Objective To establish a quality evaluation method for Abri Mollis Herba based on its morphological characteristics, microscopic features, and the determination of principal component contents. Methods The morphological characteristics of Abri Mollis Herba were identified by morphological authentication methods. Microscopic techniques were employed to observe the microscopic features of both the powdered form and cross-sectional tissue of Abri Mollis Herba. Additionally, a high-performance liquid chromatography （HPLC） method was developed to establish the quantify the main components, abrine and soyasaponin Bb, in Abri Mollis Herba. Results The morphological characteristics of Abri Mollis Herba were defined by numerous long pubescence on both the upper and lower surfaces of the leaflets, with indistinct veins and vein islands. The microscopic features mainly included non-glandular hairs, prismatic crystals, and crystal-sheathed fibers in the powdered form. In the root cross-section, xylem bundles, rays, vessels, and stone cells were visible. The stem cross-section displayed rays, vessels, and a hollow pith, while the leaf cross-section revealed collateral vascular bundles, vessels, and prismatic crystals. Conclusion The quality of Abri Mollis Herba could be effectively evaluated by the combination of morphological identification, microscopic authentication, and the quantification of main components abrine and soyasaponin Bb .

ObjectiveTo explore the molecular mechanism of aerobic exercise to improve hippocampal neuronal degeneration by regulating tryptophan metabolic pathway. Methods60 SPF-grade C57BL/6J male mice were divided into a young group (2 months old, n=30) and a senile group (12 months old, n=30), and each group was further divided into a control group (C/A group, n=15) and an exercise group (CE/AE group, n=15). An aerobic exercise program was used for 8 weeks. Learning memory ability was assessed by Y-maze, and anxiety-depression-like behavior was detected by absent field experiment. Hippocampal Trp levels were measured by GC-MS. Nissl staining was used to observe the number and morphology of hippocampal neurons, and electron microscopy was used to detect synaptic ultrastructure. ELISA was used to detect the levels of hippocampal Trp,5-HT, Kyn, KATs, KYNA, KMO, and QUIN; Western blot was used to analyze the activities of TPH2, IDO1, and TDO enzymes. ResultsGroup A mice showed significant decrease in learning and memory ability (P<0.05) and increase in anxiety and depressive behaviors (P<0.05); all of AE group showed significant improvement (P<0.05). Hippocampal Trp levels decreased in group A (P<0.05) and increased in AE group (P<0.05). Nidus vesicles were reduced and synaptic structures were degraded in group A (P<0.05), and both were significantly improved in group AE (P<0.05). The levels of Trp, 5-HT, KATs, and KYNA were decreased (P<0.05) and the levels of Kyn, KMO, and QUIN were increased (P<0.05) in group A. The activity of TPH2 was decreased (P<0.05), and the activities of IDO1 and TDO were increased (P<0.05). The AE group showed the opposite trend. ConclusionThe aging process significantly reduces the learning memory ability and increases the anxiety-depression-like behavior of mice, and leads to the reduction of the number of nidus vesicles and degenerative changes of synaptic structure in the hippocampus, whereas aerobic exercise not only effectively enhances the spatial learning memory ability and alleviates the anxiety-depression-like behavior of aging mice, but also improves the morphology and structure of neurons in hippocampal area, which may be achieved by the mechanism of regulating the tryptophan metabolic pathway.

The study aimed to investigate the effect of the CD200R1 gene deletion on microglia activation and nigrostriatal dopamine neuron loss in the Parkinson's disease (PD) process. The CRISPR-Cas9 technology was applied to construct the CD200R1^-/- mice. The primary microglia cells of wild-type and CD200R1^-/- mice were cultured and treated with bacterial lipopolysaccharide (LPS). Microglia phagocytosis level was assessed by a fluorescent microsphere phagocytosis assay. PD mouse model was prepared by nigral stereotaxic injection of recombinant adeno-associated virus vector carrying human α-synuclein (α-syn). The changes in the motor behavior of the mice with both genotypes were evaluated by cylinder test, open field test, and rotarod test. Immunohistochemical staining was used to assess the loss of dopamine neurons in substantia nigra. Immunofluorescence staining was used to detect the expression level of CD68 (a key molecule involved in phagocytosis) in microglia. The results showed that CD200R1 deletion markedly enhanced LPS-induced phagocytosis in vitro by the microglial cells. In the mouse model of PD, CD200R1 deletion exacerbated motor behavior impairment and dopamine neuron loss in substantia nigra. Fluorescence intensity analysis results revealed a significant increase in CD68 expression in microglia located in the substantia nigra of CD200R1^-/- mice. The above results suggest that CD200R1 deletion may further activates microglia by promoting microglial phagocytosis, leading to increased loss of the nigrostriatal dopamine neurons in the PD model mice. Therefore, targeting CD200R1 could potentially serve as a novel therapeutic target for the treatment of early-stage PD.
Animals ; Microglia/physiology* ; Mice ; Phagocytosis ; Parkinson Disease/genetics* ; Disease Models, Animal ; Receptors, Cell Surface/physiology* ; Dopaminergic Neurons/pathology* ; Antigens, CD/metabolism* ; Gene Deletion ; Substantia Nigra ; Mice, Inbred C57BL ; Mice, Knockout ; Cells, Cultured ; Male ; alpha-Synuclein ; CD68 Molecule ; Orexin Receptors

