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Liver fibrosis is a severe health problem, threatening the life quality and causing death, raising great concerns worldwide. Shi-Wei-Gan-Ning-Pill (SWGNP) is a traditional Tibetan recipe used to treat hepatic injuries; however, its hepatoprotective mechanism has not yet fully clarified. In this study, histological staining, biochemical assays, and elements determination were applied to evaluate the anti-fibrotic efficacy of SWGNP on a carbon tetrachloride (CCl4) induced hepato-fibrosis rat model. NMR-based metabolomics combined with orthogonal partial least squares-discriminant analysis (OPLS-DA), canonical regression analysis, and correlation networks analysis was used to characterize the potential biomarkers as well as metabolic pathways associated with the hepatoprotective activity of SWGNP. The results showed that SWGNP could significantly attenuate the pathological changes and decrease the levels of fibrosis markers (ColIV, HA, LN, and PCIII), and regulate the disordered elements distribution. Multivariate analysis and correlation network analysis revealed that SWGNP could protect rats against CCl4-induced liver fibrosis through anti-oxidation, repairing the impaired energy metabolisms and reversing the disturbed amino acids and nucleic acids metabolisms. In conclusion, this integrated metabolomics approach provided new insights into the mechanism of the hepatoprotective effect of SWGNP in liver fibrosis disease. [ABSTRACT FROM AUTHOR]

Hepatic encephalopathy (HE) is a severe neuropsychiatric complication due to acute or chronic liver failure. In this work, an acute thioacetamide induced HE mice model was established to investigate the metabolic events in the onset of HE (OHE) and the protective role of taurine (TAU). Sera for biochemical evaluation, and livers and cortexes for histopathological inspection and NMR-based metabolomic investigation were collected. Principal component analysis and orthogonal partial least squares-discriminant analysis were performed to excavate differential metabolites of OHE, and explore the protective role of TAU. Metabolites pathway analysis was performed on significant metabolites selected based on loading/S-plots and fold change plots to identify biologically meaningful metabolic patterns and relevant pathways. The most affected pathways in OHE mice were those along the liver-brain axis: among them, the alanine, aspartate and glutamate metabolism was the most important. TAU showed better performance in improving the disturbed metabolism in the cortex than in the liver of OHE mice. This pilot study based on metabolomics approach and pathway analysis should help to understand HE systematically, and to develop new therapy for HE. [ABSTRACT FROM AUTHOR]

A total of six new alkaloids, melodinhenines A–F ( 1 – 6 ), were isolated from Melodinus henryi . Melodinhenines A and B are new eburnan–vindolinine-type bisindole alkaloids and melodinhenines C–F are new quinolinic melodinus alkaloids. Their structures were elucidated through extensive spectroscopic methods including 2D NMR and HRESIMS analyses. The absolute configuration of 1 and 2 was determined using ECD exciton chirality method. To the best of our knowledge, this is the first report on the determination of the absolute configuration of eburnan–vindolinine-type bisindole alkaloid using this method. [ABSTRACT FROM AUTHOR]

From the leaves and twigs ofPsychotria henryi, a new dimeric indole alkaloid, named psychohenin, was isolated, whose structure was elucidated on the basis of extensive spectroscopic analysis. The absolute configuration of psychohenin was determined by a single-crystal X-ray diffraction study using a mirror Cu Kα radiation. [ABSTRACT FROM PUBLISHER]

Abstract: A phytochemical study on the ethanolic extract of the stem barks of Uncaria laevigata leads to the isolation and characterization of 18 triterpenoid compounds. Ten of these are new, including one novel heptanortriterpenoid (1), four ursane triterpenes (2–4, 10), and five oleanane triterpenes (5–9). Their structures were established by spectroscopic methods, especially by 2D-NMR and MS analyses. All these isolates were evaluated for their inhibitory effects on α-glucosidase: ursolic acid and 3 showed potent activities with IC50 values of 16±2.2 and 49±3.7μM, respectively. [Copyright &y& Elsevier]

Abstract: Two new sesqui-neolignans with novel conjugation way, simonol A (1), featuring a unique motif of a 5,5-dihydro-pyran with a hemiketal carbon, while simonol B (2) possessing two dihydronfuran rings in the same direction, were isolated from the ethanol extract of the fruits of Illicium simonii. Their structures were elucidated by spectroscopic methods including 1D and 2D NMR, HRESIMS, and calculation of electronic circular dichroism (ECD) using density functional theory (DFT). The two isolates were evaluated for their inhibitory activities against the growth of four lines of human cancer cells (NCI-H460, SMMC-7721, MCF-7, BGC-823): 1 showed strong activities comparable to 5-Fluorouracil, and 2 to a less content. In addition, plausible biosynthetic routes for the two compounds were also proposed. [Copyright &y& Elsevier]

Abstract: Two novel dimeric indole alkaloids were isolated from the leaves and twigs of Psychotria henryi. Their structures were established by chemical and spectroscopic methods. Compound 1 was a novel dimeric tryptamine-related alkaloid that contained an unprecedented decacyclic ring system, and compound 2 featured a pyrido[3,4-b]indole moiety adjacent to a pyrrolidinoindole skeleton. The absolute configurations of compounds 1 and 2 were determined by calculation of electronic circular dichroism (ECD) using density functional theory (DFT). [Copyright &y& Elsevier]

