In traditional Chinese medicine theory, Scutellaria baicalensis Georgi [Lamiaceae; Scutellariae radix] (SR) is bitter and cold in nature. It enters the lung, gallbladder, spleen, large intestine, and small intestine meridians. It clears heat and dries dampness, purges fire and detoxifies, stops bleeding, and stabilizes pregnancy. It excels at clearing lung fire and upper-body heat. Flavonoids, the primary active compound of SR, undergo metabolism in vivo through Phase I and Phase II reactions as well as intestinal flora-mediated processes. Modern pharmacological research indicates that flavonoid compounds exhibit diverse biological activities in immune modulation, antiviral, anti-inflammatory, antibacterial, and antitumor effects. In recent years, novel formulations such as nanomedicines and liposomes have garnered increasing attention to enhance their stability and bioavailability. This review systematically summarizes the research progress on flavonoid compounds in SR, comprehensively elaborating on their phytochemistry, extraction methods, separation and purification techniques, in vivo metabolism, immunological and pharmacological effects, toxicity, and novel dosage forms. It provides theoretical foundations and practical references for the further research, development, and rational application of these compounds.

Alcoholic liver disease (ALD) is a prevalent metabolic disorder associated with alcohol consumption, posing significant global health challenges. Ecklonia kurome, a marine traditional Chinese medicine (TCM), is recognized as a medicinal resource with hepatoprotective properties. The principal active constituents are polysaccharides, however, the bioavailability of these polysaccharides are poor. In this study, a bidirectional liquid fermentation system was established, and Inonotus hispidus was employed as the fermentation strain to enhance the efficacy of E. kurome in alleviating alcohol-induced liver injury. Compared to prefermentation levels, the concentrations of α-L-guluronic acid and β-D-mannuronic acid increased significantly by 5.86-fold and 5.65-fold, respectively. Following treatment with bidirectional fermentation mycoplasm (SH-KB), biochemical parameters such as triglycerides (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and histopathological examinations, showed a significant hepatoprotective effect. The molecular docking revealed that four active monosaccharides exhibited strong binding capabilities with AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor alpha (PPAR-α) and sterol regulatory element-binding protein 1 (SREBP-1), which are key regulators of lipid metabolism. And western blotting (WB) results also confirmed this result. All the results indicated that SH-KB significantly mitigated alcohol-induced liver injury through affecting antioxidant enzyme activities, anti-inflammatory properties, and the regulation of lipid metabolism. This study provided meaningful evidence supporting the effect of SH-KB on ALD and offered new directions for efficient utilization of natural oligosaccharide.

Puerarin is a natural flavonoid glycoside extracted from the traditional Chinese medicine Puerariae Lobatae Radix or Pueraria lobata (Willd), known for its hepatoprotective properties. While prior studies indicate that PR can mitigate ALD, the underlying mechanisms by which PR exerts its anti-ALD effects via intestinal flora remain poorly understood. This study aimed to investigate the metabolic differences of PR in normal and ALD model rats were analyzed using UHPLC-HRMS. Further validation of PR metabolic products in vivo through in vitro fecal fermentation. Additionally, the relationship between the anti-ALD properties of PR and intestinal flora was explored using 16S rRNA sequencing technology, with confirmation obtained from fecal microbiota transplantation (FMT) experiments and functional strain experiments. Finally, through non-targeted metabolomics and liver transcriptomics combined with in vitro cell pharmacological studies, the mechanism of action of PR and its in vitro fermentation metabolites against ALD was explored. In the PR metabolic test, 20 metabolites were identified in the serum, urine, and feces of normal and ALD model rats, primarily associated with reactions including deglycosylation, hydrogenation, aldehyde esterification, hydroxylation, and methylation. 6 metabolites were verified in vitro transformation system. Subsequently, we used FMT experiments and 16S rRNA sequencing to find that intestinal flora imbalance can lead to liver disease and PR can improve liver disease by regulating intestinal flora. Based on multi-omics analysis and in vitro pharmacological activity analysis, PR and its in vitro fermented metabolites inhibit MAPK and Nrf2 pathways, further reducing inflammation and oxidative stress. The results of this study show that PR can improve ALD, with its mechanism of action potentially involving regulation of the intestinal flora, suppression of inflammatory responses, and inhibition of oxidative stress.

