Biomolecules & Therapeutics最新文献

{"title":"Paeoniflorin Protects Retinal Pigment Epithelial Cells from High Glucose-Induced Oxidative Damage by Activating Nrf2-Mediated HO-1 Signaling.","authors":"Cheol Park, Hee-Jae Cha, Su Hyun Hong, Jeong Sook Noh, Sang Hoon Hong, Gi Young Kim, Jung-Hyun Shim, Jin Won Hyun, Yung Hyun Choi","doi":"10.4062/biomolther.2025.025","DOIUrl":"https://doi.org/10.4062/biomolther.2025.025","url":null,"abstract":"<p><p>Oxidative stress due to hyperglycemia damages the functions of retinal pigment epithelial (RPE) cells and is a major risk factor for diabetic retinopathy (DR). Paeoniflorin is a monoterpenoid glycoside found in the roots of <i>Paeonia lactiflora Pall</i> and has been reported to have a variety of health benefits. However, the mechanisms underlying its therapeutic effects on high glucose (HG)-induced oxidative damage in RPE cells are not fully understood. In this study, we investigated the protective effect of paeoniflorin against HG-induced oxidative damage in cultured human RPE ARPE-19 cells, an <i>in vitro</i> model of hyperglycemia. Pretreatment with paeoniflorin markedly reduced HG-induced cytotoxicity and DNA damage. Paeoniflorin inhibited HG-induced apoptosis by suppressing activation of the caspase cascade, and this suppression was associated with the blockade of cytochrome c release to cytoplasm by maintaining mitochondrial membrane stability. In addition, paeoniflorin suppressed the HG-induced production of reactive oxygen species (ROS), increased the phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2), a key redox regulator, and the expression of its downstream factor heme oxygenase-1 (HO-1). On the other hand, zinc protoporphyrin (ZnPP), an inhibitor of HO-1, abolished the protective effect of paeoniflorin against ROS production in HG-treated cells. Furthermore, ZnPP reversed the protective effects of paeoniflorin against HG-induced cellular damage and induced mitochondrial damage, DNA injury, and apoptosis in paeoniflorin-treated cells. These results suggest that paeoniflorin protects RPE cells from HG-mediated oxidative stress-induced cytotoxicity by activating Nrf2/HO-1 signaling and highlight the potential therapeutic use of paeoniflorin to improve the symptoms of DR.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"33 3","pages":"518-528"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12059356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stress Accelerates Depressive-Like Behavior through Increase of SPNS2 Expression in Tg2576 Mice.","authors":"Seung Sik Yoo, Yuri Kim, Dong Won Lee, Hyeon Joo Ham, Jung Ho Park, In Jun Yeo, Ju Young Chang, Jaesuk Yun, Dong Ju Son, Sang-Bae Han, Jin Tae Hong","doi":"10.4062/biomolther.2024.200","DOIUrl":"10.4062/biomolther.2024.200","url":null,"abstract":"<p><p>To investigate the relationship between depression and AD, water avoidance stress (WAS) was induced for 10 days in both Tg2576 mice and wild-type (WT) mice. After WAS, memory function and depressive-like behavior were investigated in Tg2576 mice. Tg2576 WAS mice exhibited more depressive-like behaviors than WT WAS and Tg2576 control (CON) mice. Strikingly, Tg2576 CON mice showed more depressive-like behaviors than WT mice. Moreover, corticosterone and phospho-glucocorticoid receptor (p-GR) levels were also higher in Tg2576 WAS mice in comparison to Tg2576 CON mice. Spinster homologue 2 (SPNS2) is a member of non-ATP-dependent transporter. The role of SPNS2 was widely known as a sphingosine-1-phosphate (S1P) transporter, which export intracellular S1P from cells. Using GEO database to analyze SPNS2 gene expression changes in patients with AD and depression, we show that SPNS2 gene expression correlates with AD and depression. Interestingly, Tg2576 WAS mice displayed significantly increased levels of SPNS2 w1hen compared to Tg2576 CON counterparts. SPNS2 levels were also higher in Tg2576 CON mice in comparison with WT CON mice. Remarkably, we found a decrease in S1P brain levels and an increase in S1P serum levels of Tg2576 WAS mice in comparison with Tg2576 CON mice. Accordingly, WAS induced group further decreased S1P levels in the brains. However, the level in the serum further increased in comparison with non-induced group. Therefore, these results suggest that AD and depression could be associated, and that Tg2576 transgenic mice are more susceptible to stress-induced depression through the release of S1P by SPNS2 up-regulation.