The traditional Chinese medicine Xanthium sibiricum Patrin ex Widder is used to treat wind-cold headache, nasal congestion, nasal discharge, allergic rhinitis, sinusitis, urticaria, and arthritis. Our previous studies found that sesquiterpene lactones, the main bioactive constituents of X. sibiricum, relieved airway inflammation in an asthma mouse model. To obtain active sesquiterpenes, five undescribed ones, including a pair of eremophilanes and three xanthanolides, together with eight known xanthanolides were isolated from X. sibiricum. Their structures were identified by IR, UV, HR-ESI-MS and NMR spectroscopic data, and their absolute configurations were determined by X-ray crystallographic diffraction analysis and the comparison between their experimental and calculated electronic circular dichroism. All isolated compounds were evaluated for their inhibitory effects on nitric oxide production, and Tnf-α, Il-1β, and Il-6 mRNA expression induced by lipopolysaccharide in the macrophage cell line RAW264.7. Further investigation showed that xanthsibiriolide and 11β-hydroxyl-13-chloro-8-epi-xanthatin exerted their anti-inflammatory effects by inhibiting the PI3K/AKT/mTOR signaling pathway. Analysis of the structure-activity relationships indicated that the α,β-unsaturated lactone ring and the 1,5-epoxide group might be the bioactive groups of xanthanolides, and these results provide a basis for further exploration of sesquiterpene-type lead compounds with anti-inflammatory activity.

Ochrathinols A and B ((±)-1 and (±)-2), two undescribed sulfur-containing racemates, and ochracids A and B (3 and 4), two unprecedented pyrrolizidine alkaloids, were isolated from an Antarctic soil-derived fungus Aspergillus ochraceopetaliformis SCSIO 05702. Their structures including absolute configurations were determined through extensive spectroscopic analysis, chiral-phase HPLC analysis, quantum ECD calculations, and X-ray single-crystal diffraction. Ochrathinols A and B are unprecedented sulfur natural products featuring a novel 3-methylhexahydro-2H-cyclopenta [b]thiophene core. Interestingly, ochrathinol A ((±)-1) outstandingly suppressed the release of LPS-induced IL-1β, IL-6, and TNF-α inflammatory cytokines with concentration of 10 μM and alleviated the unbalanced NAD+/NADH ratio caused by LPS in RAW264.7 macrophages.

Cytotoxic activity-guided isolation studies on the underground parts of Valeriana sisymbriifolia Vahl. led to the isolation of 12 secondary metabolites including two undescribed iridoids, sisymbriifolivaltrate and sisymbriifolioside, and two unreported sesquiterpene lactones, sisymbriifolins A and B. Chemical structures of the isolates were established by extensive 1D and 2D NMR analyses as well as HR-ESI-MS. The in vitro cytotoxic activities of the extract, sub-fractions and isolates on lung (A549), breast (MCF7), gastric (HGC27) and prostate (PC3) cancer cell lines were evaluated by MTS assay. Sisymbriifolivaltrate, didrovaltrate, valtrate, 7-homovaltrate and 1-α-acevaltrate exhibited promising cytotoxic activity on MCF7 cell line with IC50 values ranging from 2.5 to 12.3 μM, while valtrate demonstrated the best cytotoxicity against A549 cells with the IC50 value of 7.5 μM. Valtrate and 7-homovaltrate were found to exert noteworthy cytotoxicity towards HGC27 cell line (IC50 values: 2.3 and 3.7 μM, respectively), whereas valtrate, 7-homovaltrate and 1-α-acevaltrate (IC50 values: 2.3-9.7 μM) were found to be potent cytotoxic against PC3 cells. Among the tested compounds, particularly valepotriate-type iridoids were found to be the main cytotoxic principles of V. sisymbriifolia.

Chromatographic fractionation of the 95% EtOH extract of the roots of Stellera chamaejasme yielded 20 sesquiterpenoids of four different types, guaiane-, carotane-, sesquicarane-, and alpiniane-types. Among them, sesquistrachanoids A-F were previously undescribed ones, whose structures including absolute configurations were elucidated by spectroscopic methods, the Mo2(OAc)4-induced ECD experiment, and analysis of experimental and calculated 1D NMR and ECD data. Sesquistrachanoid A is a 2,3-seco-guaiane-type sesquiterpenoid with a α-pyrone core and sesquistrachanoid B is the first example of 8,9-seco-guaiane-type sesquiterpenoid featured with an 1,8-δ-lactone core. Sesquistrachanoid C is a guaiane sesquiterpenoid characterized by a peroxide bridge between C-8 and C-10. All sesquiterpenoids were evaluated for their neuroprotective effects on cell damage induced by sodium nitroprusside in PC-12 cells. The bioassay results showed that six compounds at 10 μM could restore the cell viability, being comparable to that of the positive control edaravone. The mechanistic study on the most pronounced activity compound, stelleraguaianone B, demonstrated that it played a neuroprotective role by promoting the mRNA expression of antioxidant enzymes to reduce oxidative stress.

