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INDONESIA
The Indonesian Biomedical Journal
Published by The Prodia Education and Research Institute
ISSN : -     EISSN : -     DOI : -
Core Subject : Health, Science,
Biochemistry, Genetics & Molecular Biology Public Health
Arjuna Subject : -
Articles 651 Documents
 62   63   64   65   66 
Elevated Serum Cathelicidin and Inverse Correlation with Vitamin D in Patients with Intestinal Tuberculosis Nuri Dyah Indrasari; Astuti Giantini; Ninik Sukartini; Dewi Wulandari; Dean Handimulya Djumaryo; Nindy Auliana; Pande Made Satrya Dharma Pathni; Fathoni Afif
The Indonesian Biomedical Journal Vol 18, No 3 (2026)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v18i3.4169

Abstract

BACKGROUND: Intestinal tuberculosis (ITB) is a type of tuberculosis (TB) that affects the gastrointestinal tract. Cathelicidin, an antimicrobial peptide, contributes to defense against Mycobacterium tuberculosis, which causes TB. Its expression is tightly regulated by vitamin D through vitamin D receptor signaling and autophagy pathways. Despite the increasing evidence on TB, studies exploring the correlation between cathelicidin and vitamin D in the ITB remain poorly characterized and almost exclusively derived from pulmonary TB. Therefore, the present study was conducted to compare serum cathelicidin and vitamin D levels between subjects with ITB and without ITB, and to determine the correlation between these two biomarkers.METHODS: This comparative cross-sectional study utilized stored serum samples obtained from participants enrolled in a previous ITB project. Twenty-two ITB and 22 non-ITB subjects aged >18 years who had undergone colonoscopy, histopathological examinations, and fulfilled predefined clinical and diagnostic criteria were included. Serum cathelicidin and vitamin D levels were measured using sandwich enzyme-linked immunosorbent assay (ELISA) and chemiluminescent microparticle immunoassay (CMIA), respectively.RESULTS: Significantly higher levels of serum cathelicidin were identified in ITB subjects, with a median level of 3.67 (2.27‒5.95) ng/mL, compared with non-ITB subjects with a median level of 2.04 (1.66‒2.46) ng/mL (p<0.0001). Although the difference was not statistically significant (p=0.091), vitamin D level tended to be lower in subjects with ITB, with a median level of 11.05 (6.80‒25.25) ng/mL, compared to non-ITB subjects with a median level of 17.95 (12.13‒23.63) ng/mL. A significant moderate negative correlation was found between cathelicidin and vitamin D (r=-0.485, p=0.001).CONCLUSION: The ITB is associated with elevated cathelicidin levels and a tendency toward lower vitamin D levels. The inverse correlation suggests a complex relationship between vitamin D status and cathelicidin expression, highlighting immunological mechanisms involved in ITB pathogenesis.KEYWORDS: antimicrobial peptide, cathelicidin, innate immunity, intestinal tuberculosis, vitamin D
Ethanol Extract of Cyclea barbata Miers Exhibited A Favorable Safety Profile at Moderate Doses in Wistar Rats Noviyanti Noviyanti; Jeri Nobia Purnama; Erick Khristian; Rika Nurhasanah; Indria Astuti
The Indonesian Biomedical Journal Vol 18, No 4 (2026)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v18i4.4290

