Scutellariae Radix, the dried root of Scutellaria baicalensis Georgi, is widely used in complementary medicine for its therapeutical effects to treat hepatitis, diarrhea and inflammation. It has been confirmed by modern research that Scutellariae Radix also exhibits anti-tumor properties. As S. baicalensis plants grow into older ages, some of the roots start to decay. The decayed Scutellariae Radix is believed to exhibit different pharmacological effects. It is essential to understand how root decay affects the chemical composition of Scutellariae Radix and, consequently, contributes to the alteration of pharmacological effects. Mass spectrometry imaging (MSI) was adopted to map out the spatial distribution of natural compounds in the decayed roots of Scutellariae Radix. Compounds that showed varied contents between decayed and non-decayed tissues were further identified with liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Identified compounds exhibiting high gastrointestinal adsorption values and high drug-likeness values were subjected to network pharmacology analysis. The influence of chemical alteration on pharmacological effects was predicted. Predictions were validated through in vitro assays on cancer cell lines (A-549, BxPC-3, KGN, and SGC-7901). A majority of compounds was observed to show significantly decreased contents in the decayed tissues of Scutellariae Radix. The shared targets of 15 key components and cancer were highly enriched in PI3K-Akt signaling pathway and multiple organ-specific cancer pathways. Apigenin, presenting the highest degree value during the establishment of component-target network, was selected as the representative component for in vitro validation of anti-tumor properties. Apigenin was found to inhibit the proliferation of four different tumor cell lines in a dose-dependent manner. The chemical composition of Scutellariae Radix was closely correlated with root decay. The contents of numerous compounds showed sharp decline within the decayed tissues of roots. It was revealed by network pharmacology analysis and in vitro study that many compounds were potential anti-tumor compounds. These findings emphasized the need for separate quality standards for decayed and non-decayed roots. This research advances current exploration of medicinal plants and highlights the importance of quality control in medicinal plant use, contributing to the development of complementary medicine.

Peucedanum praeruptorum Dunn as a traditional Chinese medicine (TCM) with many clinical applications. Praeruptorin A (PA) and Praeruptorin B (PB) are quality markers. Recently, PB has attracted attention for its difficulty in satisfying Chinese Pharmacopoeia in Peucedanum praeruptorum Dunn. However, the association between the contents of PA and PB, as well as the factors influencing this association, remains unclear. Hence, we conducted a study on PA and PB of 538 batches of samples from the main production areas of Chinese provinces. A negative correlation between PA and PB was observed for the first time, with a wide range of fluctuation coefficients and poor quality stability. This relates closely to the main production areas and growth patterns. Particularly, the sum of PA and PB reveals the quality stability and maintains the satisfactory rate to avoid quality evaluation bias. Six machine learning algorithms were used to build the model after optimisation and evaluation. We found that the prediction accuracies for the DaoDi producing regions Anhui and Zhejiang reached 93.3 % and 87 % with Stacking and SVM, respectively. The kNN predicts wild and domestic species patterns with an accuracy of 93.3 %. Compared with traditional chemometrics, machine learning has absolute advantages. This study comprehensively revealed the quality formation factors of Peucedanum praeruptorum Dunn. It provides a scientific basis for improving the quality standard, grade evaluation and scientific supervision of Peucedanum praeruptorum Dunn.

As a key representative of marine traditional Chinese medicine, Margaritifera Concha is commonly processed by calcination. However, significant differences in processing methods and quality standards have led to considerable variations in the quality of decoction pieces. Based on the theory of "quality evaluation through morphological identification," this study investigates the microstructure and crystal phase composition of Margaritifera Concha and its calcined products, aiming to establish a new quality control approach distinct from traditional chemical index-based models. The microstructure of the "brick wall-cement-brick wall" pattern in Margaritifera Concha was examined using scanning electron microscopy and microscopic computed tomography, followed by 3D reconstruction and porosity calculations. The crystal phase composition was analyzed using x-ray diffraction, thermogravimetric analysis, and Fourier transform infrared spectroscopy. The results indicate that the calcination of Margaritifera Concha is closely associated with changes in its microstructural characteristics, and porosity can serve as a quantitative index for assessing the processing degree of decoction pieces.

