Oxidative stress could lead to a variety of body dysfunctions, including neurodegeneration and cancer, which are closely associated with intracellular signal transducers such as reactive oxygen species (ROS). It has been suggested that ROS is the upstream regulator of autophagy, and that it provides a negative feedback regulation to remove oxidative damage. Defects in the ROS-autophagic redox homeostasis could lead to the increased production of ROS and the accumulation of damaged organelles that in turn promote metabolic reprogramming and induce tumorigenesis. One significant characteristic of pancreatic cancer is the reprogramming of cellular energy metabolism, which facilitates the rapid growth, invasiveness, and the survival of cancer cells. Thus, the rectification of metabolic dysfunction is essential in therapeutic cancer targeting. Isoliquiritigenin (ISL) is a chalcone obtained from the plant Glycyrrhiza glabra, which is a powdered root licorice that has been consumed for centuries in different regions of the world. ISL is known to be a natural antioxidant that possesses diversified functions, including redox regulation in cells. This review contains discussions on the herbal source, biological properties, and anticancer potential of ISL. This is the first time that the anticancer activities of ISL in pancreatic cancer has been elucidated, with a coverage of the involvement of antioxidation, metabolic redox regulation, and autophagy in pancreatic cancer development. Furthermore, some remarks on related compounds of the isoflavonoid biosynthetic pathway of ISL will also be discussed.

Polyphyllin II (PPII) is a natural steroidal saponin occurring in Rhizoma Paridis. It has been demonstrated to exhibit anti-cancer activity against a variety of cancer cells. However, the anti-colorectal cancer (CRC) effects and mechanism of action of PPII are rarely reported. In the present study, we showed that PPII inhibited the proliferation of HCT116 and SW620 cells. Moreover, PPII induced G2/M-phase cell cycle arrest and apoptosis, as well as protective autophagy, in CRC cells. We found that PPII-induced autophagy was associated with the inhibition of PI3K/AKT/mTOR signaling. Western blotting results further revealed that PPII lowered the protein levels of phospho-Src (Tyr416), phospho-JAK2 (Tyr1007/1008), phospho-STAT3 (Tyr705), and STAT3-targeted molecules in CRC cells. The overactivation of STAT3 attenuated the cytotoxicity of PPII against HCT116 cells, indicating the involvement of STAT3 inhibition in the anti-CRC effects of PPII. PPII (0.5 mg/kg or 1 mg/kg, i.p. once every 3 days) suppressed HCT116 tumor growth in nude mice. In alignment with the in vitro results, PPII inhibited proliferation, induced apoptosis, and lowered the protein levels of phospho-STAT3, phospho-AKT, and phospho-mTOR in xenografts. These data suggest that PPII could be a potent therapeutic agent for the treatment of CRC.

Aim of the study: Traditional Chinese Medicine offers a holistic approach that could provide complementary benefits for bipolar disorder treatment. However, the clinical cases in Traditional Chinese Medicine are highly dispersed, creating challenges for translational research. This study employs a novel data-mining-derived approach to identify treatment patterns and active metabolite interactions within these clinical cases.Methods and materials: Bipolar disorder-related targets were determined using DisGeNET and GeneCards databases. Active botanical drugs were extracted from the BATMAN-TCM 2.0 database. All terms for botanical drugs and diseases were confirmed via the Pharmacopoeia of the People’s Republic of China 2020 Edition and Medical Subject Headings. Networks were constructed using Cytoscape, with data analysis performed using Python. MTT cell viability and qRT-PCR analysis were used to perform in vitro experiments on SH-SY5Y neuroblastoma cells.Results: Five key botanical drugs—Glycyrrhizae Radix Et Rhizoma, Poria, Coptidis Rhizoma, Bupleuri Radix, and Polygalae Radix—were identified as core drugs in BD treatment formulas. The botanical drug-metabolite-target network was constructed. In vitro experiments using SH-SY5Y neuroblastoma cells demonstrated dose-dependent effects of palmitic acid (PA) and stearic acid (SA) on cell viability and gene expression. qRT-PCR analysis revealed bidirectional regulation of GABRA1 and ESR1 by these metabolites.Conclusion: Five botanical drugs: Glycyrrhizae Radix Et Rhizoma, Poria, Coptidis Rhizoma, Bupleuri Radix, and Polygalae Radix, were identified as the core botanical drugs in bipolar disorder treatment. The main mechanism of these botanical drugs is their effects on the gamma-aminobutyric acid type A receptor and ESR1.