Abstract

BACKGROUND: Cyclea barbata Miers has been identified as a phytoestrogenic candidate with comparable estrogen receptors (ER)α binding activity with 17β estradiol. Though phytoestrogens are reported to modulate reproductive and hormonal physiology, but no systematic in vivo toxicological evaluation of C. barbata extract has been reported. Therefore, this study was conducted to evaluate the acute and subacute oral toxicity of the ethanol extract of C. barbata (EECB) in Wistar rats.METHODS: For acute toxicity, rats received single oral doses of 2,000 or 5,000 mg/kg BW and were observed for 14 days. For subacute toxicity, EECB was administered orally at doses of 100–500 mg/kg BW/day for 28 consecutive days. Body weight, relative organ weights, haematological and biochemical parameters, and histopathological changes in major organs were evaluated.RESULTS: No mortality occurred at 2,000 mg/kg BW in either sex, whereas mortality was observed only in female rats at 5,000 mg/kg BW (20%). EECB was therefore classified as GHS Category 5 or unclassified (LD50 >2,000 mg/kg BW), indicating low acute oral toxicity. Repeated administration for 28 days caused no significant changes in body weight, organ weights, serum biochemical markers, or histopathological findings. However, a significant reduction in white blood cell counts was observed at doses ≥400 mg/kg BW/day (p<0.05). The subacute no-observed-adverse-effect-level (NOAEL) and lowest-observed-adverse-effect-level (LOAEL) were established at 300 and 400 mg/kg BW/day, respectively.CONCLUSION: Based on the parameters assessed, the acute NOAEL for EECB was 2,000 mg/kg BW, while the subacute NOAEL and LOAEL for EECB were 300 and 400 mg/kg BW/day, respectively. These findings indicate that EECB might be safe at moderate doses, providing in vivo evidence supporting its further development as a phytoestrogenic agent.KEYWORDS: Cyclea barbata Miers, ethanol extract, acute toxicity, subacute toxicity, haematological parameters
Mango-Lime Peel Nanoparticles Improve Diabetic Parameters, Lipid Profiles and Pancreatic Cell Damage in Cigarette Smoke-Exposed Diabetic Rats Yuktiana Kharisma; Raden Anita Indriyanti; Meta Maulida Damayanti; Lelly Yuniarti; Yuke Andriane; Ratih Syifa Hanifah; Saphiera Damayanti
The Indonesian Biomedical Journal Vol 18, No 4 (2026)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v18i4.4220

Abstract

BACKGROUND: Diabetes mellitus often exacerbated by cigarette smoke, which disrupts glucose homeostasis and lipid metabolism. Mango (Mangifera indica L.) and lime (Citrus amblycarpa) peels contain various phytochemical compounds, including those are reported to have metabolic and cytoprotective properties, but their combined nanoparticle formulation in cigarette smoke-exposed diabetes cases remains unexplored. Therefore, this study was conducted to evaluate the synergistic effect of mango-lime peel nanoparticles (NanoMC) on glycemic control, lipid profiles, and pancreatic cell damage in cigarette smoke-exposed diabetic rats.METHODS: Mango and lime peel ethanol extract was prepared into nanoparticles using emulsion-solvent evaporation method and followed by sonication and homogenization, and subsequently divided into three concentration groups. Rats were diabetic-induced and smoke-exposed, before being treated with/without Simvastatin + Glibenclamide, 20, 40, or 80 mg/kgBW NanoMC. Parameters including blood glucose, insulin, homeostatic model assessment of insulin resistance (HOMA-IR), homeostatic model assessment of beta-cell function (HOMA-β), hemoglobin A1c (HbA1c), and lipid profiles were then measured. To evaluate pancreatic cell damage, the pancreatic tissue was collected, fixed, and then evaluated by using Hematoxylin and Eosin (H&E) staining.RESULTS: NanoMC administration significantly reduced blood glucose, HbA1c, triglycerides, cholesterol, and low-density lipoprotein (LDL) levels (p<0.05). NanoMC treatment also increased insulin levels, HOMA-β, and high-density lipoprotein (HDL). After the treatment with NanoMC, particularly with 80 mg/kgBW concentration, fewer degenerative and necrotic cells were found compared to the other groups, showing its ability to attenuate pancreatic cell damage.CONCLUSION: The combination of NanoMC could improve glycemic status, modulate lipid profiles, and improved pancreatic cell damage in diabetic rats exposed to cigarette smoke.KEYWORDS: Mangifera indica, Citrus amblycarpa, nanoparticles, diabetes mellitus, cigarette smoke, lipid profiles, pancreatic histopathology
Concordance of KRAS Mutation in Tumor Tissues and Fecal Samples of Colorectal Carcinoma Patients Ahmad Bahrudin; Reno Rudiman; Andriana Purnama; Kiki Lukman; Yunia Sribudiani; Prapanca Nugraha
The Indonesian Biomedical Journal Vol 18, No 4 (2026)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v18i4.4279

