Chemical Constituents of Halophyte Suaeda glauca and Their Therapeutic Potential for Hair Loss.

Suaeda glauca, a halophyte in the Amaranthaceae family, exhibits remarkable resilience to high salt and alkali stresses despite the absence of salt glands or vesicles in its leaves. While there is growing pharmacological interest in S. glauca, research on its secondary metabolites remains limited. In this study, chemical constituents of the aerial parts of S. glauca were identified using 1D- and 2D-NMR experiments, and its biological activity concerning hair loss was newly reported. Eight compounds, including alkaloids (1~3), flavonoids (4~6), and phenolics (7 and 8), were isolated. The compounds, except the flavonoids, were isolated for the first time from S. glauca. In the HPLC chromatogram, quercetin-3-O-ß-d-glucoside, kaempferol-3-O-ß-d-glucoside, and kaempferol were identified as major constituents in the extract of S. glauca. Additionally, the therapeutic potential of the extract of S. glauca and the isolated compounds 1~8 on the expressions of VEGF and IGF-1, as well as the regulation of Wnt/ß-catenin signaling, were evaluated in human follicle dermal papilla cells (HFDPCs) and human umbilical vein endothelial cells (HUVECs). Among the eight compounds, compound 4 was the most potent in terms of increasing the expression of VEGF and IGF-1 and the regulation of Wnt/ß-catenin. These findings suggest that S. glauca extract and its compounds are potential new candidates for preventing or treating hair loss.

Physiological and biochemical responses of Limonium tetragonum to NaCl concentrations in hydroponic solution.

Introduction: Limonium (L.) tetragonum (Thunb.) A. A. Bullock, a halophyte that grows all over the southwest coast of Korea, is a medicinal plant with various pharmacological effects. The salt defense mechanism stimulates the biosynthesis of various secondary metabolites and improves functional substances. In this study, we investigated the optimal NaCl concentration for the growth and enhancement of secondary metabolites in hydroponically grown L. tetragonum. Methods: The seedlings grown for 3 weeks in a hydroponic cultivation system were treated with 0-, 25-, 50-, 75-, and 100-mM NaCl in Hoagland's nutrient solution for 8 weeks. No significant effect on the growth and chlorophyll fluorescence was observed for the NaCl concentrations below 100-mM. Results and discussions: The increase in the NaCl concentration resulted in the decrease in the water potential of the L. tetragonum leaves. The Na+ content accumulated in the aerial part increased rapidly and the content of K+, which acts as an antagonist, decreased with the increase in NaCl concentrations in hydroponics. The total amino acid content of L. tetragonum decreased compared to the 0-mM NaCl, and most of the amino acid content decreased as the NaCl concentration increased. In contrast, the content of urea, proline (Pro), ß-alanine, ornithine, and arginine was increased with an increase in NaCl concentration. The Pro content at 100-mM NaCl accounted for 60% of the total amino acids and was found to be a major osmoregulator as an important component of the salt defense mechanisms. The top five compounds identified in the L. tetragonum were classified as flavonoids while the flavanone compound was detected only in the NaCl treatments. A total of four myricetin glycosides were increased in comparison to the 0-mM NaCl. Among the differentially expressed genes, a significantly large change in Gene ontology was seen in the circadian rhythm. NaCl treatment enhanced the flavonoid-based substances of L. tetragonum. The optimum NaCl concentration for the enhancement of secondary metabolites of the L. tetragonum in the vertical farm-hydroponic cultivation system was 75-mM NaCl.

Sesquiterpene Lactones with Anti-Inflammatory Activity from the Halophyte Sonchus brachyotus DC.

There were five sesquiterpene lactones, belonging to the eudesmanolide class, isolated from the halophyte Sonchus brachyotus DC. The structures of the compounds were determined using spectroscopic methods, including 1D and 2D NMR spectra, MS data, and optical rotation values. Compounds 4 and 5 were characterized by the position of p-hydroxyphenylacetyl group in the sugar moiety. In the evaluation of anti-inflammatory effects on LPS-activated RAW264.7 macrophages, compound 1, 5α,6ßH-eudesma-3,11(13)-dien-12,6α-olide, potently suppressed the expression of iNOS and COS-2, as well as the production of TNF-α, IL-6, and IL-10. Treatment of 1 regulates the Nrf2/HO-1 pathway.