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"417-428"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12059362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The SIRT6 Activator MDL-800 Inhibits PPARα and Fatty acid Oxidation-Related Gene Expression in Hepatocytes.","authors":"Yeonsoo Kim, Hyeokjin Lim, Ye Eun Cho, Seonghwan Hwang","doi":"10.4062/biomolther.2024.251","DOIUrl":"10.4062/biomolther.2024.251","url":null,"abstract":"<p><p>A histone deacetylase SIRT6 regulates the transcription of various genes involved in lipid metabolism. Fatty acid (FA) oxidation plays a pivotal role in maintaining hepatic lipid homeostasis, and its dysregulation significantly contributes to lipotoxicity and inflammation, driving the progression of steatotic liver disease. While SIRT6 is known to activate peroxisome proliferator-activated receptor-alpha (PPARα), a central regulator of FA oxidation, the development of SIRT6 activators capable of enhancing FA oxidation and mitigating steatotic liver disease has yet to be achieved. This study evaluated the effect of MDL-800, a selective SIRT6 activator, on the expression of PPARα and genes related to FA oxidation. In AML12 mouse hepatocytes, MDL-800 treatment activated SIRT6 but unexpectedly decreased the expression of PPARα and its FA oxidation-associated target genes. Furthermore, OSS128167, a selective SIRT6 inhibitor, did not reverse the suppressive effects of MDL-800 on PPARα, suggesting that MDL-800 downregulates PPARα and FA oxidation-related genes through a mechanism independent of SIRT6 activation. Mechanistic investigations revealed that MDL-800 increased the production of reactive oxygen species and activated stress kinases. The inhibition of PPARα by MDL-800 was reversed by co-treatment with the antioxidant N-acetylcysteine or the JNK inhibitor SP600125. In summary, MDL-800 suppresses PPARα and FA oxidation-related genes primarily through the induction of oxidative stress in hepatocytes, independent of its role as a SIRT6 activator.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"438-446"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12059364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of Sphingosine-1-Phosphate Receptor 2 (S1P₂) Attenuates Imiquimod-Induced Psoriasis-Like Skin Inflammation in BALB/c Mice.","authors":"Ju-Hyun Lee, Dong-Soon Im","doi":"10.4062/biomolther.2024.197","DOIUrl":"https://doi.org/10.4062/biomolther.2024.197","url":null,"abstract":"<p><p>Serum and epidermal levels of sphingosine 1-phosphate (S1P) are higher in patients with psoriasis than healthy subjects. Although roles of type 1 S1P receptor, S1P₁, in the development of psoriasis has intensively been investigated, roles of S1P₂ have not been elucidated. We aim to investigate whether blockage of S1P₂ reduce imiquimod-induced psoriasis-like dermatitis using an S1P₂ antagonist, JTE-013, in combination with <i>S1pr2</i> wild-type (WT) and knock-out (KO) BALB/c mice. Imiquimod induced increase of erythematous papules and plaques with silver scaling, whereas administration of JTE-013 significantly suppressed those increases in <i>S1pr2</i> WT mice. Deficiency of <i>S1pr2</i> gene reduced the imiquimod-induced symptoms. Imiquimod increased mRNA expression levels of pro-inflammatory Th1/Th17 cytokines, whereas JTE-013 significantly suppressed those increases in <i>S1pr2</i> WT mice. Deficiency of <i>S1pr2</i> gene also suppressed the imiquimod-induced pro-inflammatory cytokine expression. Imiquimod induced enlargement of lymph nodes and spleens, whereas JTE-013 suppressed them in <i>S1pr2</i> WT mice. Imiquimod induced increase of pro-inflammatory Th1/Th17 cytokine levels and Th17 cell numbers in lymph nodes and spleens, whereas JTE-013 suppressed them in <i>S1pr2</i> WT mice. In summary, the present results suggest that blockage of S1P₂ could suppress the characteristics of psoriasis-form dermatitis and be a therapeutic strategy.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"33 3","pages":"544-553"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12059363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cynaropicrin Induces Reactive Oxygen Species-Dependent Paraptosis-Like Cell Death in Human Liver Cancer Cells.","authors":"Min Yeong Kim, Hee-Jae Cha, Su Hyun Hong, Sung-Kwon Moon, Taeg Kyu Kwon, Young-Chae Chang, Gi Young Kim, Jin Won Hyun, A-Young Nam, Jung-Hyun Shim, Yung Hyun Choi","doi":"10.4062/biomolther.2025.011","DOIUrl":"10.4062/biomolther.2025.011","url":null,"abstract":"<p><p>Cynaropicrin, a sesquiterpene lactone found in artichoke leaves exerts diverse pharmacological effects. This study investigated whether cynaropicrin has a paraptosis-like cell death effect in human hepatocellular carcinoma Hep3B cells in addition to the apoptotic effects reported in several cancer cell