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Mesona chinensis Benth. (or Platostoma palustre (Blume) A. J. Paton), an edible and medicinal plant, is the main ingredient in black jelly, Hsian-tsao tea, and beverages, and its processed products are popular in China as well as in Southeast Asian countries. Previous studies have shown that the alcohol extract of Mesona chinensis Benth. (MC) can reduce the accumulation of oleic acid and ameliorate hyperlipidemia. However, researchers have not yet determined whether it could improve intestinal permeability and metabolic dysfunction by controlling gut microbial dysbiosis and thus reducing hyperlipidemia. This study aimed to explore the potential mechanism by which MC regulates metabolic function disorders in hyperlipidemic high-fat diet (HFD)-fed rats and mice from the perspective of gut microbiota. This study analyzed the effects of MC on metabolic indices related to hyperlipidemia in HFD-fed rats and the abundance and diversity of the gut microbiota via 16S rRNA V3–4 region pyrosequencing to investigate the regulation of the gut microbiota by MC. We further confirmed that MC ameliorates hyperlipidemia by regulating the gut microbiota by simultaneously administering antibiotics and MC to C57BL/6 mice and measuring their metabolic indices. These results indicate that MC reduces the lipid concentration in the serum of HFD-fed rats, thereby significantly alleviating hyperlipidemia, and regulates the abundance ratio and diversity of the gut microbiota, thereby exerting a beneficial effect on hyperlipidemia. Our further antibiotic experiments in mice revealed that the administration of MC was unable to reduce body weight or serum and organ lipid concentrations in the antibiotic-treated group of hyperlipidemic mice. This study provides evidence that the microbiota is an alternative target for the antihyperlipidemic effect of MC. [ABSTRACT FROM AUTHOR]

The DBU‐catalyzed benzylation of 1H‐benzotriazole amides with methyl coumalate is demonstrated for the synthesis of stilbenes and biaryl derivatives. The transformation involves the base‐catalyzed Michael addition of methyl coumalate to the 6π‐electrocyclic ring opening decarboxylation aromatization. Furthermore, the novel 2‐phenylnaphthalene derivatives showed potent anti‐proliferative and anti‐invasive activities against H1299 cells. [ABSTRACT FROM AUTHOR]

Patchouli alcohol, a significant bioactive component of the herbal plant Pogostemon cablin, has considerable medicinal and commercial potential. Several genes and transcription factors involved in the biosynthesis pathway of patchouli alcohol have been identified. However, so far, regulatory factors directly interacting with patchouli synthase (PTS) have not been reported. This study was conducted to analyze the interaction between PcENO3 and PcPTS to explore the molecular regulation effect of PcENO3 on patchouli alcohol biosynthesis. PcENO3, a homologous protein of Arabidopsis ENO3 belonging to the enolase family, was identified and characterized. Subcellular localization experiments in Arabidopsis protoplast cells indicated that the PcENO3 protein was localized in both the cytoplasm and nucleus. The physical interaction between PcENO3 and PcPTS was confirmed through yeast two‐hybrid (Y2H), GST pull‐down, and bimolecular fluorescence complementation assays. Furthermore, the Y2H assay demonstrated that PcENO3 could also interact with JAZ proteins in the JA pathway. Enzymatic assays showed that the interaction with PcENO3 increased the catalytic activity of patchoulol synthase. Additionally, suppression of PcENO3 expression with VIGS (virus‐induced gene silencing) decreased patchouli alcohol content compared to the control. These findings suggest that PcENO3 interacts with patchoulol synthase and modulates patchoulol biosynthesis by enhancing the enzymatic activity of PcPTS. [ABSTRACT FROM AUTHOR]

