Immunomodulatory and antiparasitic effects of garlic-arteether combination via nitric oxide pathway in Plasmodium berghei-infected mice.

Many reports indicate medicinal value of garlic (Allium sativum), a popular herbal medicine used worldwide, and its therapeutic effect against several diseases. Earlier studies in our laboratory have shown a potential therapeutic role of garlic-artemisinin combination in mice infected with Plasmodium berghei. A single dose of α, ß-arteether with three oral doses of garlic provides almost 95% protection. The present study aims to understand the mode of action of this combination. We have documented the level of nitric oxide (NO), a key molecule of protection and have seen in the reversal of organ morphology caused by malaria infection. The combination effects on the (a) survival rate and degree of parasitemia and (b) NO levels in blood, liver, spleen and thymus of malaria-infected mice were investigated. During the study, liver, spleen and thymus cell suspensions were assessed for immunobiochemical alterations of NO levels. The increase in NO level after infection appears to be unable to protect, whereas striking increase in spleen and thymus leads to protection against infection, and is further confirmed by detection of increased inducible nitric oxide synthase mRNA expression levels in different organs by RT-PCR. In addition, the role of T cell subsets during combination treatment was also studied. All these results indicate a potential mechanism of protection through NO pathway in combination-treated animals after malaria infection and may lead to an immunotherapy trial of malaria disease.

Comparison of the crystal structures of methyl 4-bromo-2-(meth-oxy-meth-oxy)benzoate and 4-bromo-3-(meth-oxy-meth-oxy)benzoic acid.

The title compounds, C10H11BrO4, (I), and C9H9BrO4, (II), are derivatives of bromo-hy-droxy-benzoic acids. Compound (II) crystallizes with two independent mol-ecules (A and B) in the asymmetric unit. In both (I) and (II), the O-CH2-O-CH3 side chain is not in its fully extended conformation; the O-C-O-C torsion angle is 67.3 (3) ° in (I), and -65.8 (3) and -74.1 (3)° in mol-ecules A and B, respectively, in compound (II). In the crystal of (I), mol-ecules are linked by C-H⋯O hydrogen bonds, forming C(5) chains along [010]. The chains are linked by short Br⋯O contacts [3.047 (2) Å], forming sheets parallel to the bc plane. The sheets are linked via C-H⋯π inter-actions, forming a three-dimensional architecture. In the crystal of (II), mol-ecules A and B are linked to form R 2 (2)(8) dimers via two strong O-H⋯O hydrogen bonds. These dimers are linked into ⋯A-B⋯A-B⋯A-B⋯ [C 2 (2)(15)] chains along [011] by C-H⋯O hydrogen bonds. The chains are linked by slipped parallel π-π inter-actions [inter-centroid distances = 3.6787 (18) and 3.8431 (17) Å], leading to the formation of slabs parallel to the bc plane.

Assessment of in vivo antimalarial activity of arteether and garlic oil combination therapy.

The study evaluates in vivo antimalarial activity of arteether and garlic pearl oil combination in Plasmodium berghei-infected mouse model of malaria. 72 h (Day 3) post infection, at 2-4% parasitemia, mice were treated with single dose intramuscular injection of α-ß arteether, at 750 µg, in combination with three 100 µL oral doses of garlic pearl oil on Day 3, Day 4 and Day 5. Following the treatment, 100% protection and survival of mice were observed. Inhibition of parasitemia in combination treated animals and protection during recrudescence interval of α-ß arteether monotherapy was observed in Giemsa-stained blood smears. In addition, a striking increase in anti-parasite antibody IgG contributing protective immunity during the recrudescence phase was observed. These results correlate with western blot analysis, where sera from the recrudescence stage and later period of arteether and garlic oil combination treated animals found to interact with several parasite specific proteins as compared to controls. The present approach shows that arteether and garlic pearl oil combination provides complete protection in P. berghei-infected mice. Thus, for the first time, garlic pearl oil appears to be an ideal antimalarial candidate in artemisinin combination therapy.

Crystal structure of 1-(5-bromo-1-benzo-furan-2-yl)ethanone oxime.

The title compound, C10H8BrNO2, is almost planar (r.m.s. deviation for the non-H atoms = 0.031 Å) and the conformation across the C=N bond is trans. Further, the O atom of the benzo-furan ring is syn to the N atom of the oxime group. In the crystal, inversion dimers linked by pairs of O-H⋯N hydrogen bonds generate R 2 (2)(6) loops. Very weak aromatic π-π stacking inter-actions [centroid-centroid separations = 3.9100 (12) and 3.9447 (12) Å] are also observed.