ObjectiveTo investigate the mechanism of liver injury induced by tripterygium glycosides tablets （TG） and the molecular mechanism of compound glycyrrhizin tablets （CG） in alleviating the abnormalities of cholesterol metabolism caused by TG via cholesterol metabolism. MethodsAccording to the body weights， male Sprague-Dawley （SD） rats were randomly grouped as follows： control （pure water）， low-dose TG （TG-L， 189.0 mg·kg^-1·d^-1）， high-dose TG （TG-H， 472.5 mg·kg^-1·d^-1）， TG-L+CG （189.0 mg·kg^-1·d^-1 TG + 20.25 mg·kg^-1·d^-1 CG）， and TG-H+CG （472.5 mg·kg^-1·d^-1 TG + 20.25 mg·kg^-1·d^-1 CG）， with 6 rats in each group. Rats were administrated with corresponding drugs once daily for 3 weeks. At the end of the last administration， the mRNA and protein levels of liver X receptor-alpha （LXR-α）， low-density lipoprotein receptor （LDLR）， adenosine triphosphate-binding cassette transporter A1 （ABCA1）， adenosine triphosphate-binding cassette transporter G1 （ABCG1）， 3-hydroxy-3-methylglutaryl coenzyme A reductase （HMGCR）， cholesterol 7α-hydroxylase （CYP7A1）， cholesterol 12α-hydroxylase （CYP8B1）， and sterol 27-hydroxylase （CYP27A1） in the liver tissue were determined by Real-time PCR and Western blotting， respectively. The level of 3-hydroxy-3-methylglutaryl coenzyme A reductase （HMG-CoAR）， a regulatory enzyme of cholesterol synthesis， was measured by enzyme-linked immunosorbent assay （ELISA）. HepG2 cells were used to observe the effect of TG on the cell proliferation in vitro. Specifically， HepG2 cells were grouped as follows： Low-dose TG （TG-l， 15 mg·L^-1）， medium-dose TG （TG-m， 45 mg·L^-1）， high-dose TG （TG-h， 135 mg·L^-1）， fenofibrate （FB， 10 μmol·L^-1）， CG extract， TG-h+FB （135 mg·L^-1 TG + 10 μmol·L^-1 FB）， TG-m+FB （45 mg·L^-1 TG + 10 μmol·L^-1 FB）， TG-l+FB （15 mg·L^-1 TG + 10 μmol·L^-1 FB）， TG-h+CG （135 mg·L^-1 TG + 60 μmol·L^-1 CG）， TG-m+CG （45 mg·L^-1 TG + 60 μmol·L^-1 CG）， and TG-l+CG （15 mg·L^-1 TG + 60 μmol·L^-1 CG）. The mRNA and protein levels of LXR-α， ABCG1， LDLR， CYP7A1， CYP8B1， and CYP27A1 in HepG2 cells were determined by Real-time PCR and Western blotting， respectively. ResultsThe rat experiment showed that compared with the control group， the TG-H group showed down-regulated mRNA levels of CYP7A1， CYP8B1， and CYP27A1 in the liver tissue （P<0.05， P<0.01）， which were up-regulated by the application of CG （P<0.05， P<0.01）， and the TG-H+CG group showed up-regulated mRNA level of LDLR （P<0.01）. Compared with the control group， the TG-L and TG-H groups showed down-regulated protein levels of LDLR， CYP7A1， and CYP8B1 in the liver tissue （P<0.05， P<0.01）. In addition， the protein levels of ABCG1 and LXR-α were down-regulated in the TG-H and TG-L groups， respectively （P<0.05）. Compared with TG alone， TG+CG up-regulated the protein levels of ABCG1 and LDLR （P<0.05， P<0.01）， and the protein levels of CYP7A1 and CYP8B1 in the TG-H+CG group were up-regulated （P<0.05， P<0.01）. The cell experiment showed that compared with the control group， the TG-h group presented up-regulated mRNA level of LXR-α （P<0.01）， and the TG-m and TG-h groups showcased down-regulated mRNA levels of LDLR and CYP7A1 （P<0.01） and up-regulated mRNA level of CYP27A1 （P<0.01） in HepG2 cells. The combination of CG with TG restored the above changes （P<0.01）. Western blotting results showed that compared with the control group， the TG-m and TG-h groups showed down-regulated protein levels of LXR-α， ABCG1， LDLR， CYP7A1， CYP8B1， and CYP27A1 in HepG2 cells （P<0.01）. Compared with the TG-h group， the TG-h+CG group showed up-regulated protein level of LDLR （P<0.05）. Compared with the TG-m group， the TG-m+CG group showcased up-regulated protein levels of LDLR， ABCG1， CYP7A1， and CYP27A1 （P<0.05， P<0.01）. ConclusionThe administration of TG at 189.0， 472.5 mg·kg^-1 for 3 weeks could modulate the signaling pathways associated with cholesterol efflux， endocytosis， and cholesterol biotransformation in hepatocytes， leading to the accumulation of cholesterol and subsequent liver injury in rats. CG could ameliorate the liver injury induced by lipid metabolism disorders caused by TG by up-regulating the expression of LXR-α， LDLR， ABCG1， CYP7A1， CYP8B1， and CYP27A1 to promote cholesterol biotransformation.

