PMID: 

Spectrochim Acta A Mol Biomol Spectrosc. 2018 Oct 5 ;203:222-228. Epub 2018 May 26. PMID: 29870906

Abstract Title: 

Non-enzymatic conversion of primary oxidation products of Docosahexaenoic acid into less toxic acid molecules.

Abstract: 

Docosahexaenoic acid (DHA) is long chain omega-3 fatty acid with known health benefits and clinical significance. However, 4-hydroxy hexenal (HHE), an enzymatic oxidation product of DHA has recently been reported to have health-damaging effects. This conflict raises major concern on the long-term clinical use of these fatty acids. Even though the enzymatic and non-enzymatic conversion of HHE to nontoxic acid molecules is possible by the aldehyde detoxification systems, it has not yet studied. To address this, primary oxidation products of DHA in lipoxidase system were subjected to non-enzymatic conversion at physiological temperature over a period of 1 week. The reaction was monitored using HPLC, IR spectroscopy and biochemical assays (based on the loss of conjugated dienes, lipid peroxides aldehydes). Short term and long term cytotoxicity of the compounds generated at various time points were analyzed. IR and HPLC spectra revealed that the level of aldehydes in the primary oxidation products reduced over time, generating acids and acid derivatives within a week period. In short term and long term cytotoxicity analysis, initial decomposition products were found more toxic than the 1-week decomposition products. Further, when primary oxidation products were subjected to aldehyde dehydrogenase mediated oxidation, it generated products that are also less toxic. The study suggests the possible non-enzymatic conversion of primary oxidation products of DHA to less cytotoxic acid molecules. Exploration of the physiological roles of these acid molecules may explain the biological potential of omega-3 fatty acids.

read more

PMID: 

Biochem Biophys Res Commun. 2009 Jul 24 ;385(2):230-5. Epub 2009 May 19. PMID: 19450556

Abstract Title: 

Bioactivity-guided screening identifies pheophytin a as a potent anti-hepatitis C virus compound from Lonicera hypoglauca Miq.

Abstract: 

Chronic hepatitis C virus (HCV) infection is a worldwide public issue. In this study, we performed bioactivity-guided screening of the Lonicera hypoglauca Miq. crude extracts to find for naturally chemical entities with anti-HCV activity. Pheophytin a was identified from the ethanol-soluble fraction of L. hypoglauca that elicited dose-dependent inhibition of HCV viral proteins and RNA expression in both replicon cells and cell culture infectious system. Computational modeling revealed that pheophytin a can bind to the active site of HCV-NS3, suggesting that NS3 is a potent molecular target of pheophytin a. Biochemical analysis further revealed that pheophytin a inhibited NS3 serine protease activity with IC(50)=0.89 microM. Notably, pheophytin a and IFNalpha-2a elicited synergistic anti-HCV activity in replicon cells with no significant cytotoxicity. This study thereby demonstrates for the first time that pheophytin a is a potent HCV-NS3 protease inhibitor and offers insight for development of novel anti-HCV regimens.

read more

PMID: 

J Nat Med. 2010 Jul ;64(3):288-94. Epub 2010 Mar 20. PMID: 20306146

Abstract Title: 

Protective effects of Flos lonicera extract on acute liver injury by dimethylnitrosamine-induced in rats.

Abstract: 

The aim of this study is to investigate effects of Flos lonicera extract (FLE) on acute liver injury model rats which induced by 35 mg/kg dimethylnitrosamine (DMN). Model rats were divided into hepatic injury control group (administrated with water), FLE group (administrated with FLE) and silymarin group (administrated with silymarin which is hepatotherapeutic drug) as positive control. They were examined including ALT, AST, ALP, gamma-GT, ALB and TP levels in serum, and MDA, GPx levels in liver tissue. In addition, pathologic changes, particularly fibrosis, were examined by Azan staining. The results revealed that the ALT, AST, ALP, gamma-GT, MDA GPx and liver fibrosis degree in the LJE group were lower than the silymarin group and control group, ALB and TP were higher than the silymarin group and control group. These results suggested that LJE may help in inhibiting of acute liver injury greater than silymarin.

read more

PMID: 

Aging Cell. 2017 10 ;16(5):1125-1135. Epub 2017 Aug 3. PMID: 28772063

Abstract Title: 

Theω-3 fatty acid α-linolenic acid extends Caenorhabditis elegans lifespan via NHR-49/PPARα and oxidation to oxylipins.

