Glutamate-induced excitotoxicity has been implicated in a variety of neuronal degenerative disorders. In the present study, we investigated the possible neuroprotective effects of schizandrin against apoptosis of primary cultured rat cortical cells induced by glutamate. Glutamate (10 μM) administered for 24 h decreased the expression of Bcl-2 and Bcl-X_L protein, whereas increased the expression of Bax, Bak, apoptosis inducing factor (AIF), endonuclease G (Nodo G) and endoplasmic reticulum (ER) stress of caspase-12. Pretreatment with schizandrin (100 μM) before glutamate treatment increased the Bcl-X_L and Bcl-2 expression and decreased Bax, Bak, AIF, Nodo G and caspase-12 compared with those only treated with glutamate. Furthermore, glutamate-induced phosphorylation of JNK, p38 and ERK mitogen-activated protein kinases (MAPK), and these effects were attenuated by schizandrin (100 μM) treatment. These results suggest that schizandrin possesses the neuroprotective effects. The molecular mechanisms of schizandrin against glutamate-induced apoptosis may involve the regulation of Bcl-2 family proteins expression, and ER stress through blocking the activation of JNK, ERK and p38 MAPK.

Species of Cirsium (Asteraceae family) have been used in folk hepatoprotective medicine in Taiwan. We collected four Cirsium species—including the aerial part of Cirsium arisanense (CAH), the aerial part of Cirsium kawakamii (CKH), the flower part of Cirsium japonicum DC. var. australe (CJF), and Cirsii Herba (CH)—and then made extractions from them with 70% methanol. We compared the antioxidant contents and activities of these four Cirsium species extracts by a spectrophotometric method and high-performance liquid chromatography–photodiode array detector (HPLC-DAD). We further evaluated the hepatoprotective effects of these extracts on CCl₄-induced acute liver damage in C57BL/6 mice. The present study found CAH possesses the highest antioxidant activity among the four Cirsium species, and these antioxidant activities are closely related to phenylpropanoid glycoside (PPG) contents. The extracts decreased serum ALT and AST levels elevated by injection with 0.2% CCl₄. However, only CJF and CH decreased hepatic necrosis. Silibinin decreased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and hepatic necrosis caused by CCl₄. CJF and CH restored the activities of hepatic antioxidant enzymes and decreased hepatic malondialdehyde (MDA) levels. CJF further restored the expression of hepatic antioxidant enzymes including Cu/Zn-superoxide dismutase (Cu/Zn-SOD), Mn-superoxide dismutase (Mn-SOD), and glutathione S-transferase (GST) proteins. HPLC chromatogram indicated that CKH, CJF, and CH contained silibinin diastereomers (α and β). Only CJF contained diosmetin. Hence, the hepatoprotective mechanism of CJF against CCl₄-induced acute liver damage might be involved in restoring the activities and protein expression of the hepatic antioxidant defense system and inhibiting hepatic inflammation, and these hepatoprotective effects are related to the contents of silibinin diastereomers and diosmetin.

Introduction: Yi-Gan-San, Parkinson's disease, tremor-dominant, network pharmacology, molecular docking, Uncaria rhynchophylla. Methods: We identified 75 active compounds within YGS. From these, we predicted 110 gene targets, which exhibited a direct association with PD-DT. PPI network results highlighted core target proteins, including TP53, SLC6A3, GAPDH, MAOB, AKT, BAX, IL6, BCL2, PKA, and CASP3. These proteins potentially alleviate PD-DT by targeting inflammation, modulating neuronal cell apoptosis, and regulating the dopamine system. Furthermore, GO and KEGG enrichment analyses emphasized that YGS might influence various mechanisms, such as the apoptotic process, mitochondrial autophagy, Age-Rage signaling, and dopaminergic and serotonergic synapses. The core proteins from the PPI analysis were selected for the docking experiment. Results: The docking results demonstrated that the most stable ligand-receptor conformations were kaempferol with CASP3 (-9.5 kcal/mol), stigmasterol with SLC6A3 (-10.5 kcal/mol), shinpterocarpin with BCL2L1 (-9.6 kcal/mol), hirsutine with MAOB (-9.7 kcal/mol), hederagenin with PRKACA (-9.8 kcal/mol), and yatein with GAPDH (-9.8 kcal/mol). These results provide us with research objectives for future endeavors in extracting single compounds for drug manufacturing or in-depth studies on drug mechanisms. Conclusion: From these computational findings, we suggested that YGS might mitigate PD-DT via “multi-compounds, multi-targets, and multi-pathways.”

H elminthostachys zeylanica (L.) hook (HZ), has recently gained attention as a potential herbal supplement for managing ulcerative colitis (UC) through its bioactive compounds. To comprehensively investigate HZ's therapeutic effects and underlying mechanisms on UC, we utilized network pharmacology and in vitro and in vivo analyses. The therapeutic potential of HZ was evaluated using a DSS‐induced mouse model of ulcerative colitis, alongside in vitro cellular studies. A network pharmacology approach was first used to predict the active compounds and molecular targets of HZ. Subsequently, integrated experimental techniques—including ELISA, Western blotting, histological analysis, immunofluorescence, flow cytometry, and molecular docking—were employed to validate and support the predicted mechanisms. Network pharmacology analysis identified 15 active compounds in HZ, contributing to its multi‐target synergistic activity and anti‐inflammatory effects. HZ was found to modulate multiple inflammatory pathways, particularly the Toll‐like receptor 4 (TLR4) and NF‐κB signaling pathways, regulating vital inflammatory mediators such as tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6), and interleukin‐1β (IL‐1β), emphasizing its therapeutic potential in UC. ELISA, Western blot, and histological analyses confirmed that HZ significantly reduced colon inflammation. Immunofluorescence and flow cytometry analyses also demonstrated that HZ alleviated inflammation by regulating TLR4/NF‐κB and CD3 signaling pathways without involving apoptosis. Ultimately, molecular docking further identified core compounds, including Ugonin M, O, K, and R, which exhibited strong binding affinity to critical proteins in the TLR4/NF‐κB pathway, such as TAK1, IKKβ, and RELA, underscoring their role in HZ's anti‐inflammatory mechanisms. Collectively, these findings provide a solid basis for further investigation into the mechanistic effects and broader clinical potential of HZ as a therapeutic approach for UC.