Network pharmacology and experimental validation to investigate the mechanism of Nao-Ling-Su capsule in the treatment of ischemia/reperfusion-induced acute kidney injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Nao-Ling-Su Capsule (NLSC) is a traditional prescription, which is composed of fifteen herbs such as epimedium, Polygala tenuifolia, and Schisandra chinensis. It has the effect of strengthening the brain, calming nerves, and protecting the kidney, which has been used clinically for many years to strengthen the brain and kidney. However, the effect of NLSC in the treatment of acute kidney injury (AKI) is still unclear. AIM OF THE STUDY: The present study aims to elucidate the pharmacological actions of NLSC in the treatment of AKI. MATERIALS AND METHODS: Molecular targets for NLSC and AKI were obtained from various databases, and then we built networks of interactions between proteins (PPI) by employing string databases. Additionally, we employed the DAVID database to conduct gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Molecular docking was conducted to analyze the interaction between core components and their corresponding core targets. Next, the C57BL male mice model of ischemia/reperfusion damage (IRI) was developed, and the nephridial protective effect of NLSC was evaluated. The accuracy of the expected targets was confirmed using real-time quantitative polymerase chain reaction (RT-qPCR). The renal protective effect of NLSC was assessed using an immortalized human kidney tubular (HK-2) cell culture produced by oxygen-glucose deprivation (OGD). RESULTS: Network pharmacology analysis identified 199 common targets from NLSC and AKI. STAT3, HSP90AA1, TP53, MAPK3, JUN, JAK2, and VEGFA could serve as potential drug targets and were associated with JAK2/STAT3 signaling pathway, PI3K-Akt signaling pathway, etc. The molecular docking analysis confirmed significant docking activity between the main bioactive components and core targets, including STAT3 and KIM-1. Moreover, the AKI mice model was successfully established and NLSC pretreatment could improve renal function and alleviate renal damage. NLSC could alleviate renal inflammation and tubular cell apoptosis, and decrease the expression of STAT3 and KIM-1 in AKI mice. In vitro, both NLSC and drug-containing serum may protect HK-2 cells by inhibiting STAT3 signaling, especially STAT3-mediated apoptosis and KIM-1 expression. CONCLUSION: NLSC could alleviate renal inflammation and apoptosis, exerting its beneficial effects by targeting the STAT3/KIM-1 pathway. NLSC is a promising candidate for AKI treatment and provides a new idea and method for the treatment of AKI.

Research progress on chemical components and pharmacological action of Solanum lyratum Thunb.

OBJECTIVES: Solanum lyratum Thunb (SLT) is a perennial plant of the Solanaceae family, and is extensively used in the clinical practice of traditional Chinese medicine. Malaria, oedema, gonorrhoea, cancer, wind and fever, jaundiced hepatitis, cholecystitis and rheumatoid arthritis are among the diseases that it is used to treat. To offer a foundation for further development and usage of SLT, the pieces of literature about the chemical composition and pharmacological action of SLT were reviewed and analysed. KEY FINDINGS: The chemical constituents of SLT mainly included steroids, alkaloids, flavonoids, terpenoids, anthraquinones, phenylpropanoids and others. Pharmacological action mainly contains anti-tumour, antibacterial, anti-inflammatory, anti-oxidation and other pharmacological actions, among them, the anti-tumour effect is particularly outstanding. SUMMARY: At present, studies on the pharmacological effects of SLT mainly focus on alkaloids and steroidal saponins. In the follow-up studies, studies on the pharmacological activities of other chemical components in SLT, such as flavonoids and terpenoids, should be strengthened. It has the potential to pave the way for more research and development of novel SLT medicines.

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.

Analyze the Effect of Steaming on the Chemical Constituents, Defecation and Liver Injury of Polygonum Multiflorum Radix (Heshouwu) by Multiple Analysis Techniques Combined with Multivariate Statistics.

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-ß-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.

Quality Evaluation of Traditional Chinese Medicine Prescription in Naolingsu Capsule Based on Combinative Method of Fingerprint, Quantitative Determination, and Chemometrics.

Background: Naolingsu capsule (NLSC) is a well-known traditional Chinese medicine (TCM) prescription in China. It is widely used to treat neurasthenia, insomnia, cardiovascular and cerebrovascular disease, and other diseases. However, its inalienable chemical groups have not been carried out. Methods: We first established the nontargeted investigation based on fingerprinting coupled with UHPLC-Q/TOF-MS/MS. Second, the quantitative methods based on HPLC-DAD and LC-MS/MS were connected to the synchronous quantitative assurance of eleven and fourteen marker compounds. Finally, the quantitative information was processed with SIMCA-P for differentiating the distinctive bunches of samples to screen the foremost appropriate chemical markers. Results: The similarity of HPLC fingerprints of 24 batches of NLSC samples was 0.645-0.992. In total, 37 flavonoids, 21 organic acids, 22 lignans, 13 saponins, and 20 other compounds were recognized in NLSC by the UHPLC-Q/TOF-MS/MS method. The quantitative determination was approved for linearity, discovery limits, accuracy, repeatability, soundness, and precision. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) models accomplished the great classification of the samples from the five enterprises, respectively. Rehmannioside D (RD), methylophiopogonanone A (MPA), 3,6'-disinapoyl sucrose (DS), schisandrin B (SSB), epimedin C (EC), icariin (ICA), and jujuboside B (JB) were considered as the potential chemical markers for NLSC quality control. Conclusion: The experimental results illustrated that the combinative strategy was valuable for quick pharmaceutical quality assessment, which can potentially differentiate the origin, decide the realness, and assess the overall quality of the formulation.

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.