Coumarins mainly include simple coumarins, furanocoumarins, and pyranocoumarins. These compounds exhibit diverse biological activities, including anticoagulant, antibacterial, antitumor, and antioxidant effects, and thus possess high value for drug development. At present, coumarins are mainly obtained through traditional plant extraction methods. In recent years, synthetic biology has emerged as a new approach for the sustainable production of natural products. This article reviews the pharmacological effects, biosynthetic pathways, and biomanufacturing methods of different types of coumarins. It focuses on strategies for improving coumarin production, including the application of enzyme engineering based on directed evolution to modify rate-limiting enzymes and thereby enhance catalytic efficiency; the use of metabolic engineering to remodel metabolic flux, strengthen precursor supply, and weaken competing pathways, allowing more carbon flux to be directed toward target products; and the optimization of fermentation parameters through fermentation engineering to improve the viability of engineered strains and increase the yield of target compounds. These studies provide important references for the green, efficient, and sustainable production of coumarins, and are conducive to promoting the development of new coumarin-based drugs.
The frequent occurrence of continuous cropping obstacles has become a major constraint on the sustainable development of the Panax ginseng industry. As the characteristic secondary metabolites of P. ginseng, ginsenosides are released by plants into the soil and can persist in the soil environment through physical adsorption, microbial transformation and other processes, thereby exerting a sustained regulatory effect on the composition of rhizosphere microbial communities. Taking ginsenoside-mediated rhizosphere microecological succession as the core thread, this paper systematically expounded the rhizosphere release characteristics of ginsenosides and their transformation and persistence rules in soil, analyzed the intrinsic processes by which ginsenosides shaped pathogen-dominated rhizosphere microbial communities through group-specific selection and further mediated the gradual succession of rhizosphere microecology from a disease-suppressive state to a disease-conducive state, and clarified the inherent correlation between rhizosphere microecological imbalance and the formation of continuous cropping obstacles in P. ginseng. In addition, a three-stage microecological intervention strategy of "reset-reconstruction-stabilization" was proposed, aiming to provide theoretical references and practical insights for the ecological prevention and control of continuous cropping obstacles in P. ginseng.
Huangqin Qingre Chubi Capsules(HQC) are commonly used in clinical practice to treat rheumatoid arthritis(RA). It is composed of Scutellariae Radix, Gardeniae Fructus, Coicis Semen, Clematidis Radix et Rhizoma, and the stir-fried Persicae Semen. However, the pharmacological substance basis and mechanism are not yet clear. This study systematically elucidated the pharmacological substance basis and mechanism of HQC by the research strategy of "identification of target tissue migration components-network mechanism prediction-multidimensional experimental verification". An adjuvant-induced arthritis(AA) rat model was established, and the serum and synovium migration components of HQC in normal and AA model rats were analyzed using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS). These serum and synovium migration components were integrated for network pharmacology prediction, which was followed by multi-dimensional validation using molecular docking, RT-qPCR, and pharmacodynamic evaluation. The results showed that 46 serum and 13 synovium migration components were identified in normal rats, and 59 serum and 15 synovium migration components were identified in AA rats, indicating that the RA disease environment affects the entry of HQC into the bloodstream and migration to the synovium. Comparative analysis of components common and unique to normal and model groups identified geniposide, baicalin, daucosterol, coptisine, acteoside, luteolin, and crocin as migration components reaching the target site, reflecting the target tissue enrichment characteristics of HQC. Network pharmacology of the migration components screened 7 core targets: GAPDH, TNF-α, AKT1, PTGS2, NF-κB1, MAPK1, and SphK1, which were enriched in key RA signaling pathways including PI3K-AKT, HIF-1, VEGF, and TNF. Molecular docking and RT-qPCR confirmed good binding activity and regulatory capacity between key components and core targets. In vivo validation further demonstrated that HQC significantly improved joint inflammation and synovial hyperplasia in AA rats. This study confirmed that HQC exerted an anti-RA effect by targeting chronic inflammation and metabolic disorders through multi-target regulation of PI3K-Akt and other signaling pathways via serum and synovium migration components. The research provides a scientific basis for the clinical application of HQC and offers a new strategy for studying the mechanisms of TCM.
