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Summary: Despite the development of an increasing number of multi-kinase and immune checkpoint inhibitors for hepatocellular carcinoma (HCC), improvement in cancer survival remains limited due to their similar structures and targets. Natural products (NPs) maintain diverse structures and activities and are important sources of drug discovery. Currently, most of active NPs exhibit ambiguous binding targets and mechanisms. Herein, we proposed the CIPHEN (compound-protein interactions prediction based on the heterogeneous network) to predict potential antihepatoma NPs and their targets. The evaluation of canonical compound-protein interactions (CPIs) databases and independent test demonstrated the good ability of CPIHN to reveal known and unreported CPIs. Both prediction and experiment results indicated that CIPHEN could unveil relationships between actively antihepatoma sesquiterpenoid dimers (SDs) and anti-HCC targets. In conclusion, the CIPHEN provides a promising choice to investigate the mode of action of compounds, which will help to accelerate the process of drug research and development against HCC.

The frog genus Odorrana is distributed across east and southeastern Asia. Based on morphological differences and molecular phylogenetics, a new species of the genus occurring from Leigong Mountain in Guizhou Province, China is described. Phylogenetic analyses based on DNA sequences of the mitochondrial 12S rRNA, 16S rRNA, and ND2 genes supported the new species as an independent lineage. The uncorrected genetic distances between the 12S rRNA, 16S rRNA, and ND2 genes between the new species and its closest congener were 5.0%, 4.9%, and 16.3%, respectively. The new species is distinguished from its congeners by a combination of the following characters: body size moderate (SVL 39.1–49.4 mm in males, 49.7 mm in female); head width larger than head length; tympanum distinctly visible; small rounded granules scattered all over dorsal body and limbs; dorsolateral folds absent; heels overlapping when thighs are positioned at right angles to the body; tibiotarsal articulation reaching the level between eye to nostril when leg stretched forward; vocal sacs absent in male and nuptial pads present on the base of finger I.

Abstract Ten new germacrane-type sesquiterpenoids, artemyrianosins A–J (1–10), were isolated from the aerial parts of Artemisia myriantha. Their structures were elucidated by spectral analyses including UV, IR, HRESIMS, 1D and 2D NMR, ECD and the absolute configurations of compounds 1 and 7–9 were characterized using X-ray crystallography. All isolates were tested their cytotoxicity against three human hepatoma cell lines (HepG2, Huh7, and SK-Hep-1), and compounds 1–3, 7, and 10 showed cytotoxicity with IC50 values ranging from 43.7 to 89.3 μM. Among them, the most active compound 3 exhibited activity against three human hepatoma cell lines with IC50 values of 43.7 μM (HepG2), 47.9 μM (Huh7), and 44.9 μM (SK-Hep-1). Graphical Abstract

Leading by cytotoxicity against HepG2 cells, bioactivity-guided fractionation of the EtOAc fraction from Artemisia atrovirens led to the isolation of 18 new guaianolide dimers, artematrolides A–R and lavandiolides A, B, C, H, and J. Eight compounds (1, 4, 10, 12, 13, and 19–21) were unambiguously confirmed by the single-crystal X-ray diffraction analyses, and the others were elucidated based on IR, UV, HRESIMS, 1D and 2D NMR experiments, and comparison of the experimental and calculated ECD data. Structurally, all of them were [4 + 2] Diels–Alder adducts of two monomeric guaianolides. The isolates were evaluated for their cytotoxicity against three human hepatoma cell lines, and 19 compounds demonstrated cytotoxicity against HepG2, SMMC-7721, and Huh7 cell lines. Especially, compounds 1, 12, 14, and 15 exhibited cytotoxicity with IC50 values of 4.4, 3.8, 7.6, and 6.7 μmol/L (HepG2), 9.6, 4.6, 6.6, and 6.0 μmol/L (SMMC-7721), and 7.6, 4.5, 6.9, and 5.6 μmol/L (Huh7), respectively. Notably, compound 12 showed the most promising activity against three human hepatoma cell lines and dose-dependently inhibited cell migration and invasion, induced G2/M cell cycle arrest and cell apoptosis in HepG2 cells, down-regulated the expression of BCL-2 and PARP-1, and activated PARP-1 to up-regulate the expression of cleaved-PARP-1.

