Efficacy and Safety of Fig (Ficus carica L.) Leaf Tea in Adults with Mild Atopic Dermatitis: A Double-Blind, Randomized, Placebo-Controlled Preliminary Trial.

Atopic dermatitis (AD) is a chronic, recurrent pruritic skin disease with repeated remissions and exacerbations. Various factors, such as allergies, skin conditions and lifestyle, combine to cause AD, making it difficult to cure completely. Although AD symptoms are suppressed with medications, this is a long-term effort and burden on patients. Thus, safer drugs and alternatives are needed. We previously found that consumption of tea prepared from fig (Ficus carica L.) leaves alleviated allergy and AD symptoms in cultured cells and animals. Therefore, here, we conducted a double-blind, randomized, controlled study in patients with mild AD to evaluate the safety and AD-relieving effects of prolonged consumption of fig leaf tea. Positive effects of fig leaf tea consumption were confirmed in 14 of 15 participants. Eczema Area and Severity Index values were significantly lowered in the fig leaf tea-treated group than in the placebo-treated group. The effect weakened 4 weeks after the end of the intervention, suggesting that continued intake of fig leaf tea was effective. Further assessments confirmed the safety of fig leaf tea consumption and revealed no variations that might pose a health hazard. Therefore, we postulate that fig leaf tea is a natural and safe therapeutic option for AD.

Immunostimulating effects of the polyphenol-rich fraction of sugar cane (Saccharum officinarum L.) extract in chickens.

The phagocytic activity of peripheral blood leukocytes (PBL) in chickens orally administered sugar cane extracts (SCE) or polyphenol-rich fraction (PRF) of SCE (500 mg/kg/day) for 3 consecutive days increased significantly, when compared with that of saline-administered control chickens. Chickens orally administered SCE or PRF (500 mg/kg/day) for 3 consecutive days showed significantly higher antibody responses against sheep red blood cells and Brucella abortus than control chickens. In addition, oral administration of SCE or PRF also resulted in a significant increase in the number of IgM- and IgG-plaque forming cell responses of PBL, intestinal leukocytes and splenocytes, when compared with those of control chickens. Furthermore, delayed type hypersensitivity responses to human gamma globulin significantly increased in chickens orally administered SCE or PRF, compared with those of control chickens when evaluated on the basis of net increased wattle thickness at 24, 48 and 72 h after challenge. These results suggest that PRF of SCE has an immunostimulating effect in chickens.

Reduced lipopolysaccharide (LPS)-induced nitric oxide production in peritoneal macrophages and inhibited LPS-induced lethal shock in mice by a sugar cane (Saccharum officinarum L.) extract.

A sugar cane extract (SCE) has been found to have an immunostimulating effect in several animals. Lipopolysaccharide (LPS) is known to induce endotoxin shock via the production of inflammatory modulators such as tumor necrosis factor (TNF)-alpha and nitric oxide (NO). We examined in the present study the effects of SCE on the TNF-alpha and NO production in LPS-stimulated mice peritoneal cells and the endotoxin shock in mice. The supplementation of SCE to peritoneal macrophages cultured with LPS resulted in a significant decrease in NO production. All the mice injected intraperitoneally with LPS and D-galactosamine (LPS+GalN) died within 24 h. However, a peritoneal injection, but no intravenous or oral administration, of SCE (500-1,000 mg/kg) at 3 to 48 h before the LPS+GalN-challenge resulted in a significantly improved survival rate. These results suggest that SCE had a protective effect on LPS-induced endotoxin shock via one of possible mechanisms involving the suppression of NO production in the mouse peritoneal cavity.

Cytotoxicity and antigenicity of antimicrobial synthesized peptides derived from the beetle Allomyrina dichotoma defensin in mice.

Synthetic peptides, peptides A (Arg-Leu-Tyr-Leu-Arg-Ile-Gly-Arg-Arg-NH(2)) and B (Arg-Leu-Arg-Leu-Arg-Ile-Gly-Arg-Arg-NH(2)), derived from the beetle Allomyrina dichotoma defensin, have antimicrobial activities. Immunotoxicological effect of these peptides was evaluated by cytotoxicity of mouse peritoneal macrophages. In addition, antigenicity of these peptides was studied by evaluating antibody responses in mice immunized with these peptides. The toxicity of peptide A toward mouse peritoneal cells was less than that of polymyxin B, when morphologically evaluated in a cytotoxicity test. Almost all of mice injected intraperitoneally (i.p.) with either peptide A or B at 50-150 mg/kg survived, whereas all mice injected i.p. with polymyxin B at the doses of more than 25 mg/kg died within 24 h. Interestingly, almost all of mice injected intravenously with these peptides at the doses of 10 and 25 mg/kg also survived. Furthermore, mice immunized with these peptides conjugated with keyhole limpet hemocyanin (KLH) showed little or negligible anti-peptide A or B antibody production, although anti-KLH antibody was significantly produced. The results indicated that peptides A and B were less cytotoxic than polymyxin B and also had poor antigenicity to produce specific antibody in mice.

Protective effects of sugar cane extract on endotoxic shock in mice.

Sugar cane extract (SCE) has been shown to have an immunostimulating effect in chickens. This study evaluated the effect of SCE on Salmonella Abortusequi lipopolysaccharide (LPS)-induced lethal shock in d-galactosamine (GalN)-sensitized mice. Mice were administered intraperitoneally SCE (500 mg/kg) or phosphate buffered saline before or after injection of LPS and GalN. All the mice injected with LPS and GalN (control group) died of histopathologically congestive and hemorrhagic hepatic insufficiency within 24 h, showing significantly increased activities of plasma aspartate aminotransferase (AST; 380 IU/mL) and alanine aminotransferase (ALT; 130 IU/mL). Pretreatment of mice with SCE at 3 h before challenge with LPS and GalN (SCE treated group) resulted in significantly improved survival rates (92.3%) and a decrease in liver injury. These surviving mice in the SCE treated group showed no changes in the mean levels of plasma AST (60 IU/mL) and ALT (18 IU/mL). However, the level of tumor necrosis factor-alpha in the SCE treated group was not significantly different when compared with that in the control group challenged with LPS and GalN. These results suggest that SCE has protective effects on LPS-induced mortality in this mouse model.