With the progressive aging of the population in China, the incidence of osteoporosis(OP) is rising annually. This condition not only severely impacts patients' quality of life but also imposes a substantial economic burden on both families and the society. Although modern western medicine has achieved progress in inhibiting OP progression and alleviating associated clinical symptoms, its overall therapeutic efficacy remains suboptimal due to issues such as adverse drug reactions and patient tolerance. Consequently, developing efficient, safe, and cost-effective prevention and treatment strategies has become an urgent priority in current OP-related clinical and scientific research. In recent years, growing insights into the microbiome have revealed that the gut microbiota can regulate bone quantity and quality through multiple mechanisms, including immune modulation, calcium and phosphorus absorption, and the production of short-chain fatty acids, thereby improving the bone microenvironment. As an important component of traditional medicine, TCM is characterized by multi-component and multi-target effects, with therapeutic advantages in holistic regulation. Studies have shown that TCM can effectively improve bone mineral density, inhibit bone resorption, and promote bone formation, with a low incidence of adverse reactions and mild pharmacological effects, demonstrating its unique clinical value in the prevention and treatment of OP. Simultaneously, complex interactions exist between TCM and the gut microbiota. On the one hand, the active components of TCM can modulate the composition and structure of the gut microbiota, reduce systemic inflammation, and ultimately improve bone metabolism. On the other hand, the gut microbiota can metabolize and transform the active components of TCM, enhancing their bioavailability and promoting therapeutic efficacy. This article systematically reviews the roles of gut microbiota and TCM in OP, as well as the bidirectional interaction between TCM and gut microbiota in the prevention and treatment of OP, aiming to provide new insights and evidence for the clinical management of OP.
Geriatric anxiety, a major public health challenge in an aging society, often co-exists with multiple chronic physical diseases, resulting in a complex clinical problem of mind-body comorbidity. Its pathological understanding and treatment strategies require systematic elucidation. Based on the holistic view of unity of body and spirit in TCM and the physiological characteristics of "decline of all five viscera" in the elderly, this study proposed a pathological framework centered on "deficiency, stagnation and turbidity" for geriatric anxiety, and systematically elaborates on its dynamic evolution. Within this framework, "deficiency" constitutes the fundamental pathogenesis, arising from functional decline of the five viscera, particularly the deficiency of the kidney, heart, and liver, leading to insufficient nourishment of the spirit. "Stagnation" serves as the pivotal link in disease progression, characterized primarily by impaired Qi movement, which may further result in blood stasis and act as a critical mediator of mutual impairment between the body and the spirit. "Turbidity" represents the lingering manifestation of the disease, mainly involving the accumulation of pathological products such as phlegm and fire that disturb the spirit, causing the conditions to persist. These three factors interact with one another and are mutually causal, constituting a characteristic pathological pattern of geriatric anxiety described as "deficiency leading to stagnation, stagnation generating turbidity, and turbidity further damaging vital Qi". This explains its clinical features of deficiency in origin with excess in manifestation, symptom complexity, and chronicity. Based on this understanding, the fundamental therapeutic principles are established as tonifying deficiency to consolidate the root, relieving stagnation to unblock the pivot, and resolving turbidity to calm the spirit. In clinical practice, Liuwei Dihuang Decoction, Xiaoyao Powder, and Wendan Decoction serve as the principal prescriptions with syndrome-based modifications, aiming to harmonize multiple viscera, regulate both Qi and blood, and address integrated treatment of both body and spirit. This framework provides a systematic theoretical basis and practical reference for syndrome differentiation and treatment of geriatric anxiety in TCM.
Ginger volatile oil(GVO) is the key component responsible for the unique aroma and flavor of ginger. To evaluate the impact of different drying methods(sun drying, shade drying, hot-air drying, vacuum drying, and vacuum freeze-drying) on GVO, this study employed a combination of headspace gas chromatography-ion mobility spectrometry(HS-GC-IMS) and headspace gas chromatography-mass spectrometry(HS-GC-MS) techniques to characterize the changes in characteristic volatile organic compounds(VOCs) in ginger under different drying methods. Additionally, chemometric methods and machine learning were incorporated to classify and analyze the GVO obtained through different drying methods. The results showed that a total of 60 volatile components were identified in GVO based on GC-IMS, and 59 volatile components were identified based on HS-GC-MS. Principal component analysis indicated that different drying methods significantly affected the composition and relative content of VOCs in GVO. From the GC-IMS, HS-GC-MS, and fused data, 14, 10, and 23 VOCs with strong discriminatory power were selected, including key components such as β-myrcene, hexanal, and citral. Based on these features, machine learning models were used for further classification analysis. The core purpose of this research classification is to establish intelligent identification models for different drying process types based on VOCs fingerprint characteristics, in order to achieve precise traceability of the processing methods of dried ginger raw materials. The results indicated that both random forest(RF) and convolutional neural network(CNN) exhibited high accuracy and stability in GVO classification and discrimination. In summary, this study revealed the impact of different drying methods on the composition and distribution characteristics of volatile components in GVO from the perspective of volatile components, providing a scientific basis and technical support for the study of differences in ginger volatile components and the optimization of drying processes.
