Differential absorption and metabolic characteristics of organic acid components in Pudilan Xiaoyan Oral Liquid between young rats and adult rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Pudilan Xiaoyan Oral Liquid (PDL) is a proprietary Chinese medicinal preparation approved by the State for treating acute pharyngitis in both adults and children (Approval No. Z20030095). It is worth noting that children exhibit unique physiopathological characteristics compared to adults. However, the in vivo regulatory characteristics of PDL in treating acute pharyngitis in children remain incompletely understood. AIM OF THE STUDY: The differential absorption and metabolism characteristics of the main pharmacological components in PDL in young and adult rats were investigated with a view to providing a reference for preclinical data of PDL in medication for children. MATERIALS AND METHODS: This study utilized UPLC-Q-TOF-MS to investigate the pharmacodynamic material basis of PDL. The focus was on the gastrointestinal digestion and absorption characteristics of organic acid components in PDL (PDL-OAC), known as the primary pharmacodynamic components in this formulation. The research combined in vitro dynamic simulation and a Quadruple single-pass intestinal perfusion model to examine these characteristics. The permeability properties of PDL-OAC were evaluated using an artificial parallel membrane model. Additionally, an acute pharyngitis model was established to evaluate the histopathological condition of the pharynx in young rats using H&E staining. The levels of IL-1ß, TNF-α, IL-6, and IL-10 in blood and pharyngeal tissue homogenates of young rats were quantified using ELISA kits. RESULTS: A total of 91 components were identified in PDL, including 33 organic acids, 24 flavonoids, 14 alkaloids, 5 terpenoids and coumarins, 3 sugars, and 12 amino acids. The PDL-OAC exhibited a significant reduction in IL-1ß, TNF-α, IL-6, and IL-10 levels in the pharyngeal tissues of young rats with acute pharyngitis. Results from dynamic simulation studies of gastrointestinal fluids revealed that the PDL-OAC (Specifically chlorogenic acid (CGA), gallic acid (GA), chicoric acid (CRA), and caffeic acid (CA)) were effectively stabilized in the gastrointestinal fluids of both children and adults in vitro. Young rats, characterized by thinner intestinal walls and higher permeability, efficiently absorbed the four organic acids across the entire intestinal segment. The absorption of CGA, GA, and CRA followed a concentration-dependent pattern, with CGA and GA absorption being influenced by exocytosis. CONCLUSION: The efficacy of the PDL-OAC in treating acute pharyngitis was demonstrated in young rats. The absorption rate of these components was observed to be faster in young rats compared to adult rats, underscoring the need for dedicated studies on the drug's usage in children. This research provides valuable insights for the appropriate clinical use of PDL in pediatric patients.

The carrier function and inhibition effect on benign prostatic hyperplasia of a glucan from Epimedium brevicornu Maxim.

Epimedium, a traditional Chinese medicine commonly used as a dietary supplement, contains polysaccharides and flavonoids as its main bioactive ingredients. In this study, a neutral homogeneous polysaccharide (EPSN-1) was isolated from Epimedium brevicornu Maxim. EPSN-1 was identified as a glucan with a backbone of →4)-α-D-Glcp-(1→, branched units comprised α-D-Glcp-(1→6)-α-D-Glcp-(1→, ß-D-Glcp-(1→6)-ß-D-Glcp-(1→ and α-D-Glcp-(1→ connected to the C6 position of backbone. The conformation of EPSN-1 in aqueous solution indicated its potential to form nanoparticles. This paper aims to investigate the carrier and pharmacodynamic activity of EPSN-1. The findings demonstrated that, on the one hand, EPSN-1, as a functional ingredient, may load Icariin (ICA) through non-covalent interactions, improving its biopharmaceutical properties such as solubility and stability, thereby improving its intestinal absorption. Additionally, as an effective ingredient, EPSN-1 could help maintain the balance of the intestinal environment by increasing the abundance of Parabacteroides, Lachnospiraceae UGG-001, Anaeroplasma, and Eubacterium xylanophilum group, while decreasing the abundance of Allobaculum, Blautia, and Adlercreutzia. Overall, this dual action of EPSN-1 sheds light on the potential applications of natural polysaccharides, highlighting their dual role as carriers and contributors to biological activity.

