Isolates of Alpinia officinarum Hance as COX-2 inhibitors: Evidence from anti-inflammatory, antioxidant and molecular docking studies.

BACKGROUND: Inflammation triggered by oxidative stress can cause various ailments, such as cancer, rheumatoid arthritis, asthma, diabetes etc. In the last few years, there has been a renewed interest in studying the antioxidant and anti-inflammatory action of plant constituents such as flavonoids and diarylheptanoids. AIM: To evaluate the antioxidant, anti-inflammatory activity and the total phenolic content of isolated compounds from Alpinia officinarum rhizomes. Furthermore, molecular docking was performed to study the binding mode of these compounds into the active site of cyclooxygenase-2 (COX-2). METHODS: A. officinarum rhizomes were extracted by maceration, using methanol. This extract was further fractionated by partitioning with hexane, chloroform and ethyl acetate and these fractions on further purification resulted in isolation of five pure compounds. Characterization was carried out by using (1)H NMR, (13)C NMR and MS. They were further evaluated for antioxidant and anti-inflammatory activity using carrageenan-induced paw edema model in rats. Molecular docking study was performed using Glide module integrated in Schrodinger molecular modeling software. RESULTS: The compounds were identified as 1,7-diphenylhept-4-en-3-one (1), 5-hydroxy-1,7-diphenyl-3-heptanone (2), 3,5,7-trihydroxyflavone (Galangin, 3), 3,5,7-trihydroxy-4'-methoxyflavone (Kaempferide, 4) and 5-hydroxy-7-(4″-hydroxy-3″-methoxyphenyl)-1-phenyl-3-heptanone (5). The compound-3 and compound-5 (10mg/kg) showed significant (p<0.001) antioxidant and anti-inflammatory potential. Moreover, total phenolic content was detected as 72.96 mg and 51.18 mg gallic acid equivalent respectively. All the five isolates were found to be good binders with COX-2 (average docking score -9.03). CONCLUSIONS: Galangin and 5-hydroxy-7-(4″-hydroxy-3″-methoxyphenyl)-1-phenyl-3-heptanone exhibited anti-inflammatory and in-vitro antioxidant activity which may be due to presence of phenolic content in it. The molecular docking study revealed that these compounds have affinity towards COX-2 active site which can further be explored as selective COX-2 inhibitors. The results obtained in this work justify the use of A. officinarum in the treatment of inflammatory disorders like rheumatoid arthritis and inflammatory bowel diseases.

In vitro and in vivo protection provided by pinocembrin against lipopolysaccharide-induced inflammatory responses.

Pinocembrin or 5, 7-dihydroxyflavanone is a flavanone, a type of flavonoid. In the present study, we first assessed the anti-inflammatory effects of pinocembrin in RAW macrophage cells; and based on these effects, we investigated the therapeutic effects of pinocembrin in murine model of endotoxin-induced acute lung injury. We found that in vitro pretreatment with pinocembrin remarkably regulated the production of TNF-α, IL-1ß, IL-6 and IL-10 via inhibiting the phosphorylation of IκBα, ERK1/2, JNK and p38MAPK. In the mouse model of LPS-induced acute lung injury, pinocembrin (20 or 50 mg/kg, i.p.) attenuated the development of pulmonary edema, histological severities, as well as neutrophil, lymphocyte and macrophage infiltration, which were increased by LPS administration. Additionally, TNF-α, IL-1ß and IL-6 concentrations decreased significantly while the concentration of IL-10 was significantly increased after pinocembrin pretreatment. Our results also showed that pinocembrin attenuated LPS-induced lung injury through suppression of IκBα, JNK and p38MAPK activation. These findings suggest that pinocembrin may represent a novel candidate for the modulation of inflammatory responses.