The Indonesian Biomedical Journal

1-22

Authors: Anna Meiliana, Nurrani Mustika Dewi, Andi Wijaya

BACKGROUND: World Health Organization has reported four million people die every year due to obesity comorbidity, and the prevalence of obesity is keep increasing, especially after COVID-19. Obesity has been defined as a chronic disease involving adipose tissue dysfunction which leads to metabolic diseases and psychosocial consequences. The review article will highlight some recent researches regarding the new conceptual framework that integrates both metabolic drives, as well as to summarize the numerous discussions about the current understanding of hypothalamic control of food intake and energy homeostasis. CONTENT: Obesity apparently is not simply regulated only by food and exercise. Hypothalamus takes part in controlling energy intake and expenditure via appetite regulation. Hedonic control in cortical and subcortical brain areas process cognitive, reward, information, and executive function. Managing metabolic adaptation, browning the white adipose tissue, and preserving lean mass can be another strategy to safely manage obesity. SUMMARY: Obesity need to be managed in a multimodal strategy including neurophysiology and physiology approach, together with environment support. Thus, a weight regain can be prevented. Commitment from both scientific and regulation point of view can shed a light to eradicate obesity.

31-9

Authors: Edy Fachrial, Juliana Lina, Harmileni, Sari Anggraini, Widya Yanti Sihotang

BACKGROUND: Type 2 diabetes mellitus (T2DM) cases tend to rise throughout the year in all parts of the world. The α-glucosidase inhibitors are frequently used to both prevent and treat T2DM. This α-glucosidase inhibitor activity is seen in some probiotic species, and a certain strain of Pediococcus acidilactici exhibits promising characteristics as an α-glucosidase inhibitor. This study was conducted to assess the hypoglycemic activity and safety of P. acidilactici strain DNH16 (PADNH16) in experimental rats with T2DM induced by streptozotocin. METHODS: The experiment was conducted in vivo using Wistar rats. Acarbose was employed as a positive control, and Lactobacillus casei was used as a comparative. For 24 days, post-prandial blood glucose levels were assessed every 3 days, followed by serum biochemical levels measurement of liver, kidney, and lipid profiles. The pancreas was histopathologically examined utilizing the Hematoxyline-Eosin staining procedure. RESULTS: Administration of PADNH16 to T2DM rats lowered post-prandial blood glucose levels and gave hypoglycemic benefits comparable to acarbose and commercial probiotics. PADNH16 dosing did not affect serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), urea, or creatinine levels, showing that PADNH16 was not hazardous to liver or kidney function. The lipid profile assessment revealed that the values, including high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides, were comparable to the control group. The pancreatic histopathology revealed that injection of PADNH16 caused no alterations to pancreatic β cells. CONCLUSION: P. acidilactici isolate DNH16 has a hypoglycemic effect on T2DM rats, but does not affect liver function enzymes, kidneys, lipid profiles and does not provide significant changes in pancreatic β cells.

48-55

Authors: Muhammad Ridwan, Herlina Dimiati, Maimun Syukri, Ronny Lesmana, Lia Meuthia Zaini

BACKGROUND: Sodium glucose co-transporter-2 inhibitor (SGLT2-i), a new oral antidiabetic drug, has been recommended for its morbidity and mortality benefits in patients with heart failure. This study aimed to determine the effect of acute SGLT2-i therapy on the relative ratio expression of microRNA-21 (miR-21), transforming growth factor-β1 (TGF-β1), and matrix metalloproteinase-2 (MMP-2) in the process of cardiac fibrosis in the hyperglycemia Wistar rat models compared to biguanide (metformin) therapy. METHODS: We used Streptozotocin (STZ) to induce hyperglycemia in Wistar rats (n=31), randomly divided into four groups: negative control (NC, n=4), positive control (PC, n=10), hyperglycemia plus metformin (M, n=8), and hyperglycemia plus empagliflozin (E, n=9). After seven weeks, the rats were sacrificed and the heart tissue was taken for microRNA and messenger RNA (mRNA) extraction, followed by reverse transcription quantitative real time polymerase chain reaction (RT-qPCR) examination. The data was analyzed using One-way ANOVA. RESULTS: Results showed a decreasing trend in the gene expression relative ratio of miR-21 (1.0 vs. 1.9; p=0.079) and TGF-β1 (0.9 vs. 3.2; p=0.145), but a significant increase in MMP-2 gene expression (1.3 vs. 0.7; p=0.002) in the SGLT2-i (empagliflozin) vs. biguanide (metformin) groups. CONCLUSION: Empagliflozin administration may play a significant role in preventing the occurrence of cardiac fibrosis in hyperglycemia.