Plant-derived bioactive peptides (PDBPs) have become a key research focus owing to their multiple targets and high safety. However, current challenges in this field primarily include the low efficiency of traditional extraction techniques, the complex structure-activity relationships of PDBPs, the scalability of novel technologies, inadequate understanding of multisystem synergistic effects, and the scarcity of human clinical trials. To address these gaps, future research should integrate artificial intelligence to establish an integrated technological system spanning computer-aided design, targeted preparation, and activity verification, while prioritizing efforts to elucidate the mechanisms of multisystem synergism, develop environmentally friendly extraction processes and targeted delivery systems, and facilitate the translation of PDBPs from basic research to functional products. This review integrates food science, biotechnology, and pharmacology to analyze PDBPs structures, techniques, and cross-system actions, providing a theoretical and technological roadmap for applications in foods, pharmaceuticals, and cosmetics.

ETHNOPHARMACOLOGICAL RELEVANCE:Within the framework of traditional Chinese medicine, Bupleuri Radix (BR), distinguished by its bitter flavor and slightly cold properties, targets the liver and gallbladder meridians. It is traditionally used for liver soothing, depression alleviation, fever reduction, and the elevation of yang and qi. BR is a key component of traditional formulations such as Xiaochaihu Decoction and Xiaoyao Powder. Modern pharmacological investigations have identified saikosaponins as the principal active ingredients in BR, which exhibit a broad spectrum of therapeutic effects. However, current research on the pharmacology, toxicology, and development of new dosage forms for saikosaponins remains insufficient. AIM:This review examined the detailed structure of saikosaponins and explored the current research progress in areas such as their extraction, purification, identification, biotransformation, pharmacological effects, toxicity, combination therapies, and new dosage form development. The review aims to provide a scientific foundation for future research and highlight knowledge gaps in these areas. MATERIALS AND METHODS:Data for this study were systematically gathered from various sources, including journal articles, books, and academic papers, using prominent databases such as Web of Science, ScienceDirect, Google Scholar, PubMed, SpringerLink, CNKI, VIP, and Wan Fang Data. Additional verification of species distribution and scientific names was performed using online resources like 'Flora of China,' 'Flora of the World,' and the 'Chinese Pharmacopoeia.' ChemDraw 20.0 software was employed to visualize the chemical composition. RESULTS:The review summarized the most recent research on saikosaponins, focusing on extraction, purification, biotransformation, pharmacological effects, toxicity studies, combination therapies, and the development of new dosage forms. Over 130 saikosaponins have been isolated and characterized from BR in phytochemical studies. These saponins undergo glycosyl conversion through microbial or enzyme-catalyzed hydrolysis, thereby enhancing their pharmacological activity. Their effects include anti-inflammatory, antidepressant, antiepileptic, antitumor, and immune regulation properties. Despite these benefits, high doses of saikosaponins can induce toxicity, limiting their widespread clinical use. CONCLUSIONS:This review visualized 132 saikosaponin structures for the first time, covering their extraction, purification, biotransformation, pharmacological effects, toxicity evaluation, combination therapies, and new dosage form development. Compared to existing literature, this review offers a more comprehensive perspective, emphasizing key biological activities, toxicity, and the development of new dosage forms while identifying challenges in this area. Additionally, this review explored the mechanisms underlying saikosaponins' effects and proposes optimizing dosage form design as a critical direction for future research.

Daidzin, as one of isoflavone glycosides, has been reported to have multiple activities with few absorbed into body. However, the metabolic behavior of daidzin by intestinal flora has not been researched, that this defect severely constrains its applications. In this study, daidzin and its metabolites were qualitatively and quantitatively analyzed by HPLC and ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) in the fermentation system for daidzin and fecal bacteria. Meanwhile, the alterations of intestinal flora with daidzin were detected by 16S rRNA sequencing technology. Based on the results of intestinal flora, the daidzin and its metabolites transformed by the screened probiotics were quantified and qualified, which the results would corroborate the transformation of daidzin and fecal bacteria. Eventually, daidzin was decreased from 0.30158mg/mL at 0h to 0.01176mg/mL at 48h, daidzein, as the aglycone of daidzin, was increased from 0.02963mg/mL at 0h to 0.04682mg/mL at 48h, suggesting the presence of other metabolites. Next, 31 metabolites including the products of ketone removal, Retro-Diels-Alder (RDA) fragmentation, hydroxylation, methylation, C ring cracking and sulfation were identified. The results of 16S rRNA sequencing showed that the intestinal flora, especially Bifidobacterium, was dramatically altered after incubation with daidzin (p<0.05). Hereby, the fermentation systems of five probiotics (Lactobacillus 3044, Bifidobacterium adolescentis 1.2190, Bifidobacterium longum 25033, Lactobacillus plantarum F1 and Lactobacillus plantarum B2) and daidzin were approved, and these results showed that most metabolites of daidzin were able to be identified with the identical transformation reactions. The study revealed the rationality of daidzin biotransformation at the new perspective, and constructs a new model for fecal metabolites of compounds. These results will also broaden the continued research on daidzin.

