Inula helenium L. is rich source of eudesmane-type sesquiterpene lactones, mainly alantolactone and isoalantolactone, which have the various pharmacological functions. In this study, we examined the inhibitory effects of nitric oxide (NO) production of hexane, methylene chloride, ethyl acetate, butanol, and water fractions from I. helenium and investigated the anti-inflammatory effect of hexane fraction of I. helenium (HFIH) in LPS-induced RAW 264.7 cells. Quantification of alantolactone and isoalantolactone from HFIH was carried out for the standardization by multiple reaction monitoring using triple quadrupole mass spectrometer. HFIH significantly inhibited inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) protein as well as their downstream products NO and prostaglandin E₂ (PGE₂) in LPS-stimulated RAW 264.7 cells. Moreover, HFIH suppressed NF-κB transcriptional activity by decreasing the translocation of p65 to the nucleus. The in vivo study further confirmed that HFIH attenuated the paw edema induced by carrageenan in an acute inflammation model. These findings suggest that HFIH may be useful as a promising phytomedicine for inflammatory-associated diseases.
Carrageenan ; Cyclooxygenase 2 ; Edema ; Inflammation ; Inula ; Lactones ; Methylene Chloride ; Nitric Oxide ; Nitric Oxide Synthase ; RAW 264.7 Cells ; Staphylococcal Protein A ; Water

The aerial parts of Saururus chinensis (Lour.) Baill., known for its rich lignan content and diversepharmacological activities such as anti-inflammatory and anticancer effects, has not been extensively explored for its potential in preventing obesity. In this study, we investigated the inhibitory effect of methylene chloride fraction of S.chinensis (MCSC) on adipocyte differentiation using experimental models. Furthermore, we conducted a comprehensive chemical analysis employing HPLC and LC-ESI/MS to identify and characterize the main compounds responsible for these effects. MCSC significantly inhibited preadipocyte differentiation, accompanied by down-regulation of target genes involved in lipid synthesis and storage. This anti-adipogenic effect was mediated by the inhibition of CCAAT/ enhancer binding protein α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ) expression. In a mouse model, oral administration of MCSC resulted in reduced body weight and adipose tissue weight, along with improvements in serum lipid profiles in high-fat diet-induced C57BL/6 obese mice. Active ingredients were identified as manassantin A and manassantin B through comparison of their spectrometric features with previously reported data.This evidence suggests that MCSC could be a potential candidate for the treatment and prevention of obesity-associateddiseases.

Sesquiterpene lactones, a class of natural compounds abundant in the Asteraceae family, have gained attention owing to their diverse biological activities, and particularly their anti-proliferative effects on human cancer cells. In this study, we systematically investigated the structure-activity relationship of ten sesquiterpene lactones with the aim of elucidating the structural determinants for the STAT3 inhibition governing their anti-proliferative effects. Our findings revealed a significant correlation between the STAT3 inhibitory activity and the anti-proliferative effects of sesquiterpene lactones in MDA-MB-231 breast cancer cell lines. Among the compounds tested, alantolactone and isoalantolactone emerged as the most potent STAT3 inhibitors, highlighting their potential as candidates for anticancer drug development. Through protein-ligand docking studies, we revealed the structural basis of STAT3 inhibition by sesquiterpene lactones, emphasizing the critical role of hydrogen-bonding interactions with key residues, including Arg609, Ser611, Glu612, and Ser613, in the SH2 domain of STAT3. Furthermore, our conformational analysis revealed the decisive role of the torsion angle within the geometry-optimized structures of sesquiterpene lactones in their STAT3 inhibitory activity (R=0.80, p<0.01). These findings not only provide preclinical evidence for sesquiterpene lactones as promising phytomedicines against diseases associated with abnormal STAT3 activation, but also highlight the importance of stereochemical aspects in their activity.

The aerial parts of Saururus chinensis (Lour.) Baill., known for its rich lignan content and diversepharmacological activities such as anti-inflammatory and anticancer effects, has not been extensively explored for its potential in preventing obesity. In this study, we investigated the inhibitory effect of methylene chloride fraction of S.chinensis (MCSC) on adipocyte differentiation using experimental models. Furthermore, we conducted a comprehensive chemical analysis employing HPLC and LC-ESI/MS to identify and characterize the main compounds responsible for these effects. MCSC significantly inhibited preadipocyte differentiation, accompanied by down-regulation of target genes involved in lipid synthesis and storage. This anti-adipogenic effect was mediated by the inhibition of CCAAT/ enhancer binding protein α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ) expression. In a mouse model, oral administration of MCSC resulted in reduced body weight and adipose tissue weight, along with improvements in serum lipid profiles in high-fat diet-induced C57BL/6 obese mice. Active ingredients were identified as manassantin A and manassantin B through comparison of their spectrometric features with previously reported data.This evidence suggests that MCSC could be a potential candidate for the treatment and prevention of obesity-associateddiseases.

Sesquiterpene lactones, a class of natural compounds abundant in the Asteraceae family, have gained attention owing to their diverse biological activities, and particularly their anti-proliferative effects on human cancer cells. In this study, we systematically investigated the structure-activity relationship of ten sesquiterpene lactones with the aim of elucidating the structural determinants for the STAT3 inhibition governing their anti-proliferative effects. Our findings revealed a significant correlation between the STAT3 inhibitory activity and the anti-proliferative effects of sesquiterpene lactones in MDA-MB-231 breast cancer cell lines. Among the compounds tested, alantolactone and isoalantolactone emerged as the most potent STAT3 inhibitors, highlighting their potential as candidates for anticancer drug development. Through protein-ligand docking studies, we revealed the structural basis of STAT3 inhibition by sesquiterpene lactones, emphasizing the critical role of hydrogen-bonding interactions with key residues, including Arg609, Ser611, Glu612, and Ser613, in the SH2 domain of STAT3. Furthermore, our conformational analysis revealed the decisive role of the torsion angle within the geometry-optimized structures of sesquiterpene lactones in their STAT3 inhibitory activity (R=0.80, p<0.01). These findings not only provide preclinical evidence for sesquiterpene lactones as promising phytomedicines against diseases associated with abnormal STAT3 activation, but also highlight the importance of stereochemical aspects in their activity.

