A comprehensive review of natural products with anti-hypoxic activity.

Natural products exhibit substantial impacts in the field of anti-hypoxic traetment. Hypoxia can cause altitude sickness and other negative effect on the body. Headache, coma, exhaustion, vomiting and, in severe cases, death are some of the clinical signs. Currently, hypoxia is no longer just a concern in plateau regions; it is also one of the issues that can not be ignored by urban residents. This review covered polysaccharides, alkaloids, saponins, flavonoids, peptides and traditional Chinese compound prescriptions as natural products to protect against hypoxia. The active ingredients, effectiveness and mechanisms were discussed. The related anti-hypoxic mechanisms involve increasing the hemoglobin (HB) content, glycogen content and adenosine triphosphate (ATP) content, removing excessive reactive oxygen species (ROS), reducing lipid peroxidation, regulating the levels of related enzymes in cells, protecting the structural and functional integrity of the mitochondria and regulating the expression of apoptosis-related genes. These comprehensive summaries are beneficial to anti-hypoxic research and provide useful information for the development of anti-hypoxic products.

Influence of the gallate moiety on the interactions between green tea polyphenols and lipid membranes elucidated by molecular dynamics simulations.

Previous studies suggested that naturally occurring EGCG primarily acted on the bacterial cell membrane then damaged the membrane and the gallate moiety in EGCG was very important to its anti-bacterial activity. However, the detailed mechanisms were still poorly understood. In this paper, EGCG and EGC were selected to study the great contribution of gallate moiety on the anti-bacterial activities of polyphenols. The results indicated that EGCG could penetrate deeper into the POPG lipid bilayer and possess more potent structure-perturbing potency on the POPG lipid bilayer than EGC. We also found that EGCG had the ability to form hydrogen bonds with the deeper inside oxygen atoms in the POPG lipid bilayer and the gallate moiety was the key functional group for EGCG forming hydrogen bonds with the POPG lipid bilayer. Moreover, results from the binding free energy analysis demonstrated that the gallate moiety made great contribution to the high affinity between EGCG and the POPG lipid bilayer. We believed that these findings could yield useful insights into the influence mechanisms of gallate moiety on the anti-bacterial activities of polyphenols.

Study of the Mechanism of Action of Guanxin Shutong Capsules in the Treatment of Coronary Heart Disease Based on Metabolomics.

Background: Guan-Xin-Shu-Tong capsule (GXSTC) is a traditional Chinese medicine (TCM) that has been used to treat coronary heart disease (CHD) for many years in China. However, the holistic mechanism of GXSTC against CHD is still unclear. Therefore, the purpose of this paper was to systematically explore the mechanism of action GXSTC in the treatment of CHD rats using a metabolomics strategy. Methods: A CHD model was induced by ligation of the left anterior descending coronary artery (LAD). In each group, echocardiography was performed; the contents of creatine kinase (CK), lactate dehydrogenase (LDH) and aspartate transaminase (AST) in serum were determined; and the myocardial infarct size was measured. The metabolites in plasma were analyzed by UHPLC-MS/MS-based untargeted metabolomics. Then, multivariate statistical analysis was performed to screen potential biomarkers associated with the GXSTC treatment in the LAD-induced rat CHD model. Finally, the MetaboAnalyst 4.0 platform was used for metabolic pathway enrichment analysis. Results: GXSTC was able to regulate the contents of CK, LDH and AST; restore impaired cardiac function; and significantly reduce the myocardial infarction area in model rats. Twenty-two biomarkers and nine metabolic pathways of GXSTC in the treatment of CHD were identified through UHPLC-MS/MS-based untargeted metabolomics analysis. Conclusion: GXSTC regulates metabolic disorders of endogenous components in LAD-induced CHD rats. The anti-CHD mechanism of GXSTC is mainly related to the regulation of amino acid, lipid and hormonal metabolism. This study provides an overall view of the mechanism underlying the action of GXSTC against CHD.

Interactions between highly galloylated persimmon tannins and pectins.

