To investigate the effects and potential mechanisms of action of Panax notoginseng (Burk) F. H. Chen (P. notoginseng, San Qi) flowers in type 2 diabetes mellitus (T2DM) using network pharmacology, in vivo experiments, and RNA sequencing (RNA-seq).

Network pharmacology analysis was performed to identify and correlate the drug targets of flower buds of P. notoginseng (PNF) with T2DM disease targets and to predict the key targets and pathways involved in the therapeutic effects of PNF in T2DM. In vivo experiments were conducted to assess the effects of PNF on glucose and lipid metabolism in mice with T2DM. RNA-seq was performed, and the results were integrated with network pharmacology data to assess the therapeutic mechanisms of PNF in T2DM. The results from transcriptomics and network pharmacology were validated using real-time polymerase chain reaction.

A total of 27 intersecting targets were identified by overlapping 35 drug targets with T2DM targets. Further topological analysis using the Centiscape 2.2 tool revealed five core targets, including signal transducer and activator of transcription 3 (STAT3). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that the JAK/STAT signaling pathway is a key mechanism underlying the therapeutic effects of PNF in T2DM. In vivo experiments confirmed that PNF effectively regulates glycolipid metabolism in a mouse model of diabetes. KEGG pathway enrichment analysis of RNA-seq data highlighted the JAK2/STAT3 and PI3K/AKT pathway as a potential mechanism. PNF high-dose (PNFH) increased the gene expression levels of PIK3R1 and AKT2, decreased the expression of PCK1, JAK2, and STAT3, and showed a trend toward increasing INSR expression without reaching statistical significance.

PNF improves glycolipid metabolism disorders in T2DM, potentially by modulating the JAK2/STAT3 and PI3K/AKT signaling pathway.

Based on the traditional Chinese medicine theory of "simultaneous regulation of the liver and kidney," this study integrated network pharmacology prediction, molecular docking, and animal experimental validation to analyze the multi-target regulatory network of Duzhong Xionghua (the male flower of Eucommia ulmoides)-Sanqi Hua (Sanchi flower) herb pair (hereinafter called "herb pair") in modulating glucolipid metabolic disorders in type 2 diabetes mellitus (T2DM), thereby elucidating its underlying molecular mechanism.

Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals, and Wanfang Data were used to obtain the active ingredients of the male flower of Eucommia ulmoides and Sanchi flower. PubChem Compound, SwissTargetPrediction, and SuperPred were used to screen and predict the targets of the drugs; The Human Gene Database, The Online Mendelian Inheritance in Man, and Therapeutic Target Database were used to screen the key gene targets of T2DM. A "component-target-pathway" network diagram was constructed using Cytoscape software, and Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were employed to identify the functions of the relevant target genes and pathways. Molecular docking was used to verify the binding activities of the core components and the key targets. For animal experiments, spontaneous T2DM model mice were used, in which the normal group consisted of six mice (wild type) from the same litter, and the 24 successfully modeled mice were randomly divided into model, metformin (0.26 g/kg), high-dose herb pair (2.6 g/kg), and low-dose herb pair groups (1.3 g/kg) according to the blood glucose levels and body weights, with six mice per group. The drugs were administered by gavage daily for six consecutive weeks. The body weight and fasting blood glucose (FBG) levels were measured weekly, and an oral glucose tolerance test was performed in the fifth week. At the end of drug administration, body weight, naso-anal length, liver and bilateral epididymal adipose mass were measured; pathological changes in the liver were observed using HE staining; serum levels of aspartate transaminase (AST), alanine amino-transferase (ALT), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were detected using colorimetric assay; and liver tissue phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase-3β (GSK-3β) signaling pathway protein expressions were determined using Western blotting.

