Xin Yang

Antrodia cinnamomea (A. cinnamomea), an edible medicinal fungus, contains a unique class of terpenoids. In this work, we studied the activity of terpenoid-rich diethyl ether extract (termed AC-DE) for the treatment of drug-resistant triple-negative breast cancer (TNBC). In vitro assays using both 2D and 3D models demonstrated that AC-DE exhibited potent, dose-dependent cytotoxicity across multiple cancer cell lines, significantly inducing apoptosis and inhibiting the proliferation, migration, and invasion of MDA-MB-231 breast cancer cells. Mechanistic studies demonstrated that AC-DE induced mitochondrial dysfunction by upregulating pro-apoptotic proteins, including Bax, caspase-9, caspase-3, and cytochrome c, while downregulating the antiapoptotic protein Bcl-2. In addition, AC-DE suppressed the PI3K/AKT/mTOR signaling pathway, suggesting a dual mechanism involving both mitochondrial and signaling pathway regulation. In vivo, AC-DE (25, 50, and 100 mg/kg every other day) significantly suppressed tumor growth in MDA-MB-231 xenograft-bearing nude mice. Collectively, these findings highlight that AC-DE extract is promising as a functional food or therapeutic ingredient for managing drug-resistant TNBC.

Lipid vesicles consist of aqueous cores surrounded by a bilayer of phospholipids. Hybrid polymer–lipid vesicles incorporate both polymers and lipids, offering promising properties for developing pharmaceuticals, biosensors, and artificial cells. The hybrid vesicles can be symmetric, with two leaflets of identical compositions, or asymmetric, in with leaflets of dissimilar compositions, which can lead to dramatically altered properties. However, existing methods for producing symmetric and asymmetric hybrid vesicles often result in heterogenous compositions and sizes, making it challenging to quantify the effect of asymmetry and limiting applications. Here, we use a microfluidic approach to produce hybrid vesicles with either symmetric or asymmetric leaflets and precisely engineered compositions. We find that the vesicles with asymmetric leaflets are significantly stiffer and tougher than those with symmetric leaflets; moreover, the lateral diffusivity of lipids is greatly decreased. The structure for improved toughness consists of a stretchable lipid inner leaflet and a fully continuous polymer outer leaflet. This approach to precisely engineer asymmetric structures can be applied to hybrid vesicles composed of block copolymers and phospholipids soluble in chloroform and hexane, further expanding their applications.

Antrodia cinnamomea is widely known for its bioactive properties, particularly in anti-cancer, anti-inflammatory, and antibacterial areas. Despite the full use of the bioactive compounds from its fruiting body, high-value residues remain largely underexploited. This study presents a novel one-pot gel formation method, utilizing cinnamomea cellulose-riched residues to create hydrogels as an effective wound-healing dressing. The hydrogels derived from these residues show desirable properties, including non-drying characteristics, antibacterial activity against Staphylococcus aureus ATCC 1768, and cytocompatibility. Residual bioactive compounds, such as Antcin-K, Dehydroeburicoic acid, and (25S,R)-Antcin H, were identified in the residues, adding to the hydrogel’s efficacy. A UVB irradiation model was employed to evaluate the protective effects of the residues on UVB-damaged HaCaT skin cell lines, with an IC₅₀ of 0.045 mg/mL. The results indicated that A. cinnamomea residue extracts reduced the upregulation of MMP-1, MMP-2, MMP-3, MMP-7, and MMP-9 proteins caused by UVB exposure, suggesting high UV-protective activity. Additionally, antibacterial tests on Staphylococcus aureus strains, including Staphylococcus ATTC 1768, showed promising results, with inhibition zones ranging from 10.64 to 12.11 mm. In summary, Antrodia cinnamomea residue hydrogels combine UV protection with antimicrobial activity, making them a promising candidate for medical applications, particularly as a wound-healing dressing.

Antrodia cinnamomea (A. cinnamomea), a medicinal and edible mushroom endemic to Taiwan, has been traditionally valued as a health tonic. Recent studies have highlighted the diverse specialized metabolites and bioactive potential of this substance, primarily attributed to key secondary metabolites such as benzenoids, maleic and succinic acids, ubiquinone, triterpenoids, and the primary metabolite polysaccharides. These compounds exhibit a broad spectrum of pharmacological properties, including those related to antibacterial, antitumor, anti-inflammation, hepatoprotection, hypoglycaemia, and antioxidant activities, and immunomodulation and gut microbiota regulation. These findings highlight the therapeutic potential of A. cinnamomea and its potential applications in health supplements and functional foods. This review evaluated recent advancements in the cultivation, extraction, and characterization of bioactive compounds from A. cinnamomea, with a particular focus on submerged and solid-state fermentation methods. We hope to provide a comprehensive framework for promoting the efficient and scientific evidence based utilization of A. cinnamomea in novel therapeutic strategies and health-related innovations.

