Corydalis Rhizoma is a commonly used traditional Chinese medicine(TCM) for regulating Qi and relieving pain in clinical practice, with remarkable efficacy. However, its pharmacodynamic substances are not yet fully understood and require further research. In this study, 24 compounds were isolated and identified from the aqueous extracts of vinegar-processed Corydalis Rhizoma using techniques such as macroporous adsorption resin column chromatography, Sephadex LH-20 column chromatography, and semi-preparative high-performance liquid chromatography. Their structures were determined based on their physicochemical properties and spectroscopic methods, including UV, IR, HR-MS, 1D NMR, and 2D NMR. Among these, compounds 1 and 2 are two rare natural α-carbonamide alkaloids, named yanhuoxamide A(compound 1) and yanhuoxamide B(compound 2), respectively. Compounds 3-24 are known compounds, identified as xanthoplanine(3), stigmast-4-ene-3,6-dione(4), norchelerythrine(5), ethyl ferulate(6), 6-hydroxymethyl-3-pyridinol(7), 6-(\[1,3\]dioxolo\[4,5-g\]isoquinoline-5-carbonyl)-2,3-dimethoxy-benzoic acid methyl ester(8), 1H-indole-3-carbaldehyde(9), 4-hydroxy-3-methoxy ethyl cinnamate(10), berberal(11), oblongine trifluoroacetate(12), thalbaicalidine(13), cyclopiamide(14), nicotinamide(15), dehydrocorypalline trifluoroacetate(16), 6-acetonyldihydrochelerythrine(17), 6-acetonyldihydrosanguinarine(18), norsanguinarine(19), oxysanguinarine(20), bulbocapnine(21), corydine(22),(-)-(13aS)-stylopine(23), and(-)-(9S,13S)-pallidine(24). Among these, compounds 3-15 were isolated from the genus Corydalis for the first time, and compounds 16-24 were isolated from Corydalis Rhizoma for the first time. Additionally, the inhibitory activity of compounds 1 and 2 on acetylcholinesterase(AChE) was evaluated.
Corydalis/chemistry* ; Rhizome/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Molecular Structure ; Amides/chemistry* ; Magnetic Resonance Spectroscopy ; Chromatography, High Pressure Liquid ; Alkaloids/chemistry*

Chronic heart failure(CHF) is a series of clinical syndromes in which various heart diseases progress to their end stage. Its morbidity and mortality are increasing year by year, which seriously threatens people's life and health. The diseases causing CHF are complex and varied, such as coronary heart disease, hypertension, diabetes, cardiomyopathy and so on. It is of great significance to establish animal models of CHF according to different etiologies to explore the pathogenesis of CHF and develop drugs to prevent and treat CHF induced by different diseases. Therefore, based on the classification of the etiology of CHF, this paper summarizes the animal models of CHF widely used in recent 10 years, and the application of these animal models in traditional Chinese medicine(TCM) research, in order to provide ideas and strategies for studying the pathogenesis and treatment of CHF, and provide ideas for TCM modernization research.
Animals ; Medicine, Chinese Traditional ; Heart Failure ; Heart Diseases ; Chronic Disease ; Models, Animal

Severe muscle injury is hard to heal and always results in a poor prognosis. Recent studies found that extracellular vesicle-based therapy has promising prospects for regeneration medicine, however, whether extracellular vesicles have therapeutic effects on severe muscle injury is still unknown. Herein, we extracted apoptotic extracellular vesicles derived from mesenchymal stem cells (MSCs-ApoEVs) to treat cardiotoxin induced tibialis anterior (TA) injury and found that MSCs-ApoEVs promoted muscles regeneration and increased the proportion of multinucleated cells. Besides that, we also found that apoptosis was synchronized during myoblasts fusion and MSCs-ApoEVs promoted the apoptosis ratio as well as the fusion index of myoblasts. Furthermore, we revealed that MSCs-ApoEVs increased the relative level of creatine during myoblasts fusion, which was released via activated Pannexin 1 channel. Moreover, we also found that activated Pannexin 1 channel was highly expressed on the membrane of myoblasts-derived ApoEVs (Myo-ApoEVs) instead of apoptotic myoblasts, and creatine was the pivotal metabolite involved in myoblasts fusion. Collectively, our findings firstly revealed that MSCs-ApoEVs can promote muscle regeneration and elucidated that the new function of ApoEVs as passing inter-cell messages through releasing metabolites from activated Pannexin 1 channel, which will provide new evidence for extracellular vesicles-based therapy as well as improving the understanding of new functions of extracellular vesicles.
Creatine/metabolism* ; Extracellular Vesicles ; Muscle, Skeletal/metabolism* ; Myoblasts/metabolism* ; Regeneration ; Connexins/metabolism*

