Noni (Morinda citrifolia L.) fruit juice has been used in Polynesia as a traditional folk medicine and is very popular worldwide as a functional food supplement. In this study, compounds present in Hawaiian Noni fruit juice, with anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells were identified. Five compounds were isolated using a bioassay-driven technique and phytochemical analysis of noni fruit juice: asperulosidic acid (1), rutin (2), nonioside A (3), (2E,4E,7Z)-deca-2,4,7-trienoate-2-O-β-d-glucopyranosyl-β-d-glucopyranoside (4), and tricetin (5). The structures of these five compounds were determined via NMR spectroscopy and LC/MS. In an anti-inflammatory assay, compounds 1–5 inhibited the production of nitric oxide (NO), which is a proinflammatory mediator, in LPS-stimulated macrophages. Moreover, the mechanisms underlying the anti-inflammatory effects of compounds 1–5 were investigated. Parallel to the inhibition of NO production, treatment with compounds 1–5 downregulated the expression of IKKα/β, I-κBα, and NF-κB p65 in LPS-stimulated macrophages. Furthermore, treatment with compounds 1–5 downregulated the expression of nitric oxide synthase and cyclooxygenase-2. Thus, these data demonstrated that compounds 1–5 present in noni fruit juice, exhibited potential anti-inflammatory activity; these active compounds may contribute preventively and therapeutically against inflammatory diseases.

Astragalus membranaceus is a famous herb found among medicinal and food plants in East and Southeastern Asia. The Nrf2-ARE assay-guided separation of an extract from Jing liqueur led to the identification of a nontoxic Nrf2 activator, methylnissolin-3-O-β-d-glucopyranoside (MNG, a component of A. membranaceus). Nrf2 activation by MNG has not been reported before. Using Western Blot, RT-qPCR and imaging, we investigated the cytoprotective effect of MNG against hydrogen peroxide-induced oxidative stress. MNG induced the expression of Nrf2, HO-1 and NQO1, accelerated the translocation of Nrf2 into nuclei, and enhanced the phosphorylation of AKT. The MNG-induced expression of Nrf2, HO-1, and NQO1 were abolished by Nrf2 siRNA, while the MNG-induced expression of Nrf2 and HO-1 was abated and the AKT phosphorylation was blocked by LY294002 (a PI3K inhibitor). MNG reduced intracellular ROS generation. However, the protection of MNG against the H₂O₂ insult was reversed by Nrf2 siRNA with decreased cell viability. The enhancement of Nrf2 and HO-1 by MNG upon H₂O₂ injury was reduced by LY294002. These data showed that MNG protected EA.hy926 cells against oxidative damage through the Nrf2/HO-1 and at least partially the PI3K/Akt pathways.

A new polyketide containing the benzoisoquinoline-9-one moiety, peyronetide A (1), and three other new derivatives peyronetides B–D (2–4), as well as one known compound (5) were purified from the cultured broth of the endophytic fungus Peyronellaea sp. FT431, which was isolated from the Hawaiian indigenous plant, Verbena sp. The structures of the new compounds were determined through the analysis of HRMS and NMR spectroscopic data. Compounds 1, 2, and 5 showed cytotoxic activities against TK-10 (human kidney adenocarcinoma cells), cisplatin sensitive A2780S (human ovarian carcinoma cells), and cisplatin resistant A2780CisR cell lines, with IC₅₀ values between 6.7 to 29.2 μM.

