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Pomegranate peel-derived extracellular nanovesicles(PPENs) were isolated and purified by ultra-high speed centrifugation and sucrose density gradient centrifugation. Their morphology and structure were characterized. In vitro α-glucosidase inhibition assay and model test of insulin resistance(IR) in HepG2 cells showed that PPENs had good anti-diabetic activity. The IC_(50) value of α-glucosidase inhibition was(35.3±1.1) µg·mL~(-1), significantly better than the positive drug acarbose. At a concentration of 100 µg·mL~(-1), PPENs could increase the glucose absorption of IR cells significantly. Lipidome, proteome, and metabolite analysis of PPENs were performed using chromatography-mass spectrometry. MicroRNA(miRNA) sequences were identified, and target genes of miRNA were predicted. The analysis results indicated that PPENs contained abundant lipids and transport proteins, providing a material basis for the transportation and distribution of PPENs in tissue. Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis suggested that lipids and miRNAs may be the key components of PPENs to exert anti-diabetic activity.

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Mannoproteins have traditionally been recognized as effective wine organoleptic modulators, however, ambiguous understanding of the relationship between their organoleptic functions and physiochemical characteristics often lead to inappropriate application in winemaking. To reveal the possible role the physiochemical characteristics of mannoproteins play in modulating wine color and aroma properties, three water-soluble mannoproteins (MP1, MP2, MP3) with different physiochemical characteristics have been prepared, and accelerated red wine aging, malvidin pigments formation experiments, accelerated aroma release experiments have been designed to observe their organoleptic modulating functions in this research. Results suggest that the phenolic/chromatic stability of red wines could be enhanced by MP3, probably due to its low steric hindrance potential, high reactivity, and good hydro-alcoholic stability conferred by its high Mannan/Glucan ratio (8.68), abundant hydrophobic/hydrophilic amino acids (65.29 % of total protein), and low/medium molecular weight level (30.71-57.77 kDa), respectively, which protected the phenolic compounds and promoted the formation of pyranoanthocyanins. Mannoproteins could modulate the volatility of aroma compounds by expelling or retention effects, which depended on the duration of mannoprotein application (the expelling effect was firstly observed possibly because of the significant adsorption of free H2O by MPs) and the types of mannoproteins. MP1 and MP2 were prone to retain and expel aroma compounds, respectively, probably due to their medium/high molecular weight levels (60.48-135.39 kDa) that conferred abundant interacting sites, and the high proportion of hydrophobic and hydrophilic components in MP1 (97.71 % polysaccharides of total mannoprotein, 34.58 % hydrophobic amino acids of total protein) and MP2 (97.96 % polysaccharides of total mannoprotein, 28.36 % hydrophobic amino acids of total protein) guaranteed a relatively higher interacting frequency with aroma compounds and free H2O molecules, respectively.

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Six compounds were isolated from lettuce latex. They were identified as 2,5-dihydroxybenzaldehyde (1), 3ß-hydroxy-4,15-dehydrograndolide (2), annuolide D (3), lactucin (4), lactucopicrin (5), and hanphyllin (6). Bioassays showed that the inhibition rate of compound 1 (2,5-dihydroxybenzaldehyde) and 6 (hanphyllin, a sesquiterpene lactone) on the weight gain of S. litura were 52.4% and 10%, respectively, at the concentration of 100 µg/g. RNA-seq analyses showed that larval exposure to compound 1 down-regulated the genes associated with heterobiotic metabolism including drug metabolism-cytochrome P450, metabolism of xenobiotics by cytochrome P450, retinol metabolism, glutathione metabolism, and drug metabolism-other enzymes (mainly uridine diphosphate glucuronyltransferase, UGTs). RT-qPCR further confirmed that 33 genes in the family of carboxylesterase (CarE), P450s and UGTs were down-regulated by compound 1. The activities of CarE, P450s and UGTs in the larvae fed on diets containing compound 1 were significantly lower than those fed on control diets, with the inhibition for the three detoxification enzymes being 55.4%, 53.9%, and 52.9%. These findings suggest that secondary metabolites including 2,5-dihydroxybenzaldehyde in the latex play a key role in protecting lettuce from insect herbivory.