Based on ultra-high performance liquid chromatography-quadrupole-Exactive Orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap-MS) technology and network pharmacology, this study explored the pharmacodynamic substances and potential mechanisms of Huazhuo Sanjie Chubi Decoction in the treatment of gouty arthritis(GA). UPLC-Q-Exactive Orbitrap-MS technology was used to identify the components in Huazhuo Sanjie Chubi Decoction, and the qualitative analysis of its active ingredients was carried out, with a total of 184 active ingredients identified. A total of 897 active ingredient targets were screened through the PharmMapper database, and 491 GA-related disease targets were obtained from the OMIM, GeneCards, CTD databases. After Venn analysis, 60 intersecting targets were obtained. The component target-GA target network was constructed through the Cytoscape platform, and the STRING database was used to construct a protein-protein interaction network, with 16 core targets screened. The core targets were subjected to Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses, and the component-target-pathway network was constructed. It was found that the main active ingredients of the formula for the treatment of GA were phenols, flavonoids, alkaloids, and terpenoids, and the key targets were SRC, MMP3, MMP9, REN, ALB, IGF1R, PPARG, MAPK1, HPRT1, and CASP1. Through GO analysis, it was found that the treatment of GA mainly involved biological processes such as lipid response, bacterial response, and biostimulus response. KEGG analysis showed that the pathways related to the treatment of GA included lipids and atherosclerosis, neutrophil extracellular traps(NETs), IL-17, and so on. In summary, phenols, flavonoids, alkaloids, and terpenoids may be the core pharmacodynamic substances of Huazhuo Sanjie Chubi Decoction in the treatment of GA, and the pharmacodynamic mechanism may be related to SRC, MMP3, MMP9, and other targets, as well as lipids and atherosclerosis, NETs, IL-17, and other pathways.
Drugs, Chinese Herbal/therapeutic use* ; Network Pharmacology ; Arthritis, Gouty/metabolism* ; Chromatography, High Pressure Liquid/methods* ; Humans ; Mass Spectrometry/methods* ; Protein Interaction Maps/drug effects*

This study predicts the quality markers(Q-markers) for the cough-relieving and phlegm-expelling effects of Kening Granules based on pharmacodynamics, plasma drug chemistry, network pharmacology, and pharmacokinetics. Strong ammonia solution spray and phenol red secretion assays were employed to evaluate the cough-relieving and phlegm-expelling effects of Kening Granules. Twentysix absorbed prototype components of Kening Granules were identified by ultra high performance liquid chromatography coupled with QExactive Plus quadrupole/Orbitrap high resolution mass spectrometry(UHPLC-Q-Exactive Plus Orbitrap HRMS). Through network pharmacology, 11 potential active components were screened out for the cough-relieving and phlegm-expelling effects of Kening Granules. The 11 components acted on 40 common targets such as IL6, TLR4, and STAT3, which mainly participated in PI3K/Akt, HIF-1, and EGFR signaling pathways. Pharmacokinetic quantitative analysis was performed for 7 prototype components. Three compounds including azelaic acid, caffeic acid, and vanillin were identified as Q-markers for the cough-relieving and phlegm-expelling effects of Kening Granules based on their effectiveness, transmissibility, and measurability. The results of this study are of great significance for clarifying the pharmacological substance basis, optimizing the quality standards, and promoting the clinical application of Kening Granules.
Drugs, Chinese Herbal/administration & dosage* ; Network Pharmacology ; Cough/blood* ; Male ; Humans ; Animals ; Rats ; Rats, Sprague-Dawley ; Biomarkers/blood* ; Quality Control ; Chromatography, High Pressure Liquid ; Antitussive Agents/chemistry*