Protective effects of antimicrobial peptides derived from the beetle Allomyrina dichotoma defensin on endotoxic shock in mice.

Synthetic peptides, Arg-Leu-Tyr-Leu-Arg-Ile-Gly-Arg-Arg-NH2 (peptide A) and Arg-Leu-Arg-Leu-Arg-Ile-Gly-Arg-Arg-NH2 (peptide B), derived from the beetle Allomyrina dichotoma defensin, have not only antimicrobial activities but also anti-inflammatory effects by inhibiting tumour necrosis factor-alpha(TNF-alpha) production. In the present study, we evaluated the lipopolysaccharide (LPS)-binding activities and the protective effects of these peptides on LPS-induced lethal shock in d-galactosamine (GalN)-sensitized mice. These peptides were shown to bind to erythrocytes coated with LPS and the binding activity of peptide A to LPS was significantly higher than those of peptide B and polymyxin B. Mice were injected intraperitoneally with peptide A or B at doses of 25, 50, 100 and 150 mg/kg before an injection of Salmonella abortusequi LPS (5 microg/kg) and GalN (1 g/kg) (LPS+GalN). All of wild-type mice died within 24 h after challenged with LPS+GalN. All of TNF-alpha-deficient mice challenged with LPS+GalN survived. An injection of peptide A immediately after challenge with LPS+GalN resulted in significantly improved survival rates in a dose dependent manner. Peptide B showed only minor protection. The levels of TNF-alpha in the ameliorated mice by peptide A were significantly lower than those of challenge control, suggesting a suppressive effect of peptide A on TNF-alpha production. Furthermore, peptide A-treated mice showed significantly lower levels of asparate aminotransferase and alanine aminotransferase when compared to challenge control. Concordantly, hemorrhage and necrosis in the liver of peptide A-treated mice were less apparent than those of untreated control mice. These results suggest that peptide A has a protective effect on LPS-induced mortality in this mouse model.

Therapeutic effect of modified oligopeptides from the beetle Allomyrina dichotoma on methicillin-resistant Staphylococcus aureus (MRSA) infection in mice.

Anti-bacterial activity of two synthesized oligopeptides, RLYLRIGRR-NH2 (peptide A) and RLRLRIGRR-NH2 (peptide B), both which based on a putative active site of defensin, an anti-bacterial peptide from the beetle Allomyrina dichotoma, was examined by macroscopic and histopathologic assessment during the course of infection in mice inoculated with methicillin-resistant Staphylococcus aureus (MRSA) in vivo. Both peptides A and B decreased the mortality of mice inoculated with MRSA. Peptides A and B decreased the macroscopical and histopathological lesions by MRSA infection in mice even seven days after the challenge. The anti-bacterial activity of peptides A and B has a therapeutic effect on MRSA infection in mice even seven days after being challenged.

Quantification of the infectivity of Cryptosporidium parvum by monitoring the oocyst discharge from SCID mice.

Doses of 1-10(5) oocysts of Cryptosporidium parvum HNJ-1 were inoculated into severe combined immunodeficient (SCID) mice, and the discharge of oocysts was monitored for 30 days post inoculation. None of the mice discharged any oocysts after oral inoculation of one oocyst. Only one of five SCID mice discharged oocysts after oral inoculation of 10 oocysts, and the prepatent period was 17 days. The other four mice did not discharge any oocysts. All the SCID mice discharged oocysts after oral inoculation of 10(2)-10(5) oocysts. The prepatent periods were 13-17, 8-10, 8, and 10 days in SCID mice inoculated with 10(2), 10(3), 10(4), and 10(5) oocysts, respectively. A proportional correlation was observed between inoculation doses of oocysts ranging from 10 to 10(4) oocysts and the corresponding prepatent periods. The prepatent period can be used to evaluate the infectivity of C. parvum oocysts.

Isolation of Cryptosporidium andersoni Kawatabi type in a slaughterhouse in the northern island of Japan.

Fecal samples were collected from 325 adult cattle and 108 pigs in a slaughterhouse in Hokkaido, the northern island of Japan. Five adult cattle were found to be positive for oocysts of Cryptopsoridium (1.5%). The oocysts were morphologically similar to those of Cryptosporidium andersoni. The partial sequence of the 18S rRNA gene of the isolate was 100% identical with that of the C. andersoni Kawatabi strain. SCID mice were infected after oral administration. Based on the morphology of the oocysts, the sequence of the 18S rRNA gene and the infectivity to SCID mice, the isolate was concluded to be of the same type as the C. andersoni Kawatabi strain that has been isolated in Honshu, the main island of Japan.

Immunostimulating effects of sugar cane extract on X-ray radiation induced immunosuppression in the chicken.

The present study was undertaken to evaluate the effect of sugar cane (Saccharum officinarum L.) extract (SCE) on the immune system of X-ray immunosuppressed chickens. SCE (500 mg/kg/day) was administrated into the crop of 3-week-old chickens for three consecutive days before or after irradiation. The results indicated that administration of SCE before or after whole body X-ray irradiation enhanced both primary and secondary immune responses in chickens immunized with sheep red blood cells and Brucella abortus (BA) as well as cell-mediated immunity measured by delayed type hypersensitivity to human gamma-globulin.