Cardiac fibrosis is a hallmark of various cardiovascular diseases and is characterized by excessive extracellular matrix (ECM) deposition and progressive tissue stiffening. Emerging evidence suggests that ECM stiffening is not merely a mechanical consequence of fibrosis but also an active driver of pathological cellular responses. Among the mechanosensitive cells within the myocardium, macrophages play a central role in sensing and responding to mechanical cues. Through defined mechanotransduction pathways, macrophages undergo phenotypic and functional reprogramming that shapes inflammatory signaling and the progression of fibrosis. In this review, we summarize current knowledge on ECM stiffening in cardiac fibrosis and its impact on macrophage behavior. We also highlight key mechanosensors that mediate macrophage responses to biomechanical stress. Finally, we discuss emerging therapeutic strategies targeting macrophage mechanotransduction and ECM remodeling and explore their potential as antifibrotic interventions in cardiovascular disease.

β-cryptoxanthin is a provitamin A xanthophyll carotenoid that is abundant in human circulation, despite being derived from a relatively limited range of dietary sources, primarily citrus fruits, which contain approximately 0.5–10.0 mg per 100 g fresh weight. Owing to the polarity and the frequent occurrence associated with β-cryptoxanthin as esterified forms in foods, β-cryptoxanthin exhibits relatively high bioaccessibility and bioavailability. This review aims to provide a comprehensive overview of the current evidence regarding the biochemical characteristics, dietary sources, determinants of absorption, and potential health effects of β-cryptoxanthin, with particular emphasis on bone health and several cancer outcomes. Among the health outcomes examined, the evidence is most consistent for a beneficial role in skeletal health. In contrast, associations with cancer are heterogeneous and appear to depend on cancer type and population characteristics; inverse associations have been reported primarily for cancers of the upper aerodigestive tract, whereas most studies show no association with overall cancer incidence or mortality. Nonetheless, further research is required to investigate whether β-cryptoxanthin can be incorporated into evidence-based precision nutrition approaches that account for interindividual variability in metabolism, lifestyle, and disease risk.

As a highly prevalent condition in chronic kidney disease progression, mesangial proliferative glomerulonephritis (MsPGN) has limited therapeutic options, with the glomerular barrier substantially restricting drug efficacy. Reactive oxygen species (ROS), inflammation, and aberrant cellular proliferation play pivotal roles in the pathogenesis of MsPGN. To overcome limitations of conventional drugs and nanocarrier delivery systems in MsPGN treatment, this study proposed an interesting “drug-carrier integration, synergistic targeting' strategy. Our preliminary experiment found that Paotianxiong polysaccharides (PP) has the effect of inhibiting mesangial cells (MCs) proliferation. Novel self-assembling nanoparticles incorporating hydrophilic PP and hydrophobic α-lipoic acid (LA) were developed. This design integrates the ROS scavenging and anti-inflammatory functions of LA with the superiority of PP in inducing MCs apoptosis, thereby synergistically inhibiting the abnormal proliferation of MCs and improving bioavailability simultaneously. For the first time, nanoparticles were coated with LPS/PDGF-BB-activated MC membranes for biomimetic delivery, enabling targeted MsPGN therapy. The prepared nanoparticles (average size: 74 nm) demonstrated significant uptake in MCs. In vitro, they exhibited remarkable capabilities in inhibiting MCs proliferation, scavenging ROS, and reducing inflammation. In vivo, they can achieve the synergistic effect of active and passive targeting and effectively accumulate in glomerular MCs. Through the synergistic effects of regulating oxidative stress, inhibiting M1 macrophage polarization, and suppressing growth factor expression, they can effectively alleviate MsPGN. Furthermore, no significant adverse effects were observed during treatment. Overall, this study constructed a novel self-assembled nanoformulation for MsPGN treatment, provided a new and promising biomimetic nano-delivery strategy targeting glomerular MCs.

