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Background Steroid-induced osteonecrosis of the femoral head (SONFH) lacks effective early-stage interventions, and its systemic drivers remain incompletely defined. Luteolin (Lut) is reported to be protective, but the in vivo mechanism is unclear. We investigated whether Lut acts through a gut microbiota–metabolite–innate immunity axis in SONFH. Methods Male Sprague–Dawley rats underwent SONFH induction using lipopolysaccharide plus methylprednisolone and received oral Lut or L-Carnitine; gut microbiota dependence was examined using a four-antibiotic depletion regimen. Femoral heads were evaluated by histology and micro-computed tomography. Mechanisms were interrogated by integrated 16S rRNA profiling, untargeted serum Liquid Chromatography–Mass Spectrometry metabolomics, and femoral-head transcriptomics. Dexamethasone (Dex)-injuried ROS17/2.8 osteoblasts and HMEC-1 endothelial cells were used for functional validation, and IFIH1 was silenced by shRNA to test pathway necessity. Results Lut preserved trabecular microarchitecture and reduced empty osteocyte lacunae in vivo, yet minimally rescued Dex-injured osteoblasts and endothelial cells, indicating an indirect mechanism mediated by gut microbiota-derived metabolic changes. Microbiota depletion abolished Lut’s in vivo benefit, establishing microbiota dependence. Metabolomics identified an increase in circulating L-Carnitine that correlated with four bacterial genera. Exogenous L-Carnitine restored cell proliferation, reduced apoptosis, and improved endothelial tube formation, and in vivo improved trabecular indices while lowering inflammatory cytokines (IL-1β, IL-6, TNF-α). Integrated multi-omics highlighted an interferon-stimulated gene module (OAS1A, HERC6, IFIH1, IFI44), with IFIH1 most strongly associated with disease severity. L-Carnitine attenuated Dex-induced IFIH1 expression, and IFIH1 knockdown mimicked L-Carnitine and eliminated its additional anti-inflammatory effect. Conclusions Lut alleviates SONFH via gut microbiota-driven elevation of L-Carnitine, which constrains IFIH1 expression and inflammation to preserve femoral-head trabecular microarchitecture. Targeting the microbiota–L-Carnitine–IFIH1 axis may enable mechanism-based early intervention strategies for SONFH.

IgA nephropathy (IgAN) is the most common primary glomerulonephritis and the main cause of end-stage renal disease (ESRD). Luteolin (Lut), which is present in various plants, has anti-inflammatory and antioxidant properties under numerous medical conditions. This study aimed to investigate the therapeutic effects and potential mechanisms of Lut on IgAN. Mouse models of IgAN and HBZY-1 cells stimulated with Gd-IgA1 were used as experimental objects. Renal pathology, inflammation, reactive oxygen species (ROS) levels, and extracellular matrix (ECM) accumulation were measured. The results indicated that Lut improved renal pathological damage, reduced the levels of inflammatory cytokines, decreased ROS levels, and attenuated ECM accumulation. Moreover, Lut promoted the activation of the Nrf-2/HO-1 pathway. Furthermore, blocking Nrf2 reversed the suppressive effects of Lut on inflammation, oxidative stress, and the expression of ECM proteins in mesangial cells stimulated with Gd-IgA1. In conclusion, the protective effect of Lut against IgAN may occur by triggering the Nrf2/HO-1 pathway, thereby suppressing inflammation, oxidative stress, and ECM deposition.

A novel luteolin (LUT) loaded dual bionanocarrier ' ' was elaborated to allow LUT injectable delivery and liver cancer targeting. LUT-phospholipid complex was prepared and loaded into chylomicron nanocarrier. Then phytochylomicron underwent physicochemical characterization, cell culture and pharmacodynamics studies on a new liver-tumor model. Phytochylomicron showed sustained release pattern with minimum drug leakage until reaching the liver. Cell culture studies showed high growth inhibition of Hep G2 cells with 2.6-fold enhancement in cellular uptake. Pharmacodynamics demonstrated enhanced tumor growth inhibition (sixfold) with a significant tumor size reduction. Finally, cell culture results demonstrated an excellent correlation with pharmacodynamics confirming the obtained findings. A novel nanosystem was successfully elaborated with promising characteristics that promoted injectable LUT delivery and liver cancer targeting.