Background: Breast cancer is a common malignant tumor that has a high tendency to metastasis to the bone, leading to cancer-induced bone pain (CIBP). Ghrelin can not only stimulate appetite and regulate energy balance, but also alleviate CIBP by inducing NPY expression. Octanoic acid (OA), a type of medium chain fatty acids, provides an energy substrate and promotes acylation of ghrelin. However, it remains to be elucidated whether an OA-rich diet can alleviate CIBP by activating the acyl-ghrelin/NPY pathway. Methods: First, thirty-six Sprague–Dawley rats were randomly divided into the sham, CIBP, CIBP + OA (20), CIBP + OA (40), CIBP + OA (60) and CIBP + OA (80) groups to investigate the effects of diets with different ratios of OA on CIBP and the acyl-ghrelin/NPY pathway. Next, a ghrelin O-acyltransferase (GOAT) inhibitor was exogenously administered to investigate whether an OA-rich diet alleviated CIBP through increasing the level of acyl-ghrelin and activating the acyl-ghrelin/NPY pathway. Results: An OA-rich diet significantly alleviated nociceptive behaviors and increased the levels of acyl-ghrelin and NPY in a dose-dependent manner in cancer-bearing rats. With the exogenous administration of the GOAT inhibitor, the beneficial effects of an OA-rich diet on the acyl-ghrelin/NPY pathway and its pain-relieving effects were attenuated. Conclusions An OA-rich diet could alleviate CIBP through increasing the level of acyl-ghrelin and activating the acylghrelin/NPY pathway.

Epilepsy is a chronic neurological disease caused by abnormal synchronous discharge of the brain, which is characterized by recurrent and transient neurological abnormalities, mainly manifested as loss of consciousness and limb convulsions, and can occur in people of all ages. At present, anti-epileptic drugs (AEDs) are still the main means of treatment, but their efficacy is limited by the problem of drug resistance, and long-term use can cause serious side effects, such as cognitive dysfunction and vital organ damage. Although surgical resection of epileptic lesions has achieved certain results in some patients, the high cost and potential risk of neurological damage limit its scope of application. Therefore, the development of safe, accurate and personalized non-invasive treatment strategies has become one of the key directions of epilepsy research. In recent years, photobiomodulation (PBM) has gained significant attention as a promising non-invasive therapeutic approach. PBM uses light of specific wavelengths to penetrate tissues and interact with photosensitive molecules within cells, thereby modulating cellular metabolic processes. Research has shown that PBM can enhance mitochondrial function, promote ATP production, improve meningeal lymphatic drainage, reduce neuroinflammation, and stimulate the growth of neurons and synapses. These biological effects suggest that PBM not only holds the potential to reduce the frequency of seizures but also to improve the metabolic state and network function of neurons, providing a novel therapeutic avenue for epilepsy treatment. Compared to traditional treatment methods, PBM is non-invasive and avoids the risks associated with surgical interventions. Its low risk of significant side effects makes it particularly suitable for patients with drug-resistant epilepsy, offering new therapeutic options for those who have not responded to conventional treatments. Furthermore, PBM’s multi-target mechanism enables it to address a variety of complex etiologies of epilepsy, demonstrating its potential in precision medicine. In contrast to therapies targeting a single pathological mechanism, PBM’s multifaceted approach makes it highly adaptable to different types of epilepsy, positioning it as a promising supplementary or alternative treatment. Although animal studies and preliminary clinical trials have shown positive outcomes with PBM, its clinical application remains in the exploratory phase. Future research should aim to elucidate the precise mechanisms of PBM, optimize light parameters, such as wavelength, dose, and frequency, and investigate potential synergistic effects with other therapeutic modalities. These efforts will be crucial for enhancing the therapeutic efficacy of PBM and ensuring its safety and consistency in clinical settings. This review summarizes the types of epilepsy, diagnostic biomarkers, the advantages of PBM, and its mechanisms and potential applications in epilepsy treatment. The unique value of PBM lies not only in its multi-target therapeutic effects but also in its adaptability to the diverse etiologies of epilepsy. The combination of PBM with traditional treatments, such as pharmacotherapy and neuroregulatory techniques, holds promise for developing a more comprehensive and multidimensional treatment strategy, ultimately alleviating the treatment burden on patients. PBM has also shown beneficial effects on neural network plasticity in various neurodegenerative diseases. The dynamic remodeling of neural networks plays a critical role in the pathogenesis and treatment of epilepsy, and PBM’s multi-target mechanism may promote brain function recovery by facilitating neural network remodeling. In this context, optimizing optical parameters remains a key area of research. By adjusting parameters such as wavelength, dose, and frequency, researchers aim to further enhance the therapeutic effects of PBM while maintaining its safety and stability. Looking forward, interdisciplinary collaboration, particularly in the fields of neuroscience, optical engineering, and clinical medicine, will drive the development of PBM technology and facilitate its transition from laboratory research to clinical application. With the advancement of portable devices, PBM is expected to provide safer and more effective treatments for epilepsy patients and make a significant contribution to personalized medicine, positioning it as a critical component of precision therapeutic strategies.

