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Mudjahid, Mukarram
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Biochemistry, Genetics & Molecular Biology Health Professions Immunology & microbiology Medicine & Pharmacology Public Health

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Anti-aging and immunomodulatory role of caffeine in Drosophila larvae Nainu, Firzan; Sartini, Sartini; Bahar, Muhammad A.; Asbah, Asbah; Rosa, Reski A.; Mudjahid, Mukarram; As'ad, Muhammad F.; Latada, Nadila P.
Narra J Vol. 4 No. 2 (2024): August 2024
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narra.v4i2.818

Abstract

Drug repurposing is a promising approach to identify new pharmacological indications for drugs that have already been established. However, there is still a limitation in the availability of a high-throughput in vivo preclinical system that is suitable for screening and investigating new pharmacological indications. The aim of this study was to introduce the application of Drosophila larvae as an in vivo platform to screen drug candidates with anti-aging and immunomodulatory activities. To determine whether Drosophila larvae can be utilized for assessing anti-aging and immunomodulatory activities, phenotypical and molecular assays were conducted using wildtype and mutant lines of Drosophila. The utilization of mutant lines (PGRP-LBΔ and Psh[1];;ModSP[KO]) mimics the autoinflammatory and immunodeficient conditions in humans, thereby enabling a thorough investigation of the effects of various compounds. The phenotypical assay was carried out using survival and locomotor observation in Drosophila larvae and adult flies. Meanwhile, the molecular assay was conducted using the RT-qPCR method. In vivo survival analysis revealed that caffeine was relatively safe for Drosophila larvae and exhibited the ability to extend Drosophila lifespan compared to the untreated controls, suggesting its anti-aging properties. Further analysis using the RT-qPCR method demonstrated that caffeine treatment induced transcriptional changes in the Drosophila larvae, particularly in the downstream of NF-κB and JAK-STAT pathways, two distinct immune-related pathways homologue to humans. In addition, caffeine enhanced the survival of Drosophila autoinflammatory model, further implying its immunosuppressive activity. Nevertheless, this compound had minimal to no effect on the survival of Staphylococcus aureus-infected wildtype and immunodeficient Drosophila, refuting its antibacterial and immunostimulant activities. Overall, our results suggest that the anti-aging and immunosuppressive activities of caffeine observed in Drosophila larvae align with those reported in mammalian model systems, emphasizing the suitability of Drosophila larvae as a model organism in drug repurposing endeavors, particularly for the screening of newly discovered chemical entities to assess their immunomodulatory activities before proceedings to investigations in mammalian animal models.
A fruit fly-based approach to unraveling enteropathy-causing pharmaceuticals Pratama, Muhammad R.; Wahyudin, Elly; Putri, Tenri ZAD.; Hardiyanti, Widya; Fatiah, Dewita; Chaeratunnisa, Rizkya; Bapulo, Nurdewi N.; Latada, Nadila P.; Mudjahid, Mukarram; Nainu, Firzan
Narra J Vol. 4 No. 2 (2024): August 2024
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narra.v4i2.898