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BACKGROUND: Allii Macrostemonis Bulbus is also named Xiebai in China. It is an edible vegetable, and also a famous herb for treating coronary heart disease. Allium chinense G. Don (ACGD) and Allium macrostemon Bunge (AMB) are it botanical sources. The aim of this study was to explore the cardioprotective effects, and decipher the visual spatial distribution and absolute content of primary metabolites derived from these two herbs. METHODS: H9c2 cells were used to perform the hypoxia-reoxygenation (H/R)-induced myocardial injury model. Their protective effects were evaluated by apoptosis levels. Furthermore, matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry imaging approach (MALDI-TOF MSI) was carried out to present the spatial location of primary metabolites including fatty acids, amino acids, carotenoids, and vitamins in these two Allium herbs. Multiple analytical methods were applied to perform quantitative analysis of these primary metabolites in AMB and ACGD bulbs by liquid chromatography tandem mass spectrometry (LC-MS). RESULTS: First, AMB and ACGD extracts both could increase the cell viability in H9c2 cells, and attenuate H/R-induced injury. They markedly decreased apoptosis, accompanied by activating the BCL-2/BAX pathway. Further, MALDI-TOF MSI-based relative quantification results showed several amino acids, fatty acids, carotenoids, and vitamins were largely rich in the tunics and outside scales of fresh bulbs, while some primary metabolites were abundant in their developing flower buds. Absolute quantification results displayed total contents of amino acids in ACGD bulbs were higher than those in AMB, while total contents of fatty acids and vitamins provides opposite trends in these two Allium herbs. The total contents of carotenoids and trace elements showed no significant differences between AMB and ACGD samples. CONCLUSIONS: This study would be helpful to understand the myocardial injury protection effects of these two Allium herbs, and the spatial accumulation and quantitative content levels of their main nutrients.

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BACKGROUND: The excessive application of chemical fertilizers in the cultivation of Astragalus mongholicus Bunge results in a reduction in the quality of the medicinal plant and compromises the sustainable productivity of the soil. PGPB inoculant is a hot topic in ecological agriculture research. In the cultivation of Astragalus mongholicus, the screened nitrogen-fixing bacteria can promote plant growth, however, whether it can promote the accumulation of main bioactive components remains unknown. In this study, mixed inoculants containing 5 strains of growth promoting bacteria (Rhizobium T16 , Sinorhizobium T21 , Bacillus J1 , Bacillus G4 and Arthrobacter J2) were used in the field experiment. The metabolic substances in the root tissues of Astragalus mongholicus were identified during the harvest period by non-targeted metabolomics method, and the differential metabolites between groups were identified by statistical analysis. Meanwhile, high-throughput sequencing was performed to analyze the changes of rhizosphere soil and endophytic microbial community structure after mixed microbial treatment. RESULTS: The results of non-targeted metabolism indicated a significant increase in the levels of 26 metabolites after treatment including 13 flavonoids, 3 saponins and 10 other components. The contents of three plant hormones (abscisic acid, salicylic acid and spermidine) also increased after treatment, which presumed to play an important role in regulating plant growth and metabolism. Studies on endosphere and rhizosphere bacterial communities showed that Rhzobiaceae, Micromonosporaceae, and Hypomicrobiaceae in endophytic, and Oxalobactereae in rhizosphere were significantly increased after treatment. These findings suggest their potential importance in plant growth promotion and secondary metabolism regulation. CONCLUSIONS: This finding provides a basis for developing nitrogen-fixing bacteria fertilizer and improving the ecological planting efficiency of Astragalus mongholicus.

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Snake gourd is a seasonal vegetable with a high water content and medicinal value, but the short harvest period limits the large-scale application of snake gourd. Therefore, the effects of freeze-thaw pretreatment (FT) combined with hot air (HD) on the drying characteristics, active ingredients and bioactivities of snake gourd were investigated. The results showed that FT pretreatment reduced browning and shortened the drying time by 44%; the Page model was the best fit for describing the drying process. The polysaccharide contents (21.70% in alcoholic extract (TG1) and 44.34% in water extract (TG2)) and total phenol contents (1.81% in TG1 and 0.88% in TG2) of snake gourd pretreated by FT-HD were higher than those of snake gourd pretreated by the corresponding HD treatment. The FT pretreatment decreased the molecular weight of snake gourd polysaccharides and increased the molar ratio of glucose. The extracts pretreated by FT-HD showed greater chemical, cellular antioxidant capacity and α-amylase and α-glucosidase inhibition than those pretreated by HD. FT-HD can be recommended for achieving a short drying time and high quality of snake gourd and can be used for the drying of other fruits and vegetables.