Background: Breast cancer is a common malignant tumor that has a high tendency to metastasis to the bone, leading to cancer-induced bone pain (CIBP). Ghrelin can not only stimulate appetite and regulate energy balance, but also alleviate CIBP by inducing NPY expression. Octanoic acid (OA), a type of medium chain fatty acids, provides an energy substrate and promotes acylation of ghrelin. However, it remains to be elucidated whether an OA-rich diet can alleviate CIBP by activating the acyl-ghrelin/NPY pathway. Methods: First, thirty-six Sprague–Dawley rats were randomly divided into the sham, CIBP, CIBP + OA (20), CIBP + OA (40), CIBP + OA (60) and CIBP + OA (80) groups to investigate the effects of diets with different ratios of OA on CIBP and the acyl-ghrelin/NPY pathway. Next, a ghrelin O-acyltransferase (GOAT) inhibitor was exogenously administered to investigate whether an OA-rich diet alleviated CIBP through increasing the level of acyl-ghrelin and activating the acyl-ghrelin/NPY pathway. Results: An OA-rich diet significantly alleviated nociceptive behaviors and increased the levels of acyl-ghrelin and NPY in a dose-dependent manner in cancer-bearing rats. With the exogenous administration of the GOAT inhibitor, the beneficial effects of an OA-rich diet on the acyl-ghrelin/NPY pathway and its pain-relieving effects were attenuated. Conclusions An OA-rich diet could alleviate CIBP through increasing the level of acyl-ghrelin and activating the acylghrelin/NPY pathway.

Background: Breast cancer is a common malignant tumor that has a high tendency to metastasis to the bone, leading to cancer-induced bone pain (CIBP). Ghrelin can not only stimulate appetite and regulate energy balance, but also alleviate CIBP by inducing NPY expression. Octanoic acid (OA), a type of medium chain fatty acids, provides an energy substrate and promotes acylation of ghrelin. However, it remains to be elucidated whether an OA-rich diet can alleviate CIBP by activating the acyl-ghrelin/NPY pathway. Methods: First, thirty-six Sprague–Dawley rats were randomly divided into the sham, CIBP, CIBP + OA (20), CIBP + OA (40), CIBP + OA (60) and CIBP + OA (80) groups to investigate the effects of diets with different ratios of OA on CIBP and the acyl-ghrelin/NPY pathway. Next, a ghrelin O-acyltransferase (GOAT) inhibitor was exogenously administered to investigate whether an OA-rich diet alleviated CIBP through increasing the level of acyl-ghrelin and activating the acyl-ghrelin/NPY pathway. Results: An OA-rich diet significantly alleviated nociceptive behaviors and increased the levels of acyl-ghrelin and NPY in a dose-dependent manner in cancer-bearing rats. With the exogenous administration of the GOAT inhibitor, the beneficial effects of an OA-rich diet on the acyl-ghrelin/NPY pathway and its pain-relieving effects were attenuated. Conclusions An OA-rich diet could alleviate CIBP through increasing the level of acyl-ghrelin and activating the acylghrelin/NPY pathway.

