Immunostimulatory and anti-allergic potential of novel heterotrimeric lectin from seeds of Zizyphus mauritiana Lam.

Zizyphus mauritiana Lam. seeds (ZMS) have been used medicinally as sedative or hypnotic drugs in most of Asian countries. ZMS has significant benefits to the human health. Therefore, we have evaluated immunomodulatory effect of lectin extracted from these ZMSL in both in vitro and in vivo study. Anaphylaxis is a severe life-threatening allergic reaction and Arthus reaction is deposition of immune complex and complement system activation, so we hypothesized that if ZMSL can protect these severe allergic diseases. We have studied the effect of ZMSL on macrophages and Wistar albino rats and confirmed its protective effect against anaphylaxis and Arthus reaction. Results of this study suggest ZMSL have immunostimulatory and antiallergic activity.

In vivo enzymatic modulation of IgG antibodies prevents immune complex-dependent skin injury.

IgG antibodies are potent inducers of proinflammatory responses by cross-linking Fc receptors on innate immune effector cells resulting in tissue injury. The recently discovered enzymes endoglycosidase S (EndoS) and IgG-degrading enzyme (IdeS) of Streptococcus pyogenes are able to modulate the interaction between IgG antibodies and the Fc receptors, by hydrolysis of the glycan associated with the heavy chain of the IgG molecule (EndoS), or cleavage in the hinge region of the heavy IgG chain (IdeS). In this work, we investigated their ability to inhibit damage mediated by skin-bound antibodies in vivo in two different experimental models, the Arthus reaction, and epidermolysis bullosa acquisita, an autoimmune blistering skin disease associated with autoantibodies against type VII collagen. We demonstrate that both enzymes efficiently interfere with IgG-mediated proinflammatory processes, offering a great asset to specifically target pathological IgG antibodies in the skin and holding great promise for future applications in human therapy.

Immunomodulatory and therapeutic potential of a mycelial lectin from Aspergillus nidulans.

Lectins bind to surface receptors on target cells, and activate a cascade of events, eventually leading to altered immune status of host. The immunomodulatory potential of purified lectin from Aspergillus nidulans was evaluated in Swiss albino mice treated intraperitoneally with seven different doses of purified lectin. Lectin prevented BSA-induced Arthus reaction and systemic anaphylaxis. The enhanced functional ability of macrophages was evident from respiratory burst activity and nitric oxide production in splenocyte cultures. Interferon-gamma and interleukin-6 levels were significantly up-regulated in treated groups. Maximum stimulatory effect was observed at the dose of 1.5 mg/kg body weight. Therapeutic potential of A. nidulans lectin was assessed against trinitrobenzene sulfonic acid-induced ulcerative colitis in male Wistar rats. Rats pre-treated with 80 mg/kg body weight of purified lectin intraperitoneally prior to colitis induction showed lesser disease severity and recovery within 7 days, while rats post-treated with the same dose showed recovery in 11 days. The results demonstrate immunomodulatory effects of A. nidulans lectin in Swiss albino mice, resulting in improved immune status of the animals and unfold its curative effect against ulcerative colitis in rat model. This is the first report on immunomodulatory and therapeutic potential of a lectin from microfungi.

Studies on Alismatis rhizoma. I. Anti-allergic effects of methanol extract and six terpene components from Alismatis rhizoma (dried rhizome of Alisma orientale).

Methanol and aqueous extracts (TMe-ext and TAq-ext) from dried rhizomes of Alisma orientale have been screened for activity in experimental models of type I-IV allergies. In the type III allergic model, TMe-ext at oral doses of 50, 200 mg/kg showed an inhibitory effect on the direct passive Arthus reaction (DPAR) in rats, while TAq-ext did not. Four triterpenes (alisol A, alisol B, alisol A monoacetate and alisol B monoacetate) and two sesquiterpenes (alismol and alismoxide) isolated from TMe-ext also exhibited this inhibitory effect. In a type I allergic model, TMe-ext inhibited 48-h homologous passive cutaneous anaphylaxis (PCA) in rats. In a type II allergic model, it was found that TMe-ext inhibits reversed cutaneous anaphylaxis (RCA) in rats. Furthermore, in a type IV allergic model, TMe-ext had an inhibitory effect on the induction phase in picryl chloride-induced contact dermatitis (PC-CD) in mice. These results indicate that Alismatis Rhizoma not only inhibits antibody-mediated allergic reactions but also influences cell reactions and should be recognized as a material for the treatment of allergic reactions, and the anti-type III allergic components are partially attributable to the terpenes mentioned above.

Inhibitory effects of dehydrocorydaline isolated from Corydalis Tuber against type I-IV allergic models.

An alkaloidal component, dehydrocorydaline (DHC) isolated from Corydalis Tuber (tuber of Corydalis turtschaninovii forma yanhusuo), has been screened for activity against types I-IV allergic reactions. In a type I allergic models, DHC at a dose of 0.5 mmol/kg, p.o. inhibited 48 h homologous passive cutaneous anaphylaxis (PCA) in rats, which is related to IgE. DHC also exhibited an inhibitory effect on antigen-induced histamine release from peritoneal mast cells. In a type II allergic model, DHC did not inhibit reversed cutaneous anaphylaxis (RCA) in rats. In a type III allergic model, DHC showed weak inhibition on direct passive arthus reaction (DPAR) in rats. Furthermore, in a type IV allergic model, DHC had inhibitory effects on the induction phase and effector phase in picryl chloride-induced contact dermatitis (PC-CD). These results indicated that DHC not only inhibits antibody-mediated allergic reactions but also influences cell-mediated allergia reactions, and the inhibitory effect of Corydalis Tuber on allergic reactions may be partially attributed to DHC.

Inhibitory effects of methanolic extract from corydalis tuber against types I-IV allergic models.

Methanolic extract (CM-ext) from tubers of Corydalis turtschaninovii forma yanhusuo has been screened for activity in experimental models of types I-IV allergy. In type I allergic models, CM-ext at doses of 200, 500 mg/kg, p.o. inhibited 48-h homologous passive cutaneous anaphylaxis (PCA) in rats which is related to IgE, and 4-h heterologous PCA in guinea pigs which is related to IgG. The inhibition of CM-ext on 48-h PCA was also recognized in adrenalectomized rats. CM-ext exhibited the inhibitory effect on formation of IgE antibody in BALB/c mice. In type II allergic model, it was found that CM-ext inhibits reversed cutaneous anaphylaxis (RCA). In type III allergic model, CM-ext showed the inhibitory effect on direct passive arthus reaction (DPAR) in rats. Furthermore, in type IV allergic model, CM-ext had the inhibitory effects on induction phase and effector phase in picryl chloride-induced contact dermatitis (PC-CD). It also showed therapeutic action on PC-CD. These results indicated that CM-ext not only inhibits antibody-mediated allergic reactions but also influences cell-mediated allergic reactions and should be recognized as a potent material for allergic reactions, although the mechanisms and active principles of CM-ext have not yet been completely determined.