Resveratrol (Res), a naturally non-flavonoid polyphenol, shows significant therapeutic potential in suppressing tumor growth, metastasis, and enhancing chemotherapy. However, Res has some disadvantages that limit its clinical use, such as low oral bioavailability, structural instability, and non-selective tissue distribution in vivo. Stimuli-responsive drug delivery systems can overcome these issues, achieving efficient delivery in vivo and controlled release at tumor-site. Based on the endogenous physiological features of tumors and exogenous stimulation methods, this paper uses Res as an example, which reviews the current response release methods for targeted delivery of anti-tumor drugs, such as pH, ROS, and light-responsive strategies, respectively. The diversified release designs offer references for controlled release of anti-tumor drugs in the complex tumor microenvironment. It also provides new ideas and directions for personalized and smart treatment for anti-tumor active ingredients from traditional Chinese medicine.

Based on our previous finding that the traditional Chinese medicine Aglaia odorata Lour. exhibited therapeutic effects against ischemic stroke, this study aimed to identify its target proteins with stable isotope labeling by amino acids in cell culture (SILAC) combined with thermal proteome profiling (TPP) strategy using oxygen-glucose deprivation/reperfusion (OGD/R) model of rat adrenal pheochromocytoma (PC12) cell, and explore the target-associated signaling pathways to reveal the molecular mechanisms underlying neuroprotective effects. The results showed that A. odorata exerted a protective effect on OGD/R-induced neuronal cell injury by significantly increasing the viability of PC12 cells and reducing lactate dehydrogenase (LDH) release and reactive oxygen species (ROS) levels. Target identification revealed 28 proteins as potential targets of A. odorata, predominantly associated with energy metabolism-related signaling pathways, including carbon metabolism. Additionally, the verification results of the biological functions of the target group indicated that A. odorata increased the adenosine triphosphate (ATP) content in OGD/R-induced PC12 cells, enhanced the activity of mitochondrial respiratory chain complexes, elevated the mitochondrial membrane potential, reduced the production of mitochondrial superoxide, increased the phosphorylation of AMP-activated protein kinase (AMPK), and upregulated the protein expression of sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). In conclusion, A. odorata could alleviate OGD/R-induced neuronal cell injury and exhibit significant neuroprotective activity, possibly through the regulation of the AMPK/SIRT1/PGC-1α pathway and improvement of mitochondrial function and energy metabolism.

Diabetes mellitus is mainly caused by insufficient insulin secretion or impaired insulin action, and the patients exhibit varying degrees of pancreatic islet β-cell dysfunction. In the present study, Rin-m5F pancreatic islet β-cells were used to investigate the protective effect of puerarin against islet β-cell injury and its underlying mechanism. The Cell Counting Kit-8 (CCK-8) assay was performed to evaluate cell viability, so as to screen the optimal concentrations of glucose (as the injury inducer) and puerarin (as the therapeutic agent). Flow cytometry was employed to evaluate the effect of puerarin on apoptosis in the glucose-induced islet β-cell injury model. Molecular docking technology was used to analyze the binding energy between puerarin and B-cell lymphoma-2 (Bcl-2) protein, and Western blot analysis was conducted to analyze the expression levels of Bcl-2 and its downstream-related proteins. The results of CCK-8 showed that 50 mmol·L^-1 glucose induced significant injury to Rin-m5F pancreatic islet β-cells, which was improved by puerarin (25-200 μmol·L^-1) in a dose-dependent manner. Flow cytometry results demonstrated that puerarin effectively reduced cell apoptosis. Molecular docking analysis revealed a favorable binding energy between puerarin and Bcl-2 protein. Further, Western blot results indicated that puerarin upregulated the expression of Bcl-2, while downregulated the expression of apoptotic pathway-related proteins, including Bcl-2-associated X protein (Bax), cysteinyl aspartate specific proteinase-3 (Caspase-3), and poly (ADP-ribose) polymerase 1 (PARP-1). Additionally, puerarin promoted the expression of microtubule-associated protein 1 light chain 3 (LC3) Ⅱ/Ⅰ. After co-treated with Venetoclax, a Bcl-2 inhibitor, puerarin failed to protect against islet β-cell injury, inhibit apoptosis, and upregulate the expression of Bcl-2. These findings suggest that the protective effect of puerarin on islet β-cell injury is abrogated when Bcl-2 is inhibited. In conclusion, puerarin alleviates pancreatic islet β-cell injury by activating Bcl-2, providing a basis for the further investigation of the mechanism underlying the therapeutic effect of traditional Chinese medicine prescriptions containing Pueraria lobata in the treatment of diabetes mellitus.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra. Current clinical treatments for PD remain limited, highlighting the urgent need for innovative drug development. In this study, we synthesized a protonic bis-pyridazine (H-Py) compound using an intermolecular proton transfer technique. In MPP⁺-induced PD model cells, H-Py significantly improved cell viability and reduced ROS levels. In 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD model mice, H-Py demonstrated good safety and ameliorated motor dysfunction, with efficacy showing no significant difference from that of levodopa, a first-line PD therapeutic agent. Furthermore, immunofluorescence analysis of tyrosine hydroxylase (TH) levels in the substantia nigra and striatum revealed that H-Py administration significantly increased TH expression in these brain regions. Western blot analysis suggested that H-Py may protect against neuronal damage by activating the Nrf2/HO-1 pathway and alleviating oxidative stress. The experimental protocol was approved by the Animal Experiment Ethics Committee of Southwest University (approval No.: IACUC-20250714-05). In summary, this study may provide new strategies and insights for PD treatment.