In neurodegenerative diseases, microglial activation and neuroinflammation are essential for the control and progression of neurodegenerative diseases. Mitigating microglium-induced inflammation is one strategy for hindering the progression of neurodegenerative diseases. Ferulic acid (FA) is an effective anti-inflammatory agent, but its potential role and regulation mechanism in neuroinflammatory reactions have not been fully studied. In this study, the neuroinflammation model was established by lipopolysaccharide (LPS), and the inhibitory effect of FA on neuroinflammation of BV2 microglia was studied. The results showed that FA significantly reduced the production and expression of reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α), leukocyte-6 (IL-6) and interleukin-1β (IL-1β). We further studied the mechanism of FA's regulation of LPS-induced BV2 neuroinflammation and found that FA can significantly reduce the expression of mTOR in BV2 microglia induced by LPS, and significantly increase the expression of AMPK, indicating that FA may have an anti-inflammatory effect by activating the AMPK/mTOR signaling pathway to regulate the release of inflammatory mediators (such as NLRP3, caspase-1 p20 and IL-1β). We further added an autophagy inhibitor (3-MA) and an AMPK inhibitor (compound C, CC) for reverse verification. The results showed that FA's inhibitory effects on TNF-α, IL-6 and IL-1β and its regulatory effect on AMPK/mTOR were destroyed by 3-MA and CC, which further indicated that FA's inhibitory effect on neuroinflammation is related to its activation of the AMPK/mTOR autophagy signaling pathway. In a word, our experimental results show that FA can inhibit LPS-induced neuroinflammation of BV2 microglia by activating the AMPK/mTOR signaling pathway, and FA may be a potential drug for treating neuroinflammatory diseases. [ABSTRACT FROM AUTHOR]

STAT3 signaling pathway is an important target for human cancer therapy. Thus, the identification of small-molecules that target STAT3 signaling will be of great interests in the development of anticancer agents. The aim of this study was to identify novel inhibitors of STAT3 pathway from the roots of Zanthoxylum nitidum (Roxb.) DC. The bioassay-guided fractionation of MeOH extract of Z. nitidum using a STAT3-responsive gene reporter assay led to the isolation of angoline (1) as a potent and selective inhibitor of the STAT3 signaling pathway ([IC.sub.50] = 11.56 µM). Angoline inhibited STAT3 phosphorylation and its target gene expression and consequently induced growth inhibition of human cancer cells with constitutively activated STAT3 ([IC.sub.50] = 3.14-4.72 µ.M). This work provided a novel lead for the development of anti-cancer agents targeting the STAT3 signaling pathway. Keywords: STAT3 signaling pathway Inhibitor Zanthoxylum nitidum Angoline, Introduction The STAT3 signaling pathway plays key roles in cell motility, proliferation, and differentiation. However, STAT3 signaling can also lead to oncogenesis, uncontrolled cell proliferation, and metastasis of many human [...]

Rubia cordifolia L. (Rubiaceae), one of the traditional anti-rheumatic herbal medicines in China, has been used to treat rheumatoid arthritis (RA) since ancient times. Purpurin, an active compound of Rubia cordifolia L., has been identified in previous studies and exerts antibacterial, antigenotoxic, anticancer, and antioxidant effects. However, the efficacy and the underlying mechanism of purpurin to alleviate RA are unclear. In this study, the effect of purpurin on inflammation was investigated using macrophage RAW264.7 inflammatory cells, induced by lipopolysaccharide (LPS), and adjuvant-induced arthritis (AIA) rat was established to explore the effect of purpurin on joint damage and immune disorders; the network pharmacology and molecular docking were integrated to dig out the prospective target. Purpurin showed significantly anti-inflammatory effect by reducing the content of IL-6, TNF-α, and IL-1β and increasing IL-10. Besides, purpurin obviously improved joint injury and hypotoxicity in the liver and spleen and regulated the level of FOXP3 and CD4+/CD8+. Furthermore, purpurin reduced the MMP3 content of AIA rats. Network pharmacology and molecular docking also suggested that MMP3 may be the key target of purpurin against RA. The results of this study strongly indicated that purpurin has a potential effect on anti-RA. [ABSTRACT FROM AUTHOR]

An approach for the construction of furanochromanone skeletons has been developed through a DABCO‐catalyzed cascade reaction with good yields (up to 83%) and high diastereoselectivity (>20:1 dr). Notably, the asymmetric catalytic version of this reaction was further studied, obtaining furanochromanones bearing four contiguous stereogenic centers with excellent enantio‐ and diastereoselectivity (up to 98% ee, >20:1 dr). This protocol causes the formation of a variety of substituted furanochromanones via an oxa‐Michael/Michael addition/deformylation cascade reaction. [ABSTRACT FROM AUTHOR]