Polygonum multiflorum Thunb. (PM) is a starch-rich medicinal herb, but research on the changes in the structure and physical properties of the starch upon processing remains elusive. Herein, the structures and physicochemical properties, particularly the impact on intestinal flora of raw PM starch and processed Polygonum multiflorum (PMP) starch, were systematically characterized and compared. XRD and FT-IR results showed that the crystalline structure of PMP starch was disrupted, with the increase in its short-range ordering. Morphological analysis revealed that the size of PMP starch granules increased with the appearance of aggregation. Significant differences in swelling power and solubility were observed, wherein PM starch has a higher swelling power, while its solubility is lower than that of PMP starch. The PM starch also has higher thermal stability. Interestingly, the resistant starch (RS) content in PMP starch was higher, as shown by the in vitro digestibility tests, which is associated with enhanced bioactivity. Moreover, gut microbiota analysis in mice indicated that PMP starch promoted gut health by regulating specific bacterial families. Our current study has offered full insights into the changes of PM starch upon processing, laying a solid foundation for further developing PM starch-derived functional food products.

Styrax is a rare and expensive natural spice for food, known for its unique and rich aroma and sticky texture, and has a long history of consumption worldwide. There are many counterfeits in the market, but it is challenging to distinguish them with existing standards. Therefore, identifying the authenticity of styrax and evaluating its quality are challenges. A total of 34 samples of styrax were collected in this study, including 4 samples collected from the origin of Guatemala and 30 samples collected from markets in various regions of China. Gas chromatography-mass spectrometry (GC-MS) and headspace gas chromatography-mass spectrometry (HS-GC-MS) were used to analyze the chemical components of styrax qualitatively, and ultra performance liquid chromatography (UPLC) was used to quantitatively analyze cinnamic acid, cinnamyl cinnamate, and 3-phenylpropyl cinnamate in styrax. The texture, odor, and color of styrax were characterized by three modern sensory evaluation technologies: flash gas chromatography electronic nose (flash GC E-nose), rotational rheometer, and spectrophotometer. Thus, a method for identifying the authenticity of styrax was established. The results showed that a total of 73 components were identified in styrax, and qualitative analysis using GC-MS, HS-GC-MS, and PCA model, OPLS-DA model can effectively identify styrax and its counterfeits. The main adulterated ingredients in counterfeit are benzoic acid, Benzyl benzoate, and Benzyl alcohol. These compounds are toxic and can cause food safety problems. The shear viscosity and odor of styrax and its counterfeits are significantly different(p < 0.001), but the color is not significantly different(p > 0.05). Various analytical methods can be used to identify styrax and its counterfeits effectively. This study provides a more comprehensive method for authenticity identification and quality evaluation of styrax, which is conducive to ensuring the edible safety of styrax.

The quality control of Traditional Chinese Medicine (TCM) is crucial for ensuring its efficacy and safety. Traditional methods, however, have limitations in fully capturing the natural essence of TCM, thus hindering the comprehensive exhibition of its authenticity. Addressing this challenge requires the establishment of a scientific and reasonable quality control system, which poses significant complexities due to the TCM unique attributes. Our research team conducted in-depth exploration of the elemental fingerprints of TCM, amassing a robust theoretical and practical foundation. In this review, we presented a comprehensive review of the core value, advanced technologies, and classic cases of elemental fingerprints. We introduced a novel perspective that integrated inorganic and organic components, overcoming traditional paradigms. The review analysis highlighted unique role of elemental fingerprints in revealing the scientific connotation of TCM. Furthermore, we proposed an innovative strategy for identifying key components, which effectively addressed the limitations of traditional methods and elevated the overall evaluation standards for TCM. This strategy was supported by emerging technologies such as artificial intelligence, metallomics, and hyperspectral imaging. Looking ahead, the application prospects of the combined strategy of elemental fingerprints and key components were promising. It not only provided a solid foundation for the formulation of TCM quality control strategies but also introduced new methodologies and tools to the field of regulatory science and scientific oversight of TCM.

