Mingkwan Na Takuathung, Jakkrit Aisara, Suphunwadee Sawong, Nut Koonrungsesomboon
{"title":"The effects of Cissus quadrangularis on bone-related biomarkers in humans: a systematic review and meta-analysis.","authors":"Mingkwan Na Takuathung, Jakkrit Aisara, Suphunwadee Sawong, Nut Koonrungsesomboon","doi":"10.1186/s12906-025-04995-8","DOIUrl":"https://doi.org/10.1186/s12906-025-04995-8","url":null,"abstract":"<p><strong>Background: </strong>Maintaining bone health is vital, particularly for aging populations prone to bone disorders. Cissus quadrangularis (CQ), a traditional medicinal plant, is increasingly recognized for its potential benefits in promoting bone health, including the effects on bone-related biomarkers promoting bone healing and bone density improvement. This study aimed to evaluate the effects of CQ on bone-related biomarkers in humans as the primary objective and to assess its impact on other clinical outcomes as a secondary objective.</p><p><strong>Methods: </strong>A systematic search of PubMed, Embase, Scopus, and the Cochrane Library databases was conducted up to April 2025. This systematic review included studies with participants receiving Cissus quadrangularis, those reporting bone biomarkers, and those with a randomized controlled design involving human participants. No restrictions were placed on age, sex, disease severity, or administration route. The quality of the studies included was assessed using the revised Cochrane risk-of-bias tool (RoB-2), while the overall strength of evidence was appraised using the GRADE approach. The summary effect measure was the standardized mean difference (SMD) with 95% confidence intervals (95% CI).</p><p><strong>Results: </strong>Seven studies, comprising a total of 354 participants, met the inclusion criteria for meta-analysis. The analysis revealed that CQ intervention significantly elevated serum parathyroid hormone levels (SMD = 1.23; 95% CI = 0.79 to 1.67; p < 0.0001). However, the CQ intervention did not result in significant changes in other bone-related biomarkers, including calcium, phosphorus, and serum alkaline phosphatase. The RoB-2 revealed that most studies had some concerns about bias, with two evaluated as having a high risk. The certainty of evidence was very low for all four parameters assessed by GRADE.</p><p><strong>Conclusion: </strong>The CQ intervention was significantly associated with increased serum parathyroid hormone levels, with no significant effects on other bone-related biomarkers. Although there were a limited number of studies, these findings suggest its potential for modulating bone health; however, further research is needed to confirm these results and explore its clinical applications.</p><p><strong>Trial registration: </strong>The study protocol was prospectively registered with PROSPERO, and the registration number is CRD42023435351.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":9128,"journal":{"name":"BMC Complementary Medicine and Therapies","volume":"25 1","pages":"286"},"PeriodicalIF":3.3,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yingzhi Xu, Li Sun, Zhaoyou Meng, Xinxing Lai, Dayong Ma, Yuqiu An, Boxuan Du, Qiaosheng Ren, Ying Gao, Kegang Cao
{"title":"Efficacy and safety of YQFM (YiQiFuMai lyophilized injection) on acute ischemic stroke (FAST): rationale and design for a randomized, double-blind, placebo-controlled trial.","authors":"Yingzhi Xu, Li Sun, Zhaoyou Meng, Xinxing Lai, Dayong Ma, Yuqiu An, Boxuan Du, Qiaosheng Ren, Ying Gao, Kegang Cao","doi":"10.1186/s12906-025-05036-0","DOIUrl":"10.1186/s12906-025-05036-0","url":null,"abstract":"<p><strong>Background: </strong>Low blood pressure at acute ischemic stroke onset is associated with both short- and long-term adverse outcomes. Studies have shown that YQFM (YiQiFuMai lyophilized injection) can ameliorate neurological deficits in ischemic stroke.However, all of these studies are all small-sample clinical observations lacking rigorous study design for AIS with inappropriate blood pressure.</p><p><strong>Aims: </strong>To describe the design of the YQFM aimed at reducing the disability rate in AIS patients with inappropriate blood pressure.