Self-Assembled Aggregated Structures of Natural Products for Oral Drug Delivery.

The self-assembling aggregated structures of natural products have gained significant interest due to their simple synthesis, lack of carrier-related toxicity, and excellent biological efficacy. However, the mechanisms of their assembly and their ability to traverse the gastrointestinal (GI) barrier remain unclear. This review summarizes various intermolecular non-covalent interactions and aggregated structures, drawing on research indexed in Web of Science from 2010 to 2024. Cheminformatics analysis of the self-assembly behaviors of natural small molecules and their supramolecular aggregates reveals assembly-favorable conditions, aiding drug formulation. Additionally, the review explores the self-assembly properties of macromolecules like polysaccharides, proteins, and exosomes, highlighting their role in drug delivery. Strategies to overcome gastrointestinal barriers and enhance drug bioavailability are also discussed. This work underscores the potential of natural products in oral drug delivery and offers insights for designing more effective drug delivery systems.

A novel strategy for the multi-components division and discovering pharmacodynamic material basis of Chinese herbal compounds: A case study of Xian-Ling-Gu-Bao capsule.

The therapeutic effects of Chinese herbal compounds are often achieved through the synergistic interactions of multiple ingredients. However, current research predominantly focuses on individual ingredients, neglecting the holistic nature of Chinese herbal compounds. This study proposes a novel strategy to elucidate the pharmacodynamic material basis of Chinese herbal compounds based on their multi-components (components named 'ZuFen' in China, it refers to multiple ingredients with similar chemical structures) composition, using the Xian-Ling-Gu-Bao (XLGB) capsule as a case study. Cheminformatics-based components partitioning was conducted after sourcing ingredients from various databases, resulting in a total of 856 ingredients which were categorized into nine major components. Furthermore, the pharmacodynamic ingredients of XLGB capsule were determined by analyzing the ingredients that were absorbed into the bloodstream. Through a combination of these ingredients and screening for absorption, the Dipsacus asper saponin components, Psoralea corylifolia coumarin components, and Epimedium flavonoid polyglycosides components were isolated. The anti-osteoporosis efficacy of these components were evaluated in zebrafish, demonstrating their capability to reverse mineralization reduction caused by prednisolone. These findings further support the idea that these components serve as the material basis for the pharmacological efficacy of XLGB capsule. This study provides a novel systematic strategy for discovering the pharmacodynamic material basis of the efficacy of Chinese herbal compounds based on a 'multi-components' perspective.

Combined ROS Responsive Polydopamine-Coated Berberine Nanoparticles Effective Against Ulcerative Colitis in Mouse Model.

Introduction: Enhancing the efficacy of berberine (BBR) in the treatment of ulcerative colitis (UC) through the development of dopamine-coated berberine nanoparticles (PDA@BBR NPs) with ROS-responsive and adhesive properties. Methods: Berberine nanoparticles (BBR NPs) were synthesized using the nonsolvent precipitation method, and their surfaces were coated with polydopamine (PDA) through oxidative polymerization. The PDA@BBR NPs were characterized by transmission electron microscopy (TEM), size analysis, and zeta potential analysis. Drug loading and encapsulation efficiency were analyzed using fluorescence spectroscopy. The responsiveness of these nanoparticles to reactive oxygen species (ROS) was assessed in vitro, while their adhesive properties and therapeutic efficacy on UC were evaluated in vivo. Results: Physicochemical property studies showed that PDA coated BBR NPs nanoparticles have good dispersion and stability. In vitro results showed that PDA@BBR NPs could prolong the retention time of the drug at the colonic site and could realize the gradual drug release under ROS environment. In addition, animal studies showed that PDA@BBR NPs exhibited significant anti-inflammatory effects on DSS-induced colitis and effectively reduced intestinal mucosal damage. Conclusion: PDA@BBR NPs are ROS-responsive nanoparticles that adhere well and have a high drug loading capacity. They have shown therapeutic effects in mice with UC, indicating that this formulation may be a promising treatment option.

