has become a major factor seriously restricting its efficacy. Therefore, overcoming multidrug resistance to paclitaxel is an important issue that urgently needs to be addressed to improve its efficacy. In our study, twenty-three novel derivatives of Genipin were synthesized by using different intermediates of methylene indole ketones and Genipin. When they were combined with paclitaxel, most of them exhibited good reversal activity in P-gp-mediated paclitaxel-resistant non-small cell lung cancer cells (A549/Taxol cells). The most potent compound 13 could enhance the sensitivity of A549/Taxol cells with low cytotoxicity to paxlitaxel by targeting YB-1 and reducing the expression of total YB-1 protein and the level of YB-1 protein in the nucleus, thus inhibiting the expression and function of the downstream protein P-gp, further suppressing the efflux rate of paclitaxel and increasing the concentration of intracellular paclitaxel. In addition, tumour growth in paclitaxel-resistant lung cancer xenografts was significantly decreased by combination treatment with compound 13 and paclitaxel. H&E staining of mouse organs and IHC analysis of A549/Taxol tumour tissues indicated that compound 13 could enhance the paclitaxel sensitivity of paclitaxel-resistant NSCLC, with low cytotoxicity. These results clearly indicate that compound 13, by targeting YB-1, might be useful as a novel chemosensitizer in combination with paclitaxel to overcome MDR in the management of NSCLC.

Agarwood, chenxiang, is a traditional Chinese medicine. It is the resinous heartwood of Aquilaria sinensis. The qinan germplasm of A. sinensis is a high-quality resource. This study aimed to investigate the chemical compounds and biological activities of agarwood produced from the qi-nan germplasm (QNA) and evaluated the quality of the QNA according to existing standards. The QNA was extracted by using supercritical CO2 (SCE) and then by 90 % EtOH (ETE). SCE was detected with gas chromatography-mass spectrometry (GC-MS) to identify 13 compounds, including sesquiterpenoids and 2-(2-phenylethyl)chromones. ETE was isolated by using column chromatography methods to yield two new compounds: 5-hydroxy-2-[2-(4-methoxy)phenethyl]chromone (1) and qinansin A (2), and 13 known compounds (3-15). The various biological activities of SCE, ETE, and these isolated compounds were evaluated. Compound 1 , compound 2 , 2-(2-phenylethyl)chromone (4), 2-[2(-4methoxy)phenethyl]chromone (5), 2-[2-(2-hydroxy)phenethyl]chromone (6), chenanone A (8), (E)-1-chloro-4- (4-methoxyphenyl) but-3-en-2-one (9), (E)-1,5-diphenylpentan-1-en-3-one (12), and selina-4,11(13)-diene12,15-dial (14) demonstrated antifungal activity against Epidermophyton floccosum, Trichophyton rubrum, and Microsporum gypseum, with IC50 values ranging from 3.50-83.45 mu & Mcy;. Moreover, compound 12 exhibited antiinflammatory activity (NO production inhibition; IC50 = 23.42 mu M); additionally, compound 8 showed antioxidant activity (DPPH free radical scavenging; IC50 = 40.89 mu M), and compound 14 showed cytotoxicity to five cancer cell lines and human normal lung epithelial BEAS-2B cells, with IC50 values ranging from 3.35-16.95 mu M. The quality of the QNA was evaluated according to the Chinese Pharmacopoeia and the local standards of Hainan Province, China. The findings indicated that the alcoholic extract contents and the contents of 2-(2-phenylethyl) chromone and 2-[2-(4-methoxyphenyl)ethyl]chromone of QNA were within high-quality ranges, and they increased with prolonged agarwood formation time. These results could provide a basis for the further development and utilization of QNA.

