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Siegesbeckia glabrescens is generally grown in fields or roadsides in Korea and used for the treatment of inflammatory diseases. The effects of S. glabrescens on periodontitis are unknown. In this study, we determined the effects of an S. glabrescens 30% EtOH extract (SGE) on periodontitis and analyzed the antioxidant activity (DPPH, ABTS, and SOD), antimicrobial (disc diffusion, MIC, and MBC), inhibition of GTFs, biofilm formation, and the anti-inflammation of lipopolysaccharide from P. gingivalis (LPS-PG)-induced primary equine periodontal ligament fibroblasts (PDLFs). We report that SGE increased DPPH, ABTS, and SOD antioxidant activities in a dose-dependent manner. SGE caused a clear zone with a diameter of 15 mm or more against periodontal pathogens. SGE (2.50 mg/mL) inhibited GTFs and biofilm by 89.07% and 85.40%, respectively. SGE treatment (100 µg/mL) also significantly decreased the secretion of inflammatory mediators in sensitized PDLF, including cytokines and matrix metalloproteinase (MMP)-3, -8, -9, and -13. Overall, we confirmed that SGE had excellent antioxidant, antimicrobial, and anti-inflammatory effects against periodontal pathogens. These results suggest that it has the potential to develop as a prophylactic agent for periodontitis. [ABSTRACT FROM AUTHOR]

The accumulation of cholesterol-bearing macrophage foam cells in the initial stages of atherosclerosis serves as a characteristic feature of atherosclerotic lesions. The inhibitory effect of Siegesbeckia glabrescens , a species of flowering plant in the Asteraceae family, on foam cell formation in THP-1 macrophages has not yet been elucidated. In this study, we explored the effect of S. glabrescens ethanol extract (SGEE) and hot water extract (SGWE) on foam cell formation via co-treatment with oxidized low density lipoprotein (ox-LDL) and lipopolysaccharide (LPS), mimicking the occurrence of atherosclerosis in vitro , and studied the regulation of its underlying mechanisms. THP-1 cells differentiated by PMA (1 μM) for 48 h were subsequently treated with/without SGWE and SGEE for 48 h. THP-1 macrophages were treated with ox-LDL (20 μg/mL) and LPS (500 ng/mL) for 24 h. Treatment with ox-LDL and LPS for 24 h enhanced the lipid accumulation in foam cells compared to in untreated cells, as determined by oil red O staining. In contrast, SGWE and SGEE treatment inhibited lipid accumulation in foam cells. Both extracts significantly upregulated ABCA1, LXRα, and PPARγ expression in ox-LDL- and LPS-treated cells ( P <0.05). Moreover, both SGWE and SGEE decreased LOX-1, CD36, and SR-A1 expression. The co-treatment of ox-LDL and LPS increased NF-κB, COX-2, and pro-inflammatory activation and expression compared with untreated cells. However, this increase suppressed NF-κB, COX-2, and pro-inflammatory expression by SGWE and SGEE. The results indicated that both extracts can partially inhibit foam cell formation and contribute to protective effects by suppressing cholesterol accumulation during the onset of atherosclerosis., Competing Interests: AUTHOR DISCLOSURE STATEMENT The authors declare no conflict of interest., (© 2024 The Korean Society of Food Science and Nutrition.)

Siegesbeckia glabrescens is generally grown in fields or roadsides in Korea and used for the treatment of inflammatory diseases. The effects of S. glabrescens on periodontitis are unknown. In this study, we determined the effects of an S. glabrescens 30% EtOH extract (SGE) on periodontitis and analyzed the antioxidant activity (DPPH, ABTS, and SOD), antimicrobial (disc diffusion, MIC, and MBC), inhibition of GTFs, biofilm formation, and the anti-inflammation of lipopolysaccharide from P. gingivalis (LPS-PG)-induced primary equine periodontal ligament fibroblasts (PDLFs). We report that SGE increased DPPH, ABTS, and SOD antioxidant activities in a dose-dependent manner. SGE caused a clear zone with a diameter of 15 mm or more against periodontal pathogens. SGE (2.50 mg/mL) inhibited GTFs and biofilm by 89.07% and 85.40%, respectively. SGE treatment (100 µg/mL) also significantly decreased the secretion of inflammatory mediators in sensitized PDLF, including cytokines and matrix metalloproteinase (MMP)-3, -8, -9, and -13. Overall, we confirmed that SGE had excellent antioxidant, antimicrobial, and anti-inflammatory effects against periodontal pathogens. These results suggest that it has the potential to develop as a prophylactic agent for periodontitis.