Nine undescribed phloroglucinol derivatives (dryatraols A-I) with five different backbones and three known dimeric acylphloroglucinols were isolated from the rhizome of Dryopteris atrata (Wall. Ex Kunze) Ching (Dryopteridaceae). Dryatraol A contains an unprecedented carbon skeleton-a butyrylphloroglucinol and a rulepidanol-type sesquiterpene are linked via a furan ring to form a 6/5/6/6 ring system. Dryatraols B and C are the first examples of monomeric phloroglucinols coupled with the aristolane-type sesquiterpene through the C-C bond. Dryatraol D features a rare spiro [benzofuran-2',5″-furan] backbone. Dryatraols E-I are five undescribed adducts with a butyrylphloroglucinol or filicinic acid incorporated into the germacrene-type sesquiterpene via a pyran ring. These undescribed structures were determined by comprehensively analysing the spectroscopic data, X-ray diffraction results, and electronic circular dichroism calculations. The result of in vitro antiviral activity evaluation indicated that dryatraol C displayed the strongest antiviral effect against both respiratory syncytial virus and influenza A virus (H1N1), with IC50 values of 11.9 μM and 5.5 μM, respectively. Dryatraols F-H exhibited considerable inhibitory activity against herpes simplex virus type 1 (HSV-1), with IC50 values ranging from 2.6 to 6.3 μM. Analysis of the inhibitory mechanism using a time-of-addition assay revealed that dryatraol G may inhibit the replication of HSV-1 by interfering with the late stage of the viral life cycle.

Phytochemical investigations of the methanol extract from Origanum dictamnus L. (Lamiaceae) resulted in the isolation of forty compounds belonging to the classes of terpenes, resorcinol derivatives, flavonoids, depsides, neolignans and jasmonates. Chromatographic isolations were targeted by using two analytical platforms, NMR and HPLC-PDA-MS. In parallel, HPLC-PDA-MS of individual fractions enabled the unambiguous identification of additionally eight components. In total 48 constituents were isolated/identified. Among the isolated constituents are four undescribed compounds, one resorcinol derivative, one monoterpene, one diterpene and one acylated flavonoid glycoside. The structures of the isolated compounds were elucidated on the basis of spectroscopic analyses, including 1D and 2D NMR, and HPLC-ESI-MS and HRMS experiments. Representative compounds were tested for their antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa. I4-II7-dicarvacrol was the most potent constituent.

The fragrant flowers of Rosa hugonis Hemsl. Contain abundant valuable rose oil and carotenoids. However, phytochemical investigation of this resource rich in phenolics with neuroprotective activity in vitro has been rarely reported. Purification of the 70% ethanol extracts from the flowers of R. hugonis by various chromatographic methods resulted in the isolation and characterization of five undescribed acylated flavonoid glycosides (Hugonisflavonoid A-E) together with forty known phenolics. The chemical structures of the undescribed compounds were elucidated by extensive analysis of their spectroscopic data and chemical methods. All the isolates were found from R. hugonis for the first time and evaluated for their neuroprotective effects on 6-OHDA induced injury in PC12 cells. Seventeen compounds displayed remarkable protective effects at concentrations of 10 μM. Hugonisflavonoid E can reduce excessive reactive oxygen species and up-regulate mRNA expression levels of superoxide dismutase 1 and catalase. Additionally, hugonisflavonoid E activated the phosphorylated proteins such as PDK1, Akt and GSk-3β. These findings suggested that R. hugonis could be a potential source for neuroprotective agents.

Eight undescribed iboga alkaloids, polyneurines A-H, were isolated from the bark of Tabernaemontana polyneura. The structures of these alkaloids were established by interpretation of the MS and NMR data, while the configurations were determined using GIAO NMR calculations and DP4+ probability analysis, TDDFT-ECD method, or X-ray diffraction analysis. Polyneurine A possesses a γ-lactone unit embedded within the iboga skeleton, while polyneurines D and E incorporate a formylmethyl moiety at C-3 of the iboga skeleton. Biosynthetic pathways towards the formation of polyneurines A, C, D, and E were proposed.