DeCure's autonomous Psychiatry AI scientist is researching a drug-repurposing hypothesis for non-alcoholic fatty liver disease — screening already-approved drugs against its 39-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleNon-alcoholic fatty liver disease maps to a 39-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for non-alcoholic fatty liver disease is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
glucokinase regulator (GCKR) — GCKR is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet f1pdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4BB9 · 1.47 Å · ligand 1-O-phosphono-beta-D-fructopyranose (F1P). Experimental structure, not a prediction.
What the evidence adds up to
In a 2018 cross-sectional study of 96 type 2 diabetic patients in southwest Ethiopia, the prevalence of non-alcoholic fatty liver disease was 73%. Among those with the disease, 35.4% had mild, 31.3% moderate, and 6.3% severe fatty liver. Alanine aminotransferase, triacylglycerol, total bilirubin, direct bilirubin, and diabetic duration were significantly associated with the condition. The aspartate aminotransferase/alanine aminotransferase ratio in these patients was greater than one.
A 2020 rat study tested noni fruit polysaccharide at 100 mg per kg body weight for five weeks after four weeks of high-fat diet. The polysaccharide reduced body weight gain, improved lipid metabolism, and lowered hepatic oxidative stress and inflammation. It also altered gut microbiota, increasing Lactobacillus and Ruminococcaceae_UCG_014 while decreasing Prevotella_9 and Collinsella, and improved colonic barrier integrity as measured by mRNA expression of CCL5, ZO-1, and occludin. A 2019 cell study using palmitate-induced HepG2 cells found that nifuroxazide, a STAT3 inhibitor, reduced intracellular free fatty acids, triglycerides, and total cholesterol, suppressed lipid synthesis, increased glycogen content, and inhibited gluconeogenesis. The drug also inhibited the IL-6/STAT3/SOCS3 signalling pathway and enhanced insulin signalling in those cells.
Two review articles from 2017 and 2022 summarise that NAFLD pathophysiology remains multifactorial and unclear, and that lifestyle interventions are often limited. The 2022 review notes many pharmacological interventions are being studied but does not report any single therapy as proven effective. A 2015 review states that controversies still exist in pathogenesis, diagnosis, and treatment.
What is still missing are large, randomised controlled trials in humans for any of the experimental interventions. The rat and cell studies provide mechanistic clues but no clinical efficacy data. The Ethiopian cross-sectional study highlights the high disease burden but offers no treatment. No drug has been shown to reverse NAFLD in a definitive human trial, and patient stratification by disease stage, metabolic profile, or genetic risk remains largely unaddressed in the available literature.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Food & Function · 2020 · 79 citations
Alleviating effects of noni fruit polysaccharide on hepatic oxidative stress and inflammation in rats under a high-fat diet and its possible mechanisms
AbstractNon-alcoholic fatty liver disease is associated with gut microbiota, oxidative stress, and inflammation. We aimed to investigate the possible mechanism by which noni fruit polysaccharide (NFP) improved hepatic oxidative stress and inflammation in rats under a high-fat diet (HFD) by modulating short-chain fatty acids (SCFAs), the intestinal barrier, and gut microbiota. Hepatic oxidative stress, inflammation, and gut dysbiosis in rats were induced through HFD feeding for 4 weeks, followed by intervention with NFP treatment (100 mg per kg bw) for 5 weeks. The results showed that NFP reduced body weight gain and improved lipid metabolism, hepatic oxidative stress, and inflammation in rats under a HFD. Aside from these beneficial effects, NFP positively affected the SCFA production and reversed the HFD-induced gut dysbiosis as indicated by improved microbiota diversity and composition. The levels of Lactobacillus, Ruminococcaceae_UCG_014, Parasutterella, [Eubacterium]_coprostanoligenes_group, and Ruminococcus_1 improved, whereas the levels of Prevotella_9, Collinsella, Bacteroides, and Turicibacter decreased. Furthermore, NFP maintained the colonic barrier integrity (increased the mRNA relative expression of CCL5, ZO-1, and occludin in the colon, and decreased the serum CCL5 level), and decreased the serum lipopolysaccharide level. Thus, NFP may modulate the gut microflora and SCFA production and reduce the permeability of the colonic barrier and metabolic endotoxemia, thereby alleviating hepatic oxidative stress and inflammation in rats under a HFD.
Canadian Journal of Gastroenterology · 2012 · 69 citations · open access
Current Treatment Options for Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis
AbstractNonalcoholic fatty liver disease is the leading cause of liver disease in western society. It is a cause of end-stage liver disease, with increased mortality secondary to cirrhosis and its complications. It is also recognized that cardiovascular disease is a significant cause of death in these patients. Significant work evaluating various treatments has been performed in recent years; however, to date, no ideal therapy exists. Lifestyle modification remains the cornerstone of management. The present article reviews the current status of various treatment modalities evaluated in nonalcoholic fatty liver disease.
