Diarylheptanoid, a constituent isolated from methanol extract of Alpinia officinarum attenuates TNF-α level in Freund's complete adjuvant-induced arthritis in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Rheumatoid arthritis (RA) is a chronic inflammatory and destructive joint disease that affects the worldwide population. Alpinia officinarum Hance (Zingiberaceae), rhizomes are widely used ethnobotanically as an anti-inflammatory, analgesic, and antioxidant agent in traditional medicine. AIM: To investigate the efficacy and possible mechanism of isolated phytoconstituent from the methanol extract of A. officinarum (MEAO) rhizomes against Freund's complete adjuvant (FCA)-induced arthritis in rats. Furthermore, molecular docking was performed to study the binding mode of this compound into the active site of TNF-α. MATERIALS AND METHODS: Diarylheptanoid was isolated from MEAO, well characterized (HPTLC, 1H NMR, 13C NMR, and ESI-MS) and evaluated for its antiarthritic activity in female Wistar rats (170-200 g). Diarylheptanoid (5, 10 and 20 mg/kg, p.o.) was administered starting from day 12. Various behavioral, biochemical, molecular and histopathology parameters were evaluated. Molecular docking study was performed using Glide module integrated into Schrodinger molecular modeling software. RESULTS: The structure and molecular weight of the isolated compound (diarylheptanoid) were confirmed by 1D and mass spectral data and characterized as 1-phenyl-5-hydroxy-7- (4''-hydroxy-3''-methoxyphenyl) heptane-3-one (i.e., 5-HPH) with molecular formula C20H24O4. Administration of 5-HPH (10 and 20 mg/kg) significantly inhibited (p < 0.05) FCA induced increases in paw volume, joint diameter, thermal hyperalgesia and tactile allodynia. It also significantly decreased oxido-inflammatory markers (SOD, GSH, MDA, and TNF-α). FCA induced a histological alteration in ankle joint also attenuated by 5-HPH. Its Glide docking score was found to be -9.702 with binding energy (Glide energy) of -37.033 kcal/mol. CONCLUSION: 5-HPH may exhibit its anti-arthritic potential via inhibition of elevated oxido-inflammatory markers thus restoring the elevated hyperalgesia, allodynia and reducing destruction in synovial membrane and cartilage. Therefore, 5-HPH is a potential moiety bearing antioxidant and with anti-inflammatory properties to inhibit FCA-induced arthritis in rats. The results of the present investigation should enable the design of potent small-molecule inhibitors that inactivate TNF-α with high affinity and specificity.

Anti-inflammatory and antioxidant potential of Guaianolide isolated from Cyathocline purpurea: Role of COX-2 inhibition.

BACKGROUND: Inflammation activated by oxidative stress can cause various diseases, such as asthma, rheumatoid arthritis, cancer, diabetes, etc. Plant constituents with sesquiterpene lactones possess antioxidant and anti-inflammatory properties. AIM: To determine the antioxidant and anti-inflammatory potential of isolated phytoconstituent from Cyathocline purpurea Buch-Ham ex D (CP). Don in laboratory animals. Furthermore, to understand the interactions involved in the binding of this compound to cyclooxygenase-2 (COX-2) via computational docking. METHODS: Phytoconstituent was isolated, purified and well characterized (using IR, NMR, and MS) from ethyl acetate fraction of CP methanolic extract. It was then evaluated for its in-vitro antioxidant activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydrogen peroxide (H2O2) and hydroxyl (OH) radical assays as well as in-vivo anti-inflammatory potential against carrageenan-induced paw edema model in rats. The molecular docking study was performed against the crystal structure of COX-2 to evaluate the binding potential of phytoconstituent towards this enzyme. RESULTS: The isolated compound 6α-hydroxy-4 [14], 10 [15]-guainadien-8α, 12-olide (HGN) showed significant (p<0.001) antioxidant activity with IC50 values of 76µg/mL. Administration of HGN (10 and 20mg/kg) significantly (p<0.001) reduced the increased paw volume after subplantar administration of carrageenan. It also exhibits good binding affinity towards with COX-2 with a docking score of -8.98 and Glide binding energy of -36.488kcal/mol shedding light on the potential mechanism of anti-inflammatory action. CONCLUSIONS: The presence of hydroxyl group in HGN provides a credential to its in-vivo anti-inflammatory and in-vitro antioxidant activities. Furthermore, the good binding affinity of HGN for the active site of COX-2 may open novel vistas in therapeutic option with natural antioxidants like Cyathocline purpurea to treat various inflammatory disorders.

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.

Antioxidant and hypolipidemic activity of Kumbhajatu in hypercholesterolemic rats.

OBJECTIVE: To study the efficacy of Kumbhajatu in reducing the cholesterol levels and as an antioxidant in hypercholesterolemic rats. MATERIALS AND METHODS: Hypercholesterolemia was induced in normal rats by including 2% w/w cholesterol, 1% w/w sodium cholate and 2.5% w/w coconut oil in the normal diet. Powdered form of Kumbhajatu was administered as feed supplement at 250 and 500 mg/kg dose levels to the hypercholesterolemic rats. Plasma lipid profile, hepatic superoxide dismutase (SOD) activity, catalase activity, reduced glutathione and extent of lipid peroxidation in the form of malondialdehyde were estimated using standard methods. RESULTS: Feed supplementation with 250 and 500 mg/kg of Kumbhajatu resulted in a significant decline in plasma lipid profiles. The feed supplementation increased the concentration of catalase, SOD, glutathione and HDL-c significantly in both the experimental groups (250 and 500 mg/kg). On the other hand, the concentration of malondialdehyde, cholesterol, triglycerides, LDL-c and VLDL in these groups (250 and 500 mg/kg) were decreased significantly. CONCLUSION: The present study demonstrates that addition of Kumbhajatu powder at 250 and 500 mg/kg level as a feed supplement reduces the plasma lipid levels and also decreases lipid peroxidation.