2-Methoxyjuglone, a Promising Bioactive Compound for Pharmaceutical and Agricultural Purposes: A Review.

2-Methoxyjuglone, a member of the 1,4-naphthoquinone family, was first obtained through semi-synthesis based on 2-hydroxyjuglone as the precursor in 1966. It has been isolated and identified from different plant species of the Juglandaceae, Sterculiaceae, and Proteaceae families. 2-Methoxyjuglone has been demonstrated to possess a wide range of biological activities, including antitumor, antifungal, and antibacterial activities; in addition, it has been shown to poison fish and inhibit seed germination. These properties make 2-methoxyjuglone a promising bioactive compound for pharmaceutical and agricultural purposes. This review article provides an overview of the current research progress on 2-methoxyjuglone for the first time, with a primary focus on the plant sources, extraction, identification, synthesis, and biological activities associated with this compound for further development.

Exosomes from PM 2.5-treated Human Bronchial Epithelial Cells Increase Lung Cancer Metastatic Potential.

Objective: Fine particulate matter (PM 2.5) is an air pollutant that has become of great concern in recent years. Numerous studies have found that PM 2.5 may contribute to lung cancer, but the pathogenesis has not yet been fully elucidated. In this study, we explored the roles of exosomes from bronchial epithelial cells in PM 2.5-promoted lung cancer metastasis. Methods: Exosomes were isolated from cell supernatants. An animal model of lung metastasis (established by tail vein injection of A549-luc) and in vitro studies with lung cancer cell lines were used to investigate the effects of exosomes derived from PM 2.5-treated human bronchial epithelial cells (PHBE-exo). Results: The animal experiments revealed that PHBE-exo-treated mice showed stronger luciferase activity and a larger relative metastatic region in the lungs, thus indicating that PHBE-exo promoted the metastatic potential of lung cancer. Additionally, PHBE-exo promoted the migration, invasion and epithelial-to-mesenchymal transition of lung cancer cells, in a manner mediated by activation of c-Jun N-terminal kinase. Conclusion: These results implied that PM 2.5 may promote the development of lung cancer through exosomes derived from bronchial epithelial cells, thus providing a potential interventional target for lung cancer. These findings broadened our understanding of cancer-promoting mechanisms of environmental pollutants.

Resorcylic Acid Lactones from an Ilyonectria sp.

Twelve new resorcylic acid lactones (RALs) including three new 16-membered RALs (1a, 1b and 2), eight new 14-membered RALs (3-10), and one new 12-membered RAL (11), along with five known 14-membered RALs (12-16), were identified from the fermentation of the soil-derived fungus Ilyonectria sp. sb65. Their structures were established by detailed analyses of 1D and 2D NMR, HRESIMS, and X-ray diffraction crystallography. All new compounds were evaluated for their cytotoxic effects against three human cancer cell lines, along with their potential as TRAIL sensitizers in TRAIL-resistant A549 human lung adenocarcinoma cells and their in vitro immunosuppressive effects against ConA-induced T-cell and LPS-induced B-cell proliferation.

Alkaloids with Immunosuppressive Activity from the Bark of Pausinystalia yohimbe.

Ten new alkaloids (1-10), including two pairs of enantiomeric mixtures (5a,b and 6a,b), and 15 known analogues (11-25) were obtained from the bark of Pausinystalia yohimbe. The structures of 1-25 were established by spectroscopic methods, and the absolute configurations of compounds 1-10 were resolved by X-ray diffraction and ECD data analyses. The in vitro immunosuppressive activities of selected isolates were tested. Compounds 11 and 16 exhibited moderate inhibition with IC50 values of 16.8 and 27.6 µM against ConA-induced T lymphocyte proliferation and 13.5 and 40.5 µM against LPS-induced B lymphocyte proliferation, respectively.

Neuroprotective Lignans from the Fruits of Schisandra bicolor var. tuberculata.

Nine new lignans (1-9) and ten known analogues (10-19) were isolated from the fruits of Schisandra bicolor var. tuberculata. The structures of compounds 1-9 were established on the basis of spectroscopic data analysis. The absolute configuration of compound 1 was determined by single-crystal X-ray diffraction analysis with Cu Kα irradiation techniques, and the absolute configurations of compounds 2-9 were deduced by comparing their experimental ECD spectra and optical rotations with those of compound 1 or similar compounds. All isolates were evaluated for their neuroprotective activities against CoCl2, H2O2, and Aß25-35-induced SH-SY5Y cell injury, and were found to exhibit different degrees of neuroprotective effects. At a low concentration of 3.2 nM, compounds 3, 8, 9, and 14-19 in CoCl2-induced, compounds 7, 8, 13, 17, and 18 in H2O2-induced, and compounds 2, 6, 7, 9, 10, and 12-19 in Aß25-35-induced SH-SY5Y cell injury models, showed statistically significant neuroprotective activities, when compared with each negative control group.