In this paper, Lignosus rhinocerotis (Cooke) Ryvarden (L. rhinocerotis) cultivated in rice medium (LRR) and in sawdust medium (LRS) was harvested. Then, in terms of the LRR, LRS, and wild L. rhinocerotis (LRW), the total flavonoid contents, total polyphenol contents, total polysaccharide contents, and metabolites were detected; antioxidants of their aqueous extracts and anti-inflammatory of their polysaccharides were performed. In addition, the possible mechanism of the polysaccharides of L. rhinocerotis inhibiting lung damage was elucidated. The results showed that 32 compounds were characterized in L. rhinocerotis, including flavonoids, terpenoids, lignans, and steroids and there were 20 compounds in cultivated and wild L. rhinocerotis; LRR has the highest total polyphenol and flavonoid contents, as well as ABTS and DPPH scavenging capacity. The total polysaccharide contents and the FRAP scavenging capacity of wild L. rhinocerotis were higher than those of cultivated L. rhinocerotis. The inhibition of polysaccharides of LRW (PLRW) on LPS-induced MRC-5 damage was stronger than that of the polysaccharides from cultivated L. rhinocerotis. The PLRW may alleviate lung damage by inhibiting the NLRP3 pathway and thereby suppressing the inflammatory response. In summary, both cultivated and wild L. rhinocerotis are abundant in bioactive components and have antioxidant and anti-inflammatory activities. [ABSTRACT FROM AUTHOR]

In this study, the antioxidant and hypolipidemic effects of Mesona Chinensis Benth (MCB) extracts were evaluated. Seven fractions (F0, F10, F20, F30, F40, F50 and MTF) were obtained from the MCB ethanol extracts. Compared to the commercial antioxidants (vitamin C), MTF and F30 exhibited higher antioxidant activities in the antiradical activity test and the FRAP assay. The half-inhibition concentration (IC50) for MTF and F30 were 5.323 µg/mL and 5.278 µg/mL, respectively. MTF at 200 µg/mL significantly decreased the accumulation of TG in oleic acid (OA)-induced HepG2 cells and reversed the inhibitory effect of Compound C on AMPK (MTF and F30 significantly increased the glucose utilization of insulin-induced HepG2 cells). In addition, the components of MTF were identified by HPLC-MS, which were caffeic acid, quercetin 3-O-galactoside, isoquercetin, astragalin, rosmarinic acid, aromadendrin-3-O-rutinoside, rosmarinic acid-3-O-glucoside and kaempferol-7-O-glucoside. Through statistical correlations by Simca P software, it was found that the main antioxidant and hypolipidemic components of MCB might be caffeic acid, kaempferol-7-O-glucoside, rosmarinic acid-3-O-glucoside and aromadendrin-3-O-rutinoside, which may play important roles in the AMPK pathway. MTF and F30 in MCB could be potential health products for the treatment of hyperlipidemia. [ABSTRACT FROM AUTHOR]

Anthracycline dutomycin is a tetracyclic quinone glycoside produced by Streptomyces minoensis NRRL B-5482. SW91 is a C-12 demethylated dutomycin derivative, which was identified in our previous research. In vitro cytotoxicity and apoptosis assays of these two compounds were conducted to demonstrate their antiproliferation activities. The results showed that both dutomycin and SW91 block cells at the S phase, whereas dutomycin shows more significant inhibition of cell growth. Their interactions with calf thymus DNA (CT-DNA) were investigated, with dutomycin exhibiting higher binding affinity. The molecular docking demonstrated that the 12-methyl group makes dutomycin attach to the groove of DNA. These findings suggest that dutomycin has binding higher affinity to DNA and impairs DNA replication resulting in more significant antitumor activity. [ABSTRACT FROM AUTHOR]