Ethiopian Journal of Health Sciences · 2018 · 29 citations · open access
Non-alcoholic fatty liver disease and associated factors among type 2 diabetic patients in southwest Ethiopia
AbstractBACKGROUND: Non-alcoholic Fatty Liver Disease (NAFLD) among type 2 diabetic patients is completely ignored in developing regions like Africa paving the way for public health and economic burden in the region. Therefore, the main objective of this research was to evaluate non-alcoholic fatty liver disease and associated factors among type 2 diabetic patients in Southwestern Ethiopia attending Diabetic Clinic of Jimma University Specialized Hospital (JUSH). METHODS: Facility based cross-sectional study design was used. Anthropometry, fatty liver (using utrasonography), liver enzymes, and lipid profiles were measured among type 2 diabetic patients who fulfilled the inclusion criteria. Socio-demographic and clinical characteristics were assessed using standard questionnaires. RESULTS: Ninety-six (96) type 2 diabetic patients were enrolled and non-alcoholic fatty liver disease prevalence was 73%. Of non-alcoholic fatty Liver disease documented patients, 35.4%, 31.3% and 6.3% exhibited mild, moderate and severe fatty liver diseases, respectively. Alanine aminotransferase (p ≤0.001), Triacyglycerol (p ≤0.001), total bilirubin (p ≤0.05), direct bilirubin (p ≤0.05) and diabetic duration (p ≤0.01) were significantly associated with non-alcoholic fatty liver disease among type 2 diabetic patients. The Aspartate aminotransferase/Alanine aminotransferase ratio among non alcoholic fatty liver disease patients was greater than one. CONCLUSIONS: The magnitude of non-alcoholic fatty liver disease is high among study groups and it needs urgent action by healthcare systems. Therefore, targeted treatment approach inclusive of non-alcoholic fatty liver disease should be designed.
Nifuroxazide ameliorates lipid and glucose metabolism in palmitate-induced HepG2 cells
AbstractInflammation constitutes an important component of non-alcoholic fatty liver disease. STAT3 is a direct target of inflammatory cytokines, but also mediates glycolipid metabolism in the liver. As a potent inhibitor of STAT3, the effect of Nifuroxazide (Nifu) on glycolipid metabolism in liver has not been reported. In this study, we used palmitic acid (PA)-induced HepG2 cells to examine the expression of inflammatory factors and apoptosis-related proteins and the content of triglyceride (TG), total cholesterol (TC), and glycogen. The expression of hepatic lipogenic proteins (ACCα, SREBP-1c, FAS), gluconeogenesis enzymes (PEPCK, G6Pase, and IRS2), the IL-6/STAT3/SOCS3 inflammatory axis, and the insulin signaling pathway was determined. Our study shows that Nifu significantly improves lipid metabolism disorders in the PA-induced HepG2 cells, whereas, it remarkably reduced intracellular free fatty acid (FFA), TG, and TC content, suppressed lipid synthesis, and increased lipid decomposition. Our results also showed that Nifu significantly improved dysregulated glucose metabolism in the PA-treated HepG2 cells, increased glycogen content, and inhibited gluconeogenesis. Further research indicated that Nifu markedly inhibited activation of the IL-6/STAT3/SOCS3 signaling pathway. Finally, due to anti-inflammatory stress, Nifu enhanced insulin signaling in the PA-induced HepG2 cells. Therefore, Nifu can improve glucose and lipid metabolism in the PA-induced HepG2 cells, which provides new evidence that Nifu has a positive effect on PA-induced cellular hepatic steatosis and improves glucose metabolism in HepG2 cells, providing a new perspective for studying drug treatment of glucose and lipid metabolism disorders.
World Journal of Hepatology · 2022 · 20 citations · open access
Therapies for non-alcoholic fatty liver disease: A 2022 update
AbstractThe incidence of non-alcoholic fatty liver disease (NAFLD) is rapidly increasing and lifestyle interventions to treat this disease by addressing the underlying metabolic syndrome are often limited. Many pharmacological interventions are being studied to slow or even reverse NAFLD progression. This review for hepatologists aims to provide an updated understanding of the pathogenesis of NAFLD, current recommended therapies, and the most promising treatment options that are currently under development.
Nutrición Hospitalaria · 2017 · 12 citations · open access
Nonalcoholic fatty liver disease (NAFLD) pathophysiology in obese children and adolescents: update
AbstractOBJECTIVE: Although the nonalcoholic fatty liver disease was first identified in 1980, it presents multifactorial and unclear pathophysiology. In this review, we intend to update the pathophysiological mechanisms of a high morbidity and mortality associated disease that is affecting obese children worldwide. DATA SOURCES: The PubMed and the Cochrane Library databases were used in the search strategy for articles related to nonalcoholic fatty liver disease and published in the last three decades. DATA SUMMARY: This review describes the current knowledge on the different mechanisms related to the pathophysiology of nonalcoholic fatty liver disease focused on histological, anatomical and biochemical aspects involved in triggering steatohepatitis and leading to cirrhosis. CONCLUSIONS: The clinical research and advanced technological resources demonstrated several determinants pathophysiological mechanisms of nonalcoholic fatty liver disease trying to assist in their treatment and change its natural course.
DOAJ (DOAJ: Directory of Open Access Journals) · 2015 · 0 citations
Research advances in non-alcoholic fatty liver disease: a review of current status and prospect
AbstractNon-alcoholic fatty liver disease (NAFLD) affects more and more people. There are a lot of studies on the pathogenesis, diagnosis, and treatment of this disease, but controversies still exist. This article aims to highlight the latest advances and challenges in the clinical studies on NAFLD, so as to help the physicians to make the best management decisions for patients with NAFLD
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
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