Methylparaben toxicity and its removal by microalgae Chlorella vulgaris and Phaeodactylum tricornutum.

The widespread occurrence of methylparaben (MPB) has aroused great concern due to its weak estrogenic endocrine-disrupting property and potential toxic effects. However, the degradation potential and pathway of MPB by microalgae have rarely been reported. Here, microalgae Chlorella vulgaris and Phaeodactylum tricornutum were used to investigate their responses, degradation potential and mechanisms towards MPB. MPB showed low-dose stimulation (by 86.02 ± 0.07% at 1 mg/L) and high-dose inhibition (by 60.17 ± 0.05% at 80 mg/L) towards the growth of C. vulgaris, while showed inhibition for P. tricornutum (by 6.99 ± 0.05%-20.14 ± 0.19%). The degradation efficiencies and rates of MPB were higher in C. vulgaris (100%, 1.66 ± 0.54-5.60 ± 0.86 day-1) than in P. tricornutum (4.3-34.2%, 0.04 ± 0.01-0.08 ± 0.00 day-1), which could be explained by the significantly higher extracellular enzyme activity and more fluctuation of the protein ratio for C. vulgaris, indicating a higher ability of C. vulgaris to adapt to pollutant stress. Biodegradation was the main removal mechanism of MPB for both the two microalgae. Furthermore, two different degradation pathways of MPB by the two microalgae were proposed. MPB could be mineralized and completely detoxified by C. vulgaris. Overall, this study provides novel insights into MPB degradation by microalgae and strategies for simultaneous biodegradation and detoxification of MPB in the environment.

Osthole: Synthesis, Structural Modifications, and Biological Properties.

Osthole, a naturally occurring coumarin-type compound, is isolated from the Chinese herbal medicine Cnidium monnieri (L.) and exhibits a broad range of biological properties. In this review, the total synthesis and structural modifications of osthole and its analogs are described. Additionally, the progress on bioactivities of osthole and its analogs has been outlined since 2016. Moreover, the structure-activity relationships and mechanisms of action of osthole and its derivatives are discussed. These can provide references for future design, development, and application of osthole and its analogs as drugs or pesticides in the fields of medicine and agriculture.

Combined Analysis of Volatile Terpenoid Metabolism and Transcriptome Reveals Transcription Factors Related to Terpene Synthase in Two Cultivars of Dendrobium officinale Flowers.

Dendrobium officinale is a kind of traditional Chinese herbal medicine. Its flowers could be used as health care tea for its aroma flavor and medicinal value. Most recent studies demonstrated that terpenoids are the main components of the aromatic compounds in the flowers, but the biosynthesis of terpenoids is poorly understood in D. officinale. In the experiment, the flowers from two cultivars of D. officinale with different smells were collected. The transcriptome analysis and combined volatile terpenoids determination were performed to identify the genes related to the biosynthesis of the terpenoids. The results showed that the different products of volatile terpenoids are α-thujene, linalool, α-terpineol, α-phellandrene, γ-muurolene, α-patchoulene, and δ-elemene in two cultivar flowers. The transcriptome analysis detected 25,484 genes in the flowers. And 18,650 differentially expressed genes were identified between the two cultivars. Of these genes, 253 genes were mapped to the terpenoid metabolism pathway. Among these genes, 13 terpene synthase (TPS) genes may have correlations with AP2/ERF, WRKY, MYB, bHLH, and bZIP transcription factors by weighted gene co-expression network analysis (WGCNA). The transcription factors have regulatory effects on TPS genes. These results may provide ideas for the terpenoid biosynthesis and regulatory network of D. officinale flowers.

Regioselective hemisynthesis and insecticidal activity of C8-hydrazones/acylhydrazones/sulfonylhydrazones coumarin-type derivatives of osthole.