The chemical constituents of the rice solid fermentation product of the endophytic fungus Aspergillus versicolor isolated from Aucuba japonica var. variegata were separated by various separation technologies such as silica gel column chromatography, gel column chromatography, reversed-phase silica gel column chromatography, and semi-preparative high performance liquid chromatography. The planar structures and stereochemistry of the isolated compounds were determined by high-resolution electrospray ionization mass spectrometry(HR-ESI-MS), nuclear magnetic resonance(NMR) spectroscopy, and quantum chemical calculations. A total of 21 compounds were isolated from the endophytic fungus A. versicolor and identified as(1S,2S,3S)-engyodontiumone G(1),(1S,2S,3R)-engyodontiumone F(2),(1S,2S)-AGI-B4(3), aspergillusone B(4), sydoxanthone C(5), fischexanthone(6), sydowinin A(7), 7-hydroxy-2-hydroxymethyl-5-methyl-4H-chromen-4-one(8), kojic acid monomethyl ether(9),(+)-sydowic acid(10),(-)-austrosene(11), monodictyphenone(12), gibellulins A(13), 3,7-dihydroxy-1,9-dimethyldibenzofuran(14), 4-(acetylamino) butyramide(15), emodin bianthrone B(16), emodin bianthrone A(17), flufunan(18), catechol(19), vanillin(20), and uracil(21). The absolute configurations of compounds 1-3 were determined through calculated electronic circular dichroism(ECD) for the first time. Compound 3 was the enantiomer of(1R,2R)-AGI-B4 and was reported for the first time. Biological activity screening results indicated that none of the tested compounds exhibited significant antifungal effects against the tested strains, nor did they demonstrate notable antitumor activity against the tested cancer cells.
GK-A is a new compound previously isolated by our research group from TCM Ginkgo Semen, which is traditionally used for relieving cough. Pharmacological results showed that it possessed good antitussive and anti-inflammatory activities, yet its low bioavailability is a significant problem. To search for candidate molecules with strong activity and high bioavailability, this study aimed to achieve this goal through structural modification. To evaluate the effects of different N-substituents in GK-A on the activity of active compounds, the study developed a concise synthetic route for these GK-A derivatives, synthesizing 15 derivatives(compounds 10-24) based on this route. Among these derivatives, compounds 10-21 were new compounds. An in vitro inflammatory model was established by inducing RAW264.7 cells with lipopolysaccharide(LPS). The cytotoxicity of different concentrations of the derivatives on mouse RAW264.7 macrophages was assessed using the CCK-8 assay to determine the appropriate dosing concentration. Nitric oxide(NO) levels in the cell supernatant were measured via the Griess assay, and the expression levels of inflammatory cytokines(interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), and cyclooxygenase-2(COX-2) were detected by enzyme-linked immunosorbent assay(ELISA). The results showed that at a concentration of 100 μmol·L~(-1), all tested compounds significantly inhibited NO expression. Specifically, compounds 13 and 16 markedly reduced the expression levels of TNF-α, IL-6, and COX-2 in the cell supernatant. Compound 14 exhibited a significant inhibitory effect on TNF-α expression, while compound 17 significantly suppressed the expression of IL-6 and COX-2. These findings demonstrated that compounds 13, 14, 16, and 17 possessed promising anti-inflammatory activity in vitro. This discovery provides an experimental basis for screening antitussive drug candidates with high pharmacological activity, good bioavailability, and minimal side effects.
