Chalcones from the flowers of Coreopsis lanceolata and their in vitro antioxidative activity.

Three new chalcones, 3,2'-dihydroxy-4,3'-dimethoxychalcone-4'-glucoside (1), 4'-O-(2'''-O-caffeoyl)2',3',3,4-tetrahydroxychalcone (2), and 2',4',3-trihydroxy-3',4-dimethoxychalcone (3), along with five known phenolics, were isolated from Coreopsis lanceolata flowers. The structures of the new compounds were elucidated by extensive spectroscopic methods including NMR and MS. The three new chalcones showed a good in vitro HepG2 cell protecting effect against tert-butylhydroperoxide-induced oxidative stress.

Protective effect of Paeonia anomala extracts and constituents against tert-butylhydroperoxide-induced oxidative stress in HepG2 cells.

The fruit and root parts of Paeonia anomala L. are used for the treatment of many kinds of disorders in Mongolian traditional medicine. The protective effect of a fruit extract from P. anomala against tert-butylhydroperoxide-induced cell damage was evaluated in human hepatoma HepG2 cells and compared to that of a root extract from P. anomala on the basis of cell viability, generation of intracellular reactive oxygen species, cellular total glutathione concentration, and anti-genotoxicity. The fruit extract of P. anomala showed excellent protection against the oxidative stress when compared to the root extract, through free radical scavenging, enhancing cellular glutathione concentration, and inhibiting DNA damage. Chemical constituents in the fruit extract of P. anomala were investigated and two novel compounds, 2-hydroxy-6-methoxy-4-O-(6'-O-α-L-arabinofuranosyl-ß-D-glucopyranosyl)acetophenone (1) and 3,3'-di-O-methyl-4-O-(3''-O-galloyl-ß-D-glucopyranosyl)ellagic acid (2), along with 18 other known compounds were identified. Compound 2 showed better cytoprotection against tert-butylhydroperoxide than compound 1. Among other compounds isolated from the fruit extract, ellagic acid, methyl gallate, ethyl gallate, fischeroside B, and quercetin derivatives showed potent protective effects against tert-butylhydroperoxide-induced oxidative stress via inhibiting reactive oxygen species generation and increasing total glutathione levels in HepG2 cells.

Saposhnikovia divaricata root and its major components ameliorate inflammation and altered gut microbial diversity and compositions in DSS-induced colitis.

Background: The root of Saposhnikovia divaricata (Turcz.) Schischk is a well-known traditional medicinal plant, containing various bioactive compounds with anti-inflammatory, antioxidant, and analgesic properties. However, no scientific studies have validated its clinical use as an anti-inflammatory agent against inflammatory bowel disease (IBD). This study aimed to investigate whether the root extract of S. divaricata ameliorates IBD and induces gut microbial alteration, using a RAW 264.7 cell line and a DSS-induced colitis mouse model. Methods: To investigate the anti-inflammatory effects and alleviation of IBD, using a methanol extract of Saposhnikovia divaricata (Turcz.) Schischk. root (MESD), RAW 264.7, murine macrophages and a dextran sodium sulfate (DSS)-induced colitis mouse model were employed. 16S rRNA gene sequencing was conducted to determine the alterations in the gut microbiota of mice with DSS-induced colitis. Results: MESD significantly decreased nitric oxide (NO) and inflammatory cytokine levels in lipopolysaccharide (LPS)-induced RAW 264.7 cells in vitro. Oral administration of MESD reduced the expression of inflammatory cytokines in the colons of mice with DSS-induced colitis. Additionally, MESD inhibited the abundance of Clostridium sensu stricto 1 and enhanced the predicted functional pathways, including l-glutamate degradation VIII (to propanoic acid). Seven compounds with anti-inflammatory properties were isolated from the MESD. Among them, 3'-O-acetylhamaudol and 3'-O-angeloylhamaudol exhibited strong anti-inflammatory effects in vitro. Conclusion: Overall, MESD may be a potential natural product for the treatment of IBD by lowering inflammatory cytokine levels and altering gut microbiota composition.

Anti-oxidant and Antiproliferative Activities of Mongolian Medicinal Plant Extracts and Structure Isolation of Gnetin-H Compound.