Voratins A-C: Pyridinium Alkaloids from the Marine Dinoflagellate Effrenium voratum with Inhibitory Effects on Biomarkers for Benign Prostatic Hyperplasia.

Three voratin compounds (1-3) were isolated from the symbiotic marine dinoflagellate Effrenium voratum. The planar structures of 1-3 were determined by 1D and 2D NMR spectroscopy and HRESIMS, and the relative and absolute configurations were established using ROESY correlations, Mosher's method, and quantum calculations. All of the compounds are zwitterionic and contain a dihydroindolizinium ring and a spiroketal moiety. Compounds 1-3 were found to exhibit therapeutic effects against benign prostatic hyperplasia (BPH), as evaluated using testosterone propionate-treated LNCap and RWPE-1 human prostate cells. This excellent activity suggests that 1-3 are promising for the development of BPH treatments.

The Effects of Aronia melanocarpa Extract on Testosterone-Induced Benign Prostatic Hyperplasia in Rats, and Quantitative Analysis of Major Constituents Depending on Extract Conditions.

This study aimed to investigate the beneficial effects of A. melanocarpa on testosterone propionate (TP)-induced benign prostatic hyperplasia (BPH) in Wistar rats. Moreover, the bioactive constituents in the extract were determined using LC/MS and HPLC analyses. The dried fruits of A. melanocarpa were extracted using accelerated solvent extraction (ASE) under different extract conditions (temperature, 30 C or 100 C; extract solvent, 60% or 100% ethanol) to yield four extracts (T1~T4). Of the four A. melanocarpa extracts, T1 extracted under the condition of 100% ethanol/low temperature (30 C) exhibited the greatest inhibitory activity on TP-induced prostatic hyperplasia in rats. The administration of T1 (100 mg/kg body weight, p.o.) for six weeks attenuated TP-induced prostate enlargement and reduced the levels of dihydrotestosterone (DHT) and 5α-reductase in both serum and prostate tissue. The suppression of PCNA mRNA expression in prostate tissue was remarkable in T1-treated rats. In LC/MS analysis, the levels of main anthocyanins and phenolics were significantly higher in T1 than in the other extracts. Furthermore, the quantitative study showed that the contents of cyanidin-3-glucose and cyanidin-3-xylose in T1 exhibited 1.27~1.67 and 1.10~1.26 folds higher compared to those in the other extracts. These findings demonstrated that A. melanocarpa extract containing anthocyanins as bioactive constituents attenuated the development of testosterone-induced prostatic hyperplasia, and suggested that this extract has therapeutic potential to treat prostate enlargement and BPH.

Chemical constituents from the fruits of Schisandra sphenanthera and their cytotoxicity activity

Abstract Schisandra sphenanthera Rehder & E.H. Wilson, Schisandraceae, is well known as a type of traditional medicine for the treatment of hepatitis, diarrhea and insomnia in Asia. It was also reported to have antiviral and anti-HIV activities. Using various chromatographic resins and isolation techniques, a new lignan (1), erythro-4-(3,4-dimethoxyphenyl)-4-hydroxy-3-methylbutan-2yl-3,4-dimethoxybenzoate, along with fifteen known compounds, were isolated from fruits of S. sphenanthera. The structures of the compounds were identified by extensive spectroscopic and spectrometric methods including 1D and 2D NMR and MS data. All the isolated compounds were evaluated for their cytotoxicity activity against Hela, HepG2 and HCT-116 cells. Among them, compound schisanlactone C showed significant cytotoxicity activity.

Developmental and reproductive toxicity assessment in rats with KGC-HJ3, Korean Red Ginseng with Angelica gigas and Deer antlers.