This paper systematically reviews the development history of clinical trials for new TCM drugs in China and identifies the main existing problems. It proposes that, under the "three-combination" regulatory review evidence system for TCM, clinical trials of new TCM drugs should leverage the advantages of human use experience, adhere to a clinical value-oriented approach, and flexibly select clinical development pathways without necessarily following the traditional phase Ⅱ and Ⅲ staging model. Based on human use experience data to clarify the clinical advantages of prescriptions, trial objectives should be established by determining clinical positioning, and risk-benefit assessments should be conducted to support subsequent clinical trial design. While adhering to the fundamental principles of clinical trials, new design methodologies should be introduced, including the use of adaptive designs to achieve seamless phase Ⅱ and Ⅲ integration; analysis of human use experience data to identify advantageous patient populations, providing a scientific basis for inclusion and exclusion criteria; clarification of the clinical therapeutic characteristics of TCM to guide the selection of appropriate efficacy and safety endpoints; and, based on human use experience data, estimation of sample size and determination of dosing regimens, treatment duration, visit schedules, and follow-up periods. In addition, clinical trial quality control and risk management plans should be developed, and "patient-centered" clinical trials should be implemented. These approaches aim to shorten the development timeline of new TCM drugs, reduce R&D costs, and improve the success rate of drug development.
This study aimed to investigate the neuroprotective effects of paeoniflorin in a pentylenetetrazol(PTZ)-induced zebrafish model of epilepsy. Zebrafish at four days post-fertilization with normal development were randomly divided into a control group, a model group, a positive control group(sodium valproate), and paeoniflorin treatment groups(200, 400, and 800 μmol·L~(-1)). Behavioral analysis was performed to evaluate changes in locomotor activity. Fluorescence microscopy was employed to evaluate neuronal discharge in the brain, cellular apoptosis, and the accumulation of neutrophils and macrophages. The levels of reactive oxygen species(ROS) and malondialdehyde(MDA) in the brain were measured to assess antioxidant capacity. Quantitative real-time polymerase chain reaction(RT-qPCR) was used to detect the mRNA expression levels of epilepsy-related genes(c-fos, brain-derived neurotrophic factor [BDNF], and galanin [GALN]) and inflammation-related genes(interleukin [IL]-1β, IL-6, and tumor necrosis factor-α [TNF-α]). Furthermore, the TLR4 receptor agonist lipopolysaccharide(LPS) was used for intervention. Behavioral analysis and RT-qPCR were conducted to detect the mRNA expression levels of Toll-like receptor 4(TLR4), myeloid differentiation factor 88(MyD88), nuclear factor-κB(NF-κB), and IL-1β, in order to verify the role of the related signaling pathway. The results demonstrated that, compared with the model group, paeoniflorin improved PTZ-induced epileptic behaviors, reduced the total swimming distance and velocity of zebrafish, and significantly downregulated the mRNA expression levels of epilepsy-related genes c-fos, BDNF, and GALN. Meanwhile, paeoniflorin significantly inhibited PTZ-induced abnormal neuronal discharge in the brain, suppressed cellular apoptosis, and reduced ROS levels and MDA content. In addition, paeoniflorin significantly attenuated the PTZ-induced accumulation of macrophages and neutrophils in the brain and downregulated the expression of inflammatory genes IL-1β, IL-6, and TNF-α. Further findings demonstrated that LPS intervention significantly attenuated the ameliorative effects of paeoniflorin on PTZ-induced epileptiform behaviors in zebrafish. RT-qPCR results showed that LPS treatment markedly reversed the inhibitory effects of paeoniflorin on the mRNA expression levels of TLR4, MyD88, NF-κB, and IL-1β in PTZ-induced zebrafish. In conclusion, this study indicates that paeoniflorin may exert its neuroprotective effects in a PTZ-induced zebrafish epilepsy model primarily by suppressing the activity of the TLR4/NF-κB signaling pathway, thereby reducing oxidative stress and inflammatory responses in the brain, suppressing neuronal apoptosis, and alleviating abnormal neuronal discharge.
