Revealing the material basis and mechanism for the inhibition of intestinal peristalsis by Zingiber officinale Roscoe through integrated metabolomics, serum pharmacochemistry, and network pharmacology.

Abnormal relaxation and contraction of intestinal smooth muscle can cause various intestinal diseases. Diarrhea is a common and important public health problem worldwide in epidemiology. Zingiber officinale Roscoe (fresh ginger) has been found to treat diarrhea, but the material basis and mechanism of action that inhibits intestinal peristalsis remain unclear. Metabolomics and serum pharmacology were used to identify differential metabolites, metabolic pathways, and pharmacodynamic substances, and were then combined with network pharmacology to explore the potential targets of ginger that inhibit intestinal peristalsis during diarrhea treatment, and the targets identified were verified using molecular docking and molecular dynamic simulation. We found that 25 active components of ginger (the six most relevant components), 35 potential key targets (three core targets), 40 differential metabolites (four key metabolites), and four major metabolic pathways were involved in the process by which ginger inhibits intestinal peristalsis during diarrhea treatment. This study reveals the complex mechanism of action and pharmacodynamic material basis of ginger in the inhibition of intestinal peristalsis, and this information helps in the development of new Chinese medicine to treat diarrhea and lays the foundation for the clinical application of ginger.

The protective effect of Lonicera japonica Thunb. against lipopolysaccharide-induced acute lung injury in mice: Modulation of inflammation, oxidative stress, and ferroptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Various components of Lonicera japonica Thunb. (LJT) exhibit pharmacological activities, including anti-inflammatory and antioxidant effects. Nevertheless, the relationship between LJT and ferroptosis remains largely unexplored. AIM OF THE STUDY: The purpose of this research was to look into the role of LJT in regulating LPS-induced ferroptosis in ALI and to compare the effects of different parts of LJT. MATERIALS AND METHODS: We established a mice ALI model by treating with LPS. Administered mice with different doses of Lonicerae Japonicae Flos (LJF), Lonicera Japonica Leaves (LJL) and Lonicerae Caulis (LRC) extracts, respectively. The levels of IL-6, IL-1ß, TNF-α, IL-4, IL-10, and PGE2 in bronchoalveolar lavage fluid (BALF) were measured using enzyme-linked immunosorbent assay. Furthermore, the concentrations of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), reactive oxygen species (ROS), and total ferrous ions (Fe2+) in lung tissues were evaluated. Hematoxylin and eosin staining was conducted to examine the morphological structure of lung tissues. Transmission electron microscopy was used to investigate the ultrastructural morphology of mitochondria. Furthermore, the effects of LJT were evaluated via immunohistochemical staining, western blotting, and quantitative real-time polymerase chain reaction analyses. Finally, employing molecular docking and molecular dynamics research techniques, we aimed to identify crucial components in LJT that might inhibit ferroptosis by targeting nuclear factor erythroid 2-related factor 2 (Nrf2) and glutathione peroxidase 4 (GPX4). RESULTS: We observed that pretreatment with LJT significantly mitigated LPS-induced lung injury and suppressed ferroptosis. This was supported by reduced accumulation of pro-inflammatory cytokines, ROS, MDA, and Fe2+, along with increased levels of anti-inflammatory cytokines, SOD, GSH, Nrf2, and GPX4 in the lung tissues of ALI mice. Luteolin-7-O-rutinoside, apigenin-7-O-rutinoside, and amentoflavone in LJT exhibit excellent docking effects with key targets of ferroptosis, Nrf2 and GPX4. CONCLUSIONS: Pretreatment with LJT may alleviate LPS-induced ALI, possibly by suppressing ferroptosis. Our initial results indicate that LJT activates the Nrf2/GPX4 axis, providing protection against ferroptosis in ALI. This finding offers a promising therapeutic candidate for ALI treatment.

Comparison of Geqingpi and Sihuaqingpi based on ultra-high-performance liquid chromatography-tandem mass spectrometry combined with multivariate statistics, network pharmacology analysis, and molecular docking.