Introduction:Catalpol, an iridoid glycoside derived from Rehmannia glutinosa, is widely recognized for its ability to reduce blood glucose levels. However, its potential therapeutic effects on hyperlipidemia (HL) have yet to be investigated. Methods:To identify novel lipid-lowering effects of catalpol potentially exerted through the modulation of the gut microbiota and endogenous metabolic pathways, Sprague-Dawley (SD) rats were provided a high-fat diet (HFD) to induce an HL state. The lipid-lowering efficacy of catalpol was assessed using biochemical test kits. Subsequently, 16S rRNA gene sequencing was employed to analyze alterations in gut microbial composition in HL rats before and after catalpol treatment. Ultra-high-performance liquid chromatography coupled with Quadrupole Exactive Orbitrap mass spectrometry (UHPLC-Q Exactive Orbitrap MS) was used to detect and identify catalpol metabolites in plasma, urine, and feces. In addition, non-targeted metabolomics was conducted to characterize endogenous small-molecule metabolites. Results:Pharmacodynamic analysis demonstrated that catalpol markedly reduced lipid levels and inhibited hepatic lipid peroxidation. The 16S rRNA sequencing results showed that the consumption of an HFD led to a significant increase in the abundance of Firmicutes and a decrease in that of Bacteroidetes. Notably, catalpol treatment improved HL model rats' overall gut microbiota structure. Non-targeted metabolomics revealed that the HFD significantly altered the abundance of 18 endogenous metabolites, changes that were reversed following catalpol administration. Spearman correlation analysis identified the genus Lactobacillus as a positive contributor to the anti-HL effect of catalpol. Furthermore, pteridine was identified as a potential biomarker associated with catalpol's lipid-lowering activity. Discussion:Collectively, these findings demonstrate that catalpol alleviates HL by influencing gut microbiota composition and restoring plasma metabolic homeostasis.

Despite the widespread presence of polyethylene terephthalate microplastics (PET MPs) in the environment, their biotoxicity, target organs, and underlying toxicological mechanism remain poorly understood. In this study, irregularly shaped PET MPs resembling those commonly found in natural environment were selected. Mice were orally administered different amounts of PET MPs (0, 5, 50, and 500 μg/day) for 17 weeks, after which relevant pathological and biochemical indicators were assessed. The results confirmed, for the first time, that PET MPs can induce oxidative stress, lipid accumulation, and apoptosis in liver cells, resulting in structural damage and functional abnormalities in the liver. Additionally, metabolomic analysis was combined with intestinal microbiota profiling to elucidate the potential toxicological mechanism. The data revealed that chronic exposure to high doses of PET MPs substantially altered the diversity of the intestinal flora. In particular, the relative abundances of Parasutterella, Muribaculum, and Turicibacter increased, accompanied by elevated levels of lipid metabolites such as linoleic acid, taurocholic acid, and sphingosine. These changes disrupted metabolic processes and accelerated lipid deposition in the mouse liver, thereby inducing hepatotoxicity. Moreover, a validation experiment confirmed that depletion of the gut microbiota in mice alleviated PET MPs-induced hepatotoxicity. These findings provide new insights into the toxicity of PET MPs in humans and other mammals.

Bioactive peptides derived from animals have antitumor, antibacterial, antioxidant and other beneficial activities for human health. Successful application in preclinical models demonstrates the potential of animal-derived bioactive peptides to be developed into health foods and functional foods for the treatment of disease. The authors' prior studies have extensively investigated bioactive peptides, establishing a robust preparation and purification system. This review highlights optimized enzymatic hydrolysis methods that enhance peptide yield and bioactivity, combination separation methods that increase the efficiency of separating and purifying bioactive peptides, mass spectrometry methods that determine the molecular weight of bioactive peptides, their mechanisms of action and structure-activity relationships as well as the metabolic process of bioactive peptides in vivo.