Osthole, a coumarin-type natural product, is isolated from Chinese traditional herbal medicine Cnidium monnieri. In order to improve the pesticidal activity of osthole, and high value-added application of the plant Cnidium monnieri, a series of new derivatives containing hydrazone/acylhydrazone/sulfonylhydrazone skeletons at the C-8 position of osthole were regioselectively semi-prepared. The steric structure of 3c was determined by the X-ray crystal structure. Against Mythimna separata Walker, benzoylhydrazone 3b (R1 = 4-CH3Ph) showed 1.6 folds potent insecticidal activity of the precursor osthole. Introduction of the acylhydrazones on the 3'-methyl-2'-butylenyl fragment at the C-8 position of osthole can improve the insecticidal activity. These will provide a foundation for future structural modifications of osthole as pesticidal agents.

Toxicology study of fraxinellone as ovicidal agents against Mythimna separata Walker and Bombyx mori Linaeus.

Fraxinellone is a naturally occurring degraded limonoid isolated from many species of plants in Meliaceae and Rutaceae. Besides structural modification of the lead compounds, the toxicology study of the lead compounds is also a very important procedure to develop insecticidal agents. Herein the toxicology study of fraxinellone was carried out as the ovicidal agent against the eggs of two lepidopteran insects Mythimna separata Walker and Bombyx mori Linaeus. Fraxinellone selectively exhibited an ovicidal activity against the eggs of M. separata. After treatment with fraxinellone, the eggshells of M. separata were shrinked, whereas those of B. mori had no obvious change. The dynamic process of M. separata embryo development demonstrated that the distinct difference between the treated eggs and the control ones was obvious at the second day after treatment, especially, the control embryo finished blastokinesis, whereas the treated ones were still laid at pre-reversion status and a lot of yolk can be seen around the embryo. It ultimately resulted in the eggshell withered and the egg hatching inhibited.

Semisynthesis and Pesticidal Activities of Derivatives of the Diterpenoid Andrographolide and Investigation on the Stress Response of Aphis citricola Van der Goot (Homoptera: Aphididae).

To discover natural-product-based pesticides, 7ß-oxycarbonylandrographolide derivatives were stereoselectively constructed from a labdane diterpenoid andrographolide. Among them, 2'-(n)Pr-1',3'-dioxin-7ß-oxy(m-Cl)benzoylandrographolide (IIc), 2'-(n)Pr-1',3'-dioxin-7ß-oxyacetylandrographolide (IIf), 2'-(p-Me)Ph-1',3'-dioxin-7ß-oxy(o-Cl)benzoylandrographolide (Vb), and 2'-(p-Me)Ph-1',3'-dioxin-7ß-oxy(m-Cl)benzoylandrographolide (Vc) against Mythimna separata displayed the most promising growth inhibitory activity; 2'-(n)Pr-1',3'-dioxin-7ß-oxy(o-Cl)benzoylandrographolide (IIb: LC50 = 0.406 mg/mL) and IIc (LC50 = 0.415 mg/mL) exhibited the most pronounced acaricidal activity (andrographolide; LC50: 5.106 mg/mL) and good control effects against Tetranychus cinnabarinus; compounds Ic, IIe, and Va-c (LD50 = 0.035-0.039 µg/nymph) showed potent aphicidal activity (andrographolide: LD50 = 0.178 µg/nymph), and compounds IIe and Vb showed good control effects against Aphis citricola. Moreover, it was found that Hsp70 of A. citricola was an important gene involved in stress response to andrographolide and its derivatives.

Evaluation of biological activities, and exploration on mechanism of action of matrine-cholesterol derivatives.

To develop new potential pesticides, a series of matrine-cholesterol derivatives were prepared by modifications of two non-food bioactive products matrine and cholesterol. Two N-phenylsulfonylmatrinic esters (5i and 5j) showed the most potent insecticidal activity against Mythimna separata Walker. Two N-benzylmatrinic esters (5e and 5g) exhibited the most promising aphicidal activity against Aphis citricola Van der Goot. Especially compound 5e showed good control effects in the greenhouse against A. citricola. Some interesting results of their structure-activity relationships were also observed. By reverse transcription polymerase chain reaction (RT-PCR) and quantitative real-time polymerase chain reaction (qRT-PCR) analysis of HMG-CoA reductase in apterous adults of A. citricola, it demonstrated that matrine and cholesterol may be the HMG-CoA reductase inhibitors, and the hydroxyl of cholesterol or the lactam ring of matrine may be important for acting with HMG-CoA reductase in A. citricola.