Novel nano-encapsulated limonene: Utilization of drug-in-cyclodextrin-in-liposome formulation to improve the stability and enhance the antioxidant activity.

Drug-in-cyclodextrin-in-liposome (DCL) combines advantages of cyclodextrin and liposome. Here, DCL formulation was successfully prepared to encapsulate limonene (Lim), whose characterization revealed that particle size was 147.5 ± 1.3 nm and zeta potential was -48.7 ± 0.8 mV. And the complexation mechanism of Lim/HP-ß-CD inclusion complex (the intermediate of DCL) was analyzed by molecular dynamics simulation, showing that Lim was entrapped into the cavity of HP-ß-CD through electrostatic and hydrophobic interaction with a molar ratio of 1:1. Notably, DCL formulation not only reduced Lim volatilization in 25℃, but also enhanced the free radical (DPPH· and ABTS·+) scavenging ability of Lim. In summary, Lim-DCL formulation improved the stability and enhanced the antioxidant activity of Lim. DCL nanocarrier system is suitable to preserve volatile and hydrophobic compounds, enlarging their application in pharmaceutics industries.

Interpreting the efficacy enhancement mechanism of Chinese medicine processing from a biopharmaceutic perspective.

Chinese medicine processing (CMP) is a unique pharmaceutical technology that distinguishes it from natural medicines. Current research primarily focuses on changes in chemical components to understand the mechanisms behind efficacy enhancement in processing. However, this paper presents a novel perspective on the biopharmaceutics of CMP. It provides a comprehensive overview of the current research, emphasizing two crucial aspects: the role of 'heat' during processing and the utilization of processing adjuvants. The paper highlights the generation of easily absorbed components through the hydrolysis of glycosides by 'heat', as well as the facilitation of dissolution, absorption, and targeted distribution of active components through the utilization of processing adjuvants. From a biopharmaceutic perspective, this paper provides a lucid comprehension of the scientific foundation for augmenting the efficacy of CMP. Moreover, it proposes a three-dimensional research framework encompassing chemical reactions, phase transitions, and biopharmaceutical properties to further investigate the mechanisms involved in enhancing the efficacy of CMP.

Study on the intervention effect of Epimedium before and after suet-oil-processed on kidney yang deficiency rats based on intestinal flora and fecal metabolomics.

Epimedium is a Chinese herbal medicine commonly used in clinical practice to reinforce yang. Previous studies have shown that Epimedium fried with suet oil based has the best effect on warming kidney and promoting yang. Evidence suggests a relationship between kidney yang deficiency syndrome (KYDS) and metabolic disorders of the intestinal microflora. However, the specific interaction between KYDS and the intestinal microbiome, as well as the internal regulatory mechanism of the KYDS intestinal microbiome regulated by Epimedium fried with suet oil, remain unclear. The purpose of this study was to investigate the regulatory effects of different processed products of Epimedium on intestinal microflora and metabolites in rats with kidney yang deficiency, and to reveal the processing mechanism of Epimedium fried with suet oil warming kidney and helping yang. 16 S rRNA and LC-MS/MS technology were used to detect fecal samples. Combined with multivariate statistical analysis, differential intestinal flora and metabolites were screened. Then the content of differential bacteria was then quantified using quantitative real-time fluorescence PCR. Furthermore, the correlation between differential bacterial flora and metabolites was analyzed using Spearman's method. The study found that the composition of intestinal flora in rats with kidney yang deficiency changed compared to healthy rats. Epimedium fried with suet oil could increase the levels of beneficial bacteria, while significantly reducing the levels of harmful bacteria. Real-time quantitative PCR results were consistent with 16 S rRNA gene sequencing analysis. Fecal metabolomics revealed that KYDS was associated with 30 different metabolites, involving metabolic pathways steroid hormone biosynthesis etc. Moreover, differential bacteria were closely correlated with potential biomarkers. Epimedium could improve metabolic disorders associated with KYDS by acting on the intestinal flora, with Epimedium fried with suet oil demonstrating the most effective regulatory effect. Its potential mechanism may involve the regulation of abnormal metabolism and the impact on the diversity and structure of the intestinal flora.