Abstract Background Herba Siegesbeckiae (HS, Xixiancao in Chinese) is a commonly used traditional Chinese medicinal herb for soothing joints. In ancient materia medica books, HS is recorded to be the aerial part of Siegesbeckia pubescens Makino (SP) which is also the only origin of HS in the 1963 edition of the Chinese Pharmacopeia (ChP). The aerial parts of Siegesbeckia orientalis L. (SO) and Siegesbeckia glabrescens Makino (SG) have been included as two additional origins for HS in each edition of ChP since 1977. However, chemical and pharmacological comparisons among these three species have not been conducted. Methods An HPLC with diode array detector (HPLC-DAD) method combined with similarity analysis, hierarchical cluster analysis (HCA) and principal component analysis (PCA) was developed for comparing the fingerprint chromatograms of the three species. The inhibitory effects of the three species on NO production and IL-6 secretion in LPS-stimulated RAW264.7 macrophages were compared. Results Fingerprint chromatograms of the three species showed different profiles, but had 13 common peaks. Results from HCA and PCA of the common peaks demonstrated that all 14 herbal samples of the three species tended to be grouped and separated species dependently. The extents of inhibition on NO production and IL-6 secretion of the three species were different, with SG being the most and SP the least potent. Conclusions Both chemical profiles and inflammatory mediator-inhibitory effects of the three species were different. These findings provide a chemical and pharmacological basis for determining whether the three species can all serve as the origins of HS.

Siegesbeckia glabrescens (Compositae), an annual herb indigenous to Korean mountainous regions and has been eaten as a food in Korea. This study investigated ABTS, DPPH and nitric oxide (NO) radical-scavenging activities, and melanin production and TYR inhibitory effects-guided fractionation to identify therapeutic phytochemicals from S. glabrescens that can attenuate oxidation and melanogenesis in murine melanoma B16F10 cells. Nine compounds with inhibitory effects on melanin production, and TYR activity, and ABTS, DPPH, and NO radical scavenging activity were isolated from the 100% ethanol fraction from S. glabrescens. Among the nine compounds, kirenol (K), methyl ent-16α, 17-dihydroxy-kauran-19-oate (MDK) had strong inhibitory effects on melanin production and TYR activity with antioxidant effects. Western blot analysis revealed that K and MDK suppressed tyrosinase-related protein (TYRP)-1, TYRP-2 and microphthalmia-associated transcription factor (MITF) expression. Moreover, these two compounds inhibited intracellular reactive oxygen species (ROS) level in tert-butyl hydroperoxide (t-BHP)-treated B16F10 cells. Our results suggest that S. glabrescens containing active compounds such as K and MDK, which has antioxidant and antimelanogenesis effects, is the potent therapeutic and functional material for the prevention of oxidation-induced hyperpigmentation.

Two new sesquiterpenoids, siegenolides A (1) and B (2), and two known sesquiterpenes 3 and 4 were isolated from Siegesbeckia glabrescens. Their structures were elucidated by spectroscopic analyses, and they were further evaluated for their cytotoxic activities against human cancer cells (MCF-7, AsPC-1, SW480, HCT 116, HepG2, HeLa). Compounds 1–4 showed differential cytotoxic effects on the target cancer cells with IC50 values in the range of 0.9–33.3 μM.