Objective:The basic helix-loop-helix (bHLH) transcription factors (TFs) are pivotal in regulating fungal growth, development, and secondary metabolism. However, the knowledge about the Ganoderma lucidum bHLHs (GlbHLHs) in ganoderic acid (GA) biosynthesis of G. lucidum was limited. This study aimed to explore the functions of bHLH genes in ganoderic acid biosynthesis during G. lucidum growth development. Methods:First, the genome-wide identification of GlbHLHs was performed through Hidden Markov model searches and Two-way blast. Furthermore, through physicochemical properties, gene structure, and phylogenetic analysis, as well as combining the transcriptome and metabolome data from different developmental stages of G. lucidum, candidate GlbHLHs were screened. Subsequently, their regulatory roles in ganoderic acid biosynthesis were explored using yeast one-hybrid and dual-luciferase reporter assays. Results:A total of 11 GlbHLH members were characterized in G. lucidum. The upstream promoter regions of these genes enriched hormones and abiotic stress responsive elements. Although individual ganoderic acid monomers demonstrated marked differences in accumulation patterns across specific growth phases and tissue types, overall, the total GA content was consistently higher in caps than in stipes throughout development. In addition, all GlbHLHs exhibited high expression in whole G. lucidum from the primordium to maturation stages. Among them, GlbHLH5 and GlbHLH7 showed the highest expression in any stage and highly correlated with key genes associated with GA pathway. Functional validation through dual-luciferase assays and yeast one-hybrid experiments had demonstrated that GlbHLH5 activated the P2 region of the lanosterol synthase promoter, while GlbHLH7 activated the promoters of squalene epoxidase and squalene synthase. Conclusion:Compared to plants, G. lucidum harbored a small number of bHLH members but all high expression in any stages. Additionally, GlbHLH5 and GlbHLH7 with the highest expression among GlbHLHs showed activation in regulating the biosynthesis of GA. These results provide a theoretical reference for further research on ganoderic acid regulation in G. lucidum, and thereby providing a molecular foundation for enhancing ganoderic acid yield to optimize the medicinal value of G. lucidum.

Background Owing to high sensitivity and ability for absolute quantification, the droplet digital polymerase chain reaction (ddPCR) is widely used for viral and bacterial detection. However, few studies have been conducted on the application of ddPCR to identify the original plant species used in traditional Chinese medicine and Chinese patent medicine. Purpose In this study, we investigated the feasibility of using ddPCR to differentiate between Notopterygium incisum and N. franchetii to establish a sensitive and quantitative method for quality control of herbal materials and preparations. Methods Specific minor groove binding (MGB) probes and primers were designed based on stable single nucleotide polymorphisms. The ddPCR experimental conditions were designed and optimised according to the results of multiplex PCR and qPCR, which ultimately confirmed the limits of detection and quantification (LOD and LOQ, respectively) of the method for Notopterygii Rhizoma et Radix. Additionally, the original plant species of Notopterygii Rhizoma et Radix in Jiuwei Qianghuo pills circulating in the market were identified. Results The results of the multiplex PCR and qPCR indicated that the probes and primers were specific. Furthermore, a Qsep analyser and Sanger sequencing were used to confirm that the specific amplification products of N. incisum and N. franchetii were 283 and 206 bp, respectively. The optimised ddPCR system was employed to determine the LOD to be 0.000816 ng/µL, and LOQ of N. incisum and N. franchetii to be 0.00408 and 0.003312 ng/µL, respectively. In addition, Notopterygii Rhizoma et Radix in four Jiuwei Qianghuo pills was amplified and successfully identified using ddPCR assays. Conclusion This study established a multiplex ddPCR method using MGB probes to identify Notopterygii Rhizoma et Radix, providing a foundation for the identification and quantification of multi-source Chinese herbal medicines.

