Amide alkaloids and neolignans from Piper hongkongense and their inhibitory activities of PCSK9 expression.

Four undescribed amide alkaloids hongkongensines A-C and 1-(1-oxo-6-hydroxy-2E,4E-dodecadienyl)-piperidine, five known amide alkaloids, and three known neolignans were isolated from the aerial part of Piper hongkongense. The planar structures of these compounds were determined by detailed analyses of HR-ESI-MS and NMR data. The absolute configurations of hongkongensines A-C were elucidated by single-crystal X-ray diffraction analysis and ECD calculations. Moreover, the inhibitory activities of PCSK9 expression in vitro for all compounds were assessed by PCSK9 AlphaLISA screening. Kadsurenone (10) displayed a significant inhibitory activity at 5 µM with an inhibition rate of 51.98%, compared with 55.55% of berberine (BBR 5 µM).

Undescribed (2-7')-neolignans and polyoxygenated cyclohexene glycosides from the aerial parts of Piper mutabile C. DC. and their inhibitory effects on nitric oxide production.

A phytochemical study of the aerial parts of Piper mutabile C. DC. revealed seven undescribed compounds [two (2-7')-neolignans and five polyoxygenated cyclohexene glycosides] and six known propenylcatechol derivatives. The chemical structures of the isolated compounds were elucidated by extensive HR-ESI-MS and NMR analyses, as well as comparison with the literature. The absolute configurations of the (2-7')-neolignans were confirmed by GIAO 13C NMR calculations with a sorted training set strategy and TD-DFT calculation ECD spectra. The (2-7')-neolignans and polyoxygenated cyclohexene glycosides are unusual in natural sources. Undescribed neolignans 1 and 2 inhibited NO production in RAW 264.7 cells, with respective IC50 values of 14.4 and 9.5 µM.

Targeted Isolation of Anti-inflammatory Lignans from Justicia aequilabris by Molecular Networking Approach.

Herein, the isolation of secondary metabolites from the aerial parts of Justicia aequilabris guided by HPLC-MSn and molecular networking analyses is reported. Twenty-two known compounds were dereplicated. Three new lignans (aequilabrines A-C (1-3)) and three known compounds (lariciresinol-4'-O-ß-glucose (4), roseoside (5), and allantoin (6)) were obtained. The anti-inflammatory activity of compounds 1-3 was evaluated in vitro by inhibiting the nitric oxide production (NO) and pro-inflammatory activity on the cytokine IL-1ß. Compounds 2 and 3 showed significant inhibitory activity against NO production, with IC50 values of 9.1 and 7.3 µM, respectively. The maximum inhibition of IL-1ß production was 23.5% (1), 27.3% (2), and 32.5% (3).

In-vitro and in-vivo anti-allergic effects of magnolol on allergic rhinitis via inhibition of ORAI1 and ANO1 channels.

ETHNOPHARMACOLOGICAL RELEVANCE: Flos Magnoliae (the dried flower buds of Magnolia biondii Pamp, FM) is a known herbal traditional medicine used for the symptomatic relief of nasal congestion and rhinorrhea caused by rhinitis and sinusitis. Magnolol, a neolignan from the magnolia family, is a secondary metabolite known to have anti-allergic and anti-inflammatory effects. However, the underlying mechanisms and therapeutic effect of magnolol in the treatment of allergic rhinitis (AR) remain elusive. AIMS OF THE STUDY: Anoctamin 1 (ANO1), a calcium-activated anion channel, mediates mucus and electrolyte secretion in nasal airway epithelial cells, whereas calcium release-activated calcium channel protein 1 (ORAI1) participates in the activation of T-lymphocytes and mast cells. The aim of our study is to understand the mechanisms of action of magnolol against AR, i.e., whether it acts through the modulation of ANO1 and ORAI1 channels that are expressed in nasal epithelial cells and T-lymphocytes, respectively. MATERIALS AND METHODS: Whole-cell patch clamp was used to record the activity of ORAI1 and ANO1 ion channels in ORAI1 or ANO1 overexpressed HEK293T cells, while the Ussing chamber apparatus was used to measure electrolyte transport via the epithelium, in Calu-3 cells cultured in an air-liquid interface. Additionally, calcium imaging of Jurkat T-lymphocytes was used to assess changes in the intracellular calcium concentration. Magnolol toxicity was assessed using the CCK-8 assay, and its effect on T-lymphocyte proliferation was measured by labeling human primary T-lymphocytes with carboxyfluorescein succinimidyl ester. Finally, OVA-induced Balb/c mice were employed to evaluate the effect of magnolol on nasal symptoms, as well as cytokine and eosinophil infiltration in AR. RESULTS: Magnolol inhibits ORAI1 and ANO1 channels in a concentration-dependent manner. Magnolol (30 µM) inhibits anti-CD3 induced cellular proliferation and production of IL-2 via ORAI1 channels in T-lymphocytes. Further, ATP-induced electrolyte transport mediated by ANO1 channels is significantly inhibited by magnolol in IL-4 sensitized Calu-3 cells. Notably, 300 µM magnolol significantly attenuates cytokine and eosinophil infiltration, thus alleviating AR symptoms in mice OVA-induced AR. CONCLUSION: Magnolol may be a promising therapeutic agent for the treatment and prevention of AR.