Nortriterpenoids from the stems and leaves of Schisandra viridis.

An extensive phytochemical study on the stems and leaves of Schisandra viridis A. C. Smith led to the isolation of two novel highly oxygenated schinortriterpenoids, pre-schisanartanin P (1) and wuweizidilactone Q (2), together with four known ones (3-6). Their structures with absolute configurations were established on the basis of comprehensive spectroscopic methods, including HRESIMS, 1D and 2D NMR analyses and ECD experiments. All isolates were evaluated for their in vitro cytotoxicities against HepG2, MCF-7 and HT-29 cancer cell lines, none of them showed significant activities.

Triterpenoids from the fruit of Schisandra glaucescens.

Five new triterpenoids, named schiglausins P-T (1-5), together with twelve known analogues (6-17), were isolated from the fruit of Schisandra glaucescens Diels. Their structures were determined by various spectroscopic methods, including HRESIMS, 1D and 2D NMR spectra and CD experiment. Additionally, all these compounds were tested for their cytotoxicities against B16 mouse melanoma cell line. Compounds 8, 11, 14, and 15 exhibited moderate anti-proliferative effects against B16 cells with IC50 values ranging from 3.64 to 27.00µM.

Bisabolane-Type Sesquiterpenoids from the Whole Plant of Parasenecio rubescens.

Twenty-two new highly oxygenated bisabolane-type sesquiterpenoids, pararubin A-V (1-22), were isolated from the whole plant of Parasenecio rubescens. The structure determination of 1-22, including the assignment of their relative configurations, was accomplished by extensive 1D and 2D NMR spectroscopy. The absolute configuration of pararubin A (1) was established by single-crystal X-ray crystallographic analysis. The isolated compounds were evaluated for their cytotoxic effects against three cancer cell lines (B16 mouse melanoma cells, HepG2 human hepatocellular carcinoma cells, and MCF7 human breast adenocarcinoma cells) and for their antimicrobial effects against Staphylococcus aureus, Escherichia coli, and Monilia albicans.

Alkaloids from the bulbs of Lycoris longituba and their neuroprotective and acetylcholinesterase inhibitory activities.

Three novel alkaloids (1-3), together with nineteen known ones (4-22), were isolated from the bulbs of Lycoris longituba. Their structures were elucidated on the basis of extensive spectroscopic analyses, which belong to several Amaryllidaceae alkaloid skeletons. Among them, the harmane-type alkaloids (the new compound 1 and the known compounds 5, 6 and 7) were found for the first time from Lycoris genus. The isolates were tested for their neuroprotective activities against CoCl2, H2O2 and Aß25-35-induced SH-SY5Y cell injuries, and the majority of them exhibited neuroprotective activities of different degrees. The acetylcholinesterase (AChE) inhibitory activities of the isolated alkaloids were also evaluated, while compounds 12, 14-20 and 22 exhibited extremely significant AChE inhibitory activities.

Lignans from the fruit of Schisandra glaucescens with antioxidant and neuroprotective properties.

Two rare 7,8-seco-lignans (1, 2), three new lignan glycosides (3, 4a, 4b), and 10 known lignans (5-14) were isolated from the fruit of Schisandra glaucescens Diels. The absolute configurations of 1 and 2 were determined by comparing their experimental and calculated electronic circular dichroism spectra. The molecular structures of the new compounds (3, 4a, and 4b), including their absolute configurations, were determined using various spectroscopic methods and hydrolysis reactions. The antioxidant activities of the isolated compounds were tested using 2,2-diphenyl-1-picrylhydrazyl and ferric reducing antioxidant power assays. Compounds 4, 7, 8, 10, 11, and 12 exhibited antioxidant activities of varying potential in both assays. Of these compounds, 7 showed the strongest 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging capacity, with IC50 values of 15.7 (150 µM DPPH) and 34.6 µM (300 µM DPPH), respectively, and 4, 12, and 7 displayed higher total antioxidant activities than Trolox in the ferric reducing antioxidant power assay. The neuroprotective effects of these compounds against Aß25-35-induced cell death in SH-SY5Y cells were also investigated. Compounds 1, 2, 6, 7, 8, 11, and 12 exhibited statistically significant neuroprotective effects against Aß25-35-induced SH-SY5Y cell death compared with the group treated only with Aß25-35.

Two new alkaloids from the bulbs of Lycoris sprengeri.

Two new alkaloids, lycosprenine (1) and 2α-methoxy-6-O-methyllycorenine (2), along with 22 known alkaloids (3-23b), were isolated from the bulb of Lycoris sprengeri. Their structures were elucidated on the basis of spectral analysis and by comparison of the spectroscopic data with those of known compounds. Selected compounds (1-3 and 6-9) were tested for their neuroprotective activities against H2O2-, CoCl2- and Aß25-35-induced SH-SY5Y cell injury, most of which exhibited neuroprotective effects of different degrees.

