Although we believe that the cell surface sialic acids (Sias) are playing an important role in cell–cell interactions and related tumor metastasis processes, acquisition of their quantitative information has yet been a challenge to date. Here, we reported the construction of a new analytical platform for Sias-specific imaging and quantification. We used N-azidoacetyl-mannosamine tetraacylated as a metabolic sugar substrate to bioassemble azido-Sias on the surface of cells via the metabolic pathway of Sias de novo synthesis. These azido-Sias allow us to perform a duplex Sias-specific analysis with various fluorescent and elemental reporters such as DIBO-Alexa Fluor 647, DBCO-DOTA-Eu, and DBCO-PEG4-BODIPY, which can be easily labeled and/or tagged through an effective copper-free bioorthogonal click reaction. Compared to the previous reported strategies, we quantified the cell surface Sias with the LODs (3σ) down to 8.9 fmol and 0.24 pmol using 153Eu- and 10B-species unspecific isotope dilution ICPMS, in addition to their red- and green-CLSM profiling. Such a platform enables us to evaluate Sias regulation under the administration of paclitaxel, finding that 1 μM paclitaxel induced a significant Sias decrease of 67% on the surface of hepatic tumor cell SMMC-7721, while had no obvious adverse effect to that of para-carcinomatous liver cell LO2. Besides Sias, we believe that this metabolism-based click-mediated platform will provide opportunities to study other monosaccharides and their corresponding biological roles when more corresponding chemically modified sugar substrates and specific bioorthogonal reactions are developed.

Norsampsone E (1), an unprecedented decarbonyl polycyclic polyprenylated acylphloroglucinol, together with one new and two known analogues (2–4), was isolated from the aerial parts of Hypericum sampsonii. Compound 1 featured an unusual homoadamantyl skeleton with the loss of C-4 carbonyl and followed by the formation of a new C–C bond between C-3 and C-5. Their structures and absolute configurations were elucidated by extensive NMR spectroscopy, single-crystal X-ray experiments, ECD calculations and CD comparison methods, and further confirmed using the single-crystal X-ray structures of biogenetically related congeners 3 and 4. Besides, compounds 1 and 2 showed direct binding to the RXRα-LBD protein in the SPR assay with a KD of 10.28 μM and 31.70 μM, respectively. Furthermore, compound 1 (5–20 μM) showed potent RXRα transcriptional inhibitory activity in a dose dependent manner, while compound 2 (5–20 μM) slightly enhanced RXRα transactivation.

Restenosis (or neointimal hyperplasia) remains a clinical limitation of percutaneous coronary angioplasty. Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are known to be involved in the development of restenosis. The present study aimed to investigate the ability and molecular mechanisms of methyl protodioscin (1), a steroidal saponin isolated from the root of Dioscorea nipponica, to inhibit neointimal formation. Our study demonstrated that 1 markedly inhibited the growth and migration of VSMCs (A7r5 cells). A cytometric analysis suggested that 1 induced growth inhibition by arresting VSMCs at the G1 phase of the cell cycle. A rat carotid artery balloon injury model indicated that neointima formation of the balloon-injured vessel was markedly reduced after extravascular administration of 1. Compound 1 decreased the expression levels of ADAM15 (a disintegrin and metalloprotease 15) and its downstream signaling pathways in the VSMCs. Moreover, the expressions and activities of matrix metalloproteinases (MMP-2 and MMP-9) were also suppressed by 1 in a concentration-dependent manner. Additionally, the molecular mechanisms appear to be mediated, in part, through the downregulation of ADAM15, FAK, ERK, and PI3K/Akt.

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid plaques and neurofibrillary tangles in the brain. The major component of the plaques, amyloid-β (Aβ), is generated from amyloid-β precursor protein (APP) by β- and γ-secretase-mediated cleavages. Multiple lines of evidence demonstrate that overproduction/accumulation of Aβ in vulnerable brain regions is a primary cause of the pathogenesis of AD. Among the twelve polyphenols isolated from the leaf extracts of Vitis thunbergii var. taiwaniana (VTT), stenophyllol C, stenophyllol B, ampelopsin C, vitisin A, and davidiol A were shown to significantly reduce both Aβ40 and Aβ42 levels in N2a695 cells. Further studies revealed that ampelopsin C and vitisin A reduce Aβ production through inhibiting β-secretase activity, while the effects of the other active polyphenols on reducing Aβ generation are through different mechanisms. These results suggest that VTT extracts may be beneficial for AD prevention and treatment.

Worldwide, many different grains are infected by various fungi that may produce trichothecene mycotoxins. Fungi that produce trichothecenes, as well as the trichothecenes themselves, are potential problems for public health. On the other hand, trichothecenes possess multiple biological activities. Reduced toxicity may result in their applications in the pharmaceutical field. Two new trichothecenes along with seven known trichothecenes were isolated from an endophyte of the herb plant Ajuga decumbens. Their structures were deduced from 1D and 2D NMR data. The results of MTT assays revealed that new trichothecene 2′,3′-epoxymyrothecine A, 1, and myrothecine A, 3, exhibited much lower toxicity compared to other trichothecenes. New trichothecene 2′,3′-epoxymyrothecine A, 1, could induce phosphorylation of JNK (c-Jun N-terminal protein kinase) protein and the PARP (poly ADP-ribose polymerase) cleavage, and eventually induce apoptosis in cancer cells. These results point out the possibility for application of trichothecenes as chemotherapeutic agent.