Network pharmacology screening identified 38 active components and 669 potential targets of the herb pair. Intersection analysis with 1, 275 T2DM-related targets yielded 185 common targets. Protein-protein interaction network analysis and pathway enrichment revealed the PI3K/AKT signaling pathway as a key mechanism. Molecular docking confirmed the strong binding affinity of the core components to key targets such as AKT1, suggesting that the herb pair may activate the PI3K/AKT pathway and inhibit GSK-3β activity via beta-sitosterol etc. Animal experiments demonstrated that, compared with the model group, the metformin group exhibited reduced FBG, AST, and ALT levels (P < 0.01), but failed to improve body weight, Lee′s index, or epididymal fat coefficient. Both herb pair doses significantly lowered Lee′s index, hepatic index, and the epididymal fat coefficient (P < 0.01), with the low-dose herb pair group showing attenuated body weight gain in mice. In contrast, the high-dose herb pair group exhibited decreased FBG, improved glucose tolerance, reduced TC, TG, and LDL-C levels, and increased HDL-C level (all P < 0.01). HE staining revealed that all metformin and the herb pair markedly restored hepatic structure and alleviated steatosis in model mice, with more pronounced effects in the high-dose group than in the low-dose group. Western blotting result indicated that in the low-dose herb pair group, phospho-PI3K (p-PI3K), AKT, and phospho-GSK-3β (p-GSK-3β) protein expressions significantly increased (P < 0.05 or P < 0.01), whereas GSK-3β decreased (P < 0.05). The high-dose group exhibited enhanced PI3K, p-PI3K, AKT, phospho-AKT, and p-GSK-3β protein expressions (all P < 0.01), accompanied by reduced GSK-3β expression (P < 0.01).

The male flower of Eucommia ulmoides-Sanchi flower herb pair may ameliorate T2DM-related glucolipid metabolic disorders by modulating the PI3K/AKT/GSK-3β pathway.

To evaluate the effects of Wuhua herbal tea on chronic unpredictable mild stress (CUMS)-induced depression and explore its mechanism of action in combating depression.

We tested the antidepressant effects of Wuhua herbal tea in a rat model of CUMS-induced depression using fluoxetine as a positive control. The rats were divided into four groups: control group, model group, fluoxetine group, and Wuhua herbal tea group. The rats underwent body weight measurements, sucrose preference test, and open-field test. Enzyme-linked immunosorbent assay kits were used to detect the serum levels of serotonin, dopamine, adrenocorticotropic hormone (ACTH), corticosterone, norepinephrine, and interleukin-6. Intergroup comparisons and detection of brain-derived neurotrophic factor (BDNF), cAMP-response element binding protein (CREB), Janus kinase 2 (JAK2), and signal transducer and activator of transcription 3 (STAT3) mRNA expression in the hippocampus were performed using RT-PCR. Immunohistochemistry was used to identify the expression of phosphorylated JAK2 (p-JAK2) and phosphorylated STAT3 (p-STAT3) proteins in hippocampal paraffin sections of CUMS rats.

Compared with the control group, the model group rats had depressive tendencies, exhibiting low vitality and interest in various behavioral indicators which were signs of despair. The Wuhua herbal tea group statistically increased the levels of serotonin and dopamine in the serum of CUMS rats to varying degrees (P = .015 and P = .002); reduced serum levels of ACTH, corticosterone, norepinephrine, and interleukin-6 (all P < .05); and decreased mRNA expression of BDNF, CREB, JAK2, and STAT3 in the hippocampus (all P < .05); and decreased p-STAT3 protein levels (P = .006).

Wuhua herbal tea shows antidepressant potential in CUMS rats by modulating the HPA axis and inhibiting JAK2-STAT3 overactivation, alleviating neuroinflammation. It also restores BDNF-CREB pathway function, reducing depressive symptoms.

Using Chinese patents in force to investigate the frequency and patterns of Chinese herbal extract combinations claiming to treat heart disease.

Patent documents were retrieved from the official website of the State Intellectual Property Office of the People’s Republic China. Cluster, frequency, and fuzzy cluster analyses were applied.

A high number of patents in force included high-frequency herbs such as Salvia miltiorrhiza, Panax ginseng, and Panax notoginseng, as well as high-frequency herbal families such as Araliaceae, Leguminosae, Labiatae, and Umbelliferae. Herb pairs such as P. ginseng + Ophiopogon japonicus, S. miltiorrhiza + Dalbergia odorifera, and P. ginseng + Schisandra chinensis are also commonly used, as well as herbal family pairs such as Araliaceae + Liliaceae, Lauraceae + Leguminosae, and Araliaceae + Schisandraceae. Traditional treatment principles for preventing and treating heart diseases was most-commonly based on simultaneously treating the liver and heart and treating the lung and spleen secondarily for choosing herbal combinations.

Most of the high-frequency Chinese herbs in the patents investigated belong to the high-frequency herbal families, and herb pairs were commonly selected to coincide with the commonly-used herbal family pairs. Low-frequency Chinese herbs were also used, but generally belonged to the high-frequency herbal families, and were therefore similar to the high-frequency herbs in terms of traditional categories of taste and channel entered. The results reflect the use of traditional principles of formula composition, and suggest that these principles may indeed be an effective guide for further research and development of Chinese herbal extract combinations to prevent and treat heart diseases.