Protective activity of C-geranylflavonoid analogs from Paulownia tomentosa against DNA damage in 137Cs irradiated AHH-1 cells.

Radiotherapy is an important form of treatment for a wide range of cancers, but it can damage DNA and cause adverse effects. We investigated if the diplacone analogs of P. tomentosa were radio-protective in a human lymphoblastoid cell line (AHH-1). Four geranylated flavonoids, diplacone, 3'-O-methyl-5'-hydroxydiplacone, 3'-O-methyl-5'-O-methyldiplacone and 3'-O-methyldiplacol, were tested for their antioxidant and radio-protective effects. Diplacone analogs effectively scavenged free radicals and inhibited radiation-induced DNA strand breaks in vitro. They significantly decreased levels of reactive oxygen species and cellular DNA damage in 2 Gy-irradiated AHH-1 cells. Glutathione levels and superoxide dismutase activity in irradiated AHH-1 cells increased significantly after treatment with these analogs. The enhanced biological anti-oxidant activity and radioprotective activity of diplacone analogs maintained the survival of irradiated AHH-1 cells in a clonogenic assay. These data suggest that diplacone analogs may protect healthy tissue surrounding tumor cells during radiotherapy to ensure better control of radiotherapy and allow higher doses of radiotherapy to be employed.

Inhibitory effects of Asterina pectinifera extracts on melanin biosynthesis through tyrosinase activity.

The control of melanogenesis is an important strategy in the treatment of abnormal skin pigmentation for cosmetic purposes. The aim of the present study was to investigate the anti-melanogenic effect of Asterina pectinifera (A. pectinifera) extracts by cell-free mushroom tyrosinase assay, cellular tyrosinase assay, melanin content assay and the analysis of related protein expression in melan-a cells. A. pectinifera was extracted with 80% methanol (80-MAP) and further fractionated with hexane (He-AP) and ethyl acetate (EA-AP). In addition, the enzyme extract (En-AP) of A. pectinifera, to which protease was added, was processed. EA-AP and En-AP among A. pectinifera extracts showed strong inhibitory activity against the cell-free mushroom tyrosinase activity. EA-AP and En-AP induced significant inhibition of melanin production and cellular tyrosinase activity. In the action of EA-AP and En-AP on melanogenesis, they reduced the expression of melanogenic genes and proteins including tyrosinase, tyrosinase-related protein-1 (TRP-1) and dopachrome tautomerase (Dct). These results showed that EA-AP and En-AP inhibited melanogenesis by reducing tyrosinase activity and melanin production via subsequent downregulation of tyrosinase-related proteins. The overall results suggest that EA-AP and En-AP among A. pectinifera extracts may be promising candidates for the treatment of hyperpigmentation disorder and useful for self-tanning cosmetic products.

The Effects of Cynomorium songaricum on the Reproductive Activity in Male Golden Hamsters.

Cynomorium songaricum (CS) has been used in traditional Korean medicine in treating male impotence and sexual dysfunction. We investigated the effects of aqueous CS extract on the reproductive activity of golden hamsters whose spermatogenetic capacity is active in summer and inactive in winter. The animals were divided into 5 groups: long photoperiod (LP) control, short photoperiod (SP) control, and SP animals treated with low, middle, or high concentrations of CS. The animals were orally ingested with low (0.5 g/kg), middle (1.0 g/kg), or high (2.5 g/kg) concentrations of the aqueous extracts for 8 weeks on the daily basis. The control animals received the vehicle. As results, the LP control animals showed active testicular function but SP control animals displayed remarkably reduced testicular weights. The outcomes of the reproductive activity from low and middle concentrations of CS treatments were identical and marked as low dose. The consequences were a partial blocking of regressing activity by SP. On the other hand, the animals treated with high dose of CS extract showed remarkable significance in comparison to the SP control, indicative of a complete blocking effect of the CS on the regressing testes by SP. There were a dose-dependent effects of the CS on the sexual function. These results suggest that the CS extract promotes the male fertility by strengthening the spermatogenesis in the golden hamsters.

Resveratrol analogue HS-1793 induces the modulation of tumor-derived T cells.

Recent advances in the understanding of the mechanisms responsible for tumor progression suggest the possibility to control cancer growth, not only through chemotherapy-induced cancer cell destruction, but also by stimulating anticancer immunity. However, immune tolerance against tumor antigens disturbs diverse forms of immunotherapy. One of the most potent and well-studied tumor-induced immunosuppressive phenotypes found in the tumor microenvironment is the regulatory subpopulation cells (CD4(+)CD25(+)FoxP3(+) Treg cells). Among the great number of natural agents derived from plants and potentially useful for application in the complementary therapy of cancer, resveratrol is gaining attention for its immunomodulating properties in breast cancer, since the ineffectiveness of numerous immunotherapy strategies may be related, in part, to their negative effects on Treg cells. The present study was undertaken to examine whether HS-1793, a synthetic resveratrol analogue free from the restriction of the metabolic instability and high dose requirement of resveratrol, shows a direct effect on immune responses by enhancing lymphocyte proliferation or an immunomodulatory effect by inducing changes in the Treg cell population in FM3A breast tumor-bearing mice. Although HS-1793 had no direct immunostimulatory effect, it dose-dependently decreased IL-2 secretion and increased IL-4 secretion of concanavalin A-stimulated lymphocytes from tumor-bearing mice, which suggest that HS-1793 may induce changes in the subpopulations of tumor-derived T lymphocytes. The CD4(+)CD25(+) cell population from tumor-bearing mice decreased after HS-1793 treatment in a dose-dependent manner, while the CD4(+) T cell population remained unchanged. FoxP3(+)-expressing cells among the CD4(+)CD25(+) population showed a similar pattern. In contrast, the CD8(+) T cell population as well as the interferon (IFN)-γ-expressing CD8(+) T cell population and IFN-γ secretion of splenocytes from tumor-bearing mice were significantly upregulated by HS-1793 treatment. These results suggest that HS-1793 induces the modulation of tumor-derived T lymphocytes, particulary having a suppressive effect on the Treg cell population, likely contributing to enhanced tumor-specific cytotoxic T lymphocyte responses and CD4(+) T cells involving antitumor immunity. Therefore, HS-1793 may serve as a promising adjuvant therapeutic reagent in breast cancer immunotherapy.