Depression is a common mental disorder. Previous studies have found that Schisandra chinensis lignans (SCL) exhibit significant therapeutic effects on depression, though its antidepressant mechanisms remain incompletely understood. This study aims to elucidate the molecular mechanisms by which SCL exerts neuroprotective and antidepressant effects, based on SCL's modern pharmacological neuroprotective properties and the physiological function of cannabinoid type 1 receptor (CB1R) in neuronal protection. By establishing a chronic unpredictable mild stress (CUMS)-induced depression model and administering CB1R antagonist AM251 to CUMS-treated animals, we conducted pharmacobehavioral experiments to evaluate SCL's ability to improve depression-like behaviors in mice. Additionally, we employed Western blot, hematoxylin-eosin staining, immunohistochemistry, immunofluorescence, and molecular docking to investigate SCL's antidepressant mechanism through CB1R-mediated regulation of brain-derived neurotrophic factor (BDNF). The use of animals in this study was approved by the Ethics Committee of Shenyang Pharmaceutical University, with the approval number: SYPU-IACUC-C2021-11-3-115. Pharmacobehavioral results demonstrated that SCL alleviates depression-like behaviors in CUMS model mice. Hematoxylin-eosin staining revealed that SCL improves neuronal pathological damage and neuroplasticity impairment caused by CUMS in the model. Western blot analysis revealed that SCL upregulates BDNF and CB1R expression, activates the proBDNF-tPA-BDNF pathway to promote proBDNF cleavage, and exerts anti-apoptotic effects. It also activates BDNF-TrkB-MEK-ERK-PKA-CREB and PI3K-AKT pathways to reduce neuronal damage and exert antidepressant effects. Further experiments confirmed that AM251 antagonized SCL's antidepressant effects by inhibiting its depression-like behavior and modulation of BDNF-related pathways. Specifically, SCL activates proBDNF-tPA-BDNF via CB1R to enhance BDNF production and anti-apoptotic effects, while simultaneously activating the downstream classical pathway BDNF-TrkB-ERK-PI3K-AKT to protect neurons and exert antidepressant effects. Molecular docking revealed the binding sites of six major components in SCL for CB1R. The study revealed that SCL exerts antidepressant effects by regulating BDNF through CB1R to alleviate neuronal damage.