Four new compounds from the bulbs of Lycoris aurea with neuroprotective effects against CoCl2 and H2O2-induced SH-SY5Y cell injuries.

Three new alkaloids, 2α-hydroxy-6-O-n-butyloduline, O-n-butyllycorenine, (-)-N-(chloromethyl)lycoramine (1-3), and a new phenolic compound, ((7S)-7-(4-hydroxyphenyl)-7-hydroxypropyl)-2'-methylbenzene-3',6'-diol (14), along with ten known alkaloids (4-13), were isolated from the bulbs of Lycoris aurea collected from Huaihua County of Hunan Province, China. Their structures were elucidated by spectroscopic methods including HRESIMS, UV, IR, and NMR. All the isolated compounds were tested for their neuroprotective effects against CoCl2 and H2O2-induced SH-SY5Y cell death. Compounds 1-7 and 10 exhibited significant neuroprotective effects against CoCl2-induced SH-SY5Y cell injury, while compounds 1-5, 7, 10 and 12 showed obvious neuroprotective effects against H2O2-induced SH-SY5Y cell death.

Neuroprotective compounds from the bulbs of Lycoris radiata.

Three new alkaloids (1-3) and one new phenolic glycoside (4), together with twenty five known alkaloids (5-29), were isolated from the bulbs of Lycoris radiata collected from Huaihua county of Hunan province, China. Their structures were elucidated on the basis of comprehensive NMR and MS spectroscopic analysis. The isolated alkaloids were evaluated for their neuroprotective activities against CoCl2, H2O2 and Aß(25-35)-induced SH-SY5Y cell injuries. Compounds 1-3 showed significant neuroprotective effects against H2O2 or CoCl2-induced SH-SY5Y cell death, while compound 3 exhibited significant neuroprotective effects against Aß(25-35)-induced SH-SY5Y cell injury. The known alkaloids 5-29 also exhibited similar bioactivities of different degrees. These findings highlight the fact that the over 100 Amaryllidaceae alkaloids may have a big potential to neuroprotective activity.

2-methoxyjuglone induces apoptosis in HepG2 human hepatocellular carcinoma cells and exhibits in vivo antitumor activity in a H22 mouse hepatocellular carcinoma model.

In order to discover anticancer agents from natural sources, an ethanol-soluble extract of the root bark of Juglans cathayensis was investigated and showed cytotoxic effects against various human cancer cell lines. A subsequent phytochemical study on the EtOAc-soluble fraction determined 2-methoxyjuglone (1) as one of the main active constituents. Compound 1 was shown to be cytotoxic against HepG2 cells. Morphological features of apoptosis were observed in 1-treated HepG2 cells, including cell shrinkage, membrane blebbing, nuclear condensation, and apoptotic body formation. Cell cycle analysis with propidium iodide staining showed that 1 induced cell cycle arrest at the S phase in HepG2 cells. Flow cytometric analysis with annexin V and propidium iodide staining demonstrated that 1 induced HepG2 cell apoptotic events in a dose-dependent manner (0-8 µg/mL). Western blot analysis of apoptosis-related proteins revealed that 1 induces HepG2 cell apoptosis through mitochondrial cytochrome c-dependent activation of the caspase-9 and caspase-3 cascade pathway (intrinsic pathway). An in vivo experiment using tumor-bearing mice showed that treatment with 1 at 0.5 and 1.0 mg/kg per day decreased the tumor mass by 56% and 67%, respectively.

Neuroprotective lignans from the stems of Schisandra glaucescens.

Two new tetrahydrofuran lignans, schiglaucin A and B (1-2), together with eight known analogues (3-10), were isolated from the stems of Schisandra glaucescens Diels. Their structures were elucidated on the basis of spectroscopic techniques (HRESIMS, UV, IR, NMR, and CD experiments). All of the compounds were tested for their neuroprotective activities against H2O2- and CoCl2-induced cell injuries in SH-SY5Y cells, respectively. Compounds 1-10 showed significant neuroprotective effects against H2O2-induced SH-SY5Y cell death, while compounds 1-5 and 8-10 exhibited significant neuroprotective effects against CoCl2-induced SH-SY5Y cell injury.

Three new naphthalenyl glycosides from the root bark of Juglans cathayensis.

Phytochemical investigations of the root bark of Juglans cathayensis DODE. led to the isolation of three new naphthalenyl glycosides, Jugnaphthalenoside A-C (1-3). Their structures were elucidated on the basis of extensive analysis of spectroscopic data. The cytotoxicities of the three new compounds were also evaluated.

Schiglautone A, a new tricyclic triterpenoid with a unique 6/7/9-fused skeleton from the stems of Schisandra glaucescens.

Schiglautone A (1), a unique 6/7/9-fused tricyclic carbon backbone triterpenoid, was isolated from the stems of Schisandra glaucescens. Its structure was determined on the basis of spectroscopic analysis and single-crystal X-ray crystallography. A hypothetical biosynthetic pathway of 1 was postulated.