The aim of this study is to identify the minor compounds in Jing liqueur, determine the concentration of metals, amino acids, and polysaccharides, and evaluate their Nrf2 activity and cytotoxicity. Jing liqueur that contains Chinese medicine is one of the best-selling liqueurs in China, which is also marketed in the United States. Totally, we have isolated 189 minor compounds including one new molecule (7) from a concentrated Jing liqueur, with the concentrations of most isolated compounds at micromolar levels. The structures of all these compounds were determined by using MS and NMR (1D and 2D) or by comparison of their chemical and physical data with reported values in the literatures. Besides, the concentrations of iron (0.52 mg/L), zinc (0.21 mg/L), calcium (11.0 mg/L), L-proline (2.33 mg/L), L-arginine (1.73 mg/L), total amino acids (9.84 mg/L), and total polysaccharides (337.4 mg/L) were determined. Jing liqueur, the five fractions and most of the compounds isolated from Jing liqueur were screened for their activities in the Nrf2-ARE and MTT assays. At 5.2 mg/mL the crude enhanced the Nrf2 activity. At 80 μg/mL, fraction IV weakly but fraction V strongly activated Nrf2. Among the compounds screened in the Nrf2 assay, eighteen activated Nrf2 at 40 μg/mL and compounds 51 and 126 from fraction V were the most active. The crude, all the five fractions, and Nrf2 activators were not cytotoxic toward HepG2 cells. In conclusion, Jing liqueur contains different classes of compounds including flavonoids, terpenoids, alkaloids, coumarins, cinnamic acid or coumaric acid, and phenyl ethanol (or acetic acid) derivatives, benzoquinone, naphthoquinone, anthraquinones or phenanphrene derivatives, xanthones, chromone, and γ-pyrone derivatives, lignans, other aromatic compounds, and others. Jing liqueur and the eighteen compounds, which were isolated from Jing liqueur, could activate Nrf2 without any cytotoxicity.

Aspergillus is one of the most diverse genera, and it is chemically profound and known to produce many biologically active secondary metabolites. In the present study, a new aspochalasin H1 (1), together with nine known compounds (2–10), were isolated from a Hawaiian plant-associated endophytic fungus Aspergillus sp. FT1307. The structures were elucidated using nuclear magnetic resonance (NMR) (¹H, ¹H-¹H COSY, HSQC, HMBC, ROESY and 1D NOE), high-resolution electrospray ionization mass spectroscopy (HRESIMS), and comparisons with the reported literature. The absolute configuration of the new compound was established by electronic circular dichroism (ECD) in combination with NMR calculations. The new compound contains an epoxide moiety and an adjacent trans-diol, which has not been reported before in the aspochalasin family. The antibacterial screening of the isolated compounds was carried out against pathogenic bacteria (Staphylococcus aureus, Methicillin-resistant S. aureus and Bacillus subtilis). The antiproliferative activity of compounds 1–10 was evaluated against human breast cancer cell lines (MCF-7 and T46D) and ovarian cancer cell lines (A2780).

Methylnissolin-3-O-β-d-glucopyranoside (MNG) is a pterocarpan analog, which protects EA.hy926 cells against oxidative damage through the Nrf2/HO-1 pathway. However, the effects of MNG on obesity-induced inflammatory responses in adipocyte-macrophage co-culture remain unclear. A differentiated murine preadipocyte cell line (3T3-L1) was co-cultured with a murine macrophage cell line (RAW264.7). Intracellular lipid accumulation was determined using Oil Red O staining. Western blotting was performed to investigate the expression of adipogenesis- and inflammation-associated proteins. Cell culture supernatants were assayed using ELISA kits to measure the levels of proinflammatory cytokines such as interleukin 6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1). MNG inhibited lipid accumulation and the production of IL-6 and MCP-1 in the 3T3-L1 and RAW264.7 cell co-culture. Moreover, MNG inhibited the protein expression of CCAAT/enhancer-binding protein alpha (C/EBPα), C/EBPβ, peroxisome proliferator-activated receptor γ (PPARγ), cyclooxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS) under the same co-culture conditions. MNG also inhibited IL-6 and MCP-1 production compared with the co-culture control. These findings demonstrate that MNG inhibited lipid accumulation and inflammatory response by downregulating IL-6 and MCP-1 production and protein expression of C/EBPβ, C/EBPα, PPARγ, COX-2, and iNOS in co-culture conditions with 3T3-L1 and RAW264.7 cells. These results suggest that MNG may be beneficial in preventing obesity-related inflammatory status.