Iridoid Glycosides and Coumarin Glycoside Derivatives from the Roots of Nymphoides peltata and Their In Vitro Wound Healing Properties.

Nymphoides peltata has been used as a medicinal herb in traditional medicines to treat strangury, polyuria, and swelling. The phytochemical investigation of the MeOH extract of N. peltata roots led to the isolation of three iridoid glycosides and three coumarin glycoside derivatives, which were characterized as menthiafolin (1), threoninosecologanin (2), callicoside C (3), and scopolin (4), as well as two undescribed peltatamarins A (5) and B (6). The chemical structures of the undescribed compounds were determined by analyzing their 1 dimensional (D) and 2D nuclear magnetic resonance (NMR) spectra and using high-resolution (HR)-electrospray ionization mass spectroscopy (ESI-MS), along with the chemical reaction of acid hydrolysis. The wound healing activities of the isolated compounds 1-6 were evaluated using a HaCaT cell scratch test. Among the isolates, scopolin (4) and peltatamarin A (5) promoted HaCaT cell migration over scratch wounds, and compound 5 was the most effective. Furthermore, compound 5 significantly promoted cell migration without adversely affecting cell proliferation, even when treated at a high dose (100 µM). Our results demonstrate that peltatamarin A (5), isolated from N. peltata roots, has the potential for wound healing effects.

3‴-O-Foliamenthoyl-Rutin, a New Flavonoid Glycoside from the Roots of Nymphoides peltata.

Nymphoides peltata (Menyanthaceae) has been used as a medicinal herb in traditional medicines to treat conditions such as strangury, polyuria, swelling, and as a diuretic and antipyretic. In our ongoing research to discover novel structural and/or biological natural products in natural resources, five flavonoids, quercetin (1), quercitrin (2), isoquercetin (3), quercetin-3-O-vicianoside (4), and rutin (5), as well as a new flavonoid glycoside, 3‴-O-foliamenthoyl-rutin (6), were isolated from the MeOH extract of N. peltata roots. The chemical structure of the new compound (6) was determined by analyzing 1D and 2D NMR spectra and high-resolution (HR) electrospray ionization mass spectroscopy (ESIMS), along with a chemical reaction. The wound-healing activities of the isolated compounds (1-6) were evaluated using a HaCaT cell scratch test. Among the isolates, isoquercetin (3), quercetin-3-O-vicianoside (4), and 3‴-O-foliamenthoyl-rutin (6) promoted HaCaT cell migration over scratch wounds, with compound 4 being the most effective. Our findings provide experimental data supporting the potential of quercetin-3-O-vicianoside (4) as a wound-healing agent.

Plant Growth Hormones and Micro-Tuberization in Breaking the Seed Dormancy of Bunium persicum (Boiss.) Fedts.

Bunium persicum is a valuable medicinal plant with limited production but high market demand. It thrives predominantly in high-altitude regions. The main challenges hindering its widespread cultivation are seed dormancy and a lengthy seed-to-seed cycle, making its large-scale cultivation difficult. Six genotypes of Bunium persicum were collected from different altitudes to evaluate its germination behavior and seed dormancy. The study was conducted during 2020-23 and comprised three experiments (viz., seed germination under an open field, controlled conditions, and micro-tuberization). Under open field conditions, germination percent was genotype dependent, and the highest germination percentage, root length, and shoot length were recorded in Shalimar Kalazeera-1. Germination behavior assessment of the Bunium persicum revealed that treatment T9 (GA3 (25 ppm) + TDZ (9 µM/L)) is effective in breaking the dormancy of Bunium persicum as well as in obtaining a higher germination percent for early development of the tubers. Similarly, with regard to the effect of temperature and moisture conditions, stratification under moist chilling conditions showed effectiveness in breaking seed dormancy as the germination percentage in stratified seeds was at par with the most efficient growth hormone. With regard to the in vitro micro-propagation, direct regeneration showed multiple shoot primordia at the base of the tubers without intervening callus phase from the MS medium supplemented with BA (22.2 µM) and NAA (13.95 µM) 4 weeks after sub-culturing. Similarly, medium supplemented with JA (8.0 mg/L) and BA (22.2 µM) produced well-organized somatic embryos with shiny surfaces, which appeared at the swelled basal portion of apical stems. Further, the combination of JA (6.0 mg/L) and BA (22.2 M) was effective in developing the micro-tubers and also enhanced the weight and length of Bunium persicum micro-tubers.

