The complete chloroplast genome sequence and phylogenetic relationship analysis of Eomecon chionantha, one species unique to China.

Eomecon chionantha Hance, an endemic species in China, has a long medical history in Chinese ethnic minority medicine and is known for its anti-inflammatory and analgesic effects. However, studies of E. chionantha are lacking. In this study, we investigated the characteristics of the E. chionantha chloroplast genome and determined the taxonomic position of E. chionantha in Papaveraceae via phylogenetic analysis. In addition, we determined molecular markers to identify E. chionantha at the molecular level by comparing the chloroplast genomes of E. chionantha and its closely related species. The complete chloroplast genomic information indicated that E. chionantha chloroplast DNA (178,808 bp) contains 99 protein-coding genes, 8 rRNAs, and 37 tRNAs. Meanwhile, we were able to identify a total of 54 simple sequence repeats through our analysis. Our findings from the phylogenetic analysis suggest that E. chionantha shares a close relationship with four distinct species, namely Macleaya microcarpa, Coreanomecon hylomeconoides, Hylomecon japonica, and Chelidonium majus. Additionally, using the Kimura two-parameter model, we successfully identified five hypervariable regions (ycf4-cemA, ycf3-trnS-GGA, trnC-GCA-petN, rpl32-trnL-UAG, and psbI-trnS-UGA). To the best of our knowledge, this is the first report of the complete chloroplast genome of E. chionantha, providing a scientific reference for further understanding of E. chionantha from the perspective of the chloroplast genome and establishing a solid foundation for the future identification, taxonomic determination and evolutionary analysis of this species.

L-carnitine modified nanoparticles target the OCTN2 transporter to improve the oral absorption of jujuboside B.

As a bioactive saponin derived from the seeds of Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chow, jujuboside B (JuB) shows great potential in anti-anxiety, anti-depression and improving learning and memory function. However, its oral bioavailability is very poor. In this study, a novel drug-loading nanoparticles system was prepared with polyethylene glycol and polylactic-co-glycolic acid copolymer (PEG-PLGA), and further modified with L-carnitine (LC) to target intestinal organic cation/carnitine transporter 2 (OCTN2) to improve the oral absorption of JuB. Under the optimized preparation conditions, the particle sizes of obtained JuB-PEG-PLGA nanoparticles (B-NPs) and LC modified B-NPs (LC-B-NPs) were 110.67 ± 11.37 nm and 134.00 ± 2.00 nm with the entrapment efficiency (EE%) 73.46 ± 1.26 % and 76.01 ± 2.10 %, respectively. The pharmacokinetics in SD rats showed that B-NPs and LC-B-NPs increased the bioavailability of JuB to 134.33 % and 159.04 % respectively. In Caco-2 cell model, the prepared nanoparticles significantly increased cell uptake of JuB, which verified the pharmacokinetic results. The absorption of LC-B-NPs mainly depended on OCTN2 transporter, and Na+ played an important role. Caveolin and clathrin were involved in the endocytosis of the two nanoparticles. In conclusion, both B-NPs and LC-B-NPs can improve the oral absorption of JuB, and the modification of LC can effectively target the OCTN2 transporter.

Protective effects and regulatory mechanisms of Platycodin D against LPS-Induced inflammatory injury in BEAS-2B cells.

Platycodin D (PLD), a major bioactive component of triterpene saponins found in Platycodon grandiflora, is renowned for its anti-inflammatory and antioxidant properties. This study aims to explore the protective effects and regulatory mechanisms of PLD in an LPS-induced inflammation injury model of BEAS-2B cells. Initially, PLD was identified from Platycodon grandiflora extracts utilizing UPLC-Q-TOF-MS/MS technology. The effects of PLD on the viability, morphology, ROS levels, and inflammatory factors of LPS-induced BEAS-2B cells were then investigated. The results showed that PLD significantly alleviated LPS-induced oxidative stress and inflammatory injury. Further analysis revealed that PLD positively influenced apoptosis levels, mitochondrial morphology, and related gene expression, indicating its potential to mitigate LPS-induced apoptosis and alleviate mitochondrial dysfunction. Using molecular docking technology, we predicted the binding sites of PLD with mitochondrial autophagy protein. Gene expression levels of autophagy-related proteins were measured to determine the impact of PLD on mitochondrial autophagy. Additionally, the study examined whether the mitochondrial autophagy agonists rapamycin (RAPA) could modulate the upregulation of inflammasome-related factors NLRP3 and Caspase-1 in LPS-induced BEAS-2B cells. This was done to evaluate the regulator mechanisms of PLD in pulmonary inflammatory injury. Our findings suggest that PLD's mechanism of action involves the regulation of mitochondrial autophagy, which in turn modulates inflammatory responses.

Elucidating the anti-inflammatory activity of platycodins in lung inflammation through pulmonary distribution dynamics and grey relational analysis of cytokines.