Chinese herbal medicine has offered a great treasure for discovering intrinsically bioactive low molecular weight gelators (LMWGs). Herein, the two-component hydrogels comprising glycyrrhizic acid (GA) and puerarin (PUE), the primary bioactive components, respectively, from herbs Glycyrrhiza uralensis Fisch and Pueraria lobata are successfully prepared. Combined spectroscopic characterizations reveal that hydrogen bonds are formed between GA and PUE molecules, which further drives the growth of nanofiber assemblies into gel networks. Importantly, micromorphological observation by scanning electron microscopy (SEM), synchrotron small-angle X-ray scattering (SAXS), and molecular dynamic simulation suggest that a coassembly pathway is involved in the gelling process. Such two-component hydrogels exhibit good injectable, self-healing, and adhesive properties. Interestingly, the mixed GA-PUE hydrogels demonstrate a more efficient and selective antibacterial activity toward S. aureus instead of E. coli, and a PUE ratio-dependent antibacterial activity toward S. aureus is also observed. Our work highlights that CHM-derived LMWGs can provide a scaffold for developing multicomponent hydrogels, which may afford novel and distinct properties compared with their individual ones. It is assumed that more multicomponent supramolecular hydrogels derived from CHM would appear to better address the challenges, particularly in the biomedical field.

Hyperuricemia (HUA) and gout became typical metabolic disorders characterized by multiple pathogenic factors. Their incidence increased annually, affecting younger populations. Given that uric acid (UA) and inflammation were the primary disease mechanisms, the search for effective and low-side-effect UA-lowering and anti-inflammatory drugs became a pressing scientific priority. Traditional Chinese medicine (TCM) encompassed a rich array of theoretical and practical experience, along with a diverse range of chemical substances, making herbs or their components potential sources for therapeutic drugs. Despite the significant role that modern herbal medicines played in treating HUA and gout, the existing research literature remained fragmented, lacking comprehensive and systematic reviews. In this review, we focused on the regulation of UA and summarized the discovery of UA-lowering pharmacodynamic components or ingredients derived from herbs and formulas, as well as their multi-targeted mechanisms of action. Emphasizing this focus, we proposed that, compared to acute inflammation, low-grade inflammation may play a relatively “unnoticed” role in the disease process. In contrast to Western medicine, we discussed the risks and benefits of herbal medicines and their ingredients for treatment, drawing from theoretical insights and clinical practice. This review offered comprehensive perspectives on the research into anti-HUA and gout treatments using herbal medicines and their natural products. Additionally, it provided a forward-looking view on natural product discovery, the exploration of therapeutic strategies, and new drug research in this field.

Covering: 2009 up to the end of 2023Stilbenes, an emblematic group of polyphenols, have attracted the attention of numerous researchers owing to their intriguing polycyclic architectures and diverse bioactivities. In this updated review, natural stilbenes were analysed, especially oligomeric stilbenes, which are an emblematic group of polyphenols that harbor intriguing polycyclic architectures and diverse bioactivities compared with those previously anticipated. Oligomeric stilbenes with unique skeletons comprise a large majority of natural stilbenes owing to their structural changes and different substitutions on the phenyl rings. These compounds can be promising sources of lead compounds for studying new drugs and medicines. In addition, the exploration of unusual structures of oligomeric stilbenes such as polyflavanostilbenes A and B, analysing their absolute stereochemistry, and improving their yield using synthetic biology methods have recently gained interest. This review provides a systematic overview of 409 new stilbenes, which were isolated and identified over time from January 2009 to December 2023, focusing on the classification and biomimetic syntheses of oligomeric stilbenes, in addition to presenting meaningful insights into their structural diversity and biological activities, which will inspire further investigations of biological activities, structure-activity relationships, and screening of drug candidates.