A novel lindenane sesquiterpene with an unprecedented 18-membered triester ring, named chlorafortulide (1), along with one known lindenane sesquiterpene (2) and nine known lindenane sesquiterpene dimers (3–11), was isolated from the whole plant of Chloranthus fortunei. Their structures and relative configurations were elucidated on the basis of spectroscopic analysis. All the isolates were evaluated for their inhibitory effects on lipopolysaccharide-induced nitric oxide production in RAW264.7 cells. Henriol D (4), shizukaols E (8), G (9), M (10), and O (11) showed significant anti-inflammatory activities with IC50 values of 1.90, 3.68, 1.95, 7.01, and 1.95 μM, respectively. [ABSTRACT FROM AUTHOR]

Abstract: Eight new ring A-seco limonoids, aphanalides A–H (1–8) were isolated from the fruits of Aphanamixis polystachya. Aphanalides A–C (1–3) are the first examples of ring A-seco limonoids with an unusual oxetane ring between C-7 and C-14. The structures of aphanalide A (1) and aphanalide C (3) were confirmed by single-crystal X-ray studies. Their structures including absolute stereochemistry were established on the basis of extensive NMR spectroscopic analysis, by comparison of experimental and calculated electron circular dichroism (ECD) and by X-ray diffraction, representing the first report of assignment of absolute configuration of such type ring A-seco limonoids. The biogenetic origin of aphanalides A–D (1–4) from aphanalides E–H (5–8) was also postulated. [Copyright &y& Elsevier]

As part of our continuing effort to discover new potential anti-inflammatory agents, four new triterpenoids, chisopanins L-O ( 1- 4), were isolated from the twigs of Chisocheton paniculatus. Their structures were established on the basis of detailed analysis of spectroscopic data, including IR, NMR (1D and 2D NMR), and HR-ESI-MS. Their inhibitory effects against nitric oxide (NO) production were evaluated in an in vitro model of lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Compounds 1, 3, and 4 were found to exhibit moderate activity with IC50 values less than 10 μmol/L. [ABSTRACT FROM AUTHOR]

Stroke is the third most common cause of death in most industrialized countries. Polygonum multiflorum (He-Shou-Wu, HSW) is one of the traditional Chinese medicines with multiple pharmacological activities which is widely used in Chinese recipe. This study aims to explore the protective effect of HSW on ischemic stroke rat model and to elucidate the underlying mechanisms. The mortality rate, neurological deficit, cerebral infarct size, histopathology, immunohistochemistry, biochemical parameters, quantitative real-time polymerase chain reaction and western blotting were used to access the treatment effects of HSW on ischemic stroke. Proton nuclear magnetic resonance ( 1 H NMR) based metabolomics analysis disclosed that HSW could relieve stroke rats suffering from the ischemia/reperfusion injury by ameliorating the disturbed energy and amino acids metabolisms, alleviating the oxidative stress from reactive oxygen species and reducing the inflammation. HSW treatment increased levels of cellular antioxidants that scavenged reactive oxygen species during ischemia-reperfusion via the nuclear erythroid 2-related factor 2 signaling pathway, and exert anti-inflammatory effect by decreasing the levels of inflammatory factors such as cyclooxygenase-2, interleukin-1β, interleukin-6 and tumor necrosis factor-α. The integrated metabolomics approach showed its potential in understanding mechanisms of HSW in relieving ischemic stroke. Further study to develop HSW as an effective therapeutic agent to treat ischemic stroke is warranted. [ABSTRACT FROM AUTHOR]

Dichlorvos (DDVP), one of the most widely used organophosphorus pesticides (OPs), has caused serious pollution in environment. In this study, 1 H nuclear magnetic resonance (NMR) based metabolomics approach combined with histopathological and immunohistochemical examination, and biochemical assays were used to investigate toxicities of DDVP on goldfish ( Carassius auratus ). After 10 days’ exposure of DDVP at three dosages of 5.18, 2.59 and 1.73 mg/L, goldfish tissues (gill, brain, liver and kidney) and serum were collected. Histopathology revealed severe impairment of gills, livers and kidneys, and immunohistochemistry disclosed glial fibrillary acidic protein (GFAP) positive reactive astrocytes in brains. Orthogonal signal correction–partial least squares–discriminant analysis (OSC–PLS–DA) of NMR profiles disclosed that DDVP influenced many metabolites (glutamate, aspartate, acetylcholine, 4-aminobutyrate, glutathione, AMP and lactate in brain; glutathione, glucose, histamine in liver; BCAAs, AMP, aspartate, glutamate, riboflavin in kidney) dose-dependently, involved with imbalance of neurotransmitters, oxidative stress, and disorders of energy and amino acid metabolism. Several self-protection mechanisms concerning glutamate degradation and glutathione (GSH) redox system were found in DDVP intoxicated goldfish. [ABSTRACT FROM AUTHOR]