BACKGROUND: Korean Red Ginseng has been widely used in traditional oriental medicine for a prolonged period, and its pharmacological effects have been extensively investigated. In addition, Angelica gigas and deer antlers were also used as a tonic medicine with Korean Red Ginseng as the oriental herbal therapy. METHODS: This study was conducted to evaluate the potential toxicological effect of KGC-HJ3, Korean Red Ginseng with angelica gigas and deer antlers, on reproductive and developmental functions including fertility, early embryonic development, maternal function, and embryo-fetal development. KGC-HJ3 was administered by oral gavage to Sprague-Dawley rats (22 animals per sex per group) at dose levels of 0 mg/kg (control), 500 mg/kg, 1000 mg/kg, and 2000 mg/kg to evaluate the potential toxicological effect on fertility and early embryonic development. In addition, KGC-HJ3 was also administered by oral gavage to mating-proven Sprague-Dawley rats (22 females per group) during the major organogenesis period at dose levels of 0 mg/kg (control), 500 mg/kg, 1000 mg/kg, and 2000 mg/kg to evaluate the potential toxicological effect on maternal function and embryo-fetal development. RESULTS AND CONCLUSION: No test item-related changes in parameters for fertility, early embryonic development, maternal function, and embryo-fetal development were observed during the study period. On the basis of these results, it was concluded that KGC-HJ3 did not have toxicological potential on developmental and reproductive functions. Therefore, no observed adverse effect levels of KGC-HJ3 for fertility, early embryonic development, maternal function, and embryo-fetal development is considered to be at least 2000 mg/kg/day.

Chokeberry Extract and Its Active Polyphenols Suppress Adipogenesis in 3T3-L1 Adipocytes and Modulates Fat Accumulation and Insulin Resistance in Diet-Induced Obese Mice.

Berries of Aronia melanocarpa (chokeberry) are known to be a rich source of biologically active polyphenols. In the present study, the effects of seven anti-adipogenic polyphenolic phytochemicals isolated from A. melanocarpa methanol extract on adipogenic transcription factors were investigated. Amygdalin and prunasin were found to inhibit 3T3-L1 adipocyte differentiation by suppressing the expressions of PPARγ (peroxisome proliferator-activated receptor γ), C/EBPα (CCAAT/enhancer binding protein α), SREBP1c (sterol regulatory element binding protein 1c), FAS (fatty acid synthase), and aP2 (adipocyte fatty-acid⁻binding protein). A. melanocarpa extract-treated (100 or 200 mg/kg/day on body weight) high fat diet (HFD)-induced obese mice showed significant decreases in body weight, serum triglyceride (TG), and low-density lipoprotein cholesterol (LDLC) levels and improved insulin sensitivity as compared with HFD controls. This research shows A. melanocarpa extract is potentially beneficial for the suppression of HFD-induced obesity.

Antiobesity Effect of Fermented Chokeberry Extract in High-Fat Diet-Induced Obese Mice.

Black-fruited chokeberries (Aronia melanocarpa), growing mainly in the Central and Eastern European countries, have health benefits due to the high concentrations of polyphenolic compounds. However, a strong bitter taste of chokeberries limits its usage as functional food. We hypothesized that the fermented A. melanocarpa with a reduced bitter taste would improve insulin sensitivity and/or ameliorate weight gain induced by high-fat diet (HFD) in male C57BL/6J mice. The mice were administered with HFD together with the 100 mg/kg of natural A. melanocarpa (T1) or the fermented A. melanocarpa (T2) for 8 weeks. The treatment with T2 (100 mg/kg body weight, p.o.) markedly attenuated the weight gain and the increase in serum triglyceride level induced by HFD. The T2-treated group had better glucose tolerance and higher insulin sensitivity as measured by oral glucose tolerance test and intraperitoneal insulin tolerance test in comparison to the T1-treated group. Phytochemical analysis revealed that the main constituents of T2 were cyanidin-3-xyloside and 1-(3',4'-dihydroxycinnamoyl)cyclopenta-2,3-diol, and the content of cyanidin glycosides (3-glucoside, 3-xyloside) was significantly reduced during the fermentation process. From the above results, we postulated that antiobesity effect of black chokeberry was not closely correlated with the cyanidin content. Fermented chokeberry might be a viable dietary supplement rich in bioactive compounds useful in preventing obesity.

The Standardized Extract of Limonium tetragonum Alleviates Chronic Alcoholic Liver Injury in C57Bl/6J Mice.