Betulin is a naturally occurring triterpene holding great promise as a lead for developing new antitumor agents. Given that the design, synthesis and anticancer activity of betulin-succinate derivatives remain unexplored, we herein reported the synthesis and cytotoxicity evaluation of such 22 new derivatives against A172, HT29, SW579, and TCA8113 cancer cell lines in vitro using the CCK8 (Cell Counting Kit-8) assay. The results revealed that most compounds showed potent antitumor activity relative to the positive control and betulin. Particularly, compound 21 also exhibited superior activities in inducing the early apoptosis of HT29 cells and blocking the cell cycle in the G2 phase than the chemotherapeutic agent cisplatin. In vitro kinase screening results from the 207 tested kinases demonstrated that MARK2 (Microtubule Affinity-Regulating Kinase 2), significantly inhibited by compound 21, may be the potential target of betulin-succinate derivatives. Hence, the affinity and interactions between compound 21 and MARK2 were obtained by molecular docking simulations. Compound 21, which prevented tumor cell metastasis and induced tumor cell apoptosis, exhibited potent antitumor activity in a zebrafish tumor model with xenografted HT29 cells. Furthermore, the histopathological evaluation demonstrated the ability of compound 21 to reduce the proliferation and improve the atypia of tumor cells in the abdominal cavity of zebrafish.

Polygonum multiflorum Thunb (PM) is known for its potential to extend lifespan. Although the polysaccharides, the primary constituents of PM, remain largely unexplored in terms of their anti-aging effects and underlying mechanisms, this study investigates them in detail. The anti-aging effects of two purified polysaccharides from PM were evaluated: neutral polysaccharide (RPMP-N, weight average molecular weight 245.30 kDa) and acidic polysaccharide (RPMP-A, weight average molecular weight 28.45 kDa), using a D-Galactose-induced (D-Gal) aging mouse model. In the experimental group, RPMP-N and RPMP-A were administered at doses of 50 (low) and 150 mg/kg/day (high). The activity of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX), which are essential for scavenging free radicals and form a key part of the body's antioxidant defense system, was measured in aging mice. The results showed significant improvements following treatment with RPMP-N and RPMP-A. Additionally, both polysaccharides demonstrated the ability to repair and protect against liver and brain injuries. The expression of P16, P21, and P53 proteins, which regulate cellular senescence through distinct mechanisms, was significantly reduced in liver and brain tissues after treatment. Notably, untargeted metabolomics revealed that RPMP-N and RPMP-A exerted significant anti-aging effects in the D-Gal aging mouse model, primarily influencing metabolism pathways related to lysine, sphingolipids, cysteine, and methionine. In conclusion, these findings provide important insights into the anti-aging mechanisms of PM polysaccharides, supporting their potential for clinical applications, drug development, and regulatory science.

Natural products (NPs), play a crucial role in drug development. However, the discovery of NPs is accidental, and conventional identification methods lack accuracy. To overcome these challenges, an increasing number of researchers are directing their attention to Molecular networking (MN). MN based on secondary mass spectrometry has become an important tool for the separation, purification and structural identification of NPs. However, most new tools are not well known. This review started with the most basic MN tool and explains it from the principle, workflow, and application. Then introduce the principles and workflows of the remaining eight new types of MN tools. The reliability of various MNs is mainly verified based on the application of phytochemistry and metabolomics. Subsequently, the principles and applications of 12 structural annotation tools are introduced. For the first time, the scope of 9 kinds of MN tools is compared horizontally, and 12 kinds of structured annotation tools are classified from the type of compound structure suitable for identification. The advantages and disadvantages of various tools are summarized, and make suggestions for future application directions and the development of computing tools in this review. MN tools are expected to enhance the efficiency of the discovery and identification in NPs.

