{"title":"Apoptotic and Cytotoxic Potential of Carnosic Acid- and Carnosol-Rich Fractions From Salvia dorystaechas on Human Hepatoma (HepG2) Cells","authors":"İlker Çinbilgel, Naciye Erkan, Serap Kocaoğlu Cenkci, Timur Tongur, Taner Erkaymaz, Kudret Akpınar","doi":"10.1155/jfbc/4440039","DOIUrl":null,"url":null,"abstract":"<div>\n <p>Plant isolates from <i>Salvia dorystaechas</i> (Lamiaceae) were investigated for their apoptotic and cytotoxic effects on human hepatocellular carcinoma (HepG2) cells under various treatment conditions. Chromatographic isolation yielded fractions (Fr C, D, F, and H) rich in carnosic acid (CA) and carnosol (CL), with significantly higher concentrations (26.3–93.5 g/kg) compared to the crude extract (10.0 g/kg). Other phenolic compounds, including caftaric acid, epicatechin, quercetin, and rutin, were also detected in notable amounts via ultra-high-performance liquid chromatography-mass spectrometry/mass spectrometry (UHPLC-MS/MS). CA-/CL-rich fractions effectively induced caspase-9 and caspase-3 activities, decreased cell viability, and increased lactate dehydrogenase (LDH) release. These effects were significant compared to those induced by 0.1 mM hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>). Notably, Fr D and Fr H, which contained the highest CA/CL concentrations, showed caspase-9/caspase-3 activities of 1.60/1.83 and 1.63/1.94, respectively, at 25 μg/mL after 24 h of treatment, whereas the crude plant extract showed corresponding activity values of 1.33/1.36 under the same conditions. In contrast, the crude extract exhibited its strongest apoptotic and cytotoxic effects under harsher conditions (50 μg/mL and 48 h), with caspase-9/caspase-3 activities of 1.70/2.59, 12.0% cell viability, and 65.4% LDH release. Apoptosis was further supported by superoxide (O<sub>2</sub>•<sup>−</sup>) production mediated by NADPH oxidases (NOXs), as the NOX inhibitor diphenyleneiodonium (DPI) reduced O<sub>2</sub>•<sup>−</sup> levels by 28.6%–48.6%. Additionally, nuclei-stained cells revealed morphological changes, including nuclear fragmentation, apoptotic body formation, and loss of adhesion. In conclusion, CA-/CL-rich <i>S. dorystaechas</i> isolates demonstrated strong apoptotic and cytotoxic effects on HepG2 cells, with contributions from other phenolic compounds. These findings highlight the potential therapeutic value of <i>S. dorystaechas</i> isolates in liver cancer treatment.</p>\n </div>","PeriodicalId":15802,"journal":{"name":"Journal of Food Biochemistry","volume":"2025 1","pages":""},"PeriodicalIF":3.5000,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/jfbc/4440039","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Food Biochemistry","FirstCategoryId":"97","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1155/jfbc/4440039","RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Plant isolates from Salvia dorystaechas (Lamiaceae) were investigated for their apoptotic and cytotoxic effects on human hepatocellular carcinoma (HepG2) cells under various treatment conditions. Chromatographic isolation yielded fractions (Fr C, D, F, and H) rich in carnosic acid (CA) and carnosol (CL), with significantly higher concentrations (26.3–93.5 g/kg) compared to the crude extract (10.0 g/kg). Other phenolic compounds, including caftaric acid, epicatechin, quercetin, and rutin, were also detected in notable amounts via ultra-high-performance liquid chromatography-mass spectrometry/mass spectrometry (UHPLC-MS/MS). CA-/CL-rich fractions effectively induced caspase-9 and caspase-3 activities, decreased cell viability, and increased lactate dehydrogenase (LDH) release. These effects were significant compared to those induced by 0.1 mM hydrogen peroxide (H2O2). Notably, Fr D and Fr H, which contained the highest CA/CL concentrations, showed caspase-9/caspase-3 activities of 1.60/1.83 and 1.63/1.94, respectively, at 25 μg/mL after 24 h of treatment, whereas the crude plant extract showed corresponding activity values of 1.33/1.36 under the same conditions. In contrast, the crude extract exhibited its strongest apoptotic and cytotoxic effects under harsher conditions (50 μg/mL and 48 h), with caspase-9/caspase-3 activities of 1.70/2.59, 12.0% cell viability, and 65.4% LDH release. Apoptosis was further supported by superoxide (O2•−) production mediated by NADPH oxidases (NOXs), as the NOX inhibitor diphenyleneiodonium (DPI) reduced O2•− levels by 28.6%–48.6%. Additionally, nuclei-stained cells revealed morphological changes, including nuclear fragmentation, apoptotic body formation, and loss of adhesion. In conclusion, CA-/CL-rich S. dorystaechas isolates demonstrated strong apoptotic and cytotoxic effects on HepG2 cells, with contributions from other phenolic compounds. These findings highlight the potential therapeutic value of S. dorystaechas isolates in liver cancer treatment.
期刊介绍:
The Journal of Food Biochemistry publishes fully peer-reviewed original research and review papers on the effects of handling, storage, and processing on the biochemical aspects of food tissues, systems, and bioactive compounds in the diet.
Researchers in food science, food technology, biochemistry, and nutrition, particularly based in academia and industry, will find much of great use and interest in the journal. Coverage includes:
-Biochemistry of postharvest/postmortem and processing problems
-Enzyme chemistry and technology
-Membrane biology and chemistry
-Cell biology
-Biophysics
-Genetic expression
-Pharmacological properties of food ingredients with an emphasis on the content of bioactive ingredients in foods
Examples of topics covered in recently-published papers on two topics of current wide interest, nutraceuticals/functional foods and postharvest/postmortem, include the following:
-Bioactive compounds found in foods, such as chocolate and herbs, as they affect serum cholesterol, diabetes, hypertension, and heart disease
-The mechanism of the ripening process in fruit
-The biogenesis of flavor precursors in meat
-How biochemical changes in farm-raised fish are affecting processing and edible quality