BACKGROUND: Salvianolate is a compound mainly composed of salvia magnesium acetate, which is extracted from the Chinese herb Salvia miltiorrhiza . In recent years, salvianolate injection has been widely used in the treatment of cardiovascular diseases, but the mechanism of how it can alleviate cardiotoxicity remains unclear. METHODS: The cardiac injury model was constructed by treatment with doxorubicin (Dox) or azithromycin (Azi) in zebrafish larvae. Heart phenotype, heart rate, and cardiomyocyte apoptosis were observed in the study. RNA-sequencing (RNA-seq) analysis was used to explore the underlying mechanism of salvianolate treatment. Moreover, cardiomyocyte autophagy was assessed by in situ imaging. In addition, the miR-30a/becn1 axis regulation by salvianolate was further investigated. RESULTS: Salvianolate treatment reduced the proportion of pericardial edema, recovered heart rate, and inhibited cardiomyocyte apoptosis in Dox/Azi-administered zebrafish larvae. Mechanistically, salvianolate regulated the lysosomal pathway and promoted autophagic flux in zebrafish cardiomyocytes. The expression level of becn1 was increased in Dox-induced myocardial tissue injury after salvianolate administration; overexpression of becn1 in cardiomyocytes alleviated the Dox/Azi-induced cardiac injury and promoted autophagic flux in cardiomyocytes, while becn1 knockdown blocked the effects of salvianolate. In addition, miR-30a, negatively regulated by salvianolate, partially inhibited the cardiac amelioration of salvianolate by targeting becn1  directly. CONCLUSION This study has proved that salvianolate reduces cardiomyopathy by regulating autophagic flux through the miR-30a/becn1 axis in zebrafish and is a potential drug for adjunctive Dox/Azi therapy.
Animals ; Zebrafish ; MicroRNAs/genetics* ; Autophagy/drug effects* ; Myocytes, Cardiac/metabolism* ; Cardiomyopathies/metabolism* ; Beclin-1/genetics* ; Apoptosis/drug effects* ; Plant Extracts/therapeutic use* ; Doxorubicin

Cardiac fibrosis(CF) is a cardiac pathological process characterized by excessive deposition of extracellular matrix(ECM). When the heart is damaged by adverse stimuli, cardiac fibroblasts are activated and secrete a large amount of ECM, leading to changes in cardiac fibrosis, myocardial stiffness, and cardiac function declines and accelerating the development of heart failure. There is a close relationship between heart yin deficiency and cardiac fibrosis, which have similar pathogenic mechanisms. Heart Yin deficiency, characterized by insufficient Yin fluids, causes the heart to lose its nourishing function, which acts as the initiating factor for myocardial dystrophy. The deficiency of body fluids leads to stagnation of blood flow, resulting in blood stasis and water retention. Blood stasis and water retention accumulate in the heart, which aligns with the pathological manifestation of excessive deposition of ECM, as a tangible pathogenic factor. This is an inevitable stage of the disease process. The lingering of blood stasis combined with water retention eventually leads to the generation of heat and toxins, triggering inflammatory responses similar to heat toxins, which continuously stimulate the heart and cause the ultimate outcome of CF. Considering the syndrome of heart Yin deficiency, traditional Chinese medicine capable of nourishing Yin, activating blood, and promoting urination can reduce myocardial cell apoptosis, inhibit fibroblast activation, and lower the inflammation level, showing significant advantages in combating CF.
Humans ; Fibrosis/drug therapy* ; Animals ; Yin Deficiency/metabolism* ; Myocardium/metabolism* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use*