Abstract

BACKGROUND: Colorectal cancer (CRC) is a major global health problem associated with high cancer-related mortality. Profiling of Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation status has become a decisive predictive biomarker in the management of CRC. However, KRAS mutation testing is commonly performed using tumor tissue obtained through invasive biopsy or surgery; therefore, fecal DNA analysis might offer a promising non-invasive alternative. This study was conducted to evaluate the concordance of KRAS mutations between matched tumor tissue and fecal samples and their association with clinicopathological characteristics.METHODS: This cross-sectional study included 94 patients confirmed of CRC. Tumor tissue specimens were obtained during surgical resection or biopsy, while fecal samples were collected pre-operatively. KRAS mutations were analyzed using polymerase chain reaction (PCR) and DNA sequencing, and the associations with clinicopathological variables were statistically evaluated.RESULTS: KRAS mutations were detected in 45.74% of tumor tissue and 26.60% of fecal samples. The overall concordance rate was 65.96%, with a Cohen’s Kappa of 0.291 (95% CI: 0.110–0.472), indicating "fair agreement". Notably, allele-specific concordance was 100% among double-positive cases. The fecal assay demonstrated 41.86% sensitivity, 86.27% specificity, 72.00% positive predictive value (PPV), and 63.77% negative predictive value (NPV). Tumor location (colon versus rectum) was significantly associated with fecal KRAS detection (p=0.028); other variables showed no significant association (p>0.05).CONCLUSION: KRAS mutations were more frequently detected in tissue than in fecal samples, with fair agreement. High allele-specific concordance suggests fecal DNA accurately reflects the tumor's mutational profile. Tumor location significantly influences DNA detectability, supporting fecal-based KRAS testing as a potential non-invasive approach for CRC molecular assessment.KEYWORDS: colorectal neoplasms, feces, KRAS protein, human, mutation, neoplasm tissue
Combination of Insulin and UC-MSCs Secretome Therapy Demonstrates A Trend of Liver Injury Improvement in Diabetic Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD) Rat Model Shirly Gunawan; Siufui Hendrawan; Olivia Marcelina; Jennifer Lheman; Hans Ulrich Baer
The Indonesian Biomedical Journal Vol 18, No 4 (2026)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v18i4.4287

Abstract

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) coexists with diabetes mellitus and presents a significant therapeutic challenge due to its complex metabolic and hepatic pathology. Insulin therapy remains the cornerstone for glycemic management, but its effects on hepatic steatosis is inconsistent. Complementary therapies are needed to address this limitation. Umbilical cord-derived mesenchymal stem cells (UC-MSCs) secretome has emerged as therapeutic approach for metabolic disease due to its anti-inflammatory, immunomodulatory, and antioxidant properties. This study was conducted to evaluate whether adjunctive administration of UC-MSCs secretome could enhance therapeutic outcomes, particularly in alleviating hepatic steatosis in a diabetic MASLD rat model.METHODS: Male rats were grouped into normal and diabetic MASLD rat model, and treated with either growth medium, insulin, UC-MSCs secretome, or combination of insulin and UC-MSCs secretome for 4 weeks. Blood samples were collected and liver enzymatic and lipid profile were analyzed using chemistry analyzer. Liver tissue was also obtained for assessment of liver fibrosis using Hematoxylin-Eosin staining, interleukin (IL)-6 measurement using enzyme-linked immunosorbent assay (ELISA), and superoxide dismutase (SOD) activity measurement using colorimetry.RESULTS: Combined insulin and UC-MSCs secretome therapy showed a trend toward better blood glucose management and lipid parameters, although not statistically significant. Administration of insulin, secretome, and their combination was associated with higher hepatic SOD levels and lower IL-6 protein levels, although not statistically significant. Combined therapy also reduced hepatomegaly compared to untreated diabetic MASLD rat model, and improved hepatic steatosis while significantly alleviating fibrosis severity.CONCLUSION: Combination of insulin and UC-MSCs secretome therapy in diabetic MASLD was able to improve several parameters related to hepatic steatosis compared with the untreated diabetic MASLD rat model. These findings suggest that UC-MSCs secretome might serve as a potential adjunct to insulin therapy.KEYWORDS: metabolic dysfunction-associated steatotic liver disease, type 2 diabetes, cell free therapy, umbilical cord mesenchymal stem cells, secretome 
Oral Nigella sativa Oil Modulates Interleukin-1β and Interleukin-10, Improves Neurological Function, and Reduces Neuronal Necrosis after Traumatic Brain Injury in Rats Abdul Halim Gazali Hayadi; Wahyudi Wahyudi; Djoko Widodo; Joko Hendarto; Andi Asadul Islam; Nasrullah Mustamir
The Indonesian Biomedical Journal Vol 18, No 4 (2026)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v18i4.4294

