Three New Ent-Kaurane Diterpenes with Antibacterial Activity from Sigesbeckia orientalis.

Three novel ent-kaurane diterpenes, namely sigesbeckin A-C (1-3), in conjunction with eight previously identified analogues (4-11), were isolated from Sigesbeckia orientalis. Their chemical structures were resolved through multiple spectroscopic analyses. All compounds were assessed for antimicrobial bioactivity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) strains. In particular, compounds 1 and 5 demonstrated moderate efficacy, with MIC values of 64 µg/mL. Moreover, compounds 3, 5, and 11 were found to synergize with doxorubicin hydrochloride (DOX) and vancomycin (VAN) against MRSA and VRE. The aforementioned findings offer valuable insights for the development of novel alternatives to antibiotics, which can effectively tackle the escalating issue of antibiotic resistance.

Diterpenoid glucosides with anti-inflammatory activity from Sigesbeckia glabrescens.

Six previously undescribed diterpenoid glucosides, along with four known compounds, were isolated from the aerial parts of Sigesbeckia glabrescens. The structures and absolute configurations of undescribed compounds were elucidated using extensive spectroscopic techniques, ECD calculations and chemical methods. Compounds 1 and 8 exhibited anti-inflammatory activity against LPS-induced NO production in RAW 264.7 macrophages, with compound 8 demonstrating significant inhibitory activity compared to positive control minocycline, boasting an IC50 value at 14.20 µM.

Effect of Mosquitocidal, histopathological alteration and non target effects of Sigesbeckia orientalis L. on Anopheles stephensi Liston, Culex quinquefasciatus say and Aedes aegypti L.

Diseases transmitted by vectors have a significant collision on society and community health, particularly in tropical and subtropical regions, where they can cause large-scale outbreaks shortly after initial transmission. The intent of this investigation was to study the plant extract derived from Sigesbeckia orientalis L. in controlling the immature stages of Anopheles, Culex and Aedes mosquitoes, while also considering its potential toxicity to ecosystems. The immature stages were exposed to different extracts (62.5-500 ppm), and the mortality of larvae and pupae, as well as ovicidal activity, were noted after 24 and 120 h of the experiment. The hexane and ethyl aceate extract of S. orientalis presented 100% ovicidal activity against the eggs of Anopheles, Aedes and Culex at 500 ppm concentration after 5 days of treatment. The hexane and ethylacetate extracts presented strong larvicidal activity with LC50 values of 215.7, 332.0, 197.4 and 212.6, 694.9 and 201.7 ppm against treated mosquitoes at 24 h, respectively. The same extract also presented promising pupicidal activity. The LC50 values of hexane extract were 219.6, 353.6, 194.2 and LC50 values of ethyl acetate were 257.6, 387.8 and 259.07 ppm against early stage pupae of three vector mosquitoes, respectively. The extracts from S. orientalis had strong inhibitory activity against growth and development of mosquitoes. SI/PSF values showed that the extracts of S. orientalis did not harm Poecilia reticulata, Diplonychus indicus (Water bug), Gambusia affinis and dragon fly nymph at tested concentrations. Furthermore, examinations of histopathology and growth disruption revealed significant damage to the midgut cells in the treated larvae. The formulations utilizing hexane and ethyl acetate extracts exhibited potent activity without posing any toxicity towards non-target organisms. This study clearly indicated that hexane and ethylacetate extracts showed promising results against treated mosquitoes. The present study documents the first report of the extracts from S. orientalis and they can be further assessed to identify compounds for application purposes.

Effects of Siegesbeckia herba extract against particulate matter 10 (PM10 ) in skin barrier-disrupted mouse models.

OBJECTIVES: Skin barrier disruption is a significant problem of the older population in an aging society. It is characterized by increased transepidermal water loss and decreased skin water content, and particulate matter (PM) is a social issue that can contribute to the exacerbation of skin inflammation. Thus, addressing this problem is urgent. METHODS: Skin barrier-disrupted mouse models were induced by two methods using acetone application or tape-stripping. This study investigated the antioxidative and anti-inflammatory properties of the Siegesbeckia herba extract (SHE) on PM-induced changes in skin barrier-disrupted mouse models. To examine changes in skin water content, inflammatory cytokines, and keratinocyte differentiation markers, mouse models were treated with vehicle 100 µL, PM10 100 µL (100 µg/mL), SHE 100 µL, or PM10 100 µL (100 µg/mL) plus SHE 100 µL. RESULTS: SHE preserved skin hydration in the skin barrier-disrupted mouse models regardless of the presence of PM10 . SHE also inhibited the upregulation of inflammatory cytokines such as interleukin (IL)-1ß, IL-4, IL-6, IL-8, and tumor necrosis factor-α and normalized the downregulation of keratinocyte differentiation markers against PM10 in skin barrier-disrupted mouse models. CONCLUSIONS: This study elucidated the therapeutic effects of SHE against PM10 in skin barrier-disrupted mouse models.

Inhibitory Potential of Quercetin Derivatives Isolated from the Aerial Parts of Siegesbeckia pubescens Makino against Bacterial Neuraminidase.

