• Biomolecules & Therapeutics
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• v.32 no.5
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• pp.647-657
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• 2024

Gefitinib is the well-tolerated first-line treatment of non-small cell lung cancer. As it needs analgesics during oncology treatment, particularly in the context of the coronavirus disease, where patients are more susceptible to contract high fever and sore throat. This has increased the likelihood of taking both gefitinib and antipyretic analgesic acetaminophen (APAP). Given that gefitinib and APAP overdose can predispose patients to liver injury or even acute liver failure, there is a risk of severe hepatotoxicity when these two drugs are used concomitantly. However, little is known regarding their safety at therapeutic doses. This study simulated the administration of gefitinib and APAP at clinically relevant doses in an animal model and confirmed that gefitinib in combination with APAP exhibited additional hepatotoxicity. We found that gefitinib plus APAP significantly exacerbated cell death, whereas each drug by itself had little or minor effect on hepatocyte survival. Mechanistically, combination of gefitinib and APAP induces hepatocyte death via the apoptotic pathway obviously. Reactive oxygen species (ROS) generation and DNA damage accumulation are involved in hepatocyte apoptosis. Gefitinib plus APAP also promotes the expression of Kelch-like ECH-associated protein 1 (Keap1) and downregulated the antioxidant factor, Nuclear factor erythroid 2-related factor 2 (Nrf2), by inhibiting p62 expression. Taken together, this study revealed the potential ROS-mediated apoptosis-dependent hepatotoxicity effect of the combination of gefitinib and APAP, in which the p62/Keap1/Nrf2 signaling pathway participates and plays an important regulatory role.

• The Journal of Internal Korean Medicine
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• v.40 no.3
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• pp.295-311
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• 2019

Objectives: This research aimed to investigate Chinese clinical studies on the treatment of central post-stroke pain (CPSP) and thalamic syndrome after stroke with traditional herbal medicine (THM). Methods: Randomized controlled trials verifying the effects of herbal medicine on treating CPSP and thalamic syndrome after stroke were included in the study. Electrical and hand search were conducted in the China National Knowledge Infrastructure (CNKI), National Discovery for Science Leaders (NDSL), Research Information Sharing Service (RISS), Oriental Medicine Advanced Searching Integrated System (Oasis) for CPSP and thalamic syndrome after stroke. A literature search was performed in the Chinese and Korean databases for papers published from January 1, 2010 to October 1, 2018. The selected literature was assessed by Cochrane's risk of bias. Results: Twelve reports on randomized controlled trials met the inclusion criteria from the 227 identified reports. Effective rate, comparison of visual analogy scale, present pain intensity, pain grading index, recurrence rate, follow-up, and a 36-item short form survey instrument were used to evaluate the treatments. The effective rate of the treatment group was significantly higher than that of the control group in all papers. Side effects occurred less frequently in the treatment group than in the western medicine control group. Conclusions: The treatment of CPSP and thalamic syndrome after stroke with THM was shown to be highly effective. Additional well-designed clinical trials are needed. This study can be used as a basis for further research on the treatment of CPSP and thalamic syndrome after stroke.

• The Journal of Korean Obstetrics and Gynecology
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• v.32 no.3
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• pp.227-244
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• 2019

Objectives: To evaluate the effectiveness and safety of application of Traditional East Asian Herbal Medicine (TEAM) in the treatment of Atrophic Vaginitis (AV). Methods: Randomized Controlled Trials (RCTs) were obtained from PubMed, Cochrane Library, Embase, CNKI, RISS, NDSL, and KISS. The risk of bias was assessed by using Cochrane's risk of bias tool, and RevMan 5.3 software was used. Results: 26 RCTs with 3,162 patients were identified and reviewed. Among them, 21 RCTs observe the effect of integrated traditional Chinese and Western medicine. 23 RCTs reported treatment groups was statistically effective than control groups in the study. Also, the recurrence rate was estimated in 10 RCTs and was lower than control groups. 12 studies observed adverse events (AEs) and severe AEs were not reported. Conclusions: This review suggested that TEAM was safe and effective in the treatment of AV. TEAM may also decrease the recurrence rate. However, this could not be proven conclusively. To ensure evidence-based clinical practice, well-designed trials with larger sample sizes are needed.