BACKGROUND: In traditional folk medicine, Limonium tetragonum is used in the treatment of uterine hemorrhage, tinnitus, and oligomenorrhea. OBJECTIVE: This study aimed to identify the therapeutic effect of L. tetragonum EtOAc extract (EALT) on liver of mice with chronic alcohol poisoning. MATERIALS AND METHODS: C57BL/6J mice were administered 100 mg/kg of EALT with a single binge ethanol/Lieber-DeCarli liquid diet for 8 weeks. RESULTS: The chronic-binge ethanol diet induced a significant increase in liver marker enzyme activities. Coadministration of EALT reversed the elevation of serum total cholesterol and triglyceride as well as aspartate aminotransferase and alanine aminotransferase due to chronic alcohol consumption. Histologic findings including markedly attenuated fat accumulation in hepatocytes were observed in EALT-treated mice. EALT supplementation prevented alcoholic liver injury through attenuation of inflammatory mediators such as toll-like receptor-4, cytochrome P4502E1, and cyclooxygenase-2, and inflammatory cytokine interleukin-6. CONCLUSION: Results provided direct experimental evidence for the hepatoprotective effect of EALT in the NIAAA mouse model. Therapeutic attempts with the L. tetragonum extract might be useful in the management of alcoholic liver disease. SUMMARY: Halophyte Limonium tetragonum has recently been of interest in Korea for its nutritional value and salty taste which made it an ideal vegetablePhytochemical analysis of L. tetragonum EtOAc extract (EALT) resulted in nine compounds including catechins and myricetin glycosides as main componentsAdministration of EALT for 8 weeks showed hepatoprotective effect on Lieber-DeCarli diet-fed mouse modelA significant decrease in liver marker enzymes and inflammatory mediators was also detected. Abbreviations used: EALT: L. tetragonum EtOAc extract; TC: Total cholesterol; TG: Triglyceride; ROS: Reactive oxygen species; CYP2E1: Cytochrome P4502E1; TLR-4: Toll-like receptor-4; COX-2: Cyclooxygenase-2.

Estrogenic activity of constituents from the rhizomes of Rheum undulatum Linné.

Stilbenes have been reported to be phytoestrogen compounds owing to its structural similarity to the estrogenic agent diethylstilbestrol. To find new stilbene-derivative phytoestrogens, isolation of stilbene-rich R. undulatum was performed and led to identify six new compounds (1-5 and 28), one newly determined absolute configurations compound (27) together with 21 previously reported compounds (6-26). The structures of compounds were determined on the basis of extensive spectroscopic methods including 1D and 2D NMR and CD spectra data. All the isolated compounds were tested for their estrogenic activities in HepG2 cells transiently transfected with ERα, ERß and ERE-reporter plasmid. Among them, stilbene-derivatives, piceatannol 3'-O-ß-d-xylopyranoside (12), cis-rhaponticin (16) and rhapontigenin 3'-O-ß-d-glucopyranoside (17), showed the more potent binding affinity for estrogen receptors than 17ß-estrodiol.

Subchronic oral toxicity study of Korean red ginseng extract in Sprague-Dawley rats with a 4-week recovery period.

Ginseng is a major herbal remedy used in Asian countries for thousands of years and known to restore and enhance vital energy. Korean red ginseng, which is processed by steaming and drying fresh Panax ginseng, is most popular and contains unique ginsenosides, which have anticancer and anti-inflammatory properties. The present study was carried out to evaluate the repeated oral dose toxicity of Korean red ginseng extract. The test article was administered orally once a day to male and female Sprague-Dawley rats at dose levels of 0, 500, 1000, or 2000 mg/kg/day for 13 consecutive weeks (15 animals/sex/group in the vehicle control and 2000 mg/kg/day groups, and 10 animals/sex/group in the 500 and 1000 mg/kg/day groups). Ten animals per group were sacrificed at the end of the 13-week treatment period, and the remaining rats were sacrificed after a 4-week recovery period. Administration of Korean red ginseng extract did not result in any toxicologically significant changes in mortality, body weight, food consumption, ophthalmoscopy, hematology, serum biochemistry, gross pathological findings, absolute/relative organ weights, or histopathology. It was established that the no observed adverse effect level (NOAEL) of the test article was 2000 mg/kg/day for both sexes in this study.

Anti-obesity Effect of Halophyte Crop, Limonium tetragonum in High-Fat Diet-Induced Obese Mice and 3T3-L1 Adipocytes.

