Traditional Chinese medicine for atopic eczema: PentaHerbs formula suppresses inflammatory mediators release from mast cells.

BACKGROUND: PentaHerbs formula (PHF) containing Cortex Moutan, root bark of Paeonia suffruticosa Andr. (Ranunculaceae), Cortex Phellodendri, bark of Phellodendron chinensis Schneid. (Rutaceae), Flos Lonicerae, flower of Lonicera japonica Thunb. (Capri-foliaceae), Herba Menthae, aerial part of Mentha haplocalyx Briq. (Labiatae) and Rhizoma Atractylodis, rhizome of Atractylodes lancea (Thunb.) DC. (Compositae) at the ratio of 2:2:2:1:2 was useful in the management of eczema. AIM OF THE STUDY: Since the mechanism of action of PHF is not known, we aimed to investigate the actions of PHF on mast cell activation. MATERIALS AND METHODS: Effects of aqueous extracts of PHF and individual component herb on mediator release from rat peritoneal mast cells (RPMCs) and cytokine production from HMC-1 were investigated. RESULTS: PHF, Cortex Moutan and Herba Menthae significantly attenuated histamine release and prostaglandin D(2) synthesis from RPMC activated by anti-IgE and compound 48/80 (p<0.05). While Flos Lonicerae and Rhizoma Atractylodis suppressed only mediator release from compound 48/80 activated RPMC, Cortex Phellodendri potentiated only anti-IgE induced mediator release (p<0.05). However, with the exception of Cortex Moutan, PHF and the other four component herbs failed to affect cytokine production in HMC-1. CONCLUSIONS: Although individual herbs demonstrated different modulating effects on mast cells, inhibition of inflammatory mediator release from mast cells would contribute to the therapeutic efficacy of PHF.

Immunomodulatory and anti-SARS activities of Houttuynia cordata.

BACKGROUND: Severe acute respiratory syndrome (SARS) is a life-threatening form of pneumonia caused by SARS coronavirus (SARS-CoV). From late 2002 to mid 2003, it infected more than 8000 people worldwide, of which a majority of cases were found in China. Owing to the absence of definitive therapeutic Western medicines, Houttuynia cordata Thunb. (Saururaceae)(HC) was shortlisted by Chinese scientists to tackle SARS problem as it is conventionally used to treat pneumonia. AIM OF THE STUDY: The present study aimed to explore the SARS-preventing mechanisms of HC in the immunological and anti-viral aspects. RESULTS: Results showed that HC water extract could stimulate the proliferation of mouse splenic lymphocytes significantly and dose-dependently. By flow cytometry, it was revealed that HC increased the proportion of CD4(+) and CD8(+) T cells. Moreover, it caused a significant increase in the secretion of IL-2 and IL-10 by mouse splenic lymphocytes. In the anti-viral aspect, HC exhibited significant inhibitory effects on SARS-CoV 3C-like protease (3CL(pro)) and RNA-dependent RNA polymerase (RdRp). On the other hand, oral acute toxicity test demonstrated that HC was non-toxic to laboratory animals following oral administration at 16 g/kg. CONCLUSION: The results of this study provided scientific data to support the efficient and safe use of HC to combat SARS.

DNA cleavage potency, cytotoxicity, and mechanism of action of a novel class of enediyne prodrugs.

We have discovered a novel class of (E)-3-acyloxy-4-(arylmethylidene)cyclodeca-1,5-diynes which exhibit promising enediyne-like DNA cleavage and cytotoxic activities. LC-MS analysis of the incubation mixture (pH 8.5, 37 degrees C) confirmed formation of 10-membered ring enediyne presumably via an allylic cation and suggested that the 1,4-benzenoid diradical might be one of the active species for DNA damage and cytotoxicity.

Regioselective Synthesis of Acyclic cis-Enediynes via an Acid-Catalyzed Rearrangement of 1,2-Dialkynylallyl Alcohols. Syntheses, Computational Calculations, and Mechanism.

A novel synthesis of acyclic cis-enediynes 2 has been established by an acid-catalyzed rearrangement of 1,2-diyn-2-propen-1-ols 1 possessing a C3-aryl group in the presence of water, alcohols, or thiols. Reactivity of allyl alcohols and regio- and cis/trans diastereoselectivity of the allylic migration were examined. In the presence of (±)-10-camphorsulfonic acid (CSA), the parent allyl alcohol 5 and the C3-methyl-substituted 9 failed to give enediynes, whereas the C3-aryl-substituted 12 and 29 underwent the allylic rearrangement to provide predominantly cis-enediynes 16 and 31 at room temperature or below. Under similar acidic conditions, enediyne alcohol 13 produced 16b and 16d with the same regio- and cis/trans diastereoselectivity observed for 12. Allyl alcohol 30, an isomer of 29, also provided enediynes 31c and 32c after a prolonged reaction (90 h) at room temperature in the presence of CSA and EtOH. These results suggested that the same allylic cations were obtained from allyl alcohols 12 and 13 or 29 and 30 even though the ease of ionization differed for each substrate. Involvement of allylic cations in the product-forming step was confirmed by the finding that chiral allyl alcohols (-)-12 and (-)-18c furnished racemic products. In general, the p-MeOPh-substituted allyl alcohol 29 gave a better regioselectivity than the Ph-substituted 12. In the reactions with alcohols, the regioisomeric ratios were 100:0 (31:33) for 29 and ca. 96:4 (16:17) for 12; the ratios decreased to ca. 90:10 (31:33) for 29 and ca. 70:30 (16:17) for 12 when thiols were used. The cis/trans diastereoselectivity is higher for allyl alcohol 12 (100% for 16 at 20 °C) compared to that for 29 (31:32 = 80:20-94:6 at 0 °C). Computational calculations at the RHF/3-21G level, carried out on the model compounds and allylic cations, indicated that nucleophilic trapping takes place preferentially at the C3 carbon to form the thermodynamically much more stable enediynes. Under the best reaction conditions (1 equiv of CSA and 2 equiv of EtOH in CH2Cl2, 20 °C), a number of acyclic cis-enediynes can be synthesized in three steps from the commercially available α-bromocinnamaldehyde (10).