The crude methanol extract of the dried aerial parts of Siegesbeckia glabrescens (Compositae) showed antibacterial activity against the foodborne pathogen Staphylococcus aureus. Bioactivity-guided separation led to the isolation of 3-(dodecanoyloxy)-2-(isobutyryloxy)-4-methylpentanoic acid from nature for the first time. The structure was determined by spectroscopic data analysis (UV, MS, and NMR). The minimal inhibitory concentration (MIC) of 3-(dodecanoyloxy)-2-(isobutyryloxy)-4-methylpentanoic acid against S. aureus was found to be 3.12 μg/mL. In addition, in a further antimicrobial activity assay against Gram-positive (B. subtilis, E. faecalis, P. acnes, S. epidermidis, S. schleiferi subsp. coagulans, S. agalactiae and S. pyrogens), and Gram-negative bacteria (E. coli and P. aeruginosa), and yeast strains (C. alibicans and F. neoformans), the antimicrobial activity of the compound was found to be specific for Gram-positive bacteria. The MIC values of the compound for Gram-positive bacteria ranged from 3.12 to 25 mg/mL. Furthermore, it was found that the 2-(isobutyryloxy)-4-methylpentanoic acid substituent may operate as a key factor in the antibacterial activity of the compound, together with the laurate group.

Pancreatic cancer is aggressive and therefore difficult to treat; however, continued efforts have been made with the aim of developing an effective therapy against the disease. The Hedgehog (Hh) signaling pathway is reportedly involved in the proliferation and survival of pancreatic cancer cells. The transcription factor glioma-associated oncogene (Gli) is a key component of the Hh signaling pathway and the primary effector of pancreatic cancer development. Inhibiting Gli is a proven therapeutic strategy for this disease. The present study examined the regulation of Gli and the expression of its target genes to identify an inhibitor of the Sonic Hh (Shh) pathway. A germacranolide sesquiterpene lactone (GSL) was isolated from Siegesbeckia glabrescens as an inhibitor of Gli-mediated transcription. The results demonstrated that GSL inhibited Shh-induced osteoblast differentiation and Gli homolog 1 (Gli1)-mediated transcriptional activity in mesenchymal C3H10T1/2 stem cells. Furthermore, GSL suppressed Gli-mediated transcriptional activity in human pancreatic cancer PANC-1 and AsPC-1 cells, which resulted in reduced cancer cell proliferation and downregulated expression of the Gli-target genes, Gli1 and cyclin D1. A sesquiterpene lactone from S. glabrescens may therefore serve as a candidate for the treatment of Hh/Gli-dependent pancreatic cancer. [ABSTRACT FROM AUTHOR]

Siegesbeckia glabrescens (SG) is a plant growing in Korea that is used as a traditional medicine for various inflammatory diseases. In this study, we investigated the protective effects of SG extract on allergic asthma in an ovalbumin (OVA)-induced asthma murine model and lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Female BALB/c mice were sensitized by intraperitoneal injection of OVA on days 0 and 14 and then challenged with OVA from days 21 to 23. SG (30 mg/kg) was administered by oral gavage 1 h before the OVA challenge. LPS-stimulated RAW264.7 cells were evaluated to determine their levels of nitric oxide (NO). The SG significantly reduced the number of inflammatory cells in bronchoalveolar lavage (BAL) fluid and also reduced IL-4, IL-5, IL-13, eotaxin and immunoglobulin E in OVA-sensitized/challenged mice. SG also effectively reduced airway inflammation and mucus overproduction in lung tissue in addition to decreasing the expression of iNOS and COX-2. In LPS-stimulated RAW264.7 cells, SG treatment significantly reduced the levels of NO. These findings indicate that SG effectively suppressed inflammatory responses, and its effects appear to be related to reduction in iNOS and COX-2 expression. Therefore, we suggest that SG may have potential use as a therapeutic agent for inflammatory diseases such as allergic asthma. [ABSTRACT FROM AUTHOR]