In order to compare the differences in growth and secondary metabolite accumulation of Panax quinquefolius between understory and field planting, growth indexes, photosynthetic characteristics, soil enzyme activities, secondary metabolite contents, and antioxidant activities of P. quinquefolius under different planting modes were examined and compared, and One-way analysis of variance(ANOVA) and correlation analyses were carried out by using the software SPSS 25.0 and GraphPad Prism 9.5. The Origin 2021 software was used for plotting. The results showed that compared with those under field planting, the plant height, leaf length, leaf width, photosynthetic rate, and chlorophyll content of P. quinquefolius under understory planting were significantly reduced, and arbuscular mycorrhizal fungi(AMF) infestation rate and infestation intensity, ginsenoside content, and antioxidant activity were significantly increased. The activities of inter-root soil urease, sucrase, and catalase increased, while the activities of non-inter-root soil urease and alkaline phosphatase increased. Correlation analyses showed that the plant height and leaf length of P. quinquefolius plant were significantly positively correlated with net photosynthetic rate, transpiration rate, chlorophyll content, and electron transfer rate(P<0.05), while ginsenoside content was significantly negatively correlated with net photosynthetic rate, chlorophyll content, and electron transfer rate(P<0.05) and significantly positively correlated with AMF infestation rate and infestation intensity(P<0.05). In addition, ginsenoside content was significantly positively correlated with the activities of inter-root soil sucrase, urease, and catalase(P<0.05). This study provides basic data for revealing the mechanism of secondary metabolite accumulation in P. quinquefolius under understory planting and for exploring and practicing the ecological mode of P. quinquefolius under understory planting.
Panax/microbiology* ; China ; Secondary Metabolism ; Soil/chemistry* ; Photosynthesis ; Plant Leaves/metabolism* ; Chlorophyll/metabolism* ; Mycorrhizae

Based on copper death, this study investigates the effect and mechanism of Shenmai Injection on isoproterenol(ISO)-induced myocardial fibrosis(MF) in rats. SPF-grade male SD rats were randomly divided into a normal group, model group, captopril(5 mg·kg~(-1)) positive control group, and Shenmai Injection low(6 mL·kg~(-1)), medium(9 mL·kg~(-1)), and high(12 mL·kg~(-1)) dose groups. Except for the normal group, the rats in the other groups were subcutaneously injected with ISO(5 mg·kg~(-1)) once a day for 10 consecutive days to establish an MF model. Starting from the second day after successful modeling, intraperitoneal injections of the respective treatments were administered for 28 consecutive days. Hematoxylin-eosin(HE) and Masson staining were used to observe pathological changes and fibrosis levels in the myocardial tissue. Colorimetry was employed to detect serum Cu~(2+) concentration in rats. The levels of inflammatory cytokines interleukin-6(IL-6), interleukin-1β(IL-1β), interleukin-18(IL-18), tumor necrosis factor-α(TNF-α), as well as mitochondrial energy metabolites adenosine triphosphate(ATP), adenosine diphosphate(ADP), and adenosine monophosphate(AMP) in serum were measured using enzyme-linked immunosorbent assay(ELISA). Western blot was performed to detect the expression of collagen Ⅰ(Col-Ⅰ), collagen Ⅲ(Col-Ⅲ), and copper death-related proteins dihydrolipoamide acetyltransferase(DLAT), ferredoxin 1(FDX1), lipoic acid synthetase(LIAS), and heat shock protein 70(HSP70) in myocardial tissue. Immunofluorescence was used to detect the expression of DLAT, FDX1, and HSP70, while immunohistochemistry was conducted to examine the expressions of DLAT, FDX1, LIAS, and HSP70. The results showed that, compared to the model group, the myocardial structure disorder and collagen fiber deposition in the drug treatment groups were significantly improved, the cardiac index level was reduced, serum Cu~(2+), IL-6, IL-1β, IL-18, TNF-α, ADP, and AMP levels were significantly decreased, ATP levels were significantly increased, and the expressions of Col-Ⅰ, Col-Ⅲ, and HSP70 proteins in myocardial tissue were significantly reduced, while the expressions of DLAT, FDX1, and LIAS proteins were significantly elevated. In conclusion, Shenmai Injection effectively alleviates myocardial structure disorder and interstitial collagen fiber deposition in ISO-induced MF rats, promotes copper excretion, and reduces copper death in the ISO-induced rat MF model.
Animals ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Rats ; Myocardium/metabolism* ; Drug Combinations ; Fibrosis/metabolism* ; Copper/blood* ; Cardiomyopathies/genetics* ; Humans

