The Indonesian Biomedical Journal (Prodia Education and Research Institute)
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Lycopene Enhances the Beta Cell Capacity and Antihyperlipidemic Effects of Metformin on Type 2 Diabetic Rats
Get PDFBACKGROUND: Hyperglycemia causes dyslipidemia in type 2 diabetes mellitus (T2DM). Metformin monotherapy is known to be less effective at improving glycemic status, insulin function, and lipid profiles. Lycopene is a potential antioxidant and has been shown to be hypoglycemic and hypocholesterolemic. However, the effects lycopene and metformin combination are still up for debate. This study was conducted to determine the potential of lycopene in enhancing the ability of metformin to improve glycemic status, insulin resistance, beta cell capacity, and lipid profile of T2DM rats.METHODS: Thirty male Wistar rats were randomly divided into six groups: control (N), T2DM-untreated (D), T2DM + metformin (DM), T2DM + metformin + 10 mg/kgBW lycopene (DMLy-10), T2DM + metformin + 20 mg/kgBW lycopene (DMLy-20), and T2DM + metformin + 40 mg/kgBW lycopene (DMLy-40). The treatment was administered once daily through oral route and lasted for 28 days, before blood samples were collected. Fasting blood glucose (FBG) was assessed by oxidase-peroxidase method, fasting serum insulin and HbA1c were measured using enzyme-linked immunosorbent assay (ELISA), while lipid profile was determined using enzymatic methods. The homeostatic model assessment for insulin resistance (Homa-IR) as well as the homeostatic model evaluation of β-cell function (Homa-B) were then calculated.RESULTS: Fasting serum insulin levels increased significantly (p<10.05) in the DMLy-20 and DMLy-40 groups, but Homa-B or high-density lipoprotein (HDL) did not significantly increase. Additionally, the FBG, HbA1c, Homa-IR, total cholesterol, triglyceride, and low-density lipoprotein levels were not significantly decreased than in the group treated with metformin alone.CONCLUSION: Lycopene can enhance the ability of metformin to improve the glycemic status, insulin resistance, beta-cell capacity, and lipid profile of T2DM rats.KEYWORDS: dyslipidemia, Homa-B, insulin resistance, lycopene, metformin, type 2 diabetes mellitu
Lactococcus lactis D4 Decreases NF-κB and α-SMA in Rat Models of Obstructive Jaundice
Get PDFBACKGROUND: Obstructive jaundice, often due to choledocholithiasis or malignancies, leads to immune suppression, intestinal damage, and bacterial translocation, worsening outcomes. Some inflammatory mediators like nuclear factor kappa B (NF-κB), alpha-smooth muscle actin (α-SMA), and interleukin-6 (IL-6) are important in this process. Current treatments remain inadequate, highlighting the need for novel approaches. Probiotics, such as Lactococcus lactis D4 (LLD4), may help reduce inflammation and bacterial translocation, thus offering a potential therapeutic option. This study was conducted to evaluate the effects of LLD4 on NF-κB, α-SMA, and IL-6 in obstructive jaundice rat models.METHODS: This post-test randomized controlled study involved 15 male Wistar rats divided into three groups: sham, bile duct ligation (BDL), and BDL+LLD4 groups. The rats were maintained for 7–10 days, with the rats in BDL+LLD4 group received fermented milk containing LLD4 via gavage at a dose of 112 mg/20 gBW per day for 7 days. The expression levels of NF-κB, α-SMA, and IL-6 were analyzed using immunohistochemistry.RESULTS: Administration of LLD4 were able to significantly reduced NF-κB expression compared to the BDL group (40.20±21.276 vs. 53.60 ± 20.403) in obstructive jaundice rat models. Though not significant, BDL+LLD4 group showed lower α-SMA expression compared to BDL group (58.40±14.271 vs. 63.20±9.16). However, administration of LLD4 did not give any significant effect on IL-6 expression.CONCLUSION: LLD4 reduces inflammation in models of obstructive jaundice by lowering the NF-κB and α-SMA expression. This indicates that LLD4 might be potential as an adjunct therapy for reducing morbidity in obstructive jaundice cases.KEYWORDS: obstructive jaundice, bile duct ligation, Lactococcus lactis D4, NF-κB, α-SMA, IL-
