3 research outputs found
Inhibition of NO2, PGE2, TNF-α, and iNOS EXpression by Shorea robusta L.: An Ethnomedicine Used for Anti-Inflammatory and Analgesic Activity
This paper is an attempt to evaluate the anti-inflammatory and analgesic activities and the possible mechanism of action of tender leaf extracts of Shorea robusta, traditionally used in ailments related to inflammation. The acetic-acid-induced writhing and tail flick tests were carried out for analgesic activity, while the anti-inflammatory activity was evaluated in carrageenan-and dextran- induced paw edema and cotton-pellet-induced granuloma model. The acetic-acid-induced vascular permeability, erythrocyte membrane stabilization, release of proinflammatory mediators (nitric oxide and prostaglandin E2), and cytokines (tumor necrosis factor-α, and interleukins-1β and -6) from lipopolysaccharide-stimulated human monocytic cell lines were assessed to understand the mechanism of action. The results revealed that both aqueous and methanol extract (400 mg/kg) caused significant reduction of writhing and tail flick, paw edema, granuloma tissue formation (P < 0.01), vascular permeability, and membrane stabilization. Interestingly, the aqueous extract at 40 μg/mL significantly inhibited the production of NO and release of PGE2, TNF-α, IL-1β, and IL-6. Chemically the extract contains flavonoids and triterpenes and toxicity study showed that the extract is safe. Thus, our study validated the scientific rationale of ethnomedicinal use of S. robusta and unveils its mechanism of action. However, chronic toxicological studies with active constituents are needed before its use
Synthesis and Anti-HCV Activity of 4‑Hydroxyamino α‑Pyranone Carboxamide Analogues
High genetic variability in hepatitis
C virus (HCV), emergence of drug resistant viruses and side effects
demand the requirement for development of new scaffolds to show an
alternate mechanism. Herein, we report discovery of new scaffold <b>I</b> based on 4-hydroxyamino α-pyranone carboxamide as
promising anti-HCV agents. A comprehensive structure–activity
relationship (SAR) was explored with several newly synthesized compounds.
In all promising compounds (<b>17</b>–<b>19</b>, <b>21</b>–<b>22</b>, <b>24</b>–<b>25</b>, and <b>49</b>) with EC<sub>50</sub> ranging 0.15
to 0.40 μM, the aryl group at C-6 position of α-pyranone
were unsubstituted. In particular, <b>25</b> demonstrated potential
anti-HCV activity with EC<sub>50</sub> of 0.18 μM in cell based
HCV replicon system with lower cytotoxicity (CC<sub>50</sub> >
20 μM) and provided a new scaffold for anti-HCV drug development.
Further investigations, including biochemical characterization, are
yet to be performed to elucidate its possible mode of action