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.

Steaming is a characteristic pharmaceutical skill in Traditional Chinese Medicine (TCM). Polygonum multiflorum radix (PM) and its steamed products have been used in Asia for centuries. Raw Polygonum multiflorum radix (RPM) is commonly used to promote defecation but can exert toxicity, especially in liver injury. However, RPM can be made converted into Polygoni multiflori radix praeparata (PMP) by steaming; this is considered a good method to reduce defecation and liver injury caused by PM in Asia. The chemical constituents of TCM are the key to its action. We systematically analyzed the effect of steaming on PM constituents, defecation, and liver injury. We identified 13 main constituents from PM and PMP; the results showed that after being steamed, two constituents (TSG, catechin) had decreased, six constituents (such as procyanidin B1 or B2) had disappeared, four constituents (such as emodin, physcion) had increased, emodin-8-O-β-D-glucoside remained unchanged in PMP. Pharmacological experiments showed that PM could promote defecation; however, there were no obvious effects in response to PMP. Only a high dose of PM for 14 days caused some degree of liver injury, although this injury disappeared after 14 days of drug withdrawal. Network pharmacology and molecular docking studies showed that TSG, emodin and physcion were the most effective in promoting defecation and causing liver injury. Collectively, our findings show that steaming can reduce the effect of PM on promoting defecation and reducing liver injury. TSG may be one of the important constituents in PM that can promote defecation and cause liver injury.

Objective. To identify and quantify the active phenolic components in Lonicerae japonicae flos (LJF) for fever treatment and their mechanism of action using network pharmacology and molecular docking. Methods. Based on qualitative analysis of LJF, 194 phenolics were obtained, including 81 phenolic acids and 113 flavonoids. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were used to identify potential targets for these components to interact with fever. Molecular docking with microsomal PGE2 synthase-1, EP1, EP2, EP3, and EP4 targets was used to determine antipyretic components. The antipyretic efficacy of the main components was verified by in vivo experiments. Finally, high-performance liquid chromatography-tandem mass spectrometry was used to quantify the main antipyretic components of LJF. Results. Phenolics in LJF may prevent and treat fever by participating in calcium signaling, regulating TRP channels, and cAMP signaling. Luteolin-7-O-glucoside, apigenin-7-O-glucoside, 3,5-O-dicaffeoylquinic acid, luteolin, and other components have a good docking effect with PGE2 synthase-1 and its four subtypes. 3,5-O-dicaffeoylquinic acid, luteolin-7-O-glucoside, and apigenin-7-O-glucoside have good antipyretic effects in a yeast-induced pyrexia model. The content of these antipyretic components varies with the developmental period of LJF. Phenolic acids are the main components that distinguish the different developmental periods of LJF. Conclusion. The potential antipyretic components and molecular mechanisms of phenolics provide a basis for the traditional medicinal effects and future development and utilization of LJF.