Analysis of Clinical Trials Using Anti-Tumor Traditional Chinese Medicine Monomers.

The potential anti-cancer effect of traditional Chinese medicine (TCM) monomers has been widely studied due to their advantages of well-defined structure, clear therapeutic effects, and easy quality control during the manufacturing process. However, clinical trial information on these monomers is scarce, resulting in a lack of knowledge regarding the research progress, efficacy, and adverse reactions at the clinical stage. Therefore, this study systematically reviewed the clinical trials on the anti-cancer effect of TCM monomers registered in the Clinicaltrials.gov website before 2023.4.30, paying special attention to the trials on tumors, aiming to explore the research results and development prospects in this field. A total of 1982 trials were started using 69 of the 131 TCM monomers. The number of clinical trials performed each year showed an overall upward trend. However, only 26 monomers entered into 519 interventional anti-tumor trials, with vinblastine (194, 37.38%) and camptothecin (146, 28.13%) being the most used. A total of 45 tumors were studied in these 519 trials, with lymphoma (112, 21.58%) being the most frequently studied. Clinical trials are also unevenly distributed across locations and sponsors/collaborators. The location and the sponsor/collaborator with the highest number of performed trials were the United States (651,32.85%) and NIH (77). Therefore, China and its institutions still have large room for progress in promoting TCM monomers in anti-tumor clinical trials. In the next step, priority should be given to the improvement of the research and development ability of domestic enterprises, universities and other institutions, using modern scientific and technological means to solve the problems of poor water solubility and strong toxic and side effects of monomers, so as to promote the clinical research of TCM monomers.

Prenylated Flavonoids in Sophora flavescens: A Systematic Review of Their Phytochemistry and Pharmacology.

Sophora flavescens has been widely used in traditional Chinese medicine for over 1700 years. This plant is known for its heat-clearing, damp-drying, insecticidal, and diuretic properties. Phytochemical research has identified prenylated flavonoids as a unique class of bioactive compounds in S. flavescens. Recent pharmacological studies reveal that the prenylated flavonoids from S. flavescens (PFS) exhibit potent antitumor, anti-inflammatory, and glycolipid metabolism-regulating activities, offering significant therapeutic benefits for various diseases. However, the pharmacokinetics and toxicological profiles of PFS have not been systematically studied. Despite the diverse biological effects of prenylated flavonoid compounds against similar diseases, their structure-activity relationship is not yet fully understood. This review aims to summarize the latest findings regarding the chemical composition, drug metabolism, pharmacological properties, toxicity, and structure-activity relationship of prenylated flavonoids from S. flavescens. It seeks to highlight their potential for clinical use and suggest directions for future related studies.

Banxia Xiexin decoction modulates gut microbiota and gut microbiota metabolism to alleviate DSS-induced ulcerative colitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Banxia Xiexin decoction (BXD) is a classic traditional Chinese medicine prescription for treating ulcerative colitis (UC). However, its potential mechanism of action is still unclear. AIM OF THE STUDY: Reveal the correlation between the beneficial impacts of BXD on UC and the composition of the gut microbiota. MATERIALS AND METHODS: The major constituents of BXD were identified using the HPLC-DAD technique. An experimental model of UC was induced in male C57BL/6 mice by administering dextran sodium sulfate (DSS). A total of 48 mice were divided into different groups, including control, model, high-dose BXD treatment, medium-dose BXD treatment, low-dose BXD treatment, and a group treated with 5-amino acid salicylic acid (5-ASA). Body weight changes and disease activity index (DAI) scores were documented; colon length, colon index, spleen index, and thymus index scores were determined; myeloperoxidase (MPO) and tumor necrosis factor-α (TNF-α) activities were assessed; and histological staining with hematoxylin-eosin and alcian blue/phosphate Schiff was performed. The immunofluorescence technique was employed to examine the presence of ZO-1 and occludin in the colon tissue. 16S rRNA sequencing was employed to assess the gut microbiota's diversity and metabolomics was utilized to examine alterations in metabolites within the gut microbiota. The impact of BXD on the gut microbiota was confirmed through fecal microbiota transplantation (FMT). RESULTS: BXD exhibited a positive impact on UC mice, particularly in the high-dose BXD treatment group. The BXD group experienced weight recovery, decreased DAI scores, improved colon length, and restored of spleen and thymus index scores compared to the DSS group. Additionally, BXD alleviated colon damage and the inflammatory response while restoring intestinal barrier function. FMT in BXD-treated mice also showed therapeutic effects in UC mice. At the phylum level, the relative abundance of Desulfobacterota, Deferribacterota and Actinobacteriota increased; at the genus level, g__norank__f__Muribaculaceae, Dubosiella, Akkermansia, and Lactobacillus increased, whereas Faecalibaculum, Alloprevotella, Turicibacter, and g_Paraprevotella decreased. g__norank_f__Muribaculaceae was positively correlated with body weight and colon length and negatively with colon index scores, splenic index scores, and MPO levels; Alloprevotella was positively correlated with splenic index scores, histological scores, and TNF-α levels and negatively with thymus index scores and thymus index scores. Faecalibaculum was positively correlated with colon index scores and MPO levels. Metabolic investigations revealed 58 potential indicators, primarily associated with the metabolism of amino acids, purines, and lipids. Alloprevotella, g_Paraprevotella, and Bifidobacterium were strongly associated with metabolic pathways. CONCLUSION: BXD showed beneficial therapeutic effects in UC mice. The mechanism may be by promoting the balance and variety of gut microbiota, as well as regulating the metabolism of amino acids, purines, and lipids.