Halophyte Limonium tetragonum has recently been of interest in Korea for its nutritional value and salty taste which made it an ideal vegetable. In this study, the potential of L. tetragonum preventing excess weight gain, obesity and the related health problem has been evaluated in vitro and in vivo. The treatment with 100 mg/kg of L. tetragonum EtOAc soluble fraction (EALT) apparently prevented the body weight gain, adipose tissue weight gain, and the increase of triglyceride and total cholesterol level in mice fed a high-fat diet for 8 weeks. In addition, both glucose tolerance and insulin resistance in dietary obese mice were improved by EALT administration. A marked decrease in adipocyte differentiation was observed in the EALT (50 µg/mL)-treated 3T3-L1 cells, which was mediated by the suppression of adipogenesis-related transcription factors including peroxisome proliferator-activated receptor (PPAR) γ, CCAAT/enhancer binding protein (C/EBP)α, and Sterol regulatory element binding protein-1 (SREBP-1) and adipocyte-specific proteins such as fatty acid synthase (FAS), lipoprotein lipase (LPL), and adipocyte fatty acid-binding protein (aP2). The major components contained in EALT were identified as (-)-epigallocatechin-3-(3″-O-methyl) gallate, (-)-epigallocatechin-3-gallate, and myricetin-3-O-ß-D-galactopyranoside based on its phytochemical analysis. Results suggested that EALT might be available as functional crop and bioactive diet supplement for the prevention and/or treatment of obesity.

The Standardized Extract of Juniperus communis Alleviates Hyperpigmentation in Vivo HRM-2 Hairless Mice and in Vitro Murine B16 Melanoma Cells.

In European folk medicine, the fruits of Juniperus communis are used in the treatment of skin-related disorders such as skin infection, itching, and psoriasis. Previously, we reported that the EtOAc fraction of J. communis (EAJC) contained tyrosinase inhibition properties in vitro non-cellular experiment. The aim of this study was to evaluate anti-melanogenic effect of standardized EAJC on a hyperpigmentation animal model. Therapeutic effects of EAJC toward skin hyperpigmentation were confirmed by both in vivo experiment and in vitro cell-based assay. Skin depigmenting effect was detected by topical treatment of EAJC for 11 d to HRM-2 melanin-possessing hairless mice. Histologic findings including significantly decreased melanin depositions could be observed in dorsal skin samples of EAJC-treated group. In addition, the EAJC (50 µg/mL) attenuated melanin production through down-regulation of tyrosinase activity and protein expression in B16 murine melanoma cells. According to the phytochemical analysis, EAJC was found to contain hypolaetin-7-O-ß-D-xylopyranoside and isoscutellarein-7-O-ß-D-xylopyranoside as main components. Hypolaetin-7-O-ß-D-xylopyranoside was responsible for the skin-lightening effect of EAJC by reducing the number of melanocytes in dorsal skins of HRM-2 mice. The present study provided direct experimental evidence for skin-lightening effect of EAJC in UV-irradiated hairless mouse model. Therapeutic attempts with the J. communis might be useful in the management of skin pigmentation-related diseases.

Comparative Evaluation of Sulfur Compounds Contents and Antiobesity Properties of Allium hookeri Prepared by Different Drying Methods.

Despite the nutritional and medicinal values of Allium hookeri, its unique flavor (onion or garlic taste and smell) coming from sulfur containing compounds limits its usage as functional food. For comparative study, A. hookeri roots were prepared under two different drying conditions, namely, low-temperature drying that minimizes the volatilization of sulfur components and hot-air drying that minimizes the garlic odor and spicy taste of A. hookeri. In GC/MS olfactory system, the odorous chemicals and organosulfur compounds such as diallyl trisulfide, dimethyl trisulfide, and dipropyl trisulfide were significantly decreased in hot-air drying compared to low-temperature drying. The spiciness and saltiness taste were noticeably reduced, while sourness, sweetness, and umami taste were significantly increased in hot-air dried A. hookeri according to electronic tongue. Although the content of volatile sulfur components was present at lower level, the administration of hot-air dried A. hookeri extract (100 mg/kg p.o.) apparently prevented the body weight gain and improved insulin resistance in C57BL/6J obese mice receiving high fat diet. Results suggested that the hot-air dried A. hookeri possessing better taste and odor might be available as functional crop and bioactive diet supplement for the prevention and/or treatment of obesity.

Protective Effects of Ethyl Acetate Soluble Fraction of Limonium tetragonum on Diethylnitrosamine-Induced Liver Fibrosis in Rats.