Antioxidant, Antiviral, and Anti-Inflammatory Activities of Lutein-Enriched Extract of Tetraselmis Species.

Microalgae are proposed to have powerful applications for human health in the pharmaceutical and food industries. Tetraselmis species (sp.), which are green microalgae, were identified as a source of broad-spectrum health-promoting biological activities. However, the bioactivity of these species has not been elucidated. We aimed to confirm the antioxidant, antiviral, and anti-inflammatory effects of Tetraselmis sp. extract (TEE). TEE showed 2,2-diphenyl-1-picryl-hydrazyl-hydrate radical and hydrogen peroxide scavenging activities and reduced plaque formation in Vero E6 cells infected with vaccinia virus. TEE treatment also significantly inhibited nitric oxide (NO) production and improved cell viability in lipopolysaccharide (LPS)-induced RAW264.7 cells. These anti-inflammatory effects were further analyzed in LPS-induced RAW 264.7 cells and the zebrafish model. Further, TEE reduced induced NO synthase expression and proinflammatory cytokine release, including tumor necrosis factor-α, interleukin-6, and interleukin-1ß, through MAPKs and NF-κB-dependent mechanisms. Further analysis revealed that TEE increased the survival rate and reduced cell death and NO production in an LPS-stimulated zebrafish model. Further, high-performance liquid chromatography revealed a strong presence of the carotenoid lutein in TEE. Overall, the results suggest that lutein-enriched TEE may be a potent antioxidant, antiviral, and anti-inflammatory agent that could be sustainably utilized in industrial applications.

Stimulatory effects of wavelength-dependent photobiomodulation on proliferation and angiogenesis of colorectal cancer.

In recent decades, the laser treatment of cancer has been introduced as a promising treatment option. Because of the maldistribution of optical energy and an ambiguous boundary between the normal and tumor tissues, laser irradiation can stimulate residual cancer cells, leading to a cancer regrowth. As photobiomodulation (PBM) is involved in an extensive range of cellular responses, profound comprehension of photo-stimulated mechanisms against the cancer cells is required to establish a safety margin for PBM. Therefore, we aimed to identify the stimulant effects of PBM at various wavelengths against the tumor cells to establish a safety margin for the laser treatment. CT26 murine colon cancer cells were exposed to either 405 (BL), 635 (VIS), or 808 (NIR) nm laser lights at the fluences of 0, 10, 30, and 50 J/cm2. In addition, CT26 tumor-bearing mice were irradiated with BL, VIS, or NIR at a fluence of 30 J/cm2. Both the proliferation and angiogenesis potential of the CT26 cells and tumors were evaluated using the MTT assay, western blot, and immunohistochemistry (IHC) staining analyses. Although cell viability was not statistically significant, BL significantly induced p-ERK upregulation in the CT26 cells, indicating that PBM with BL can stimulate proliferation. In vivo tests showed that the NIR group exhibited the maximum relative tumor volume, and BL yielded a slight increase compared to the control. In the IHC staining and western blot analyses, both BL and NIR increased the expression of EGFR, VEGF, MMP-9, and HIF-1α, which are related to the proliferation and angiogenesis-related factors. Further investigations will be pursued to clarify the molecular pathways that depend on the cancer cell types and laser wavelengths for the establishment of safety guidelines in clinical environments.

Ameliorative Effects of Pueraria lobata Extract on Postmenopausal Symptoms through Promoting Estrogenic Activity and Bone Markers in Ovariectomized Rats.

Pueraria lobata (Willd.) Ohwi, known as kudzu, is one of the most popular traditional medicines in Asian countries. It has been widely used as a natural alternative to hormone replacement therapy for treating postmenopausal symptoms. This study aimed to investigate the estrogenic effect of P. lobata extract (PE) against postmenopausal osteoporosis in ovariectomized (OVX) rats. OVX rats were treated with PE (25-1600 mg/kg) for 8 weeks. Biochemical parameters, estradiol, and bone turnover markers (e.g., osteocalcin, C-terminal telopeptide fragment of type I collagen, deoxypyridinoline, and pyridinoline) were measured in plasma samples. In addition, estrogen receptor-alpha (ER-α) protein expression and morphology of uterine were evaluated. Long-term treatment with PE did not cause liver damage in OVX rats. PE supplementation reduced body weight gain in obese rats with high lipid accumulation induced by ovariectomy. Furthermore, PE exhibited a protective effect against insulin resistance, hyperlipidemia, and hepatic lipid peroxidation. PE treatment increased uterine weight and thickness of the uterine layers in cases of uterus atrophy due to removal of ovaries. The levels of bone turnover markers, which were significantly increased in OVX rats, were decreased by PE treatment. Western blotting analysis showed that ER-α protein expression was upregulated in PE-treated rats compared with OVX rats. These results suggest that PE could be a promising alternative functional food for improving menopausal symptoms.