Butterfly Pea and Roselle Combination Extracts Reduce V-CAM, ICAM, and IL-6 Levels in High Fat Atherogenic Diet Rats
Get PDFBACKGROUND: Atherosclerosis, driven by inflammation and oxidative stress, increases the risk of coronary heart disease (CHD). Flavonoids in butterfly pea and roselle are known for their potent antioxidant and anti-inflammatory properties. While their individual effects on cardiovascular health have been studied, no studies have explored the combined impact on atherosclerosis biomarkers, including vascular cell adhesion molecules (VCAM)-1, intercellular adhesion molecule (ICAM)-1, and interleukin (IL)-6. Therefore, this study was performed to evaluate the synergistic effects of butterfly pea and roselle combination extracts (BPRCE) on these biomarkers.METHODS: A study with a post-test control group design using 36 male white rats was performed. The rats were randomly assigned to 6 groups; 1 group was fed with standard feed, while 5 groups were fed with a high-fat atherogenic diet (HFAD) to create atherosclerosis rat models. The HFAD rats were given either no treatment, sodium carboxymethylcellulose (Na-CMC), 300, 400, or 500 mg/kgBW BPRCE. Serum levels of VCAM-1, ICAM-1, and IL-6 of rats were measured using enzyme-linked immunosorbent assay (ELISA) methods.RESULTS: Increasing doses of BPRCE resulted in a significant reduction in VCAM-1, ICAM-1, and IL-6 compared to the other groups. The group with the highest dose, 500 mg/kgBW BPRCE, showed the greatest reduction of VCAM-1 level (32.73±3.57 pg/mL), ICAM-1 level (5.68±1.17 ng/mL), and IL-6 levels (21.49±4.62 pg/mL).CONCLUSION: Administration of BPRCE in atherosclerosis rats model reduces VCAM-1, ICAM-1, and IL-6 in a dose-dependent manner. This study showed that using BPRCE as a traditional remedy for preventing and treating CHD at an optimal dose of 500 mg/kgBW might be a potential future application in reducing atherosclerosis biomarkers.KEYWORDS: VCAM-1, ICAM-1, IL-6, butterfly pea, rosella, atherosclerosi
Lactiplantibacillus plantarum IS-10506 Supplementation Improves Clinical Outcome and Immunology Markers in Psoriasis Vulgaris Patients: A Randomized Controlled Trial
Get PDFBACKGROUND: Probiotics may modify the gut microbiome and have been proven to improve psoriasis vulgaris. Lactiplantibacillus plantarum IS-10506 is a probiotic strain of Indonesian origin. It offers a safe and effective probiotic for psoriasis patients in Indonesia. This study was conducted to evaluate the effect of L. plantarum IS-10506 on clinical and immunology markers in psoriasis vulgaris.METHODS: This randomized, placebo-controlled, and double-blind trial compared L. plantarum IS-10506 (2×1010 CFU/day) and placebo in 49 patients mild-moderate psoriasis vulgaris, which were divided into intervention (n=24) and control groups (n=25). The interventions were given twice daily for 12 weeks. Both groups received topical corticosteroid and emollient as standard treatment. Psoriasis area and severity index (PASI), dermatology life quality index (DLQI), interleukin (IL)-10, IL-17, and forkhead box protein (Foxp3) were then assessed.RESULTS: Mean PASI score for the the subjects in probiotic group was significantly reduced compared to placebo at week-6 (p=0.024), and was sustained until week-12 (p=0.049). At week-12, DLQI scores in the probiotic group were lower than placebo (7.57±5.77 vs. 7.79±5.48). IL-17 level was significantly decreased (p=0.013), while the IL-10 and Foxp3 were significantly increased (p≤0.001 and p=0.048, respectively) in probiotic group. Six months after the completion of study, subjects in probiotic group had a lower probability of flares (52.2%) compared to placebo (79.2%). Two subjects receiving probiotics and one receiving placebo noticed changes in defecation frequency, while another subject in the placebo group complained of mild nausea.CONCLUSION: L. plantarum IS-10506 might effectively improve clinical outcomes and immune biomarkers in psoriasis vulgaris patients, potentially acting as an adjuvant therapy.KEYWORDS: psoriasis, probiotic, clinical severity, immune marker, human and healt