Diethylnitrosamine (DEN) is a potent toxic material that can cause necrosis and subsequent fibrosis in the liver. Based on the previously reported hepatoprotective effect of Limonium tetragonum against the proliferation of hepatic stellate cells, we tested the EtOAc soluble fraction of L. tetragonum extract (EALT) in a DEN-induced hepatotoxic rat model. The development of hepatotoxicity including mononuclear cell infiltration and fibrosis induced by intraperitoneal injections of DEN (70 mg/2 mL/kg body weight (b.w.) per week) was observed at 4, 6 and 8 weeks after the first DEN treatment. Administration of EALT (200 mg/kg body weight, per os (p.o.)) induced significant reductions in serum alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), and triglycerides (TG) in DEN-injected rats. Increased oxidative stress in DEN-induced liver fibrosis rats was diminished by EALT treatment through a decrease in malondialdehyde (MDA) and increase in superoxide dismutase (SOD). Histologic findings that included markedly attenuated mononuclear cell infiltration and fibrosis could be observed in liver samples from the EALT-treated groups. An extract of Hovenia dulcis fruit and Sylimarin were used as positive controls. The present study provides direct experimental evidence for EALT attenuated hepatic injury and fibrosis in DEN-treated mice. The L. tetragonum EtOAc fraction might be useful in treating fibrotic liver diseases.

Anti-obesity Effect of Dioscorea oppositifolia Extract in High-Fat Diet-Induced Obese Mice and Its Chemical Characterization.

Dioscorea oppositifolia is a well-known edible and traditional medicine for the treatment of gastrointestinal diseases. In our previous study, D. oppositifolia exhibited both pancreatic lipase inhibition and an anti-adipogenesis effect in vitro. This study was performed to investigate the anti-obesity effect of D. oppositifolia on high-fat diet-induced obese mice. Female ICR mice were fed a high-fat diet with the 100 mg/kg of D. oppositifolia n-BuOH extract for 8 weeks. The high-fat diet mice received the 15 mg/kg Orlistat orally as a positive control. The body weight, parametrial adipose tissue weight, and the levels of triglyceride (TG), total cholesterol (TC), and low density lipoprotein (LDL)-cholesterol in blood serum of female ICR mice were significantly decreased by feeding a high-fat diet with the n-BuOH extract of D. oppositifolia. An inhibitory effect of D. oppositifolia extract on dietary fat absorption was also clearly shown. The D. oppositifolia sample was found to contain 3,5-dimethoxy-2,7-phenanthrenediol and (3R,5R)-3,5-dihydroxy-1,7-bis(4-hydroxyphenyl)-3,5-heptanediol as main components based on its phytochemical analysis. The present study is the first report of the anti-obesity effect by D. oppositifolia n-BuOH extract using an established disease model. The increase in fecal fat excretion by treatment of D. oppositifolia may be an effective approach for treating obesity and related diseases.

Antifibrotic compounds from Liriodendron tulipifera attenuating HSC-T6 proliferation and TNF-α production in RAW264.7 cells.

The inhibition of hepatic stellate cell (HSC) proliferation has been considered as an effective therapeutic target for the treatment of liver fibrosis. The methanolic extract of Liriodendron tulipifera showed significant inhibitory activity against the proliferation of HSCs. Bioactivity-guided isolation afforded twelve compounds including (-)-sesamin (1), (-)-syringaresinol (2), (+)-dihydrodehydrodiconiferyl alcohol (3), salvinal (4), (+)-guaiacylglycerol-8-O-4'-dihydroconiferyl ether (5), (±)-guaiacylglycerol-8-O-4'-sinapyl alcohol ether (6), tanegool (7), (+)-5,5'-dimethoxy-7-oxolariciresinol (8), 3-hydroxy-4-methoxyacetophenone (9), 4-acetoxymethylphenol (10), (-)-paramicholide (11), and blumenol A (12). Among the compounds isolated, 2, 3 and 4 significantly attenuated the proliferation of the activated HSC-T6 cells. The maximal dose of these compounds, however, showed no cytotoxicity in primary cultured rat hepatocytes. Collagen deposition in the activated HSC-T6 cells was reduced by 2, 3 and 4. Also, the increased production of the pro-inflammatory cytokine tumor necrosis factor (TNF)-α induced by lipopolysaccharide was decreased by 3 and 4 in RAW264.7 macrophage cells. Collectively, (-)-syringaresinol (2), (+)-dihydrodehydrodiconiferyl alcohol (3), and salvinal (4) isolated from L. tulipifera leaves and twigs exhibited selective antifibrotic activities toward the activated HSCs and suppressed TNF-α production in RAW264.7 macrophages. These compounds may be useful candidates for developing therapeutic agents for the prevention and treatment of hepatic fibrosis.