This study aimed to explore whether Tongmai Yangxin Pills(TMYX) can improve cardiac arrhythmia in rats after ischemia-reperfusion(I/R) by inhibiting inflammation and apoptosis through the advanced glycation end products(AGE)-receptor for AGE(RAGE) signaling pathway. This study employed the Langendorff isolated heart perfusion system for electrophysiological mapping to determine the safe concentration range of TMYX. Subsequently, network pharmacology was utilized to predict the potential targets and key signaling pathways of TMYX against cardiac arrhythmia. Finally, the in vivo I/R cardiac arrhythmia model in rats was established through left anterior descending coronary artery ligation for verification. In the in vitro experiment, the control group and the TMYX group were used to explore the safe concentration of TMYX, and the I/R group and the TMYX group were used to observe the incidence of cardiac arrhythmia. The animals for the in vivo experiment were randomly divided into the control, I/R, low/high-dose TMYX, metoprolol, and RAGE inhibitor FPS-ZM1 groups, and corresponding interventions were given. During the experiment, cardiac arrhythmia was monitored by electrocardiograms, and cardiac function was evaluated by echocardiograms. The myocardial infarction area was observed by triphenyltetrazolium chloride(TTC) staining, aggregation of inflammatory cells was observed by hematoxylin-eosin(HE) staining, and cell apoptosis was detected by TUNEL staining. The levels of inflammatory factors were determined by enzyme-linked immunosorbent assay(ELISA). Network pharmacology was used to find the potential targets and key signaling pathways of TMYX, and the changes in the expression levels of related proteins were detected by Western blot. When the dose did not exceed the clinical equivalent dose(5 mg·mL~(-1)), TMYX had little effect on the electrophysiological parameters of isolated hearts of rats. TMYX could significantly improve the cardiac arrhythmia induced by I/R injury in in vivo and isolated hearts, reduce the incidence and duration of ventricular premature beats, ventricular tachycardia, and ventricular fibrillation, and improve left ventricular systolic function. TMYX treatment could reduce the myocardial infarction area, attenuate the aggregation of inflammatory cells in myocardial tissue, lower the level of cell apoptosis, and down-regulate the abnormal increase in the expression of serum interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α). At the same time, it was observed that TMYX treatment could inhibit the activation of the AGE-RAGE signaling pathway in I/R myocardial tissue and the changes in the protein expression of B-cell lymphoma-2(Bcl-2) and Bcl-2 associated X protein(Bax). This study, through the integration of experimental strategies, has for the first time confirmed TMYX may inhibit the activation of the AGE-RAGE signaling pathway in I/R myocardial tissue of rats, thereby reducing inflammation and apoptosis, and ultimately improving I/R cardiac arrhythmia.
This study employed ultra-performance liquid chromatography coupled with quadrupole-Orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive-Orbitrap-MS) to investigate the chemical constituents of the classic formula Baizhu San and their prototype components and metabolites in rats, aiming to elucidate the potential pharmacologically active substances of this formula. Following the final intragastric administration of Baizhu San, plasma, urine, and feces samples were collected from rats and analyzed in both positive and negative ion modes using Full MS-ddMS~2 scanning. The mass spectral data were processed using Xcalibur 4.5 and Compound Discoverer 3.3 software to identify the chemical constituents in Baizhu San and the prototype components and metabolites in the biological samples. A total of 125 constituents were identified in the Baizhu San extract, comprising 51 flavonoids, 44 triterpenoids, 9 lactones, 8 organic acids, 4 phenylpropanoids, and 9 other compounds. A total of 69 prototype components and 79 metabolites were identified in the rat biological samples, and the metabolic pathways involved phase I reactions such as deglycosylation, oxidation, and hydrolysis, as well as phase Ⅱ reactions including glucuronidation, sulfation, and glutathione conjugation. This study presents the first systematic characterization of the chemical constituents of Baizhu San and their absorption and metabolism characteristics in rats, offering an important reference for the investigation of the pharmacodynamically active substances and quality control of this formula.