Abstract: 

The dietary intake ofω-3 polyunsaturated fatty acids has been linked to a reduction in the incidence of aging-associated disease including cardiovascular disease and stroke. Additionally, long-lived Caenorhabditis elegans glp-1 germ line-less mutant animals show a number of changes in lipid metabolism including the increased production of the ω-3 fatty acid, α-linolenic acid (ALA). Here, we show that the treatment of C. elegans with ALA produces a dose-dependent increase in lifespan. The increased longevity of the glp-1 mutant animals is known to be dependent on both the NHR-49/PPARα and SKN-1/Nrf2 transcription factors, although the mechanisms involved are incompletely understood. We find that ALA treatment increased the lifespan of wild-type worms and that these effects required both of these transcription factors. Specifically, NHR-49 was activated by ALA to promote the expression of genes involved in the β-oxidation of lipids, whereas SKN-1 is not directly activated by ALA, but instead, the exposure of ALA to air results in the oxidation of ALA to a group of compounds termed oxylipins. At least one of the oxylipins activates SKN-1 and enhances the increased longevity resulting from ALA treatment. The results show that ω-3 fatty acids inhibit aging and that these effects could reflect the combined effects of the ω-3 fatty acid and the oxylipin metabolites. The benefits of ω-3 fatty acid consumption on human health may similarly involve the production of oxylipins, and differences in oxylipin conversion could account for at least part of the variability found between observational vs. interventional clinical trials.

read more

PMID: 

Food Chem Toxicol. 2010 Jun ;48(6):1555-61. Epub 2010 Mar 21. PMID: 20332009

Abstract Title: 

Polyphenolic fraction of Lonicera caerulea L. fruits reduces oxidative stress and inflammatory markers induced by lipopolysaccharide in gingival fibroblasts.

Abstract: 

The most common oral diseases have a microbial aetiology. Pathogenic bacteria liberate a number of irritating agents including a lipopolysaccharide (LPS) that activates pro-inflammatory cytokines promoting increased activity of polymorphonucleocytes (PMN). Release of PMN-derived free radicals into an infected gingival area affects gums, periodontal ligaments and alveolar bone. Berries of Lonicera caerulea L. (blue honeysuckle) are rich in phenolics, particularly phenolic acids, flavonoids and anthocyanins that have multiple biological activities in vitro and in vivo such as antiadherence, antioxidant and anti-inflammatory. Studies have shown that polyphenols suppress a number of LPS-induced signals and thus could be effective against gingivitis. Here we assessed effects of the polyphenolic fraction of L. caerulea fruits (PFLC; containing 77% anthocyanins) on LPS-induced oxidative damage and inflammation in human gingival fibroblasts. Application of PFLC (10-50mug/ml) reduced reactive oxygen species (ROS) production, intracellular glutathione (GSH) depletion as well as lipid peroxidation in LPS-treated cells. PFLC treatment also inhibited LPS-induced up-regulation of interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) and it suppressed expression of cyclooxygenase-2 (COX-2). The effects are presumably linked to its antioxidant and anti-inflammatory activities and suggest its use in attenuating the inflammatory process, including periodontal disease.

read more

PMID: 

Biochimie. 2016 Jan ;120:56-61. Epub 2015 Jun 23. PMID: 26112019

Abstract Title: 

Non-enzymatic cyclic oxygenated metabolites of omega-3 polyunsaturated fatty acid: Bioactive drugs?

Abstract: 

Non-enzymatic oxygenated metabolites derived from polyunsaturated fatty acids (PUFA) are formed in vivo through free radical reaction under oxidative stress conditions. It has been over twenty-five years since the discovery of cyclic oxygenated metabolites derived from arachidonic acid (20:4 n-6), the isoprostanes, and since then they have become biomarkers of choice for assessing in vivo OS in humans and animals. Chemical synthesis of n-3 PUFA isoprostanoids such as F3-Isoprostanes from eicosapentaenoic acid (20:5 n-3), and F4-Neuroprostanes from docosahexaenoic acid (22:6 n-6) unravelled novel and unexpected biological properties of such omega-3 non-enzymatic cyclic metabolites as highlighted in this review.

read more

PMID: 

J Pharm Biomed Anal. 2010 Sep 21 ;53(1):98-102. Epub 2010 Mar 17. PMID: 20371156

Abstract Title: 

Metabonomics study of the protective effects of Lonicera japonica extract on acute liver injury in dimethylnitrosamine treated rats.

Abstract: 

A metabonomics approach, consisting of gas chromatography coupled to mass spectrometry (GC/MS) and a multivariate statistical technique, was developed to estimate the protective effects of Lonicera japonica extract (LJE) on acute liver injury. A high dose of dimethylnitrosamine (DMN) was used to induce an acute stage of hepatic injury in 21 male Wistar rats. The rats were divided into three groups: normal, model and treatment. Pathological changes, particularly fibrosis, were also examined by Azan staining. The results indicate that clear and consistent biochemical changes occur. Nine candidate biomarkers for DMN treatment and LJE intervention under controlled conditions were identified using chemometric analysis. Pathological analysis suggests that LJE has a protective effect to the liver. This work suggests that a metabonomics approach can be used to estimate pharmacodynamic action of naturally occurring drugs in a dynamic and non-invasive way.

read more

PMID: 

Biochim Biophys Acta. 2015 Apr ;1851(4):485-95. Epub 2014 Sep 28. PMID: 25263947

Abstract Title: 

Omega-3 polyunsaturated fatty acids and oxygenated metabolism in atherothrombosis.