Abstract Two new sesquiterpenoids, artemlavanins A (1) and B (3), together with fifteen known compounds (2 and 4−17) were isolated from the EtOH extract of Artemisia lavandulaefolia. The structures of new compounds were elucidated by extensive spectroscopic analyses (HRESIMS, 1D and 2D NMR) and ECD calculations. Compound 1 was a sesquiterpenoid lactone possessing a rearranged eudesmane skeleton; compounds 2–5, 6–8, 9 and 10–12 belonged to the eudesmane, guaiane, oppositane and farnesane sesquiterpenoids, respectively; compounds 13–17 were the phenyl derivatives with a 4-hydroxyacetophenone moiety. Twelve compounds (1–3, 5–7, 10–12, 14, 15 and 17) displayed cytotoxicity against hepatic stellate cell line LX2 (HSC-LX2) with IC50 values ranging from 35.1 to 370.3 μM. Compounds 2, 7, 10–12 and 17 exhibited the stronger cytotoxicity than silybin (IC50, 169.6 μM) with IC50 values of 82.1, 35.1, 95.0, 83.8, 81.6 and 90.1 μM. Compound 7 as the most active one showed significant inhibition on the deposition of human collagen type I (Col I), human hyaluronic acid (HA) and human laminin (HL) with IC50 values of 10.7, 24.5 and 13.3 μM. Graphic Abstract

Abstract Four new sesquiterpenoids, artemyrianins A–D (1–4), and three new norlignans, artemyrianins E–G (5–7), together with five known compounds (8–12), were isolated from the aerial parts of Artemisia myriantha (Asteraceae). The new compounds were established by spectroscopic data analyses (HRMS, IR, 1D and 2D NMR), and their absolute configurations were confirmed by the single-crystal X-ray diffraction or ECD calculations. The isolates showed cytotoxicity against HepG2 cells with IC50 values ranging from 33.3 to 145.2 μM. Graphic Abstract

Abstract Uncariae Ramulus Cum Uncis (Gou-Teng), the dried hook-bearing stems of several Uncaria plants (Rubiaceae), is a well-known herbal medicine in China. The clinical application of Gou-Teng is bewildered for the morphological and chemical similarity between different species. In order to discern their chemical and biological difference, an ultra-fast liquid chromatography equipped with ion trap time-of-flight mass spectrometry (UFLC-IT/TOF-MS) combining with melatonin (MT1 and MT2) and 5-hydroxytryptamine (5-HT1A and 5-HT2C) receptors agonistic assay in vitro was conducted on seven Uncaria species. As a result, 57 compounds including 35 indole alkaloids, ten flavonoids, five triterpenoids, five chlorogenic analogues, and two other compounds were characterized based on their MS/MS patterns and UV absorptions. Specifically, cadambine-type and corynanthein-type alkaloids were exclusively present in U. rhynchophylla and U. scandens, whereas corynoxine-type alkaloids were commonly detected in all the seven Uncaria plants. Three Uncaria species, U. rhynchophylla, U. macrophylla, and U. yunnanensis showed obviously agnostic activity on four neurotransmitter receptors (MT1, MT2, 5-HT1A, and 5-HT2C). This first-time UFLCMS-IT-TOF analyses integrated with biological assay on seven Uncaria plants will provide scientific viewpoints for the clinical application of Gou-Teng. Graphic Abstract

Abstract Gastrodia elata is a famous traditional Chinese herb with medicinal and edible application. In this study, three new polybenzyls, gastropolybenzylols G-I (1–3) were isolated from the EtOAc extract of G. elata. Their structures were identified by extensive spectroscopic analyses involving HRESIMS, UV, IR, 1D and 2D NMR. Compound 1 showed agonistic effects on MT1 and MT2 receptors with agonistic rates of 55.91±4.84% and 165.13±5.65% at the concentration of 0.5 mM, respectively, and an EC50 value of 76.24 μM on MT2 receptor. Graphic Abstract

Abstract Oligostilbenes have attracted much interest due to their intricate structures and diverse bioactivities. In this study, two stilbene dimers, (−)-7,8-cis-ε-viniferin (1) and carasiphenol A (2), and two trimers, suffruticosol A (3) and suffruticosol C (4), were investigated by electrospray ionization ion-trap time-of-flight multistage mass spectrometry (ESI-IT-TOF-MSn). Based on the MSn study, the fragmentation pathways and diagnostic ions of four oligostilbenes in both positive and negative modes were proposed. The consecutive elimination of phenol (C6H6O) and resorcinol (C6H6O2) moieties were the particular dissociation for oligostilbenes due to the presence of 1,2-diphenylethylene nucleus. The present MSn fragmentation study will provide valuable information for the fast characterization of oligostilbenes from complicated natural mixtures. Graphical Abstract

Abstract Mentha haplocalyx (Mentha canadensis) is widely used as a medicinal plant in traditional Chinese medicine, and the extracts of its aerial parts are found to significantly inhibit the activity of α-glucosidase with an IC50 value of 21.0 μg/mL. Bioactivity-guided isolation of the extracts afforded two new compounds (1 and 2), together with 23 known ones (3–25). Their structures were established by extensive spectroscopic analyses (1D and 2D NMR, MS, IR and UV). Compounds 1–17 and 21–25 were evaluated for their α-glucosidase inhibitory activities. Compound 11 was the most active ones with an IC50 values of 83.4 μM. These results verify the α-glucosidase inhibitory activity of M. haplocalyx (M. canadensis) and specify its active compounds for the first time. Graphical Abstract