Two new bicyclic lactones, myrotheciumones A (1) and B (2) which possessed a rare ring-fusion system were isolated from Myrothecium roridum (M. roridum), an endophytic fungus of the medicinal herb plant Ajuga decumbens (A. decumbens) via an in vitro cytotoxicity assay. Structures were deduced from 1D and 2D NMR (Nuclear magnetic resonance) data. Myrotheciumone A’s in vitro cytotoxicity and apoptotic activity were evaluated and myrotheciumone A was shown to exert cytotoxicity via inducing apoptosis in cancer cell line.

We report the design and synthesis of a trifunctional probe for seeing and counting cancer cells using both fluorescence imaging (FI) and inductively coupled plasma mass spectrometry (ICPMS) for the first time. It consisted of a guiding cyclic RGD peptide unit to catch cancer cells via targeting the αvβ3 integrin overexpressed on their surface, a 5-amino-fluorescein moiety for FI using confocal laser scanning microscopy (CLSM) as well as a 2-aminoethyl-monoamide-DOTA group for loading stable europium ion and subsequent ICPMS quantification of the cancer cells without the use of radioactive isotopes. In addition to FI, the LOD (3σ) of the αvβ3 integrin was down to 69.2–309.4 amol per cell depending on the type of the αvβ3-positive cancer cells when using ICPMS and those of the cancer cell number reached 17–75. This probe developed enables us not only to see but also to count the αvβ3-positive cancer cells ultrasensitively, paving a new way for early diagnosis of cancer.

Src homology-2 domain-containing protein tyrosine phosphatase (Shp2), a novel proto-oncogenic protein, is an important target in cancer therapy research. Approximately 2000 plant extracts were screened to find its natural specific inhibitors, with the ethyl acetate (EtOAc) active extract of the root of Angelica dahurica showing considerable inhibitory effects (IC50 = 21.6 mg/L). Bioguided isolation of EtOAc extract led to 13 compounds, including 10 fatty acids and derivatives. All these compounds were isolated from the plant for the first time. The inhibitory effects of these compounds on the enzyme activities of Shp2, VH1-related human protein (VHR), and hematopoietic protein tyrosine phosphatase (HePTP) were investigated. 8Z,11Z-Feptadecadienoic acid (4), 14Z,17Z-tricosadienoic acid (5), caffeic acid (9), and 2-hydroxy-3-[(1-oxododecyl) oxy]propyl-β-d-glucopyranoside (11) showed considerable selective inhibition of Shp2 activity. After treatment of HepG2 cells with the compounds, only compound 5, a polyunsaturated fatty acid, strongly induced poly (ADP-ribose) polymerase (PARP) cleavage in a dose- and time-dependent manner and increased the activities of caspase-3, caspase-8, and caspase-9 at 100 μM. Compound 5 also inhibited colony formation of HepG2 cells in a dose-dependent manner. Thus, this study reported fatty acids as specific Shp2 inhibitors and provided the molecular basis of one active compound as novel potential anticancer drug.

Tyrosine phosphatase Src-homology phosphotyrosyl phosphatase 2 (Shp2) was identified as a potential molecular target for therapeutic treatment of diabetes and obesity. However, there is still no systematic research on the enhancers for the Shp2 enzyme. The present study established a novel powerful model for the high-throughput screening of Shp2 enhancers and successfully identified a new specific Shp2 enhancer, oleanolic acid, from Chinese herbs.A compound extracted from Forsythia suspensa specifically promoted shp2 activity in a dose-dependent manner and was identified as oleanolic acid (OA).

•Three cytochalasans along with two new ent-eudesmane sesquiterpenes and one known ent-eudesmane sesquiterpene were isolated.•Phenochalasin B (4) could induce the PARP cleavage in a time- and dose-dependent manner and induce apoptosis in HepG 2 liver cancer cells.•[12]-Cytochalasin (5) could strongly inhibite the expression of CDK 4 with a time dependent manner which may lead to the apoptosis in HepG 2 cell line.•[1,3] Dioxacyclotridecino (6) which possess the same skeleton did not show any cytotoxic activity.Available online from an cytotoxic endophytic fungus Botryotinia fuckeliana A-S-3, three cytochalasans phenochalasin B (4), [12]-cytochalasin (5) and one [1,3] dioxacyclotridecino (6), along with two new ent-eudesmane sesquiterpenes, 1-keto-4α,15-epoxyeudesm-11-ol (1), and ent-4(15)-eudesmen-5,6-ol-1-one (2), and one known ent-eudesmane sesquiterpene ent-4(15)-eudesmen-11-ol-1-one (3) were isolated. The structures of these compounds were elucidated by interpretation of spectroscopic data. Among these compounds, two cytotoxic constituents were identified.Download full-size image