This study aimed to explore the multi-target mechanism of action of the innovative Chinese herbal compounds YCNHF Ⅰ (comprising 6 herbs with both edible and medicinal values, including Gardenia jasminoides and others)/Ⅱ (comprising 6 herbs without edible value, including Scutellaria baicalensis and others) in treating inflammatory bowel disease (IBD). We screened the active components of the compounds and IBD-related targets by mining multiple databases, then constructed a "compound-target-pathway" network and validated it using molecular docking. Ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was employed to identify components that entered the bloodstream, and their antioxidant capacity was assessed. In lipopolysaccharide (LPS)-induced inflammatory Caco-2 cell models, we measured the expression of interleukin-6 (IL-6) and interleukin-1β (IL-1β), as well as mitochondrial membrane potential. Additionally, we established a rat model of ulcerative colitis (UC) induced by dextran sulfate sodium (DSS), after administering the compounds via intragastric gavage, colonic pathology was observed via hematoxylin and eosin (HE) staining, and p-Akt expression in colon tissues was detected by Western blot. Results showed that YCNHF Ⅰ and YCNHF Ⅱ shared 191 and 186 common targets with IBD-related targets, respectively. These targets were mainly enriched in signaling pathways such as PI3K-Akt and in mitochondrial function regulatory networks. Components like quercetin showed strong binding affinity to targets including IL-6. The two compounds had 53 and 72 blood-entering components, respectively, exhibited antioxidant activity, inhibited pro-inflammatory factor expression, and improved mitochondrial membrane potential. They also alleviated pathological damage in UC rats and regulated the PI3K-Akt pathway. This experiment was approved by the Medical Ethics Committee of the Yan'an University (approval number: IIT-G-2025064).

This study explored the effect and mechanism of Dracocephalum moldavica L. on acute kidney injury (AKI) based on network pharmacology, molecular docking and animal experiments. Through online pharmacological studies, the effective components and targets of Dracocephalum moldavica L. in the treatment of AKI were obtained. Seventeen active components and 60 intersection targets were screened out, among which there were 12 core targets. Through the analysis of the function of Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, it was screened out that it was mainly related to pathways such as cancer. Molecular docking was conducted between the active ingredients and the core targets. The results showed a strong association with matrix metalloprotein 9 (MMP9) and glycogen synthase kinase-3β (GSK-3β). The experiment selected the extract of Dracocephalum moldavica L. as the therapeutic drug and randomly divided ICR mice into normal group, model group, low, medium, and high (90, 180, 360 mg·kg^-1) dose groups of Dracocephalum moldavica L. extract, amifostine group (200 mg·kg^-1), and Uremic Clear Granules group (3 750 mg·kg^-1). Intragastric administration was given 7 days in advance. On the 7^th day, the amifostine group was injected with amifostine solution. Two hours after the end of intragastric administration on the 7^th day, except for the normal group, the other groups were intraperitoneally injected with cisplatin (CDDP) solution to establish an AKI mouse model. Samples were collected 72 hours after modeling. This experiment was approved by the Animal Ethics Committee of Xinjiang Institute of Materia Medica (approval number: XJIMM-20240802). The organ indices of liver, spleen, and kidney were calculated; the levels of serum creatinine (SCr) and blood urea nitrogen (BUN) in mouse serum, glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD) in mouse kidney were determined by kits; the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in mouse kidney were detected by ELISA kits; the pathological changes of the kidney were observed by hematoxylin-eosin (HE) staining and periodic acid-Schiff (PAS) staining; and the expression of MMP9, GSK-3β, β-catenin, as well as Bcl-2 associated X-protein (Bax) and B-cell lymphoma-2 protein (Bcl-2) in renal tissue was verified by Western blot. The experimental results showed that the extract of Dracocephalum moldavica L. could significantly improve the organ indices of spleen, liver, and kidney in AKI mice; significantly reduce the levels of SCr and BUN in blood; reduce the levels of TNF-α, IL-6, and IL-1β; up-regulate the levels of GSH-PX and SOD; improve the pathological damage of kidney; and regulate the expression of MMP9, GSK-3β, β-catenin, Bax and Bcl-2 in renal tissue. It suggests that the extract of Dracocephalum moldavica L. may exert a protective effect on AKI caused by CDDP through regulating the expression of the GSK-3β/β-catenin signaling pathway.

