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1.  The curative effect of fucoidan on visceral leishmaniasis is mediated by activation of MAP kinases through specific protein kinase C isoforms 
Cellular and Molecular Immunology  2014;11(3):263-274.
Fucoidan can cure both antimony-sensitive and antimony-resistant visceral leishmaniasis through immune activation. However, the signaling events underlying this cellular response remain uncharacterized. The present study reveals that fucoidan induces activation of p38 and ERK1/2 and NF-κB DNA binding in both normal and Leishmania donovani-infected macrophages, as revealed by western blotting and electrophoretic mobility shift assay (EMSA), respectively. Pharmacological inhibition of p38, ERK1/2 or the NF-κB pathway markedly attenuated fucoidan-induced pro-inflammatory cytokine synthesis and inducible nitric oxide synthase (iNOS) gene transcription, resulting in a reduction of parasite clearance. To decipher the underlying mechanism of fucoidan-mediated parasite suppression, the expression and functionality of various protein kinase C (PKC) isoforms were evaluated by immunoblotting and enzyme activity assay. Fucoidan elicited an increase in expression and activity of PKC-α, -βI and -βII isoforms in infected macrophages. Functional knockdown of PKC-α and -β resulted in downregulation of p38 and ERK1/2, along with a marked reduction of IL-12 and TNF-α production in fucoidan-treated infected macrophages. Collectively, these results suggest that the curative effect of fucoidan is mediated by PKC-dependent activation of the mitogen-activated protein kinase (MAPK)/NF-κB pathway, which ultimately results in the production of nitric oxide (NO) and disease-resolving pro-inflammatory cytokines.
PMCID: PMC4085487  PMID: 24561457
fucoidan; MAPK; NF-κB; PKC; visceral leishmaniasis
2.  Clinical effect of Virechana and Shamana Chikitsa in Tamaka Shwasa (Bronchial Asthma) 
Ayu  2012;33(2):238-242.
To evaluate comparative efficacy of Samshodhana and Samshamana Chikitsa, the current study is planned in 24 patients of Tamaka Shwasa. Thirteen patients (Group A) were treated with Samshodhana, particularly with Virechana Karma. The patients of this group received Abhyantara Snehana with Tila Taila followed by Bahya Snehana with Tila Taila and Saindhava Lavana. After observations of proper signs of Snehana; Virechana Karma was performed with Aragvadha Phala Majja. Samsarjana Krama was followed for five days. Subsequently all the patients were given the trial drug (powder of Badara). The patients of group B, were treated only with the powder of dried ripe fruits of Badara. In both groups, the dose of Badara powder was 5 g, twice a day, with luke warm water, for a period of 60 days. In group A, maximum number of patients (61.45 %) showed good response, while in group B, 45.45 % patients showed good response. No side effects were observed during the clinical trial. Based on the observations, it was concluded that, group A is more effective than group B.
PMCID: PMC3611644  PMID: 23559796
Aragvadha Phala Majja; Badara Phala Majja; Bronchial Asthma; Tamaka Shwasa; Virechana Karma
3.  Curative Effect of 18β-Glycyrrhetinic Acid in Experimental Visceral Leishmaniasis Depends on Phosphatase-Dependent Modulation of Cellular MAP Kinases 
PLoS ONE  2011;6(12):e29062.
We earlier showed that 18β-glycyrrhetinic acid (GRA), a pentacyclic triterpenoid from licorice root, could completely cure visceral leishmaniasis in BALB/c mouse model. This was associated with induction of nitric oxide and proinflammatory cytokine production through the up regulation of NF-κB. In the present study we tried to decipher the underlying cellular mechanisms of the curative effect of GRA. Analysis of MAP kinase pathways revealed that GRA caused strong activation of p38 and to a lesser extent, ERK in bone marrow-derived macrophages (BMDM). Almost complete abrogation of GRA-induced cytokine production in presence of specific inhibitors of p38 and ERK1/2 confirmed the involvement of these MAP kinases in GRA-mediated responses. GRA induced mitogen- and stress-activated protein kinase (MSK1) activity in a time-dependent manner suggested that GRA-mediated NF-κB transactivation is mediated by p38, ERK and MSK1 pathway. As kinase/phosphatase balance plays an important role in modulating infection, the effect of GRA on MAPK directed phosphatases (MKP) was studied. GRA markedly reduced the expression and activities of three phosphatases, MKP1, MKP3 and protein phosphatase 2A (PP2A) along with a substantial reduction of p38 and ERK dephosphorylation in infected BMDM. Similarly in the in vivo situation, GRA treatment of L. donovani-infected BALB/c mice caused marked reduction of spleen parasite burden associated with concomitant decrease of individual phosphatase levels. However, activation of kinases also played an important role as the protective effect of GRA was significantly abrogated by pharmacological inhibition of p38 and ERK pathway. Curative effect of GRA may, therefore, be associated with restoration of proper cellular kinase/phosphatase balance, rather than modulation of either kinases or phosphatases.
PMCID: PMC3237588  PMID: 22194991

Results 1-3 (3)