IntroductionThe southern mountainous area of Kunyu Mountain is in the Jiaodong Peninsula of China, which is rich in medicinal plant resources. For a long time, the residents in the Southern Mountain area of Kunyu Mountain have used a variety of plants for pharmacy practice and have accumulated rich knowledge of medicinal plants. Although medicinal plants were widely used, there were no reports on the medicinal plants used by residents in the southern mountainous area of Kunyu Mountain. This study aimed to document the medicinal plants and evaluate the associated traditional knowledge possessed by residents of the southern mountainous area of Kunyu Mountain.MethodsThrough face-to-face interviews with 256 residents, the species, preparation, and use of medicinal plants, and related traditional medicinal knowledge were quantitatively analyzed using the Informant Consensus Factor (FIC) and the Relative Frequency of Citation (RFC).ResultsWe identified 338 species of medicinal plants in this study, belonging to 87 families and 230 genera. Among these, Asteraceae was the dominant family and the whole grass was the most commonly used part for drug preparation, and decoction and oral administration were the most common preparation methods and routes of administration, respectively. In terms of utilization rate, Crataegus pinnatifida var. major (0.2), Crataegus pinnatifida (0.2), Platycodon grandiflorus (0.2), Yulania denudata (0.2), and Zanthoxylum bungeanum (0.2) had higher RFC values, and the five plants above were the most important medicinal plants used by the residents in this area. Besides, compared with China Pharmacopoeia, four new therapeutic uses of three known plants were found. Among the 16 disease categories in the International Classification of Primary Care (ICPC-2), Respiratory system diseases (FIC: 0.8), Digestive system diseases (FIC: 0.8), and General and unspecified system diseases (FIC: 0.8) were the most reported.DiscussionThis study lists the species of medicinal plants on the southern mountainous area of Kunyu Mountain. It records their therapeutic uses, which could provide a reference for further chemical and pharmacological studies on medicinal plants.

Both phloretin and phlorizin (phloretin 2′-O-glucoside) extracted from the peel of apples are attributed to particular flavonoid dihydrochalcones with multiple pharmacological activities. However, metabolite structural characterization of these two components, which may accumulate to exert their pharmacological effects, remains insufficient. The present study aimed to comparatively clarify the metabolic pathways of phloretin and phlorizin after oral administration individually to Sprague-Dawley (SD) rats. Therefore, a rapid, integrate and systematic analytical strategy based on characteristic fragment ion fishing was proposed for the screening and identification of metabolites coming from phloretin and phlorizin using UHPLC-Q-Exactive Orbitrap mass spectrometry in parallel reaction monitoring mode. As a result, a total of 50 phloretin metabolites and 52 phlorizin metabolites were individually identified from different biological samples including rat plasma, urine, and faeces. Moreover, glucuronidation, sulfation, carbonylation and hydrolyzation were revealed to be the main metabolic pathways of phlorizin, while decarbonylation, glucuronidation and sulfation were regarded as the predominant biotransformation pathways as for phloretin. This is the first systematic study on comparison of metabolic profiles of phlorizin and phloretin in disease states, which was helpful to declare the complicated structure activity relationships between phlorizin and phloretin and shed light to their action mechanism.

The prevalence of hyperuricemia (HUA) is rising annually due to societal growth and changes in lifestyle. Bidirectional solid-state fermentation of substrates has demonstrated encouraging uses in the clinical treatment of HUA. To investigate the powerful therapeutic potential of solid-state fermentation products of Radix astragali and Paecilomyces cicadidae (RPF), multi-omics analysis was applied. Spearman analysis between serum biomarkers and differential expressed genes (DEGs) was used to estimate the potential mechanism of RPF against HUA, which was induced by high purine diet (HPD) and potassium oxonate. This study found that the serum uric acid, triglycerides, glucose, and creatinine level were decreased in HUA rats after RPF treatment. In addition, RPF effectively attenuated renal inflammation and lipid accumulation in the livers. Untargeted metabolomics and transcriptome sequencing technology demonstrated that the pathway regulated by RPF were “caffeine metabolism”, “fatty acid biosynthesis”, and “AMPK signaling”. Moreover, the correlation demonstrated that metabolites (allantoin, pyridoxamine, cytidine, cortodoxone, corticostrone) and DEGs (Phald3, Ccdc80) showed significantly positive correlations under RPF influence. Overall, findings of current study indicated the interactions between serum metabolites and renal genes. In line with these findings, the mechanism of the anti-HUA effect of RPF was revealed. In summary, the current study suggest pharmacological support for treating HUA with RPF.