Twenty-six compounds, including one new 2-(2-phenylethyl)chromone derivative, (R)-2-(1-hydroxy-2- phenylethyl)chromone (1), and one new resorcylic acid lactone, (S)-de-O-methylhispidulactone A (2), were isolated from the nonresinous heartwood of Aqualaria sinensis (Lour.) Spreng. Among these compounds, (S)-de-O-methylhispidulactone A (2), 2-(2-phenylethyl)chromone (4), 2-[2-(4-hydroxyphenyl)ethyl]chromone (7), 6-methoxy-2-(2-phenylethyl)chromone (8), 6-methoxy-2-[2-(3-methoxyphenyl)ethyl]chromone (9), 2-[2-(3-methoxyphenyl)ethyl]chromone (10), 6,7-dimethoxy-2-(2-phenylethyl)chromone (11), 8-chloro-6- hydroxy-2-[2-(4-methoxyphenyl)ethyl]chromon-4-one (13), (+)-(R)-de-O-methyllasiodiplodin (14), lasiodiplodin (15), and (3R)-(–)-melliein (20) exhibited antifungal activity against Epidermophyton floccosum, Trichophyton rubrum, and Microsporum gypseum, with MIC values ranging from 5.8 to 51.6 μM. Furthermore, (R)-2-(2-hydroxy-2-phenylethyl)chromone (3b), 7, 8, 9, 14, 15, 5-hydroxy-7,3′,4′- trimethoxyflavone (17), and velutin (18) demonstrated antibacterial effects against Staphylococcus aureus, with MIC values ranging from 20.2 to 96.0 μM.

Mesua ferrea L. has traditionally utilized in folk medicine for its antidiabetic properties, and contemporary pharmacological studies have confirmed its hypoglycemic activity. While, the specific components responsible for these effects have not yet been fully elucidated. In this study, we employed a bioactivity-guided fractionation approach to isolate 22 prenylated polyphenols from M. ferrea leaves, including two novel 4-phenylcoumarins, mesuol A (1) and mesuol B (2), along with 20 previously identified compounds. The majority of these compounds, including 13 4-phenylcoumarins and two xanthones, exhibited significant stimulatory effect on glucose uptake in 3 T3-L1 adipocytes. Notably, at a concentration of 2 μM, isomesuol (14), disparinol D (17), and isodisparinol A (19) exhibited glucose uptake stimulatory effect that were either superior or equivalent to that of insulin (positive control). The structure-activity relationship analysis revealed that cyclization of 4-phenylcoumarins to form a furan ring markedly diminished their glucose uptake stimulatory effects, thereby reducing their hypoglycemic potential. In contrast, non-cyclized and pyran ring-cyclized 4-phenylcoumarins demonstrated stronger glucose uptake-stimulatory activities. These findings highlight the non-cyclized and pyran ring-cyclized 4-phenylcoumarins as promising leads for the development of anti-diabetic agents, with M. ferrea leaves serving as a valuable source of these bioactive compounds.

Mesua ferrea L. is used in Ayurvedic and Thai medicine for treating various diseases, including diabetes. This study aimed to isolate and identify the bioactive constituents from M. ferrea leaves with potential α‐glucosidase inhibitory activity using a bioassay‐guided fractionation approach. From the ethyl acetate fraction with the most potent inhibitory effect, we isolated eight polyphenols, including six coumarins (1−6) and two flavonoids (7−8). Notably, five compounds (1, 2, 4, 6, and 8) displayed significant α‐glucosidase inhibitory activity with IC50 value ranging from 1.81 to 42.97 µM. Quercetin 3‐O‐(3″,4″‐di‐E‐p‐coumaroyl)‐α‐L‐rhamnoside (8) and mammea A/AA cyclo D (6) were identified as potent α‐glucosidase inhibitors, with IC50 value of 1.81 ± 0.12 µM and 6.69 ± 0.27 µM, respectively, surpassing that of the positive control, quercetin (IC50 = 7.82 ± 0.21 µM). Furthermore, mammea A/AA (3) and mammea A/AB (4) exhibited a dual effect by inhibiting α‐glucosidase and promoting glucose uptake in 3T3‐L1 adipocytes, indicating in developing multi‐targeted antidiabetic therapeutics. These findings demonstrated the potential of M. ferrea leaves as a source of novel antidiabetic agents.