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

Central sensitization(CS) is an important factor in inducing neuropathic pain(NPP), and the association between signal transduction protein 1(Epac1) and piezoelectric type mechanosensitive ion channel component 2(Piezo2) is a new and significant pathway for initiating CS. This study whether the central analgesic effect of Maxiong Powder is achieved through the synchronized regulation of the Epac1-Piezo2 signaling pathway in the medial habenular nucleus(MHb) and interpeduncular nucleus(IPN) of the brain. Dynamic in vivo microdialysis, combined with high-performance liquid chromatography-fluorescence detection(HPLC-RFC), behavioral assessments, immunohistochemistry, Western blot, and quantitative reverse transcription PCR, were employed in rats with partial sciatic nerve injury(SNI) to investigate the distribution and expression of Epac1 and Piezo2 proteins and genes in the MHb and IPN regions, and the changes in the extracellular levels of glutamate(Glu), aspartic acid(Asp), and glycine(Gly). Compared with the sham group, rats in the SNI group showed significantly reduced analgesic activity, a significant increase in cold pain sensitivity scores, and elevated Glu levels in the MHb and IPN regions. Additionally, the number of Piezo2-positive cells in these regions, as well as the expression levels of Epac1 and Piezo2 proteins and genes, were significantly increased. Compared with the SNI group, after Maxiong Powder administration, the analgesic activity in rats significantly increased, and cold pain sensitivity scores were significantly reduced. Maxiong Powder also significantly decreased the Glu content in the MHb and IPN regions and the Gly content in the MHb region, while significantly increasing the Asp content in both regions. Furthermore, Maxiong Powder significantly reduced the number of Piezo2-positive cells and lowered the protein and gene expression levels of Epac1 and Piezo2 in both brain regions. The central analgesic effect of Maxiong Powder may be related to its inhibition of Glu and Gly release in the extracellular fluid of the MHb and IPN regions, the increase of Asp levels in these regions, and the regulation of the Epac1-Piezo2 pathway through the reduction of Epac1 and Piezo2 protein and gene expression. These results provide partial scientific evidence for the clinical analgesic efficacy of Maxiong Powder and offer new ideas and approaches for the clinical treatment of NPP.
Animals ; Neuralgia/genetics* ; Rats ; Signal Transduction/drug effects* ; Male ; Rats, Sprague-Dawley ; Guanine Nucleotide Exchange Factors/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Habenula/drug effects* ; Ion Channels/genetics* ; Humans