</p><p><strong>Methods: </strong>This trial is a prospective, multicenter, randomized, double-blind, placebo-controlled, superiority trial aimed at evaluating the efficacy and safety of YQFM in reducing the disability rate in patients with acute hypoperfusion stroke within 90 days. We will recruit 480 patients with AIS within 48 h of symptom onset from 24 hospitals, who have large atherosclerosis, systolic pressure ≤ 155 mmHg, and an NIHSS score of 4-18. Eligible patients will be randomly assigned to receive either YQFM or 0.9% NaCl injection once daily for 10 days and will be followed up until the 90th day after stroke onset.The primary outcome will be the proportion of patients with mRS ≤ 2 at 90 days after patient recruitment. Secondary outcomes will include the proportion of early neurological deterioration at 7 days, patient self-reported outcomes and the syndrome score at 10 days, MMSE scale and BI scale at 90 days.During the trial, adverse events will be recorded. These data will be analyzed according to the predetermined statistical analysis plan.</p><p><strong>Conclusion: </strong>This study is the first randomized controlled double-blind trial to evaluate the efficacy and safety of YQFM in patients with AIS. This trial will provide evidence-based data for YQFM application in AIS with inappropriate blood pressure.</p><p><strong>Clinical trial registration: </strong>ChiCTR2300074125 was registered on 31 July, 2023. For more information, please visit Clinical Trials.gov at https://www.chictr.org.cn/showproj.html?Proj=200686 .</p>","PeriodicalId":9128,"journal":{"name":"BMC Complementary Medicine and Therapies","volume":"25 1","pages":"284"},"PeriodicalIF":3.3,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Boram Lee, Gyu Tae Chang, Hyelim Lee, Sun Haeng Lee, Tae Hwan Kim, Mi Mi Ko, Sumin Seo, Bok-Nam Seo, Su Eun Lim, Mi Ju Son
{"title":"Korean medicine registry for allergic rhinitis in real-world settings (KOREA-R): a multicenter registry protocol.","authors":"Boram Lee, Gyu Tae Chang, Hyelim Lee, Sun Haeng Lee, Tae Hwan Kim, Mi Mi Ko, Sumin Seo, Bok-Nam Seo, Su Eun Lim, Mi Ju Son","doi":"10.1186/s12906-025-05030-6","DOIUrl":"10.1186/s12906-025-05030-6","url":null,"abstract":"<p><strong>Background: </strong>Allergic rhinitis is a prevalent immune disorder with a significant impact on quality of life and socioeconomic burden. Korean Medicine treatments such as herbal medicine and acupuncture are widely utilized for allergic rhinitis due to clinical effectiveness and patient preferences. In particular, herbal decoctions, a key component of Korean Medicine treatment for allergic rhinitis, offer personalized treatment but pose challenges for randomized controlled trials due to the difficulty of placebo development. This study aims to establish a registry utilizing real-world data (RWD) on Korean Medicine treatment for allergic rhinitis, focusing on the effectiveness, safety, and cost-effectiveness of herbal decoctions in clinical practice.</p><p><strong>Methods: </strong>The KOrean medicine REgistry for Allergic rhinitis in Real-world settings (KOREA-R) aims to enroll 400 patients with allergic rhinitis receiving Korean Medicine treatment at two Korean Medicine hospitals from February 2025 to June 2028. Patients will be examined in three visits at 2-week intervals, followed by two additional online follow-ups at 6 and 12 months after week 4. RWD on symptom severity, quality of life, treatment administration and compliance, adverse events, and laboratory blood tests will be collected. Participation is voluntary, with no restrictions on treatment types or dosages. Statistical analyses, including propensity score matching and difference-in-difference, will be used to evaluate the effectiveness, safety, and cost-effectiveness of Korean Medicine treatment, particularly herbal decoctions. Data management ensures confidentiality and quality through a validated electronic data capture system and regular monitoring.</p><p><strong>Conclusion: </strong>The findings of KOREA-R will provide insights into the effectiveness and safety of Korean Medicine treatment for allergic rhinitis, with a focus on herbal decoctions tailored to individual patient symptoms and pattern identifications. Additionally, by systematically collecting RWD for multidimensional analysis, KOREA-R will offer valuable information on the cost-utility and cost-effectiveness of herbal decoctions for both patients and healthcare policymakers.</p><p><strong>Study registration: </strong>Clinical Research Information Service, KCT0010133 (Registration date: January 13, 2025).</p>","PeriodicalId":9128,"journal":{"name":"BMC Complementary Medicine and Therapies","volume":"25 1","pages":"282"},"PeriodicalIF":3.3,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nouran M Fahmy, Haidy A Gad, Masarra M Sakr, Mai I Shahin, Shaimaa Fayez