Two novel capsaicinoids (3, 3, 4 ) , a new amide alkaloid (1), 1 ), and three new natural compounds(7, 7, 10, 12 )in addition to seven known capsaicinoids (5, 5, 6, 8, 9, 11, 13, 14 ) and one known amide alkaloid (2), 2 ), were isolated from Capsicum annuum var. conoides. Structure of these novel compounds were elucidated by HRESIMS and 1D/ 2D NMR spectroscopy data. Compounds 1-14 - 14 were tested against five human cells (A549, MCF-7, HEPG2, SKOV3, L02) by means of a proliferation assay using CCK-8 to evaluate their toxicity. The results showed that compound 3 (IC50 50 20.50 +/- 0.49 mu M) had inhibitory activity against MCF-7 cells which was superior to HCPT (24.87 +/- 0.91 mu M). Compound 3 pairs of confocal mitochondrial potential measurements and apoptosis studies had shown that it induces dose-dependent apoptosis in MCF-7 cells. The prediction of compound 3 and breast cancer-related targets through network pharmacology and molecular docking suggests that it has the potential to be developed into an anti-tumor drug and may offer valuable insights for future therapeutic strategies.

Wound healing is often hindered by bacterial infection, oxidative stress, and bleeding. Traditional dressings cannot simultaneously regulate multiple microenvironments. To address the shortcomings of traditional dressings, this study constructed a dual-network photothermal responsive multifunctional hydrogel OBCTCu based on four natural ingredients, including Bletilla striata polysaccharide (BSP), chitosan (CS), tannic acid (TA), and Cu2+. Firstly, we systematically characterized the structural integrity of OBCTCu hydrogels, with an Oxidized Bletilla striata polysaccharide (OBSP) oxidation degree of 31.93 %. The hydrogel can rapidly absorb exudate (absorbing 6 times its own weight within 1 h) and maintain a moist wound environment. It also possesses multifunctional properties such as self-healing, self-adaptation, injectability, near-infrared (NIR) responsiveness, and adhesiveness. The OBCTCu hydrogel exhibits broad-spectrum antibacterial activity against Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa), and Candida albicans (C. albicans). Among these, the antibacterial effect against C. albicans is the most significant (minimum inhibitory concentration (MIC) 0.1 g/mL, minimum bactericidal concentration (MBC) 0.2 g/mL), achieving 100 % antibacterial activity after near-infrared treatment. Additionally, OBCTCu hydrogel can efficiently remove various reactive oxygen species and achieve rapid hemostasis. In the vivo wound healing experiment shows that the OBCTCu hydrogel can significantly promote wound healing. The excellent biocompatibility of this hydrogel makes it safe for clinical application (cell viability >80 % in all groups, hemolysis rate < 3 %). This study innovatively combines natural active ingredients with green synthesis strategies to provide a novel non-antibiotic dressing solution for drug-resistant bacterial infections. The solution features mechanical adaptability, smart response, and multifunctional integration.

Background: Roots and rhizomes of Curcuma phaeocaulis Val. are used as distinct traditional Chinese medicines with a reported blood-circulating and stasis-removing effect. This may be related to differences in the accumulation and distribution of active compounds. Purpose: This study investigates spatial variations in secondary metabolites across different parts of Curcuma phaeocaulis Val. and explores the underlying pharmacological basis. Methods: Ultra-high-performance liquid chromatography-quadruple Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) coupled with desorption electrospray ionization mass spectrometry imaging (DESI-MSI) was employed to analyze the spatial distribution of metabolites in different parts of Curcuma phaeocaulis Val. Multivariate statistical analysis was performed to identify differential metabolites. DESI-MSI visualization further characterized the spatial distribution. Network pharmacology was subsequently employed to predict the pharmacological mechanisms of key differential components. Results: UHPLC-Q-Orbitrap HRMS analysis identified 54 chemical compounds in different parts of Curcuma phaeocaulis Val., primarily sesquiterpenes and curcuminoids. Rhizomes exhibited significantly higher levels of these compounds compared to roots. Multivariate statistical analysis using UHPLC-Q-Orbitrap HRMS and DESI-MSI identified 23 and 20 differentially abundant metabolites in roots and rhizomes, respectively, with 14 compounds common to both methods. DESI-MSI imaging localized β-elemene and curcumenol predominantly to the rhizome cortex. Network pharmacology suggests STAT3, PIK3CA, PIK3R1 and AKT1 as potential key targets for Curcuma phaeocaulis Val. in treating blood stasis. Conclusion: Spatial metabolomics revealed differential metabolite content and spatial distribution across different parts of Curcuma phaeocaulis Val. Differences in metabolite biosynthesis and accumulation likely contribute to the potential of both roots and rhizomes to ameliorate blood stasis.