Honokiol suppresses 2,6-dinitrochlorobenzene-induced atopic dermatitis in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Magnolia officinalis constitutes a traditional Korean medicine used for the treatment of atopic dermatitis, and honokiol is an active diphenyl compound present in Magnolia officinalis. AIM OF THE STUDY: The aim of the study was to investigate the therapeutic effects of honokiol on atopic dermatitis in vivo. MATERIALS AND METHODS: The therapeutic effects of honokiol were evaluated in a 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis model. RESULTS: Administration of honokiol (10 mg/kg) significantly suppressed mast cell accumulation and inflammation induced by DNCB in skin tissues. Moreover, DNCB-induced increases in serum immunoglobulin E levels were reversed by honokiol treatment. In addition, DNCB-induced elevation of inflammatory cytokines (interleukin (IL)-4, IL-13, IL-17, and interferon-γ) in the skin and lymph nodes was significantly ameliorated by honokiol administration. Furthermore, the increase in lymph nodes sizes induced by DNCB treatment was reduced by honokiol administration. CONCLUSION: DNCB-induced atopic responses in the ears and lymph nodes were significantly suppressed by honokiol treatment. These results suggested that honokiol is a potential therapeutic agent for atopic dermatitis.

Schisandrol A, the main active ingredient of Schisandrae Chinensis Fructus, inhibits pulmonary fibrosis through suppression of the TGF-ß signaling pathway as revealed by UPLC-Q-TOF/MS, network pharmacology and experimental verification.

ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra chinensis decoction derived from the book of Waitai Miyao (Tao Wang, Tang dynasty) is often used in the treatment of idiopathic pulmonary fibrosis (IPF), which is included in the Grand Ceremony of Chinese formulae (Huairen Peng, 1994). Schisandrae Chinensis Fructus (Sch) is one of the most important herbs in this formula. According to the "Shennong's Herbal Classicherbal" of the Han Dynasty, Sch has sour taste, warm nature, which has the effect of tonifying qi and curing cough. In addition, according to the "Compendium of Materia Medica" of the Ming Dynasty, Sch is used to treat cough and asthma, which has the effect of moistening the lung and tonifying the kidney. However, the active ingredients of Sch absorption into the plasma and its pharmacological mechanism of treatment for IPF still remained unclear. AIM OF THE STUDY: Our research aimed at identifying the absorbed active ingredients and metabolized of Sch in rat plasma and the mechanism of anti-IPF based on serum pharmacochemistry. MATERIALS AND METHODS: First, the rats were divided into control group and Sch group. Sch sample was orally administrated to the rats for seven days. The blood samples were drawn into an Eppendorf tube after the last dosing. The ultrahigh performance liquid chromatography coupled with quadrupole-time of flight mass spectrometry (UPLC-Q-TOF/MS) was applied to identify the absorption components and metabolites of Sch in rat plasma. Second, the network pharmacology combined with molecular docking analysis was further investigated to illuminate its potential mechanism of treatment for IPF by the biological targets regulating related pathways. Finally, the mechanism of action was verified by experimental in vitro and in vivo. RESULTS: A total of 78 compounds, consist of 13 prototype lignans and 65 metabolites (including isomers) were identified. Network pharmacology study and molecular docking analysis indicated that schisandrol A (L1) play an anti-fibrosis role by regulating the TGF-ß signaling pathway. Experimental in vitro and in vivo verified that the schisandrol A could inhibiting pulmonary fibrosis through TGF-ß signaling pathway. The effect and mechanism of schisandrol A inhibiting pulmonary fibrosis were reported for the first time. CONCLUSIONS: In this study, the absorption active ingredients of Sch in rat plasma were combined with the network pharmacology investigation and experimental in vitro and in vivo to elucidate its biological mechanism of treatment for IPF. The results provided a theoretical support for understanding the bioactive compounds and the pharmacological mechanism of Sch.