Citri Reticulatae Pericarpium Viride is used in traditional Chinese medicine as Geqingpi and Sihuaqingpi varieties. We used the ultra-high-performance liquid chromatography-quadrupole-Exactive Orbitrap-mass spectrometry method and high-performance liquid chromatography-triple quadrupole-tandem mass spectrometry to analyze the chemical compounds in these varieties. Principal components analysis and orthogonal partial least squares discriminant analysis were used to analyze the quantitative results. Network pharmacology and molecular docking technology were used to forecast Citri Reticulatae Pericarpium Viride treatment mechanisms in irritable bowel syndrome. We identified 44 main compounds in Citri Reticulatae Pericarpium Viride. Compared to Sihuaqingpi, Geqingpi had higher narirutin, didymin, naringenin, and hesperetin, and lower hesperidin, isosinensetin, nobiletin, 3,5,6,7,8,3',4'-hexamethoxyflavone, tangeretin. Tangeretin, nobiletin, narirutin, didymin, and isosinensetin were the main compounds distinguishing Geqingpi from Sihuaqingpi. We found that the MAPK signaling pathway, which is closely related to irritable bowel syndrome, was an important target pathway. TP53, HRAS, MAPK1, AKT1, and EGFR were important targets in this pathway. Eriodictyol-7-O-rutinoside, narirutin, limonin, and hesperidin showed a good binding ability to the five targets. Orientin, unique to Sihuaqingpi, bound well to TP53, MAPK1, AKT1, and EGFR, while rhoifolin bound well to TP53, HRAS, MAPK1, AKT1, and EGFR. Hesperetin, unique to Geqingpi, bound well to TP53, HRAS, and MAPK1, while naringenin bound well to HRAS. Hesperidin and didymin bound well to TP53, MAPK1, AKT1, and EGFR.

Quality consistency evaluation on three species of North Patrininae herba by high-performance liquid chromatography coupled with electrospray ion trap time-of-flight mass spectrometry and network pharmacology approaches.

North Patrininae herba, a perennial herbaceous plant, has long been used in traditional Chinese medicine to treat appendicitis, enteritis, and dysentery. Sonchus arvensis L., Sonchus oleraceus L., and Ixeris chinensis (Thunb.) Nakai are used as substitutes for North Patrininae in different regions, but the consistency of chemical composition and efficacy of these three species is still unknown. In this study, a detailed chemical analysis was carried out of the extract obtained from Sonchus arvensis L., Ixeris chinensis (Thunb.) Nakai and Sonchus oleraceus L. and a chemical component not previously reported in Ixeris chinensis (Thunb.) Nakai was found-Luteolin-7-O-(6''-malonylglucoside). The mechanism of action of the extract against inflammation and type II diabetes was investigated using network pharmacology and analysis of blood-absorbed components following oral dosing of rats. Finally, a highly accurate and reliable method was established for quality control purposes. The results showed that Sonchus arvensis L. and Sonchus oleraceus L. may be considered potential resources of a medicinal compound, whereas Ixeris chinensis (Thunb.) Nakai requires further evaluation.

Analyses of Physical and Chemical Compositions of Different Medicinal Specifications of CRPV by Use of Multiple Instrumental Techniques Combined with Multivariate Statistical Analysis.