Based on latent structure model and association rule analysis, this study investigates the prescription patterns used by professor YANG Zhong-qi in treating hypertension with traditional Chinese medicine(TCM) and infers the associated TCM syndromes, providing a reference for clinical syndrome differentiation and treatment. The observation window spanned from January 8, 2013, to June 26, 2024, during which qualified herbal decoction prescriptions meeting efficacy criteria were extracted from the outpatient medical record system of the First Affiliated Hospital of Guangzhou University of Chinese Medicine and compiled into a standardized database. Statistical analysis of high-frequency herbs included frequency counts and herbal property-channel tropism analysis. Latent structure modeling and association rule analysis were performed using R 4.3.2 and Lantern 5.0 software to identify core herbal combinations and infer TCM syndrome patterns. A total of 2 436 TCM prescriptions were included in the study, involving 263 drugs with a cumulative frequency of 29 783. High-frequency herbs comprised Uncariae Ramulus cum Uncis, Poria, Glycyrrhizae Radix et Rhizoma, Puerariae Lobatae Radix, and Alismatis Rhizoma, predominantly categorized as deficiency-tonifying, heat-clearing, and blood-activating and stasis-resolving herbs. Latent structure analysis identified 18 latent variables, 74 latent classes, 5 comprehensive clustering models, and 15 core herbal combinations, suggesting that the core syndrome clusters include liver Yang hyperactivity pattern, Yin deficiency with Yang hyperactivity pattern, phlegm-stasis intermingling pattern, and liver-kidney insufficiency pattern. Association rule analysis revealed 22 robust association rules. RESULTS:: indicate that hypertension manifests as a deficiency-rooted excess manifestation, significantly associated with functional dysregulation of the liver, lung, spleen-stomach, heart, and kidney. Key pathogenic mechanisms involve liver Yang hyperactivity, phlegm-stasis interaction, and liver-kidney insufficiency. Therapeutic strategies should prioritize liver-calming, spleen-fortifying, and deficiency-tonifying principles, supplemented by dynamic regulation of Qi-blood and Yin-Yang balance according to syndrome evolution, alongside pathogen-eliminating methods such as phlegm-resolving and stasis-dispelling. Synergistic interventions like mind-tranquilizing therapies should be tailored to individual conditions.
Hypertension/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Medicine, Chinese Traditional ; Drug Prescriptions ; Latent Class Analysis

This study explored the efficacy and mechanisms of Shenqi Buqi Granules in treating chronic heart failure(CHF) of Qi deficiency using proteomics and bioinformatics methods. A total of 18 healthy participants(health group) and 19 patients with Qi deficiency-type CHF(experimental group) were enrolled and treated with Shenqi Buqi Granules for 12 weeks. Clinical indicators, including Qi deficiency scores, complete blood count, biochemical parameters, lipid profiles, and cardiac function, were collected from pre-and post-experimental groups. Serum proteomics analysis was performed. Differential proteins were screened through differential analysis and K-means clustering. Further analyses, including subcellular localization, Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment, and protein-protein interaction(PPI) network construction, were conducted to identify pathways and proteins associated with Shenqi Buqi Granules treatment. Spearman correlation analysis focused on proteins most correlated with the core phenotype of CHF of Qi deficiency. The results show that Shenqi Buqi Granules treatment reduced Qi deficiency scores and brain natriuretic peptide levels of pre-experimental group. A total of 1 594 proteins were quantified in the proteomics analysis, with 98 proteins showing differential expression between healthy group and experimental group before and after treatment. Subcellular localization analysis revealed 6 protein sources, while KEGG pathway enrichment highlighted biological processes including angiogenesis, immune inflammation, calcium homeostasis, cytoskeletal regulation, protein synthesis, and energy metabolism. Core genes identified included CD34, CSF1, CALM1, CALML3, PPP1CA, PFN1, and 3 ribosomal large subunit proteins. Correlation analysis between core proteins and Qi deficiency scores revealed that CD34(r=-0.67, P<0.05) and PPP1CA(r=0.62, P<0.01) were most strongly associated with Qi deficiency scores. This study suggests that Shenqi Buqi Granules improves Qi deficiency scores and CHF symptoms by regulating angiogenesis, immune inflammation, calcium homeostasis, cytoskeletal regulation, protein synthesis, and energy metabolism. CD34 and PPP1CA are identified as core proteins involved in the therapeutic effects of Shenqi Buqi Granules on Qi deficiency.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Heart Failure/metabolism* ; Male ; Female ; Proteomics ; Middle Aged ; Qi ; Aged ; Protein Interaction Maps/drug effects* ; Adult ; Chronic Disease