{"title":"Minneola tangelo essential oil exhibits antibacterial activity against multidrug-resistant pathogens while maintaining cell safety.","authors":"Nouran M Fahmy, Haidy A Gad, Masarra M Sakr, Mai I Shahin, Shaimaa Fayez","doi":"10.1186/s12906-025-05015-5","DOIUrl":"10.1186/s12906-025-05015-5","url":null,"abstract":"<p><strong>Background: </strong>The significant rise in antibiotic resistance has become an alarming situation urging the search for new antibacterial agents. Nature has always been a limitless source of bioactives with high safety profile. This study evaluates the antibacterial activity of essential oils from the leaves and fruit peels of Minneola tangelo cultivated in Egypt. In vitro cytotoxicity assay was conducted to ensure the safety profile of the active essential oils.</p><p><strong>Methods: </strong>The antibacterial activity of clinical isolates of Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus was assessed using the Kirby-Bauer disk diffusion method. Chemical profiling of the leaf and peel essential oils was performed using GC-MS. In vitro cytotoxicity assay of the leaf essential oil was conducted using sulforhodamine B assay. In silico docking study was conducted to explore the possible antibacterial mechanisms.</p><p><strong>Results: </strong>The leaf essential oil exhibited antibacterial activity against the tested isolates, whereas the peel oil was inactive. GC-MS analysis showed differences in the chemical composition of the leaf and fruit peel oils, where 60% of the leaf oil is dominated by linalool (31.6%), cis-β-ocimene (16.1%), and γ-terpinene (14.3%), whereas the fruit peel oil is solely dominated by D-limonene (82%). Cytotoxicity assay on Caco-2 cell line showed IC<sub>50</sub> value of 277.36 µg/mL while that on fibroblast HFB4 cell line was > 1000 µg/mL. In silico studies revealed high affinity of linalool to FabI, a crucial enzyme in the fatty acid biosynthesis pathway of MRSA as well as an affinity to Penicillin binding protein PBP2a. Binding of linalool to shikimate kinase of Acinetobacter baumannii was also demonstrated.</p><p><strong>Conclusion: </strong>Essential oil of M. tangelo is a promising antibacterial agent against multidrug resistant strains with a high safety profile.</p>","PeriodicalId":9128,"journal":{"name":"BMC Complementary Medicine and Therapies","volume":"25 1","pages":"281"},"PeriodicalIF":3.3,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Investigation of differential Multi-Mode antibacterial mechanisms of essential oils of Satureja montana L. and Leptospermum scoparium J.R.Forst. & G.Forst. Against Porphyromonas gingivalis.","authors":"Yue Yuan, Xiuli Hui, Zixuan Liu, Jinlong Sun, Rifat Nowshin Raka, Junsong Xiao, Zhongwei Zhang, Hua Wu","doi":"10.1186/s12906-025-05007-5","DOIUrl":"https://doi.org/10.1186/s12906-025-05007-5","url":null,"abstract":"<p><strong>Background: </strong>Globally, according to WHO estimates, severe periodontitis affects over 1 billion people. Porphyromonas gingivalis (P. gingivalis) is a keystone pathogen in the development of chronic periodontitis. Although two commercial essential oils (EOs) derived from Satureja montana L. (EO1) and Leptospermum scoparium J.R.Forst. & G.Forst. (EO2) have demonstrated promising antibacterial potential, their mechanisms against P. gingivalis and the influence of their distinct metabolite profiles remain unclear.</p><p><strong>Methods: </strong>EO metabolite profiles were analyzed using gas chromatography-mass spectrometry. Antibacterial activity was assessed using the disk diffusion, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and bacterial growth curves. Their effects on hemagglutination, hemolytic, black pigmentation formation, autoaggregation, hydrophobicity, biofilm formation and virulence gene expression were evaluated. Molecular docking simulated interactions between metabolites and the virulence proteins. Cytotoxicity at MIC was tested in RAW264.7 cells using MTT assays.