Mining association rules between the granulation feasibility and physicochemical properties of aqueous extracts from Chinese herbal medicine in fluidized bed granulation.

Fluidized bed granulation (FBG) is a widely used granulation technology in the pharmaceutical industry. However, defluidization caused by the formation of large aggregates poses a challenge to FBG, particularly in traditional Chinese medicine (TCM) due to its complex physicochemical properties of aqueous extracts. Therefore, this study aims to identify the complex relationships between physicochemical characteristics and defluidization using data mining methods. Initially, 50 types of TCM were decocted and assessed for their potential influence on defluidization using a set of 11 physical properties and 10 chemical components, utilizing the loss rate as an evaluation index. Subsequently, the random forest (RF) and Apriori algorithms were utilized to uncover intricate association rules among physicochemical characteristics and defluidization. The RF algorithm analysis revealed the top 8 critical factors associated with defluidization. These factors include physical properties like glass transition temperature (Tg) and dynamic surface tension (DST) of DST100ms, DST1000ms, DST10ms and conductivity, in addition to chemical components such as fructose, glucose and protein contents. The results from Apriori algorithm demonstrated that lower Tg and conductivity were associated with an increased risk of defluidization, resulting in a higher loss rate. Moreover, DST100ms, DST1000ms and DST10ms exhibited a contrasting trend in the physical properties Specifically, defluidization probability increases when Tg and conductivity dip below 29.04℃ and 6.21 ms/m respectively, coupled with DST10ms, DST100ms and DST1000ms values exceeding 70.40 mN/m, 66.66 mN/m and 61.58 mN/m, respectively. Moreover, an elevated content of low molecular weight saccharides was associated with a higher occurrence of defluidization, accompanied by an increased loss rate. In contrast, protein content displayed an opposite trend regarding chemical properties. Precisely, the defluidization likelihood amplifies when fructose and glucose contents surpass 20.35 mg/g and 34.05 mg/g respectively, and protein concentration is less than 1.63 mg/g. Finally, evaluation criteria for defluidization were proposed based on these results, which could be used to avoid this situation during the granulation process. This study demonstrated that the RF and Apriori algorithms are effective data mining methods capable of uncovering key factors affecting defluidization.

Chemical and pharmacological difference between honey-fried licorice and fried licorice.

ETHNOPHARMACOLOGICAL RELEVANCE: According to textual research of books from ancient times till now, there are three main preparation methods of "fried licorice", including frying licorice without excipients (F), frying licorice after dipping with water (W), and frying licorice with honey (H). However, with the development over many successive generations, honey frying has gradually become the main processing form of licorice, whereas the fried licorice is nowadays rarely used. AIM OF THE STUDY: The objectives of this study were to clarify the differences of the three forms of "fried licorice" in chemical composition and pharmacological activities, and to screen quality markers for differently processed licorice. It is expected to provide a scientific basis for the rational choice of "fried licorice" as medicine. MATERIALS AND METHODS: Non-target metabolomic analysis based on UHPLC-QE-Orbitrap-MS was conducted to compare the chemical differences between the differently processed licorice material. Pharmacodynamically, the differences in immunomodulatory activity (including intestinal flora experiment), anti-inflammatory activity, and hepatoprotective activity of the differently processed licorice were evaluated. Furthermore, multivariate statistical analysis was performed to screen potential quality markers of honey-fried licorice. The serum concentration of selected markers was determined by UHPLC-QqQ-MS. RESULTS: Metabolomic analysis showed no difference in the chemical composition of F and W, whereas the chemical composition of H was significantly different from that of F and R. The immunomodulatory activity, anti-acute inflammatory effect, and hepatoprotective effect of licorice were significantly improved after frying with honey; No significant differences were observed between F and H in term of immunomodulatory activity and anti-acute inflammatory effect, whereas, H is better than F in terms of liver-protective activity. The intestinal flora experiment confirmed that H does have immunomodulatory activity, while F may induce an increased abundance of certain pathogenic bacteria in the intestine. Multivariate statistical analysis suggests that the content of liquiritin (2), liquiritigenin (3), isoliquiritin (5), isoliquiritigenin (6) and glycyrrhizic acid (7) plusing glycyrrhetinic acid (8) in H group is closely correlated with its improved effects. CONCLUSIONS: This study provides a scientific rational for the selection of "fried licorice" processing methods. In addition, it provides a scientific basis for the selection of quality markers of differently processed licorice.