Background: Breast cancer is a common malignant tumor that has a high tendency to metastasis to the bone, leading to cancer-induced bone pain (CIBP). Ghrelin can not only stimulate appetite and regulate energy balance, but also alleviate CIBP by inducing NPY expression. Octanoic acid (OA), a type of medium chain fatty acids, provides an energy substrate and promotes acylation of ghrelin. However, it remains to be elucidated whether an OA-rich diet can alleviate CIBP by activating the acyl-ghrelin/NPY pathway. Methods: First, thirty-six Sprague–Dawley rats were randomly divided into the sham, CIBP, CIBP + OA (20), CIBP + OA (40), CIBP + OA (60) and CIBP + OA (80) groups to investigate the effects of diets with different ratios of OA on CIBP and the acyl-ghrelin/NPY pathway. Next, a ghrelin O-acyltransferase (GOAT) inhibitor was exogenously administered to investigate whether an OA-rich diet alleviated CIBP through increasing the level of acyl-ghrelin and activating the acyl-ghrelin/NPY pathway. Results: An OA-rich diet significantly alleviated nociceptive behaviors and increased the levels of acyl-ghrelin and NPY in a dose-dependent manner in cancer-bearing rats. With the exogenous administration of the GOAT inhibitor, the beneficial effects of an OA-rich diet on the acyl-ghrelin/NPY pathway and its pain-relieving effects were attenuated. Conclusions An OA-rich diet could alleviate CIBP through increasing the level of acyl-ghrelin and activating the acylghrelin/NPY pathway.

Background: Breast cancer is a common malignant tumor that has a high tendency to metastasis to the bone, leading to cancer-induced bone pain (CIBP). Ghrelin can not only stimulate appetite and regulate energy balance, but also alleviate CIBP by inducing NPY expression. Octanoic acid (OA), a type of medium chain fatty acids, provides an energy substrate and promotes acylation of ghrelin. However, it remains to be elucidated whether an OA-rich diet can alleviate CIBP by activating the acyl-ghrelin/NPY pathway. Methods: First, thirty-six Sprague–Dawley rats were randomly divided into the sham, CIBP, CIBP + OA (20), CIBP + OA (40), CIBP + OA (60) and CIBP + OA (80) groups to investigate the effects of diets with different ratios of OA on CIBP and the acyl-ghrelin/NPY pathway. Next, a ghrelin O-acyltransferase (GOAT) inhibitor was exogenously administered to investigate whether an OA-rich diet alleviated CIBP through increasing the level of acyl-ghrelin and activating the acyl-ghrelin/NPY pathway. Results: An OA-rich diet significantly alleviated nociceptive behaviors and increased the levels of acyl-ghrelin and NPY in a dose-dependent manner in cancer-bearing rats. With the exogenous administration of the GOAT inhibitor, the beneficial effects of an OA-rich diet on the acyl-ghrelin/NPY pathway and its pain-relieving effects were attenuated. Conclusions An OA-rich diet could alleviate CIBP through increasing the level of acyl-ghrelin and activating the acylghrelin/NPY pathway.

ObjectiveTo improve the quality standard of Yuanhu Zhitong oral liquid in order to strengthen the quality control of this oral liquid. MethodThin layer chromatography（TLC） was used for the qualitative identification of Corydalis Rhizoma and Angelicae Dahuricae Radix in Yuanhu Zhitong oral liquid by taking tetrahydropalmatine， corydaline reference substances and Corydalis Rhizoma reference medicinal materials as reference， and cyclohexane-trichloromethane-methanol（5∶3∶0.5） as developing solvent， Corydalis Rhizoma was identified using GF254 glass thin layer plate under ultraviolet light（365 nm）. And taking petroleum ether（60-90 ℃） -ether-formic acid（10∶10∶1） as developing solvent， Angelicae Dahuricae Radix was identified using a silica gel G TLC plate under ultraviolet light（305 nm）. High performance liquid chromatography（HPLC） was performed on a Waters XSelect HSS T3 column（4.6 mm×250 mm， 5 μm） with acetonitrile（A）-0.1% glacial acetic acid solution（adjusted pH to 6.1 by triethylamine）（B） as the mobile phase for gradient elution（0-10 min， 20%-30%A； 10-25 min， 30%-40%A； 25-40 min， 40%-50%A； 40-60 min， 50%-60%A）， the detection wavelength was set at 280 nm， then the fingerprint of Yuanhu Zhitong oral liquid was established， and the contents of tetrahydropalmatine and corydaline were determined. ResultIn the thin layer chromatograms， the corresponding spots of Yuanhu Zhitong oral liquid， the reference substances and reference medicinal materials were clear， with good separation and strong specificity. A total of 12 common peaks were identified in 10 batches of Yuanhu Zhitong oral liquid samples， and the peaks of berberine hydrochloride， dehydrocorydaline， glaucine， tetrahydropalmatine and corydaline. The similarities between the 10 batches of samples and the control fingerprint were all >0.90. The results of determination showed that the concentrations of corydaline and tetrahydropalmatine had good linearity with paek area in the range of 0.038 6-0.193 0， 0.034 0-0.170 0 g·L^-1， respectively. The methodological investigation was qualified， and the contents of corydaline and tetrahydropalmatine in 10 batches of Yuanhu Zhitong oral liquid samples were 0.077 5-0.142 9、0.126 1-0.178 2 g·L^-1， respectively. ConclusionThe established TLC， fingerprint and determination are simple， specific and reproducible， which can be used to improve the quality control standard of Yuanhu Zhitong oral liquid.