</p><p><strong>Results: </strong>EO1 showed stronger antibacterial effects than EO2, with inhibition zone diameters (42.06 ± 1.62 versus 40.36 ± 0.47 mm), lower MIC (71.33 versus 305.00 µg/mL), and MBC (142.66 µg/mL versus 1220.00 µg/mL). The bacterial growth curves demonstrated sustained inhibition. EO1 can inhibit P. gingivalis hemagglutination, hemolysis (p < 0.05), and heme accumulation at 1/8 - 1/2 MIC, while EO2 only affected heme accumulation. Both EOs reduced P. gingivalis hydrophobicity levels below 50% at 1/4 to 1/2 MIC and achieved biofilm inhibition rates exceeding 85% at MIC (p < 0.05). The distinct inhibitory mechanisms against the pathogenic processes of P. gingivalis likely stem from their differing metabolite profiles. EO1 was dominated by monoterpenes (56.00 ± 0.55%), and the main metabolites were γ-terpinene (20.20 ± 0.38%), p-cymene (16.01 ± 0.66%), and carvacrol (14.50 ± 0.35%), whereas EO2 contained up to 71.19 ± 0.18% sesquiterpenes, its main metabolites were leptospermone (17.44 ± 0.40%). Molecular docking analysis predicted these metabolites as key active components. Besides, at MIC, cell viability was 86.68% for EO1 and 68.81% for EO2.</p><p><strong>Conclusion: </strong>The comprehensive analysis reveals that EO1 and EO2 exert multi-mode antibacterial effects through different mechanisms. Notably, EO1 demonstrated greater potential against P. gingivalis, which may be attributed to its unique metabolite composition. These findings offer a theoretical foundation and new insights for advancing the application of EOs in the prevention and adjunctive management of periodontitis.</p>","PeriodicalId":9128,"journal":{"name":"BMC Complementary Medicine and Therapies","volume":"25 1","pages":"283"},"PeriodicalIF":3.3,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sahar Akrami, Shirin Omidvar Kordshouli, Ahmad Tahmasebi, Ali Moghadam, Farzaneh Aram, Ali Golestan, Amin Ramezani, Ali Niazi
{"title":"Cytotoxic effects of five Iranian medicinal plants on pancreatic cancer cell lines and investigation of induced changes in the expression of several key genes.","authors":"Sahar Akrami, Shirin Omidvar Kordshouli, Ahmad Tahmasebi, Ali Moghadam, Farzaneh Aram, Ali Golestan, Amin Ramezani, Ali Niazi","doi":"10.1186/s12906-025-04970-3","DOIUrl":"https://doi.org/10.1186/s12906-025-04970-3","url":null,"abstract":"<p><p>Cancer is a deadly and fast-spreading disease that is a growing health problem worldwide due to a lack of comprehensive screening and appropriate medication. However, natural products derived from medicinal plants have gained attention as potential sources of bioactive compounds that selectively remove cancerous lesions and are nontoxic and safe. Pancreatic cancer (PC) is a major therapeutic challenge and is predicted to surpass breast cancer as the third leading cause of cancer death. This study investigated the cytotoxic effects of methanolic extracts from five Iranian medicinal plants, Cuscuta epithymum, Achillea millefolium, Salvia officinalis, Salvia hydrangea, and Teucrium polium, on pancreatic cancer cell lines (MIA PaCa-2 and PaTu8902). Additionally, we examined the changes in the expression of key genes following treatment with C. epithymum extract. The findings revealed that the plant extracts had a dose-dependent effect on the cell viability of the lines, with the C. epithymum extract exhibiting the greatest cytotoxic effect (IC50 values of 85.03 µg/mL for MIA PaCa-2 and 156.57 µg/mL for PaTu 8902). GC‒MS analysis revealed 25 bioactive compounds in C. epithymum, with quinic acid (14.13%), p-vinylphenol (13.22%), and valeraldehyde (11.21%) as the most abundant. The study also investigated the changes in the expression of the STAT4, PIK3CD, EMP1, and RAB11FIP3 genes in MIA PaCa-2 and PaTu 8902 pancreatic cancer cell lines after treatment with the extract from C. epithymum. A correlation was detected between the expression levels of PIK3CD, STAT4, EMP1, and RAB11FIP3 and various concentrations of C. epithymum extract. The results revealed that the extract increased the mRNA levels of STAT4, PIK3CD, and EMP1, whereas RAB11FIP3 was reduced in the treated cells. Accordingly, C. epithymum extract has strong cytotoxic effects on pancreatic cancer cells and influences the expression of key cancer-related genes, suggesting its potential as a therapeutic candidate for PC treatment. Further in vivo studies are recommended to explore its mechanisms of action and clinical applicability.</p>","PeriodicalId":9128,"journal":{"name":"BMC Complementary Medicine and Therapies","volume":"25 1","pages":"285"},"PeriodicalIF":3.3,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yujin Choi, Pyung-Wha Kim, In-Chul Jung, Ae-Ran Kim, Hyo-Ju Park, Ojin Kwon, Jun-Hwan Lee, Joo-Hee Kim