This study aimed to investigate the potential benefits of using precise boiling techniques on the solubility of two forms of Scutellaria baicalensis (S. baicalensis) powder, Scutellaria precision-boiled powder (SPBP) and Scutellaria traditional decoction pieces (STDP), using UHPLC-Q-Orbitrap MS/MS technology. The UHPLC-Q-Orbitrap MS/MS technique, along with data-analysis methodologies, were employed to compare the active components between SPBP and STDP. A total of ninety-three chemical components were detected in S. baicalensis. By comparing the weights of extracts, conducting a weighted analysis, and using network pharmacology, SPBP demonstrated a higher concentration of active components and improved beneficial benefits compared to STDP. The quality and potential effectiveness of SPBP were evaluated by comparing its chemical components with those of STDP. These findings lay a foundational framework for in-depth exploration of the mechanisms underlying the decoction of S. baicalensis powder, offering significant potential for future research in functional foods and nutraceuticals.

Ophiopogonis Radix (OR) is a traditional Chinese medicine. In recent years, in order to achieve the purpose of drying, bleaching, sterilizing and being antiseptic, improving appearance, and easy storage, people often use sulfur fumigation for its processing. However, changes in the chemical composition of medicinal herbs caused by sulfur fumigation can lead to the transformation and loss of potent substances. Therefore, the development of methods to rapidly reveal the chemical transformation of medicinal herbs induced by sulfur fumigation can guarantee the safe clinical use of medicines. In this study, a combined full scan-parent ions list-dynamic exclusion acquisition-diagnostic product ions analysis strategy based on UHPLC-LTQ-Orbitrap MS was proposed for the analysis of steroidal saponins and their transformed components in sulfur-fumigated Ophiopogonis Radix (SF-OR). Based on precise mass measurements, chromatographic behavior, neutral loss ions, and diagnostic product ions, 286 constituents were screened and identified from SF-OR, including 191 steroidal saponins and 95 sulfur-containing derivatives (sulfates or sulfites). The results indicated that the established strategy was a valuable and effective analytical tool for comprehensively characterizing the material basis of SF-OR, and also provided a basis for potential chemical changes in other sulfur-fumigated herbs.

The screening and identification of drug metabolites in biological matrices is challenging, and ultra-high performance liquid chromatography-Q- Exactive Orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap MS) has become a powerful technological tool for drug metabolites analysis due to its high sensitivity. However, the spectral information contained in existing chemical standards and databases is very limited, and the UHPLC-Q-Exactive Orbitrap MS technique alone cannot satisfy the identification of complex and diverse metabolites. Therefore, there is an urgent need for a new strategy to achieve comprehensive drug metabolic profile. Based on this, we have innovatively constructed a “recursive tree” analysis strategy and bridged it with network pharmacology for elucidating the pharmacological mechanisms of drugs. In this paper, we investigated the overall metabolic profile of formononetin as an example and utilized the primary branching metabolites of formononetin as effective ingredients for the study of the anti-NAFLD mechanism. The results showed that a total of 131 metabolites (prototype drug included) were detected and identified. Among them, 106 metabolites were found in rats and 31 metabolites were found in liver microsomes. Glucose conjugation, demethylation, sulfation, glucuronidation, and their complex reactions were the major processes of formononetin biotransformation. Network pharmacology results screened 104 potential targets and 20 major signaling pathways. Their mechanisms may be additive and/or synergistic effects. In addition, the therapeutic effects of formononetin against NAFLD were investigated based on palmitic acid / oleic acid-induced HepG2 cells. In summary, the recursive tree analysis strategy provides a convenient method for the identification of metabolites, and its seamless integration with network pharmacology lays the foundation for studying the pharmacological activities of natural products.