Sesquiterpene lactones, a class of natural compounds abundant in the Asteraceae family, have gained attention owing to their diverse biological activities, and particularly their anti-proliferative effects on human cancer cells. In this study, we systematically investigated the structure-activity relationship of ten sesquiterpene lactones with the aim of elucidating the structural determinants for the STAT3 inhibition governing their anti-proliferative effects. Our findings revealed a significant correlation between the STAT3 inhibitory activity and the anti-proliferative effects of sesquiterpene lactones in MDA-MB-231 breast cancer cell lines. Among the compounds tested, alantolactone and isoalantolactone emerged as the most potent STAT3 inhibitors, highlighting their potential as candidates for anticancer drug development. Through protein-ligand docking studies, we revealed the structural basis of STAT3 inhibition by sesquiterpene lactones, emphasizing the critical role of hydrogen-bonding interactions with key residues, including Arg609, Ser611, Glu612, and Ser613, in the SH2 domain of STAT3. Furthermore, our conformational analysis revealed the decisive role of the torsion angle within the geometry-optimized structures of sesquiterpene lactones in their STAT3 inhibitory activity (R=0.80, p<0.01). These findings not only provide preclinical evidence for sesquiterpene lactones as promising phytomedicines against diseases associated with abnormal STAT3 activation, but also highlight the importance of stereochemical aspects in their activity.

The aerial parts of Saururus chinensis (Lour.) Baill., known for its rich lignan content and diversepharmacological activities such as anti-inflammatory and anticancer effects, has not been extensively explored for its potential in preventing obesity. In this study, we investigated the inhibitory effect of methylene chloride fraction of S.chinensis (MCSC) on adipocyte differentiation using experimental models. Furthermore, we conducted a comprehensive chemical analysis employing HPLC and LC-ESI/MS to identify and characterize the main compounds responsible for these effects. MCSC significantly inhibited preadipocyte differentiation, accompanied by down-regulation of target genes involved in lipid synthesis and storage. This anti-adipogenic effect was mediated by the inhibition of CCAAT/ enhancer binding protein α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ) expression. In a mouse model, oral administration of MCSC resulted in reduced body weight and adipose tissue weight, along with improvements in serum lipid profiles in high-fat diet-induced C57BL/6 obese mice. Active ingredients were identified as manassantin A and manassantin B through comparison of their spectrometric features with previously reported data.This evidence suggests that MCSC could be a potential candidate for the treatment and prevention of obesity-associateddiseases.

The aerial parts of Saururus chinensis (Lour.) Baill., known for its rich lignan content and diversepharmacological activities such as anti-inflammatory and anticancer effects, has not been extensively explored for its potential in preventing obesity. In this study, we investigated the inhibitory effect of methylene chloride fraction of S.chinensis (MCSC) on adipocyte differentiation using experimental models. Furthermore, we conducted a comprehensive chemical analysis employing HPLC and LC-ESI/MS to identify and characterize the main compounds responsible for these effects. MCSC significantly inhibited preadipocyte differentiation, accompanied by down-regulation of target genes involved in lipid synthesis and storage. This anti-adipogenic effect was mediated by the inhibition of CCAAT/ enhancer binding protein α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ) expression. In a mouse model, oral administration of MCSC resulted in reduced body weight and adipose tissue weight, along with improvements in serum lipid profiles in high-fat diet-induced C57BL/6 obese mice. Active ingredients were identified as manassantin A and manassantin B through comparison of their spectrometric features with previously reported data.This evidence suggests that MCSC could be a potential candidate for the treatment and prevention of obesity-associateddiseases.

Sesquiterpene lactones, a class of natural compounds abundant in the Asteraceae family, have gained attention owing to their diverse biological activities, and particularly their anti-proliferative effects on human cancer cells. In this study, we systematically investigated the structure-activity relationship of ten sesquiterpene lactones with the aim of elucidating the structural determinants for the STAT3 inhibition governing their anti-proliferative effects. Our findings revealed a significant correlation between the STAT3 inhibitory activity and the anti-proliferative effects of sesquiterpene lactones in MDA-MB-231 breast cancer cell lines. Among the compounds tested, alantolactone and isoalantolactone emerged as the most potent STAT3 inhibitors, highlighting their potential as candidates for anticancer drug development. Through protein-ligand docking studies, we revealed the structural basis of STAT3 inhibition by sesquiterpene lactones, emphasizing the critical role of hydrogen-bonding interactions with key residues, including Arg609, Ser611, Glu612, and Ser613, in the SH2 domain of STAT3. Furthermore, our conformational analysis revealed the decisive role of the torsion angle within the geometry-optimized structures of sesquiterpene lactones in their STAT3 inhibitory activity (R=0.80, p<0.01). These findings not only provide preclinical evidence for sesquiterpene lactones as promising phytomedicines against diseases associated with abnormal STAT3 activation, but also highlight the importance of stereochemical aspects in their activity.