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Cordyceps cicadae is recognized for its medicinal properties, attributed to bioactive constituents like polysaccharides and adenosine, which have been shown to improve kidney and liver functions and possess anti-tumor properties. Rho GTPase activating proteins (Rho GAPs) serve as inhibitory regulators of Rho GTPases in eukaryotic cells by accelerating the GTP hydrolysis of Rho GTPases, leading to their inactivation. In this study, we explored the function of the CcRga8 gene in C. cicadae, which encodes a Rho-type GTPase activating protein. Our study found that the knockout of CcRga8 resulted in a decrease in polysaccharide levels and an increase in adenosine concentration. Furthermore, the mutants exhibited altered spore yield and morphology, fruiting body development, decreased infectivity, reduced resistance to hyperosmotic stress, oxidative conditions, and cell wall inhibitors. These findings suggest that CcRga8 plays a crucial role in the development, stress response, and bioactive compound production of C. cicadae.

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Areca nut (AN), the fruit or seed of Areca catechu Linn, has many uses, including chewing and medicinal purposes. It has sparked worries about health due to the presence of alkaloids. Chewing AN may have a variety of negative consequences; however, the medicinal use of AN has no notable adverse effects. To completely understand and effectively use AN, researchers have investigated its chemical makeup or biological activity, analyzed the variations between different AN species and different periods, and improved extraction and processing procedures. Today, an increasing number of researchers are exploring the underlying reasons for AN variations, as well as the molecular mechanisms of biosynthesis of chemical components, to comprehend and change AN at the genetic level. This review presents an overview of the clinical study, pharmacology, and detection of the main bioactive components in AN, and the main factors influencing their content, delving into the omics applications in AN research. On the basis of the discussions and summaries, this review identifies current research gaps and proposes future directions for investigation.

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Background: Chemotherapy-induced myelosuppression (CIM) is a common adverse reaction with a high incidence rate that seriously affects human health. Shengyu Decoction (SYD) is often used to treat CIM. However, its pharmacodynamic basis and therapeutic mechanisms remain unclear. Purpose: This study aimed to clarify the active components and mechanisms of SYD in CIM. Methods: LC-QTOF/MS was used to identify the absorbable components of SYD. A series of network pharmacology methods have been applied to explore hub targets and potential mechanisms. Molecular docking was used to identify the binding ability of potential active ingredients and hub targets. Finally, in vitro experiments were performed to validate these findings. Results: In this study, 33 absorbable prototype components were identified using LC-QTOF/MS. A total of 62 possible targets of SYD in myelosuppression were identified. KEGG pathway enrichment analyses showed that some signaling pathways such as PI3K-Akt and HIF-1 may be the mechanisms by which it functions. Among them, we verified the PI3K-Akt pathway. 6 Hub proteins were screened by Protein-protein interaction (PPI) network analysis. Molecular docking results showed that four absorbable components in SYD showed good binding with six Hub targets. The effectiveness of the four predicted compounds and the mechanism were verified in vitro. It has also been shown that the active component could promote the proliferation of bone marrow stromal cells (BMSCs) and block apoptosis of BMSCs, which may be related to the PI3K-Akt pathway. This result is consistent with the network pharmacology approach and molecular docking predictions. Conclusion: Our results provided not only the candidate active component of SYD, but also a new insights into mechanism of SYD in the treatment of CIM.

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ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Qiling granules (FQG), derived from the traditional Qiling Decoction with a longstanding clinical history, is utilized for the treatment of hyperuricemia (HUA). FQG is formulated with a combination of seven Chinese herbs based on the principles of traditional Chinese medicine (TCM) theories. Clinical evidence indicates that FQG exhibits favorable therapeutic effects in reducing uric acid (UA) levels and attenuating renal damage. AIM OF THIS STUDY: To elucidate the potential active components and pharmacological mechanism of FQG in the treatment of HUA, and to provide an experimental basis for the development of efficient and low-toxicity TCM for HUA treatment. MATERIALS AND METHODS: A HUA rat model induced by potassium oxonate and adenine was established to initially evaluate the hypouricemic effects of FQG. Chemical analyses were conducted using an ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Network pharmacology was used to investigate the active components and mechanism of FQG in the treatment of HUA. Potential Xanthine oxidase (XOD) inhibitors were screened from FQG based on ultrafiltration liquid chromatography and mass spectrometry (UF-LC-MS). Molecular docking, surface plasmon resonance (SPR) and circular dichroism (CD) spectroscopy were applied to validate the interactions between the active components and XOD. RESULTS: In comparison to the model group, treatment with FQG significantly decreased serum UA, serum creatinine (CREA), serum blood urea nitrogen (BUN), and liver XOD activity. Additionally, the FQG administration notably ameliorated HUA-induced renal injury in rats. Through the pharmacodynamics of the HUA rat models and network pharmacology, it was found that XOD was a key pathway enzyme in UA metabolism. 18 XOD inhibitors were screened from FQG by UF-LC-MS, and 11 compounds with strong affinity were verified by SPR, molecular docking and CD spectroscopy. CONCLUSION: In summary, flavonoids, organic acids and saponins may be the active components in FQG that alleviate HUA. The primary mechanism of FQG involves inhibiting XOD enzyme activity in the plasma to reduce UA production, alleviating renal tubular epithelial cell necrosis, tubulointerstitial injury, fibrosis, and urate deposition, ultimately exerting a therapeutic effect on HUA.