ETHNOPHARMACOLOGICAL RELEVANCE:Hydrargyrum chloratum compositum(Hcc) is a traditional Chinese medicine for external use, with the efficacy of 'transforming corrosion and pulling out toxins, removing corrosion and regenerating muscles'. The main components are mercuric chloride (HgCl2) and mercurous chloride (Hg2Cl2), which have antibacterial, corrosive and tissue repairing effects. However, the therapeutic mechanism and toxicity risk of its topical application for treating difficult-to-heal wounds have not been clearly explained. AIMS OF THE STUDY:To investigate the therapeutic mechanism of Baishuidan on chronic non-healing wounds in rats and to assess the risk of mercury toxicity. METHODS:The antimicrobial activity of Hcc against Staphylococcus aureus, Candida albicans, Pseudomonas aeruginosa, and Streptococcus-β haemolyticus was assessed by the circle of inhibition assay, Minimum inhibitory concentration(MIC) and Minimum bactericidal concentration(MBC) assay and 24-h inhibition curve. SD rats were used to establish a chronic difficult-to-heal wound model. The efficacy of C. albicans and its effects on inflammatory and angiogenic factors were assessed by wound healing rate, histopathological analysis, immunohistochemical staining, and Elisa assay. The pathological effects of Hcc on the principal organs of rats and the accumulation of mercury ions were detected by hematoxylin-eosin (H&E) staining and atomic absorption spectrophotometry (AAS). RESULTS:Hcc showed different degrees of bacteriostatic effects on Staphylococcus aureus, Streptococcus-β haemolyticus, Pseudomonas aeruginosa, and Candida albicans. Among them, the most significant inhibitory effect was on S. aureus (MIC 4 μg/mL, MBC 8 μg/mL). Hcc significantly promoted the healing of skin wounds in rats, with the best effect in the middle-dose group. Pathological analysis showed that collagen fibre production and neocapillary formation increased and inflammatory cell infiltration decreased in the treatment group. Hcc improved the microenvironment of wounds by decreasing the level of the pro-inflammatory factor IL-6 and increasing the level of the anti-inflammatory factor IL-10. By activating the Pi3k - Akt and Notch1 - Vegfa signalling pathways, Hcc promotes cell proliferation and angiogenesis, accelerating wound healing. Hcc did not cause significant pathological damage to the major organs of rats at the therapeutic dose. However, a significant accumulation of mercury ions was detected in the kidneys, suggesting that long-term use may cause damage to renal function. CONCLUSION:This study is the first to systematically investigate the multi-target, multi-pathway mechanism of action of Hydrargyrum Chloratum Compositum (Hcc) in treating chronic hard-to-heal wounds and to comprehensively assess its potential mercury toxicity risk. Through in vitro antimicrobial assays, animal models, histopathological analyses, protein expression and mercury ion accumulation assays, the present study revealed the unique mechanisms of Hcc in promoting wound healing, including inhibition of bacterial growth, modulation of immune-inflammatory responses, promotion of angiogenesis, and activation of key signalling pathways (Pi3k-Akt and Notch1-Vegfa pathways). In addition, this study is the first to evaluate the accumulation of mercury ions in Hcc in different organs, especially the significant accumulation in the kidney, which provides important safety data for clinical application. Compared with the existing literature, the present study verified the antimicrobial activity of Hcc, and revealed its specific mechanism in promoting wound healing, providing a scientific basis for the clinical use of Hcc.

Rationale: Adipose tissue buffers dietary lipids to maintain postprandial lipid homeostasis. Adipose tissue macrophages (ATMs) mediate the phagocytosis of postprandial lipids from the exogenous diet, generating high-density lipoprotein (HDL) particles that facilitate lipid circulation and excretion. However, the underlying mechanisms remain poorly understood. This study investigates the effects of esculetin, a coumarin compound, on postprandial cholesterol circulation and excretion following a high-fat meal. Methods: Mice were fed a lipid-rich meal for three days to assess the effects of esculetin on postprandial lipid circulation, using serum lipid profiling and metabolomics analysis. Epididymal white adipose tissue (eWAT) removal and flow cytometry were performed to analyze ATMs and confirm their role in mediating esculetin's effects on postprandial lipemia. Epigenetic profiling, transcriptome analysis, chromatin immunoprecipitation, and Terahertz chemical microscopy were employed to elucidate the molecular targets and mechanisms of esculetin. Results: Esculetin significantly elevates postprandial HDL cholesterol levels to values comparable to pitavastatin and modifies serum metabolites involved in bile-mediated cholesterol excretion, leading to increased bile acid concentrations in the bile. This effect is mediated by an increased ratio and phagocytic activity of a subset of ATMs expressing the scavenger receptor CD36, as eWAT removal and CD36 blockade inhibit this response. Furthermore, esculetin enhances the uptake of oxidized LDL via CD36, as demonstrated in cultured macrophages, and induces epigenetic changes controlled by the key transcription factor C/EBPβ, accompanied by increased C/EBPβ binding to the Cd36 promoter. A direct interaction between esculetin and C/EBPβ was observed using Terahertz chemical microscopy. Additionally, the activation of C/EBPβ by esculetin in ATMs was confirmed in vivo. Conclusion: Esculetin accelerates postprandial lipid circulation by binding to C/EBPβ and enhancing CD36-dependent phagocytosis in ATMs.