BACKGROUND: Reactive oxygen species are involved in the etiology and progress of many kinds of diseases such as cancer, cardiovascular diseases, inflammatory and neurodegenerative disorders. Epidemiological studies reported that fruits, vegetables, and wines containing a high percentage of phenolics and flavonoids showed a positive impact in treating inflammatory diseases, reducing cancer risk, and increasing life expectancy. OBJECTIVE: Some Mongolian medicinal plants were studied for their antioxidant activity and anticancer effects. METHODS: Selected Mongolian medicinal plant extracts were examined for their antioxidant activity by the DPPH-radical scavenging assay, the content of phenolics and flavonoids by Folin-Ciocalteu and the Dowd method, respectively, and anti-cancer activities in human hepatoma cell line HepG2 cells by MTT assay. RESULTS: Methanol extract from Hippophae rhamnoides L. leaf and ethanol extract from Artemisia macrocephala Jacq. ex Bess. showed the highest efficiency to scavenge free radicals. Ethanol extracts from Hippophae rhamnoides L. grain and Paeonio anomala L. leaf showed the highest total phenolics content, whereas Hippophae rhamnoides L. fruit methanol extract and ethanol extract from Caragana leucophloea pojark. mentioned the highest flavonoids content. The Artemisia macrocephala Jacq. ex Bess seed wallet and Paeonia anomala L. seed wallet showed the most potent antiproliferative effects against human liver cancer HepG2 cell line. Gnetin-H compound was isolated from the Paeonio anomala L. seed wallet extract, and its molecular structure was determined by 1H and 13C NMR spectrum and IR spectroscopy methods. CONCLUSION: The screening study on anti-oxidative effects of 21 extracts from 15 Mongolian medicinal plants showed anti-oxidative activities and was rich in phenolics and flavonoids. Among these, methanol extract of the Hippophae rhamnoides L. leaf showed a better anti-oxidative effect than the ethanol extract. Artemisia macrocephala Jacq. ex Bess and Paeonia anomala L. seed wallet mentioned the best anti-cancer effects. Gnetin-H, methyl gallate, ethylgallate were the major components in the extract from the Paeonio anomala L. seed wallet. Finally, the molecular structure of gnetin-H was determined by NMR and IR spectroscopy. Further investigation, especially in vivo antioxidant activity, is needed to justify the use of a natural source of antioxidants to prevent the progression of diseases such as cancer.

Gnetin H isolated from Paeonia anomala inhibits FcεRI-mediated mast cell signaling and degranulation.

ETHNOPHARMACOLOGICAL RELEVANCE: Paeonia anomala L. is used in Mongolian traditional medicine to treat various diseases including indigestion, abdominal pain, kidney disorders, inflammation, and female diseases. In this study we examined the effects of Paeonia anomala extract (PAE) and compounds derived from Paeonia anomala on immunoglobulin E (IgE)-mediated type I hypersensitivity responses in vitro. MATERIALS AND METHODS: Degranulation assay, reverse transcription PCR, enzyme-lined immunosorbent assays, western blot analyses were performed to measure allergic and proinflammatory mediators in IgE-stimulated rat basophilic leukemia (RBL)-2H3 mast cells treated with or without PAE or gnetin H. RESULTS: Seventeen compounds were isolated, and ß-hexosaminidase release from IgE-stimulated RBL-2H3 mast cells was measured. Of the seventeen isolated compounds, gnetin H, a resveratrol derivative, significantly inhibited ß-hexosaminidase release from RBL-2H3 cells with an IC50 value of 0.3 µM. Notably, Gnetin H reduced ß-hexosaminidase release at lower concentrations than resveratrol. Furthermore, PAE and gnetin H inhibited histamine secretion, decreased the production and mRNA expression of tumor necrosis factor-α and interleukin-4 and suppressed translocation of nuclear factor κB. PAE and gnetin H also reduced the expression of cyclooxygenase-2 and production of prostaglandin E2. PAE and gnetin H suppressed the phosphorylation of Syk, protein kinase C (PKC)µ, phospholipase Cγ, and the mitogen-activated protein kinases, c-Jun N-terminal kinase, p38, and extracellular signal-regulated kinase. CONCLUSIONS: These results suggest that PAE and its active compound gnetin H could be promising therapeutic agents for allergic disorders.

Antioxidant activity of phenolics in leaves of three red pepper (Capsicum annuum) cultivars.

