[Prediction and analysis of Q-markers of Elephantopus scaber based on its UPLC fingerprint, content determination of components, and in vitro a nti-tumor activity].

This study aimed to provide scientific evidence for predicting quality markers(Q-markers) of Elephantopus scaber by establishing UPLC fingerprint of E. scaber from different geographical origins and determining the content of 13 major components, as well as conducting in vitro anti-cancer activity investigation of the main components. The chromatographic column used was Waters CORTECS UPLC C_(18)(2.1 mm×150 mm, 1.6 µm), and the mobile phase consisted of acetonitrile and 0.1% formic acid solution(gradient elution). The column temperature was set at 30 ℃, and the flow rate was 0.2 mL·min~(-1). The injection volume was 1 µL, and the detection wavelength was 240 nm. The UPLC fingerprint of E. scaber was fitted using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012 edition) to determine common peaks, evaluate similarity, identify and determine the content of major components. The CCK-8 assay was used to explore the inhibitory effect of the main components on the proliferation of lung cancer cells. The results showed that in the established UPLC fingerprint of E. scaber, 35 common peaks were identified. Thirteen major components, including neochlorogenic acid(peak 1), chlorogenic acid(peak 2), cryptochlorogenic acid(peak 3), caffeic acid(peak 4), schaftoside(peak 6), galuteolin(peak 9), isochlorogenic acid B(peak 10), isochlorogenic acid A(peak 12), isochlorogenic acid C(peak 18), deoxyelephantopin(peak 28), isodeoxyelephantopin(peak 29), isoscabertopin(peak 31), and scabertopin(peak 32) were identified and quantified, and a quantitative analysis method was established. The results of the in vitro anti-cancer activity study showed that deoxyelephantopin, isodeoxyelephantopin, isoscabertopin, and scabertopin in E. scaber exhibited inhibition rates of lung cancer cell proliferation exceeding 80% at a concentration of 10 µmol·L~(-1), higher than the positive drug paclitaxel. These results indicate that the fingerprint of E. scaber is highly characteristic, and the quantitative analysis method is accurate and stable, providing references for the research on quality standards of E. scaber. Four sesquiterpene lactones in E. scaber show significant anti-cancer activity and can serve as Q-markers for E. scaber.

Catechol-Modified and MnO2-Nanozyme-Reinforced Hydrogel with Improved Antioxidant and Antibacterial Capacity for Periodontitis Treatment.

Periodontitis is an inflammatory disease characterized by tooth loss and alveolar bone resorption. Bacteria are the original cause of periodontitis, and excess reactive oxygen species (ROS) encourage and intensify inflammation. In this study, a mussel-inspired and MnO2 NPs-reinforced adhesive hydrogel capable of alleviating periodontitis with improved antibacterial and antioxidant abilities was developed. The hydrogel was created by combining polyvinyl alcohol (PVA), 3,4-dihydroxy-d-phenylalanine (DOPA), and MnO2 nanoparticles (NPs) (named PDMO hydrogel). The hydrogel was demonstrated to be able to scavenge various free radicals (including total ROS─O2•- and OH•) and relieve the hypoxia in an inflammatory microenvironment by scavenging excess ROS and generating O2 due to its superoxide dismutase (SOD)/catalase (CAT)-like activity. Besides, under 808 nm near-infrared (NIR) light, the photothermal performance of the PDMO hydrogel displayed favorable antibacterial and antibiofilm effects toward Escherichia coli, Staphylococcus aureus, and Porphyromonas gingivalis (up to nearly 100% antibacterial rate). Furthermore, the PDMO hydrogel exhibited favorable therapeutic efficacy in alleviating gingivitis in Sprague-Dawley rats, even comparable to or better than the commercial PERIO. In addition, in the periodontitis models, the PDMO2 group showed the height of the residual alveolar bone and the smallest shadow area of low density among other groups, indicating the positive role of the PDMO2 hydrogel in bone regeneration. Finally, the biosafety of the PDMO hydrogel was comprehensively investigated, and the hydrogel was demonstrated to have good biocompatibility. Therefore, the developed PDMO hydrogel provided an effective solution to resolve biofilm recolonization and oxidative stress in periodontitis and could be a superior candidate for local drug delivery system in the clinical management of periodontitis with great potential for future clinical translation.

Electroacupuncture Modulates 5-HT4R-Mediated cAMP/PKA Signaling to Improve Intestinal Motility Disorders in a Thy1-αSyn Parkinson's Mouse Model.

Constipation is one of the most common nonmotor symptoms in patients with Parkinson's disease (PD) and often occurs before motor symptoms. Electroacupuncture effectively improves the symptoms of constipation in patients with PD. In the present study, we used thymus cell antigen 1-α-synuclein (Thy1-αSyn) transgenic mice as a model of intestinal motility disorders in PD to determine the therapeutic effect of electroacupuncture and the underlying mechanisms. Electroacupuncture significantly improved fecal excretion and accelerated the rate of small-intestinal propulsion in Thy1-αSyn mice by upregulating the serotonin concentration and the expression of the serotonin 4 receptor. Consequently, the downstream cyclic AMP/protein kinase A (cAMP/PKA) pathway was affected, and to upregulate and downregulate, the expression of substance P was upregulated, and the expression of calcitonin gene-related peptide was downregulated. In summary, electroacupuncture improved intestinal motility in PD mice by affecting serotonin levels, serotonin 4 receptor expression, and the cAMP/PKA pathway, providing a potentially effective and promising complementary and alternative therapy for relieving constipation symptoms in patients with PD.

Paclitaxel-Containing Extract Exerts Anti-Cancer Activity through Oral Administration in A549-Xenografted BALB/C Nude Mice: Synergistic Effect between Paclitaxel and Flavonoids or Lignoids.

Taxus yunnanensis is a paclitaxel-containing herb with traditional usage in cancer treatment, and its extract possesses great oral bioavailability of paclitaxel. However, it is elusive whether paclitaxel-containing extract (HDS-1) can exert anti-tumor effect through oral administration and how other components contribute to its efficacy. Therefore, we investigate the oral-route anti-tumor effect of HDS-1 in A549-bearing mice. HDS-1-derived flavonoids (HDS-2) and lignoids (HDS-3) are hypothesized to contribute to HDS-1's efficacy, and their effects of enhancing enterocytic absorption and cytotoxicity of paclitaxel are validated in 2 permeability experiments and apoptosis-related assay, respectively. In vivo, A549 growth is significantly inhibited by 86.1 ± 12.94% (P < 0.01) at 600 mg/kg of HDS-1 and 65.7 ± 38.71% (P < 0.01) at 200 mg/kg. HDS-2 and HDS-3 significantly reduce the efflux ratio of paclitaxel to 2.33 and 3.70, respectively, in Caco-2 permeability experiment and reduce paclitaxel reflux in MDCK-MDR1 experiment. Furthermore, HDS-2 and HDS-3 potentiated paclitaxel-induced cytotoxicity by 19.1-22.45% (P < 0.05) and 10.52-18.03% (P < 0.05), respectively, inhibited the expression of cyclinB1, Bcl-2, and pMCL-1, and increased the percentage of necrosis cell in the condition of paclitaxel exposure. Conclusively, paclitaxel-containing extracts exert anti-cancer effects through oral administration, and flavonoid and lignoids contribute to its anti-cancer effect through simultaneously improving enterocytic absorption of paclitaxel and the cytotoxic effect of paclitaxel.