Background and aims: The increasing incidence of cardiovascular diseases has created an urgent need for safe and effective anti-thrombotic agents. Leech, as a traditional Chinese medicine, has the effect of promoting blood circulation and removing blood stasis, but its real material basis and mechanism of action for the treatment of diseases such as blood stasis and thrombosis have not been reported. Methods: In this study, Whitmania Pigra Whitman (WPW), Hirudo nipponica Whitman (HNW) and Whitmania acranutata Whitman (WAW) were hydrolyzed by biomimetic enzymatic hydrolysis to obtain the active peptides of WPW (APP), the active peptides of HNW (APH) and the active peptides of WAW (APA), respectively. Then their structures were characterized by sykam amino acid analyzer, fourier transform infrared spectrometer (FT-IR), circular dichroism (CD) spectrometer and LC-MS. Next, the anti-thrombotic activities of APP, APH and APA were determined by carrageenan-induced tail vein thrombosis model in mice, and the anti-thrombotic mechanisms of high-dose APP group (HAPP), high-dose APH group (HAPH) and high-dose APA group (HAPA) were explored based on UHPLC-Q-Exactive Orbitrap mass spectrometry. Results: The results showed that the amino acid composition of APP, APH and APA was consistent, and the proportion of each amino acid was few different. The results of FT-IR and CD showed that there were no significant differences in the proportion of secondary structures (such as β-sheet and random coil) and infrared absorption peaks between APP, APH and APA. Mass spectrometry data showed that there were 43 common peptides in APP, APH and APA, indicating that the three have common material basis. APP, APH and APA could significantly inhibit platelet aggregation, reduce black-tail length, whole blood viscosity (WBV), plasma viscosity (PV), and Fibrinogen (FIB), and prolong coagulation time, including activated partial thrombin time (APTT), prothrombin time (PT) and thrombin time (TT). In addition, 24 metabolites were identified as potential biomarkers associated with thrombosis development. Among these, 19, 23, and 20 metabolites were significantly normalized after administration of HAPP, HAPH, and HAPA in the mice, respectively. Furthermore, the intervention mechanism of HAPP, HAPH and HAPA on tail vein thrombosis mainly involved in linoleic acid metabolism, primary bile acid biosynthesis and ether lipid metabolism. Conclusion: Our findings suggest that APP, APH and APA can exert their anti-blood stasis and anti-thrombotic activities by interfering with disordered metabolic pathways in vivo , and there is no significant difference in their efficacies.

ObjectivesThe purpose of the present study was to explore the influencing factors of hyperuricemia (HUA) in different populations in Shandong Province based on clinical biochemical indicators. A prediction model for HUA was constructed to aid in the early prevention and screening of HUA.MethodsIn total, 705 cases were collected from five hospitals, and the risk factors were analyzed by Pearson correlation analysis, binary logistic regression, and receiver operating characteristic (ROC) curve in the gender and age groups. All data were divided into a training set and test set (7:3). The training set included age, gender, total protein (TP), low-density lipoprotein cholesterol (LDL-C), and 15 other indicators. The random forest (RF) and support vector machine (SVM) methods were used to build the HUA model, and model performances were evaluated through 10-fold cross-validation to select the optimal method. Finally, features were extracted, and the ROC curve of the test set was generated.ResultsTP, LDL-C, and glucose (GLU) were risk factors for HUA, and the area under the curve (AUC) value of the SVM validation set was 0.875.ConclusionThe SVM model based on clinical biochemical indicators has good predictive ability for HUA, thus providing a reference for the diagnosis of HUA and the development of an HUA prediction model.

AimThis research aimed to probe the effects of fecal microbiota and Lactobacillus acidophilus on the metabolism of Radix Astragali (RA) and Poria cocos solid fermenting Radix Astragali (FRA). It further explores pharmacological effects of RA, Poria cocos, and FRA on HUA mouse model and the mechanisms in HUA treatment.MethodsFecal microbiota and Lactobacillus acidophilus were used to ferment FRA and RA in vitro to probe the impacts of microbiota on the metabolism of active compound. A HUA mouse model was used to carry out pharmacodynamic experiment of anti-hyperuricemia. Network pharmacology and molecular docking was utilized to elucidate the underlying mechanisms of RA and Poria cocos in the treatment of HUA.ResultsThe results indicated that astragaloside IV (AG IV), total saponins, and flavonoids continuously decreased in FRA and RA during 48 h fecal microbiota colonic fermentation. During Lactobacillus acidophilus fermentation, in FRA, the content of AG IV peaked at 12 h with a value of 1.14 ± 0.20 mg/g; total saponins and flavonoids reached the highest values of 136.34 ± 6.15 mg/g at 12 h and 6.35 ± 0.06 mg/g at 6 h; AG IV and total saponins reached the highest values 0.63 ± 0.05 mg/g and 115.12 ± 4.12 mg/g at 12 h and 24 h in RA, respectively; and total flavonoids consecutively decreased. The counts of Lactobacillus acidophilus increased significantly in FRA compared with RA. Pharmacodynamic outcomes revealed that FRA effectively reduced blood levels of uric acid (UA), triglycerides (TG), xanthine oxidase (XOD), alanine aminotransferase (ALT), and aspartate transaminase (AST) in HUA mice, exerting protective effects on the liver and kidney. Network pharmacology showed that there were 93 common targets for RA, Poria cocos, and HUA with the top five core targets tumor necrosis factor (TNF), signal transducer and activator of transcription 3 (STAT3), cysteinyl aspartate specific proteinase 3 (CASP3), jun proto-oncogene (JUN), and estrogen receptor 1 (ESR1). Molecular docking analysis revealed that AG IV, calycosin and formononetin bond well to the core targets.ConclusionThis research revealed the interaction of RA and FRA with fecal microbiota and Lactobacillus acidophilus, RA and Poria cocos were featured with multiple components, target points, and signaling pathways in HUA treatment, which provided fresh insights for further HUA therapeutics.