• Journal of Ginseng Research
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• v.46 no.5
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• pp.666-674
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• 2022

Background: Ginsenosides and their metabolites have antidepressant-like effects, but the underlying mechanisms remain unclear. We previously identified 14-3-3 ζ as one of the target proteins of 20 (S)-protopanaxadiol (PPD), a fully deglycosylated ginsenoside metabolite. Methods: Corticosterone (CORT) was administered repeatedly to induce the depression model, and PPD was given concurrently. The tail suspension test (TST) and the forced swimming test (FST) were used for behavioral evaluation. All mice were sacrificed. Golgi-cox staining, GSK 3β activity assay, and Western blot analysis were performed. In vitro, the kinetic binding analysis with the Biolayer Interferometry (BLI) was used to determine the molecular interactions. Results: TST and FST both revealed that PPD reversed CORT-induced behavioral deficits. PPD also ameliorated the CORT-induced expression alterations of hippocampal Ser9 phosphorylated glycogen synthase kinase 3β (p-Ser9 GSK 3β), Ser133 phosphorylated cAMP response element-binding protein (p-Ser133 CREB), and brain-derived neurotrophic factor (BDNF). Moreover, PPD attenuated the CORT-induced increase in GSK 3β activity and decrease in dendritic spine density in the hippocampus. In vitro, 14-3-3 ζ protein specifically bound to p-Ser9 GSK 3β polypeptide. PPD promoted the binding and subsequently decreased GSK 3β activity. Conclusion: These findings demonstrated the antidepressant-like effects of PPD on the CORT-induced mouse depression model and indicated a possible target-based mechanism. The combination of PPD with the 14-3-3 ζ protein may promote the binding of 14-3-3 ζ to p-GSK 3β (Ser9) and enhance the inhibition of Ser9 phosphorylation on GSK 3β kinase activity, thereby activating the plasticity-related CREBeBDNF signaling pathway.

• The Journal of Korean Obstetrics and Gynecology
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• v.34 no.4
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• pp.46-61
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• 2021

Objectives: The purpose of this review is to overview the studies of traditional herbal medicine for chronic pelvic inflammatory disease. Methods: We searched relevant studies using seven databases (The Journal of Korean obstetrics & gynecology, National Digital Science Library (NDSL), Research Information Sharing Service (RISS), Oriental Medicine Advanced Searching Integrated System (OASIS), Pubmed, Cochrane, Chinese National Knowledge Infrastructure (CNKI)). Data retrieval was carried out on April 5, 2021 and the papers published from January 1, 2015 to March 31, 2021 were included. The risk of bias was assessed by using Cochrane's risk of bias tool. Results: 524 studies were searched in domestic and foreign databases, and 7 studies were finally selected. In all studies, the treatment group was treated with oral traditional herbal medicine and the control group was treated with western medicine. Although the evaluation index was slightly different for each study, all studies used total efficacy rate index. In all 7 studies, the treatment group was more effective than the control group. Conclusions: Traditional herbal medicine can be an effective option in treating chronic pelvic inflammatory disease. Further high quality studies which include large number should be carried out to confirm the evidence and safety of traditional herbal medicine treatment.

• Journal of Oriental Neuropsychiatry
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• v.33 no.3
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• pp.301-316
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• 2022