Exosomal miRNAs as Potential Biomarkers for Preeclampsia: miR-1283 Has the Highest Expression, while miR-152-3p Has the Lowest Expression
Get PDFBACKGROUND: Preeclampsia management is necessary, as it is one of the leading causes of death during pregnancy. Exosomal microRNAs (miRNAs) can serve as biomarkers for early detection, diagnosis, and prognosis of preeclampsia. NanoStrings is an effective method for identifying exosomal miRNA due to their high sensitivity and ability to work with small amounts of miRNA; however, the analysis using this method for determining preeclampsia biomarker is still limited. Therefore, this study was conducted to utilize the NanoStrings method in identifying preeclampsia biomarkers related to its underlying pathophysiology.METHODS: This study involved 12 pregnant women at 20–40 weeks of gestation, including 6 preeclampsia women and 6 normotension women. The miRNAs from plasma exosomes were processed using NanoStrings method with NanoString nCounter SPRINT Profiler. Enrichment analysis of The Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways were performed to examine the pathophysiological pathways of preeclampsia, using the DIANA–miRPath v3.0.RESULTS: Forty-eight miRNAs were downregulated and 7 were upregulated (miR-1283, miR-613, miR-520a-3p, miR-3185, miR-556-3p, miR-1973, and miR-598-3p) in women with preeclampsia. The highest expression was observed in miR-1283 (log fold-change: 3.69) and the most lowest expression was in miR-152-3p (log fold-change: 1.41). Enrichment analysis showed that the most upregulated miRNAs pathways was estrogen signaling pathway, and the most downregulated was Hippo signaling pathways.CONCLUSION: miR-1283 has the highest expression, while and miR-152-3p has the lowest expression in preeclampsia women. These miRNAs are shown to be linked to specific pathways, shedding light on the pathophysiology of preeclampsia, and may serve as promising biomarkers.KEYWORDS: exosomes, biomarker, miRNAs, pathophysiology, preeclampsia, pregnanc
Andrographis paniculata Leaf Extract Increases Interleukin-2 in Malnutrition Rat Model
Get PDFBACKGROUND: Malnutrition is a global health concern that results in changes in nutritional status, as indicated by alterations in phenotypic markers, hematological and biochemical parameters, and increased susceptibility to infection, as shown by decreased interleukin (IL)-2 levels. Andrographolide, the active component of Andrographis paniculata, stimulates the immune system and exhibits antibacterial and antiviral activity. Therefore, A. paniculata may serve as a potential adjuvant therapy for malnutrition. This study was conducted to analyze the effect of A. paniculata as an immunomodulator against malnutrition with characteristics of environmental enteric dysfunction (EED) and a low-protein diet by examining phenotypic markers, hematological, biochemical, and IL-2 levels.METHODS: Forty-five male Wistar rats were divided into seven groups. They were fed either a standard or a low-protein diet before receiving oral administration of various concentrations of A. paniculata leaf extract (APLE). APLE was administered 21 days after the initial low-protein diet. Hematological, biochemical, and phenotypic markers were assessed to determine the nutritional status of the rats. The protective effects of APLE were evaluated by measuring IL-2 levels using enzyme-linked immunosorbent assay (ELISA).RESULTS: Malnourished rats exhibited slow body growth, physical and behavioral changes, reduced leukocyte count, total protein, albumin, cholesterol, and villi length. Malnourished rats treated with APLE showed a more effective and significant increase in IL-2 levels, with higher concentrations of APLE resulting in higher IL-2 levels.CONCLUSION: APLE, in a concentration-dependent manner, can increase IL-2 levels, suggesting that APLE may have potential protective effects in a rat model of malnutrition.KEYWORDS: Andrographis paniculata, environmental enteric dysfunction, interleukin (IL)-2, low protein, malnutritio
