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Breviscapine is one of the extracts of several flavonoids of Erigeron breviscapus. Scutellarin is the main active component of breviscapine, and the qualitative or quantitative criteria as well. Scutellarin and its analogs share a similar skeleton of the flavonoids. Breviscapine has been widely used in the treatment of cerebral infarction and its sequelae, cerebral thrombus, coronary heart disease (CHD), and angina pectoris. Breviscapine has a broad spectrum of pharmacological activities, such as increasing blood flow, improving microcirculation, dilating blood vessels, decreasing blood viscosity, promoting fibrinolysis, inhibiting platelet aggregation, and thrombosis formation, etc. In addition, breviscapine and its analogs have significant value for drug research and development because of the superiority of those significant bioactivities. Furthermore, an increasing number of pharmacokinetic studies have explored the mechanism of scutellarin and its analogs. To provide a comprehensive understanding of the current research on breviscapine, scutellarin, and the analogs, the structural features, distribution situation, preparation method, content determination method, clinical applications, pharmacological action as well as pharmacokinetics are summarized in the present review.

Ethnopharmacological relevance Sparganii Rhizoma (SR), a traditional Chinese medicine (TCM), is the rhizome of Sparganium stoloniferum Buch.-Ham. mainly distributed in East Asia. It has been used for eliminating blood stasis, promoting the flow of Qi, removing the retention of undigested food and relieving pain in China for hundreds of years. Aim of the review This review summarizes comprehensive information in traditional clinical application, processing, phytochemistry, pharmacology, quality control and toxicity of SR, in exploring future scientific and therapeutic potentials. Materials and methods Pertinent information was systematically collected from several electronic scientific databases (e.g., Web of Science, PubMed, China Knowledge Resource Integrated, Springer, Elsevier, ScienceDirect, and Google Scholar), PhD and MS dissertations, and classic Chinese medical books. Results SR is a gynecological drug which is often used to treat dysmenorrhea, mass in the abdomen, amenorrhea due to blood stasis, and abdominal distension in TCM. Two kinds of processed products of SR are included in Chinese Pharmacopoeia, which have better pharmacological effects than the crude herb. Approximately 180 compounds have been identified from SR, including phenylpropanoids, flavonoids, anthraquinones, organic acids, alkaloids, steroids, volatile oils, diarylheptanes, etc. The crude extracts and isolated components of SR have been reported to have anti-tumor, antithrombotic, estrogen antagonistic , anti-inflammatory, analgesic, antioxidant, anti organ fibrosis and other pharmacological activities. SR also has reproductive toxicity. Conclusions As an important TCM, SR has been demonstrated by modern pharmacological researches to have significant bioactivities, especially on anti-tumor, antithrombotic, and estrogen antagonistic activities. These activities provide prospects for the development of new drugs and therapeutics for future applications. Nevertheless, quality control and evaluation, in-depth pharmacological mechanism, and toxicological effect of SR require further detailed research.

Ethnopharmacological relevance Curcumae Rhizoma-Sparganii Rhizoma (CR-SR), an ancient and classical herbal couple, has been extensively used for tumor treatment in clinic of traditional Chinese medicines (TCMs). Aim of the study The study aimed to uncover the anti-tumor active materials of CR-SR water decoction (CR:SR = 1:1) via an integrated approach of spectrum-effect relationship, molecular docking, and ADME evaluation. Materials and methods The anti-tumor activities toward A549, HepG2, Hela, BGC-823, and MCF-7 cells of the different polar elution fractions (DPEFs) of CR, SR, and CR-SR were determined by Cell Counting Kit-8 (CCK-8) assay. Likewise, the DPEFs’ combinations of CR and SR were also tested. The chemical fingerprints of these fractions were profiled by HPLC. Meanwhile, HPLC-ESI-Q-TOF-MS/MS was applied for the identification of chemical components. The main effect-related compounds were screened out by spectrum-effect relationship and molecular docking method. The oral bioavailability and druggability of these active components were subsequently evaluated. Finally, five monomeric compounds were validated experimentally using HepG2 cells. Results The 80% ethanol elution fraction of CR, SR, and CR-SR showed strong anti-tumor effects toward five cells. Also, the combinations with the 80% ethanol elution fraction of CR and SR showed stronger tumor inhibition effects among the DPEFs’ combinations of CR and SR. By spectrum-effect relationship, HPLC-MS, and molecular docking analysis, 24 main effect-related compounds seemed to have potential anti-tumor effects. ADME evaluation showed rutin performed low oral bioavailability and druggability. Therefore, we suppose that 23 compounds (including 4 unknown compounds) are the primary anti-tumor active components of CR-SR water decoction. Among them, zederone, curcumol, chlorogenic acid, calycosin, and curcumenol were validated successfully with good tumor inhibition effects. Conclusions In summary, this study demonstrated that the multi-components of CR-SR contribute to its anti-tumor effects. It established a rapid and useful strategy to explore the active material basis of traditional Chinese herbal couples with a multi-technology integrated approach in practice, including chromatography, mass spectrometry, machine algorithm models, online databases, and in vitro cell experiments.