Hongsheng Dan, historically referred to as the "surgical sacred medicine", is at risk of losing its refining technology in contemporary times. This study aimed to preserve and innovate this traditional non-heritage refining technology. By utilizing the analytic hierarchy process(AHP) combined with the entropy weight method, this study established the hierarchical structure model of refining process of Hongsheng Dan and conducted a single factor experiment and an L_9(3~4) orthogonal experiment to optimize the refining method of Hongsheng Dan. Additionally, the study employed infrared thermal imaging to monitor temperature variations of Hongsheng Dan during the refining process. The optimized refining parameters for Hongsheng Dan were established as follows: a slow fire temperature of 175 ℃ with a duration of 30 minutes, a strong fire temperature of 270 ℃ with a duration of 60 minutes, and a tail fire temperature of 180 ℃ with a duration of 15 minutes. The stability and feasibility of this optimized process were confirmed through validation tests. The research focused on the material transformation of Hongsheng Dan, starting from the material changes during the refining process of Hongsheng Dan and the synthesis of mercuric oxide from nitric acid. The study investigated elemental transformations, physical phase changes, and alterations in thermal properties. 78.98% of the mercury in Hongsheng Dan and 80.21% of the mercury in mercuric oxide from nitric acid were retained. The diffraction peak intensity of the(011) crystal plane of Hongsheng Dan was highest at approximately 30.07°, indicating that the(011) crystal plane had a preferred crystalline orientation. Furthermore, the temperature range for the alteration in thermal properties during the refining process of Hongsheng Dan was found to be between 80 ℃ and 130 ℃. This research not only optimized the refining technology of Hongsheng Dan but also pioneered the application of infrared thermal imaging to study temperature changes throughout the refining process. By exploring the material transformation patterns of Hongsheng Dan and the synthesis of mercuric oxide from nitric acid, the study provided technical support for the preservation and innovation of Hongsheng Dan.

Bile-processed Coptidis Rhizoma (BPCR) exhibits stronger efficacy in treating T2DM than Coptidis Rhizoma(CR) alone. However, the synergistic mechanism of its processing remains unknown. This study utilized HPLC to determine the content and dissolution characteristics of alkaloid components in BPCR before and after processing. The results indicated that the diffusion of the alkaloids in BPCR is stronger than that of CR, and their dissolution conforms to the Weibull equation. Additionally, BPCR significantly reduced fasting blood glucose (FBG) and serum insulin (FINS) levels in T2DM rats induced by a high-fat diet (HFD) and streptozotocin (STZ), improved glucose and lipid metabolism, and mitigated liver damage. Serum metabolomics analysis based on UPLC-Q-TOF-MS revealed that BPCR significantly regulates 27 endogenous differential biomarkers. The underlying mechanism may be related to glycerophospholipid metabolism, linoleic acid metabolism, steroid biosynthesis, and arachidonic acid metabolism pathways.