The clinical treatment of ischemic stroke(IS) has long been plagued by the time window and complication risks of recanalization therapies, as well as the bleeding risk of antithrombotic therapy, making it urgent to explore safe and effective new regimens. Salvianolic Acid for Injection(SAFI), a TCM preparation with neuroprotective properties and the ability to improve cerebral blood flow, lacks large-sample clinical validation regarding its systematicness, efficacy, and safety of application in IS patients. This study relied on a clinical trial based on a multicenter, prospective, single-arm objective performance criteria method(registration No. ChiCTR1900026178), enrolling 2 203 IS patients with an onset time of 7-90 d and National Institutes of Health Stroke scale(NIHSS) scores of 4-20. All patients received intravenous infusion of SAFI at dose of 100 mg per day for 14 consecutive days. The primary efficacy indicator was the proportion of patients with a modified Rankin scale(mRS) scores of 0-1 at 90 d after treatment(preset target value of 35%). Secondary efficacy indicators include the proportion of patients with mRS scores recovers to 0-1 at 28 d after treatment, the comparison of NIHSS scores at 7, 14 d after treatment with the baseline, the proportion of patients with Barthel index(BI) scores≥75 at 7, 14, 28, and 90 d after treatment, and the comparison of MMSE scores with the baseline. The incidence, severity, and drug correlation of adverse events were evaluated via vital sign monitoring, laboratory examinations, etc. The binomial test(one-sided α=0.025) was used for primary endpoint analysis, and the 95%CI was calculated by the Clopper-Pearson. RESULTS:: show that among 2 127 patients who completed the trial, 47.91% of these patients(95%CI[45.77%, 50.06%]) achieve the primary endpoint, which is significantly higher than the preset objective value(P<0.000 1). NIHSS scores of patients decrease significantly from baseline scores of(6.57±3.20) to(4.62±3.33) at 14 d after treatment(P<0.000 1), with 23.79% of patients achieving scores improvement of ≥4 points or scores of 0-1. The proportion of patients with BI scores ≥75 increases from the baseline of 41.18% to 74.52% at 90 d after treatment(P<0.000 1), and MMSE scores rises from baseline scores of(22.16±8.03) to(23.95±7.38) at 90 d after treatment(P<0.000 1). In terms of safety, the incidence rates of adverse events and serious adverse reactions are 27.49% and 3.19%, respectively, with no fatal event reported. This study confirmed that SAFI can significantly improve neurological function, capabilities of daily living, and cognitive function in patients with mild to moderate IS at 7-90 d after onset, with a favorable safety profile. The trial design combining single-arm and objective performance criteria method employed in this study provides an innovative paradigm for the clinical evaluation of TCM injections and offers high-quality evidence for the clinical treatment of IS.
This study employed a combination of in vivo and in vitro experiments to investigate the effects and mechanism of Gualou Xiebai Banxia Decoction(GXBD) on pulmonary vascular remodeling in rats with hypoxic pulmonary hypertension(HPH). For the in vivo experiment, 36 specific-pathogen-free(SPF)-grade Sprague-Dawley(SD) rats were randomly divided into six groups(n=6 per group): control group, hypoxic model group, low-, middle-, and high-dose GXBD groups, and sildenafil group. The rats in the hypoxic model group and all treatment groups were exposed to a hypobaric oxygen chamber simulating an altitude of 5 500 m for 28 days to establish the HPH model, during which they received corresponding drug intervention, while the control group was raised normally. Relevant indicators were assessed using right ventricular catheterization, hematoxylin-eosin(HE) staining, transmission electron microscopy, and Western blot analysis. For the in vitro experiment, primary pulmonary artery smooth muscle cells(PASMCs) were isolated and cultured, and GXBD-containing serum was prepared. After exposure to 1% oxygen and screening of the optimal intervention concentration via cell counting kit-8(CCK-8), EdU staining, flow cytometry, and Western blot were used to detect cell proliferation, apoptosis, and the expression of related proteins. The results showed that compared to the hypoxic model group, all doses of GXBD significantly reduced the mean pulmonary artery pressure(mPAP) of rats, alleviated pulmonary vascular remodeling and right ventricular hypertrophy, and attenuated the ultrastructural abnormalities of PASMCs. In the in vitro experiments, 10% and 15% GXBD-containing serum effectively inhibited hypoxia-induced excessive proliferation of PASMCs, promoted their apoptosis, and downregulated the expression of proliferation-related protein PCNA and the anti-apoptotic protein Bcl-2. In conclusion, GXBD exerts a protective effect against HPH in rats by regulating the balance between proliferation and apoptosis of PASMCs, thereby inhibiting pulmonary vascular remodeling. These findings provide an experimental basis for the clinical prevention and treatment of HPH.
Chaenomelis Fructus is the dried near-mature fruit of Chaenomeles speciosa. It is warm in nature and sour in taste with the effects of relaxing sinew, activating collaterals, harmonizing stomach, and resolving dampness. At present, the chemical constituents isolated from Chaenomelis Fructus are triterpenoids, sesquiterpenoids, flavonoids, etc. Among them, triterpenoids are the main active components. Chaenomelis Fructus has pharmacological effects such as anti-inflammatory and analgesic effects, immune enhancement, liver protection, protection against digestive tract injury, and anti-gastric cancer activity. In this review, the related studies on the chemical constituents and pharmacological effects of Chaenomelis Fructus in recent years were summarized in order to provide reference for its follow-up research, development, and utilization.
