Effects of the Aqueous Extract of Epimedii Herba on the Induction of Oral Tolerance in Mice.

Abstract

It has long been recognized that oral administration of an antigen induces immunological unresponsiveness to the antigen, this is termed oral tolerance.1,2) Induction of oral tolerance is proposed to be an immunotherapy of allergic and autoimmune diseases. [3][4][5] The physiological significance of oral tolerance is not yet clear, but possibilities include anergy and deletion of antigen-specific lymphocytes 6,7) and suppression by inhibitory cytokines including transforming growth factor-b and interleukin-4 (IL-4) secreted from regulatory T cells. 8,9) For instance, Garside et al. 10) showed that feeding of 25 mg ovalbumin (OVA) reduced production of Th2 cytokines including IL-4 as well as the Th1 cytokine IFN-g. Similar results were observed by Yoshino and Ohsawa. 11)Melamed et al.12) also found that continuous feeding of OVA decreased IL-4 secretion. In particular, it was demonstrated that feeding of antigen at high doses favored anergy in mice.13) These findings suggest that high doses of oral antigen may suppress the secretion of various cytokines. Modulation of oral tolerance by drugs and chemicals is believed to promote allergic responses via enhanced production of antibodies to the antigen in inhibitory modulation, or to be available for immunotherapy of allergy in stimulatory modulation. In a previous study, we showed that cyclophosphamide (CP) abrogates oral tolerance to OVA in mice.14) CP also can enhance delayed-type hypersensitivity responses through the elimination of suppressor T cells in BALB/c mice by oral OVA 15,16) ; it thus could be a modulator of oral tolerance. Nevertheless, the use of CP as a modulator of the oral tolerance in vivo has a disadvantage since CP is a potent pharmacological agent with a wide range of actions, including a potential for damaging the intestine.17) Therefore, it would be important to modulate an animal model of oral tolerance using agents with a more physiological action, with little or no adverse side-effects to promote immune responses via enhanced Th cell functions in inhibitory modulation.Epimedii Herba is the dry aboveground part of Epimedium koreanum NAKAI (Berberidaceae) collected in summer and fall when the plant is mature. It is an important traditional Chinese herbal medicine widely used as a tonic and in the treatment of rheumatic. 18,19) The main constituent in Epimedium species is icariin, a glycoside of prenylflavones. [20][21][22][23] The icariin decreased the production of T suppressor cells and antibody titer was thus greatly elevated.24) It has been shown that a polysaccharide with a molecular weight of about 75000 isolated from E. koreanum may be used as an immune adjuvant.25) The methanol extract of E. sagittatum also significantly augmented the leukocyte count and lymphocyte transformation rate of patients with vital energy deficiency, 26) and further promoted phagocytic activity of the reticuloendothelial system in mice and humans. 27,28) We demonstrated that the fractions of E. koreanum have immunostimulating effects in mice. 29) In partic...

Inhibition of human cytochrome P450 isoforms and NADPH-CYP reductase in vitro by 15 herbal medicines, including Epimedii herba

“…Epimedii herba , the aerial part of Epimedium koreanum , is an important traditional Chinese HM widely used as a stimulant in men, as a tonic, and to reduce blood pressure (22). It inhibited the metabolic activities of all of the CYP isoforms tested (Table 1).…”

“…Epimedii herba, Glycyrrhizae radix, Leonuri herba, Angelicae gigantis radix, Salviae miltiorrhizae radix and Eucommiae cortex produced dose-dependent inhibition of one or more of the human liver CYP isoforms. Epimedii herba, the aerial part of Epimedium koreanum, is an important traditional Chinese HM widely used as a stimulant in men, as a tonic, and to reduce blood pressure (22). It inhibited the metabolic activities of all of the CYP isoforms tested (Table 1).…”

Oral Gene Application Using Chitosan-DNA Nanoparticles Induces Transferable Tolerance

“…To induce oral tolerance, mice were given an oral administration of 25 mg ovalbumin (OVA) in phosphate-buffered saline (PBS) on days 0 and 2 as the established treatment arm (1,25,41) or OVA-encoding chitosan-DNA NP (OVA-NP) containing 50 g plasmid-DNA (OVA/pcDNA3) on days 0, 2, 5, 7, and 9. Four groups of control animals received either a corresponding amount of chitosan-DNA NP encoding the enhanced green fluorescent protein (EGFP/pcDNA3.1) or pure chitosan solution, or 50 g naked OVA/ pcDNA3-plasmid, or PBS.…”

“…In this study, we analyzed chitosan-DNA NP for their ability to induce oral tolerance to ovalbumin. The effect of the chitosan-DNA NP was compared with that obtained with an established regimen of oral OVA-protein application, which has been shown to reduce the levels of the cellular and humoral anti-OVA immune response (1,25,41). Application of OVA-NP suppressed the OVA-specific DTH response, IgG formation, and spleen cell proliferation as effectively as the treatment with OVA protein.…”

Oral gene application using chitosan-DNA nanoparticles induces transferable tolerance

“…to reduce the levels of the cellular and humoral anti-OVA immune response (1,25,41). Application of OVA-NP suppressed the OVA-specific DTH response, IgG formation, and spleen cell proliferation as effectively as the treatment with OVA protein.…”