Enhancing the Biopharmacological Characteristics of Asperosaponin VI: Unveiling Dynamic Self-Assembly Phase Transitions in the Gastrointestinal Environment.

Purpose: Asperosaponin VI (ASP VI) as an active ingredient of Dipsacus asperoides, which has a wide range of biological and pharmacological activity. However, its development and application are restricted due to the poor gastrointestinal permeability and oral bioavailability. This investigation aims to reveal the influence of the self-assembled structure by the interaction between ASP VI and endogenous components NaTC and/or DOPC in the gastrointestinal environment on its biopharmaceutical properties, and novelty elucidated the molecular mechanism for the formation of self-assembled nanomicelles. Methods: This change in phase state in gastrointestinal fluids is characterized by dynamic light scattering (DLS) and transmission electron microscope (TEM). UPLC-Q-TOF-MS was used to analyze the composition of phase components and the exposure of nanomicelles in vivo. Molecular dynamics simulation (MDS) was applied to preliminarily elucidate the self-assembly mechanism of ASP VI in the gastrointestinal environment. Furthermore, theS8 promoting absorption mechanism of nanomicelles were investigated through in vivo pharmacokinetic experiments, parallel artificial membrane permeability assay (PAMPA), quadruple single-pass intestinal perfusion in rats, and Caco-2 cell monolayer model. Results: We demonstrated that the ASP VI could spontaneously form dynamic self-assembled structures with sodium taurocholate (NaTC) and dipalmitoyl phosphatidylcholine (DOPC) during gastrointestinal solubilization, which promoted the gastrointestinal absorption and permeability of ASP VI and increased its exposure in vivo, thus improving the biopharmacological characteristics of ASP VI. Moreover, ASP VI-NaTC-DOPC-self-assembled nanostructures (ASP VI-NaTC-DOPC-SAN) manifested higher cellular uptake in Caco-2 cells as evidenced by flow cytometry and confocal microscopy, and this study also preliminarily revealed the mechanism of self-assembly formation of ASP VI with endogenous components NaTC and DOPC driven by electrostatic and hydrogen bonding interactions. Conclusion: This study provides evidence that the dynamic self-assembled phase transition may play a key role in improving the biopharmacological characteristics of insoluble or low permeability active ingredients during the gastrointestinal dissolution of Chinese medicines.

[Improvement of solubility of epimedium flavonoid secondary glycoside components by traditional Chinese medicine polysaccharides and its mechanism].