lines. Cynaropicrin-induced cytotoxicity and cytoplasmic vacuolation, a key characteristic of paraptosis, were not ameliorated by inhibitors of necroptosis, autophagy, or pan caspase inhibitors in Hep3B cells. Our study showed that cynaropicrin-induced cytotoxicity was accompanied by mitochondrial dysfunction and endoplasmic reticulum stress along with increased cellular calcium ion levels. These effects were significantly mitigated by endoplasmic reticulum stress inhibitor or protein synthesis inhibitor. Moreover, cynaropicrin treatment in Hep3B cells increased reactive oxygen species generation and downregulated apoptosis-linked gene 2-interacting protein X (Alix), a protein that inhibits paraptosis. The addition of the reactive oxygen species scavenger <i>N</i>-acetyl-L-cysteine (NAC) neutralized cynaropicrin-induced changes in Alix expression and endoplasmic reticulum stress marker proteins counteracting endoplasmic reticulum stress and mitochondrial impairment. This demonstrates a close relationship between endoplasmic reticulum stress and reactive oxygen species generation. Additionally, cynaropicrin activated p38 mitogen activated protein kinase and a selective p38 mitogen activated protein kinase blocker alleviated the biological phenomena induced by cynaropicrin. NAC pretreatment showed the best reversal of cynaropicrin induced vacuolation and cellular inactivity. Our findings suggest that cynaropicrin induced oxidative stress in Hep3B cells contributes to paraptotic events including endoplasmic reticulum stress and mitochondrial damage.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"470-482"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12059367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum to \"Morroniside Protects C2C12 Myoblasts from Oxidative Damage Caused by ROS-mediated Mitochondrial Damage and Induction of Endoplasmic Reticulum Stress\" [Biomol Ther 32(3), 349-360 (2024)].","authors":"Hyun Hwangbo, Cheol Park, EunJin Bang, Hyuk Soon Kim, Sung-Jin Bae, Eunjeong Kim, Youngmi Jung, Sun-Hee Leem, Young Rok Seo, Su Hyun Hong, Gi-Young Kim, Jin Won Hyun, Yung Hyun Choi","doi":"10.4062/biomolther.2025.006","DOIUrl":"https://doi.org/10.4062/biomolther.2025.006","url":null,"abstract":"","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"33 3","pages":"555"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12059355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum to \"Suppression of Lipopolysaccharide-induced Inflammatory and Oxidative Response by 5-Aminolevulinic Acid in RAW 264.7 Macrophages and Zebrafish Larvae\" [Biomol Ther 29(6), 685-696 (2021)].","authors":"Seon Yeong Ji, Hee-Jae Cha, Ilandarage Menu Neelaka Molagoda, Min Yeong Kim, So Young Kim, Hyun Hwangbo, Hyesook Lee, Gi-Young Kim, Do-Hyung Kim, Jin Won Hyun, Heui-Soo Kim, Suhkmann Kim, Cheng-Yun Jin, Yung Hyun Choi","doi":"10.4062/biomolther.2025.002","DOIUrl":"https://doi.org/10.4062/biomolther.2025.002","url":null,"abstract":"","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"33 3","pages":"554"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12059357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-Inflammatory Activity of Cell-Penetrating Peptide Nucleic Acids Targeting Indoleamine 2,3-Dioxygenase 1 in IFNγ-Treated Human Keratinocytes.","authors":"Daram Jung, Sungjin Ahn, In Guk Park, Yeasel Jeon, Sangbong Lee, Minsoo Noh","doi":"10.4062/biomolther.2024.207","DOIUrl":"https://doi.org/10.4062/biomolther.2024.207","url":null,"abstract":"<p><p>Indoleamine 2,3-dioxygenase 1 (IDO1) is an enzyme that plays a pivotal role in immune regulation by metabolizing tryptophan into kynurenine, leading to T cell suppression and promoting immune tolerance. However, persistent activation of IDO1 can lead to prolonged immune stimulation in inflammatory conditions such as skin diseases and chronic inflammation. In this study, we developed modified peptide nucleic acids (PNAs) conjugated with cationic lipid chains to target IDO1 pre-mRNA and evaluated their anti-inflammatory effects in human keratinocytes. The modified PNAs demonstrated enhanced solubility, robust binding affinity, and effective penetration into keratinocytes. Quantitative PCR results showed significant downregulation of IDO1 and pro-inflammatory cytokines such as IL-6, IL-8, and PTGS2 in interferon γ (IFNγ)-treated keratinocytes. These findings suggest that cell-penetrating PNAs targeting IDO1 hold potential as a therapeutic approach for inflammatory skin disorders and chronic inflammation.