Yuan Lu

Euphorbia helioscopia L. (Zeqi, ZQ) is a traditional Chinese herb used to treat various tumors, but its molecular mechanisms against hepatocellular carcinoma (HCC) remain unclear. This study aims to elucidate the anti-HCC mechanisms of ZQ using chemical profiling, bioinformatics, Mendelian randomization (MR), and experimental validation. A total of 104 compounds were identified from ZQ, with 18 targeting HCC-related proteins. Bioinformatics and MR analyses revealed PTK2 as a core target associated with HCC risk. ZQ significantly suppressed H22 tumor growth in male ICR mice and inhibited PTK2/PI3K/AKT phosphorylation. Molecular docking and dynamics simulations confirmed stable binding between key ZQ compounds and PTK2. These results suggest that ZQ exerts anti-HCC effects through PTK2 inhibition and modulation of the PI3K/AKT pathway, supporting its potential as a multi-targeted therapeutic for HCC.

This study systematically analyzed commercially available traditional Chinese medicines for As, Hg, Pb, Cd, and Cu, classifying them into roots and rhizomes (underground parts), stems and leaves, whole herbs, flowers, fruits and seeds (aboveground parts), and animal-derived decoction pieces. The concentration ranges of five elements in underground parts were 0~7.09, 0~0.29, 0~4.1, 0~1.1 and 0~49.2 mg/kg, with exceedance rates of 0–2.3%. Aboveground parts showed ranges of 0~1.54, 0~1.02, 0~13, 0~0.96 and 0~43.4 mg/kg, with exceedance rates of 0–8.8%. Animal-derived decoction pieces showed ranges of 0.07~27.18, 0~1, 0~55, 0~4.11 and 0.23~43.9 mg/kg, with exceedance rates of 6.7–41.3%. Principal component and cluster analyses indicated distinct contamination sources between animal-derived and plant-derived materials. The pollution index showed that animal-derived materials required special attention. Among plant-derived materials, Notoginseng Radix et Rhizoma, and Artemisiae Argyi Folium were also of concern. Health risk assessment indicated low non-carcinogenic risks across all categories (HI < 1), and uncertainty analysis showed a 0% probability of HI > 1. The 95th percentile carcinogenic risk for all categories was −4. Sensitivity analysis identified metal concentrations and daily intake as key uncertainty contributors. The findings underscore distinct contamination patterns between material types, highlighting the need for targeted control strategies, including strengthened source management and standardized dosing.

Background: Polygonum orientale L. (PO) has demonstrated notable efficacy in treating coronary heart disease. Previous research identified eight key active components in PO for cardiomyocyte protection, but the underlying mechanisms remained unclear; Methods: Network pharmacology and molecular docking were used to identify potential target proteins of PO’s active components. Experimental models assessed the cardioprotective effects and mechanisms; Results: Network analysis and molecular docking revealed that the active components exhibited the highest binding affinity with SOD2, indicating it as a key element in the cardiac protection of PO. In vivo, PO extract improved myocardial structure and function, and increased SOD2 protein levels. In vitro, the active components of PO (Mixture) mitigated oxidative stress and apoptosis, upregulating SIRT3 and decreasing acetylated SOD2, leading to increased SOD2 and reduced ROS levels. The observed effects were reversed by a SIRT3 inhibitor, indicating the involvement of the SIRT3/SOD2 signaling pathway; Conclusions: This comprehensive approach elucidated the critical mechanisms underlying the cardioprotective properties of PO’s bioactive constituents, highlighting the regulation of the SIRT3/SOD2 signaling pathway as a new mechanism for PO’s anti-cardiovascular disease effects, and suggesting the Mixture’s potential as a promising drug candidate.

Introduction:Cynanchum auriculatum (CA) is usually used to treat digestive disorders, such as anorexia, enteritis, dysentery, and indigestion. Functional dyspepsia (FD) is characterized by a group of symptoms associated with the gastroduodenal region. Recent pharmacological studies have demonstrated the efficacy of CA for treating FD. However, the pharmacokinetics (PK) and tissue distribution of CA in physiological and FD states is still unclear. The present study aimed to clarify the differences in PK parameters and tissue distribution of the four major active components of CA (baishouwu benzophenone, deacylmet-aplexigenin, qingyangshengenin, and syringic acid) under both physiological and FD states.Methods: For this, normal and FD rats were orally administered 10 mg/kg CA extract. Then, plasma and tissue (heart, liver, spleen, lung, kidney, brain, stomach, and small intestine) samples were obtained. The four active components of CA in rat plasma and tissues were quantified by developing and validating a fast and reliable ultra–high–performance liquid chromatography–mass spectrometry method.Results: The area under the plasma concentration–time curve from time zero to time t (AUC_0-t) of baishouwu benzophenone was significantly lower in the FD group than in the normal group (p < 0.01). The FD group had significantly lower (p < 0.001) apparent volume of distribution and plasma clearance of qing-yangshengenin and significantly higher (p < 0.05) AUC_0-t of deacylmetaplexigenin and qingyangshengenin. The four active components were rapidly distributed into various tissues, and the main target organs of CA activity were the stomach and small intestine. In addition, baishouwu benzophenone, deacylmetaplexigenin, and qingyangshengenin could cross the blood-brain barrier, indicating that the brain may be another target organ in the treatment of FD.Discussion: These results indicate that the pathological state of FD alters the PK behavior and tissue distribution characteristics of baishouwu benzophenone, deacylmetaplexigenin, qingyangshengenin, and syringic acid in the CA extract, providing an experimental basis for the role of CA in FD treatment.

Although Polygonum orientale L. (PO) has a beneficial effect on treatment of myocardial ischemia (MI), its mechanism remains unclear. This study aimed to explore the pharmacological mechanism of PO against MI through MAPK signaling pathways. Firstly, the therapeutic effect of PO was evaluated for treatment of MI mice. Using Western blot and immunohistochemistry, the influence of PO on MAPK signaling pathways and cell apoptosis was investigated. Subsequently, one key pathway (ERK) of MAPK signaling pathways was screened out, on which PO posed the most obvious impact. Finally, an inhibitor of ERK1/2 was utilized to further verify the regulatory effect of PO on the MAPK/ERK signaling pathway. It was found that PO could reduce the elevation of the ST segment; injury of heart tissue; the activity of LDH, CK, NOS, cNOS and iNOS and the levels of NO, BNP, TNF-α and IL-6. It is notable that PO could significantly modulate the protein content of p-ERK/ERK in mice suffering from MI but hardly had an effect on p-JNK/JNK and p-p38/p38. Additionally, the expressions of bax, caspase3 and caspase9 were inhibited in heart tissue in the PO-treated group. To evaluate whether ERK1/2 inhibitor (PD98059) could block the effect of PO on treatment of MI, both PO and PD98059 were given to mice with MI. It was discovered that the inhibitor indeed could significantly reverse the regulatory effects of PO on the above indicators, indicating that PO could regulate p-ERK/ERK. This study provides experimental evidence that PO extenuates MI injury, cardiomyocyte apoptosis and inflammation by activating the MAPK/ERK signaling pathway.