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Active components of natural products, which include paclitaxel, curcumin, gambogic acid, resveratrol, triptolide and celastrol, have promising anti-inflammatory, antitumor, anti-oxidant, and other pharmacological activities. However, their clinical application is limited due to low solubility, instability, low bioavailability, rapid metabolism, short half-life, and strong off-target toxicity. To overcome these drawbacks, cell membrane-based biomimetic nanosystems have emerged that avoid clearance by the immune system, enhance targeting, and prolong drug circulation, while also improving drug solubility and bioavailability, enhancing drug efficacy, and reducing side effects. This review summarizes recent advances in the preparation and coating of cell membrane-coated biomimetic nanosystems and in their applications to disease for targeted natural products delivery. Current challenges, limitations, and prospects in this field are also discussed, providing a research basis for the development of multifunctional biomimetic nanosystems for natural products.

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AIM: The aim of the present review is to shed light on the nanotechnological approaches adopted to overcome the shortcomings associated with the delivery of venom peptides which possess inherent anti-cancer properties. BACKGROUND: Venom peptides although have been reported to demonstrate anti-cancer effects, they suffer from several disadvantages such as in vivo instability, off-target adverse effects, limited drug loading and low bioavailability. This review presents a comprehensive compilation of different classes of nanocarriers while underscoring their advantages, disadvantages and potential to carry such peptide molecules for in vivo delivery. It also discusses various nanotechnological aspects such as methods of fabrication, analytical tools to assess these nanoparticulate formulations, modulation of nanocarrier polymer properties to enhance loading capacity, stability and improve their suitability to carry toxic peptide drugs. CONCLUSION: Nanotechnological approaches bear great potential in delivering venom peptide-based molecules as anticancer agents by enhancing their bioavailability, stability, efficacy as well as offering a spatiotemporal delivery approach. However, the challenges associated with toxicity and biocompatibility of nanocarriers must be duly addressed. PERSPECTIVES: The everlasting quest for new breakthroughs for safer delivery of venom peptides in human subjects is fuelled by unmet clinical needs in the current landscape of chemotherapy. In addition, exhaustive efforts are required in obtaining and purifying the venom peptides followed by designing and optimizing scale up technologies.

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Bailing capsule (BLC), a drug that is clinically administered to modulate the autoimmune system, exhibits promising therapeutic potential in the treatment of thyroiditis. This study elucidates the chemical profile of BLC and its potential therapeutic mechanism in thyroiditis, leveraging network pharmacology and molecular docking techniques. Utilizing ultra-high-performance liquid chromatography coupled with linear trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap MS), 58 compounds were identified, the majority of which were nucleosides and amino acids. Utilizing the ultra-high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UHPLC QqQ MS/MS) strategy, 16 representative active components from six batches of BLCs were simultaneously determined. Network pharmacology analysis further revealed that the active components included 5'-adenylate, guanosine, adenosine, cordycepin, inosine, 5'-guanylic acid, and l-lysine. Targets with higher connectivity included AKT1, MAPK3, RAC1, and PIK3CA. The signaling pathways primarily focused on thyroid hormone regulation and the Ras, PI3K/AKT, and MAPK pathways, all of which were intricately linked to inflammatory immunity and hormonal regulation. Molecular docking analysis corroborated the findings from network pharmacology, revealing that adenosine, guanosine, and cordycepin exhibited strong affinity toward AKT1, MAPK3, PIK3CA, and RAC1. Overall, this study successfully elucidated the material basis and preliminary mechanism underlying BLC's intervention in thyroiditis, thus laying a solid basis for further exploration of its in-depth mechanisms.