Objective:To investigate the prevalence of liver fibrosis in patients with HBV infection detected by ultrasound transient elastography.Methods:A total of 2 689 patients with HBV infection who received liver transient elastography examination at the Department of Hepatology, Zhongnan Hospital of Wuhan University from November 2021 to April 2022 were enrolled in the study. The severity of liver fibrosis was graded according to the liver stiffness value. The association of liver fibrosis detection rate with gender, age and physiological stages of patients was analyzed, and the correlation between liver stiffness value and HBV DNA, HBsAg, HBeAg level, alanine aminotransferase (AST), aspartate aminotransferase (ALT) and serum albumin levels was further analyzed.Results:Among 2 689 patients with chronic HBV infection, there were 1 417 males aged 46 (34, 57) years and 1 272 females aged 45 (33, 55) years. A total of 1 382 patients (51.03%) showed varying degrees of liver fibrosis, including 381 cases (14.20%) of significant liver fibrosis and 259 (9.60%) cases of progressive fibrosis. Male patients had a significantly higher prevalence of liver fibrosis than that of female patients [60.78%(840/1 382) vs. 39.22%(542/1 382), χ2=74.566, P<0.001]. There were significant differences in liver stiffness values and liver fibrosis detection rates ( F=46.516, 199.079, P<0.001) among patients of different age groups. The liver stiffness index (9.41±4.49 vs. 8.10±3.89, t=9.011, P<0.001) and the prevalence of liver fibrosis in males was higher than those in females in age groups younger than 60 years [61.59%(643/1 044) vs. 38.41%(401/1 044), χ2=78.418, P<0.001]; However, there was no significant gender difference in people over 60 years of age [73.80%(200/271) vs. 71.71%(142/198), χ2=0.252, P>0.05; 20.30%(55/271) vs. 21.21%(42/198), χ2=0.059, P>0.05]. The prevalence of liver fibrosis was significantly lower in premenopausal and perimenopausal females than that in males of the same age groups [29.70%(188/633)and 52.20%(154/295) vs. 64.50%(202/313), χ 2=56.683, P<0.001; χ 2=9.519, P=0.029], whereas there was no significant difference between postmenopausal females and males in the same age group [65.40%(220/336) vs. 72.20%(319/441), χ 2=5.822, P=0.061]. The prevalence of liver fibrosis increased significantly in postmenopausal females as compared to premenopausal females[38.40%(497/1 294) vs. 67.50%(532/787), χ 2=56.683, P=0.002]. The value of liver stiffness in patients with chronic HBV infection was positively correlated with total bilirubin, AST and ALT levels( r=0.208, 0.227, 0.218, P<0.05). Conclusions:The prevalence of liver fibrosis detected by ultrasound transient elastography in chronic HBV-infected patients is substantial, the liver stiffness value and detection rate are higher in males than those in females, however, the prevalence is increased in postmenopausal females. The liver stifness value is related to some biochemical indicators of the liver.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

The pharmacodynamic substances of traditional Chinese medicine(TCM) are the basis for the research of TCM and the development of innovative drugs. However, the lack of clarity of targets and molecular mechanisms is the bottleneck problem that restricts the research of pharmacodynamic substances of TCM. Bioactive components are the material basis of the efficacy of TCM, which exert activity by regulating the corresponding targets. Therefore, it is very important to identify the targets of the bioactive components to elucidate the pharmacological mechanism of TCM. Proteins are the most important drug targets, and study of the interaction between the proteins and bioactive components of TCM plays a key role in the development of pharmacological mechanism of TCM. In recent years, the main techniques for detecting the interaction between the bioactive components and proteins include surface plasmon resonance, fluorescence resonance energy transfer, bio-layer interference, molecular docking, proteome chip, target fishing, target mutant, and protein crystallization techniques, etc. This review summarized the biological target detection techniques and their applications in locating the targets of the bioactive components in TCM in the last decade, and this paper will provide useful strategies to elucidate the pharmacological mechanisms of TCM.
Drugs, Chinese Herbal/pharmacology* ; Medicine, Chinese Traditional ; Molecular Docking Simulation ; Proteome