The interactions between pectins of different degrees of esterification (DE) and highly galloylated persimmon tannins with average degrees of polymerisation (DP26 and DP5) were investigated by UV-Vis spectrophotometry, dynamic light scattering, transmission electron microscopy, isothermal titration calorimetry and pyrene fluorescence methods Pectins displayed strong effects on the self-aggregation of persimmon tannins and improved the homogeneity of condensed tannin aggregates. The interaction between tannins and pectins may result from hydrogen bonding and hydrophobic interactions; by contrast, electrostatic interactions, which involve charged molecules in general, played no dominant role. In addition, the presence of gallate moieties in the high-polymerisation proanthocyanidin could enhance affinity with highly methylated pectins. Stronger association was observed with the high-polymerisation tannins (DP26) with high-methoxyl pectin (DE74) (Ka=(8.50±3.0)×103M-1) than with low-methylated pectin (DE30) (Ka=(3.62±1.92)×103M-1). The present results are expected to promote the application of the formed complexes as functional ingredients in food.

Hepatotoxicity in Rats Induced by Aqueous Extract of Polygoni Multiflori Radix, Root of Polygonum multiflorum Related to the Activity Inhibition of CYP1A2 or CYP2E1.

The objective of this study is to investigate the relationship between the hepatotoxicity induced by Polygoni Multiflori Radix (PMR, root of Polygonum multiflorum Thunb., He Shou Wu) and the activity of CYP1A2 or CYP2E1 in the rat liver. Levels of rat serum transaminases ALT and AST were not altered but the activity of CYP1A2 or CYP2E1 in the rat liver was significantly inhibited after oral administration of aqueous extract of PMR under the experimental dosage. However, levels of ALT and AST were significantly increased and the activity of CYP1A2 or CYP2E1 was significantly decreased after injection of specific inhibitor for CYP1A2 or CYP2E1 combined with oral administration of aqueous extract of PMR, especially under the repeated treatment over interval times. Liver histopathological observation showed that a moderate liver injury occurred in rats receiving PMR treatment with the activity of CYP1A2 or CYP2E1 inhibited, but there was no significant liver damage in rats receiving PMR treatment or CYP inhibitor alone. These suggested that low level activity of CYP1A2 or CYP2E1 from genetic polymorphism among people might be one of the important reasons for the hepatotoxicity induced by PMR in clinical practice.

Screening of key antioxidant compounds of longan (Dimocarpus longan Lour.) seed extract by combining online fishing/knockout, activity evaluation, Fourier transform ion cyclotron resonance mass spectrometry, and high-performance liquid chromatography electrospray ionization mass spectrometry methods.

To figure out the key phenolic compounds accounting for the antioxidant effects of longan (Dimocarpus longan Lour.) seed extract, online fishing/knockout method, activity evaluation assays, Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS), and high-performance liquid chromatography electrospray ionization mass spectrometry (HPLC-ESI-MS) analysis were used jointly for the first time. p-Coumaric acid-glycoside, (S)-flavogallonic acid, ellagic acid derivative, and methyl-ellagic acid glucopyranoside were first identified in longan seeds. In addition, our study revealed that ellagic acid as well as its derivative and p-coumaric acid-glycoside had important contribution to the potent antioxidant activity of longan seed extract, while gallic acid, corilagin, (S)-flavogallonic acid, methyl-ellagic acid glucopyranoside, and ethyl gallate showed very little contribution to the total antioxidant activity of longan seed extract. The combining use of the online fishing/knockout method, activity evaluation assays, FT-ICR-MS, and HPLC-ESI-MS analysis is a useful and simple strategy for screening of key bioactive compounds from complex extracts.

Persimmon tannin accounts for hypolipidemic effects of persimmon through activating of AMPK and suppressing NF-κB activation and inflammatory responses in high-fat diet rats.