Emerging biotechnology applications in natural product and synthetic pharmaceutical analyses.

Pharmaceutical analysis is a discipline based on chemical, physical, biological, and information technologies. At present, biotechnological analysis is a short branch in pharmaceutical analysis; however, bioanalysis is the basis and an important part of medicine. Biotechnological approaches can provide information on biological activity and even clinical efficacy and safety, which are important characteristics of drug quality. Because of their advantages in reflecting the overall biological effects or functions of drugs and providing visual and intuitive results, some biotechnological analysis methods have been gradually applied to pharmaceutical analysis from raw material to manufacturing and final product analysis, including DNA super-barcoding, DNA-based rapid detection, multiplex ligation-dependent probe amplification, hyperspectral imaging combined with artificial intelligence, 3D biologically printed organoids, omics-based artificial intelligence, microfluidic chips, organ-on-a-chip, signal transduction pathway-related reporter gene assays, and the zebrafish thrombosis model. The applications of these emerging biotechniques in pharmaceutical analysis have been discussed in this review.

Synergistic mechanism for the bioactivity fortification of licorice by honey.

ETHNOPHARMACOLOGICAL RELEVANCE: Honey-processed licorice has been used since ancient times. It was recorded that honey-processing has the effect of improving the immunomodulatory efficacy of licorice, which has been confirmed by modern pharmacological studies. However, it is still unknown why honey-processing can enhance the immunomodulatory activity of licorice. Our previous research demonstrated that honey has natural deep eutectic solvent (NADES) characteristics. In this study, we investigated the synergistic effect of honey on licorice to elucidate the possible potentiation of honey-frying on licorice. MATERIALS AND METHODS: Immunological experiments were conducted to investigate whether the honey-processing could enhance the immunomodulatory efficacy of licorice in vivo. Then, the synergistic mechanism of honey and licorice was explored based on cell bioactivity tests, metabolomics analysis, bioavailability test, and Fourier transform-infrared (FT-IR) spectra. RESULTS: Pharmacological experiment verified that honey-processing enhanced the immunomodulatory efficacy of licorice. Moreover, honey increased the total flavonoid and polysaccharide contents in licorice decoction, improved the thermal stability and oral bioavailability of certain pharmacologically active constituents, and augmented their overall immunostimulatory functions. Similar effects of honey were also observed with a honey analogue GFSH, a NADES made of glucose, fructose, and sucrose with certain amount of water. The above effects might be due to multiple molecular interactions between active compounds and sugar molecules of honey. CONCLUSION: These findings indicate that the biological activities of medicinal plants might be fortified by honey due to the synergism between licorice and honey. At the meantime, these findings provide theoretical and empirical basis for potential novel applications of honey or other NADESs at augmenting the health-promoting effects of medicinal plants.

Diastereo- and enantioselective nitro-Mannich reaction of α-substituted nitroacetates to N-phosphoryl imines catalyzed by cinchona alkaloid thiourea organocatalysts.

The asymmetric nitro-Mannich reaction of N-phosphoryl imines with α-substituted nitroacetates was performed by using cinchona alkaloid thioureas as organocatalysts in toluene at -20 °C. The present method was highly tolerable to functionalized N-phosphoryl imines and provided a reliable synthetic route to obtain the corresponding ß-nitro ethylphosphoramidates with adjacent quaternary and tertiary chiral centers in high yield (up to 86%) and high enantiostereoselectivity (up to 99% ee) and diastereoselectivity (up to 99 : 1, anti-selectivity).