The antioxidant properties and phenolic profiles were first investigated in this paper on the leaves of three red pepper cultivars, Blackcuban (BCPL), Hongjinju (HPL), and Yeokgang-hongjanggun (YHPL). Of the ethanol extract of the three cultivars, BCPL showed potent antioxidant activities against the 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) and the 2,2-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical. Nine antioxidative compounds from the red pepper leaves were isolated and identified as one polyamine phenolic conjugate, N-caffeoylputrescine (1); three chlorogenic acid derivatives, 5-O-caffeoylquinic acid (2), 5-O-caffeoylquinic acid methyl ester (4), and 5-O-caffeoylquinic acid butyl ester (9); one anthocyanin, delphinidin-3-[4-trans-coumaroyl-l-rhamnosyl(1→6)glucopyranoside]-5-O-glucopyranoside (3); and four flavone glycosides, luteolin-7-O-apiofuranosyl(1→2)glucopyranoside (5), luteolin-7-O-glucopyranoside (6), apigenin 7-O-apiofuranosyl(1→2)glucopyranoside (7), apigenin-7-O-glucopyranoside (8). 1 and 3 had the greatest potential for radical-scavenging activity and HepG2 cells protecting effect against oxidative stress. BCPL exhibited the highest content of 1 and 3. Of the three cultivars BCPL may be considered a good source of antioxidants.

Gymnaster koraiensis and its major components, 3,5-di-O-caffeoylquinic acid and gymnasterkoreayne B, reduce oxidative damage induced by tert-butyl hydroperoxide or acetaminophen in HepG2 cells.

We investigated the protective effects of Gymnaster koraiensis against oxidative stress-induced hepatic cell damage. We used two different cytotoxicity models, i.e., the administration of tert-butyl hydroperoxide (t-BHP) and acetaminophen, in HepG2 cells to evaluate the protective effects of G. koraiensis. The ethyl acetate (EA) fraction of G. koraiensis and its major compound, 3,5-di-O-caffeoylquinic acid (DCQA), exerted protective effects in the t-BHP-induced liver cytotoxicity model. The EA fraction and DCQA ameliorated t-BHP-induced reductions in GSH levels and exhibited free radical scavenging activity. The EA fraction and DCQA also significantly reduced t-BHP-induced DNA damage in HepG2 cells. Furthermore, the hexane fraction of G. koraiensis and its major compound, gymnasterkoreayne B (GKB), exerted strong hepatoprotection in the acetaminophen-induced cytotoxicity model. CYP 3A4 enzyme activity was strongly inhibited by the extract, hexane fraction, and GKB. The hexane fraction and GKB ameliorated acetaminophen-induced reductions in GSH levels and protected against cell death.

Youngia denticulata protects against oxidative damage induced by tert-butylhydroperoxide in HepG2 cells.

Improvement of liver function is one of the most popular commercial health claims of functional foods in Asian countries, including Korea. After examining the potential of several traditional Korean wild vegetables for enhancing liver function, we found that Youngia denticulata Kitam. has strong hepatoprotective effects against oxidative stress induced by tert-butylhydroperoxide (t-BHP). We are the first to report that the extract and ethyl acetate fractions of Y. denticulata have radical scavenging activities and inhibit oxidative stress-induced cell death and DNA damage in HepG2 cells. The extract and ethyl acetate fractions significantly decreased cellular reactive oxygen species production and apoptosis induced by t-BHP in HepG2 cells. In addition, they prevented the depletion of cellular glutathione, which is an important defense molecule against oxidizing xenobiotics. Chlorogenic acid and 3,5-dicaffeoylquinic acid were found to be major active components responsible for the activity of Y. denticulata and could serve as marker compounds for standardization. These data suggest that Y. denticulata could be promoted as a potential antioxidative functional food candidate, particularly for hepatoprotection against oxidative stress.

A polyacetylene from Gymnaster koraiensis exerts hepatoprotective effects in vivo and in vitro.

In the present study, we isolated a polyacetylene, gymnasterkoreayne B (GKB), from Gymnaster koraiensis and investigated the effect of GKB on the protection from oxidative stress-induced cytotoxicity through induction of the expression of cellular defense enzymes. GKB induced mRNA expression and enzyme activity of NAD(P)H:quinone oxidoreductase (NQO1) in vitro and in vivo, and potently increased expression of many cellular defense genes including glutathione-S-transferases, UDP-glucuronosyltransferase, and glutathione reductase (GSR) in normal rat liver. The nuclear factor erythroid 2-related factor 2 (Nrf2) which is known to induce various antioxidant and cytoprotective genes, and the genes containing the antioxidant response element (ARE), including NQO1, hemeoxygenease-1, GSR were induced by GKB in HepG2 human hepatocarcinoma cells. Pre-treatment of the cells with GKB accelerated the production of glutathione and mitigated menadione-induced cytotoxicity in HepG2 cells. Taken together, we found that GKB was a novel inducer of phase II detoxification enzymes and cellular defense enzymes, resulting in protection of the cells from oxidative stress and hepatotoxicity through regulation of detoxifying and antioxidant systems.