Oral administration of taheebo (Tabebuia avellanedae Lorentz ex Griseb.) water extract prevents DSS-induced colitis in mice by up-regulating type II T helper immune responses.

BACKGROUND: Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders that are mediated by pathogenic Th1 and Th17 cells. Previous studies have demonstrated that taheebo water extract (TWE) derived from Tabebuia avellanedae Lorentz ex Griseb., as folk remedy, has been used to treat various inflammatory diseases. Although TWE has been previously shown to display anti-inflammatory activities, the in vivo effects of TWE on mucosal immune responses remain unclear. METHODS: We examined the anti-inflammatory effects of TWE on innate immune cells such as dendritic cells (DCs) and macrophages and also on the differentiation of T helper cells. Lastly, adopting a method for dextran sulfate sodium (DSS)-induced colitis, we investigated whether the oral administration of TWE can modulate mucosal inflammatory responses. RESULTS: We found that TWE could activate DCs to produce immunosuppressive IL10 and polarize macrophages toward an anti-inflammatory phenotype in the mesenteric lymph node (MLN). Such alterations in DCs and macrophages resulted in a significant increase in anti-inflammatory Th2 and Foxp3+ Treg cells and a dramatic decrease in pro-inflammatory Th1 and Th17 cells in the MLN. Upon induction of colitis with DSS treatment, TWE significantly reduced the clinical symptoms, including body weight loss and colonic tissue inflammation, by up-regulating type II T helper immune responses. CONCLUSIONS: Taken together, these data suggest that TWE is an excellent natural product with therapeutic effects to help improve inflammatory disorders such as colitis.

Highly efficient extraction of anthocyanins from grape skin using deep eutectic solvents as green and tunable media.

Deep eutectic solvents (DESs) were investigated as tunable, environmentally benign, yet superior extraction media to enhance the extraction of anthocyanins from grape skin, which is usually discarded as waste. Ten DESs containing choline chloride as hydrogen bond acceptor combined with different hydrogen bond donors were screened for high extraction efficiencies based on the anthocyanin extraction yields. As a result, citric acid, D-(+)-maltose, and fructose were selected as the effective DES components, and the newly designed DES, CM-6 that is composed of citric acid and D-(+)-maltose at 4:1 molar ratio, exhibited significantly higher levels of anthocyanin extraction yields than conventional extraction solvents such as 80% aqueous methanol. The final extraction method was established based on the ultrasound-assisted extraction under conditions optimized using response surface methodology. Its extraction yields were double or even higher than those of conventional methods that are time-consuming and use volatile organic solvents. Our method is truly a green method for anthocyanin extraction with great extraction efficiency using a minimal amount of time and solvent. Moreover, this study suggested that grape skin, the by-products of grape juice processing, could serve as a valuable source for safe, natural colorants or antioxidants by use of the eco-friendly extraction solvent, CM-6.

Ginseng treatment attenuates autophagic cell death in chronic cyclosporine nephropathy.