Research on mechanism of charred hawthorn on digestive through modulating "brain-gut" axis and gut flora.

ETHNOPHARMACOLOGICAL RELEVANCE: Hawthorn is a traditional Chinese medicine for high-calorie-diet-induced dyspepsia (HC-DID) for thousands of years old. Based on traditional Chinese medicine (TCM) theory and clinical and non-clinical trials, its stir-frying processed product, charred hawthorn, possesses better effect. At present, most research mainly focuses on chemical constituents of hawthorn before and after stir-frying process, but there is no relevant action-mechanism study about fragrant odor promoting HC-DID during the stir-frying process of the hawthorn. AIM OF THE STUDY: The purpose of the present study is to research on mechanism of hawthorn decoction coupled with odor of charred hawthorn on digestive in rats with HC-DID. MATERIALS AND METHODS: The SPF Kunming (KM) mice and Sprague Dawley (SD) rats were randomly divided into 7 groups: control group, model group, cisapride group, hawthorn group (HT), charred hawthorn group (CHT), odor of charred hawthorn (OCHT), CHT + OCHT group. The rats were modeled as HC-DID, whose treatment by intragastric administration and odor administration. Obvious symptoms of HC-DID were observed. Gastrointestinal motility were detected. Histopathology was performed in hypothalamus and gastrointestinal tract. Related brain-gut peptides were assayed in serum, hypothalamus and gastrointestinal tract. Illumina Miseq platform was used for 16S rDNA high-throughput sequencing to detect the intestinal flora structure of the caecum of rats. RESULTS: Traditional Chinese medicine decoction of hawthorn (HT and CHT) regulated the body weight, food intake, gastrointestinal motility and abnormal secretion of brain-gut peptides in rats with HC-DID, and the odor of charred hawthorn also had good curative effect for it. Moreover, the intestinal dysbiosis was induced by high-calorie diet in rats with dyspepsia, and hawthorn decoction could ease this trend. CONCLUSION: The above study showed that hawthorn decoction coupled with the odor of charred hawthorn effectively alleviate HC-DID in rats by regulating the "Brain-Gut" axis and gut flora. Odor treatment of hawthorn could be a potential therapeutic approach for HC-DID.

Silver nanoparticles exert concentration-dependent influences on biofilm development and architecture.

OBJECTIVES: To investigate the impact of silver nanoparticles (AgNPs) on the biofilm growth and architecture. MATERIALS AND METHODS: Silver nitrate was reduced by d-maltose to prepare AgNPs in the presence of ammonia and sodium hydroxide. The physicochemical properties of AgNPs were characterized by transmission electron microscopy, ultraviolet-visible spectroscopy and inductively coupled plasma mass spectrometry. The development of biofilm with and without AgNPs was explored by crystal violet stain. The structures of mature biofilm were visually studied by confocal laser scanning microscopy and scanning electron microscopy. Bacterial cell, polysaccharide and protein within biofilm were assessed quantitatively by colony-counting method, phenol-sulphuric acid method and Bradford assay, respectively. RESULTS: The spherical AgNPs (about 30 nm) were successfully synthesized. The effect of AgNPs on Pseudomonas aeruginosa biofilm development was concentration-dependent. Biofilm was more resistant to AgNPs than planktonic cells. Low doses of AgNPs exposure remarkably delayed the growth cycle of biofilm, whereas high concentration (18 µg/mL) of AgNPs fully prevented biofilm development. The analysis of biofilm architecture at the mature stage demonstrated that AgNPs exposure at all concentration led to significant decrease of cell viability within treated biofilms. However, sublethal doses of AgNPs increased the production of both polysaccharide and protein compared to control, which significantly changed the biofilm structure. CONCLUSIONS: AgNPs exert concentration-dependent influences on biofilm development and structure, which provides new insight into the role of concentration played in the interaction between antibacterial nanoparticles and biofilm, especially, an ignored sublethal concentration associated with potential unintended consequences.