66-71

Authors: Ryco Giftyan Ardika, Bernardus Parish Budiono, Nyoman Suci Widiastiti, Nani Maharani, Neni Susilaningsih, Ferry Sandra

BACKGROUND: Microcirculation and cellular disturbances caused by sepsis might trigger significant intestinal damage. Andrographis paniculata extract decreases inflammatory intestinal epithelial cells with its role as an antiparasitic and anti-inflammatory agent. However, A. paniculata extract’s effect on sepsis have not been commonly studied, especially in the intestinal tissues. Therefore, this study was conducted to determine A. paniculata leaves extract (APLE) effect in sepsis-induced intestinal tissues of rats by examining the expression of inflammatory cytokines involved in sepsis, namely tumor necrosis factor (TNF)-α and Caspase-3. METHODS: Rats were divided into five groups; two groups received no pretreatment and the other three groups received 200, 400, and 500 mg/kg BW/day APLE, respectively. Three pretreated groups and one group with no pretreatment were then injected with 1 mg/200 g BW lipopolysaccharides (LPS) intraperitoneally to create septic rat models. Three days after the LPS-induction, rats were euthanized and the expression of TNF-α and Caspase-3 were assessed based on the immunohistochemical staining of rats’ intestinal tissues. RESULTS: Compared with NaCl (sham), LPS significantly (p<0.001) induced TNF-α expression from 6.60±1.36 to 25.37±1.74. Pretreatment of 200, 400, and 500 mg/kg BW/day APLE could significantly (p<0.001) inhibit the LPS-induced TNF-α expression (18.82±1.36, 11.45±1.18, and 6.89±1.90, respectively). Similar with TNF-α, compared with NaCl (sham), LPS significantly (p<0.001) induced Caspase-3 expression from 6.92±1.66 to 23.59±2.25. Pretreatment of 200, 400, and 500 mg/kg BW/day APLE could significantly (p<0.001) inhibit the LPS-induced Caspase-3 expression (17.47±1.68, 12.99±1.51, and 5.59±1.51, respectively). CONCLUSION: The pretreatment of APLE could inhibit the LPS-induced TNF-α and Caspase-3 expression, therefore APLE could be suggested as a potential sepsis-preventing agent.

79-87

Authors: Ujang Saeful Hikmat, Ani Retno Prijanti, Heri Wibowo, Indriyanti Rafi Sukmawati, Dicky Levenus Tahapary

BACKGROUND: Type 2 Diabetes (T2D) impairs the innate immune system including monocytes. Monocytes are divided into two subgroups depending on the expression of cluster of differentiation (CD)14 and CD16 receptors, namely CD14+CD16- and CD14+CD16+. CD14+CD16+ are proinflammatory monocytes and develop into M1 type macrophages, which contribute to foam cell production, a risk factor for cardiovascular disease (CVD). Therefore, it is important to determine the influence of T2D conditions on changes in monocyte subsets and whether these changes correlate with CVD risk markers. METHODS: Peripheral blood mononuclear cell (PBMC) was obtained from 10 T2D subjects and 10 healthy donors. Subsequently, PBMC was incubated for 24 hours with and without 10 mL lipopolysaccharide. Flow cytometry was used to evaluate CD14 and CD16 expression, while multiplex immunoassays were applied to measure interleukin (IL)-1b and IL-10 concentrations in supernatants. RESULTS: In T2D, the percentage of CD14+CD16+ monocytes increased (p=0.07), and an increase in CD14+CD16+ monocytes more than 6.8% was linked with CVD risk markers (r=10.146, p=0.002). Meanwhile, inflammatory mediators released by monocytes shown an increase in IL-1b (p=0.041) but not in IL-10 (p=0.082) in T2D subjects. Fasting blood glucose levels were also found to be substantially linked with an increase in CD14+CD16+ monocytes (r=0.530, p=0.016). CONCLUSION: T2D patients had a higher percentage of CD14+CD16+ monocytes and IL-1b levels than healthy donors. An increase in CD14+CD16+ monocytes above 6.8% associated with CVD risk markers in T2D patients.