{"title":"Acupuncture for patients with mild cognitive impairment: a randomized, patient-assessor-blinded, sham-controlled pilot study.","authors":"Yujin Choi, Pyung-Wha Kim, In-Chul Jung, Ae-Ran Kim, Hyo-Ju Park, Ojin Kwon, Jun-Hwan Lee, Joo-Hee Kim","doi":"10.1186/s12906-025-05023-5","DOIUrl":"10.1186/s12906-025-05023-5","url":null,"abstract":"<p><strong>Background: </strong>Mild cognitive impairment (MCI) is the transitional stage between normal aging and early dementia. Although acupuncture is a promising non-pharmacological treatment, higher-quality evidence is needed to confirm its effectiveness.</p><p><strong>Methods: </strong>A randomized, patient- and assessor-blinded, sham-controlled, pilot clinical trial was conducted to evaluate the feasibility of acupuncture for treating MCI. In total, 30 participants were randomized into acupuncture and sham acupuncture groups. The participants underwent 24 treatment sessions over 12 weeks. The primary outcome was a change in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) score over 12 weeks, whereas the secondary outcomes included the Seoul Neuropsychological Screening Battery (SNSB-II) score. Adverse events and the success of blinding were also assessed.</p><p><strong>Results: </strong>Of the 30 participants, 28 completed the study. Participants in the acupuncture and sham acupuncture groups exhibited a decrease in ADAS-cog scores from 10.27 ± 4.03 and 11.47 ± 3.85 at baseline to 5.78 ± 3.04 and 6.27 ± 2.83 at week 12, respectively. Both groups exhibited clinically meaningful improvements, with no significant difference between groups (P = 0.6590). The SNSB-II memory domain exhibited a moderate effect size favoring acupuncture (Cohen's d = 0.57, P = 0.1317). No intervention-related adverse events were reported, and participant blinding was adequate throughout the trial.</p><p><strong>Conclusions: </strong>The 12-week acupuncture treatment is feasible for patients with MCI and may improve memory. Although the primary outcomes did not reach statistical significance, the secondary outcomes suggested potential benefits. Larger confirmatory trials are warranted to investigate the effectiveness of acupuncture in patients with MCI.</p><p><strong>Trial registration: </strong>Clinical Research Information Service (cris.nih.go.kr) KCT0001938 (Registered on June 3, 2016).</p>","PeriodicalId":9128,"journal":{"name":"BMC Complementary Medicine and Therapies","volume":"25 1","pages":"277"},"PeriodicalIF":3.3,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12275449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Discovery of pyroptosis-inducing natural products in neuroblastomas: computational studies with experimental validation.","authors":"Beni Lestari, Rohmad Yudi Utomo, Faaza Aulia Rahman, Dyaningtyas Dewi Pamungkas Putri, Ummi Maryam Zulfin, Yusuke Suenaga, Edy Meiyanto, Yoshitaka Hippo","doi":"10.1186/s12906-025-05004-8","DOIUrl":"10.1186/s12906-025-05004-8","url":null,"abstract":"<p><strong>Background: </strong>Neuroblastomas evade apoptosis due to oncogene mutations and antiapoptotic proteins, necessitating novel therapeutics that work in concert with other forms of cell death. Pyroptosis has potential as a strategic cell death mechanism in neuroblastoma. This study aimed to identify compounds that modulate pyroptosis, specifically those that target gasdermin D (GSDMD) oligomerization.</p><p><strong>Methods: </strong>The study employed computational analysis and in vitro screening. The COCONUT database provides the natural compound dataset. Drug-likeness analysis and pharmacophore fitting were applied to screen potential GSDMD oligomerization modulators. Hit compounds underwent molecular docking with MOE and molecular dynamic (MD) simulations with NAMD 2.14 to analyse structural changes. The computational screening results were corroborated by in vitro assays, including the WST-8 assay, Western blot, and immunofluorescence, which target pyroptosis-specific caspase-1.