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Amentotaxus yunnanensis H.L.Li is a threatened conifer distributed only in China, Laos, and Vietnam, whose fungal endophytes have not been exploited yet. The aims of this study were to screen and characterize antioxidant metabolites from endophytic fungi obtained from A. yunnanensis. Using the surface sterilization method, sixteen endophytic fungi were isolated from A. yunnanensis and classified into seven genera including Fusarium, Penicillium, Aspergillus, Diaporthe, Neopestalotiopsis, Purpureocillium, and Simplicillium through the analysis of Internal Transcribed Spacer (ITS) gene sequences. Among the ethyl acetate crude extracts, Fusarium foetens AQF6 contained the highest amount of polyphenol (117.76 ± 0.94 mg gallic acid equivalent/g) and flavonoid (169.01 ± 2.09 mg quercetin equivalent/g). Importantly, 400 µg/mL AQF6 extract exhibited 95.75 ± 1.1% and 85.66 ± 1.91% of 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radical-scavenging activities, respectively. Chemical investigation led to the isolation and identification of a new bisabolane-type sesquiterpene fusafoetriol (FUS) and 14 known compounds, among which six pure compounds showed free-radical scavenging activity against DPPH and hydroxyl radicals. Under H2O2 stress, the yeast model Saccharomyces cerevisiae treated with 4 mM FUS showed 43.31% increase in viability. FUS has the potential to be applied in nutraceutical, pharmaceutical and food technological applications. Thus, this is the first report demonstrating the presence of endophytic fungi inhabiting A. yunnanensis and their potential as a prolific source of antioxidant metabolites.

A chemical investigation of the methanol extract from the roots of Cudrania tricuspidata resulted in the isolation of 16 compounds, including prenylated xanthones 1–9 and flavonoids 10–16. Their structures were identified by NMR spectroscopy and mass spectrometry and comparisons with published data. Compounds 1–9 and 13–16 significantly inhibited PTP1B activity in a dose dependent manner, with IC50 values ranging from 1.9–13.6 μM. Prenylated xanthones showed stronger PTP1B inhibitory effects than the flavonoids, suggesting that they may be promising targets for the future discovery of novel PTP1B inhibitors. Furthermore, kinetic analyses indicated that compounds 1 and 13 inhibited PTP1B in a noncompetitive manner; therefore, they may be potential lead compounds in the development of anti-obesity and -diabetic agents.

In the course of studies on bioactive metabolites from marine fungi, a new 10-membered lactone, named penicillinolide A (1) was isolated from the organic extract of Penicillium sp. SF-5292 as a potential anti-inflammatory compound. The structure of penicillinolide A (1) was mainly determined by analysis of NMR and MS data and Mosher’s method. Penicillinolide A (1) inhibited the production of NO and PGE2 due to inhibition of the expression of iNOS and COX-2. Penicillinolide A (1) also reduced TNF-α, IL-1β and IL-6 production, and these anti-inflammatory effects were shown to be correlated with the suppression of the phosphorylation and degradation of IκB-α, NF-κB nuclear translocation, and NF-κB DNA binding activity. In addition, using inhibitor tin protoporphyrin (SnPP), a competitive inhibitor of HO activity, it was verified that the inhibitory effects of compound 1 on the production of pro-inflammatory mediators and NF-κB DNA binding activity were partially associated with HO-1 expression through Nrf2 nuclear translocation.

Inflammation is important in biomedical research, because it plays a key role in inflammatory diseases including rheumatoid arthritis and other forms of arthritis, diabetes, heart disease, irritable bowel syndrome, Alzheimer’s disease, Parkinson’s disease, allergies, asthma, and even cancer. In the present study, we describe the inhibitory effect of crude extracts and steroids isolated from the starfish Astropecten polyacanthus on pro-inflammatory cytokine (Interleukin-12 (IL-12) p40, interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α)) production in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells (BMDCs). Among those tested, compounds 5 and 7 showed potent inhibitory effects on the production of all three pro-inflammatory cytokines with IC50 values ranging from 1.82 ± 0.11 to 7.00 ± 0.16 μM. Potent inhibitory activities were also observed for compound 1 on the production of IL-12 p40 and IL-6 with values of 3.96 ± 0.12 and 4.07 ± 0.13 μM, respectively, and for compounds 3 and 4 on the production of IL-12 p40 with values of 6.55 ± 0.18 and 5.06 ± 0.16 μM, respectively. Moreover, compounds 2 (IC50 = 34.86 ± 0.31 μM) and 6 (IC50 = 79.05 ± 2.05 μM) exhibited moderate inhibitory effects on the production of IL-12 p40, whereas compounds 3 (IC50 = 22.80 ± 0.21 μM) and 4 (IC50 = 16.73 ± 0.25 μM) moderately inhibited the production of TNF-α and IL-6, respectively.

Excessive microglial stimulation has been recognized in several neurodegenerative diseases, including Parkinson’s disease (PD), Alzheimer’s disease (AD), amyotropic lateral sclerosis (ALS), HIV-associated dementia (HAD), multiple sclerosis (MS), and stroke. When microglia are stimulated, they produce proinflammatory mediators and cytokines, including nitric oxide (NO) derived from inducible NO synthase (iNOS), prostaglandin E2 (PGE2) derived from cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-12 (IL-12), and interleukin-6 (IL-6). These inflammatory reactions are related to the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Therefore, the modulation of NF-κB and MAPK is vital to prevent microglial activation and confer resistance against neuronal injury. In this study, steppogenin (1) isolated from Cudrania tricuspidata suppressed the neuroinflammatory responses to lipopolysaccharide (LPS). Steppogenin (1) inhibited the production of proinflammatory mediators and cytokines in LPS-challenged BV2 and rat primary microglial cells. Moreover, western blot analysis and immunofluorescence revealed that the nuclear translocation of NF-κB was inhibited in LPS-induced BV2 and rat primary microglial cells. The LPS-stimulated activation of BV2 and rat primary microglial cells was inhibited by steppogenin (1) through the suppression of c-Jun NH2-terminal kinase (JNK) and p38 MAPK signaling. These results suggested that steppogenin (1) exerted antineuroinflammatory effects against acute neuroinflammation in BV2 and rat primary microglial cells by suppressing the activation of NF-κB and MAPK signaling and the production of proinflammatory mediators and cytokines.

Cudrania tricuspidata Bureau (Moraceae) is an important source of traditional Korean and Chinese medicines used to treat neuritis and inflammation. Cudratricusxanthone A (1), a prenylated xanthone, isolated from C. tricuspidata, has a variety of biological and therapeutic activities. The goal of this study was to examine the effects of compound 1 on neuroinflammation and characterize its mechanism of action in lipopolysaccharide (LPS)-stimulated BV2 microglia. Cudratricusxanthone A (1) suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 enzymes and decreased the production of iNOS-derived nitric oxide and COX-2-derived prostaglandin E2 in LPS-stimulated mouse BV2 microglia. The compound also decreased tumor necrosis factor-α, interleukin (IL)-1β, and IL-12 production; inhibited the phosphorylation and degradation of IκB-α; and blocked the nuclear translocation of p50 and p65 in mouse BV2 microglia induced by LPS. Cudratricusxanthone A (1) had inhibitory effects on nuclear factor kappa B DNA-binding activity. Additionally, it inhibited the p38 mitogen-activated protein kinase signaling pathway. Our data suggests that cudratricusxanthone A (1) may be a useful therapeutic agent in the treatment of neurodegenerative diseases caused by neuroinflammation.