Abstract A new flavane, bropapyriferol (1), and eleven known ones were isolated from the EtOAc part of Broussonetia papyrifera under the guidance of bioassay. The structure of compound 1 was determined by extensive 1D and 2D NMR, [α]D spectroscopic data and quantum computation. Daphnegiravan F (2) and 5,7,3′,4′-tetrahydroxy-3-methoxy-8,5′-diprenylflavone (3) showed significantly anti-oral microbial activity against five Gram-positive strains and three Gram-negative strains in vitro. Especially, compound 3 was more potent in suppressing Actinomyces naeslundii and Porphyromonas gingivalis (MIC = 1.95 ppm) than the positive control, triclosan. Graphical Abstract

Abstract Hepatitis B virus (HBV) infection causing acute and chronic hepatitis is a serious problem worldwide, whereas the current treatment methods are unsatisfactory. Traditional Chinese herbs that have long been used for medicinal purposes are fascinating sources for novel anti-HBV candidates. This paper summarizes the progress of anti-HBV constituents from diverse medicinal plants in China to provide information for searching new anti-HBV drugs from natural sources. Graphical Abstract

Colorectal carcinoma (CRC) is a common cause of morbidity and mortality worldwide. Two pathogenic pathways are involved in the development of adenoma to CRC. The first pathway involves APC/β-catenin characterized by chromosomal instability resulting in the accumulation of mutations. The second pathway is characterized by lesions in DNA mismatch repair genes. Aberrant DNA methylation in selected gene promoters has emerged as a new epigenetic pathway in CRC development. CRC screening is the most efficient strategy to reduce death. Specific DNA methylation events occur in multistep carcinogenesis. Epigenetic gene silencing is a causative factor of CRC development. DNA methylations have been extensively examined in stool from CRC and precursor lesions. Many methylated genes have been described in CRC and adenoma, although no definite DNA methylation biomarkers panel has been established. Multiple DNA methylation biomarkers, including secreted frizzled-related protein 2, secreted frizzled-related protein 1, tissue factor pathway inhibitor 2, vimentin, and methylguanine DNA methyltransferase, have been further investigated, and observations have revealed that DNA methylation biomarkers exhibit with high sensitivity and specificity. These markers may also be used to diagnose CRC and adenoma in early stages. Real time polymerase chain reaction (qPCR) is sensitive, scalable, specific, reliable, time saving, and cost effective. Stool exfoliated markers provide advantages, including sensitivity and specificity. A stool qPCR methylation test may also be an enhanced tool for CRC and adenoma screening.

A series of (E)-N-phenylstyryl-N-alkylacetamides, 5, were synthesized by direct reduction-acetylation of β-arylnitroolefins, followed by N-alkylation. The title compounds were characterized by 1H-NMR, EIMS and IR analysis. All the synthesized compounds were assayed as HIV-1 non-nucleoside reverse transcriptase inhibitors. A SAR study revealed that when group R1 in 5 was ortho-substituted, the resulting compounds showed better inhibitory activities against HIV-1 RT. Among the tested compounds, 5i (R1 = 2-Br, R2 = 3,5-difluorobenzyl) exhibited the highest enzyme activity, with a 88.89% inhibitory ratio against HIV-1 reverse transcriptase at the tested concentration. Further cell-based anti-HIV-1 assays showed that compound 5i exhibited a SI value of 29 with an EC50 value of 4 μM in C8166 cells.

Hemsleyaconitines F and G ( and , resp.) were isolated from the EtOH extract of Aconitum hemsleyanum. Their structures were elucidated by extensive analyses of the IR, 1D- and 2D-NMR, and MS data. The two C-diterpenoid alkaloids and possess a novel skeleton, featuring a five-membered D-ring between C(9), C(13), C(14), C(15), and C(16), which is quite different from the previously isolated six-membered D-ring analogs. [ABSTRACT FROM AUTHOR]

Two new C-diterpenoid alkaloids, named aconicarchamines A and B ( and , resp.), were isolated from Aconitum carmichaelii. By UV, IR, MS, and 1D- and 2D-NMR analyses, their structures were elucidated as 14,17-dihydro-14,17-dihydroxyajabicine and 15- O-acetyllassiocarpine. Compound is the third C-diterpenoid alkaloid with the lycoctine skeleton bearing an exocyclic C-atom at C(14). [ABSTRACT FROM AUTHOR]

Four new, highly oxygenated nortriterpenoids with the unique schisanartane skeleton, propindilactones A–D (1–4), were isolated from the aerial parts of Schisandra propinqua var. propinqua, together with four known schisanartane-type compounds. The structures of the new plant constituents were established on the basis of extensive spectroscopic methods. [ABSTRACT FROM AUTHOR]

The article focuses on the chemical components of the aquatic weed Pistia stratiotes L., commonly known as water lettuce in South and East China. The important aquatic weed has the ability to scatter wind-fever. The structures of the weed were determined by spectroscopic analysis. Information on the extraction and isolation of the plant are discussed.