Dietary flavones 6,3´,4´-trihydroxyflavone (6,3´,4´-HOFL) and 7,3´,4´-trihydroxyflavone (7,3´,4´-HOFL) showed preliminary antioxidant and anti-inflammatory activities in a two-dimensional (2D) cell culture model. However, their action mechanisms remain unclear, and the anti-inflammatory activities have not been studied in a reliable three-dimensional (3D) cell model. Therefore, in the current study, the antioxidant potency was examined by their scavenging ability of cellular reactive oxygen species. Anti-inflammatory activities were examined via their inhibitory effects on inflammatory mediators in vitro on 2D and 3D macrophage models, and their mechanisms were determined through transcriptome. In the 3D macrophages, two flavones were less bioactive than they were in 2D macrophages, but they both significantly suppressed the overexpression of proinflammatory mediators in two cell models. The divergent position of the hydroxyl group on the A ring resulted in activity differences. Compared to 6,3´,4´-HOFL, 7,3´,4´-HOFL showed lower activity on NO, IL-1β suppression, and c-Src binding (IC₅₀: 12.0 and 20.9 µM) but higher ROS-scavenging capacity (IC₅₀: 3.20 and 2.71 µM) and less cytotoxicity. In addition to the IL-17 and TNF pathways of 6,3´,4´-HOFL, 7,3´,4´-HOFL also exerted anti-inflammatory activity through JAK-STAT, as indicated by the RNA-sequencing results. Two flavones showed prominent antioxidant and anti-inflammatory activities on 2D and 3D models.

Flavones benefit human health through their anti-inflammatory activity; however, their structure-activity relationship is unclear. Herein, we selected 15 flavones with the same backbone but different substituents and systematically assessed their anti-inflammatory activities in RAW 264.7 regarding cellular-Src kinase (c-Src) affinity, suppression of IκBα phosphorylation, inhibition of nitric oxide (NO) and inducible nitric oxidase (iNOS) production, and downregulation of genes of proinflammatory cytokines interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor α (TNF-α). Overall, our results showed that the double bond between C2-C3 and C3'- and C4'-OH promoted anti-inflammatory activity, while C8- and C5'-OH and the methoxy group on C4' attenuated the overall anti-inflammatory and antioxidant activities. The hydroxyl groups at other positions exhibited more complicated functions. The two most effective flavones are 3',4'-dihydroxyflavone and luteolin with inhibitory concentration (IC₅₀) values for inhibiting the LPS-induced nitric oxide level are 9.61 ± 1.36 and 16.90 ± 0.74 μM, respectively. Furthermore, they suppressed the production of iNOS by approximately 90% and inhibited IL-1β and IL-6 by more than 95%. Taken together, our results established a relationship between the flavone structure and anti-inflammatory activity in vitro.

Flavonoids, a class of polyphenolic substances widely present in the plant realm, are considered as ideal hypochlorite scavengers. However, to our knowledge, little study has focused on the structure-activity relationship between flavonoids and hypochlorite scavenging capacity. Herein, we report for the first time the three-dimensional quantitative structure and activity relationship (3D-QSAR) combined with comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Four models derived from CoMFA and CoMSIA with different combinations of descriptors were built and compared; the CoMFA model, which included both steric and electrostatic fields, showed great potential (R² = 0.989; Q² = 0.818) in predictive quality according to both internal and external validation criteria. Additionally, the average local ionization energy (ALIE), electrostatic potential (ESP), and orbital weighted dual descriptor (OWDD) were determined to identify the key structural moiety for scavenging capacity of flavonoids against hypochlorite. The computational results indicated that hypochlorous acid (HClO) serves as an electrophile undergoing electrophilic addition to the C6 carbon, which has the highest negative charge density, which are influenced by the functional groups on the flavones. The DFT calculated mechanism revealed the catalytic role of water of mono- and di-chlorination reactions, characterized by low activation barriers, and the involvement of neutral, instead of high-energy carbocation, intermediates.

Antrodia cinnamomea is a precious edible mushroom originating from Taiwan that has been popularly used for adjuvant hepatoprotection and anti-inflammation; however, the chemical principle for its anti-inflammatory activity has not been elucidated, which prevents the quality control of related products. Using the RAW264.7 model for the anti-inflammatory activity assay as a guide, we reported the isolation and structural elucidation of three potent anti-inflammatory compounds from isolated ergostanes (16) and lanostanes (6). Their structures were elucidated on the basis of spectroscopic data analysis including NMR and HR-QTOF-MS. Particularly, the absolute configurations of (25R)-antcin K, (25R)-antcin A, versisponic acid D, and (25R)-antcin C were determined by single crystal X-ray diffraction (XRD). The representative and most promising compound antcin A was shown to suppress pro-inflammatory biomolecule release via the down-regulation of iNOS and COX-2 expression through the NF-κB pathway while the mRNA levels of IL-1β, TNF-α and IL-6 were also decreased. The high dependency on structural variation and activity suggests that there might be special biological targets for antcin A. Our work makes it possible to develop evidence-based dietary supplements from Antrodia cinnamomea based on anti-inflammatory constituents.

For rapid and portable detection of ethylene in commercial fruit ripening storage rooms, we designed a smartphone-based optical fiber sensor (SOFS), which is composed of a 15 mW 365 nm laser for fluorescence signal excitation and a bifurcated fiber system for signal flow direction from probe to smartphone. Paired with a pyrene-tagged Grubbs catalyst (PYG) probe, our SOFS showed a wide linearity range up to 350 ppm with a detection limit of 0.6 ppm. The common gases in the warehouse had no significant interference with the results. The device is portable (18 cm × 8 cm × 6 cm) with an inbuilt power supply and replaceable optical fiber sensor tip. The images are processed with a dedicated smartphone application for RGB analysis and ethylene concentration. The device was applied in detection of ethylene generated from apples, avocados, and bananas. The linear correlation data showed agreement with data generated from a fluorometer. The SOFS provides a rapid, compact, cost-effective solution for determination of the fruit ethylene concentration dynamic during ripening for better fruit harvest timing and postharvest management to minimize wastage.