This study aims to investigate, from the perspective of pathologic-symptom toxicology, the effects of salt processing on Psoraleae Fructus(BGZ)-induced liver injury in a rat model of kidney-Yin deficiency(Yin) and to elucidate the underlying mechanisms through metabolomics. A Yin model was established in rats and treated with BGZ or salt-processed BGZ(YBGZ). Yin manifestations were evaluated based on body weight, anal temperature, and the serum cyclic adenosine monophosphate(cAMP)/cyclic guanosine monophosphate(cGMP) ratio. Liver injury was assessed based on serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST) levels, as well as histopathological changes of the liver. Untargeted metabolomics was employed to characterize the hepatic metabolic alterations induced by BGZ and YBGZ, and the proposed mechanisms were further validated by integrating indices related to energy metabolism and inflammatory responses. Compared with BGZ, YBGZ markedly alleviated Yin symptoms, reduced serum ALT and AST levels, and mitigated hepatic inflammatory infiltration. Metabolomic profiling identified 17 differential metabolites co-regulated by BGZ and YBGZ, mainly enriched in pathways including glycolysis/gluconeogenesis, arachidonic acid metabolism, and sphingolipid metabolism, which were closely associated with hepatic energy metabolism and inflammation. Mechanism verification showed that YBGZ significantly downregulated the expression of glucose transporter 1(GLUT1), hexokinase 2(HK2), and pyruvate kinase M2(PKM2) in the liver, and correspondingly decreased serum lactate dehydrogenase(LDH) and lactic acid(LA) levels. In addition, YBGZ suppressed the levels of the pro-inflammatory cytokines interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α), while elevating the anti-inflammatory cytokine interleukin-10(IL-10) level. Collectively, salt processing alleviates BGZ-induced liver injury under the Yin condition by modulating glycolytic metabolism and inflammatory responses in the liver.
Macrophages are the central regulators of immune microenvironment homeostasis in lung tissue. Their polarization imbalance not only amplifies inflammatory storms and exacerbates pulmonary parenchymal injury, but also induces immune evasion, drives pathological repair, and promotes tumor progression, playing an important role in the development and prognosis of pulmonary diseases. They have therefore become a key therapeutic target for intervention in lung-related diseases. A large body of research has demonstrated that both TCM compound formulas and bioactive monomeric components can dynamically regulate the M1/M2 macrophage polarization balance at different stages of disease through a network-based mechanism involving multiple components, multiple targets, and multiple pathways. This holistic regulatory effect not only effectively blocks the malignant progression from "inflammation-fibrosis-tumor", but also benefits from the low toxicity and high bioavailability characteristics of most TCM constituents, offering novel individualized strategies for the prevention and treatment of pulmonary diseases. Based on the pathological axis of "macrophage polarization imbalance-immune microenvironment disorder-disease progression", this review systematically summarizes recent advances in TCM interventions targeting macrophage polarization in the treatment of acute lung injury(ALI)/acute respiratory distress syndrome(ARDS), pulmonary infection(PI), asthma, pulmonary fibrosis(PF), chronic obstructive pulmonary disease(COPD), and lung cancer(LC). It highlights key molecules, signaling pathways, and transcriptional regulatory axes targeted by TCM compound formulas and monomeric compounds in regulating macrophage function and remodeling the immune microenvironment. In addition, this article identifies current limitations in the field, aiming to provide TCM-based strategies and a scientific foundation for the precise prevention and treatment of pulmonary diseases.
As the primary carrier of clinical treatment in traditional Chinese medicine(TCM), TCM formulae require elucidation of the interaction laws between their chemical substance basis and biological activities, which represents a key scientific issue in TCM research. The "TCM integrative pharmacology" theory previously proposed by our team has become an important paradigm in modern TCM research. However, current studies still face several limitations, including a static analytical perspective, insufficient spatiotemporal information, and unclear mechanisms of cross-organ coordinated regulation. Based on these challenges, this paper further proposes the innovative concept of a "TCM digital human". Guided by the integrative pharmacology research paradigm, and drawing on advanced technologies such as virtual cells and virtual physiological human systems, this framework integrates artificial intelligence and multiscale modeling approaches to construct a computable virtual life system with TCM characteristics, ranging from virtual cells and virtual organs to a digital human. This system provides key support for the digital representation of TCM theory and for the scientific elucidation of the mechanisms underlying the therapeutic effects of TCM formulae.