Resveratrol analog, HS-1793 enhance anti-tumor immunity by reducing the CD4+CD25+ regulatory T cells in FM3A tumor bearing mice.

Natural agents with the immunomodulating property have been gaining traction to be employed in the complementary therapy of cancer because the ineffectiveness of numerous therapeutic strategies may be related in part to the tumor-induced immunosuppressive phenotypes, especially regulatory T (Treg) cells found in the tumor microenvironment. The present study was undertaken to examine whether HS-1793, synthetic resvertrol analog free from the restriction of metabolic instability and high dose requirement of resveratrol, induces an in vivo anti-tumor effect in FM3A tumor bearing mice through the suppression of Treg cells, which contribute to an increase in tumor specific cytotoxic T cell responses. Intraperitoneal injections of HS-1793 showed not only therapeutic benefits on established tumors, but also preventive anti-tumor effects. Treg cells (CD4+CD25+Foxp3+ cells) were significantly reduced in the total splenocytes as well as tumor tissues from HS-1793-administered mice, and the production of TGF-ß inducing Treg showed a similar pattern. On the contrary, the administration of HS-1793 increased IFN-γ-expressing CD8+ T cells, upregulated IFN-γ production, and enhanced the cytotoxicity of splenocytes against FM3A tumor cells both in therapeutic and preventive experimental animals. These results demonstrated the suppressive role of HS-1793 on the function of Treg cells contributing to tumor specific cytotoxic T lymphocyte responses in tumor-bearing mice, which explained the underlying mechanism of the anti-tumor immunity of HS-1793.

Effects of White Radish (Raphanus sativus) Enzyme Extract on Hepatotoxicity.

Raphanus sativus (Cruciferaceae), commonly known as radish is widely available throughout the world. From antiquity it has been used in folk medicine as a natural drug against many toxicants. The present study was designed to evaluate the hepatoprotective activity of radish (Raphanus sativus) enzyme extract (REE) in vitro and in vivo test. The IC50 values of REE in human liver derived HepG2 cells was over 5,000 µg/ml in tested maximum concentration. The effect of REE to protect tacrine-induced cytotoxicity in HepG2 cells was evaluated by MTT assay. REE showed their hepatoprotective activities on tacrineinduced cytotoxicity and the EC50 value was 1,250 µg/ml. Silymarin, an antihepatotoxic agent used as a positive control exhibited 59.7% hepatoprotective activitiy at 100 µg/ml. Moreover, we tested the effect of REE on carbon tetrachloride (CCl4)-induced liver toxicity in rats. REE at dose of 50 and 100 mg/kg and silymarin at dose of 50 mg/kg were orally administered to CCl4-treated rats. The results showed that REE and silymarin significantly reduced the elevated levels of serum enzyme markers induced by CCl4. The biochemical data were supported by evaluation with liver histopathology. These findings suggest that REE, can significantly diminish hepatic damage by toxic agent such as tacrine or CCl4.

Protective effect of fermented sea tangle against ethanol and carbon tetrachloride-induced hepatic damage in Sprague-Dawley rats.

Sea tangle has long been used as Korean folk remedy to promote material health, and is one of the popular dietary supplement. This study was designed to evaluate the protective effect of fermented sea tangle (FST) against ethanol and carbon tetrachloride (CCl(4))-induced hepatotoxicity in rats. Sprague-Dawley rats were orally treated with FST (25, 250, 2500 mg/kg/day) with administration of ethanol (5 mL/kg) for 13 weeks and the single intraperitoneal (i.p.) dose of 50% CCl(4) (5 mL/kg/day, CCl(4) in olive oil) at 12 week, and repeated i.p. dose of 20% CCl(4) (2 mL/kg/day) for 1 week. Hepatotoxicity was evaluated by measuring the serum levels of glutamic pyruvate transaminase (GPT), gamma glutamyl transpeptidase (gamma-GT) and malondialdehyde (MDA) as well as the tissue levels of antioxidant enzyme such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Ethanol and CCl(4)-induced the rat liver damage, and significantly increased (p<0.05) the GPT, gamma-GT and MDA levels, and decreased the SOD, CAT and GPx levels. However, treatment with FST could decrease serum GPT, gamma-GT, and MDA levels significantly in plasma, and increase the activities of SOD, CAT, and GPx in liver tissues compared with ethanol and CCl(4)-treated group.