This study aims to explore whether Naoxintong Capsules improve multiple cerebral infarctions and myocardial injury via promoting angiogenesis, thereby exerting a simultaneous treatment effect on both the brain and heart. Male SD rats were randomly divided into six groups: sham-operated group, model group, high-dose, medium-dose, and low-dose groups of Naoxintong Capsules(440, 220, and 110 mg·kg~(-1)), and nimodipine group(10.8 mg·kg~(-1)). Rat models of multiple cerebral infarctions were established by injecting autologous thrombus, and samples were collected and tested seven days after modeling. Evaluations included multiple cerebral infarction model assessments, neurological function scores, grip strength tests, and rotarod tests, so as to evaluate neuromotor functions. Morphological structures of brain and heart tissue were observed using hematoxylin-eosin(HE) staining, Nissl staining, and Masson staining. Network pharmacology was employed to screen the mechanisms of Naoxintong Capsules in improving multiple cerebral infarctions and myocardial injury. Neuronal and myocardial cell ultrastructures were observed using transmission electron microscopy. Apoptosis rate in brain neuronal cells was detected by TdT-mediated dUTP nick end labeling(TUNEL) staining, and reactive oxygen species(ROS) levels in myocardial cells were measured. Immunofluorescence was used to detect the expression of platelet endothelial cell adhesion molecule-1(CD31), antigen identified by monoclonal antibody Ki67(Ki67), hematopoietic progenitor cell antigen CD34(CD34), and hypoxia inducible factor-1α(HIF-1α) in brain and myocardial tissue. Western blot, and real-time quantitative polymerase chain reaction(RT-qPCR) were used to detect the expression of HIF-1α, vascular endothelial growth factor(VEGF), vascular endothelial growth factor receptor 2(VEGFR2), sarcoma(Src), basic fibroblast growth factor(bFGF), angiopoietin-1(Ang-1), and TEK receptor tyrosine kinase(Tie-2). Compared with the model group, the medium-dose group of Naoxintong Capsules showed significantly lower neurological function scores, increased grip strength, and prolonged time on the rotarod. Pathological damage in brain and heart tissue was reduced, with increased and more orderly arranged mitochondria in neurons and cardiomyocytes. Apoptosis in brain neuronal cells was decreased, and ROS levels in cardiomyocytes were reduced. The microvascular density and endothelial cells of new blood vessels in brain and heart tissue increased, with increased overlapping regions of CD31 and Ki67 expression. The relative protein and mRNA expression levels of HIF-1α, VEGF, VEGFR2, Src, Ang-1, Tie-2, and bFGF were elevated in brain tissue and myocardial tissue. Naoxintong Capsules may improve multiple cerebral infarctions and myocardial injury by mediating HIF-1α/VEGF expression to promote angiogenesis.
Animals ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Rats ; Cerebral Infarction/genetics* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Vascular Endothelial Growth Factor A/genetics* ; Capsules ; Signal Transduction/drug effects* ; Humans ; Brain/metabolism* ; Myocardium/metabolism* ; Apoptosis/drug effects*

Panax species are mostly valuable medicinal plants. While some species' seeds are sensitive to dehydration, the dehydration tolerance of seeds from other Panax species remains unclear. The phospholipase D(PLD) gene plays an important role in plant responses to dehydration stress. However, the characteristics of the PLD gene family and their mechanisms of response to dehydration stress in seeds of Panax species with different dehydration tolerances are not well understood. This study used seeds from eight Panax species to measure the germination rates and PLD activity after dehydration and to analyze the correlation between dehydration tolerance and seed traits. Bioinformatics analysis was also conducted to characterize the PnPLD and PvPLD gene families and to evaluate their expression patterns under dehydration stress. The dehydration tolerance of Panax seeds was ranked from high to low as follows: P. ginseng, P. zingiberensis, P. quinquefolius, P. vietnamensis var. fuscidiscus, P. japonicus var. angustifolius, P. japonicus, P. notoginseng, and P. stipuleanatus. A significant negative correlation was found between dehydration tolerance and seed shape(three-dimensional variance), with flatter seeds exhibiting stronger dehydration tolerance(r=-0.792). Eighteen and nineteen PLD members were identified in P. notoginseng and P. vietnamensis var. fuscidiscus, respectively. These members were classified into five isoforms: α, β, γ, δ, and ζ. The gene structures, subcellular localization, physicochemical properties, and other characteristics of PnPLD and PvPLD were similar. Both promoters contained regulatory elements associated with plant growth and development, hormone responses, and both abiotic and biotic stress. During dehydration, the PLD enzyme activity in P. notoginseng seeds gradually increased as the water content decreased, whereas in P. vietnamensis var. fuscidiscus, PLD activity first decreased and then increased. The expression of PLDα and PLDδ in P. notoginseng seeds initially increased and then decreased, whereas in P. vietnamensis var. fuscidiscus, the expression of PLDα and PLDδ consistently decreased. In conclusion, the dehydration tolerance of Panax seeds showed a significant negative correlation with seed shape. The dehydration tolerance in P. vietnamensis var. fuscidiscus and dehydration sensitivity of P. notoginseng seeds may be related to differences in PLD enzyme activity and the expression of PLDα and PLDδ genes. This study provided the first systematic comparison of dehydration tolerance in Panax seeds and analyzed the causes of tolerance differences and the optimal water content for long-term storage at ultra-low temperatures, thus providing a theoretical basis for the short-term and ultra-low temperature long-term storage of medicinal plant seeds with varying dehydration tolerances.
Seeds/metabolism* ; Panax/physiology* ; Plant Proteins/metabolism* ; Gene Expression Regulation, Plant ; Phospholipase D/metabolism* ; Plants, Medicinal/enzymology* ; Germination ; Multigene Family ; Water/metabolism* ; Dehydration ; Phylogeny

