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.

Papaya leaves have been used as food and traditional herbs for the treatment of cancer, diabetes, asthma, and virus infections, but the active principle has not been understood. We hypothesized that the anti-inflammatory activity could be the predominant underlying principle. To test this, we extracted papaya leaf juice with different organic solvents and found that the ethyl acetate (EA) fraction showed the most outstanding anti-inflammatory activity by suppressing the production of nitric oxide (NO, IC₅₀ = 24.94 ± 2.4 μg/mL) and the expression of pro-inflammatory enzymes, such as inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2), and cytokines including interleukins (IL-1β and IL-6), and a tumor necrosis factor (TNF-α) in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Transcriptomic analysis and Western blot results revealed its anti-inflammatory mechanisms were through the MAPK signaling pathway by inhibiting the phosphorylation of ERK1/2, JNKs, and p38 and the prevention of the cell surface expression of TLR4. Furthermore, we discovered that the EA fraction could inhibit the replication of alpha-coronavirus (HCoV-229E) and beta-coronavirus (HCoV-OC43 and SARS-CoV-2) and might be able to prevent cytokine storms caused by the coronavirus infection. From HPLC-QTOF-MS data, we found that the predominant phytochemicals that existed in the EA fraction were quercetin and kaempferol glycosides and carpaine. Counter-intuitively, further fractionation resulted in a loss of activity, suggesting that the synergistic effect of different components in the EA fraction contribute to the overall potent activity. Taken together, our results provide preliminary evidence for papaya leaf as a potential anti-inflammatory and anti-coronavirus agent, warranting further study for its use for human health promotion.

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.

Antrodia cinnamomea (AC), a potential medicinal fungus which possesses anti-inflammatory and anticancer activities, has been previously reported to be able to ameliorate muscle wasting in cisplatin-treated lung tumor-bearing mice via AC extract. However, whether AC extract modulates muscle cell differentiation, apoptosis, and cell cycle progression remains unclear. Here, we show that the ethanol extract of AC (EEAC) significantly restored cisplatin-reduced quadricep mass in mice. EEAC attenuated cisplatin/gemcitabine (C/G)-suppressed elongated myotube formation, which is differentiated from C2C12 cells. Moreover, EEAC synergized with C/G to inhibit cell growth of LLC1 cells, whereas EEAC attenuated C/G-reduced proliferation of C2C12 cells. Although EEAC protected C/G-induced apoptosis of both LLC1 and C2C12, EEAC suppressed cyclin D expression in LLC1 while partially restoring C/G-reduced cyclin D level in C2C12 cells. Finally, as and participate in inducing skeletal muscle atrophy, we found that C/G induced and expression in C2C12 cells but with its effect significantly attenuated by EEAC. Our findings indicate that AC extract is a potential natural agent for attenuating cisplatin-induced muscle atrophy. Practical Applications. Muscle atrophy is one of the major side effects caused by chemotherapy. In addition to inducing cell death, chemotherapeutic agents inhibit cell growth of both cancer and normal cells as well. Our current findings indicated that AC extract attenuates cisplatin-induced muscle wasting and apoptosis of C2C12 cells. AC extract is a potential dietary supplement used for ameliorating chemotherapy-induced muscle atrophy.

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.