ETHNOPHARMACOLOGICAL RELEVANCE:Hongsheng Dan, a traditional Chinese medicine, has been utilized in China for centuries due to its therapeutic properties. Its primary active component, mercuric oxide (HgO), is known for its efficacy in extracting toxins, pus drainage, necrotic tissue removal, and tissue regeneration. Despite its longstanding clinical application, the precise therapeutic mechanisms and comprehensive safety profile of Hongsheng Dan warrant further scientific investigation. AIMS OF THE STUDY:This study aims to elucidate the therapeutic mechanisms of Hongsheng Dan in the treatment of chronic, refractory skin ulcers and to evaluate its potential toxicity risks. METHODS:A rat model of chronic refractory wound was successfully established to evaluate the therapeutic effects of Hongsheng Dan. Wound healing efficacy was systematically assessed through multiple approaches, including wound closure rate, histopathological examination, immunohistochemical and immunofluorescence staining, and Hyp content analysis. To elucidate the underlying mechanisms, qRT-PCR and WB analyses were performed. Additionally, H&E staining was conducted to examine pathological alterations in major organs, while AAS was employed to quantify mercury ion accumulation. RESULTS:Hongsheng Dan demonstrated significant wound-healing efficacy in a rat model, with optimal therapeutic outcomes observed in the medium-dose treatment group. Histopathological analysis revealed substantial improvements in wound tissue architecture, characterized by diminished inflammatory cell infiltration and enhanced collagen deposition with robust granulation tissue formation. These morphological improvements were supported by immunohistochemical evidence showing significantly upregulated VEGF expression.At the molecular level, Hongsheng Dan treatment modulated key wound-healing mediators, suppressing IL-6 while promoting Hyp synthesis, thereby facilitating extracellular matrix remodeling. Gene expression analysis revealed coordinated regulation of critical healing pathways, with upregulation of VEGF, TGF-β1, and Smad3 mRNA, concurrent with downregulation of Notch1 signaling. WB analysis confirmed these findings at the protein level, showing increased VEGF and decreased Notch1 expression.Notably, while therapeutic doses of Hongsheng Dan caused no observable histopathological abnormalities in major organs, atomic absorption spectrometry detected significant mercury accumulation in renal tissue, suggesting potential nephrotoxic risk during extended therapeutic use. CONCLUSION:This investigation adopted a dual-focused approach to evaluate both the therapeutic mechanisms and potential toxicity of Hongsheng Dan. Prior to the systematic research, we performed quality control to ascertain the mercury valence state and concentration. Following this, a chronic refractory wound model in SD rats was studied using an integrated methodological framework that combining histopathological, molecular biological, and toxicological analyses. Our findings demonstrated that Hongsheng Dan promotes chronic wound healing through multi-pathway synergistic mechanisms. Concurrent concomitant toxicity revealed mercury accumulation-related toxicity, providing crucial evidence for risk-benefit evaluation in clinical applications.

Bile-Processed Coptidis Rhizoma (BPCR), which is processed with Coptidis Rhizoma (CR) and pig bile (PB), exhibits stronger efficacy in treating type 2 diabetes mellitus (T2DM) than CR alone. However, the impact of PB processing on the pharmacokinetics of active components in CR is still unclear. This study aims to investigate the pharmacokinetics and tissue distribution of BPCR in T2DM rats and clarify the enhancement mechanisms of PB processing. This study employed ultrahigh-performance liquid chromatography quadrupole-orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) to identify chemical components in the serum of rats after oral BPCR administration. A T2DM rat model was induced using a high-fat diet and streptozotocin. T2DM rats received 10 g/kg of CR, fried Coptidis Rhizoma (FCR), or BPCR, whereas the control group received the same dose of BPCR. Berberine levels in plasma and tissues were measured using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-QQQ-MS)/MS. Serum pharmacochemical analysis after oral BPCR administration identified one parent compound, berberine, and four metabolites. Pharmacokinetic studies revealed significant differences in maximum plasma concentration (Cmax), time to peak concentration (Tmax), and HL_Lambda_z (h) for BPCR compared to FCR and CR in T2DM rats (p < 0.05). In T2DM rats, significant differences in area under the concentration-time curve (AUClast) and clearance rate/bioavailability (Cl_F_obs) were observed compared to the normal group (p < 0.05). The concentration of berberine in various tissues after BPCR administration was consistently higher than that after FCR and CR. Additionally, T2DM rats showed significantly increased berberine concentrations after BPCR administration compared to the control group (p < 0.05). PB processing significantly influences the pharmacokinetics and tissue distribution of berberine in T2DM rats.

