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According to traditional Chinese medicine, Scutellaria baicalensis Georgi possesses the therapeutic properties of heat-clearing, dampness-drying, diarrhea alleviation, and detoxification, making it a clinically used remedy for respiratory infections. The objective of this study was to investigate the changes in constituent content, pharmacodynamic effects, and material basis of Scutellaria baicalensis Georgi in the plasma of mice infected with respiratory syncytial virus (RSV). The results showed that a sensitive and efficient high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) method was established in this study. Multiple quantitative analyses of Baicalein, Apigenin-7-glucuronide, Baicalin, Oroxylin A 7-O-beta-d-glucuronide, Wogonoside, Norwogonin, Wogonin, Chrysin, and Oroxylin A in mouse plasma revealed a bimodal absorption phenomenon within the time frame of 0.167 h to 6 h post-administration, with the exception of chrysin. Following 6 h of administration, the concentrations of 9 components continued to decrease until they became undetectable. In comparison to the model group, all administered groups exhibited significant reductions in lung index and viral load, with their lung index repair rate and viral suppression rate aligning with the blood concentration-time curve. Finally, through the application of the gray correlation analysis method, we identified Baicalein, Baicalin, Oroxylin A 7-O-beta-d-glucuronide, Wogonoside, Norwogonin, and Wogonin as potential pharmacodynamic material bases of Scutellaria baicalensis Georgi against RSV infection.

Traditional Chinese medicine (TCM) processing is the summary of long-term clinical experience, processing can change the property, taste and meridian of TCM, achieve the purpose of reducing toxicity and increasing efficiency, to ensure the safety of clinical medication. This paper summarizes the research advance of salt processing in recent years from the aspects of the types of excipients, salt processing methods, salt processing purpose and the influence of salt process on the chemical composition, pharmacodynamic effect and in vivo behavior of TCM, and analyzes and discusses the shortcomings of the current research, so as to provide ideas for the further research and development of salt processing of TCM. The literatures were classified and summarized by consulting the scientific database (such as SciFinder Scholar, CNKI, Google Scholar, Baidu Scholar, etc . ), Chinese herbal classics and Chinese Pharmacopoeia and so on. The results show that salt processing is helpful to introduce drugs into the kidney channel and enhance the effect of nourishing Yin and falling fire. The pharmacological effect, chemical composition and in vivo behavior of TCM will change after salt processing. In the future, we should strengthen the research on standardizing the dosage of excipients, the quality standard after processing, the relationship between the change of chemical composition after salt processing and the enhancement of pharmacological efficacy, so as to deeply explain the principle of salt processing, and further improve and optimize the salt making process. By combing the influence of the of salt processing of TCM and analyzed the current problems, we hope to provide guidance for the in-depth study of the salt processing mechanism of TCM and the inheritance and innovation of TCM processing technology.

Atractylodes macrocephala Koidz. has been used as an invigorating spleen drug for eliminating dampness and phlegm in China. According to recent researches, different processing methods may affect the drug efficacy, so we collected A. macrocephala from the Zhejiang Province, produced with different processing methods, crude A. macrocephala (CA) and bran-processed A. macrocephala (BA), then analyzed its essential oils (EOs) by GC/MS. The results showed 34 components representing 98.44% of the total EOs of CA were identified, and 46 components representing 98.02% of the total EOs of BA were identified. Atractylone is the main component in A. macrocephala. Compared with CA, BA has 46 detected compounds, 28 of which were identical, and 6 undetected compounds. Pharmacodynamic results revealed that the EOs of CA and atractylone exhibited more effective anticancer activity in HepG2, MCG803, and HCT-116 cells than the EOs of BA; while the EOs of BA exhibited simple antiviral effect on viruses H3N2, both the EOs and atractylone show anti-inflammatory activity by inhibiting the lipopolysaccharide (LPS)-induced nitric oxide (NO) production in ANA-1 cells.

Traditional Chinese Medicine (TCM) is extensively utilized in clinical practice due to its therapeutic and preventative treatments for various diseases. With the development of high-throughput sequencing and systems biology, TCM research was transformed from traditional experiment-based approaches to a combination of experiment-based and omics-based approaches. Numerous academics have explored the therapeutic mechanism of TCM formula by omics approaches, shifting TCM research from the “one-target, one-drug” to “multi-targets, multi-components” paradigm, which has greatly boosted the digitalization and internationalization of TCM. In this review, we concentrated on multi-omics approaches in principles and applications to gain a better understanding of TCM formulas against various diseases from several aspects. We first summarized frequently used TCM quality assessment methods, and suggested that incorporating both chemical and biological ingredients analytical methods could lead to a more comprehensive assessment of TCM. Secondly, we emphasized the significance of multi-omics approaches in deciphering the therapeutic mechanism of TCM formulas. Thirdly, we focused on TCM network analysis, which plays a vital role in TCM-diseases interaction, and serves for new drug discovery. Finally, as an essential source for storing multi-omics data, we evaluated and compared several TCM databases in terms of completeness and reliability. In summary, multi-omics approaches have infiltrated many aspects of TCM research. With the accumulation of omics data and data-mining resources, deeper understandings of the therapeutic mechanism of TCM have been acquired or will be gained in the future.