AIMS: Chronic cyclosporine (CsA) treatment induces autophagic cell death characterized by excessive autophagosome formation and decreased autophagic clearance. In this study, we evaluated the influence of ginseng treatment on autophagy in chronic CsA nephropathy. METHODS: Mice were treated with CsA (30 mg/kg) with or without Korean red ginseng (KRG) extract (0.2, 0.4 g/kg) for 4 weeks. The effect of KRG on CsA-induced autophagosome formation was measured using phospholipid-conjugated form of LC3-II, beclin-1, and autophagic vacuoles were visualized with electron microscopy. Autophagic clearance was evaluated by accumulation of p62/sequestosome 1 (p62) and ubiquitin, then double immunolabeling for p62 and either LC3-II or ubiquitin. To demonstrate the association between the effects of KRG treatment on autophagy and apoptosis, double immunolabelling for LC3-II and active caspase-3 was performed. Multiple autophagy pathways were also examined. RESULTS: KRG co-treatment significantly decreased the expression of LC3-II, beclin-1, and the number of autophagic vacuoles compared with the CsA group, and these changes were accompanied by improvements in renal dysfunction and fibrosis. CsA-induced accumulation of p62 and ubiquitin was also decreased by KRG treatment, and these proteins were colocalized with LC3-II and with each other. KRG treatment simultaneously reduced the expression of both active caspase-3 and LC3-II in the injured area. KRG treatment during chronic CsA nephropathy induced the expression of AKT/mTOR, which is a pathway that inhibits autophagy, and reduced AMPK expression. CONCLUSION: Ginseng treatment attenuated CsA-induced excessive autophagosome formation and autophagic aggregates. These findings suggest that ginseng has a renoprotective effect against CsA-induced autophagic cell death.

Oral administration of ginseng ameliorates cyclosporine-induced pancreatic injury in an experimental mouse model.

BACKGROUND: This study was performed to investigate whether ginseng has a protective effect in an experimental mouse model of cyclosporine-induced pancreatic injury. METHODS: Mice were treated with cyclosporine (30 mg/kg/day, subcutaneously) and Korean red ginseng extract (0.2 or 0.4 g/kg/day, oral gavage) for 4 weeks while on a 0.01% salt diet. The effect of ginseng on cyclosporine-induced pancreatic islet dysfunction was investigated by an intraperitoneal glucose tolerance test and measurements of serum insulin level, ß cell area, macrophage infiltration, and apoptosis. Using an in vitro model, we further examined the effect of ginseng on a cyclosporine-treated insulin-secreting cell line. Oxidative stress was measured by the concentration of 8-hydroxy-2'-deoxyguanosine in serum, tissue sections, and culture media. RESULTS: Four weeks of cyclosporine treatment increased blood glucose levels and decreased insulin levels, but cotreatment with ginseng ameliorated the cyclosporine-induced glucose intolerance and hyperglycemia. Pancreatic ß cell area was also greater with ginseng cotreatment compared with cyclosporine monotherapy. The production of proinflammatory molecules, such as induced nitric oxide synthase and cytokines, and the level of apoptotic cell death also decreased in pancreatic ß cell with ginseng treatment. Consistent with the in vivo results, the in vitro study showed that the addition of ginseng protected against cyclosporine-induced cytotoxicity, inflammation, and apoptotic cell death. These in vivo and in vitro changes were accompanied by decreases in the levels of 8-hydroxy-2'-deoxyguanosine in pancreatic ß cell in tissue section, serum, and culture media during cotreatment of ginseng with cyclosporine. CONCLUSIONS: The results of our in vivo and in vitro studies demonstrate that ginseng has a protective effect against cyclosporine-induced pancreatic ß cell injury via reducing oxidative stress.

Ginseng treatment attenuates chronic cyclosporine nephropathy via reducing oxidative stress in an experimental mouse model.

BACKGROUND: This study was performed to investigate whether ginseng extract has a protective effect in an experimental mouse model of chronic cyclosporine (CsA) nephropathy. METHODS: Mice were treated with CsA (30 mg/kg/day, subcutaneously) with or without Korean red ginseng extract (KRG) (0.2, 0.4 g/kg/day, orally) on a 0.01% salt diet for 4 weeks. The effect of KRG on CsA-induced renal injury was evaluated by assessing renal function and pathology, mediators of inflammation, tubulointerstitial fibrosis and apoptotic cell death. Using an in vitro model, we also examined the effect of KRG on CsA-treated proximal tubular cells (HK-2). Oxidative stress was measured by assessing 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in 24-hour urine, tissue sections, and culture media. RESULTS: Four weeks of CsA treatment caused renal dysfunction, typical pathologic lesions and apoptotic cell death. KRG treatment reduced serum creatinine and blood urea nitrogen and histopathology and increased creatinine clearance. Proinflammatory and profibrotic molecules such as induced nitric oxide synthase, cytokines, transforming growth factor (TGF)-ß1 and TGF-ß1-inducible gene h3 and apoptotic cell death, also decreased with KRG treatment. Consistent with these results, in vitro studies showed that addition of KRG protected against CsA-induced morphological changes, cytotoxicity, inflammation, and apoptotic cell death as demonstrated by annexin V binding. These changes were accompanied by decrease in the level of 8-OHdG in urine and culture supernatant after KRG treatment. CONCLUSION: The results of our in vivo and in vitro studies demonstrate that KRG has a protective effect in CsA-induced renal injury via reducing oxidative stress.