Tumor Differentiation is Correlated with Estrogen Receptor Beta (ERβ) Expression but Not with Interleukin-6 (IL-6) Expression in Colorectal Carcinoma
Get PDFBACKGROUND: Colorectal carcinoma (CRC), the third most common malignant disease worldwide, is associated with estrogen receptor β (ERβ) and interleukin-6 (IL-6). ERβ is known to down-regulate IL-6 in prostate cancer, lung carcinoma, and CRC cell lines; however, its effect on human with CRC remains unclear. Therefore, this study was conducted to investigate the association between ERβ and IL-6 expressions with the clinicopathological features of CRC.METHODS: This was an analytic observational study using 40 paraffin blocks of CRC patients. ERβ and IL-6 expression was measured by immunohistochemistry (IHC) staining. The percentage of immunoreactive tumor cell per 1000 cells was manually recorded and tumor differentiation as well as tumor infiltration were determined. Tumor differentiation was graded according to the World Health Organization (WHO) 2010 criteria, while tumor infiltration was defined based on the American Joint Committee on Cancer (AJCC) 8th edition.RESULTS: Fifty percent of samples were well-differentiated CRC, and 57.5% samples were T3 infiltration tumors. IHC staining showed 35.5% of samples were positive for ERβ expression, while 70.86% were positive for IL-6 expression. There were negative correlation of ERβ expression with tumor differentiation (p=0.018; r=-0.371), but no correlation with tumor infiltration (p=0.836) were found. There was no correlation between ERβ expression with IL-6 expression (p=0.154).CONCLUSION: There is statistically significant correlation between tumor differentiation and ERβ expression, wherein improved tumor differentiation is linked to higher levels of positive ERβ expression. However, there is no discernible relationship between IL-6 and tumor differentiation. These findings suggest that while IL-6 was involved in the growth of the tumor, ERβ expression might have an impact on tumor differentiation.KEYWORDS: colorectal carcinoma, estrogen receptor beta, interleukin-6, cell differentiatio
Cardamom Essential Oil Extract Suppress the Progression of Triple-Negative Breast Cancer 4T1 Cell Line
Get PDFBACKGROUND: Cardamom (Amomum cardamom) essential oil (CEO) contains monoterpenes with antioxidant activity and is reported to exhibit anticancer activity against some cancer cell lines. Triple-negative breast cancer (TNBC) has the lowest prognosis among breast cancer types due to its aggressive characteristics. This study was conducted to explore the potency of CEO in inhibiting 4T1 cell proliferation and migration and compared its activity to sappan (Caesalpinia sappan) wood extract (CSE).METHODS: We used the 4T1 cell line as the TNBC cell model and tested the cytotoxicity of CEO by using a trypan blue exclusion assay. We studied the senescence induction ability of CEO using SA-β-Gal assay, the migratory inhibition activity using scratch wound healing assay, and inhibition of matrix metalloproteinase 9 (MMP-9) expression using gelatin zymography. RESULTS: CEO showed cytotoxicity toward 4T1 cells with the IC50 values of 60 µg/mL. CEO at ½ IC50 and IC50 concentration significantly increased cell senescence, but CSE did not. CEO at IC50 also reduced cell ability to migrate and also considerably reduced MMP-9 activity. Moreover, these activities related to the inhibition of the cell metastasis process were weaker compared than that of CSE.CONCLUSION: CEO showed potency as a chemopreventive agent on the TNBC 4T1 cell line model with moderate cytotoxicity. CEO induced 4T1 cell senescence, inhibited cell migration and suppressed MMP-9 expression.KEYWORDS: Amomum cardamom, Caesalpinia sappan, 4T1, senescence, cell migration, triple-negative breast cancer