Salicortin-derivatives from Salix pseudo-lasiogyne twigs inhibit adipogenesis in 3T3-L1 cells via modulation of C/EBPα and SREBP1c dependent pathway.

Obesity is reported to be associated with excessive growth of adipocyte mass tissue as a result of increases in the number and size of adipocytes differentiated from preadipocytes. To search for anti-adipogenic phytochemicals, we screened for inhibitory activities of various plant sources on adipocyte differentiation in 3T3-L1 preadipocytes. Among the sources, a methanolic extract of Salix pseudo-lasiogyne twigs (Salicaceae) reduced lipid accumulation in a concentration-dependent manner. During our search for anti-adipogenic constituents from S. pseudo-lasiogyne, five salicortin derivatives isolated from an EtOAc fraction of this plant and bearing 1-hydroxy-6-oxo-2-cyclohexene-carboxylate moieties, namely 2',6'-O-acetylsalicortin (1), 2'-O-acetylsalicortin (2), 3'-O-acetylsalicortin (3), 6'-O-acetylsalicortin (4), and salicortin (5), were found to significantly inhibit adipocyte differentiation in 3T3-L1 cells. In particular, 2',6'-O-acetylsalicortin (1) had the most potent inhibitory activity on adipocyte differentiation, with an IC50 value of 11.6 µM, and it significantly down-regulated the expressions of CCAAT/enhancer binding protein α (C/EBPα) and sterol regulatory element binding protein 1 (SREBP1c). Furthermore, 2',6'-O-acetylsalicortin (1) suppressed mRNA expression levels of C/EBPß during the early stage of adipocyte differentiation and stearoyl coenzyme A desaturase 1 (SCD-1), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS) expression, target genes of SREBP1c. In the present study, we demonstrate that the anti-adipogenesis mechanism of 2',6'-O-acetylsalicortin (1) may be mediated via down-regulation of C/EBPα and SREBP1c dependent pathways. Through their anti-adipogenic activity, salicortin derivatives may be potential novel therapeutic agents against obesity.

Plant-derived juvenile hormone III analogues and other sesquiterpenes from the stem bark of Cananga latifolia.

Juvenile hormone III (JH III) is a larval metamorphosis-regulating hormone present in most insect species. JH III was first isolated from the plant, Cyperus iria L., but the presence of JH III has not been reported in other plant species. In the present study, proof of the existence of JH III and its analogues from Cananga latifolia was established. From an aqueous MeOH extract of C. latifolia stem bark, six compounds were isolated along with nine known compounds. These were identified by using spectroscopic analyses as: (2E,6E,10R)-11-butoxy-10-hydroxy-3,7,11-trimethyldodeca-2,6-dienoic acid methyl ester, (2E,6E)-3,7,11-trimethyl-10-oxododeca-2,6-dienoic acid methyl ester, (2E)-3-methyl-5-[(1S,2R,6R)-1,2,6-trimethyl-3-oxocyclohexyl]-pent-2-enoic acid methyl ester, 1ß-hydroxy-3-oxo-4ß, 5α,7α-H-eudesmane 11-O-α-l-rhamnopyranoside, 4-epi-aubergenone 11-O-2',3'-di-O-acetyl-α-l-rhamnopyranoside and 4-epi-aubergenone 11-O-2',4'-di-O-acetyl-α-l-rhamnopyranoside. Three of the previously known compounds, (2E,6E,10R)-10-hydroxy-3,7,11-trimethyldodeca-2,6,11-trienoaic acid methyl ester, (2E,6E,10R)-10,11-dihydroxy-3,7,11-trimethyldodeca-2,6-dienoic acid and (2E,6S)-3-methyl-6-hydroxy-6-[(2R,5R)-5-(2-hydroxypropan-2-yl)-2-methyltetrahydrofuran-2-yl]-hex-2-enoaic acid methyl ester have now been found in a plant species. Ultra performance liquid chromatography-quadruple time-of-flight mass spectroscopy (UPLC-QTOF/MS) analysis of the chemical constituents of C. latifolia showed that several were predominant in the sub-fractions of a C. latifolia stem bark extract.