Abstract: 

Numerous epidemiological studies and clinical trials have reported the health benefits of omega-3 polyunsaturated fatty acids (PUFA), including a lower risk of coronary heart diseases. This review mainly focuses on the effects of alpha-linolenic (ALA), eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids on some risk factors associated with atherothrombosis, including platelet activation, plasma lipid concentrations and oxidative modification of low-density lipoproteins (LDL). Special focus is given to the effects of marine PUFA on the formation of eicosanoids and docosanoids, and to the bioactive properties of some oxygenated metabolites of omega-3 PUFA produced by cyclooxygenases and lipoxygenases. The antioxidant effects of marine omega-3 PUFA at low concentrations and the pro-oxidant effects of DHA at high concentrations on the redox status of platelets and LDL are highlighted. Non enzymatic peroxidation end-products deriving from omega-3 PUFA such as hydroxy-hexenals, neuroketals and EPA-derived isoprostanes are also considered in relation to atherosclerosis. This article is part of a Special Issue entitled"Oxygenated metabolism of PUFA: analysis and biological relevance".

read more

PMID: 

J Agric Food Chem. 2010 Nov 24 ;58(22):11653-61. Epub 2010 Oct 19. PMID: 20958047

Abstract Title: 

Luteolin ameliorates experimental lung fibrosis both in vivo and in vitro: implications for therapy of lung fibrosis.

Abstract: 

Lonicera japonica (Caprifoliaceae) has been known as an anti-inflammatory herb in traditional Chinese medicine for thousands of years and is used constantly for upper respiratory tract infections. Luteolin, an active flavonoid compound isolated from Lonicera japonica, has a spectrum of biological activities, especially with antioxidative and anti-inflammatory properties. However, whether luteolin has a direct inhibitory effect on lung fibrosis has not been established. In this study, we examined the effects of luteolin on lung fibrosis both in vivo and in vitro. We found that oral administration of luteolin (10 mg/kg) efficiently suppressed the neutrophil infiltration as well as TNF-α and IL-6 elevation in the bronchoalveolar lavage fluid in bleomycin-instilled C57BL/6J mice. Luteolin also alleviated collagen deposition, TGF-β1 expression, and lung fibrosis upon bleomycin instillation. A similar tendency was observed in both early and delayed luteolin-treated groups. Next, our in vitro studies showed that luteolin inhibited TGF-β1-induced α-SMA, type I collagen, and vimentin expression in primary cultured mouse lung fibroblasts. Moreover, luteolin significantly blocked TGF-β1-mediated epithelial marker (E-cadherin) downregulation and mesenchymal cell markers (fibronectin and vimentin) upregulation, as well as retaining epithelial morphology in human alveolar epithelial-derived A549 cells. Additionally, luteolin could attenuate TGF-β1-induced Smad3 phosphorylation in both lung fibroblasts and A549 cells. These findings suggest that luteolin has a potent antifibrotic activity; this effect was mediated, at least in part, by inhibition of lung inflammation and suppression of myofibroblast differentiation as well as epithelial-to-mesenchymal transition.

read more

PMID: 

Food Chem Toxicol. 2011 Apr ;49(4):1011-9. Epub 2011 Jan 12. PMID: 21237235

Abstract Title: 

The neuroprotective effects of Lonicera japonica THUNB. against hydrogen peroxide-induced apoptosis via phosphorylation of MAPKs and PI3K/Akt in SH-SY5Y cells.

Abstract: 

We investigated the neuroprotective effects of Lonicera japonica THUNB. (Caprifoliaceae) (LJ) extract against hydrogen peroxide (H(2)O(2)), a toxin created by oxidative stress and implicated in neurodegenerative diseases, in human SH-SY5Y neuroblastoma cells. We examined the effects of LJ against H(2)O(2)-induced cytotoxicity, apoptosis, the production of reactive oxygen species (ROS), the proteolysis of cleaved poly-ADP-ribose polymerase (PARP), and the expression of Bcl-2, Bcl-xL, and cleaved caspase-3. Moreover, we attempted to determine whether LJ suppressed the phosphorylation of Akt, c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), and extracellular signal-regulated kinase 1/2 (ERK 1/2). We found that LJ improved cell viability, inhibited cytotoxicity and apoptosis, and attenuated elevations in ROS and nuclear condensation. In addition, LJ showed radical scavenging ability in 2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azinobis-(3-ethyl-benzthiazoline-6-sulfonic acid) (ABTS) assays. Western blot data revealed that LJ inhibited H(2)O(2)-induced up- and down-regulation of cleaved PARP, cleaved caspase-3, Bcl-2, and Bcl-xL. Furthermore, LJ significantly attenuated the H(2)O(2)-induced phosphorylation of Akt, JNK, p38 MAPK, and ERK1/2. These results demonstrate that LJ possesses potent neuroprotective activity. Its potential to treat neurodegenerative diseases warrants further research.

read more