This study aimed to investigate the mechanism of the Coptidis Rhizoma and Cinnamomi Cortex (HL-RG) drug pair in the intervention of renal cell carcinoma (RCC) using network pharmacology, molecular docking, and cell experiments. Network pharmacology analysis predicted 42 active components in HL-RG and identified 227 potential targets. Among these, 50 targets were specifically associated with RCC, and 18 were identified as hub genes. Three components (quercetin, oleic acid, tetrandrine) were highlighted as particularly effective. The results of the gene ontology (GO) annotation showed that HL-RG may treat RCC by regulating biological processes such as inflammation, immune response, cell cycle process, and lipid metabolism. Kyoto Gene and Genome Encyclopedia (KEGG) enrichment revealed that the key targets of HL-RG in treating RCC were enriched in the proteoglycans in cancer, and the HIF-1 signaling pathway. Molecular docking results demonstrated that 87% of the interactions exhibited binding energies stronger than -5.0 kcal/mol, indicating favorable binding affinity between the core active components and key targets. Experimental validation using quantitative real-time polymerase chain reaction and Western blot in 786-O cells demonstrated that tetrandrine (TET) and quercetin (QUE) downregulated the mRNA and protein levels of G1/S-specific cyclin-D1 (CCND1) and Transforming growth factor beta-1 (TGFB1), and upregulated the mRNA levels of Catalase (CAT). Additionally, QUE downregulated the mRNA levels of Receptor tyrosine-protein kinase erbB-2 (ERBB2) and upregulated the mRNA levels of Pro-epidermal growth factor (EGF). Furthermore, oleic acid (OA), TET, and QUE downregulated the protein levels of Matrix metalloproteinase-9 (MMP9). In conclusion, the therapeutic effect of the HL-RG combination against RCC is primarily mediated by its bioactive components, QUE, OA, and TET. These components regulate the HIF-1 signaling pathway, activating genes involved in the cellular response to hypoxia and modulating the expression of proteins that control glucose metabolism, cell proliferation, and angiogenesis.

BACKGROUND:The airway epithelium serves as the first line of defense between the lung's internal environment and the external environment, functioning through physical barriers and mucus-ciliary clearance to protect against external allergens and other harmful substances. Airway epithelial damage is a common feature of asthma, and research has shown that apoptosis plays a significant role in airway injury and inflammation in asthma. Although Kechuan Decoction (KCD) has demonstrated clinical efficacy in treating pediatric asthma, its precise mechanism of action remains unclear. OBJECTIVE:To elucidate the therapeutic mechanism of KCD in mitigating apoptosis of airway epithelial cells (AECs) in a house dust mite (HDM)-induced asthma mouse model. METHODS:To evaluate the effects of KCD on asthma-associated airway inflammation and AECs apoptosis, an asthma model was established in C57BL/6 J mice using HDM. The major chemical constituents of KCD were analyzed using LC-MS. Subsequently, we utilized network pharmacology approaches to predict the potential targets and mechanisms of KCD in asthma. Additionally, we conducted lipidomics analysis of lung tissue and mitochondria in the lung was conducted using LC-MS. Finally, the mechanisms underlying the effects of KCD on AECs apoptosis in asthmatic mice were investigated through Western blotting, qPCR, and Transmission electron microscopy (TEM) examination techniques. RESULTS:The efficacy of KCD has been shown to improve lung function, reduce airway inflammation, and prevent apoptosis of AECs in a HDM-induced asthma model. Through the use of UPLC-LTQ-Orbitrap-MS, we identified 24 potential active components of KCD. Network pharmacology analysis revealed that KCD shares 102 core targets with asthma. GO enrichment analysis, in conjunction with a literature review, indicated that the targets of KCD treatment for AECs apoptosis primarily focus on the mitochondrial membrane. Furthermore, lipidomics analysis of lung tissue and mitochondria in the lungs of mice with HDM-induced asthma revealed disruptions in lipid metabolism, with a decrease in phosphatidylcholine (PC) content in asthmatic mice, which was effectively restored by KCD treatment. KCD reinstates the expression of START domain-containing protein 7 (StarD7) and START domain-containing protein 10 (StarD10) in lung tissue, leading to increase in PC within the mitochondrial membrane. This regulation indirectly influences mitochondrial fusion and fission proteins, promoting mitochondrial membrane stability and reducing cytochrome c (Cyt c) release into the cytoplasm. Ultimately, this process helps mitigate mitochondria-mediated apoptosis of AECs. CONCLUSION:KCD can restore the content of PC in the mitochondria of AECs by regulating StarD7 and StarD10. It also restores proteins associated with mitochondrial fusion and fission, stabilizing mitochondrial structure, effectively reducing the release of Cyt c into the cytoplasm, and ultimately inhibiting mitochondria-mediated apoptosis of AECs induced by HDM in asthmatic mice.