The poor solubility of insoluble components of traditional Chinese medicine(TCM) is an important factor restricting the development of its preparations. Natural polysaccharides of TCM can be used as functional components to increase the solubility of insoluble components. Epimedium flavonoid secondary glycoside components(EFSGC) have been shown to have positive effects on the prevention and treatment of osteoporosis, but they exhibit poor solubility. Therefore, the strategy of solubilizing EFSGC with TCM polysaccharides was adopted, and its effect on the permeability and stability of EFSGC was evaluated in this study. Based on the equilibrium solubility experiment of EFSGC, it was found that Panax notoginseng crude polysaccharide(PNCP) had the best solubilization effect on EFSGC among the ten kinds of TCM polysaccharides, which increased the solubility of EFSGC from 0.8 mg·mL~(-1) to 13.3 mg·mL~(-1). It should be noted that after the solubilization of EFSGC by preparation technology, the effects on permeability and stability should be considered. Therefore, this study also investigated these two properties. The results showed that PNCP increased the effective transmittance of EFSGC from 50.5% to 71.1%, which could increase the permeability of EFSGC significantly. At the same time, it could improve the stability of EFSGC in the simulated gastric juice environment. In order to explain the solubilization mechanism of PNCP on EGSGC, critical micelle concentration, particle size, potential, differential scanning calorimetry, and infrared spectroscopy were analyzed. It was preliminarily inferred that the mechanism was as follows: PNCP and EFSGC could self-assemble into aggregates for solubilization by intermolecular hydrogen bonding interaction in water. In summary, PNCP can not only improve the solubility of EFSGC but also improve its permeability and stability. This study lays the foundation for the application of TCM polysaccharides as a functional component to solubilize insoluble components.

A Multi-Component Nano-Co-Delivery System Utilizing Astragalus Polysaccharides as Carriers for Improving Biopharmaceutical Properties of Astragalus Flavonoids.

Purpose: Enhancing the dissolution, permeation and absorption of active components with low solubility and poor permeability is crucial for maximizing therapeutic efficacy and optimizing functionality. The objective of this study is to investigate the potential of natural polysaccharides as carriers to improve the biopharmaceutical properties of active components. Methods: In this study, we employed four representative flavonoids in Astragali Radix, namely Calycosin-7-O-ß-D-glucoside (CAG), Ononin (ON), Calycosin (CA) and Formononetin (FMN), as a demonstration to evaluate the potential of Astragalus polysaccharides (APS) as carriers to improve the biopharmaceutical properties, sush as solubility, permeability, and absorption in vivo. In addition, the microstructure of the flavonoids-APS complexes was characterized, and the interaction mechanism between APS and flavonoids was investigated using multispectral technique and molecular dynamics simulation. Results: The results showed that APS can self-assemble into aggregates with a porous structure and large surface area in aqueous solutions. These aggregates can be loaded with flavonoids through weak intermolecular interactions, such as hydrogen bonding, thereby improving their gastrointestinal stability, solubility, permeability and absorption in vivo. Conclusion: We discovered the self-assembly properties of APS and its potential as carriers. Compared with introducing external excipients, the utilization of natural polysaccharides in plants as carriers may have a unique advantage in enhancing dissolution, permeation and absorption.

Integrated metabolome-microbiome analysis investigates the different regulations of Pudilan Xiaoyan oral liquid in young rats with acute pharyngitis compared to adult rats.

BACKGROUND: Pudilan Xiaoyan Oral Liquid (PDL) is a famous traditional Chinese prescription recorded in the Chinese Pharmacopeia, which is widely used to treat inflammatory diseases of the respiratory tract in children and adults. However, the endogenous changes in children and adults with PDL in the treatment of acute pharyngitis remain unclear. PURPOSE: The differential regulatory roles of PDL in endogenous metabolism and gut microbes in young and adult rats were investigated with a view to providing a preclinical data reference for PDL in medication for children. METHODS: An acute pharyngitis model was established, and serum levels of inflammatory factors and histopathology were measured. This study simulated the growth and development of children in young rats and explored the endogenous metabolic characteristics and intestinal microbial composition after the intervention of PDL by using serum metabolomic technique and 16S rRNA high-throughput sequencing technique. RESULTS: The results showed that PDL had therapeutic effects on young and adult rats with acute pharyngitis. Sixteen biomarkers were identified by metabolomics in the serum of young rats and 23 in adult rats. PDL can also affect intestinal microbial diversity and community richness in young and adult rats. Alloprevotella, Allobaculum, Alistipes, Bifidobacterium, and Enterorhabdus were prominent bacteria in young rats. Bacteria from the phylum Firmicutes of the adult rats changed more significantly under the treatment of PDL. In young rats, amino acid metabolism was the primary regulatory mode of PDL, whereas, in adult rats, glycerophospholipid metabolism was studied. CONCLUSION: The regulation of PDL on the serum metabolite group and intestinal microflora in young rats was different from that in adult rats, indicating the necessity of an independent study on children's medication. PDL may also exert therapeutic effects on young and adult rats by regulating gut microbial homeostasis. The results support the clinical application of PDL.