Astraglaus polysaccharide protects diabetic cardiomyopathy by activating NRG1/ErbB pathway.

Diabetic cardiomyopathy (DCM) is one of the main cardiac complications among diabetic patients. According to previous studies, the pathogenesis of DCM is associated with oxidative stress, apoptosis and proliferation of local cardiac cells. It showed, NRG1 can improve the function of mitochondria, and thereby, increasing proliferation and decreasing apoptosis of cardiac muscle cell via ErbB/AKT signaling, also, exert antioxidative function. Besides, NRG1/ErbB pathway was impaired in the DCM model which suggested this signaling played key role in DCM. Astraglaus polysaccharide (APS), one of the active components of Astragalus mongholicus, showed striking antioxidative effect. Here, in this study, our data showed that APS can promote proliferation and decrease apoptosis in AGE-induced DCM cell model, besides, APS can decrease intracellular ROS level, increase activity of SOD, GSH-Px and lower level of MDA and NO in DCM cell model, indicating APS exerted antioxidative function in DCM model cells. Besides, western blot results revealed APS induced NRG1 expressing and the phosphorylation level of ErbB2/4. In addition, the elevated NRG1 promoted AKT and PI3k phosphorylation which indicated APS may exert its function by NRG1/ErbB and the downstream AKT/PI3K signaling. Canertinib is ErbB inhibitor. The effect of APS on proliferation, apoptosis, antioxidation and NRG1/ErbB pathway was partly abolished after the cells were co-treated with APS and canertinib. Taken together, these results suggested APS may display its protective function in DCM cells by activating NGR1/ErbB signaling pathway. And our study increased potential for prevention and therapy to DCM.

Prenatal High Estradiol Exposure Induces Sex-Specific and Dietarily Reversible Insulin Resistance Through Decreased Hypothalamic INSR.

An adverse intrauterine environment may induce adult disease in offspring, but the mechanisms are not well understood. It is reported that fresh embryo transfer (ET) in assisted reproductive technology leads to high maternal estradiol (E2), and prenatal high E2 exposure increases the risk of organ disorders in later life. We found that male newborns and children of fresh ET showed elevated fasting insulin and homeostasis model of assessment for insulin resistance index (HOMA-IR) scores. Male mice with high prenatal estradiol exposure (HE) grew heavier than control mice and developed insulin resistance; they also showed increased food intake, with increased orexigenic hypothalamic neuropeptide Y (NPY) expression. The hypothalamic insulin receptor (INSR) was decreased in male HE mice, associated with elevated promoter methylation. Chronic food restriction (FR) in HE mice reversed insulin resistance and rescued hypothalamic INSR expression by correcting the elevated Insr promoter methylation. Our findings suggest that prenatal exposure to high E2 may induce sex-specific metabolic disorders in later life through epigenetic programming of hypothalamic Insr promoter, and dietary intervention may reverse insulin resistance by remodeling its methylation pattern.

Synergistic anticancer effects of triptolide and celastrol, two main compounds from thunder god vine.

Triptolide and celastrol are two main active compounds isolated from Thunder God Vine with the potent anticancer activity. However, the anticancer effect of triptolide in combination with celastrol is still unknown. In the present study, we demonstrated that the combination of triptolide with celastrol synergistically induced cell growth inhibition, cell cycle arrest at G2/M phase and apoptosis with the increased intracellular ROS accumulation in cancer cells. Pretreatment with ROS scavenger N-acetyl-L-cysteine dramatically blocked the apoptosis induced by co-treatment with triptolide and celastrol. Treatment with celastrol alone led to the decreased expressions of HSP90 client proteins including survivin, AKT, EGFR, which was enhanced by the addition of triptolide. Additionally, the celastrol-induced expression of HSP70 and HSP27 was abrogated by triptolide. In the nude mice with xenograft tumors, the lower-dose combination of triptolide with celastrol significantly inhibited the growth of tumors without obvious toxicity. Overall, triptolide in combination with celastrol showed outstanding synergistic anticancer effect in vitro and in vivo, suggesting that this beneficial combination may offer a promising treatment option for cancer patients.