Parkinson’s disease (PD), the second most common neurodegenerative disorder globally, arises from selective dopaminergic neuron degeneration. While current therapies address symptoms, disease-modifying agents remain an unmet need. Herein, we investigated Nicotiana tabacum L. (Solanaceae), a plant linked epidemiologically to reduced PD risk, as a source of multi-target neuroprotective compounds. From ultra-low nicotine (< 0.04

This study first integrates genomic and chemical analyses of Botryosphaeria dothidea isolated from Aquilaria sinensis to investigate its role in agarwood formation. Whole-genome sequencing revealed a 44.33 Mb assembly encoding 69 biosynthetic gene clusters (BGCs). antiSMASH analysis revealed that 37 of these BGCs (53.6

The role of fungi in agarwood resin formation remains incompletely understood. This study investigated the metabolic effects of Botryosphaeria dothidea strain ket49 on the nonresinous heartwood of Aquilaria sinensis. HPLC analysis revealed that, compared with the control treatment, fermentation with ket49 induced a time-dependent metabolic shift, markedly increasing the accumulation of agarotetrol, a pharmacopeial marker, by 4.5-fold. UPLCQTOFMS/MS analysis of the fermented extract tentatively revealed 14 2-(2-phenylethyl)chromones. Subsequent isolation yielded 11 compounds, including the new (R)-2-[2-hydroxy-2-(2-hydroxyphenyl)ethyl]chromone (1). These findings revealed the possibility that 2-(2-phenylethyl)chromones are hydroxylated by this fungus. The increase in agarotetrol production by fungi may be a sustainable strategy for high-quality agarwood induction.

Calotropis gigantea (Giant milkweed, GM) has the potential to be utilized as a new feed additive for ruminants, however, the presence of unpalatable or toxic compounds decreases animal feed intake. This study aimed to valorize GM as a potential new feed resource through the chemical and microbial biotransformation of toxic compounds that will henceforth, make the plant palatable for cows. After GM’s ensiling using fermentative bacteria, the plant was sampled for UHPLC-MS/MS to analyse the metabolomic changes. Illumina Miseq of the 16 S rRNA fragment genes and ITS1 were used to describe the microbial composition and structure colonizing GM silage and contributing to the biodegradation of toxic compounds. Microbial functions were predicted from metataxonomic data and KEGG pathways analysis. Eight Holstein dairy cows assigned in a cross-over design were supplemented with GM and GM silage to evaluate palatability and effects on milk yield and milk protein. Cows were fed their typical diet prior to the experiment (positive control). After ensiling, 23 flavonoids, 47 amino acids and derivatives increased, while the other 14 flavonoids, 9 amino acids and derivatives decreased, indicating active metabolism during the GM ensiling process. Lactobacillus buchneri, Bacteroides ovatus, and Megasphaera elsdenii were specific to ensiled GM and correlated to functional plant metabolites, while Sphingomonas paucimobilis and Staphylococcus saprophyticus were specific to non-ensiled GM and correlated to the toxic metabolite 5-hydroxymethylfurfural.''Xenobiotics biodegradation and metabolism'', ''cancer overview'' and ''neurodegenerative disease'' were the highly expressed microbial KEGG pathways in non-ensiled GM. Non-ensiled GM is unpalatable for cows and drastically reduces the animal’s feed intake, whereas ensiled GM does not reduce feed intake, milk yield and milk protein. This study provides essential information for sustainable animal production by valorizing GM as a new feed additive.

Despite being recognized as a specialty food in four Chinese provinces with established safety standards, Dendrobium officinale Kimura et Migo (Orchidaceae) leaf physicochemical indices overlook vital flavonoid glycoside components. Given the inconsistency in flavonoid quality under current standards, we devised a quantitative analysis targeting vicenin 2, vicenin 3, rutin, and isoviolanthin. Our analysis revealed significant seasonal variations, with harvests yielding the highest total content of these four flavonoid glycosides in February (1.6378 mg/g) and July (2.0642 mg/g). This finding provides a scientific basis for optimal collection timing, enhancing quality control and utilization. Furthermore, we optimized the extraction conditions (59.63 °C, 22.44 min, 1:37.91 g/mL solid-to-liquid ratio, 43.24 % ethanol) to maximize the flavonoid glycoside content. This study lays a foundation for refining D. officinale leaf quality standards and advancing related product development in China.