eng Oriental Scientific Publishing Company Biomedical and Pharmacology Journal 0974-6242 2026-06-16 19 2 72263 article Arifah Ahmad Damahuri 1 Thuhairah Hasrah Abdul Rahman 3 B. Vimala R.M.T Balasubramaniam 5 Awla Mohd Azraai 4 Mohd Salleh Rofiee 7 Nasibah Azme 9 Laboratory Animal Care Unit, Faculty of Medicine, UniversitiTeknologi MARA, Malaysia Institute of Medical Molecular Biotechnology, Faculty of Medicine, UniversitiTeknologi MARA, Malaysia Cardiovascular Advancement Research Excellence Institute (CARE-i), UniversitiTeknologi MARA, Malaysia Department of Pathology, Faculty of Medicine, UniversitiTeknologi MARA, Malaysia Nutrition, Metabolism & Cardiovascular Research Centre, Institute for Medical Research, Malaysia Department of Clinical Diagnostic Laboratories, Hospital Al-Sultan Abdullah UniversitiTeknologi MARA, Malaysia High-fat diet (HFD)-induced inflammation is characterized by widespread infiltration of inflammatory cells across multiple organs. Celastrol, an emerging drug derived from Tripterygiumwilfordii, has demonstrated anti-inflammatory effects in multiple models, including ApoE-knockout mice. However, quantitative evaluation of multi-organ histopathological inflammation and its association with systemic inflammatory response remains to be determined. This study aimed to evaluate anti-inflammatory effects of celastrol in multi-organ via Hematoxylin and Eosin (H&E)-stained tissues and its association with systemic inflammation through circulating TNF-α levels in HFD-fed ApoE-knockout mice. Male ApoE-knockout mice were divided into five groups (n=6/group). Four groups were fed an HFD for 12 weeks, while the control group received a normal diet. During the last 4 weeks, three HFD groups received intraperitoneal celastrol (1.5, 2, and 2.5 mg/kg/day), while controls received 2% DMSO/day. At the end of the treatment, the heart, lungs, liver, and kidneys were harvested for H&E staining, and inflammatory cell infiltration was quantified using NDP.view 2. Plasma TNF-α levels were measured using ELISA. The 2.5mg celastrol-treated group showed a significant reduction in the area of inflammatory cell infiltration across all organs compared to the HFD group (heart, p<0.01; lung, p<0.001; liver, p<0.05; kidney, p<0.01). Additionally, 2 and 2.5 mg of celastrol were reported to significantly decrease plasma TNF-α levels (p<0.05). Celastrol attenuates multi-organ histopathological inflammation and reduces circulating TNF-α levels in HFD-fed ApoE-knockout mice, supporting its potential as a multi-target anti-inflammatory agent. Further studies are required to elucidate the underlying mechanisms. https://biomedpharmajournal.org/vol19no2/multi-organ-histopathological-and-systemic-anti-inflammatory-effects-of-celastrol-in-high-fat-diet-fed-apoe-knockout-mice/ ApoE-knockout mice Celastrol H and E staining Inflammatory cell infiltration TNF-α