New enantiomeric lignans and new meroterpenoids with nitric oxide release inhibitory activity from Piper puberulum.

Six new lignans with various type of linkage between two C6-C3 fragments (1a, 1b, 2a, 2b, 3, 4), two new meroterpenoids (5, 6) and 24 known compounds (7-30) were isolated from an EtOH extract of the stems and leaves of Piper puberulum. The absolute configurations of enantiomers 1a and 1b were determined by single-crystal X-ray diffraction analysis, 2a and 2b were determined by comparing their calculated and experimental ECD spectra. Biogenetically, all the new lignans may come from the polymerization of two molecules of hydroxychavicol (30). In the anti-neuroinflammation activity assay, the IC50 values of fifteen compounds were lower than those of the positive control minocycline, and compound 1a showed good activity, but its enantiomer 1b showed no activity. Compound 1a have notable anti-neuroinflammatory activity, and can significantly decrease mRNA levels of proinflammatory cytokines (IL-1ß, IL-6, TNF-α) in a dose-dependent manner.

Effect of Piper cubeba total extract and isolated lignans on head and neck cancer cell lines and normal fibroblasts.

The objective of the present study was to evaluate the action of the crude hydroalcoholic extract of Piper cubeba fruits and isolated lignans (cubebin, dihydrocubebin, ethylcubebin, hinokinin and methylcubebin) on head and neck cancer cells. We evaluated the influence of the Piper cubeba extract and isolated lignans (10, 50 e 100 µg/mL) for 4, 24, 48 and 72 h, in the larynx (Hep-2) and oral (SCC-25) squamous cell carcinoma cells and normal fibroblasts, on morphology, cell proliferation and migration, cytotoxicity, genotoxicity and gene and protein expression (PTGS2, PTGER3, PTGER4, MMP2, MMP9). The results showed that the P. cubeba extract and different lignans do not alter the cellular morphology, but decrease cell proliferation and migration, have low cytotoxic and genotoxic effects, probably due to the alteration of the expression of genes and proteins involved with inflammatory process. From these data, we can conclude that the lignans cubebin and methylcubebin had a greater effect on head and neck cancer cells in the antiproliferative, antimigratory and genotoxic action, and could be the target of the development of new therapies including possible new drugs as a therapeutic resource for the treatment of head and neck cancer due to its immense range of biological properties.

Wood Extractives of Silver Fir and Their Antioxidant and Antifungal Properties.

The chemical composition of extractives in the sapwood (SW), heartwood (HW), knotwood (KW), and branchwood (BW of silver fir (Abies alba Mill.) was analyzed, and their antifungal and antioxidant properties were studied. In addition, the variability of extractives content in a centripetal direction, i.e., from the periphery of the stem towards the pith, was investigated. The extracts were analyzed chemically with gravimetry, spectrophotometry, and chromatography. The antifungal and antioxidative properties of the extracts were evaluated by the agar well diffusion method and the diphenyl picrylhydrazyl radical scavenging method. Average amounts of hydrophilic extractives were higher in KW (up to 210.4 mg/g) and BW (148.6 mg/g) than in HW (34.1 mg/g) and SW (14.8 mg/g). Extractives identified included lignans (isolariciresinol, lariciresinol, secoisolariciresinol, pinoresinol, matairesinol) phenolic acids (homovanillic acid, coumaric acid, ferulic acid), and flavonoids epicatechin, taxifolin, quercetin). Secoisolariciresinol was confirmed to be the predominant compound in the KW (29.8 mg/g) and BW (37.6 mg/g) extracts. The largest amount of phenolic compounds was extracted from parts of knots (281.7 mg/g) embedded in the sapwood and from parts of branches (258.9 mg/g) adjacent to the stem. HW contained more lignans in its older sections. Hydrophilic extracts from knots and branches inhibited the growth of wood-decaying fungi and molds. KW and BW extracts were better free radical scavengers than HW extracts. The results of the biological activity tests suggest that the protective function of phenolic extracts in silver fir wood can also be explained by their antioxidative properties. The results of this study describe BW as a potential source of phenolic extractives in silver fir.