Higher Nrf2 Level is Correlated with Metabolic Parameters in Type 2 Diabetes Mellitus
Get PDFBACKGROUND: Type 2 diabetes mellitus (T2DM) is the most common metabolic disorder associated with oxidative stress and chronic inflammation. Understanding the regulatory mechanisms related to the role of nuclear factor erythroid 2 (Nrf2), a master regulator of cellular antioxidant defenses, in individuals with T2DM, is essential. Therefore, in-depth investigation regarding the associations between Nrf2 levels, and metabolic parameters, such as waist circumference, fasting glucose levels, HbA1C, and serum inflammatory markers expressions is needed to elucidate the mechanisms driving T2DM and its metabolic disturbances.METHODS: This was a cross-sectional study including 90 T2DM and 25 healthy subjects. Nrf2 level; serum inflammatory markers levels, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, interferon (IFN)-α2, IFN-g, monocyte chemoattractant protein (MCP)-1, IL-10, IL-12p70, IL-17A, IL-18 and IL-23; as well as waist circumference; fasting glucose levels; and HbA1C were measured. Nrf2 concentrations in peripheral blood mononuclear cells were determined using enzyme-linked immunosorbent assay (ELISA), while serum inflammatory markers concentrations were quantified with flowcytometry.RESULTS: Nrf2, TNF-α, and IL-17A levels were significantly higher in the T2DM group, while IL-1β, IFN-α 2, IL-10, IL-12p70, and IL-23 levels were elevated in healthy controls Nrf2 exhibited positive correlations with waist circumference, fasting glucose, HbA1C, and TNF-α. Conversely, an inverse correlation of Nrf2 was observed with IL-1β, IL-12p70 and IL-17A.CONCLUSION: Correlations between Nrf2 and metabolic clinical parameters suggest its role in regulating glucose metabolism and adiposity. Elevated Nrf2 levels observed in T2DM patients may present novel therapeutic avenues for enhancing endogenous antioxidant defenses.KEYWORDS: type 2 diabetes mellitus, Nrf2, oxidative stress, inflammation, metabolic regulation, therapeutic strategie
Efficacy and Safety of Undenatured Type II Collagen in The Treatment of Osteoarthritis of The Knee: A Randomized, Double-blind, Placebo-controlled Trial
Get PDFBACKGROUND: Available medication for pain and joint stiffness release in osteoarthritis (OA) often gives considerable side effects. Undenatured type II collagen (UC-II) has been considered as a treatment for OA for its ability to prevent the progress of articular cartilage damage. Hence, this study aimed to evaluate the efficacy and safety of UC-II in modulating knee joint function.METHODS: This was a randomized, double-blind, placebo-controlled study involving 102 OA subjects. Subjects were randomized into two groups: receiving an oral daily dose of 40 mg/day UC-II or placebo containing microcrystalline cellulose for 90 days. Efficacy was evaluated by using the Western Ontario McMaster Osteoarthritis Index (WOMAC), Lequesne’s Functional Index (LFI), and Visual Analogue Scale (VAS) score on day-1, -7, -30, -60, and -90. Safety was evaluated by assessing the adverse events (AEs) and abnormal laboratory findings.RESULTS: The WOMAC total score showed a significant difference between the UC-II group vs. the placebo group from day-7 (p<0.05) to day-90 (p<0.01). UC-II was more effective in reducing the WOMAC total scores by 81.6% compared to 19.2% in the placebo group after 90 days. The total LFI and VAS score was significantly reduced in subjects supplemented with UC-II compared to the placebo group (75.8% vs. 7.8%; 67.9% vs. 12.2%, respectively). No significant changes were observed in vital signs and clinical laboratory tests compared to the placebo. The UC-II had a good safety profile with no serious adverse events among participants.CONCLUSION: UC-II significantly improved the knee pain, stiffness, and functional mobility of OA patients and was well-tolerated.KEYWORDS: osteoarthritis, undenatured type II collagen, WOMAC, VAS, LF