BACKGROUND:Bile-Processed Rhizoma Coptidis (BPRC) is a processed products of Rhizoma Coptidis (RC) commonly used to treat type 2 diabetes mellitus (T2DM). However, the synergistic mechanism of its processing remains unknown. Current research indicates that the gut microbiota and its metabolites, such as short-chain fatty acids (SCFAs), are closely associated with the progression of T2DM. PURPOSE:This study aims to investigate the effects of BPRC on the gut microbiota and its metabolite SCFAs in T2DM rats. METHODS:T2DM rat model was induced by a high-fat diet (HFD) combined with streptozotocin (STZ), followed by a 4-week treatment with BPRC to observe its therapeutic effects. The impact of BPRC on the gut microbiota was studied through metagenomic sequencing. Quantitative analysis of SCFAs was conducted using GC-MS. Western blot and quantitative real-time PCR (qRT-PCR) were conducted to investigate the potential mechanisms of BPRC. RESULTS:BPRC significantly improved insulin resistance in T2DM rats, downregulated levels of pancreatic cell apoptosis factors, and upregulated the abundance of Bacteroides uniformis, Bacteroides sp A1C1, Anaerostipes caccae, Alistipes finegoldii and Blautia sp.N6H1-15 in T2DM rats. Additionally, BPRC increased the levels of seven SCFAs in the intestines of T2DM rats. It activated intestinal TGR5, GPR41, GPR43, and GPR109a receptors, collectively upregulating GLP-1 protein expression, and exerted therapeutic effects on T2DM. CONCLUSION:The results indicate that the synergistic mechanism of BPRC in treating T2DM is associated with modulating the gut microbiota, increasing SCFAs content in the intestines, and regulating intestinal GLP-1 production.

ETHNOPHARMACOLOGICAL RELEVANCE:Coptis chinensis, a traditional Chinese herb, has demonstrated potential therapeutic effects against IR and T2DM. Pig bile is the gallbladder bile extracted from the domestic pig, Sus scrofa domestica Brisson. The "Compendium of Materia Medica" documents that it is primarily used to treat conditions such as typhoid fever, heat-induced thirst, bone heat, extreme fatigue, and diabetes. The traditional way of making Bile-processed Coptidis Rhizoma (BRC), which is a processed form of Coptis chinensis(RC) using pig bile. Processing Coptis chinensis with bile aligns with the traditional Chinese medicine processing principles of "mutual reinforcement through combination" and "enhancing cold properties with cold ingredients." Furthermore, this method represents a unique technique within traditional Chinese medicine. Nevertheless, the pharmacological mechanisms behind bile-processed Coptis chinensis in treating type 2 diabetes mellitus (T2DM)necessitate further investigation. AIM OF THE STUDY:In traditional Chinese medicine, diabetes is known as "Xiao Ke," considered a heat syndrome. Both Coptis and bile have records of treating "Xiao Ke" in ancient texts, and we believe that bile-processed Coptis can combine the hypoglycemic properties of both, enhancing the treatment of diabetes. The point of this study was to look into how BRC water extract affects glucosamine-induced insulin resistance in HepG2 cells. MATERIALS AND METHODS:UPLC-QQQ-MS quantified the alkaloids and bile acids in BRC and RC. Cell viability was assessed using the CCK-8 assay. Insulin-resistant HepG2 (IR-HepG2) cells were established via 24-h incubation with 9 mM glucosamine. Glucose consumption and glycogen content were measured after BRC treatment (25-100 μg/mL). Periodic Acid-Schiff (PAS) staining was used to look for glycogen, and Oil Red O staining was used to look for lipid buildup. Quantitative real-time PCR (qRT-PCR) and Western blotting were used to look at the levels of gene and protein expression. RESULTS:After processing, the content of some alkaloids was significantly increased. BRC treatment increased the amount of glucose used by IR-HepG2 cells (p < 0.01), raised the amount of glycogen in cells (p < 0.01), and decreased the production of lipids. Mechanistically, BRC increased the phosphorylation and total protein levels of PI3K/AKT/FOXO1 in IR-HepG2 cells (p < 0.01), leading to a decrease in the expression of glucose-6-phosphatase (G6Pase) in IR-HepG2 cells (p < 0.01). CONCLUSION:By starting up the PI3K/AKT/FOXO1 signaling pathway, BRC helps HepG2 cells that are insulin-resistant because of glucosamine. This returns glycolipid metabolic homeostasis. These results back up the traditional use of processing bile to make Coptis chinensis work better as an anti-diabetic.