The traditional Chinese medicine(TCM) contains very complex constituents. Besides the major constituents, there are a large number of unclear trace constituents with novel skeletons and potent bioactivities, which have been regarded as one of the important therapeutic substances and the great resources of innovative drugs derived from TCM. The present review highlighted that the development of the trace therapeutic substances of TCM is closely depends on the advanced technologies for their identification, isolation, structure elucidation, and bioactivity evaluation. Additionally, this paper reviewed the novel trace compounds derived from Chinese herbal medicines which have been published in Organic Letters during 2001-2021, and summarized the important licensed drugs originated from the trace therapeutic substances and the discovery and development of trace therapeutic substances of 8 kinds of Chinese herbal medicines. This review provides references for the research and development of TCM therapeutic substances and innovative drugs.
Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional

Two new neolignans and one new lignan (1-3) were obtained from the roots of Paeonia lactiflora. Their structures were unambiguously elucidated based on extensive spectroscopic analysis, single-crystal X-ray crystallography, and the calculated and experimental electronic circular dichroism (ECD) spectra. Compound 1 was a racemic mixture and successfully resolved into the anticipated enantiomers via chiral-phase HPLC. Compound 3 demonstrated moderate inhibitory activity against human carboxylesterase 2A1 (hCES2A1) with an IC₅₀ value of 7.28 ± 0.94 μmol·^-1.
Chromatography, High Pressure Liquid ; Humans ; Lignans/chemistry* ; Paeonia ; Plant Roots/chemistry* ; Stereoisomerism

Dendrobii officinalis, with a definite effect of nourishing Yin and clearing heat, has been a folk habit for drinking after being mixed with water. Because its superfine powder has the advantages of high dissolution and convenient drinking, we observed the effect of D. officinalis superfine powder on metabolic hypertension model rats and its possible mechanism in this experiment, which can be used as a reference for its clinical application for hypertension. The overeating greasy-induced metabolic hypertension model was established with high-fat, high-sugar and high-purine diet. These rats were orally administered with 400 mg·kg~(-1) and 200 mg·kg~(-1) of D. officinalis superfine powder for 20 consecutive weeks. During this period, blood pressure, blood lipid, blood glucose, insulin and other related indexes of glucose and lipid metabolism were monitored; the levels of lipopolysaccharide(LPS), C-reactive protein(CRP), interleukin 6(IL-6) and other inflammatory mediators were measured; the levels of nitric oxide(NO) and endothelin-1(ET-1) were detected, and the histomorphological and ultrastructural changes of aorta were observed. In addition, the expression of LPS/TLR4 pathway-related molecules in aorta was determined. The results showed that long-term administration of D. officinalis superfine powder significantly reduced the levels of systolic blood pressure(SBP), diastolic blood pressure(DBP) and mean arterial pressure(MBP) in metabolic hypertension model rats, decreased the levels of total cholesterol(TC), triglyceride(TG), low density lipoprotein cholesterol(LDL-c), glucose(Glu), and insulin(INS) levels in blood, increased the contents of high density lipoprotein cholesterol(HDL-c),decreased the LPS, CRP, IL-6 and ET-1 levels in blood and increased NO content. Furthermore, it improved the abnormality of aortic histomorphology and endothelial ultrastructure, and inhibited the protein expression of TLR4, myeloid differentiation factor(MyD88), IL-6, interleukin-1 β(IL-1β), and tumor necrosis factor-α(TNF-α) as well as mRNA expression of TNF-α and IL-1β in aorta. In conclusion, D. officinalis superfine powder may improve the abnormal function and structure of blood vessels by inhibiting the activation of LPS/TLR4 pathway, thus playing a role against metabolic hypertension.
Animals ; Dendrobium/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Hyperphagia ; Hypertension/drug therapy* ; Interleukin-6 ; Powders ; Rats ; Tumor Necrosis Factor-alpha

(±)-Bicoryanhunine B (1), a new dimeric benzylisoquinoline alkaloid was isolated from the dried tubers of Corydalis yanhusuo by various chromatographic methods, including silica gel, Sephadex LH-20, reverse phase C18, and semi-preparative HPLC. Its structure was determined by spectroscopic methods, including UV, IR, ESI-MS, HR-ESI-MS and 1D/2D NMR. (±)-Bicoryanhunine B (1) was a moderate PD-1/PD-L1 interaction inhibitor with an IC₅₀ value of 7.80 ± 0.49 μmol·L^-1. In addition, 1 exhibited potent inhibitory activities against LPS-induced NO production in RAW 264.7 macrophages with an IC₅₀ value of 4.83 ± 2.21 μmol·L^-1.