The antidiabetic effects of an herbal formula composed of Alnus hirsuta, Rosa davurica, Acanthopanax senticosus and Panax schinseng in the streptozotocin-induced diabetic rats.

A folk prescription consisting of Alnus hirsuta, Rosa davurica, Acanthopanax senticosus and Panax schinseng has been used in the treatment of diabetes mellitus. The aim of the present investigation was to evaluate the antidiabetic effects of the herb formula extract (HFE) composed of Alnus hirsuta, Rosa davurica, Acanthopanax senticosus and Panax schinseng in the streptozotocin (STZ)-induced diabetic rats. The HFE was mixed in the food supply of the healthy and STZ-induced diabetic male Sprague-Dawley rats, and its effects on the body weight, water and food intake, hyperglycemia, hypolipidemic and islet structure were studied. The treatment of the rats with STZ for 6 weeks resulted in marasmus, polydipsia, polyphagia, hyperglycemia and hypoinsulinemia. In addition, the diabetic rats showed an apparent decrease in the insulin immunoreactivity and the number of ß-cells in the pancreas. The addition of the HFE to the rats' food supply significantly lowered the serum glucose and the serum triglycerides level and preserved the normal histological appearance of the pancreatic islets. These results indicate that the HEF have a strong antidiabetic potential along with the significant hypoglycemic and hypolipidemic effects, which may be applicable in the pharmaceutical industry.

Involvement of the p38 MAPK and ERK signaling pathway in the anti-melanogenic effect of methyl 3,5-dicaffeoyl quinate in B16F10 mouse melanoma cells.

Methyl 3,5-dicaffeoyl quinate (MDQ), an active compound present in Kalopanax pictus, Salicornia herbacea L., Aster oharai and Solidago virga-aurea var. gigantean, is a dicaffeoylquinic acid derivative esterified by methanol. Recent studies have revealed that MDQ possesses multiple pharmacological activities, such as antitumor, antioxidative and cytoprotective activities. To date, there has been no attempt to test the action of MDQ in melanocytes. In this study, we investigated the effect of MDQ on melanogenesis in B16F10 mouse melanoma cells. MDQ inhibited melanin production and tyrosinase activity in B16F10 mouse melanoma cells without a direct inhibitory effect on mushroom tyrosinase activity. Furthermore, we also found that MDQ decreased protein expression levels of microphthalmia-associated transcription factor (MITF) and tyrosinase in B16F10 melanin cells. Meanwhile, phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) was significantly reduced after 6h MDQ treatment, and this expression recovered at 48 h. The phosphorylation of extracellular signal-regulated kinase (ERK) was significantly enhanced at 12-48 h, whereas no effect was observed in the phosphorylation of Akt. In addition, MDQ treatment did not significantly alter the expression levels of total p38 MAPK, ERK, and Akt. Thus, it seems that inhibition of phospho-p38 MAPK and activation of phospho-ERK may lead to the suppression of melanogenesis in MDQ-treated B16F10 mouse melanoma cells.

Effects of laser irradiation on machined and anodized titanium disks.