Hepatoprotective Constituents of Total Dibenzocyclooctadiene Lignans from Schisandra chinensis Based on the Spectrum-Effect Relationship.

To scientifically clarify the hepatoprotective constituents of Fructus Schizandrae chinensis, eleven batches samples of total dibenzocyclooctadiene lignans (TDL) from Schisandra chinensis were prepared by using the optimum extraction technique. Characteristic high-performance liquid chromatography (HPLC) chromatograms were obtained through HPLC analysis technology, and the hepatoprotective effects of the eleven batches of TDL were evaluated by MTT assay. Based on the chemical and biological activity results, the spectrum-effect relationship between the characteristic HPLC fingerprints and the hepatoprotective effect of TDL was established using Minitab 16.0 data analysis software. On the basis of the spectrum-effect relationship, thirteen compounds (1-13) were obtained from the TDL by chemical natural product chemical separation and purification technology, and their structures were identified on the basis of the spectral data and the literature. Based on these compounds, thirteen common peaks among the thirty-three chromatographic peaks in the above HPLC fingerprints were identified. Our findings showed that some components, including, schisandrin B (2), schisandrin A (3), and schisandrol B (7) had significant roles in promoting hepatoprotective activity. Preliminary verification of the spectrum-effect relationship of TDL from S. chinensis was carried out, and the results confirmed that the activity of a composite of these three key components in optimal ratios was better than that of any individual compound, which potentially confirmed the reliability of the spectrum-effect relationship and the synergistic effects of traditional Chinese medicine.

New lignans from the fruits of Leonurus japonicus and their hepatoprotective activities.

Twelve tetrahydrofuran lignans (1-12), including six new compounds (1-6), were isolated from the 70% EtOH extract of the fruits of Leonurus japonicus. Spectroscopic analyses and ECD and OR calculations were used to determine their structures. Compounds 5 and 6 were unusual alkaloidal lignans with a butyrolactam unit. Based on the beneficial effects of the fruits of L. japonicus (Chongweizi in Chinese) on the liver in traditional Chinese medicine (TCM), the hepatocyte protective activities of the isolates were studied by MTT, Hoechst 33,342 staining, and western blotting. The MTT results revealed that compounds 1, 2, 7, and 8 significantly increased the survival rates of HL-7702 cells injured by acetaminophen, with EC50 values of 10.41 ± 0.90 µM, 19.86 ± 3.13 µM, 9.68 ± 1.93 µM, and 21.35 ± 3.58 µM, respectively. In the Hoechst 33,342 fluorescence staining, compounds 1 and 7 suppressed the apoptosis of the injured HL-7702 cells. Furthermore, the western blot analysis showed that compounds 1 and 7 increased the Bcl-2/Bax protein expression ratio and procaspase-3 protein expression, indicating that compounds 1 and 7 may exert hepatoprotective activity by regulating the mitochondrial apoptotic pathway.

A new skeleton flavonoid and a new lignan from Portulaca oleracea L. and their activities.

A new skeleton flavonoid, identified as (5aR)-10-hydroxy-8-methoxy-5aH,11H-chromeno[2,3-b]chromen-11-one (1), named oleracone G, and a new lignan, confirmed as 8-(4-hydroxy-3-methoxyphenyl)-3-methoxynaphthalen-2-ol (2), named oleralignan B, were isolated from Portulaca oleracea L., and the structures of them were determined using spectroscopic methods including UV, IR, 1D NMR, 2D NMR, and UHPLC-ESI-QTOF/MS. In addition, compounds 1-2 were applied to investigate the anti-inflammatory activities on lipopolysaccharide-stimulated macrophages and scavenging effects in 1,1-diphenyl-2-picryl-hydrazyl (DPPH) free radical. The results showed that the two compounds at 10 µM and 20 µM could dose-dependently decrease the secretion of interleukin 1ß in RAW 264.7 cells by enzyme-linked immunosorbent assay, moreover, presented remarkable antioxidant activities with IC50 values of 27.57, 20.12 µM, respectively.