Atorvastatin (AT) is a widely used lipid-regulating drug to reduce cholesterol and triglycerides. Its poor aqueous solubility and hepatic metabolism require development of drug delivery systems able to improve its solubility and bypass hepatic effect. For this purpose, atorvastatin nanostructured lipid carriers (AT-NLCs) were prepared and characterized. AT-NLCs were prepared by emulsification using high-speed homogenization followed by ultrasonication. The prepared NLCs showed particle size between 162.5 ± 12 and 865.55 ± 28 nm while zeta potential values varied between −34 ± 0.29 and −23 ± 0.36 mV. They also showed high encapsulation efficiency (>87%) and amorphous state of the drug in lipid matrix. Pharmacokinetic parameters of optimized formulation (NLC-1; composed of 2% Gelucire® 43/01, 8% Capryol® PGMC, 2% Pluronic®F68 and 0.5% lecithin) revealed 3.6- and 2.1-fold increase in bioavailability as compared to atorvastatin suspension and commercial product (Lipitor®), respectively. Administration of NLC-1 led to significant reduction (p < .05) in the rats’ serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) and significant increase in high-density lipoprotein (HDL). This improvement was confirmed histologically by minimizing the associated hepatic steatosis. These investigations demonstrated the superiority of NLCs for improvement of oral bioavailability and in vivo performance of AT.

Lobeline is an alkaloid derived from the leaves of an Indian tobacco plant (Lobelia inflata), which has been prepared by chemical synthesis. It is classified as a partial nicotinic agonist and has a long history of therapeutic usage ranging from emetic and respiratory stimulant to tobacco smoking cessation agent. The presence of both cis and trans isomers in lobeline is well known, and many studies on the relationship between the structure and pharmacological activity of lobeline and its analogs have been reported. However, it is a remarkable fact that no studies have reported the differences in pharmacological activities between the two isomers. In this article, we found that different degrees of isomerization of lobeline injection have significant differences in respiratory excitatory effects in pentobarbital sodium anesthetized rats. Compared with cis-lobeline injections, the respiratory excitatory effect was significantly reduced by 50.2% after administration of injections which contained 36.9% trans-lobeline. The study on the influencing factors of isomerization between two isomers shown that this isomerization was a one-way isomerism and only converted from cis to trans, where temperature was the catalytic factor and pH was the key factor. This study reports a new discovery. Despite the widespread use of ventilators, first-aid medicines such as nikethamide and lobeline has retired to second line, but as a nonselective antagonist with high affinity for a4b2 and a3b2 nicotinic acetylcholine receptors (nAChRs). In recent years, lobeline has shown great promise as a therapeutic drug for mental addiction and nervous system disorders, such as depression, Alzheimer disease and Parkinson disease. Therefore, we suggest that the differences between two isomers should be concerned in subsequent research papers and applications.

Craib ( ), a traditional treatment for rheumatoid arthritis (RA), faces resource scarcity, leading to the emergence of potential substitutes in the market. Although these potential substitutes have shown properties that alleviate RA-symptoms, their therapeutic equivalence to still requires systematic validation. This study aims to identify suitable potential substitutes for and elucidate their therapeutic mechanisms for RA by conducting comparative analyses of metabolites and pharmacology among these potential substitutes. Six botanical samples were analyzed LC-MS/MS for metabolite profiling and phenolic quantification. Pharmacological comparisons employed LPS-stimulated RAW264.7/MC3T3-E1 and MH7A cell models. Mechanistic studies on macrophage polarization (LPS/IL-4-induced RAW264.7), osteoblast mineralization, and synoviocyte behaviors (proliferation/migration/invasion) were conducted for top candidates. A total of 54 metabolites were identified in the samples by LC-MS/MS. showed the highest metabolite similarity to , and both and V contained higher levels of phenolic compounds than . Combined with the pharmacodynamic results, was superior V in anti-RA efficacy and was the only comparable potential substitute. Mechanistically, both and : Modulated M1/M2 macrophage polarization; Enhanced osteogenic markers (Runx2, Osx, Ocn) and mineralization; Inhibited synoviocyte proliferation/migration/invasion via Bcl-2 suppression and Caspase-3 activation. Multidimensional analysis confirmed that is the optimal potential substitute for , with high similarity in both metabolites and biological activities between the two. Both botanical medicines can slow the progression of RA by regulating immune responses, stimulating osteoblast differentiation, and inducing synoviocyte apoptosis. This study provides critical evidence for the sustainable utilization of resources and expands treatment options for RA.