PURPOSE: Although the laser has become one of the most commonly used tools for implant dentistry, research is lacking on whether or not the laser causes any changes on the surface of titanium (Ti) implants. The present study analyzed the morphology, composition, crystal structure, and surface roughness changes of machined and anodized Ti surfaces, irradiated with erbium chromium-doped yttrium-scandium-gallium-garnet (Er,Cr:YSGG), erbium-doped yttrium-aluminum-garnet (Er:YAG), and carbon dioxide (CO2) lasers. MATERIALS AND METHODS: Seventy-two Ti disks were fabricated by machining commercially pure Ti (grade 3); 36 of them were anodized at 300 V. The disks were irradiated with Er,Cr:YSGG, Er:YAG, and CO2 lasers at five different powers (1, 2, 3, 4, and 5 W). The irradiated disks were examined with scanning electron microscopy, electron probe microanalysis, x-ray diffractometry, and optical interferometry. RESULTS: Surface changes were observed on both types of Ti surfaces irradiated with the Er,Cr:YSGG laser when more than 3 W of power were applied. Surface changes were observed on both types of Ti surfaces when irradiated with the Er:YAG laser with more than 2 W of power. No change was observed when the disks were irradiated with the CO2 laser. The proportion of oxide in the machined Ti disk increased after the application of the Er,Cr:YSGG or Er:YAG laser. In the anodized Ti disk, the anatase peak intensity decreased and the rutile peak intensity increased after laser irradiation. The irradiated Ti disks were significantly rougher than the nonirradiated Ti disks. CONCLUSIONS: The Er:YAG and Er,Cr:YSGG laser resulted in surface changes on the Ti disks according to the power output. The CO2 laser did not affect the surface of the Ti disks, irrespective of the power output.

Induction of cell cycle arrest and apoptosis by the ethyl acetate fraction of Kalopanax pictus leaves in human colon cancer cells.

Kalopanax pictus is a deciduous tree used in traditional medicine; its leaves are also consumed as a vegetable. In this study, the ethyl acetate fraction of K. pictus leaves (EFK) was tested in vitro for anticancer activity against four cell lines: human colon cancer (HT-29) cells, human stomach cancer (NCI-N87) cells, human breast cancer (MDA-MB231) cells, and mouse melanoma (B16F1) cells. Results indicated that EFK showed the most potent tumor selective growth inhibitory activity against HT-29 cells with less cytotoxic effect on normal cell lines. Cytotoxicity of EFK on HT-29 cells was associated mainly with cell chromatin condensation, DNA fragmentation, and loss of membrane phospholipid asymmetry with appearance of G2/M phase arrest. Cell death induced by EFK displayed features characteristic of apoptosis, and was associated with generation of reactive oxygen species (ROS) and increase of Bax/Bcl-2 ratio. These findings suggest that K. pictus leaves have anticancer properties and may be valuable for application in pharmaceutical industry.

Antioxidant and hepatoprotective activities of Cirsium setidens Nakai against CCl4-induced liver damage.

The antioxidant activity and hepatoprotective potential of Cirsium setidens Nakai, a widely used medicinal plant, were investigated. The n-butanol (n-BuOH) fraction of leaves and roots of C. setidens had a higher 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity than the other soluble fractions. The n-BuOH fraction of roots of C. setidens had a significant hepatoprotective activity at a dose of 500 mg/kg compared to that of a standard agent. The biochemical results were confirmed by histological observations indicating that C. setidens extract decreased ballooning degeneration in response to CCl(4) treatment. The n-BuOH fraction reduced CCl(4)-induced liver injury in rats, and transcript levels of genes encoding antioxidant enzymes such as glutathione peroxidase 1 (GPO1), glutathione peroxidase 3 (GPO3) and superoxide dismutase (SOD1) were elevated in the livers of rats treated with this fraction (500 mg/kg). Based on these results, we suggest that the C. setidens extract has hepatoprotective effect related to its antioxidant activity.

Antidiabetic properties of 2,5-dihydroxy-4,3'-di(beta-D-glucopyranosyloxy)-trans-stilbene from mulberry (Morus bombycis koidzumi) root in streptozotocin-induced diabetic rats.

We investigated the antidiabetic properties of 2,5-dihydroxy-4,3-di(beta-D-glucopyranosyloxy)-trans-stilbene (DGTS) isolated from Morus bombycis Koidzumi in streptozotocin (STZ)-induced diabetic rats. The DGTS prevented the increase in aspartate aminotransferase, alanine aminotransferase, and blood urea nitrogen levels in serum of diabetic rats. At doses of 200-800 mg/kg, DGTS improved hyperglycemia in the rats, and the hypoglycemic effect of DGTS was comparable to that of tolbutamide. The histological observations showed that DGTS prevented atrophy of pancreatic beta-cells and vascular degenerative changes in the islets. DGTS reversed STZ-induced diabetes and had antioxidant activity in assays of FeCl(2)/ascorbic acid-induced lipid peroxidation in the rats. Levels of cytochrome P450 2E1 mRNA, as measured by reverse transcription-polymerase chain reaction, were lower in the livers of the DGTS-treated rats than those of the control group. These results suggest that DGTS might be beneficial in the treatment of type 1 diabetes.