The neurotrophic and antineuroinflammatory effects of phenylpropanoids from Zanthoxylum nitidum var. tomentosum (Rutaceae).

Three novel lignans (1, 5 and 6) and two novel quinic acids (16 and 17) along with 15 known phenylpropanoids were obtained from the ethanol extract of Zanthoxylum nitidum var. tomentosum (Rutaceae). Their structures were confirmed by comprehensive spectroscopic data (NMR and HRESIMS), and the absolute configurations of all novel compounds were elucidated based on electronic circular dichroism (ECD) spectroscopic data. The production of nitric oxide (NO) in BV-2 microglial cells induced through lipopolysaccharide (LPS) was used to evaluate in vitro anti-neuroinflammatory activity of compounds 1-20. Compound 2, 3, 7 and 16 showed excellent inhibition of LPS-induced NO production. The structure-activity relationships of the isolates were investigated. In addition, the mechanism of action of 2 was elucidated by RT-PCR and Western blotting analysis, which indicated that it reduced neuroinflammatory mainly through NLRP3/caspase1 signaling pathways in LPS-induced BV2 microglial cells.

A network pharmacology strategy to investigate the anti-osteoarthritis mechanism of main lignans components of Schisandrae Fructus.

Osteoarthritis (OA) is a chronic age-related progressive joint disorder. Degradation of the cartilage extracellular matrix (ECM) is considered a hallmark of OA and may be a target for new therapeutic methods. Schisandrae Fructus (SF) has been shown to be effective in treating OA. The major active components of SF are lignans. However, the targets of SF and the pharmacological mechanisms underlying the effects of SF lignans in the treatment of OA have not been elucidated. Therefore, based on network pharmacology, this research predicted the treatment targets of six lignans in SF, constructed a protein-protein interaction network and identified 15 hub genes in the OA-target protein-protein interaction network. Through Gene Ontology function and pathway analyses, the gene functions of lignans in the treatment of OA were determined. Finally, the anti-OA effects of lignans and underlying mechanisms identified in the network pharmacology analysis were verified by molecular docking, real-time PCR and western blotting in vitro. The biological processes of the genes and proteins targeted by lignans in the treatment of OA included the immune response, inflammatory response, cell signal transduction and phospholipid metabolism. Moreover, 20 metabolic pathways were enriched. Network pharmacology, molecular docking and in vitro and in vivo experimental results revealed that SF, schisanhenol and gamma-schisandrin inhibited EGFR and MAPK14 gene expression by inhibiting SRC gene expression and activity and then decreased MMP 13 and collagen II protein and gene expression. This research provides a basis for further study of the anti-OA effects and mechanisms of SF, schisanhenol and gamma-schisandrin.

Lignans from Lepidium meyenii and Their Anti-Inflammatory Activities.

Meyeniines A-C (1-3), three new lignans, two known neolignans (4-5), and three known lignans (6-8) were isolated from the rhizomes of Lepidium meyenii. Their structures were identified by comprehensive spectroscopic analyses and computational methods. Compound 1 represents a unique lignan featuring an aromatic ring migration. Compounds 2 and 4-6 were analyzed by chiral HPLC column as enantiomers. Biological evaluation revealed that compound 8 could inhibit IL-6 production in lipopolysaccharide (LPS) induced RAW264.7 cells in a dose-dependent manner.

Structure elucidation and anti-inflammatory mechanism of difengpienol C, a new neolignan isolated from Illicium difengpi.