Objectives In this study, a polymer micelle containing berberine (Ber) was prepared. The micelle was composed of Pluronic F127 and Ber. The hypoglycemic effect was verified by animal experiments. Methods The Ber-loaded micelles were prepared with a thin-film hydration method. Encapsulation efficiency, surface morphology, particle size, zeta potential, differential scanning calorimetry (DSC), and X-ray diffraction (XRD) were determined. The drug release profile of Ber was studied with the dialysis method. In addition, the streptozocin (STZ)-induced type 2 diabetic model in mice was used to examine the hypoglycemic effect. Key Findings The average size of the prepared micelles was 91.1 nm with a polydispersity of 0.285. Compared with the Ber ethanol solution, the in vitro release of Ber from micelles presented the sustained-release property. The animal experiments verified the micelles increased body weight and decreased food and water intake of type 2 diabetic mice. Also, the level of blood glycosylated hemoglobin (GHb), total cholesterol (TC), total triglyceride (TG), and non-esterified fatty (NEFA) was lowered, from which we inferred that the Ber-F127 micelles had the expected hypoglycemic effect. Conclusions Our results suggested that F127 micelles might serve as a promising nanocarrier to improve the solubility and bioavailability of Ber.

Introduction: Indoleamine 2,3-dioxygenase (IDO) was a potential tumor immunotherapy target. IDO inhibitors showed inconsistent results in clinical trials, but no preclinical comparative study was reported. The purpose of this study was to evaluate the differences of representative IDO inhibitors (PCC0208009, INCB024360, NLG919) from the pharmacological perspective. Methods: In vitro experiments included: inhibition effects on IDO activity in cell and enzyme-based assay, effects on IDO expression in HeLa cells, and enhancement of proliferation and activation of peripheral blood mononuclear cell (PBMC). In vivo experiments included: pharmacokinetics and tumor distribution in CT26-bearing mice, effects on Kyn/Trp and anti-tumor effect and immunological mechanism in CT26 and B16F10 tumor-bearing mice. Results: Compared with INCB024360 and NLG919, PCC0208009 effectively inhibited IDO activity at lower dose 2 nM and longer duration more than 72 h, had higher enhancements on PBMC proliferation and activation, and could inhibit the IDO expression in Hela cells. The pharmacokinetics characteristics of three IDO inhibitors were similar in CT26-bearing mice. In CT26 and B16F10 tumor-bearing mice, PCC0208009 and INCB024360 had similar effects in Kyn/Trp reduction, and more potent than NLG919; three IDO inhibitors had similar effects in tumor suppression, changes of the percentages of CD3+CD8+ and CD3+CD4+ T cells, and activation of tumor infiltrating lymphocytes, while PCC0208009 had a better tendency than INCB024360 and NLG919. Conclusion: PCC0208009, INCB024360, and NLG919 were all effective IDO inhibitors, but the comprehensive pharmacological activity of PCC0208009 was better than INCB024360 and NLG919, which was basically consistent with the results or progresses of clinical trials.

Introduction Dulaglutide is a recombinant glucagon-like peptide-1 immunoglobulin G4 Fc fusion protein approved for treating patients with type 2 diabetes (T2D). The aim of this study was to assess postprandial data over 4 weeks for dulaglutide (0.75 mg) versus placebo after a standardized test meal in Japanese patients with T2D. Methods The pharmacodynamic (PD) effects of once-weekly dulaglutide (0.75 mg) in Japanese patients with T2D on diet and exercise therapy ( N  = 12) were evaluated by assessing postprandial data up to week 4 in a phase 4, single-center, randomized, cross-over, single-blind, placebo-controlled study. The primary end point was the change in 4-h glucose area under the concentration versus time curve [AUC (0–4 h)] from baseline to week 4. Secondary end points included changes from baseline in other PD parameters (insulin, C-peptide, glucagon, and triglycerides) at weeks 1, 2, and 4 and the safety and tolerability of dulaglutide 0.75 mg. Continuous glucose monitoring (CGM) during the 1st week was performed as an exploratory measure in each treatment period. Results The decrease in AUC (0–4 h) from baseline to week 4 following dulaglutide administration was statistically significant compared with placebo at weeks 1, 2, and 4 ( P  < 0.0001). Insulin and C-peptide levels were also significantly increased ( P  < 0.05) with dulaglutide versus placebo at weeks 2 and 4. There were no statistically significant differences between groups in glucagon and triglyceride levels. Daily average glucose concentrations were decreased on the day after the first administration of dulaglutide and remained at similar levels for 4 days. The incidence of treatment-emergent adverse events was slightly higher with dulaglutide versus placebo. Conclusion In conclusion, dulaglutide decreased postprandial glucose from week 1 in Japanese patients with T2D, indicating that dulaglutide treatment is associated with favorable PD effects soon after treatment begins. Trial Registration ClinicalTrials.gov identifier: NCT03315780. Funding Eli Lilly Japan K.K. (Kobe, Japan).