Siegesbeckia glabrescens (SG) Makino (Compositae) has been used as a traditional medicine for the treatment of allergic and inflammatory diseases. In the present study, we examined the effects and molecular mechanism of the ethanol extract of SG on cell proliferation and invasion in p53 wild-type A549 and p53-deficient H1299 non-small cell lung cancer (NSCLC) cells. SG treatment markedly inhibited the proliferation and invasion in both cell lines, independently of p53 expression. The anti-proliferative effect of SG on A549 cells was mediated by the inactivation of Akt and p70S6K as evidenced by treatment with LY294002 and rapamycin, respectively. In addition, anti-invasive activity of SG in A549 cells was found to be associated with the inhibition of p70S6K. In contrast, in H1299 cells the inactivation of p38MAPK appeared to be involved in SG-mediated inhibition of cell proliferation and invasion. Collectively, these findings suggest that SG modulates cellular fates such as proliferation and invasion by differential regulation of signaling pathways, depending on the status of p53 expression in NSCLC, and support the development of SG as a potent therapeutic agent for the treatment of NSCLC. [ABSTRACT FROM AUTHOR]

The crude methanol extract of the dried aerial parts of Siegesbeckia glabrescens (Compositae) showed antibacterial activity against the foodborne pathogen Staphylococcus aureus. Bioactivity-guided separation led to the isolation of 3-(dodecanoyloxy)-2- (isobutyryloxy)-4-methylpentanoic acid from nature for the first time. The structure was determined by spectroscopic data analysis (UV, MS, and NMR). The minimal inhibitory concentration (MIC) of 3-(dodecanoyloxy)-2-(isobutyryloxy)-4-methylpentanoic acid against S. aureus was found to be 3.12 μg/mL. In addition, in a further antimicrobial activity assay against Gram-positive (B. subtilis, E. faecalis, P. acnes, S. epidermidis, S. schleiferi subsp. coagulans, S. agalactiae and S. pyrogens), and Gram-negative bacteria (E. coli and P. aeruginosa), and yeast strains (C. alibicans and F. neoformans), the antimicrobial activity of the compound was found to be specific for Gram-positive bacteria. The MIC values of the compound for Gram-positive bacteria ranged from 3.12 to 25 μg/mL. Furthermore, it was found that the 2-(isobutyryloxy)-4-methylpentanoic acid substituent may operate as a key factor in the antibacterial activity of the compound, together with the laurate group. [ABSTRACT FROM AUTHOR]

Abstract: The immunomodulatory effect of Siegesbeckia glabrescens extract-supplementation diets on innate immune response and disease resistance of kelp grouper, Epinephelus bruneus against Vibrio parahaemolyticus at weeks 1, 2, and 4 is reported. The serum lysozyme activity was significantly enhanced with any enriched diet from weeks 1–4 when compared to control diet (0%). The alternative complement haemolytic activities significantly were enhanced with all enriched diets on weeks 2 and 4 whereas the cellular reactive oxygen species (ROS) was significantly enhanced only with 1.0% and 2.0% diets. The reactive nitrogen intermediate (RNI) value was significantly enhanced with any enriched diet on weeks 2 and 4, but on first week it did not differ from control. The myeloperoxidase (MPO) production significantly increased with 1.0% and 2.0% diets from second week onwards; with other enriched diets the increase manifested on fourth week; but during first week it did not vary from that of the control with any enriched diet. The protection in terms of cumulative mortality was the least being 25% and 20% when fed with 1.0% and 2.0% diets. The present results indicate that feeding kelp grouper with S. glabrescens extract enriched diet at 1.0% and 2.0% levels significantly enhance the immunological parameters, increase the disease resistance and minimize the cumulative mortality in E. bruneus against V. parahaemolyticus. [Copyright &y& Elsevier]

