Achyranthes bidentata polysaccharide enhances immune response in weaned piglets.

Immunopharmacol Immunotoxicol. 2009; 31(2): 253-60Chen Q, Liu Z, He JHThe acquired immunity is underdeveloped at 3-4 weeks of age when piglets are usually weaned on commercial farms, and weaning is associated with compromised immunity. Dietary supplementation with immunomodulatory phytochemicals may enhance immune responses in the weaned piglets. This study is conducted to investigate the effects of dietary supplemental achyranthes bidentata polysaccharide (ABP) on proliferation activity of lymphocytes, and production of antibodies, complements and cytokines in weaned piglets. Results showed that lymphocyte proliferation activity in piglets fed diets supplementing with 1000 and 1500 mg/kg ABP increased (P < 0.05) on days 14 and 28 compared with the non-additive piglets, as well as serum contents of IgG, IgA, IgM, C(3), C(4), IL (interleukin)-2 and IFN (interferon)-gamma. The ABP had dose-dependent immunomodulatory activity and the dose of 1500 mg/kg presented the strongest stimulating activity in vivo. In addition, the ABP increased (P < 0.05) the proliferation activity and production of IL-2 and IFN-gamma of cultured lymphocytes in dose- or time-dependent manner. The proliferation activity of peripheral T cells and splenic lymphocytes in 400 microg/ml of ABP group arrived at their peak values, as well as the production of IL-2 and IFN-gamma at 72 and 12 h after the treatment, respectively. Collectively, these findings suggested that dietary supplementation with ABP to weaned piglets enhances cellular and humoral immune responses, and ABP addition to culture medium also increases the proliferation activity and cytokine production of lymphocytes cultured in vitro, which indicate that dietary supplementation with the herbal polysaccharide may offer an effective alternative to antibiotics for weaned piglets.

The effects of beta-glucan on human immune and cancer cells.

J Hematol Oncol. 2009 Jun 10; 2(1): 25Chan GC, Chan WK, Sze DMABSTRACT: Non-prescriptional use of medicinal herbs among cancer patients is common around the world. The alleged anti-cancer effects of most herbal extracts are mainly based on studies derived from in vitro or in vivo animal experiments. The current information suggests that these herbal extracts exert their biological effect either through cytotoxic or immunomodulatory mechanisms. One of the active compounds responsible for the immune effects of herbal products is in the form of complex polysaccharides known as beta-glucans. beta-glucans are ubiquitously found in both bacterial or fungal cell walls and have been implicated in the initiation of anti-microbial immune response. Based on in vitro studies, beta-glucans act on several immune receptors including Dectin-1, complement receptor (CR3) and TLR-2/6 and trigger a group of immune cells including macrophages, neutrophils, monocytes, natural killer cells and dendritic cells. As a consequence, both innate and adaptive response can be modulated by beta-glucans and they can also enhance opsonic and non-opsonic phagocytosis. In animal studies, after oral administration, the specific backbone 13 linear -glycosidic chain of beta-glucans cannot be digested. Most beta-glucans enter the proximal small intestine and some are captured by the macrophages. They are internalized and fragmented within the cells, then transported by the macrophages to the marrow and endothelial reticular system. The small beta-glucans fragments are eventually released by the macrophages and taken up by other immune cells leading to various immune responses. However, beta-glucans of different sizes and branching patterns may have significantly variable immune potency. Careful selection of appropriate beta-glucans is essential if we wish to investigate the effects of beta-glucans clinically. So far, no good quality clinical trial data is available on assessing the effectiveness of purified beta-glucans among cancer patients. Future effort should direct at performing well-designed clinical trials to verify the actual clinical efficacy of beta-glucans or beta-glucans containing compounds.

Substrates, Inducers, Inhibitors and Structure-Activity Relationships of Human Cytochrome P450 2C9 and Implications in Drug Development.

Curr Med Chem. 2009 Sep 1; Zhou SF, Zhou ZW, Yang LP, Cai JPCytochrome P450 2C9 (CYP2C9) is one of the most abundant CYP enzymes in the human liver. CYP2C9 metabolizes more than 100 therapeutic drugs, including tolbutamide, glyburide, diclofenac, celecoxib, torasemide, phenytoin losartan, and S-warfarin). Some natural and herbal compounds are also metabolized by CYP2C9, probably leading to the formation of toxic metabolites. CYP2C9 also plays a role in the metabolism of several endogenous compounds such as steroids, melatonin, retinoids and arachidonic acid. Many CYP2C9 substrates are weak acids, but CYP2C9 also has the capacity to metabolise neutral, highly lipophilic compounds. A number of ligand-based and homology models of CYP2C9 have been reported and this has provided insights into the binding of ligands to the active site of CYP2C9. Data from the site-directed mutagenesis studies have revealed that a number of residues (e.g. Arg97, Phe110, Val113, Phe114, Arg144, Ser286, Asn289, Asp293 and Phe476) play an important role in ligand binding and determination of substrate specificity. The resolved crystal structures of CYP2C9 have confirmed the importance of these residues in substrate recognition and ligand orientation. CYP2C9 is activated by dapsone and its analogues and R-lansoprazole in a stereo-specific and substrate-dependent manner, probably through binding to the active site and inducing positive cooperativity. CYP2C9 is subject to induction by rifampin, phenobarbital, and dexamethasone, indicating the involvement of pregnane X receptor, constitutive androstane receptor and glucocorticoid receptor in the regulation of CYP2C9. A number of compounds have been found to inhibit CYP2C9 and this may provide an explanation for some clinically important drug interactions. Tienilic acid, suprofen and silybin are mechanism-based inhibitors of CYP2C9. Given the critical role of CYP2C9 in drug metabolism and the presence of polymorphisms, it is important to identify drug candidates as potential substrates, inducer or inhibitors of CYP2C9 in drug development and drug discovery scientists should develop drugs with minimal interactions with this enzyme. Further studies are warranted to explore the molecular determinants for ligand-CYP2C9 binding and the structure-activity relationships.