Abstract

Enteropathy is a gastrointestinal disorder characterized by inflammation in the small intestine and one of the causes of enteropathy is the side effects of certain drugs, such as non-steroidal anti-inflammatory drugs (NSAIDs). The mechanism of NSAIDs, such as indomethacin, could inhibit prostaglandin synthesis, leading to a decrease in mucus production and small intestine integrity. To test the effects of a drug, it is necessary to undergo preclinical testing using animal models. Commonly used animal models such as mice and rats have several drawbacks including high cost, ethical issues, and long lifespan. Therefore, alternatives such as using invertebrate animals like Drosophila melanogaster as a more economical in vivo platform with genetic similarity to mammals and devoid of ethical concerns are needed. The aim of this study was to evaluate Drosophila melanogaster as an in vivo model organism in testing the side effects of pharmaceuticals that cause enteropathy. In this study, flies aged 3–5 days were starved and then placed into treatment vials comprising untreated control and indomethacin-treated (3.75 mM, 7.5 mM, and 15 mM). Survival analysis was conducted during the treatment period, followed by a Smurf assay test after seven days of treatment. Subsequently, the expression of pro-inflammatory cytokine-related genes (drs and totA), mitochondria stability-related genes (tom40), and endogenous antioxidant-related genes (sod1, sod2, and cat) was performed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Our data indicated that indomethacin did not impact lifespan or cause intestinal damage. However, we observed increased expression of pro-inflammatory cytokine-related genes, including drs, and a twofold increase in totA gene expression. Furthermore, there was a significant upregulation of mitochondrial stability gene tom40, endogenous antioxidant genes sod1 and cat, and a threefold increase in sod2 at 15 mM indomethacin. Although no phenotypical changes in gut integrity were detected, the increased expression of pro-inflammatory cytokine genes suggests the occurrence of inflammation in the indomethacin-treated flies.
Undernutrition-induced stunting-like phenotype in Drosophila melanogaster Putri, Tenri ZAD.; Wahyudin, Elly; Pratama, Muhammad R.; Fatiah, Dewita; Hardiyanti, Widya; Chaeratunnisa, Rizkya; Latada, Nadila P.; Fatmawati, Fatmawati; Mudjahid, Mukarram; Nainu, Firzan
Narra J Vol. 4 No. 3 (2024): December 2024
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narra.v4i3.999

Abstract

Stunting resulting from undernutrition is a significant global health challenge, particularly in developing countries, yet its underlying mechanisms and consequences remain inadequately understood. This study utilizes Drosophila melanogaster as an in vivo model to investigate the molecular basis of stunting. Due to the conserved nature of signaling pathways between Drosophila and vertebrates, this organism serves as an effective model for studying growth disorders. The aim of this study was to establish a Drosophila model exhibiting a stunting-like phenotype and to elucidate the molecular mechanisms underlying this condition. The stunting phenotype was induced through dietary manipulation, involving a standard nutrient-rich diet (100%) and treatment diets with reduced concentrations of sucrose, glucose, yeast, and cornmeal at 50%, 25%, and 12.5%. Phenotypic assessments included measurements of larval body size, fecundity, survival rates, and locomotor activity, alongside molecular analyses of gene expression related to metabolism, cell proliferation, and survival, using RT-qPCR. Results demonstrated that undernutrition profoundly affected D. melanogaster, causing growth retardation, reduced larval body size, diminished fecundity, and lower survival rates, though locomotor function remained unaffected. Molecular analysis revealed a significant decrease in the expression of the totA gene and notable increases in the expression of dilp5, srl, and indy genes, with no significant changes observed in the expression of the pepck gene. These findings indicate that undernutrition induces a stunting-like phenotype, likely driven by alterations in the expression of genes associated with metabolism, cell proliferation, and survival. Overall, this study establishes D. melanogaster as a valuable in vivo model for studying stunting-like phenotypes resulting from nutritional deficiencies and provides insights into the molecular pathways involved in growth impairment.
Exploring the antidiabetic potential of Sulawesi ethnomedicines: A study of Cordia myxa and Syzygium malaccense in a Drosophila model of hyperglycemia Nainu, Firzan; Bahar, Muhammad A.; Habibie, Habibie; Najib, Ahmad; Zubair, Muhammad S.; Arba, Muhammad; Asbah, Asbah; Mudjahid, Mukarram; Latada, Nadila P.; Filmaharani, Filmaharani; Putri, Annisa A.
Narra J Vol. 5 No. 1 (2025): April 2025
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narra.v5i1.1712