ETHNOPHARMACOLOGICAL RELEVANCE:Traditionally, Calomelas and its preparations have been employed in traditional Chinese medicine (TCM) for the management of scabies and ulcers, exhibiting empirically validated efficacy in wound management protocols, with persistent contemporary utilization. Nevertheless, significant concerns regarding its mercury composition have prompted modern scrutiny. Crucially, a rigorous systematic evaluation of Calomelas and its preparations was still lacking in the existing literature, which hindered their evidence-based application and potential advancement. AIM OF THE REVIEW:This review aims to clarify the medicinal benefits and toxicity of Calomelas and its preparations, supporting the development of modern treatments for refractory skin ulcers while promoting the safe and rational integration of Calomelas-containing preparations into dermatological practice. MATERIALS AND METHODS:Data on Calomelas and its preparations were systematically collated from scientific databases, including PubMed, Google Scholar, ACS Publications, Web of Science, ScienceDirect, CNKI, and WANGFANG. RESULTS:Calomelas, a mercury-based compound utilized in TCM since the Tang dynasty, has exhibited pronounced therapeutic efficacy in the management of various refractory wound conditions. Several Calomelas-containing preparations, such as Shengji Yuhong Ointment, Babao Pill, Baodu Shengji Powder, Taiyi Ointment, and Calomelas Powder, are routinely utilized in clinical practice for the treatment of diverse skin ulcers and stubborn wounds, including diabetic foot ulcers, postoperative impairments, pressure injuries, and burn wounds. The pharmacological basis of these therapeutic effects relies on their biological activity properties, including antibacterial, anti-inflammatory, antioxidant, pro-angiogenic, and pro-gliogenic activities. Despite ongoing safety concerns related to the inherent toxicity of mercury, Calomelas and its preparations exhibited an acceptable safety profile when administered in accordance with established clinical protocols. CONCLUSION:Calomelas and its preparations are supported by clinical validation and modern pharmacological research, confirming their definite therapeutic efficacy and controllable safety profile. These findings highlight their significant clinical value and broad application prospects in the surgical practice of TCM.

Ethnopharmacological relevance Chen Xiang Qu (CXQ) is a traditional Chinese medicinal preparation originating from the Qing Dynasty and documented in multiple classical Chinese medical texts. Composed of agarwood, sandalwood, ginger-processed magnolia bark, and Massa Medicata Fermentata, it possesses the traditional efficacy of “regulating the liver and harmonizing the stomach, strengthening the spleen and eliminating food stagnation.” Clinically, it is used to treat symptoms such as chest and abdominal distension and pain, belching, and vomiting caused by liver-stomach disharmony and spleen deficiency with dampness stagnation. Aims of the study The present study aims to validate CXQ’s traditional application in functional dyspepsia treatment, providing modern pharmacological evidence for its clinical application. Methods This study first employed UPLC-Q-TOF/MS technology to conduct a comprehensive chemical composition analysis of CXQ, establishing a material foundation for subsequent pharmacodynamic and mechanism investigations. Subsequently, a rat model of FD was developed through a combination of tail pinching, physical restraint, and irregular feeding. The effects of CXQ on gastrointestinal function were evaluated by measuring rat body weight, gastric retention rate, and small intestinal propulsion rate. Additionally, Western blot analysis was performed to analyze the protein levels. Furthermore, depressive-like behaviors in rats through sucrose preference and open field tests were examined. UPLC-QQQ-MS technology was employed to quantitatively detect monoamine neurotransmitter levels in brain tissue. Network pharmacology methods were employed to predict potential targets and signaling pathways, and validated by qPCR assay and Western blot. Results 116 chemical constituents in CXQ and 10 key components in the plasma and brain tissues of rats. CXQ significantly improved gastrointestinal motility disorders in FD rats by reducing the gastric retention rate and enhancing the small intestinal propulsion rate. CXQ also downregulated the protein overexpression of CCKBR and Nesfatin-1 in gastric tissue, and effectively alleviated depressive-like behaviors. Mechanistically, 21 intersecting targets were identified through network pharmacology screening. GO and KEGG enrichment analyses identified the TNF signaling pathway as a key mechanism for CXQ treatment. CXQ attenuated duodenal inflammatory responses in FD rats through the suppression of TNF-α, NF-κB, and IL-6 mRNA levels and p-NF-κB p65 protein expression in duodenal tissues. Conclusion These data suggest that CXQ ameliorates FD by restoring gastrointestinal motility and alleviating depressive-like behaviors as well as low-grade duodenal inflammation through inhibition of the TNF-α/NF-κB/IL-6 inflammatory signaling axis.