Citri Reticulatae Pericarpium Viride (CRPV) is the processed product of Citrus reticulata Blanco. We systematically analyzed two CRPV types, Geqingpi (GQP) and Sihuaqingpi (SHQP), based on powder color, microscopic characteristics, and chemical composition. In addition, we characterized their constituents via ultra-high-performance liquid chromatography with hybrid quadrupole-orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap-MS). Both showed significant differences in their powder color and microscopic characteristics. Fourier-transform infrared (FT-IR) spectroscopic analysis results showed that the C=O peak absorption of carboxylic acids and their carbonyl esters in SHQP was higher than that of GQP, while the C-OH and C-H plane bending peaks of polysaccharides were lower than those of GQP. We analyzed these data via similarity analysis, PCA, and OPLS-DA. GQP and SHQP had large distinct differences. Based on the mass measurements for molecular and characteristic fragment ions, we identified 44 main constituents from CRPV, including different flavonoid glycosides and flavonoid aglycones in SHQP and GQP, respectively. We found luteolin-6-C-glucoside, orientin, rhoifolin, and pilloin solely in SHQP, and naringenin and hesperetin only in GQP. The peak area measurements showed GQP having a higher flavonoid glycoside (narirutin, hesperidin, etc.) content, whereas SHQP had a higher polymethoxyflavone (nobiletin, tangeretin, etc.) content. Since we holistically analyzed two CRPV types, the results can not only support future pharmacological research, but also provide a scientific basis for formulating more reasonable CRPV quality standards and guide its clinical potential as a precision medicine.

Study on phenolic acids of Lonicerae japonicae Flos based on ultrahigh performance liquid chromatography-tandem mass spectrometry combined with multivariate statistical analysis.

Lonicerae japonicae Flos, a traditional Chinese medicine, has the function of evacuating heat and detoxifying. To promote the optimization of Lonicerae japonicae Flos germplasms and improve the quality of medicinal materials, 55 batches of five Lonicerae japonicae Flos germplasms with the same origin were collected during different periods, a UHPLC-TOF-MS method was established, and 22 kinds of phenolic acids were found and qualitatively analysed. Seventeen phenolic acids were selected for quantitative analysis by UHPLC-QqQ-MS/MS, and the quantitative results were analysed by principal component analysis, orthogonal partial least squares-discriminant analysis, and partial least squares discriminant analysis. The contents of phenolic acids in periods S1-S6 were found to be significantly different. There were also significant differences in the accumulation of phenolic acids in Lonicerae japonicae Flos during different growth periods. Ferulic acid, 5-O-caffeoylquinic acid, and caffeic acid were determined to be important components to distinguish the different growth periods of Lonicerae japonicae Flos. There were significant differences in the phenolic acid content of different germplasms of Lonicerae japonicae Flos, and the total amount of 17 phenolic acids and total acids (chlorogenic acid, 3,5-di-O-caffeoylquinic acid, and 4,5-di-O-caffeoylquinic acid) in "Hua Jin No. 6" was highest, so the quality of "Hua Jin No. 6" was better than that of the four other germplasms. In addition, chlorogenic acid methyl ester and caffeic acid were the smallest markers in combination to distinguish the five germplasms of Lonicerae japonicae Flos.

Systematic characterization of the absorbed components of Ligustri Lucidi Fructus and their metabolic pathways in rat plasma by ultra-high-performance liquid chromatography-Q-Exactive Orbitrap tandem mass spectrometry combined with network pharmacology.

Ligustri Lucidi Fructus is a dried and mature fruit of Ligustrum lucidum Ait., which has the effects of nourishing liver and kidney. Herein, an accurate and sensitive method was established for the separation and identification of the absorbed constituents and metabolites of Ligustri Lucidi Fructus in rat plasma based on ultra-high-performance liquid chromatography-Q-Exactive Orbitrap tandem mass spectrometry. A total of 73 prototype constituents and 148 metabolites were identified or characterized in administered plasma, and the possible metabolic pathways of constituents mainly involved hydroxylation, sulfation, demethylation, and glucuronidation. Besides, the network pharmacology was further investigated to illuminate its potential mechanism of treatment for liver injury by the biological targets regulating related pathways. Network pharmacological analysis showed that target components through 399 targets regulate 220 pathways. The docking results showed that 36 key target components were closely related to liver injury. Overall, the study clearly presented the metabolic processes of Ligustri Lucidi Fructus and gave a comprehensive metabolic profile of Ligustri Lucidi Fructus in vivo first. Combining with network pharmacology and molecular docking discovered potential drug targets and disclose the biological processes of Ligustri Lucidi Fructus, which will be a viable step toward uncovering the secret mask of study for traditional Chinese medicine.