Illicium difengpi is well-known as its stem barks that have been widely used in the Traditional Chinese Medicine (TCM) for therapy rheumatoid arthritis and traumatic injury. To comprehensive utilization of resources, the phytochemical investigation on the branches and leaves of this plant was carried out, which led to the isolation of an undescribed neolignan along with three known lignans. Their structures were elucidated on the basis of extensive spectroscopic data and the new compound was elucidated as a neolignan possessing a dihydropyran ring formed by a unique conjugation way and named difengpienol C. Difengpienol C showed the strongest anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, which powerfully inhibited nitric oxide (NO), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α) production and suppressed the mRNA transcription of inducible nitric oxide synthase (iNOS), IL-6 and TNF-α. Besides, difengpienol C blocked the activation of TLR4/MyD88/NF-κB signaling pathway. Therefore, difengpienol C might be a potent agent for anti-inflammatory drug development, and the non-traditional medicinal parts of Illicium difengpi can be identified as the source of natural anti-inflammatory molecules.

Eupomatenes A - E: Neolignans isolated from the leaves of Australian rainforest plant Eupomatia laurina.

A detailed phytochemical investigation of the leaves of the Australian rainforest tree Eupomatia laurina, led to the discovery of five new neolignans, eupomatenes A - E and eight known compounds, eupomatenoid-2, trans-(2'S)-2-[1'-(4-methoxyphenyl)prop-2'-yl]anethol, chlorogenic acid, chlorogenic acid-methyl ester, tyrosol-1-O-ß-xylopyranosyl-1(1 â†’ 6)-O-ß-glucopyranoside, leucoside, kaempferol-3-O-neohesperidoside, and pachypodol. The structures of all the compounds were determined by detailed spectroscopic analysis. All compounds were also evaluated for their anti-inflammatory properties by assessing their inhibitory effects on nitric oxide (NO) production and TNF- α release in RAW 264.7 macrophages. Whilst slight anti-inflammatory activity (in terms of inhibition of NO production) was observed with eupomatenes A - E, this was also associated with high levels of cell growth inhibition.

Identification of neolignans with PCSK9 downregulatory and LDLR upregulatory activities from Penthorum chinense and the potential in cholesterol uptake by transcriptional regulation of LDLR via SREBP2.

ETHNOPHARMACOLOGICAL RELEVANCE: Penthorum chinense has been used in East Asia for the treatment of cholecystitis, infectious hepatitis, jaundice and to treat liver problems. Recent evidences provided the potential for the clinical use of P. chinense in the treatment of metabolic disease. AIM OF THE STUDY: Based on the traditional use and recent evidences, we investigated the effects of constituents from P. chinense with modulation on proprotein convertase subtilisin/kexin type 9 (PCSK9) and low-density lipoprotein receptor (LDLR) expression, and the effect of the most active substance on cholesterol uptake, and genes relevant to lipid metabolism. MATERIALS AND METHODS: The isolation of compounds from the BuOH-soluble extract of 80% methanol extract of P. chinense was conducted using chromatographic methods and the structures were established by interpreting spectroscopic data. Quantitative real time-PCR, and Western blot analysis were performed to monitor the regulatory activity on PCSK9 and LDLR expression. PCSK9-LDLR binding interaction was also tested. The cholesterol uptake in hepatocyte was measured using 1,1-dioctadecyl-3,3,3,3-tetramethylindocarbocyanine perchlorate (DiI)-labeled LDL cholesterol. Additionally, gene network analysis of LDLR and responses of its target proteins were carried out to discover genes germane to the effect of active compound on HepG2 cells. Moreover, we performed protein-protein interaction analysis via String and constructed the compound target network using Cytoscape. RESULTS: Two new neolignans and 37 known compounds were characterized from P. chinense. Of the isolated compounds, (7'E,8S)-2',4,8-trihydroxy-3-methoxy-2,4'-epoxy-8,5'-neolign-7'-en-7-one (3), penthorin A (4) and methyl gallate (25) were found to suppress PCSK9 mRNA expression with IC50 values of 5.13, 15.56 and 11.66 µM, respectively. However, all the isolated compounds were found to be inactive in PCSK9-LDLR interaction assay. Additionally, a dibenzoxepine-type lignan analog, (7'E,8S)-2',4,8-trihydroxy-3-methoxy-2,4'-epoxy-8,5'-neolign-7'-en-7-one (3) demonstrated to upregulate LDLR mRNA and protein expression via transcriptional factor sterol regulatory element-binding protein 2 (SREBP2). Furthermore, (7'E,8S)-2',4,8-trihydroxy-3-methoxy-2,4'-epoxy-8,5'-neolign-7'-en-7-one (3) increase the LDL-cholesterol uptake in DiI-LDL assay. CONCLUSION: (7'E,8S)-2',4,8-trihydroxy-3-methoxy-2,4'-epoxy-8,5'-neolign-7'-en-7-one (3) seemed to increase potentially cholesterol uptake via the downregulation of PCSK9 and the activation of LDLR in hepatocytes. Moreover, SREBP2 was found to play an important role in regulation of PCSK9 and LDLR by (7'E,8S)-2',4,8-trihydroxy-3-methoxy-2,4'-epoxy-8,5'-neolign-7'-en-7-one.

