RESUMEN
Bioassay-guided isolation from acetone extract of the roots of Artemisia pallens Wall yielded two spiro compounds (1 and 2). The structures of these compounds were determined on the basis of spectroscopic techniques such as IR, MS, 1 D and 2 D- NMR. The acetone extract, fractions and the isolated two compounds were investigated for their antibacterial activity against two gram negative (E. coli, P. aeruginosa) and two gram positive (S. aureus, B. subtilis) bacterial strains. Compound (2) showed the best spectra of activity with IC50 and MIC values between 2.48-3.08 and 12.78 - 21.77 µM and Compound (1) with 2.57-3.69 and 38.17 - 80.57 µM, respectively, for the four bacterial strains, whereas inactive against Mycobacterium tuberculosis. Molecular docking study could further help in understanding the various interactions between these compounds and DNA gyrase active site in detail and thereby could provide valuable insight into the mechanism of action.
Asunto(s)
Artemisia , Compuestos de Espiro , Acetona , Antibacterianos/química , Antibacterianos/farmacología , Bacterias , Escherichia coli , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Extractos Vegetales/química , Extractos Vegetales/farmacología , Pseudomonas aeruginosa , Compuestos de Espiro/farmacología , Staphylococcus aureusRESUMEN
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 (170-200â¯g). Diarylheptanoid (5, 10 and 20â¯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 20â¯mg/kg) significantly inhibited (pâ¯<â¯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 -37.033â¯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.
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Alpinia , Antiinflamatorios/farmacología , Artritis Experimental/metabolismo , Diarilheptanoides/farmacología , Factor de Necrosis Tumoral alfa/metabolismo , Animales , Articulación del Tobillo/efectos de los fármacos , Articulación del Tobillo/patología , Antiinflamatorios/uso terapéutico , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/patología , Diarilheptanoides/uso terapéutico , Femenino , Metanol/química , Simulación del Acoplamiento Molecular , Fitoterapia , Extractos Vegetales , Ratas Wistar , Solventes/química , Factor de Necrosis Tumoral alfa/sangreRESUMEN
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.
Asunto(s)
Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Ciclooxigenasa 2/metabolismo , Edema/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Fitoterapia/métodos , Sesquiterpenos de Guayano/uso terapéutico , Animales , Asteraceae/inmunología , Compuestos de Bifenilo/inmunología , Carragenina/toxicidad , Células Cultivadas , Edema/inducido químicamente , Femenino , Humanos , Peróxido de Hidrógeno/metabolismo , Masculino , Ratones , Estrés Oxidativo/efectos de los fármacos , Picratos/inmunología , Ratas , Ratas WistarRESUMEN
Phytochemical investigation of methanol extract of the rhizomes of Alpinia officinarum Hance afforded four known diarylheptanoids 1,7-diphenylhept-4-en-3-one (1), 5-hydroxy-1,7-diphenyl-3-heptanone (2), 5-hydroxy-7-(4â³-hydroxy-3â³-methoxyphenyl)-1-phenyl-3-heptanone (3), and 7-(4â³-hydroxy-3â³-methoxyphenyl)-1-phenyl heptan-3-one (4).The acetate derivative of (4), 7-(4â³-actetate-3â³-methoxy phenyl)-1-phenyl heptan-3-one (5), was prepared. These diarylheptanoids exhibited promising in vitro and ex vivo antitubercular activity for the first time against dormant Mycobacterium tuberculosis H37Ra with the IC50 values between 0.34-47.69 and 0.13-22.91 µM, respectively. All compounds showed comparable activity against Mycobacterium bovis BCG (dormant phage) and did not show any activity against two gram + ve and two gram -ve bacterial strains. These compounds were also weakly cytotoxic up to 300 µM against three human cancer cell lines THP-1, Panc-1 and A549.
RESUMEN
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-(4â³-hydroxy-3â³-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-(4â³-hydroxy-3â³-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.
Asunto(s)
Alpinia/inmunología , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Inhibidores de la Ciclooxigenasa 2/farmacología , Extractos Vegetales/farmacología , Animales , Antiinflamatorios/aislamiento & purificación , Antioxidantes/aislamiento & purificación , Ciclooxigenasa 2/metabolismo , Inhibidores de la Ciclooxigenasa 2/aislamiento & purificación , Femenino , Flavonoides/aislamiento & purificación , Ácidos Heptanoicos/aislamiento & purificación , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Chaperonas Moleculares/metabolismo , Extractos Vegetales/aislamiento & purificación , Unión Proteica/efectos de los fármacos , Ratas , Ratas Wistar , RizomaRESUMEN
One pot synthesis of 3-Aracylphthalide was accomplished in good yield by reacting 2-carboxy benzaldehyde with various aromatic methyl ketones in presence of methane sulphonic acid. Various phthalides thus obtained were characterized with spectral techniques. These phthalides were subjected to in vitro antitubercular screening against Mycobacterium tuberculosis H37Ra (MTB) by using XRMA protocol. Among the phthalides screened, four exhibited half maximal inhibitory concentration (IC(50)) in the range of 0.81-1.24 µg/ml thereby providing potential lead compounds for future drug discovery studies.