The aim of this study is to elucidate the anti-inflammatory effects of Siegesbeckia glabrescens extract in vitro. The n-butanol fraction (100 µg/ml) of S. glabrescens had an approximately 92% inhibitory effect on nitrite production from lipopolysaccharide (LPS)-induced macrophage cells, whereas other fractions showed relatively low nitric oxide (NO) inhibition. The n-butanol and ethyl acetate fractions of S. glabrescens showed significant chemical NO quenching to approximately 39-46% in the cell-free system, and showed the decreases of inducible nitric oxide synthase (iNOS) transcription potently. The hexane, n-butanol, and ethyl acetate fractions of S. glabrescens showed approximately 90-96% inhibition of prostaglandin E2 (PGE2) synthesis. The ethyl acetate, n-butanol, and aqueous fractions of S. glabrescens showed a potent inhibition of LPS-induced cyclooxygenase-2 (COX-2) mRNA transcription. All S. glabrescens extract-fractions showed significant decreases of IL-1β biosynthesis to 69.7-97.0%, as compared to LPS-induced IL-1β production in macrophage cells. [ABSTRACT FROM AUTHOR]

Abstract: Four flavones, 3,4′-O-dimethylquercetin (1), 3,7-O-dimethylquercetin (2), 3-O-methylquercetin (3) and 3,7,4′-O-trimethylquercetin (4) were isolated as the inhibitors of nitric oxide production in activated microglia (IC50 values: 11.1, 4.2, 3.8, and 25.1μM, respectively). They suppressed the expression of protein and mRNA of inducible nitric oxide synthase. Furthermore, compounds 2 and 3 showed scavenging activity of peroxynitrite with SC50 values of 1.75 and 0.77μM, respectively. [Copyright &y& Elsevier]

Protein tyrosine phosphatase 1B (PTP1B) is considered as a therapeutic target for the treatment of diabetes and obesity. In our preliminary screening study, a MeOH extract of the aerial part of Siegesbeckia glabrescens was found to inhibit PTP1B activity at 30 μg/mL. Bioassay‐guided fractionation led to the isolation of two active diterpenes, ent -16βH,17-isobutyryloxy-kauran-19-oic acid ( 1 ) and ent -16βH,17-acetoxy-18-isobutyryloxy-kauran-19-oic acid ( 2 ), along with ent -16βH,17-hydroxy-kauran-19-oic acid ( 3 ). Compounds 1 and 2 inhibited the PTP1B activity with IC 50 values of 8.7 ± 0.9 and 30.6 ± 2.1 μM, respectively. Kinetic studies suggest that both 1 and 2 are non-competitive inhibitors of PTP1B. However, compound 3 substituted with a hydroxyl group at C-17 in kaurane-type showed no inhibitory effects towards PTP1B. [ABSTRACT FROM AUTHOR]

Siegesbeckia glabrescens (Compositae), an annual herb indigenous to Korean mountainous regions and has been eaten as a food in Korea. This study investigated ABTS, DPPH and nitric oxide (NO) radical-scavenging activities, and melanin production and TYR inhibitory effects-guided fractionation to identify therapeutic phytochemicals from S. glabrescens that can attenuate oxidation and melanogenesis in murine melanoma B16F10 cells. Nine compounds with inhibitory effects on melanin production, and TYR activity, and ABTS, DPPH, and NO radical scavenging activity were isolated from the 100% ethanol fraction from S. glabrescens. Among the nine compounds, kirenol (K), methyl ent-16α, 17-dihydroxy-kauran-19-oate (MDK) had strong inhibitory effects on melanin production and TYR activity with antioxidant effects. Western blot analysis revealed that K and MDK suppressed tyrosinase-related protein (TYRP)-1, TYRP-2 and microphthalmia-associated transcription factor (MITF) expression. Moreover, these two compounds inhibited intracellular reactive oxygen species (ROS) level in tert-butyl hydroperoxide (t-BHP)-treated B16F10 cells. Our results suggest that S. glabrescens containing active compounds such as K and MDK, which has antioxidant and antimelanogenesis effects, is the potent therapeutic and functional material for the prevention of oxidation-induced hyperpigmentation. [ABSTRACT FROM AUTHOR]