Ethnopharmacological relevance Curcumae Rhizoma and Sparganii Rhizoma (CR-SR) are the classical herbal couple for activating blood circulation and treating tumor in clinics. Aim of the study: To investigate the anti-tumor activity and to clarify the bioactive ingredients of herbal couple CR-SR and the single herbs Curcumae Rhizoma (CR) and Sparganii Rhizoma (SR). Materials and methods The active fractions of CR-SR decoction were fractioned by column chromatography. And isolated compounds were characterized by IR, ESI-MS, 1D and 2D-NMR techniques. Detecting linear-diarylheptanoids in CR-SR, CR and SR was realized through UPLC-LTQ-Orbitrap MSn, based on the fragmentation pathways established in this study, comparison with MS data of isolated compounds and references. The anti-tumor activities of different solvent fractions from CR-SR, CR and SR, as well as isolated ingredients were tested by CCK-8 method. Results Ultimately, a new compound (1), having a sulfonic acid group at C-3, named demethoxyshogasulfonic acid, along with another structurally similar 17 known linear-diarylheptanoids were isolated. These linear-diarylheptanoids (1–18) were divided into 12 categories based on the differences of substituents at C-3 and C-5 on the straight chain of seven carbons. Six fragmentation pathways were established by summarizing MS data of the 18 isolated compounds collected from UPLC-MS. Based on that, and retention times and MS fragmentation ions, 47 linear-diarylheptanoids were identified in CR-SR and CR, in which 12 linear-diarylheptanoids were also detected in SR. Most importantly, 5 sulfonated linear-diarylheptanoids were new compounds detected in CR and CR-SR. And the biological assay indicated that compounds 1–4 and 12–15 significantly reduced the proliferation and inhibited colony formation of MCF-7 and HepG2 cells. Conclusion The new compound (1) exhibited good anti-cancer activity, which suggests that a great effort has to be paid to investigate the bioactivity of sulfonated compounds. The fractions of CR-SR decoction exhibited stronger anti-tumor activities than that of CR and SR against 5 different cancer cells. As for chemical composition, it is the first time to report that diarylheptanoids are in Sparganiaceae and the sulfonated compounds in Zingiberaceae. Moreover, the linear-diarylheptanoids found in SR which being tested to possess good anti-tumor activity, plus those compounds in CR enhance the capacity of CR-SR. It shows importance of TCM compatibility.

Glioblastoma (GBM) is a typical malignant tumor, and there are no effective drugs capable of improving patient survival. Docosahexaenoic acid (DHA), a nutrient essential to animal health and neurodevelopment, exerts an anticancer effect in several types of cancer. However, the function of DHA in GBM is still unclear. Here, we showed that DHA could repress the migration and invasion of GBM U251 cells and promote their apoptosis in a dose- and time-dependent manner, indicating that DHA has an anticancer effect on GBM cells. Whole-transcriptome analysis indicated that DHA treatment mainly regulates the genes associated with receptor binding, oxidoreductase activity, organic acid transmembrane transporter activity, and carboxylic acid transmembrane transporter activity. Long non-coding RNAs (LncRNAs) involved in the regulation network of DHA were also identified, and their targets were assigned to the Gene Ontology (GO) categories. In silico analysis was conducted to predict the pathways related to the differentially expressed genes by DHA treatment. Our findings suggest that DHA acts as an antitumor agent in GBM, which may provide a suitable means of improving the efficacy of GBM treatment in the future.