目的 以猪皮为原料,氯化亚铁为铁源,探讨经蛋白酶酶解后的猪皮胶原肽与亚铁离子螯合的最佳工艺条件.方法 对新鲜猪皮进行脱脂处理,采用菠萝蛋白酶和碱性蛋白酶对脱脂猪皮进行酶解,制备猪皮胶原肽,并利用超滤法将其按照分子量进行分段;以螯合率和螯合物得率为指标,对猪皮胶原肽-亚铁螯合物(PCPF)的制备条件(抗氧化剂用量、肽-亚铁摩尔比、螯合pH值、螯合温度、螯合时间、肽浓度和醇沉时间)进行单因素考察,然后采用正交法进一步优化螯合条件,并采用硫化钠法对制备得到的PCPF进行定性鉴定.结果 通过单因素实验和正交实验确定了猪皮胶原蛋白肽与亚铁离子螯合的最佳条件:取猪皮胶原肽溶液(0.15 g/mL),按质量比mVc∶mFeCl2·4H2O =0.3∶1 加入抗氧化剂,用 10%盐酸调pH值至5.00,按摩尔比肽∶Fe2+=3∶1 加入铁盐,在40℃下螯合40 min,然后用 6 倍体积无水乙醇醇沉,慢加快搅,冷藏静置24h后收集沉淀,并用无水乙醇洗涤,50℃烘干后即得PCPF.验证实验表明,该螯合工艺稳定可靠.硫化钠定性检测实验表明,螯合物中不存在游离的猪皮胶原肽,进而确定猪皮胶原肽与亚铁离子己充分螯合.不同分子量猪皮胶原肽螯合活性实验表明,分子量为 1～3kDa的猪皮胶原肽的螯合活较高.结论 PCPF的制备工艺稳定可靠.

Radix Astragali is one of the most famous and frequently used health food supplements and herbal medicines. Among more than 227 components of Radix Astragali , Astragaloside IV (AG IV) is famous functional compound and is commonly used as a quality marker for Radix Astragali . However, the relatively low content of AG IV in Radix Astragali (< 0.04%, w/w) severely limits its application. The purpose of this study is to improve the biotransformation of AG IV and its bioaccessibility during in vitro digestion by Poria cocos solid fermenting Radix Astragali . The optimum fermentation conditions were as follows: Inoculation amount 8 mL; fermentation time 10 d; fermentation humidity 90%. Through fermentation, the content of AG IV was increased from 384.73 to 1986.49 μg/g by 5.16-fold. After in vitro digestion, the contents of genistin, calycosin, formononetin, AG IV, Astragaloside II (AG II) and total flavonoids in fermented Radix Astragali (FRA) of enteric phase II (ENTII) were 34.52 μg/g, 207.32 μg/g, 56.76 μg/g, 2331.46 μg/g, 788.31 μg/g, 3.37 mg/g, which were 2.08-fold, 2.51-fold, 1.05-fold, 8.62-fold, 3.22-fold and 1.50-fold higher than those of control, respectively. The Scanning electron microscopy (SEM) of FRA showed rough surface and porous structure. The DPPH and ABTS radical scavenging rate of FRA were higher than those of control. These results showed that the Poria cocos solid fermentation could increase the content of the AG IV in Radix Astragali and improve the bioaccessibility and antioxidant activity of Radix Astragali , which is providing new ideas for future development and utilization of Radix Astragali .