Seven rare oxylipins, siegesbeckins A–G (1 – 7) representing further bioactive constituents different from the general terpenyl compounds found in Siegesbeckia species, have been obtained from the aerial parts of Siegesbeckia glabrescens. These isolates were identified to be a series of methyl 4-methylpentanoates incorporating fatty acid moieties of different chain lengths, based on spectroscopic techniques, and their absolute configurations were determined via chemical degradation and comparison of experimental and theoretically calculated ECD spectra. With respect to bioactivity, antibacterial, anti-inflammatory and cytotoxic properties of selected compounds were evaluated. Compounds 1 and 5 showed moderate antibacterial activity against two Gram-positive bacteria with MIC values of 4.3 μg/mL, while 3 showed no pronounced activity in these assays. Unlabelled Image • Seven rare oxylipins were separated and identified from the aerial parts of Siegesbeckia glabrescens. • The absolute configurations were established via chemical degradation and analysis of ECD data. • Two compounds with shorter fatty acid chains displayed mild antibacterial activity against Gram-positive bacteria. [ABSTRACT FROM AUTHOR]

Anti-photoaging effects of standardized Siegesbeckia glabrescens extract (SGE) and its major active compound kirenol were investigated using Hs68 human dermal fibroblasts and hairless mice, respectively. UVB-irradiated hairless mice that received oral SGE (600 mg/kg/day) showed reduced wrinkle formation and skinfold thickness compared with the UVB-irradiated control. Furthermore, SGE treatment increased the mRNA levels of collagen synthesis genes (COL1A1, COL3A1, COL4A1, and COL7A1) and activated antioxidant enzyme (catalase), while suppressing matrix metalloproteinase (MMP-2, -3, -9, and -13) expression. In Hs68 fibroblasts, kirenol also significantly suppressed MMP expression while increasing the expression of COL1A1, COL3A1, and COL7A1. Collectively, our data demonstrate that both SGE and kirenol attenuated UVB-induced photoaging in hairless mice and fibroblasts through inhibition of the mitogen-activated protein kinases and nuclear factor kappa B pathways, suggesting that SGE has potential to serve as a natural anti-photoaging nutraceutical.

Pancreatic cancer is aggressive and therefore difficult to treat; however, continued efforts have been made with the aim of developing an effective therapy against the disease. The Hedgehog (Hh) signaling pathway is reportedly involved in the proliferation and survival of pancreatic cancer cells. The transcription factor glioma-associated oncogene (Gli) is a key component of the Hh signaling pathway and the primary effector of pancreatic cancer development. Inhibiting Gli is a proven therapeutic strategy for this disease. The present study examined the regulation of Gli and the expression of its target genes to identify an inhibitor of the Sonic Hh (Shh) pathway. A germacranolide sesquiterpene lactone (GSL) was isolated from Siegesbeckia glabrescens as an inhibitor of Gli-mediated transcription. The results demonstrated that GSL inhibited Shh-induced osteoblast differentiation and Gli homolog 1 (Gli1)-mediated transcriptional activity in mesenchymal C3H10T1/2 stem cells. Furthermore, GSL suppressed Gli-mediated transcriptional activity in human pancreatic cancer PANC-1 and AsPC-1 cells, which resulted in reduced cancer cell proliferation and downregulated expression of the Gli-target genes, Gli1 and cyclin D1. A sesquiterpene lactone from S. glabrescens may therefore serve as a candidate for the treatment of Hh/Gli-dependent pancreatic cancer.

A new sesquiterpene lactone was isolated from Siegesbeckia glabrescens as an inhibitor of nitric oxide and prostaglandin E2 synthesis in the LPS-activated RAW264.7 macrophage cell line. It dose-dependently decreased the protein and mRNA levels of inducible nitric oxide synthase and cyclooxygenase-2. Reporter gene assay revealed that the compound attenuated the LPS-induced DNA transcriptional activity of nuclear factor-kappa B (NF-κB). In addition, it inhibited the nuclear translocation of the p65 subunit of NF-κB by blocking the inhibitory kappa B-α degradation. This compound from Siegesbeckia glabrescens might be beneficial for the treatment of inflammation-related diseases., (Copyright © 2011 John Wiley & Sons, Ltd.)