This study aims to investigate the therapeutic effect of Tianshu Capsules(TS) on migraine rat model and explore its potential mechanism of action from the perspectives of the structure of the gut microbiota and functional pathway regulation. A migraine rat model was established via subcutaneous injection of nitroglycerin. The Sprague-Dawley rats were randomly divided into a control group, a model group, a low-dose TS group, a medium-dose TS group, a high-dose TS group, and an ibuprofen group. The efficacy of TS in improving migraine was evaluated by general condition observation and measurement of the craniofacial pain threshold. The expression of the gene c-fos in the trigeminal ganglion was determined by quantitative real-time polymerase chain reaction(PCR). The contents of endothelin-1(ET-1), calcitonin gene-related peptide(CGRP), and 5-hydroxytryptamine(5-HT) in serum were measured by enzyme-linked immunosorbent assay(ELISA). Fecal samples were subjected to metagenomic sequencing for systematic analysis of gut microbial diversity, taxonomic composition difference, and functional pathway changes of Kyoto Encyclopedia of Genes and Genomes(KEGG), and their correlations with behavioral and biochemical indices were further evaluated. The results show that TS significantly improves the increased body temperature and decreased craniofacial pain threshold in migraine rats. It also markedly suppresses the elevated expression levels of the gene c-fos in the trigeminal ganglion and reduces the levels of ET-1, CGRP, and 5-HT in serum. Metagenomic beta diversity analysis and differential taxonomic abundance analysis reveal that the migraine model induces significant gut microbiota dysbiosis, characterized by enrichment of harmful genera, including Streptococcus and Enterococcus, as well as a decline in the abundance of beneficial bacteria such as Allobaculum, Eubacterium, and Muribaculum. Functional pathway analysis results of KEGG further reveal that the relative abundances of pathways associated with biosynthesis of phenylalanine, tyrosine, and tryptophan, bacterial secretion system, citrate cycle, and biosynthesis of secondary metabolites are significantly decreased in the model group. TS intervention increased the abundance of the genus, such as Parabacteroides, Eubacterium, Allobaculum, and Muribaculum, while decreasing levels of microbiota, including Staphylococcus. TS also significantly upregulated pathways associated with barrier function(tight junction), amino acid biosynthesis pathways, and biosynthesis pathways of neurotransmitter precursors such as cysteine and methionine metabolism. In addition, it downregulated inflammatory pathways(Toll and IMD signaling) and pathways related to Staphylococcus aureus infection, thereby restoring the structure and function of the microbiota to a state close to those of the normal group. Spearman correlation analysis reveals that partial gut microbiota are significantly associated with migraine-related behavioral and biochemical indices(c-fos, ET-1, CGRP, and 5-HT). In conclusion, TS can regulate the disrupted gut microbiota structure and microbial functions related to neurotransmitter metabolism, intestinal barrier function, and inflammatory regulation in migraine model rats, which may be one of the potential key ways through which TS exert its anti-migraine effect.
This study aimed to clarify the degree of fruit phenotypic variation and the characteristics of genetic diversity, population structure, and genetic differentiation of Forsythia suspensa resources in Shanxi, providing an important basis for germplasm conservation and breeding of superior varieties. A total of 46 F. suspensa fruits were collected, and 12 agronomic traits were measured and analyzed. The population genetic structure and genetic diversity of F. suspensa germplasm were evaluated using simplified genome sequencing technology. For the five quality traits of the 46 fruits, the Shannon-Wiener index ranged from 0.631 to 1.074, and the Simpson index ranged from 0.379 to 0.560. The seven quantitative traits exhibited abundant genetic variation, with coefficients of variation ranging from 9.764%(fruit shape index) to 45.494%(forsythin content). Principal component analysis reduced the 12 phenotypic traits to four factors, with a cumulative variance contribution of 74.547%. Sequencing data showed mean Q20 and Q30 values of 98.13% and 94.33%, respectively, with an average GC content of 35.95%. After filtering, a total of 12 347 327 high-quality single nucleotide polymorphism(SNP) loci were obtained. Based on these high-quality SNPs, principal component analysis, population structure analysis, and phylogenetic tree construction were carried out. The 46 germplasm resources were divided into four groups; however, grouping showed little relationship with geographic origin, and intermixing occurred among regions. Mantel test revealed a significant but weak positive correlation between phenotypic and genetic distances(r=0.159, P=0.001). At the molecular level, the four groups exhibited moderate genetic diversity overall, and the genetic differentiation index among populations ranged from 0.027 to 0.084, indicating low to moderate differentiation. The rich genetic diversity of the main phenotypic traits provides a solid material basis for screening superior germplasm and genetic breeding of F. suspensa.