Idiosyncratic drug-induced liver injury (IDILI) has long posed a challenging and pivotal concern in pharmaceutical research. The complex composition of traditional Chinese medicine (TCM) has introduced a bottleneck in current research, hindering the elucidation of the component basis associated with IDILI in TCM. Using Epimedii Folium (EF) and Psoraleae Fructus (PF) as illustrative examples, this study endeavors to establish an in vitro evaluation model, providing a high-throughput and preliminary assessment method for screening components related to TCM-induced IDILI. A TNF-α-mediated HepG2 susceptible model was first established in this study, with the focus on the index components present in EF and PF. The release of lactate dehydrogenase (LDH) in the cell supernatant served as the detection index. A concentration-toxicity response curve was constructed, and the hepatotoxic components of EF and PF were identified utilizing the synergistic toxicity index. The LDH results unveiled the hepatotoxic effects of bavachin, backuchiol, isobavachin, neobavaisoflavone, psoralidin, isobavachalcone, icarisid I, and icarisid II on both normal and susceptible cells, categorizing these 8 components as both direct hepatotoxicity components and idiosyncratic hepatotoxicity components. Bavachin and neobavaisoflavone exhibited no hepatotoxicity on normal cells but demonstrated significant effects on susceptible cells, designating them as potential idiosyncratic susceptible hepatotoxicity components. The study further delineated that 10 EF components and 3 PF components were direct immune-promoting hepatotoxicity components. Additionally, 14 idiosyncratic immune-promoting hepatotoxicity components were identified, encompassing 10 EF components and 4 PF components, with neobavaisoflavone, bavachinin, and isobavachin being potential idiosyncratic susceptible immune-promoting hepatotoxicity components. Synergistic toxicity index results indicated that 13 idiosyncratic immune-promoting hepatotoxicity components (except anhydroicaritin) combined with bavachin demonstrated synergistic hepatotoxicity on susceptible cells. Notably, 3 idiosyncratic susceptible immune-promoting hepatotoxicity components combined with bavachin exhibited synergistic hepatotoxicity, with neobavaisoflavone displaying the highest synergistic toxicity index and bavachinin the lowest. In summary, this methodology successfully screens hepatotoxic and immune-promoting hepatotoxic components in EF and PF, distinguishing the types of components inducing hepatotoxicity, evaluating the hepatotoxicity degree of each component, and elucidating the synergistic relationships among them. Importantly, these findings align with the characteristics of IDILI. The method provides an effective model tool for the fundamental research of TCM-related IDILI components.

Objective To investigate the impact of silymarin(SM)on the malignant growth of glioma cells and the regulatory mechanism on the miR-124-3p/WEE1 axis.Methods Glioma U87 cells were grouped into control,SM low,medium,and high concentration groups,and SM high concentration + miR-124-3p inhibitor group(SM high + miR-124-3p inhibitor group).CCK-8 was used to measure the proli-feration rate of cells;Transwell? assay was applied to assay the migration and invasion of cells;cell cycle progression was detected by flow cytometry;Western blotting was applied to measure the expression of cyclin D1 and apoptosis-related proteins;the levels of miR-124-3p and WEE1 mRNA were determined by qRT-PCR;and a luciferase activity test was applied to verify the targeting relationship between miR-124-3p and WEE1;in addition,the establishment,administration,and analysis of a NOD/SCID mouse model of intracranial trans-planted tumor were conducted.Results Compared with the control group,the cell proliferation,the numbers of migrating and invading cells,the expression of cyclin D1,and the level of WEE1 mRNA in the various SM treatment groups decreased,the number of cells in G0/G1 phase,the expression of cleaved caspase-8,cleaved caspase-9,cleaved caspase-3 and miR-124-3p increased(P＜0.05);furthermore,transfection of miR-124-3p inhibitor reversed the inhibitory effect of SM on the malignant behavior of glioma cells.In vivo experiments with mice showed that the weights and volumes of tumors in the SM treatment group were lower than those in the model group(P＜0.05),and there was no discernible change in the weight of the mice(P＞0.05).Conclusion SM can inhibit the malignant growth of glioma cells by upregulating miR-124-3p and downregulating WEE1.