Abstract

The escalating prevalence of diabetes represents a critical challenge to global health and quality of life. Indonesia, particularly the Sulawesi region, is home to a diverse array of endemic plants with potential as sources of novel antidiabetic compounds. However, traditional preclinical models for evaluating these candidates are limited by high costs and lengthy timelines. The aim of this study was to explore the antidiabetic potential of Cordia myxa and Syzygium malaccense extracts using Drosophila melanogaster as a novel, cost-effective and efficient in vivo model. Hyperglycemia was induced in D. melanogaster larvae through a high-sugar diet, and the plant extracts were incorporated into the larval diets at concentrations ranging from 0.3125% to 2.5%. Phenotypic parameters, including body size, body weight, crawling activity, and hemolymph glucose levels, were evaluated, and the expression of metabolism-related genes (dilp2, dilp5, and srl) was analyzed using RT-qPCR. This study found that C. myxa and S. malaccense extracts improved crawling activity and body size in hyperglycemic larvae. Notably, C. myxa extract significantly reduced hemolymph glucose levels (p<0.01), increased body weight (p<0.01), and upregulated the expression of metabolic genes such as dilp2 (p<0.001), dilp5 (p<0.001), and srl (p<0.0001). In contrast, S. malaccense extract showed less pronounced effects, highlighting the efficacy of C. myxa extract in alleviating hyperglycemia and restoring metabolic homeostasis. The study highlights that C. myxa extract demonstrated promising antidiabetic properties in the Drosophila model, underscoring the utility of this model for early-stage antidiabetic drug screening and supporting further preclinical investigation into the therapeutic potential of C. myxa for managing hyperglycemia.
Dual effects of Camellia sinensis and Andrographis paniculata on hyperglycemia and infection in Drosophila Nainu, Firzan; Sartini, Sartini; Subehan, Subehan; Sari, Dwi K.; Bahar, Muhammad A.; Mudjahid, Mukarram; Latada, Nadila P.; Asbah, Asbah; Hardiyanti, Widya; Pratama, Muhammad R.; Suhenro, Suhenro
Narra J Vol. 5 No. 1 (2025): April 2025
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narra.v5i1.1972

Abstract

The coexistence of hyperglycemia and infectious diseases represents a critical global health challenge, particularly in resource-limited settings where it amplifies disease severity and complicates treatment approaches. Medicinal plants such as Camellia sinensis and Andrographis paniculata have gained recognition for their antioxidant, anti-inflammatory, and antimicrobial properties, making them promising candidates for addressing this double health burden. The aim of this study was to establish a preclinical model of hyperglycemia and infection (HI model) using Drosophila melanogaster and to investigate the therapeutic potential of C. sinensis and A. paniculata extracts in alleviating the burden associated with the HI condition. In this study, the HI model was established by simultaneously exposing D. melanogaster larvae to a high-concentration sucrose solution and Staphylococcus aureus for 24 hours. The larvae were then transferred to a high-sucrose diet supplemented with C. sinensis or A. paniculata extracts. Survival assays and molecular analyses were subsequently performed to evaluate the outcomes. Our findings revealed that the combination of hyperglycemia and infection significantly reduced survival rates in the Drosophila model. However, treatment with 1.25% C. sinensis and A. paniculata extracts notably improved survival, attributed to their antibacterial activity and regulation of key molecular pathways involved in immune responses, metabolic balance, and endogenous antioxidant defenses. These findings validate the utility of D. melanogaster as a model organism for investigating the double burden of HI. Furthermore, the study offers compelling evidence of the dual therapeutic potential of C. sinensis and A. paniculata in mitigating the detrimental effects of this condition. Overall, this research underscores the significant promise of plant-derived compounds in managing HI and paves the way for future studies to explore their underlying mechanisms and potential clinical applications.
Co-Authors Ahmad Najib Arba, Muhammad As'ad, Muhammad F. Asbah, Asbah Bahar, Muhammad A. Bapulo, Nurdewi N. Chaeratunnisa, Rizkya Dewita Fatiah Elly Wahyudin Fatmawati Fatmawati Filmaharani, Filmaharani Firzan Nainu Habibie Habibie Hardiyanti, Widya Latada, Nadila P. Pratama, Muhammad R. Putri, Annisa A. Putri, Tenri ZAD. Rosa, Reski A. Sari, Dwi K. Sartini Sartini Subehan, Subehan Suhenro, Suhenro Zubair, Muhammad S.