Abstract

BACKGROUND: Current management of traumatic brain injury (TBI) is primarily directed toward preventing secondary brain injury, while specific pharmacological therapies targeting post-traumatic neuroinflammation remain limited. Bioactive constituents of Nigella sativa, particularly thymoquinone, have demonstrated anti-inflammatory and antioxidant properties that may modulate mechanisms involved in secondary brain injury. This study was conducted to evaluate the effects of oral N. sativa oil on serum interleukin (IL)-1β and IL-10 levels as inflammatory parameters, neurological function and necrosis in a rat model of TBI.METHODS: Sixteen male Wistar rats underwent Marmarou weight-drop TBI and were randomly assigned into two groups given either oral N. sativa oil or distilled water (n=8/group) for 7 days. Serum IL-1β and IL-10 concentrations were measured using rat-specific enzyme-linked immunosorbent assays (ELISA), and neurological function was assessed using the modified Neurological Severity Score (mNSS) at post-injury baseline and on treatment day-1, -3, and -7. After day-7, brain tissue was examined using hematoxylin–eosin (H&E) staining, and necrotic-cell count was assessed.RESULTS: IL-1β concentrations were significantly lower in the N. sativa group from day-1 onward, whereas IL-10 concentrations were significantly higher and mNSS scores were significantly lower from day-3 onward. By day-3, all three outcomes differed significantly: lower IL-1β (56.38±10.21 vs. 111.98±47.64 pg/mL; p=0.013), higher IL-10 (102.38±33.42 vs. 40.20±6.02 pg/mL; p=0.001), and lower mNSS (median: 4 (3-5) vs. 5 (5-6); p=0.003) than placebo group. These differences persisted through day-7, which also supported by lower necrotic-cell counts in the N. sativa group (3164.13±771.38 vs. 4028.38±204.58; p=0.008).CONCLUSION: Administration of oral N. sativa oil shifted the circulating cytokine profile toward an anti-inflammatory pattern and was accompanied by better neurological function and fewer neuronal necrosis after TBI. These findings suggest that N. sativa oil may have beneficial effect on neuroinflammation after TBI.KEYWORDS: Nigella sativa, traumatic brain injury, interleukin-1 beta, interleukin-10, neuroinflammation, modified Neurological Severity Score
Elevated Serum Netrin-1, Platelet-to-Lymphocyte Ratio, and Monocyte-to-Lymphocyte Ratio are Associated with Impaired Fasting Glucose in Adults with Central Obesity Brian Eka Putera; Meita Hendrianingtyas; Nyoman Suci Widyastiti; Dwi Retnoningrum; Purwanto Adipireno
The Indonesian Biomedical Journal Vol 18, No 4 (2026)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v18i4.4282

Abstract

BACKGROUND: Adults with central obesity may develop impaired fasting glucose (IFG) due to chronic low-grade inflammation. Although C-reactive protein (CRP) is a common marker of systemic inflammation, it is nonspecific and cannot fully capture obesity-related inflammatory pathways. Netrin-1 promotes macrophage retention in visceral adipose tissue, thereby sustaining inflammation and insulin resistance, while platelet-to-lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratio (MLR) reflect complementary inflammatory pathways; however, their discriminatory performance and associations with IFG remain uncertain. Therefore, this study was conducted to evaluate these markers in adults with central obesity.METHODS: Blood samples from 88 adults with central obesity were obtained, and fasting glucose concentration was measured using hexokinase method to determine IFG status. Serum Netrin-1 was measured using an enzyme-linked immunosorbent assay (ELISA), serum CRP was measured using fluorescence immunoassay (FIA); PLR and MLR were calculated from complete blood counts. Receiver operating characteristic (ROC) analysis assessed discriminatory performance, while exploratory logistic regression adjusted for age, sex, and BMI to examine biomarker associations with IFG.RESULTS: Among 88 participants, 54.5% had IFG. The AUCs were 0.694, 0.627, 0.689, and 0.532 for Netrin-1, PLR, MLR, and CRP, respectively. In crude prevalence-ratio (PR) analysis, Netrin-1 ≥315.35 pg/mL (PR=1.742; p=0.006), PLR ≥132.43 (PR=1.593; p=0.019), and MLR ≥0.20 (PR=2.119; p<0.001) were associated with IFG, whereas CRP was not. In separate ROC analysis, MLR had an AUC of 0.689 (p=0.002). After adjustment for age, sex, and BMI; MLR ≥0.20 remained associated with IFG (adjusted OR=7.516; p<0.001).CONCLUSION: Elevated serum Netrin-1, PLR, and MLR were associated with IFG in adults with central obesity. MLR showed the strongest crude association and was the only evaluated inflammatory biomarker retained in the exploratory adjusted logistic regression model. As an inexpensive index derived from a routine complete blood count, MLR may complement fasting-glucose assessment by helping characterize the inflammatory phenotype of adults with central obesity.KEYWORDS: central obesity, C-reactive protein, impaired fasting glucose, netrin-1, monocyte-to-lymphocyte ratio, platelet-to-lymphocyte ratio
Asiatic Acid Modulates Il6 and Tgfb1 mRNA Expression and Soluble Collagen Levels in RAW 264.7–NIH 3T3 Co-culture Cells under High-Glucose and LPS Stimulation Rizki Awaluddin; Dwi Aris Agung Nugrahaningsih; Eti Nurwening Sholikhah; Hermanus Ehe Hurit
The Indonesian Biomedical Journal Vol 18, No 4 (2026)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v18i4.4296