Identification and properties of 2,5-dihydroxy-4,3'-di(beta-D-glucopyranosyloxy)-trans-stilbene from Morus bombycis Koidzumi roots.

2,5-Dihydroxy-4,3'-di(beta-d-glucopyranosyloxy)-trans-stilbene was identified from Morus bombycis Koidzumi roots. The 2,5-dihydroxy-4,3'-di(beta-D-glucopyranosyloxy)-trans-stilbene at a dose of 400-600 mg/kg had hepatoprotective activity comparable to the standard agent, silymarin. The biochemical assays were confirmed by histological observations showing that the 2,5-dihydroxy-4,3'-di(beta-d-glucopyranosyloxy)-trans-stilbene from Morus bombycis Koidzumi roots decreased cell ballooning in response to CCl4 treatment. These results demonstrate that the 2,5-dihydroxy-4,3'-di(beta-d-glucopyranosyloxy)-trans-stilbene component has a liver protective action against CCl4-induced hepatotoxicity.

Antioxidant effects and hepatoprotective activity of 2,5-dihydroxy-4,3'-di(beta-d-glucopyranosyloxy)-trans-stilbene from Morus bombycis Koidzumi roots on CCl4-induced liver damage.

We investigated hepatoprotective activity and antioxidant effect of the 2,5-dihydroxy-4,3'-di(beta-D-glucopyranosyloxy)-trans-stilbene that purified from Morus bombycis Koidzumi roots against CCl4-induced liver damage in rats. The 2,5-dihydroxy-4,3'-di(beta-D-glucopyranosyloxy)-trans-stilbene displayed dose-dependent superoxide radical scavenging activity (IC50 = 430.2 microg/ml), as assayed by the electron spin resonance (ESR) spin-trapping technique. The increase in aspartate aminotransferase (AST) activities in serum associated with carbon tetrachloride (CCl4)-induced liver injury was inhibited by 2,5-dihydroxy-4,3'-di(beta-D-glucopyranosyloxy)-trans-stilbene and at a dose of 400 - 600 mg/kg samples had hepatoprotective activity comparable to the standard agent, silymarin. The biochemical assays were confirmed by histological observations showing that the 2,5-dihydroxy-4,3'-di(beta-d-glucopyranosyloxy)-trans-stilbene decreased cell ballooning in response to CCl4 treatment. These results demonstrate that the 2,5-dihydroxy-4,3'-di(beta-D-glucopyranosyloxy)-trans-stilbene is a potent antioxidant with a liver protective action against CCl4-induced hepatotoxicity.

STAT3 and NF-kappaB signal pathway is required for IL-23-mediated IL-17 production in spontaneous arthritis animal model IL-1 receptor antagonist-deficient mice.

IL-23 is a heterodimeric cytokine composed of a p19 subunit and the p40 subunit of IL-12. IL-23 has proinflammatory activity, inducing IL-17 secretion from activated CD4(+) T cells and stimulating the proliferation of memory CD4(+) T cells. We investigated the pathogenic role of IL-23 in CD4(+) T cells in mice lacking the IL-1R antagonist (IL-1Ra(-/-)), an animal model of spontaneous arthritis. IL-23 was strongly expressed in the inflamed joints of IL-1Ra(-/-) mice. Recombinant adenovirus expressing mouse IL-23 (rAd/mIL-23) significantly accelerated this joint inflammation and joint destruction. IL-1beta further increased the production of IL-23, which induced IL-17 production and OX40 expression in splenic CD4(+) T cells of IL-1Ra(-/-) mice. Blocking IL-23 with anti-p19 Ab abolished the IL-17 production induced by IL-1 in splenocyte cultures. The process of IL-23-induced IL-17 production in CD4(+) T cells was mediated via the activation of Jak2, PI3K/Akt, STAT3, and NF-kappaB, whereas p38 MAPK and AP-1 did not participate in the process. Our data suggest that IL-23 is a link between IL-1 and IL-17. IL-23 seems to be a central proinflammatory cytokine in the pathogenesis of this IL-1Ra(-/-) model of spontaneous arthritis. Its intracellular signaling pathway could be useful therapeutic targets in the treatment of autoimmune arthritis.