This study aimed to isolate bacterial neuraminidase (BNA) inhibitory O-methylated quercetin derivatives from the aerial parts of S. pubescens. All the isolated compounds were identified as O-methylated quercetin (1-4), which were exhibited to be noncompetitive inhibitors against BNA, with IC50 ranging from 14.0 to 84.1 µM. The responsible compounds (1-4) showed a significant correlation between BNA inhibitory effects and the number of O-methyl groups on quercetin; mono (1, IC50 = 14.0 µM) > di (2 and 3, IC50 = 24.3 and 25.8 µM) > tri (4, IC50 = 84.1 µM). In addition, the binding affinities between BNA and inhibitors (1-4) were also examined by fluorescence quenching effect with the related constants (KSV, KA, and n). The most active inhibitor 1 possessed a KSV with 0.0252 × 105 L mol-1. Furthermore, the relative distribution of BNA inhibitory O-methylated quercetins (1-4) in S. pubescens extract was evaluated using LC-Q-TOF/MS analysis.

Therapeutic effects of Siegesbeckia orientalis L. and its active compound luteolin in rheumatoid arthritis: network pharmacology, molecular docking and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Rheumatoid arthritis (RA) is a common difficult disease with a high disability rate. Siegesbeckia orientalis L. (SO), a Chinese medicinal herb that is commonly used for treating RA in clinical practice. While, the anti-RA effect and the mechanisms of action of SO, as well as its active compound(s) have not been elucidated clearly. AIM OF THE STUDY: We aim to explore the molecular mechanism of SO against RA by using network pharmacology analysis, as well as the in vitro and in vivo experimental validations, and to explore the potential bioactive compound(s) in SO. METHODS: Network pharmacology is an advanced technology that provides us an efficient way to study the therapeutic actions of herbs with the underlying mechanisms of action delineated. Here, we used this approach to explore the anti-RA effects of SO, and then the molecular biological approaches were used to verify the prediction. We first established a drug-ingredient-target-disease network and a protein-protein interaction (PPI) network of SO-related RA targets, followed by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Further, we used lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and vascular endothelial growth factor-A (VEGFA)-induced human umbilical vein endothelial cell (HUVEC) models, as well as adjuvant-induced arthritis (AIA) rat model to validate the anti-RA effects of SO. The chemical profile of SO was also determined by using the UHPLC-TOF-MS/MS analysis. RESULTS: Network pharmacology analysis highlighted inflammatory- and angiogenesis-related signaling pathways as promising pathways that mediate the anti-RA effects of SO. Further, in both in vivo and in vitro models, we found that the anti-RA effect of SO is at least partially due to the inhibition of toll like receptor 4 (TLR4) signaling. Molecular docking analysis revealed that luteolin, an active compound in SO, shows the highest degree of connections in compound-target network; moreover, it has a direct binding to the TLR4/MD-2 complex, which is confirmed in cell models. Besides, more than forty compounds including luteolin, darutoside and kaempferol corresponding to their individual peaks were identified tentatively via matching with the empirical molecular formulae and their mass fragments. CONCLUSION: We found that SO and its active compound luteolin exhibit anti-RA activities and potently inhibit TLR4 signaling both in vitro and in vivo. These findings not only indicate the advantage of network pharmacology in the discovery of herb-based therapeutics for treating diseases, but also suggest that SO and its active compound(s) could be developed as potential anti-RA therapeutic drugs.

ent-Pimarane Diterpenes from the Aerial Parts of Siegesbeckia pubescens.

Five new ent-pimarane diterpenes (1-5) and five known analogs (6-10) were isolated from the aerial parts of Siegesbeckia pubescens. Their structures, including absolute configurations, were determined by comprehensive spectroscopic methods especially 1D and 2D NMR and quantum chemical electronic circular dichroism calculations. All the isolated compounds were evaluated for their cytotoxicity against human BT549, A549 and H157 cancer cell lines. Among them, compounds 1 and 2 showed mild cytotoxicity against lung cancer cell lines H157 with IC50 values of 16.35±2.59 and 18.86±4.83 µM, respectively.

Diterpenoids from Sigesbeckia glabrescens with anti-inflammatory and AChE inhibitory activities.

Fourteen previously undescribed diterpenoids, including seven ent-pimarane-type diterpenoids and seven phytane-type diterpenes, together with five known ones, were isolated from the aerial parts of Sigesbeckia glabrescens. The structures and absolute configurations of undescribed compounds were elucidated based on extensive spectroscopic techniques, ECD calculations, Mo2(OAC)4-induced ECD, Rh2(OCOCF3)4-induced ECD, calculated 13C NMR, and chemical methods. In the anti-inflammatory bioassay, siegetalis H showed potent inhibitory effect on LPS-induced NO production in RAW264.7 murine macrophages with an IC50 value at 17.29 µM. Furthermore, siegetalis H suppressed the protein expression of iNOS and COX-2 in LPS-stimulated RAW264.7 cells. Mechanistically, siegetalis H suppressed the phosphorylation and degradation of IκBα, as well as the activation of the NF-κB signaling pathway. In addition, the AChE inhibition assay displayed that 3-O-acetyldarutigenol had a remarkable inhibitory effect against AChE with an IC50 value at 7.02 µM. Kinetic study on 3-O-acetyldarutigenol indicated that it acted as a mixed-type inhibitor, and the binding mode was explored by molecular docking.