Sarcopenia is an age-related progressive disease characterized by the loss of skeletal muscle mass and function, which seriously threatens the quality of life and survival of elderly individuals. Shiquandabu Decoction is a classical traditional Chinese herbal formula known for its effects in benefiting Qi and nourishing blood, and modern studies have demonstrated its potential therapeutic effects on sarcopenia. To investigate the protective effects and underlying mechanisms of Shiquandabu Decoction against sarcopenia, this study prepared its water decoction, administered it to rats by gavage, collected the drug-containing serum, and identified the components absorbed into the blood using UHPLC-Q-TOF-MS. The animal experiments in this study were conducted in compliance with the regulations of the Scientific Research Ethics Committee of Shanxi University of Chinese Medicine and approved by the Animal Experimentation Ethics Review (approval No.: AWE202403229). The drug-containing serum was used to treat a D-galactose (D-gal)-induced senescent C2C12 myotube model. CCK-8 was used to detect cell activity, DCFH-DA probe was used to detect reactive oxygen species (ROS) levels, JC-1 staining was used to detect mitochondrial membrane potential, flow cytometry was used to analyze the cell cycle, and RT-qPCR was used to detect the expression of myogenic differentiation-related factors (MyoD, MyoG, and Mstn) and senescence gene (p53). LC-MS proposed targeted metabolomics to screen for differential metabolites and analyze related pathways. The results showed that 15% drug-containing serum was able to significantly increase the cell survival rate, reduce the ROS levels, restore the mitochondrial membrane potential, reduce the G0/G1 phase cellular block, and promote the cell cycle process, and it was able to up-regulate the expression of MyoD and MyoG, and down-regulate the expression of Mstn and p53. Metabolomics studies of the proposed target cells showed that intervention with drug-containing serum resulted in the callback of 119 differential metabolites (42 up-regulated and 77 down-regulated), mainly related to amino acids, carbohydrates, lipids, nucleotides and energy metabolic pathways. These results suggest that the drug-containing serum of Shiquandabu Decoction exerts a protective effect against D-gal-induced myocyte attenuation through multi-target and multi-pathway synergistic effects, improving mitochondrial function, regulating the cell cycle and promoting myo-differentiation.

Phenolic and flavonoid glycosides have the multi-target regulatory advantages in anti-colitis. Using lactose and galactose as starting materials, five novel phenolic glycosides G-6a, G-6b, G-9, G-13 and G-Ⅱ-3a were synthesized through glycosylation, hydrolysis, reduction, and recrystallization. Using a mouse colitis model induced by dextran sulfate sodium, animal experiments have been approved by the Animal Ethics Committee of Ocean University of China (approval number: OUC-SMP-2024-06-05), the in vivo anti-colitis experiments showed that compound G-Ⅱ-3a exhibited significant anti-colitis effects at a daily dose of 25 mg·kg^-1, effectively inhibiting weight loss in mice, reducing disease activity index scores, alleviating colonic shortening, maintaining the integrity of colonic mucosal structure, and reducing inflammatory cell infiltration. Its anti-inflammatory effect is superior to mesalazine. G-Ⅱ-3a can inhibit the release of inflammatory factors IL-6, TNF-α, and NO from lipopolysaccharide induced mouse monocyte macrophages RAW264.7. Compound G-Ⅱ-3a is a potential lead compound for the treatment of inflammatory bowel disease.

A systematic study of the chemical constituents of the n-butanol extraction of Ephedra intermedia (E. intermedia) was carried out and 15 compounds were isolated using various column chromatography combinations with modern wave spectroscopy. Their structures were identified as (7R, 8S, 7′R, 8′S, 7″R, 8″S)-ephnan A (1), 4-methoxy garcimangosone D (2), garcimangosone D (3), (+)-syringaresinol (4), (+)-syringaresinol-O-β-D-glucopyranoside (5), methyl benzoate-4-β-glucoside (6), 3-methoxy-4-O-β-D-glucopyranosyloxy-benzoic acid methyl ester (7), methyl syringate 4-O-β-D-glucopyranoside (8), trans-4-O-β-D-glucopyranosyl ferulic acid (9), 3, 5-dimethoxy-4-O-β-D-glucopyranosyl-cinnamic acid (10), raspberry ketone O-β-D-glucopyranoside (11), E-melilotoside (12), β-D-glucopyranosyl-benzoate (13), 3, 4-dihydroxybenzoic acid 3-O-β-D-glucoside (14), 3, 5-dihydroxy-4-O-β-D-glucopyranosyl acetophenone (15). Compounds 1 and 2 were new compounds, compounds 6-9 and 13-15 were isolated from Ephedra for the first time. Compounds 7, 11-14 exhibited potential anti-pneumonia activity.