Moringa oleifera Lam.: a comprehensive review on active components, health benefits and application.

Moringa oleifera Lam. is an edible therapeutic plant that is native to India and widely cultivated in tropical countries. In this paper, the current application of M. oleifera was discussed by summarizing its medicinal parts, active components and potential mechanism. The emerging products of various formats such as drug preparation and product application reported in the last years were also clarified. Based on literature reports, the unique components and biological activities of M. oleifera need to be further studied. In the future, a variety of new technologies should be applied to the development of M. oleifera products, to enrich the varieties of dosage forms, improve the bitter taste masking technology, and make it better for use in the fields of food and medicine.

Multidisciplinary strategies to enhance therapeutic effects of flavonoids from Epimedii Folium: Integration of herbal medicine, enzyme engineering, and nanotechnology.

Flavonoids such as baohuoside I and icaritin are the major active compounds in Epimedii Folium (EF) and possess excellent therapeutic effects on various diseases. Encouragingly, in 2022, icaritin soft capsules were approved to reach the market for the treatment of hepatocellular carcinoma (HCC) by National Medical Products Administration (NMPA) of China. Moreover, recent studies demonstrate that icaritin can serve as immune-modulating agent to exert anti-tumor effects. Nonetheless, both production efficiency and clinical applications of epimedium flavonoids have been restrained because of their low content, poor bioavailability, and unfavorable in vivo delivery efficiency. Recently, various strategies, including enzyme engineering and nanotechnology, have been developed to increase productivity and activity, improve delivery efficiency, and enhance therapeutic effects of epimedium flavonoids. In this review, the structure-activity relationship of epimedium flavonoids is described. Then, enzymatic engineering strategies for increasing the productivity of highly active baohuoside I and icaritin are discussed. The nanomedicines for overcoming in vivo delivery barriers and improving therapeutic effects of various diseases are summarized. Finally, the challenges and an outlook on clinical translation of epimedium flavonoids are proposed.

Zengshengping improves lung cancer by regulating the intestinal barrier and intestinal microbiota.