Bioprosthetic heart valves (BHVs) originating from pigs are extensively used for heart valve replacement in clinics. However, recipient immune responses associated with chronic calcification lead to structural valve deterioration (SVD) of BHVs. Two well-characterized epitopes on porcine BHVs have been implicated in SVD, including galactose-α1,3-galactose (αGal) and N-glycolylneuraminic acid (Neu5Gc) whose synthesis are catalyzed by α(1,3) galactosyltransferase (encoded by the GGTA1 gene) and CMP-Neu5Ac hydroxylase (encoded by the CMAH gene), respectively. It has been reported that BHV from αGal-knockout pigs are associated with a significantly reduced immune response by human serum. Moreover, valves from αGal/Neu5Gc-deficient pigs could further reduce human IgM/IgG binding when compared to BHV from αGal-knockout pigs. Recently, another swine xenoantigen, Sd(a), produced by β-1,4-N-acetyl-galactosaminyl transferase 2 (β4GalNT2), has been identified. To explore whether tissue from GGTA1, CMAH, and β4GalNT2 triple gene-knockout (TKO) pigs would further minimize human antibody binding to porcine pericardium, TKO pigs were successfully produced by CRISPR/Cas9 mediated gene targeting. Our results showed that the expression of αGal, Neu5G and Sd(a) on TKO pigs was negative, and that human IgG/IgM binding to pericardium was minimal. Moreover, the analysis of collagen composition and physical characteristics of porcine pericardium from the TKO pigs indicated that elimination of the three xenoantigens had no significant impact on the physical proprieties of porcine pericardium. Our results demonstrated that TKO pigs would be an ideal source of BHVs. Statement of significance Surgical heart valve replacement is an established lifesaving treatment for diseased heart valve. Bioprosthetic heart valves (BHVs) made from glutaraldehyde-fixed porcine or bovine tissues are widely used in clinics but exhibit age-dependent structural valve degeneration (SVD) which is associated with the immune response against BHVs. Three major xenoantigens present on commercial BHVs, Galactosea α1,3 galactose (αGal), N-glycolylneuraminic acid (Neu5Gc) and glycan products of β-1,4-N-acetyl-galactosaminyl transferase 2 (β4GalNT2) are eliminated through CRISPR/Cas9 mediated gene targeting in the present study. The genetically modified porcine pericardium showed reduced immunogenicity but comparable collagen composition and physical characteristics of the pericardium from wild-type pigs. Our data suggested that BHVs from TKO pigs is a promising alternative for currently available BHVs from wild-type pigs.

The genus Alnus (Betulaceae) is comprised of more than 40 species. Many species of this genus have a long history of use in folk medicines. Phytochemical investigations have revealed the presence of diarylheptanoids, polyphenols, flavonoids, terpenoids, steroids and other compounds. Diarylheptanoids, natural products with a 1,7-diphenylheptane structural skeleton, are the dominant constituents in the genus, whose anticancer effect has been brought into focus. Pure compounds and crude extracts from the genus exhibit a wide spectrum of pharmacological activities both in vitro and in vivo. This paper compiles 273 naturally occurring compounds from the genus Alnus along with their structures and pharmacological activities, as reported in 138 references.

The anti-rheumatic fraction (ARF), is responsible for the anti-inflammatory and analgesic effects of Dianbaizhu derived from the aerial part of Gaultheria leucocarpa var. yunnanensis (Ericaceae). The gastrointestinal metabolism of ARF was investigated in vitro through simulating a series of models-gastric juice, intestinal juice, and human intestinal bacteria, analyzed by HPLC-DAD and UPLC-LTQ-Orbitrap-MSn. ARF includes three categories: methyl salicylate glycosides, organic acids and the others. The primordial and metabolic components of ARF bio-transformed by simulated gastric fluid (36 and 13), intestinal fluid (29 and 7) and two human fecal bacteria (34 and 34, 40 and 25) were characterized, respectively. The methyl salicylate glycosides, MSTG-B, MSTG-A and gaultherin, with terminal-xylosyl-moiety in sugar chain were always being found in the whole gastrointestinal incubation processing. The metabolites were formed through hydrolysis of ester and glucosidic bond, as well as methylation, hydroxylation, acetylation, sulfation, reduction, decarboxylation, deglycosylation and glucuronidation. The metabolic conversion effect of the four index compounds, MSTG-B, MSTG-A, gaultherin, and chlorogenic acid by human intestinal bacteria exhibited much stronger. Those markers' variation in content-time curve in volunteer A gut flora were faster than that in volunteer B's. These results indicate that ARF is relatively stable in the gastrointestinal tract.