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Liver fibrosis is a key pathological stage in the progression of chronic liver disease. If the disease is mistreated, it can further deteriorate into liver failure, which seriously affects the quality of life of patients and brings heavy medical costs. Hepatic stellate cell(HSC) activation triggers extracellular matrix(ECM) deposition, which plays an important driving role in liver fibrosis, and ferroptosis is an effective strategy to clear or reverse the activation of HSCs into a deactivated phenotype. Therefore, inhibiting the activation and proliferation of HSCs by regulating ferroptosis is the key to the treatment of this disease, so as to derive the prospect of inducing ferroptosis of HSCs(including RNA-binding proteins, non-coding RNA, chemicals, and active components of traditional Chinese medicine) to intervene in liver fibrosis. On this basis, this paper started from the activation of HSCs to induce ECM deposition and focused on summarizing the mechanism of inducing HSC ferroptosis in delaying the progression of liver fibrosis, so as to continuously enrich the clinical practice of liver fibrosis and provide a reference for subsequent basic research.

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Extracellular polymeric substances (EPS) participate in the removal of organic micropollutants (OMPs), but the primary pathways of removal and detailed mechanisms remain elusive. We evaluated the effect of EPS on removal for 16 distinct chemical classes of OMPs during anaerobic digestion (AD). The results showed that hydrophobic OMPs (HBOMPs) could not be removed by EPS, while hydrophilic OMPs (HLOMPs) were amenable to removal via adsorption and biotransformation of EPS. The adsorption and biotransformation of HLOMPs by EPS accounted up to 19.4 ± 0.9 % and 6.0 ± 0.8 % of total removal, respectively. Further investigations into the adsorption and biotransformation mechanisms of HLOMPs by EPS were conducted utilizing spectral, molecular dynamics simulation, and electrochemical analysis. The results suggested that EPS provided abundant binding sites for the adsorption of HLOMPs. The binding of HLOMPs to tryptophan-like proteins in EPS formed nonfluorescent complexes. Hydrogen bonds, hydrophobic interactions and water bridges were key to the binding processes and helped stabilize the complexes. The biotransformation of HLOMPs by EPS may be attributed to the presence of extracellular redox active components (c-type cytochromes (c-Cyts), c-Cyts-bound flavins). This study enhanced the comprehension for the role of EPS on the OMPs removal in anaerobic wastewater treatment.

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Panax ginseng is reputed to be capable of replenishing healthy Qi and bolstering physical strength, and P. notoginseng can resolve blood stasis and alleviate pain. P. ginseng and P. notoginseng are frequently employed to treat ischemic heart diseases caused by blockages in the heart vessels. Mitochondrial dysfunction often coexists with abnormal mitochondrial morphology, and mitochondrial plasticity and dynamics play key roles in cardiovascular diseases. In this study, primary neonatal rat cardiomyocytes were exposed to 4 hours of hypoxia(H) followed by 2 hours of reoxygenation(R). MitoTracker Deep Red and Hoechst 33342 were used to label mitochondria and nuclei, respectively. Fluorescence images were then acquired using ImageXpress Micro Confocal. Automated image processing and parameter extraction/calculation were carried out using ImagePro Plus. Subsequently, representative parameters were selected as indicators to assess alterations in mitochondrial morphology and function. The active compounds of P. ginseng and P. notoginseng were screened out and identified based on the UPLC-Triple-TOF-MS results and mitochondrial morphometric parameters. The findings demonstrated that RS-2, RS-4, SQ-1, and SQ-4 significantly increased the values of three key morphometric parameters, including mitochondrial length, branching, and area, which might contribute to rescuing morphological features of myocardial cells damaged by H/R injury. Among the active components of the two medicinal herbs, 20(R)-ginsenoside Rg_3, ginsenoside Re, and gypenoside ⅩⅦ exhibited the strongest protective effects on mitochondria in cardiomyocytes. Specifically, 20(R)-ginsenoside Rg_3 might upregulate expression of optic atrophy 1(OPA1) and mitofusin 2(MFN2), and ginsenoside Re and gypenoside ⅩⅦ might selectively upregulate OPA1 expression. Collectively, they promoted mitochondrial membrane fusion and mitigated mitochondrial damage, thereby exerting protective effects on cardiomyocytes. This study provides experimental support for the discovery of novel therapeutic agents for myocardial ischemia-reperfusion injury from P. ginseng and P. notoginseng and offers a novel approach for large-scale screening of bioactive compounds with cardioprotective effects from traditional Chinese medicines.