Objectives: To compare Korean medicine (KM) and traditional Chinese medicine (TCM) psychotherapy for anxiety. Methods: Databases including MEDLINE (via PubMed), EMBASE (via Elsevier), Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, and Oriental Medicine Advanced Searching Integrated System were comprehensively searched. Prospective clinical studies on KM or TCM psychotherapy for patients with anxiety disorder or individuals with elevated anxiety levels published up to August 3, 2022 were reviewed. Psychotherapy was divided into counselling, art therapy, and meditation according to its characteristics. Results: A total of 12 clinical studies were reviewed, including nine randomized controlled trials. The most common disorder investigated was post-traumatic stress disorder. Ten studies used TCM psychotherapy and two used KM psychotherapy. As for differences between TCM psychotherapy and KM psychotherapy, TCM psychotherapy utilized pattern identification in the procedure more actively than KM psychotherapy. In addition, some TCM studies have attempted to directly converge Western psychotherapy (i.e., hypnosis) and Eastern psychotherapy (i.e., Taoin qigong therapy). In the case of KM psychotherapy, there was an attempt to incorporate psychotherapy with Sasang constitutional medicine. Reported effects of TCM psychotherapy and KM psychotherapy on anxiety were positive. Conclusions: Research status of KM psychotherapy and TCM psychotherapy for anxiety was investigated, revealing some of their characteristics, commonalities, and differences. Findings of this review have the potential to provide a clue to the development of conventional KM psychotherapy and new medical technology for KM psychotherapy.

• Nutrition Research and Practice
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• v.17 no.6
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• pp.1070-1083
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• 2023

BACKGROUND/OBJECTIVES: Sanghuangporus sanghuang (SS) has various medicinal effects, including anti-inflammation and anticancer activities. Despite the extensive research on SS, its molecular mechanisms of action on lung cancer are unclear. This study examined the impact of an SS alcohol extract (SAE) on lung cancer using in vitro and in vivo models. MATERIALS/METHODS: Different concentrations of SAE were used to culture lung cancer cells (A549 and H1650). A cell counting kit-8 assay was used to detect the survival ability of A549 and H1650 cells. A scratch assay and transwell cell invasion assay were used to detect the migration rate and invasive ability of SAE. Western blot analysis was used to detect the expression of B-cell lymphoma-2 (Bcl-2), Bcl2-associated X (Bax), cyclin D1, cyclin-dependent kinases 4 (CDK4), signal transducer and activator of transcription 3 (STAT3), and phosphorylated STAT3 (p-STAT3). Lung cancer xenograft mice were used to detect the inhibiting ability of SAE in vivo. Hematoxylin and eosin staining and immunohistochemistry were used to detect the effect of SAE on the structural changes to the tumor and the expression of Bcl-2, Bax, cyclin D1, CDK4, STAT3, and p-STAT3 in lung cancer xenograft mice. RESULTS: SAE could inhibit lung cancer proliferation significantly in vitro and in vivo without cytotoxicity. SAE suppressed the viability, migration, and invasion of lung cancer cells in a dose and time-dependent manner. The SAE treatment significantly decreased the proapoptotic Bcl-2/Bax ratio and the expression of pro-proliferative proteins Cyclin D1 and CDK4 in vitro and in vivo. Furthermore, SAE also inhibited STAT3 expression. CONCLUSIONS: SAE reduced the cell viability and suppressed cell migration and invasion in human lung cancer cells. Moreover, SAE also exhibited anti-proliferation effects in vivo. Therefore, SAE may have benefits in cancer therapy.

• Journal of Ginseng Research
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• v.45 no.4
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• pp.465-472
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• 2021

Background: Ginseng can help regulate brain excitability, promote learning and memory, and resist cerebral ischemia in the central nervous system. Ginsenosides are the major effective compounds of Ginseng, but their protein targets in the brain have not been determined. Methods: We screened proteins that interact with the main components of ginseng (ginsenosides) by affinity chromatography and identified the 14-3-3 ζ protein as a potential target of ginsenosides in brain tissues. Results: Biolayer interferometry (BLI) analysis showed that 20(S)-protopanaxadiol (PPD), a ginseng saponin metabolite, exhibited the highest direct interaction to the 14-3-3 ζ protein. Subsequently, BLI kinetics analysis and isothermal titration calorimetry (ITC) assay showed that PPD specifically bound to the 14-3-3 ζ protein. The cocrystal structure of the 14-3-3 ζ protein-PPD complex showed that the main interactions occurred between the residues R56, R127, and Y128 of the 14-3-3 ζ protein and a portion of PPD. Moreover, mutating any of the above residues resulted in a significant decrease of affinity between PPD and the 14-3-3 ζ protein. Conclusion: Our results indicate the 14-3-3 ζ protein is the target of PPD, a ginsenoside metabolite. Crystallographic and mutagenesis studies suggest a direct interaction between PPD and the 14-3-3 ζ protein. This finding can help in the development of small-molecular compounds that bind to the 14-3-3 ζ protein on the basis of the structure of dammarane-type triterpenoid.