Abstract

BACKGROUND: Chronic inflammation contributes to diabetes-associated fibrosis, through persistent hyperglycemia, leading to increased interleukin-6 (IL-6), transforming growth factor-β (TGF-β), and collagen levels. While metformin effectively controls blood glucose, it may not adequately suppress these pathogenic pathways. Asiatic acid has demonstrated anti-inflammatory and antifibrotic properties, although its effects within a direct-contact macrophage–fibroblast microenvironment such as in co-culture models remain unclear. This study was conducted to evaluate the effects of asiatic acid on Il6, Tgfb1, and soluble collagen levels in a RAW 264.7–NIH 3T3 co-culture under high-glucose and lipopolysaccharide (HG–LPS) stimulation.METHODS: RAW 264.7 and NIH 3T3 cells were co-cultured at ratios of 1:1–1:6, and the selected co-culture was treated with asiatic acid (2.5, 5.0, and 10.0 µg/mL) for 24 h while HG–LPS stimulation was maintained. Unstimulated NIH 3T3 monocultures and untreated HG–LPS co-cultures served as controls. The inflammatory and profibrotic markers such as Il6 and Tgfb1 mRNA expression were quantified by polymerase chain reaction (PCR), and soluble collagen was measured using a modified Sirius Red assay.RESULTS: Among the tested ratios, the 1:1 co-culture exhibited the highest Tgfb1 mRNA expression (0.35±0.02) and soluble collagen level (1.30±0.00) and was selected for subsequent experiments, whereas Il6 mRNA expression did not differ significantly among co-culture ratios. Under HG–LPS stimulation, Il6 and Tgfb1 mRNA expression increased 3.5-fold and 10.3-fold, respectively, compared with unstimulated NIH 3T3 monocultures. Asiatic acid significantly reduced Il6 mRNA expression at 5.0 and 10.0 µg/mL, Tgfb1 mRNA expression at 2.5 µg/mL, and soluble collagen levels at all tested concentrations, indicating a non-monotonic concentration–response pattern.CONCLUSION: The 1:1 RAW 264.7–NIH 3T3 co-culture was the most responsive under HG–LPS stimulation and could be in vitro platform for investigating macrophage–fibroblast interactions under hyperglycemic inflammatory conditions. Asiatic acid modulated Il6 and Tgfb1 mRNA expression and soluble collagen levels in RAW 264.7–NIH 3T3 co-culture, which suggest that Asiatic acid may be potential for the management of fibrotic inflammation.KEYWORDS: co-culture, collagen, fibroblast dysfunction, NIH 3T3 fibroblast, RAW 264.7 macrophage
Computational Predicted Mechanism of Tiliroside Compound Against Triple-Negative Breast Cancer Using Network Pharmacology and Induced-Fit Docking Approach Tegar Achsendo Yuniarta; Dwi Syah Fitra Ramadhan; Zulfikar Ali Hasan; Mansur Mansur
The Indonesian Biomedical Journal Vol 18, No 4 (2026)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v18i4.4284