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"33 3","pages":"494-500"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12059366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual Disruption of DNA Repair by a Novel CHK2 Inhibitor, ART-446, and Olaparib is a Promising Strategy for Triple-Negative Breast Cancer Therapy.","authors":"Hong-Jun Kang, Young-Woo Kang, Ha-Young Lee, Sojung Ha, Jong Oh Kim, Woo-Young Kim, Taegon Baik","doi":"10.4062/biomolther.2025.029","DOIUrl":"10.4062/biomolther.2025.029","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) is an aggressive cancer subtype lacking targeted therapies and is characterized by high recurrence rates and poor prognosis. Recent advances in targeting DNA damage response (DDR) pathways using poly (ADP‒ribose) polymerase (PARP) inhibitors offer promising therapeutic strategies, especially for TNBC patients with BRCA1/2 mutations. This study reports the development and characterization of ART-446, a novel and selective CHK2 inhibitor. ART-446 showed potent activity against TNBC, regardless of BRCA deficiency, and it also reversed PARP inhibitor resistance. ART-446 potently inhibited CHK2 (IC₅₀: 9.06 nM) with high selectivity over other kinases; it synergized with the PARP inhibitor olaparib, enhancing DNA damage, inducing G2/M cell cycle arrest, and promoting apoptosis in both BRCA-mutant and wild-type TNBC cells. Mechanistic analyses revealed that ART-446 sensitized BRCA mutant and WT cells to PARP inhibitors by impairing DNA repair and increasing the accumulation of DNA damage. Importantly, ART-446 disrupted both homologous recombination and nonhomologous end-joining repair pathways, addressing a key limitation of PARP inhibitor monotherapy-resistance in BRCA-proficient cancers. <i>In vivo</i>, the combination of ART-446 and olaparib significantly reduced tumor growth in TNBC xenograft models without noticeable toxicity. The combined treatment increased DNA damage signaling, as evidenced by elevated γH2AX levels, and enhanced the sensitivity of BRCA2-deficient cells to ART-446. These findings underscore the potential of ART-446 to exploit DNA repair deficiencies and overcome resistance mechanisms associated with PARP inhibitors. By addressing the limitations of current treatments and expanding the utility of PARP inhibitors, ART-446 represents a promising candidate for DDR-targeted therapies, offering a novel approach to improve the outcomes of patients with TNBC.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"458-469"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12059358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"1,3,5-Tricaffeoylquinic Acid from <i>Ipomoea batatas</i> Vines Induced Ovarian Cancer Cell Apoptosis and Inhibited Endothelial Tube Formation.","authors":"Dahae Lee, Jaekyoung Kim, Soyoon Baek, Jin Woo Lee, Changyeol Lee, Ki Sung Kang, Sang Hee Shim","doi":"10.4062/biomolther.2024.239","DOIUrl":"10.4062/biomolther.2024.239","url":null,"abstract":"<p><p>Ovarian cancer usually metastasizes from the ovary to adjacent organs through direct invasion with blood vessels formed by endothelial cells. Targeting apoptosis of ovarian cancer and angiogenesis is promising for anticancer therapy. Leaves of <i>Ipomoea</i> sp. have reportedly shown promise in treating ovarian cancer. Here, we investigated the apoptosis-inducing and anti-angiogenic effects of compounds isolated from <i>Ipomoea batatas</i> vines (IBV). Phytochemical examination of IBV led to the isolation and verification of eight compounds (<b>1-8</b>): chlorogenic acid (<b>1</b>), 3,4-dicaffeoylquinic acid (<b>2</b>), 3,5-dicaffeoylquinic acid (<b>3</b>), 4,5-dicaffeoylquinic acid (<b>4</b>), 1,3,5-tricaffeoylquinic acid (<b>5</b>), <i>N-trans</i>-feruloyltyramine (<b>6</b>), scopoletin (<b>7</b>), and esculetin (<b>8</b>). Of these, 1,3,5-tricaffeoylquinic acid (5) showed the highest cytotoxicity in A2780 human ovarian cancer cells, inducing apoptotic death in more than 37% cells and decreasing viability to less than 25% at 100 μM. Compound <b>5</b> increased the levels of cleaved caspase-8, Bax, cleaved PARP, and caspase-3/9, and decreased the levels of cleaved Bcl-2. Further, <b>5</b> inhibited tubule formation in HUVECs. VEGFR2, ERK, PI3K, Akt, and mTOR protein expression was also suppressed by <b>5</b>. Then, a simple, rapid, and reliable LC-MS/ MS method was developed to determine the contents of the isolated compounds from IBV. Overall, <b>5</b> has potential for treating ovarian cancer as it induces apoptosis in ovarian cancer cells and inhibits tube formation.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"483-493"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12059361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}