</p><p><strong>Results: </strong>Pharmacophore fitting, molecular docking, and molecular dynamics simulations identified the top five compounds, namely, quercetin, naringenin, hesperetin, curcumin, and galangin, as potent modulators of GSDMD oligomerization. Among these compounds, curcumin, quercetin, and galangin exerted potent cytotoxic effects on GSDMD-expressing neuroblastoma SK-N-AS cells, with IC<sub>50</sub> values of 21, 37, and 49 µM, respectively. Curcumin and quercetin also promoted apoptosis via increased caspase-3 cleavage and reduced procaspase-7 and -8 levels, as shown by immunoblotting. Curcumin and galangin upregulated caspase-1 expression, as demonstrated by the detection of a fluorescent-labelled inhibitor of caspase-1 by immunostaining, suggesting that these two compounds could induce pyroptosis. Hesperetin and naringenin showed low cytotoxicity, had no effect on caspase activation, and did not exhibit signs of pyroptosis in SK-NA-S cells.</p><p><strong>Conclusions: </strong>Our study successfully identified curcumin as a strong regulator of both apoptosis and pyroptosis, quercetin as a strong modulator of apoptosis, and galangin as a strong modulator of pyroptosis. Further research on these compounds is crucial for the development of novel therapeutic strategies for neuroblastoma treatment.</p>","PeriodicalId":9128,"journal":{"name":"BMC Complementary Medicine and Therapies","volume":"25 1","pages":"279"},"PeriodicalIF":3.3,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12276684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Neveen Adel Madbouly, Doaa Mohammad Ali, Alyaa Ahmed Farid
{"title":"Nanoparticles from grape seed extract inhibit inflammatory cytokines and ameliorate CCl<sub>4</sub>-induced hepatotoxicity.","authors":"Neveen Adel Madbouly, Doaa Mohammad Ali, Alyaa Ahmed Farid","doi":"10.1186/s12906-025-05005-7","DOIUrl":"10.1186/s12906-025-05005-7","url":null,"abstract":"<p><strong>Background: </strong>Xenobiotic-induced liver injury is a clinically reverent condition which may influence the development of steatohepatitis via affecting numerous pathways such as oxidative stress, inflammation, mitochondorial functioning and fatty acid biosynthesis. The current study was conducted to survey the antioxidant effect of grape seeds extract nanoparticles (GS extract NPs) against CCl<sub>4</sub>-induced oxidative stress, hepatic dysfunction and inflammatory changes.</p><p><strong>Methods: </strong>Hydroethanolic Grape seed (GS) extract was prepared and characterized using high performance liquid chromatography (HPLC), inductively coupled plasma-mass spectrometry (ICP-MS) and gas chromatography-mass spectrometry (GC-MS). Then, GS extract NPs were synthesized and in vitro antioxidant, anticoagulant, cytotoxicity and anti-inflammatory testes confirmed biological activity. Finally, Twenty-five male Sprague-Dawley rats were divided into five groups (n = 5/group). Either GS extract (200 mg/kg/day) or GS extract NPs (100 mg/kg/day) were orally administrated independently to CCL<sub>4</sub>-intoxicated (0.5 ml/kg twice a week for 3 weeks) rats. Four weeks after the treatment, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) were monitored. In addition, hepatic Malondialdehyde (MDA), Superoxide dismutases (SOD), Glutathione (GSH) and catalase (CAT) and hepatic inflammatory cytokines were assessed.</p><p><strong>Results: </strong>GS extract NPs were spherical-shaped and regular particles (size: 16.5 to 22.5 nm and zeta potential: -39.42 mv). CCL<sub>4</sub> -intoxicated rats showed increase of serum ALT, AST, ALP, elevation in MDA level accompanied by a decline in SOD, GSH and CAT levels in liver, compared with CCL<sub>4</sub>-untreated rats. Immunologically, serum C-Reactive Protein (CRP) and hepatic interleukin 1β (IL-1β), IL-4, IL-6 and Tumor Necrosis Factor-alpha (TNF-α) showed significant elevation, compared with CCL<sub>4</sub> -untreated rats. Conversely, GS extract NPs supplementation potentially ameliorate hepatic functions by normalization of serum ALT, AST and ALP, reduced MDA level, improved antioxidant CAT, regulated liver inflammatory cytokines via maximal reduction of hepatic IL-1β, IL-4, IL-6 and TNF-α.</p><p><strong>Conclusion: </strong>GS extract NPs augmented the antioxidant and anti-inflammatory properties of GS extract thereby protecting the liver against oxidative stress induced by CCl<sub>4</sub> as hepatic xenobiotic.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":9128,"journal":{"name":"BMC Complementary Medicine and Therapies","volume":"25 1","pages":"276"},"PeriodicalIF":3.3,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12275419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}