Lung cancer is a common malignant tumor in clinical practice, and its morbidity and mortality are in the forefront of malignant tumors. Radiotherapy, chemotherapy, and surgical treatment play an important role in the treatment of lung cancer, however, radiotherapy has many complications and even causes partial loss of function, the recurrence rate after surgical resection is high, and the toxic and side effects of chemotherapy drugs are strong. Traditional Chinese medicine has played a huge role in the prognosis and improvement of lung cancer, among them, Zengshengping (ZSP) has the effect of preventing and treating lung cancer. Based on the "gut-lung axis" and from the perspective of "treating the lung from the intestine", the purpose of this study was to research the effect of Zengshengping on the intestinal physical, biological, and immune barriers, and explore its role in the prevention and treatment of lung cancer. The Lewis lung cancer and urethane-induced lung cancer models were established in C57BL/6 mice. The tumor, spleen, and thymus were weighed, and the inhibition rate, splenic and thymus indexes analyzed. Inflammatory factors and immunological indexes were detected by enzyme-linked immunosorbent assay. Collecting lung and colon tissues, hematoxylin and eosin staining was performed on lung, colon tissues to observe histopathological damage. Immunohistochemistry and Western blotting were carried out to detect tight junction protein expression in colon tissues and expression of Ki67 and p53 proteins in tumor tissues. Finally, the feces of mice were collected to investigate the changes in intestinal microbiota using 16SrDNA high-throughput sequencing technology. ZSP significantly reduced tumor weight and increased the splenic and thymus indexes. It decreased expression of Ki67 protein and increased expression of p53 protein. Compared with Model group, ZSP group reduced the serum levels of interleukin (IL)-1ß, IL-6, tumor necrosis factor α (TNF-α), and ZSP group increased the concentration of secretory immunoglobulin A (sIgA) in the colon and the bronchoalveolar lavage fluid (BALF). ZSPH significantly increased the level of tight junction proteins such as ZO-1, Occludin and Claudin-1. Model group significantly reduced the relative abundance of Akkermansia (p < 0.05) and significantly promoted the amount of norank_f_Muribaculaceae, norank_f_Lachnospiraceae (p < 0.05) compared with that in the Normal group. However, ZSP groups increased in probiotic strains (Akkermansia) and decreased in pathogens (norank_f_Muribaculaceae, norank_f_Lachnospiraceae). Compared with the urethane-induced lung cancer mice, the results showed that ZSP significantly increased the diversity and richness of the intestinal microbiota in the Lewis lung cancer mice. ZSP played an important role in the prevention and treatment of lung cancer by enhancing immunity, protecting the intestinal mucosa and regulating the intestinal microbiota.

Characterization of metabolites of sagittatoside B in rats using UPLC-QTOF-MS spectrometry.

Sagittatoside B is one of the principal diglucosides in Herba Epimedii. In this work, an ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UPLC/Q-TOF-MS) was applied to the rapid analysis of sagittatoside B metabolites in rats after oral administration. A total number of 17 metabolites were detected or tentatively identified from rat plasma, bile, urine and feces. The major metabolic pathways of sagittatoside B in rats were hydrolysis, hydrogenation, hydroxylation, dehydrogenation, demethylation, decarbonylation and conjugation with glucuronic acid and different sugars. This work revealed the metabolism of sagittatoside B in vivo, and reported the characteristic metabolic reactions of sagittatoside B for the first time. This provided the basis for the further research and development of sagittatoside B, and also provided reference for the metabolism of active flavonoid compounds.

[Substitution mode of rare and endangered Chinese medicinal materials and research strategy of multi-component replacement].

Rare and endangered Chinese medicinal materials are the material basis for innovation and development of Chinese medicinal materials and their curative effects are remarkable. However, the resources are in shortage due to various man-made or natural factors such as rising demand, overexploitation and environmental degradation. Therefore, finding alternatives is a feasible and effective solution. This study systematically sorted out the list of rare and endangered Chinese medicinal materials, and combed relevant policies and regulations. According to existing research, the substitution model of rare and endangered Chinese medicinal materials was constructed from the theoretical level. In view of the slow search for substitutes, the failure to follow the basic theory of traditional Chinese medicine in the process of research and development, the difficulty in breaking through technologies and the incomplete guarantee of the clinical efficacy of substitutes, a multi-component replacement was proposed to replace the originals with more effective components from a wide range of sources. This study was expected to promote the study on the substitutes of rare and endangered Chinese medicinal materials to step into a new stage.

Integrating strategies of metabolomics, network pharmacology, and experiment validation to investigate the processing mechanism of Epimedium fried with suet oil to warm kidney and enhance yang.