Bornyl acetate (BA) is known as a natural aromatic monoterpene ester with a wide range of pharmacological and biological activities. Borneol acetyltransferase (BAT), catalyzing borneol and acetyl-CoA to synthesize BA, is alcohol acetyltransferase, which belongs to the BAHD super acyltransferase family, however, BAT, responsible for the biosynthesis of BA, has not yet been characterized. The seeds of Wurfbainia villosa (homotypic synonym: Amomum villosum) are rich in BA. Here we identified 64 members of the BAHD gene family from the genome of W. villosa using both PF02458 (transferase) and PF07247 (AATase) as Hidden Markov Model (HMM) to screen the BAHD genes. A total of sixty-four WvBAHDs are distributed on 14 chromosomes and nine unanchored contigs, clustering into six clades; three WvBAHDs with PF07247 have formed a separated and novel clade: clade VI. Twelve candidate genes belonging to clade I-a, I-b, and VI were selected to clone and characterize in vitro , among which eight genes have been identified to encode BATs acetylating at least one type of borneol to synthesize BA. All eight WvBATs can utilize (−)-borneol as substrates, but only five WvBATs can catalyze (+)-borneol, which is the endogenous borneol substrate in the seeds of W. villosa ; WvBAT3 and WvBAT4 present the better catalytic efficiency on (+)-borneol than the others. The temporal and spatial expression patterns of WvBATs indicate that WvBAT3 and WvBAT4 are seed-specific expression genes, and their expression levels are correlated with the accumulation of BA, suggesting WvBAT3 and WvBAT4 might be the two key BATs for BA synthesis in the seeds of W. villosa. This is the first report on BAT responsible for the last biosynthetic step of BA, which will contribute to further studies on BA biosynthesis and metabolism engineering of BA in other plants or heterologous hosts. [ABSTRACT FROM AUTHOR]

Ilex asprella is a plant from Aquifoliaceae. Its root is commonly used as folk medicinal materials in southern China. The chemical compositions of I. asprella are rich in pentacyclic triterpenoids, which show various biological activities and demonstrate a good prospect for drug development. The elucidation of biosynthesis mechanism of triterpenoids in I. asprella could lay important foundations for the production of these precious plant secondary metabolites by metabolic engineering. Our previous studies have revealed IaAO1 (a CYP716A210 homolog) responsible for the C-28 oxidation of α- and β-amyrin. Herein, we reported the identification of three more cytochrome P450 monooxygenase genes IaAO2 (a CYP716A212 homolog), IaAO4 (CYP714E88), IaAO5 (CYP93A220), and a cytochrome P450 reductase gene IaCPR by using Saccharomyces cerevisiae eukaryotic expression system and gas chromatography-mass spectrometry. Among them, the protein encoded by IaAO2 can catalyze the C-28 oxidation of α-amyrin and β-amyrin, IaAO4 can catalyze the C-23 oxidation of ursolic acid and oleanolic acid, while IaAO5 is responsible for the C-24 oxidation of β-amyrin. By introducing three genes IaAO1 , IaAO4 and IaCPR into S. cerevisiae. We constructed an engineered yeast strain that can produce C-23 hydroxyl ursane-type triterpenoid derivatives. This study contributes to a thorough understanding of triterpenoid biosynthesis of medicinal plants and provides important tools for further metabolic engineering. [ABSTRACT FROM AUTHOR]

The standalone metallo‐β‐lactamase‐type thioesterase (MβL‐TE), belongs to the group V nonreducing polyketide synthase agene cluster, catalyzes the rate‐limiting step of product releasing. Our work first investigated on the orthologous MβL‐TEs from different origins to determine which nonconserved amino acid residues are important to the hydrolysis efficiency. A series of chimeric MβL‐TEs were constructed by fragment swapping and site‐directed mutagenesis, in vivo enzymatic assay showed that two nonconserved residues A19 and E75 (numbering in HyTE) were critical to the catalytic performance. Protein structure modeling suggested that these two residues are located in different areas of HyTE. A19 is on the entrance to the active sites, whereas E75 resides in the linker between the two β strands which hold the metal‐binding sites. Combining with computational simulations and comparative enzymatic assay, different screening criteria were set up for selecting the variants on the two noncatalytic and nonconserved key residues to improve the catalytic activity. The rational design on A19 and E75 gave five candidates in total, two (A19F and E75Q) of which were thus found significantly improved the enzymatic performance of HyTE. The double‐point mutant was constructed to further improve the activity, which was increased by 28.4‐fold on product accumulation comparing to the wild‐type HyTE. This study provides a novel approach for engineering on nonconserved residues to optimize enzymatic performance. [ABSTRACT FROM AUTHOR]