• International Journal of Stem Cells
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• v.16 no.3
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• pp.326-341
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• 2023

Background and Objectives: Osteoarthritis (OA) is a degenerative disease that leads to the progressive destruction of articular cartilage. Current clinical therapeutic strategies are moderately effective at relieving OA-associated pain but cannot induce chondrocyte differentiation or achieve cartilage regeneration. We investigated the ability of wedelolactone, a biologically active natural product that occurs in Eclipta alba (false daisy), to promote chondrogenic differentiation. Methods and Results: Real-time reverse transcription-polymerase chain reaction, immunohistochemical staining, and immunofluorescence staining assays were used to evaluate the effects of wedelolactone on the chondrogenic differentiation of mesenchymal stem cells (MSCs). RNA sequencing, microRNA (miRNA) sequencing, and isobaric tags for relative and absolute quantitation analyses were performed to explore the mechanism by which wedelolactone promotes the chondrogenic differentiation of MSCs. We found that wedelolactone facilitates the chondrogenic differentiation of human induced pluripotent stem cell-derived MSCs and rat bone-marrow MSCs. Moreover, the forkhead box O (FOXO) signaling pathway was upregulated by wedelolactone during chondrogenic differentiation, and a FOXO1 inhibitor attenuated the effect of wedelolactone on chondrocyte differentiation. We determined that wedelolactone reduces enhancer of zeste homolog 2 (EZH2)-mediated histone H3 lysine 27 trimethylation of the promoter region of FOXO1 to upregulate its transcription. Additionally, we found that wedelolactone represses miR-1271-5p expression, and that miR-1271-5p post-transcriptionally suppresses the expression of FOXO1 that is dependent on the binding of miR-1271-5p to the FOXO1 3'-untranscribed region. Conclusions: These results indicate that wedelolactone suppresses the activity of EZH2 to facilitate the chondrogenic differentiation of MSCs by activating the FOXO1 signaling pathway. Wedelolactone may therefore improve cartilage regeneration in diseases characterized by inflammatory tissue destruction, such as OA.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7389-7394
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• 2014

Background: Chemotherapy is one of the major means for control of malignancies, with cisplatin (CDDP) as one of the main agents, widely used for the treatment of various malignant solid tumors. However, prevention of hepatotoxicity from cisplatin is one of the urgent issues in cancer chemotherapy. In this study, we aimed to investigate the effects of pu-erh tea on hepatotoxicity through body weight and tissue antioxidant parameters like, liver coefficient, serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), malondialdehyde(MDA) and glutathione (GSH) levels, and light microscopic evaluation by histological findings. Materials and Methods: The rats were randomly divided into five groups: Control (n=10), cisplatin (3 mg/kg p.i., n=10), cisplatin+pu-erh (0.32 g/kg/day i.g., n=10), cisplatin+pu-erh (0.8 g/kg/day i.g., n=10) and cisplatin+pu-erh (1.6 g/kg/day i.g., n=10). Pu-erh tea powder was administrated for 31 consecutive days. The rats were sacrificed at the end on the second day after a single dose of cisplatin treatment for measuring indices. Results: Pu-erh tea powder exhibited a protective effect by decreasing MDA and GSH and increasing the SOD and GSH-PX levels and GSH-PX/MDA ratio in camparison with the control group. Besides, pu-erh tea was also able to alleviate the pathological damage to some extent. Conclusion: Pu-erh tea powder is protective against cisplatin-induced liver oxidative damages, especially at the medium dosage (0.8 g/kg/d).