ETHNOPHARMACOLOGICAL RELEVANCE: Platycodonis Radix (PR) is a traditional herbal remedy used to prevent and treat lung inflammation, and platycodins are speculated to be the major active constituents. However, concrete experimental verification for this assertion remains absent thus far. AIM OF THE STUDY: This study aims to compare the pulmonary distribution dynamics of five platycodins and analyze their effects on cytokines. Through the grey relational analysis (GRA) between pulmonary active components and cytokines, the study ascertains platycodins as the potential effective component against lung inflammation. MATERIALS AND METHODS: A rat lung inflammation model was created using lipopolysaccharides (LPS). Pulmonary distribution dynamics were analyzed via LC-MS/MS. Cytokine changes and distribution patterns in lung tissues were studied by multi-factor reagent kit. GRA was applied to determine correlations between pulmonary components and cytokines. Finally, the anti-inflammatory properties of platycodins were further studied using LPS-induced BEAS-2B cells in vitro. RESULTS: The results showed that five platycodins (Platycodin D, Platycodin D3, Deapio Platycodin D, 3-O-ß-D-Glucopyranosyl Platycodigenin, and Platycodigenin) featured fast absorption rate, short time to peak, and slow metabolism rate. The pulmonary distribution dynamics were significantly affected within 2 h after LPS modeling. At the same time, PR altered the relationships among different cytokines induced by LPS stimulation, particularly inflammatory cytokines IL-6 and IFN-γ. The GRA results indicated good correlation between the pulmonary distribution dynamics of the five platycodins components and the changing patterns of cytokine levels, with Platycodin D3 contributing the most. Additionally, Platycodin D3 exhibited a protective role against LPS-induced inflammation by reducing the production of pro-inflammatory mediators such as IL-1ß, IL-8, and ROS, as well as increasing the expression of the anti-inflammatory mediator IL-10. CONCLUSIONS: Platycodins are the main anti-inflammatory agents in PR and there is a good correlation with cytokines. This contributes to the anti-pneumonia effect of PR.

Research on the potential mechanism of Deapioplatycodin D against pulmonary fibrosis based on bioinformatics and experimental verification.

BACKGROUND: Pulmonary fibrosis (PF) is a group of respiratory diseases that are extremely complex and challenging to treat. Due to its high mortality rate and short survival, it's often referred to as a "tumor-like disease" that poses a serious threat to human health. OBJECTIVE: We aimed validate the potential of Deapioplatycodin D (DPD) to against PF and clarify the underlying mechanism of action of DPD for the treatment of PF based on bioinformatics and experimental verification. This finding provides a basis for the development of safe and effective therapeutic PF drugs based on DPD. METHODS: We used LPS-induced early PF rats as a PF model to test the overall efficacy of DPD in vivo. Then, A variety of bioinformatics methods, such as WGCNA, LASSO algorithm and immune cell infiltration (ICI), were applied to analyze the gene microarray related to PF obtained from Gene Expression Omnibus (GEO) to obtained key targets of PF. Finally, an in vitro PF model was constructed based on BEAS-2B cells while incorporating rat lung tissues to validate the regulatory effects of DPD on critical genes. RESULTS: DPD can effectively alleviate inflammatory and fibrotic markers in rat lungs. WGCNA analysis resulted in a total of six expression modules, with the brown module having the highest correlation with PF. Subsequently, seven genes were acquired by intersecting the genes in the brown module with DEGs. Five key genes were identified as potential biomarkers of PF by LASSO algorithm and validation dataset verification analysis. In the ICI analysis, infiltration of activated B cell, immature B cell and natural killer cells were found to be more crucial in PF. Ultimately, it was observed that DPD could modulate key genes to achieve anti-PF effects. CONCLUSION: In short, these comprehensive analysis methods were employed to identify critical biomarkers closely related to PF, which helps to elucidate the pathogenesis and potential immunotherapy targets of PF. It also provides essential support for the potential of DPD against PF.

Multitarget Protective Effects of JUB on Aß-Induced Neurotoxicity and the Mechanism Predication Using Network Pharmacology Analysis.

Amyloid-ß (Aß) is one of the core factors in the pathogenesis of Alzheimer's disease (AD), and the accumulation of its aggregates in the brain can form age-related plaques, leading to brain cell damage and intellectual decline, which may be the common intersection of all causes of neurotoxicity. Jujuboside B (JUB) has many characteristics such as hypnosis, sedation, antianxiety, and antioxidant stress. However, it is still unclear whether JuB can alleviate the neurotoxicity caused by Aß. Our study demonstrates that JUB improves learning and memory deficits in the nematode model. At the same time, JUB increases the antioxidant activity, prevents excessive accumulation of lipid synthesis, and resists endogenous lipofuscin deposition, thereby inhibiting the toxic effect of Aß. In vitro, JUB can improve Aß1-42-induced neuronal apoptosis level through the Bax/Bcl-2/caspase-3 signaling pathway and restore mitochondrial function in SH-SY5Y cells. The network pharmacology has been used to predict the potential neuroprotective mechanism of JUB. In summary, JUB exhibits neuroprotective properties employing both a neural cell and a nematode, which provides a basis for screening candidate ingredients for preventing AD.

Human FcRn can mediate the transport across intestinal mucosal barrier and prolong the half-life of rabbit IgG in vivo

FcRn (neonatal Fc receptor) plays an important role in IgG transportation, antigen presentation and signal transmission. In this study, the complement fixation test and flow cytometry test were performed to verify whether the heterologous antibody could be transmitted to the serum or leukocyte with FcγR (Fc gamma receptor) across the intestinal mucosa. The results showed that rabbit anti-bovine IgG could be detected in both the serum and the leukocytes, which indicated that the heterologous antibody could transport across the intestinal mucosa to enter the blood and be effectively delivered to the leukocytes with FcγR. In addition, the results also showed that the rabbit anti-bovine IgG still could be detected in the leukocyte group (P=0.044<0.05) after 21 days. It indicated that the rabbit IgG could exist in the body for a long term (up to 21 days) after being transported to the cells containing FcγR.