BackgroundAlzheimer’s disease (AD) is a progressive neurodegenerative disorder with no effective treatment currently available. The Panax ginseng C.A.Mey. and Polygonum multiflorum Thunb. formula (GSPM) has shown potential neuroprotective effects, but its therapeutic efficacy and underlying mechanisms in AD remain unclear and require further investigation.MethodsIn this study, senescence-accelerated mouse prone 8 (SAMP8) mice, an AD model, were treated with GSPM (low: 117 mg/kg, high: 234 mg/kg) or donepezil (1.3 mg/kg) via gavage for 2 months. Cognitive function was assessed using the Morris water maze. Hippocampal morphology was evaluated by H&E staining, and neuronal apoptosis was detected by TUNEL assay. Microgliosis and astrogliosis were analyzed by Iba1 and GFAP immunohistochemistry. Levels of phosphorylated Tau, Aβ1-42, Aβ1-40, inflammatory cytokines, oxidative stress markers, and senescence markers were measured. Gut microbiota composition was analyzed by 16S rRNA sequencing. In vitro, the effects of GSPM were evaluated in Aβ1-42-stimulated HT22 hippocampal neurons. Cell viability was assessed via CCK-8, and apoptosis was detected by flow cytometry. The AMPK/Sirt1 pathway was investigated by Western blotting, and SIRT1-dependent effects were evaluated following EX527 treatment, a SIRT1 inhibitor.ResultsGSPM treatment improved cognitive function, reduced hippocampal tissue damage, and decreased neuronal apoptosis in AD mice. It alleviated neuroinflammation by reducing microgliosis and astrogliosis and lowered the levels of p-Tau protein and Aβ accumulation in both the hippocampus and cerebrospinal fluid. Additionally, GSPM reversed the enhanced inflammation, oxidative stress, and neuronal senescence observed in AD mice. Furthermore, GSPM modulated gut microbiota composition by reducing microbial diversity and restoring the Firmicutes/Bacteroidetes ratio to levels similar to those in control mice. GSPM increased the abundance of Lactobacillus, which was negatively correlated with inflammation, Aβ1-42, p-Tau, and senescence markers. It also decreased the abundance of bacteria, such as Oscillibacter, Helicobacter, and Odoribacter, which are associated with inflammation, oxidative stress, and neuronal senescence. In line with in vivo findings, GSPM increased cell viability, reduced apoptosis, and alleviated oxidative stress in Aβ1-42-stimulated HT22 hippocampal neurons. It also decreased the production of pro-inflammatory cytokines and reduced expression of senescence markers in vitro. Furthermore, GSPM restored AMPK phosphorylation and Sirt1 expression in neurons. Notably, inhibition of Sirt1 by EX527 reversed the neuroprotective effects of GSPM.ConclusionOur data demonstrated that GSPM exhibits protective effects on AD via suppressing the inflammation, oxidation, and senescence, possibly through regulating the Sirt1 signaling. These findings provided a novel therapeutic approach for AD.

Cantharidin, an active compound with well-established clinical efficacy, is a defensive secondary metabolite primarily derived from insects in the Meloidae family. The study of cantharidin's synthetic pathway is not only one of the most intriguing research areas within the Meloidae family, but also holds promise in bridging the gap between biological defense mechanisms and clinical applicability. This paper provides a concise overview of the cantharidin-related biological characteristics of Meloidae beetles. It then summarizes recent advances in research on the synthetic pathway of cantharidin, focusing on three key areas: the synthesis of sesquiterpene precursors, the production and metabolism of farnesol, and its connection to juvenile hormone metabolism. The hypothesis is proposed that the biosynthetic pathway starts with the mevalonate pathway, which synthesizes farnesol, the identified precursor of cantharidin. Farnesol is subsequently converted by enzymes into farnesoic acid, which is further transformed into juvenile hormone acid. Juvenile hormone acid is then converted into juvenile hormone acid diol, which participates in the synthesis of cantharidin. Finally, we propose a speculative synthesis pathway for cantharidin based on current research findings and discuss its implications.