Biomineralized separation, concentration, and evaluation of the effectiveness of Schisandra chinensis fruit extract.

Here, we detail the biomineralization-assisted separation and concentration of crude food extract and an evaluation of its effectiveness. Schisandra chinensis fruit extract was used as a model plant extract. Hybrid grape-like mineral was assembled by calcium carbonate mineralization. The hybrid particles of S. chinensis mineral were fully characterized using field emission scanning electron microscopy, X-ray diffraction, thermogravimetric analysis, and particle size analysis. Data including the Brunauer-Emmett-Teller surface area, single point total pore volume, and adsorption/desorption analysis of pore size were also investigated. Organic molecules, including lipids such as palmitic acid, stearic acid, and linolenic acid in the Schisandra chinensis fruit, affect the formation of complex structures involving the CaCO3 mineralization pathway by inhibiting crystallization. However, the cosmetic active primary components were entrapped in a similar proportion in the preserved extract, and were efficiently separated without additional filtering and concentration steps for purification. In addition, the hybrid mineral was enriched (10.5 times) in Gomisin N, a representative component of S. chinensis fruit, relative to its concentration in the initial extract samples. The hybrid mineral inhibited both intracellular and extracellular melanin production and increased the 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity. The data provide the first evidence of the potential use of fruit extract for obtaining hybrid minerals and the effectiveness of the biomineralization-based separation and concentration strategy.

Research for improvement on the extract efficiency of lignans in traditional Chinese medicines by hybrid ionic liquids: As a case of Suhuang antitussive capsule.

Recently, efficient extraction of natural products from traditional Chinese medicines (TCMs) by green solvents is deemed an essential area of green technology and attracts extensive attentions. In this work, a green protocol for simultaneous ultrasonic-extraction of the native compounds with different polarities of TCMs by using a hybrid ionic liquids (HILs)-water system was reported for the first time. As a case study, three superior ILs (1-ethyl-3-methylimidazolium tetrafluoroborate ([EMIM][BF4]), 1-ethyl-3-methylimidazolium acetate ([EMIM][OAc]), and 1-allyl-3-methylimidazolium chloride ([AMIM]Cl)) were chosen as the compositions of the HILs system, and the TCMs Suhuang antitussive capsule (SH) containing different-polarity lignans was selected. Primarily, an ultra-performance liquid chromatography coupled to triple quadrupole tandem mass spectrometry (UPLC-QqQ-MS/MS) method in the multiple reaction monitoring (MRM) mode was established for qualitative and quantitative analysis of 18 lignans. After majorization by uniform design experiment, the HILs prepared with [AMIM]Cl, [EMIM][BF4], and [EMIM][OAc] at a volume ratio of 1:5:5 could simultaneously extract multi-polarity lignans compared to single IL. Subsequently, the conditions of ultrasonic extraction employing with HILs and traditional organic solvent were optimized by the response surface methodology, respectively. The results indicated that the extract efficiency of the HILs system for target compounds was significantly improved compared with the traditional organic solvent-extraction, i.e. the content of total lignans in ethanol system was up to 47 mg/g, while that in the HILs system was up to 69 mg/g, with an increasing of 47%. Additionally, 1H-NMR and 13C-NMR spectra were used to characterize the hydrogen-bond interactions in the HILs-lignan mixtures. Extraction with the HILs in TCMs is a new application schema of ILs, which not only avoids the use of volatile toxic organic solvents, but also shows the potential to be comprehensively applied for the extraction of bioactive compounds from TCMs.