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Traditional Chinese medicine is precious treasure of ancient Chinese science and a key to unlocking the treasure trove of Chinese civilization. To elucidate the efficacy and mechanism of traditional Chinese medicines, scientists have been engaged in the research on the molecular basis and regulatory targets. Molecular docking is a computer-aided drug design method capable of visualizing the interaction between components and target proteins. With the progress in the modernization of traditional Chinese medicine and the advancement of algorithms and computing power, molecular docking has become an essential approach in the development of new traditional Chinese medicines. This article summarizes the recent research progress in molecular docking in the development of traditional Chinese medicine, aiming to provide valuable references for further screening of active components and offering insights for improving the development of new traditional Chinese medicines.

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Sepsis is a systemic inflammatory response syndrome caused by infection, with high morbidity and mortality. Sepsis-induced liver injury(SILI) is one of the manifestations of sepsis-induced multiple organ syndrome. At present, there is no recommended pharmacological intervention for the treatment of SILI. traditional Chinese medicine(TCM), based on the holism and dialectical treatment concept, shows the therapeutic characteristics of multi-target and multi-pathway and can comprehensively prevent and treat SILI by interfering with inflammatory factors, inflammatory signaling pathways, and anti-oxidative stress and inhibiting apoptosis. This article reviewed the experimental studies on the treatment of SILI with TCM to clarify its pathogenic mechanism and therapeutic characteristics, so as to provide more ideas and directions for the development or preparation of new drugs.

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As ethnic medicine, the whole grass of plants in Cirsium was used as antimicrobial. This review focuses on the antimicrobial activity of plants in Cirsium, including antimicrobial components, against different types of microbes and bacteriostatic mechanism. The results showed that the main antimicrobial activity components in Cirsium plants were flavonoids, triterpenoids and phenolic acids, and the antimicrobial ability varied according to the species and the content of chemicals. Among them, phenolic acids showed a strong antibacterial ability against Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterococcus faecium. The antibacterial mechanisms include: (1) damaging the cell membrane, cell walls, mitochondria and nucleus of bacteria; (2) inhibiting the synthesis of proteins and nucleic acids; (3) suppressing the synthesis of enzymes for tricarboxylic acid cycle pathways and glycolysis, and then killing the bacteria via inhibition of energy production. Totally, most research results on antimicrobial activity of Cirsium plants are reported based on in vitro assays. The evidence from clinical data and comprehensive evaluation are needed.

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ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine has great potential and advantages in the treatment of liver fibrosis, with Fuzheng Huayu formula (FZHY) serving as a prime example due to its remarkable efficacy in delaying and reversing liver fibrosis while simultaneously improving clinical symptoms for patients. AIM OF THE REVIEW: In this paper, we present a comprehensive review of recent studies on the therapeutic potential of FZHY and its components/ingredients in the treatment of liver fibrosis and cirrhosis, with the aim of providing insights for future research endeavors. MATERIALS AND METHODS: A comprehensive literature search was conducted on FZHY, TCM319, traditional Chinese medicine 319, liver fibrosis and cirrhosis using multiple internationally recognized databases including PubMed, Embase, Springer, Web of science, SciVerse ScienceDirect, Clinical Trails. Gov, CNKI, Wanfang, and VIP. RESULTS: FZHY is widely used clinically for liver fibrosis and cirrhosis caused by various chronic liver diseases, with the effects of improving serum liver function, liver pathological histology, serological indices related to liver fibrosis, decreasing liver stiffness values and portal hypertension, as well as reducing the incidence of hepatocellular carcinoma and morbidity/mortality in patients with cirrhosis. Numerous in vivo and in vitro experiments have demonstrated that FZHY possesses anti-fibrotic effects by inhibiting hepatic stellate cell activation, reducing inflammation, protecting hepatocytes, inhibiting hepatic sinusoidal capillarization and angiogenesis, promoting extracellular matrix degradation, and facilitating liver regeneration. In recent years, there has been a growing focus on investigating the primary active components/ingredients of FZHY, and significant strides have been made in comprehending their synergistic mechanisms that enhance efficacy. CONCLUSION: FZHY is a safe and effective drug for treating liver fibrosis. Future research on FZHY should focus on its active components/ingredients and their synergistic effects, as well as the development of modern cocktail drugs based on its components/ingredients. This will facilitate a more comprehensive understanding of the molecular mechanisms and targets of FZHY in treating liver fibrosis, thereby further guide clinical applications and drug development.

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