ETHNOPHARMACOLOGICAL RELEVANCE:UC, characterized by chronic inflammation primarily affecting the colon and rectum, follows a protracted relapsing course marked by inflammation and an abundance of free radicals at the onset. Hudichangrong Capsule (HDCRC), a traditional Chinese medicinal formula, has long been employed in the treatment of UC and chronic bacillary dysentery, exhibiting positive therapeutic outcomes and a high rate of cure in clinical practice. AIM OF THE STUDY:The precise mechanism underlying its efficacy for UC remains elusive. Our objective was to investigate the anti-inflammatory effect and underlying mechanisms of HDCRC on TNBS-induced UC. MATERIALS AND METHODS:Here, we introduced HDCRC and induced UC using TNBS. SPF BALB/c mice were divided into 6 groups as follows: control group, colitis model group, colitis treated with sulfasalazine (400 mg/kg) group, and colitis treated with HDCRC (156, 312, and 624 mg/kg) groups. To assess the effects of HDCRC on colitis, we measured body weight loss, disease activity index (DAI), colon length, tissue damage, degree of inflammation, immune capacity, and oxidative stress. Additionally, we evaluated the TLR-4/MyD88 pathway and its downstream signaling using immunohistochemistry, real-time qPCR, and Western blot. Network pharmacology was used for main target prediction. 16s rRNA was employed for gut microbiota detechtion and UPLC-QTOF-MS was used for its and its metabonomics. RESULTS:HDCRC significantly slowed weight loss, ameliorated DAI, restored colon length, alleviated TNBS-induced tissue damage. It exerted the therapeutic effects via reducing oxidative stress, restoring immune balance, normalizing the inflammatory mediator levels and restoring intestinal barrier integrity. Furthermore, HDCRC mainly alleviate UC via suppressing the TLR-4/MyD88 pathway and its downstream signaling. The key components of the downstream pathway, including TLR-4, MyD88, NF-κB p65, ERK, p-JNK, p38, p-JAK1, JAK1, p-STAT3, and STAT3, were improved, thereby ameliorating the TNBS-induced injury. In addition, HDCRC could regulate gut microbiota (eg. Erysipelaloclostridium,etc.) and its metabonomics (eg. Vitamin B6 metabolism) in UC mice. CONCLUSIONS:In conclusion, HDCRC exerts a protective effect against TNBS-induced UC in mice by inhibiting the TLR-4/MyD88 pathway and its downstream signaling, and partially JAK1/STAT3, suppressing oxidative stress, regulating immunity, restoring intestinal barrier integrity, and regulating gut microbiota and its metabonomics.

Hyperuricemia (HUA) and gout became typical metabolic disorders characterized by multiple pathogenic factors. Their incidence increased annually, affecting younger populations. Given that uric acid (UA) and inflammation were the primary disease mechanisms, the search for effective and low-side-effect UA-lowering and anti-inflammatory drugs became a pressing scientific priority. Traditional Chinese medicine (TCM) encompassed a rich array of theoretical and practical experience, along with a diverse range of chemical substances, making herbs or their components potential sources for therapeutic drugs. Despite the significant role that modern herbal medicines played in treating HUA and gout, the existing research literature remained fragmented, lacking comprehensive and systematic reviews. In this review, we focused on the regulation of UA and summarized the discovery of UA-lowering pharmacodynamic components or ingredients derived from herbs and formulas, as well as their multi-targeted mechanisms of action. Emphasizing this focus, we proposed that, compared to acute inflammation, low-grade inflammation may have played a relatively "unnoticed" role in the disease process. In contrast to Western medicine, we discussed the risks and benefits of herbal medicines and their ingredients for treatment, drawing from theoretical insights and clinical practice. This review offered comprehensive perspectives on the research into anti-HUA and gout treatments using herbal medicines and their natural products. Additionally, it provided a forward-looking view on natural product discovery, the exploration of therapeutic strategies, and new drug research in this field.

Animal medicines,which boast a lengthy history as treasures of traditional Chinese medicine(TCM),frequently encounter safety challenges stemming from the accumulation of heavy metals and harmful elements,such as arsenic(As)[1].The toxicity of As differs by species,especially inorganic arsenic(iAs),and current methods for assessing herbal risks based on total arsenic(tAs)content are insufficient[2].To address this,studies have focused on As contamination in TCMs,especially leeches.Widely used for anticoagulant and other pharmacological activities,leeches are susceptible to water contamination and high As levels due to immature farming technology[3].The aim of this study was to comprehensively analyze the distribution of tAs and toxic elements in leeches from multiple sources and batches.We used advanced analytical techniques(e.g.,liquid chromatography-inductively coupled plasma mass spectrometry(LC-ICPMS))to accurately identify As forms.This study aims to investigate the biological effects at the exposure point through in vitro experi-ments(simulating physiological conditions)and assess the po-tential clinical risks associated with iAs.