The study investigated the intrinsic changes in material basis of Angelicae Sinensis Radix during wine processing by headspace-gas chromatography-ion mobility spectrometry(HS-GC-IMS), headspace-solid phase microextraction-gas chromatography-mass spectrometry(HS-SPME-GC-MS), and ultra-high performance liquid chromatography-quadrupole-orbitrap mass spectrometry(UPLC-Q-Orbitrap-MS) combined with chemometrics. HS-GC-IMS fingerprints of Angelicae Sinensis Radix before and after wine processing were established to analyze the variation trends of volatile components and characterize volatile small-molecule substances before and after processing. Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were employed for differentiation and difference analysis. A total of 89 volatile components in Angelicae Sinensis Radix were identified by HS-GC-IMS, including 14 unsaturated hydrocarbons, 16 aldehydes, 13 ketones, 9 alcohols, 16 esters, 6 organic acids, and 15 other compounds. HS-SPME-GC-MS detected 118 volatile components, comprising 42 unsaturated hydrocarbons, 11 aromatic compounds, 30 alcohols, 8 alkanes, 6 organic acids, 4 ketones, 7 aldehydes, 5 esters, and 5 other volatile compounds. UPLC-Q-Orbitrap-MS identified 76 non-volatile compounds. PCA revealed distinct clusters of raw and wine-processed Angelicae Sinensis Radix samples across the three detection methods. Both PCA and OPLS-DA effectively discriminated between the two groups, and 145 compounds(VIP>1) were identified as critical markers for evaluating processing quality, including 4-methyl-3-penten-2-one, ethyl 2-methylpentanoate, and 2,4-dimethyl-1,3-dioxolane detected by HS-GC-IMS, angelic acid, β-pinene, and germacrene B detected by HS-SPME-GC-MS, and L-tryptophan, licoricone, and angenomalin detected by UPLC-Q-Orbitrap-MS. In conclusion, the integration of the three detection methods with chemometrics elucidates the differences in the chemical material basis between raw and wine-processed Angelicae Sinensis Radix, providing a scientific foundation for understanding the processing mechanisms and clinical applications of wine-processed Angelicae Sinensis Radix.
Wine/analysis* ; Gas Chromatography-Mass Spectrometry/methods* ; Chromatography, High Pressure Liquid/methods* ; Angelica sinensis/chemistry* ; Solid Phase Microextraction/methods* ; Drugs, Chinese Herbal/isolation & purification* ; Chemometrics ; Volatile Organic Compounds/chemistry* ; Principal Component Analysis ; Ion Mobility Spectrometry/methods*

Since the promulgation of the first Drug Administration Law of the People's Republic of China 40 years ago in 1984, China has undergone four main stages in the traditional Chinese medicine(TCM) regulation: the initial establishment of TCM regulation rules(1984-1997), the formation of a modern TCM regulatory system(1998-2014), the reform of the review and approval system for new TCM drugs(2015-2018), and the construction of a scientific regulation system for TCM(2019-2024). Over the past five years, a series of milestone achievements of TCM regulation in China have been achieved in the six aspects, including its strategic objectives and the establishment of a science-based regulatory system, the reform of the review and approval system for new TCM drugs, the optimization and improvement of the TCM standard system and its formation mechanism, comprehensive enhancement of regulatory capabilities for TCM safety, international harmonization of TCM regulation and its role in promoting innovation. Looking ahead, centered on advancing TCMRS to establish a sound regulatory framework tailored to the unique characteristics of TCM, TCM regulation will evolve into new reform patterns, advancing and extending across eight critical fronts, including the legal framework and policy architecture, the review and approval system for new TCM drugs, the quality standard and management system of TCM, the comprehensive quality & safety regulation and traceability system, the research and transformation system for TCMRS, AI-driven innovations in TCM regulation, the coordination between high-quality industrial development and high-level regulation, and the leadership in international cooperation and regulatory harmonization. In this way, a unique path for the development of modern TCM regulation with Chinese characteristics will be pioneered.
Humans ; China ; Drugs, Chinese Herbal/standards* ; History, 20th Century ; History, 21st Century ; Medicine, Chinese Traditional/trends*