The present study was to investigate whether high molecular weight persimmon tannin (HMWPT) is the main component associated with the anti-hyperlipidemic effect of consuming persimmon and its underlying mechanism. Male wistar rats were given a basic diet (control), a high-fat diet, a high-fat diet plus 0.5% of HMWPT or 4.2% of lyophilized fresh persimmon fruit (with the same diet HMWPT content in the two groups) for 9 weeks. Administration of HMWPT or persimmon fruit significantly (p < 0.05) lowered serum triglycerides and free fatty acids, enhanced the excretion of triglycerides, cholesterol and bile acids, and improved hepatic steatosis in rats fed a high-fat diet. Dietary HMWPT or persimmon fruit significantly decreased the protein levels of fatty acid synthase (FAS), and stimulated AMP-activated protein kinase (AMPK) phosphorylation and down-regulated genes involved in lipogenesis, including transcriptional factor sterol regulatory element binding protein 1 (SREBP1) and acetyl CoA carboxylase (ACC). In addition, the expression of proteins involved in fatty acid oxidation, such as carnitine palmitoyltransferase-1 (CPT-1), was notably up-regulated. Furthermore, HMWPT and persimmon fruit suppressed inflammatory cytokines such as tumor necrosis factor α (TNFα) and C-reactive protein (CRP) and the protein level of nuclear factor-kappa B (NFκB) in the liver. Taken together, our findings demonstrated that HMWPT reproduced the anti-hyperlipidemic effects of persimmon fruit, and was a pivotal constituent of persimmon fruit accounting for prevention of liver steatosis and its progression to nonalcoholic steatohepatitis (NASH) by activation of the AMPK and regulation of its downstream targets, suppressing NF-κB activation and inflammatory responses, and inhibiting lipids and bile acid absorption.

Preparation of A-type proanthocyanidin dimers from peanut skins and persimmon pulp and comparison of the antioxidant activity of A-type and B-type dimers.

We have established a simple method for preparing large quantities of A-type dimers from peanut skin and persimmon for further structure-activity relationship study. Peanut skins were defatted with hexane and oligomeric proanthocyanidins were extracted from it with 20% of methanol, and the extract was fractionated with ethyl acetate. Persimmon tannin was extracted from persimmon with methanol acidified with 1% hydrochloric acid, after removing the sugar and small phenols, the high molecular weight persimmon tannin was partially cleaved with 6.25% hydrochloric acid in methanol. The ethyl acetate fraction from peanut skins and persimmon tannin cleaved products was chromatographed on AB-8 macroporous resin followed by Toyopearl HW-50F resin to yield about 378.3mg of A-type (epi)catechin (EC) dimer from 1 kg dry peanut skins and 34.3mg of A-type (epi)catechin-3-O-gallate (ECG) dimer and 37.7 mg of A-type (epi)gallocatechin-3-O-gallate (EGCG) dimer from 1 kg fresh persimmon fruit. The antioxidant properties of the A-type and B-type dimers were compared in five different assays, namely, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, 2,2-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical, hydroxyl radical, lipid peroxidation in mice liver homogenate and erythrocyte hemolysis in rat blood. Our results showed that both A-type and B-type dimers showed high antioxidant potency in a dose-dependent manner. In general, B-type dimers showed higher radical scavenging potency than A-type ones with the same subunits in aqueous systems. But in tissue or lipid systems, A-type dimers showed similar or even higher antioxidant potency than B-type ones.

Effect of Kangxin Capsule on the expression of nerve growth factors in parietal lobe of cortex and hippocampus CA1 area of vascular dementia model rats.

OBJECTIVE: To observe the effect of Kangxin Capsule (KXC) on the expression of nerve growth factor (NGF) as well as the morphology and amount of nerve synapse in the cortical parietal lobe and hippocampus CA, area of vascular dementia ( VD) model rats. METHODS: The model rats of VD made by photochemical reaction technique were randomly divided into five groups: the model group (MG), the high-dose, middle-dose and low-dose KXC groups (HDG, MDG and LDG), and the Western medicine hydergin control group (WMG). They were treated respectively with distilled water, high, middle and low dosage of KXC suspended liquid, and hydergin for a month. Besides, a blank group consisting of normal (non-model) rats was set up for control (CG). The ultrastructure of nerve synapse in the cortical parietal lobe and hippocampus CA1 area of the rats were observed and its density estimated. The condition of NGF positive neurons in the above-mentioned two regions were also observed by immunohistochemical stain. RESULTS: All the KXC or hydergin treated groups demonstrated a normal amount of nerve synapse with integral structure in the cortical parietal lobe and hippocampus CA, area, which approached that in the CG and was superior to that in the MG. Also, the NGF positive neuron in all the treated groups was much more than that in MG with significant difference ( P<0.01), approaching to that in the CG. CONCLUSION: KXC could elevate the expression of NGF in the cortical parietal lobe and hippocampus CA, area, preserve the number and morphology of synapse, thus to protect the function of nerve system from ischemic injury.