Friday, December 10, 2010
17-O-acetylacuminolide (AA), a diterpenoid labdane, was isolated for the first time from the plant species Neouvaria foetida. The anti-inflammatory effects of this compound were studied both in vitro and in vivo.
Plant extracts were initially tested against LPS-stimulated release of tumor necrosis factor alpha (TNF-α) from murine macrophages (RAW264.7 cells). Based on bioassay-guided fractionation, the active compound was identified as AA. AA was tested for its ability to reduce nitric oxide (NO) production, and the inducible nitric oxide synthase (iNOS) expression. The inhibition of a panel of inflammatory cytokines (TNF, IL-1β, IL-6, KC, and GM-CSF) by AA was assessed at the expression and the mRNA levels. Moreover, the effect of AA on the translocation of the transcription factor nuclear factor kappa B (NF-κB) was evaluated in LPS-stimulated RAW264.7 cells and in TNF-stimulated L929 cells. Subsequently, AA was tested in the inhibitor of NF-κB kinase beta (IKKβ) activity assay. Lastly, the anti-inflammatory activity of AA in vivo was evaluated by testing TNF production in LPS-stimulated Balb/c mice.
AA effectively inhibited TNF-α release with an IC50 of 2.7 µg/mL. Moreover, AA significantly inhibited both NO production and iNOS expression. It significantly and dose-dependently inhibited TNF and IL-1β proteins and mRNA expression; as well as IL-6 and KC proteins. Additionally, AA prevented the translocation of NF-κB in both cell lines; suggesting that it is acting at a post receptor level. This was confirmed by AA's ability to inhibit IKKβ activity, a kinase responsible for activating NF-κB, hence providing an insight on AA's mechanism of action. Finally, AA significantly reduced TNF production in vivo.
This study presents the potential utilization of this compound, as a lead for the development of an anti-inflammatory drug.
Professor Rais Mustafa (in picture) is a smiling, calm person who has the responsibility of being the Deputy Dean (Research) of the Medical Faculty at the UM Kuala Lumpur. Professor Rais was recently 'baptized' by us to get his research showcased in PLoS ONE! His paper published in PLoS ONE just a few days ago has already put him at an advantage of being at the forefront of the proposed 'International Network of Excellence on goodness of Malaysian natural compounds'.
Saturday, December 4, 2010
Click on the latest Forbes List of Top 10 Billionaires in the world and there are two Indian names, both within the top five. Now do the same with the list of top 10 philanthropists in the world and not a single Indian name emerges! Why? What explains this huge disconnect between wealth and giving? Why are Indians more niggardly when it comes to parting with their wealth? One reason could be cultural. We tend to be much more inward-looking and family-oriented than our western counterparts, notwithstanding the Vasudhaiva Kutumbakam (the world is one family) worldview that many Indians profess. Another could be that many of the newer Indian billionaires are yet to get comfortable with their wealth. And a third, no less important, could be our unimaginative tax policies that almost dissuade charitable donations. In a rational world, you would expect those who have more to give more, even if it was Karl Marx, the avowed enemy of capitalism who said, 'from each according to his ability … Those whom fortune has favoured must be more willing to share their wealth with those less privileged. That has been the guiding philosophy of many American philanthropists who set up some of its great universities. But not in India, or so it seemed! Till now when, thanks to an astoundingly generous act from Azim Premji, chairman, Wipro Foundation, an Indian is all set to make it to the list of top philanthropists in the world. Compare the size of Premji's endowment (approx $2 billion) with the average $ 4.1 billion given by top 50 US philanthropists last year (according to the Chronicle of Philanthropy) and the scale of his generosity is manifest. The Azim Premji Foundation has been engaged in improving the quality of schooling in Karnataka and with this latest endowment should now be able to contribute even more. Admittedly, it may be difficult for many of India's corporate leaders to match Premji's generosity, though it is worth noting that the top donors in the US last year Stanley and Fiona Druckenmiller — are not the richest. But the good thing is, over the years, there has definitely been more giving than in the past. Now with Premji showing the way, will others follow? And will tax policy foster the culture of giving to advance the collective good? (in syndication with - The economic times)