Traditional Chinese medicine(TCM) resources are an important foundation for the theory and practice of TCM. Rare and endangered TCM, as a significant component of these resources, plays an essential role. Conducting research on substitutes for rare and endangered TCM resources is of great significance for alleviating resource shortages, promoting the sustainable utilization of TCM, and advancing TCM modernization. This paper reviews the conservation achievements of rare and endangered Chinese medicinal materials in China and organizes the substitution methods for these materials. Currently, the main substitution approaches include introduction and domestication, tissue culture, varietal replacement, and artificial synthesis. Furthermore, this paper proposes the following approaches for researching the application scenarios of rare and endangered medicinal materials, i.e., tracing the historical context of their use to clarify foundational principles; verifying disease classifications to strengthen the clinical application scenarios of these materials; analyzing the evolution patterns of prescription formulations to strengthen the mining of the compatibility application scenarios of rare and endangered medicinal materials; scientifically evaluating to strengthen the application scenario research and development of endangered Chinese patent medicine industry. These efforts aim to promote the scientific substitution and sustainable utilization of rare and endangered medicinal materials and their substitutes.
Drugs, Chinese Herbal/chemistry* ; Humans ; Medicine, Chinese Traditional ; China ; Plants, Medicinal/growth & development* ; Endangered Species ; Conservation of Natural Resources ; Animals

Case 1: A 19-day-old male infant presented with poor feeding and decreased activity for 2 weeks, worsening with poor responsiveness for 3 days. At 5 days old, he developed poor feeding and poor responsiveness, was hospitalized, and was found to have elevated blood ammonia and thrombocytopenia. Whole-genome genetic analysis revealed a pathogenic homozygous mutation in the PCCA gene, NM-000282.4: c.1834-1835del (p.Arg612AspfsTer44), leading to a diagnosis of propionic acidemia. Case 2: A 4-day-old male infant presented with poor responsiveness and feeding difficulties since birth, with elevated blood ammonia for 1 day. He showed weak sucking and deteriorating responsiveness, with blood ammonia >200 µmol/L. Genetic testing identified two heterozygous mutations in the MMUT gene: NM_000255.4: c.1677-1G>A and NM_000255.4: ex.5del, confirming methylmalonic acidemia. Case 3: A 20-day-old male infant presented with poor feeding for 15 days and skin petechiae for 8 days. He developed feeding difficulties at 5 days old and lower limb petechiae at 12 days old, with blood ammonia measured at 551.6 µmol/L. Genetic analysis found two heterozygous mutations in the PCCA gene: NM_000282.4: c.1118T>A (p.Met373Lys) and NM_000282.4: ex.16-18del, confirming propionic acidemia. In the first two cases, continuous hemodiafiltration was performed for 30 hours and 20 hours, respectively, before administering carglumic acid. In the third case, carglumic acid was administered orally without continuous hemodiafiltration, resulting in a decrease in blood ammonia from 551.6 µmol/L to 72.0 µmol/L within 6 hours, with a reduction rate of approximately 20-25 µmol/(kg·h), similar to the first two cases. Carglumic acid was effective in all three cases, suggesting it may help optimize future treatment protocols for organic acidemia.
Humans ; Male ; Infant, Newborn ; Propionic Acidemia/drug therapy* ; Amino Acid Metabolism, Inborn Errors/genetics* ; Mutation ; Methylmalonyl-CoA Decarboxylase/genetics* ; Citrates/administration & dosage* ; Carbon-Carbon Ligases/genetics* ; Glutamates