Abstract: Two new alkaloids, longphyllinesides A (1) and B (2), were isolated from Daphniphyllum longeracemosum. Their structures were elucidated using 1D and 2D NMR spectra. The key step in their biogenetic pathway is indicated to be Diels–Alder cycloaddition via asynchronous concerted mechanism by density functional theory calculations. The possibility of involvement of a Diels–Alderase is also discussed. [Copyright &y& Elsevier]

A novel aporphine alkaloid, magnofficine (1), has been isolated from the root barks of the Chinese medicinal plant Magnolia officinalis, along with seven known compounds. Elucidations of their structures were achieved by spectroscopic methods. Magnofficine is the first example of an adduct of aporphine alkaloid and 4-hydroxyphenethylamino bridged by a methylene. [Copyright &y& Elsevier]

25 flavors of the turquoise pill, a traditional Tibetan medicine for the treatment of various types of hepatitis, has not been investigated on its safety, especially the component mineral turquoise, which is believed to be essential but worried for its potential toxicity. Aim of the study : To explore the potential acute toxicity and function of 25 flavors of the turquoise pill and turquoise, the possible mechanism of the effects of turquoise and 25 flavors of the turquoise pill were systematically studied based on 1H NMR metabolomics. The rats were administered with turquoise and 25 flavors of the turquoise pill by gavage for 7 days, and samples of serum, liver, and kidney were collected. The potential toxicity and function of turquoise and 25 flavors of the turquoise pill on the liver and kidney of SD rats were evaluated by 1H NMR metabonomics, histopathology, and biochemical indexes. The results demonstrated that 25 flavors of the turquoise pill could scavenge free oxygen radicals, strengthen aerobic respiration and inhibit glycolysis in the liver. It did not cause oxidative stress in the kidney with no obvious damage. By modulation of branched-chain amino acids (BCAAs), 25 flavors of the turquoise pill can improve the utilization of glucose and promote aerobic respiration of the kidney. Considering the high dosage and short duration used in this study relative to their typical clinical usage, administration of 25 flavors of the turquoise pill and its component mineral turquoise are safe to livers and kidneys. [Display omitted] • The drug safety of turquoise and 25 flavors of the turquoise pill in rats were firstly studied by 1H NMR-based metabolomics. • 25 flavors of the turquoise pill can promote the aerobic respiration of the kidney and liver in rats. • Considering the large dosage used in this experiment, both 25 flavors of the turquoise pill and turquoise are safe. [ABSTRACT FROM AUTHOR]

Abstract: Sumadains A (1) and B (2), a pair of unique isomeric sesquiterpene–chalcone conjugates with unprecedented skeletons, were isolated from the seeds of Alpinia katsumadai. Their structures and relative configurations were established by NMR spectroscopy and X-ray crystallography. [Copyright &y& Elsevier]

Abstract: Three monoterpene–chalcone conjugates, including two novel compounds isorubraine (2) and sumadain C (3), and a known compound rubraine (1) were isolated from the seeds of Alpinia katsumadai. Their structures and relative configurations were established by NMR spectroscopy and X-ray crystallography. Cytotoxic activities of these compounds were evaluated against cell lines HepG2, MCF-7 and MAD-MB-435, and compound 3 exhibited potent cytotoxic activity. [Copyright &y& Elsevier]

Gastrodiae Rhizoma (GR), a well-known and commonly-used TCM (Traditional Chinese Medicine) for treating headache, dizziness, tetanus, epilepsy, and etc., has been proven to relieve chronic atrophic gastritis (CAG). Due to its complex ingredients, the active fractions responsible for the treatment of CAG remain largely unknown. To explore the underlying material and interpret its underlying mechanism, the therapeutic effect of extract from different polar parts of Gastrodiae Rhizoma on autoimmune CAG was studied based on the 1H NMR metabolomics. The rat model of CAG was established by autoimmune method. The modeled CAG rats were then treated with 4 polar parts (T1-4 in descending polarity, corresponding to water, n-butanol, ethyl acetate and petroleum ether extracts, respectively) of Gastrodiae Rhizoma for 21 consecutive days. The stomach and serum samples were collected and then subjected to histopathology observation, biochemical measurement (MDA, SOD, GSH, NO, XOD and pepsin), 1H NMR metabolic profiling and multivariate/univariate statistical analysis. The results showed that T1 had the best therapeutic effect, T2 the second, and T3 and T4 the poorest with no obvious therapeutic effect, demonstrating that the effective components of Gastrodiae Rhizoma should be compounds of high polarity. T1 achieved good therapeutic effects due to the anti-inflammatory and anti-oxidant activities, and by rectifying the disturbed energy and amino acid metabolism in CAG model. This integrated metabolomics approach proved the validity of the therapeutic effect of extract from different polar parts of Gastrodiae Rhizoma on autoimmune CAG, providing new insights into the underlying mechanisms, and demonstrating the feasibility of metabolomics to evaluate efficacy of herbal drug, which is often difficult by traditional means. Image 1 [ABSTRACT FROM AUTHOR]