Pancreatic ductal adenocarcinoma (PDAC), a highly aggressive malignancy with increasing incidence and low survival rates, urgently requires novel therapeutic strategies to overcome the limitations posed by current treatment agents like gemcitabine. Licochalcone A (LHA), a bioactive flavonoid derived from Glycyrrhiza species, exhibits anticancer properties in multiple cancers, yet its efficacy and mechanisms in PDAC remain unexplored. This study aims to investigate the anticancer potential of LHA in PDAC. In vitro assays demonstrated that LHA dose-dependently inhibited PDAC cell proliferation and induced pyroptosis, a lytic inflammatory cell death, while autophagy inhibition synergistically enhanced the cytotoxicity of LHA. Furthermore, LHA suppressed the migration of PDAC cells. Mechanistically, molecular docking and functional studies revealed that LHA directly binds to eukaryotic elongation factor 2 kinase (eEF2K), reducing its expression and downstream phosphorylation of eukaryotic elongation factor 2 (p-eEF2). Notably, eEF2K overexpression reversed LHA-induced pyroptosis in PDAC cells. In vivo, LHA significantly reduced tumor growth and altered tumor histopathology in a PDAC xenograft model, along with downregulated eEF2K and upregulated pyroptosis executors (GSDMD/GSDME). Collectively, these findings identify LHA as a dual-function agent: a natural eEF2K inhibitor and a pyroptosis inducer with potent antitumor activity against PDAC. This study provides a foundational rationale for further clinical exploration of LHA as a promising chemotherapeutic agent or adjuvant to enhance PDAC treatment outcomes.

Hyperuricemia (HUA), a metabolic disorder characterized by elevated serum uric acid resulting from imbalanced production and excretion, is associated with gout and other serious health issues. This study aimed to screen out the potential probiotics with HUA-alleviating properties among 20 Lactobacillus strains. The results showed that L. reuteri Urob-7 exhibited the highest degradation rates for inosine and guanosine (82.10% and 88.78%, respectively) and strong xanthine oxidase (XOD) inhibitory activity (62.86%). In a HUA mouse model induced by inosine, guanosine, and potassium oxonate, L. reuteri Urob-7 intervention significantly reduced serum uric acid levels by 46.54%, restoring them to levels similar to control groups, and improved kidney function indicators. Moreover, Urob-7 reduced hepatic XOD activity by 37.6% and downregulated XOD expression in the intestines, decreasing excessive uric acid synthesis. It also significantly inhibited the NF-κB/NLRP3 inflammatory pathway, reducing the expression levels of NF-κB and NLRP3 in the kidneys by 39.3% and 47.6%, respectively. Furthermore, L. reuteri Urob-7 increased the abundance of short-chain fatty acid-producing bacteria (e.g., Ruminococcus and Intestinimonas) while reducing the proportion of pathogenic bacteria (e.g., Bacteroides and Anaerovorax), thus ameliorating gut microbiota dysbiosis and intestinal barrier dysfunction. In summary, L. reuteri Urob-7 effectively relieved HUA by modulating uric acid metabolism, suppressing inflammation, and improving gut microbiota balance. These results highlighted its potential as a promising candidate for HUA.

Aim of the study: Traditional Chinese herbs have a unique therapeutic effect on stroke and numerous successful clinical cases. However, these clinical cases are highly dispersed, creating challenges for translational research. This study employs a new paradigm to identify treatment patterns and the active compound interactions contained within these clinical cases, with experimental validation after target screening. Methods and Materials: Stroke-related targets were identified through GEO, DisGeNET, and Genecards. Active ingredients were extracted from BATMAN-TCM 2.0. All herbs and diseases were confirmed by the Pharmacopoeia of the People’s Republic of China (2020 edition) and Medical Subject Heading (MeSH). All networks in this study were constructed by Cytoscape, and data analysis was done by Python. All formulations and herbs were retrieved from the literature review. For the molecular docking process, Autodock was applied as the docking platform, and all the protein structures were downloaded from PDB. For experimental validation after target screening, HT22 cells were incubated with glucose-free DMEM and placed in an anaerobic chamber for 2 h. Subsequently, HT22 cells were reoxygenated for 24 h. Estrogen Receptor 1 (ESR1) protein levels were measured in vitro. Results: seven materials, including Angelicae Sinensis Radix, Pheretima, Chuanxiong Rhizoma, Persicae Semen, Astragali Radix, Carthami Flos, and Radix Paeoniae Rubra, were identified as the core herbs for the treatment of stroke. The targets of the stroke mechanism were screened, and the herbs-compound-target network was constructed. Among them, paeoniflorin (PF) was identified as the core active compound, and its interaction with ESR1 was verified by molecular docking as the key interaction for the treatment of stroke. In vitro experiments showed that PF inhibited cell apoptosis under hypoxia by increasing the expression of ESR1 compared with the oxygen-glucose deprivation-reperfusion (OGD/R) model group. Western showed that PF (100 μM, 200 μM) can significantly increase the decreased ESR1 protein level caused by the OGD/R model. Conclusions: seven key herbs were screened. Further bioinformatics and network pharmacology studies suggested that PF is expected to become a new active compound for the treatment of stroke. In vitro validation further demonstrated that PF enhanced neuronal survival and ESR1 expression under ischemic conditions, supporting its therapeutic candidacy.