Introduction: Epimedium, a traditional Chinese medicine (TCM) commonly used in ancient and modern China, is one of the traditional Chinese medicines clinically used to treat kidney yang deficiency syndrome (KYDS). There are differences in the efficacy of Epimedium before and after processing, and the effect of warming the kidney and enhancing yang is significantly enhanced after heating with suet oil. However, the active compounds, corresponding targets, metabolic pathways, and synergistic mechanism of frying Epimedium in suet oil to promote yang, remain unclear. Methods: Herein, a strategy based on comprehensive GC-TOF/MS metabolomics and network pharmacology analysis was used to construct an "active compounds-targets-metabolic pathways" network to identify the active compounds, targets and metabolic pathways involved. Subsequently, the targets in kidney tissue were further validated by real-time quantitative polymerase chain reaction (RT-qPCR). Histopathological analysis with physical and biochemical parameters were performed. Results: Fifteen biomarkers from urine and plasma, involving five known metabolic pathways related to kidney yang deficiency were screened. The network pharmacology results showed 37 active compounds (13 from Epimedium and 24 from suet oil), 159 targets, and 267 pathways with significant correlation. Importantly, integrated metabolomics and network pharmacologic analysis revealed 13 active compounds (nine from Epimedium and four from suet oil), 7 corresponding targets (ALDH2, ARG2, GSTA3, GSTM1, GSTM2, HPGDS, and NOS2), two metabolic pathways (glutathione metabolism, arginine and proline metabolism), and two biomarkers (Ornithine and 5-Oxoproline) associated with improved kidney yang deficiency by Epimedium fried with suet oil. Discussion: These finds may elucidate the underlying mechanism of yang enhancement via kidney warming effects. Our study indicated that the mechanism of action mainly involved oxidative stress and amino acid metabolism. Here, we demonstrated the novel strategies of integrating metabolomics and network pharmacology in exploring of the mechanisms of traditional Chinese medicines.

Astragalus polysaccharides alleviate type 1 diabetes via modulating gut microbiota in mice.

Type 1 diabetes (T1D) is a serious health problem that needs to be addressed worldwide. Astragalus polysaccharides (APS), the main chemical components of Astragali Radix, have anti-diabetic activity. As most plant polysaccharides are difficult to digest and absorb, we hypothesised that APS exert hypoglycaemic effects through the gut. This study intends to investigate the modulation of T1D associated with gut microbiota by neutral fraction of Astragalus polysaccharides (APS-1). T1D mice were induced with streptozotocin and then treated with APS-1 for 8 weeks. Fasting blood glucose levels were decreased and the insulin levels were increased in T1D mice. The results demonstrated that APS-1 improved gut barrier function by regulating ZO-1, Occludin and Claudin-1 expression, and reconstructed gut microbiota by increasing the relative abundance of Muribaculum, Lactobacillus and Faecalibaculum. In addition, APS-1 significantly increased the levels of acetic acid, propionic acid, butyric acid and inhibited the expression of pro-inflammatory factors IL-6 and TNF-α in T1D mice. Further exploration revealed that APS-1 alleviation of T1D may be associated with short-chain fatty acids (SCFAs)-producing bacteria, and that SCFAs binds to GPRs and HDACs proteins and modulate the inflammatory responses. In conclusion, the study supports the potential of APS-1 as a therapeutic agent for T1D.

Structural elucidation of a novel polysaccharide from Ophiopogonis Radix and its self-assembly mechanism in aqueous solution.

Ophiopogonis Radix polysaccharides with various bioactivities have caught people's attention in the pharmaceutical and functional food industries. It is necessary to reveal their structures, chain conformations, and solvent behaviors. A neutral polysaccharide named ORP-1 with molecular weight of 3667 Da was obtained from Ophiopogonis Radix. It was composed of d-fructofuranose and d-glucopyranose in the ratio of 0.85:0.15. Methylation, FT-IR and NMR analysis indicated ORP-1 consisted of 2,6-linked-Fruf units as the main chain and 1-linked-Glcp residue at the end. Congo red assay showed ORP-1 had no triple-helix structure. The observation of TEM and AFM found ORP-1 could self-assemble to form colloidal aggregate in water. This phenomenon was verified using CMC determination and MD simulation. Furthermore, intermolecular hydrogen bonds and hydrophobic interactions would be the main forces driving the aggregate. These results provided reference for the study of the chain conformation and behavior of polysaccharides in aqueous solution.