Abstract

BACKGROUND: Triple-negative breast cancer (TNBC) progression is driven by dysregulation of multiple interconnected signaling pathways rather than a single molecular abnormality, but current treatment strategies TNBC primarily rely on single-target therapy, highlighting the need for therapeutic candidates that may target multiple signaling pathway of TBNC. Tiliroside, a naturally occurring flavonoid glycoside, has demonstrated promising anticancer activity; however, its predicted effects on TNBC-associated oncogenic signaling networks remain poorly understood. Therefore, this study aimed to investigate the predicted molecular mechanisms by which tiliroside may modulate TNBC-associated oncogenic signaling networks.METHODS: Integrated computational approach combining network pharmacology, comparative molecular docking, and induced-fit docking was employed. Potential targets of tiliroside were predicted using SwissTargetPrediction and intersected with TNBC-associated genes retrieved from GeneCards. Protein–protein interaction and KEGG pathway enrichment analyses were performed to identify key molecular targets and signaling pathways. Comparative molecular docking was subsequently conducted using 19 structurally related flavonoids with reported anticancer activities against the identified hub proteins, followed by induced-fit docking to characterize the binding mechanism of tiliroside.RESULTS: Fifteen overlapping targets were identified between tiliroside and TNBC. Network analysis highlighted Akt serine/threonine kinase 1 (AKT1), sarcoma (SRC), and epidermal growth factor receptor (EGFR) as the principal hub genes, while the KEGG enrichment revealed significant involvement of phosphoinositide 3-kinase (PI3K)–AKT, erythroblastic leukemia viral oncogene B (ErbB), EGFR tyrosine kinase inhibitor resistance, focal adhesion, and vascular endothelial growth factor (VEGF) signaling pathways. Tiliroside consistently exhibited one of the most favorable binding profiles among the evaluated flavonoids, with binding energies of −9.41, −8.62, and −8.25 kcal/mol toward AKT1, SRC, and EGFR, respectively. Induced-fit docking further confirmed stable hydrogen-bond and hydrophobic interactions within the active sites of these proteins.CONCLUSION: Tiliroside exerts potential anti-TNBC activity through multitarget modulation of interconnected oncogenic signaling pathways, suggesting that tiliroside might be a promising lead compound for TNBC.KEYWORDS: tiliroside, triple-negative breast cancer, network pharmacology, induced-fit docking
Potential Interaction of Propyl Gallate and Butylated Hydroxyanisole with EGFR–PI3K–Akt–mTOR Proteins in Oral and Gastrointestinal Carcinogenic Signaling Pathway: An in silico Molecular Docking Study Ferry Sandra; Visi Endah Pratitis; Dewi Priandini; Andrian Nova Fitri; Maria Leny Raiyon; Kyung Hoon Lee
The Indonesian Biomedical Journal Vol 18, No 4 (2026)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v18i4.4329

Abstract

BACKGROUND: Synthetic food preservatives are widely used to improve food stability and shelf life, but prolonged exposure may contribute to oral and gastrointestinal carcinogenesis. Epidermal growth factor receptor (EGFR)–phosphoinositide 3-kinase (PI3K)–protein kinase B (Akt)–mammalian target of rapamycin (mTOR) axis plays a pivotal role in regulating tumor initiation and progression; however, the potential interactions with cancer-related signaling proteins remain poorly understood. This study computationally evaluated the predicted binding interactions of commonly used synthetic food preservatives with proteins using molecular docking.METHODS: Propyl gallate (PG), butylated hydroxyanisole (BHA), tertiary-butylhydroquinone (TBHQ), potassium sorbate (PS), sodium benzoate (SB), and sodium metabisulfite (SMB) were evaluated for physicochemical properties using SwissADME. Molecular docking with EGFR, PI3K, Akt-1, and mTOR was performed using CB-Dock 2.0. Predicted ligand–protein interactions were analyzed using BIOVIA Discovery Studio 2016 and root mean square fluctuation (RMSF) was evaluated using CABS-flex 3.0.RESULTS: PG and BHA exhibited the most predicted binding affinities among the investigated preservatives. PG showed the strongest interactions with EGFR (−6.1 kcal/mol), PI3K (−6.8 kcal/mol), and mTOR (−6.7 kcal/mol), whereas BHA demonstrated the highest affinity toward PI3K (−6.8 kcal/mol) and Akt-1 (−6.5 kcal/mol). These interactions were supported by multiple hydrogen bonds, hydrophobic interactions, and van der Waals contacts.CONCLUSION: PG and BHA exhibited the highest binding affinity toward proteins of the EGFR–PI3K–Akt–mTOR associated with oral and gastrointestinal carcinogenesis. These computational findings provide a basis for future experimental studies to determine the biological relevance of the predicted protein–ligand interactions under long-term dietary exposure.KEYWORDS: synthetic food preservatives, molecular docking, oral carcinogenesis, gastrointestinal carcinogenesis

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