Previous studies have shown that aspirin is used in colon cancer treatment. However, long-term of Aspirin usage is limited to gastric and renal toxicity. Luteolin (LUT) has cancer prevention and anti-inflammatory effects. The present study was designed to investigate the effect of LUT supplementation and Aspirin treatment in dimethylhydrazine (DMH)-induced carcinogenesis in rats. DMH (20 mg/kg BW/week) treated rats received gavages with Aspirin (50 mg/kg BW/week) and LUT (0.2 mg/kg BW/day) for 15 weeks. DMH injections induce colon polyps and renal bleeding, significantly increasing carcinoembryonic antigen (CEA), cyclooxygenase-2 (COX-2), oxidative stress, and kidney function tests and reducing antioxidant markers. Either Aspirin or LUT gavages alone or combined produce a significant decrease in colon polyp number and size, significantly decreasing CEA, COX-2, and oxidative stress and increasing antioxidant markers. In conclusion, the supplementations of LUT adjacent to Aspirin in the treatment of DMH-induced carcinogenesis in rats reflect a better effect than the use of Aspirin alone.

In this study, we investigated whether treatment with palmitoylethanolamide and luteolin (PEA-LUT) leads to improvement in the quantitative or qualitative measures of olfactory dysfunction or relief from mental clouding in patients affected by long COVID. Patients with long COVID olfactory dysfunction were allocated to different groups based on the presence (“previously treated”) or absence (“naïve”) of prior exposure to olfactory training. Patients were then randomized to receive PEA-LUT alone or in combination with olfactory training. Olfactory function and memory were assessed at monthly intervals using self-report measures and quantitative thresholds. A total of 69 patients (43 women, 26 men) with an age average of 40.6 + 10.5 were recruited. PEA-LUT therapy was associated with a significant improvement in validated odor identification scores at the baseline versus each subsequent month; assessment at 3 months showed an average improvement of 10.7 + 2.6, CI 95%: 6–14 (p < 0.0001). The overall prevalence of parosmia was 79.7% (55 patients), with a significant improvement from the baseline to 3 months (p < 0.0001), namely in 31 patients from the Naïve 1 group (72%), 15 from the Naïve 2 group (93.7%), and 9 from the remaining group (90%). Overall, mental clouding was detected in 37.7% (26 subjects) of the cases, with a reduction in severity from the baseline to three months (p = 0.02), namely in 15 patients from the Naïve 1 group (34.8%), 7 from the Naïve 2 group (43.7%), and 4 from the remaining group (40%). Conclusions. In patients with long COVID and chronic olfactory loss, a regimen including oral PEA-LUT and olfactory training ameliorated olfactory dysfunction and memory. Further investigations are necessary to discern biomarkers, mechanisms, and long-term outcomes.

Purpose Few evidence-based therapies are available for chronic olfactory dysfunction after COVID-19. This study investigated the relative efficacy of olfactory training alone, co-ultramicronized palmitoylethanolamide with luteolin (um-PEA–LUT, an anti-neuroinflammatory supplement) alone, or combined therapy for treating chronic olfactory dysfunction from COVID-19. Methods This double-blinded controlled, placebo-controlled multicenter randomized clinical trial was conducted in 202 patients with persistent COVID-19 olfactory dysfunction of > 6 month duration. After a screening nasal endoscopy, patients were randomized to: (1) olfactory training and placebo; (2) once daily um-PEA–LUT alone; (3) twice daily um-PEA–LUT alone; or (4) combination of once daily um-PEA–LUT with olfactory training. Olfactory testing (Sniffin’ Sticks odor identification test) was performed at baseline and at 1, 2, and 3 months. The primary outcome was recovery of over three points on olfactory testing, with outcomes compared at T 0 , T 1 , T 2 and T 3 across groups. Statistical analyses included one-way ANOVA for numeric data and chi-square for nominal data. Results All patients completed the study, and there were no adverse events. At 90 days, odor identification scores improved by > 3 points in 89.2% of patients receiving combined therapy vs. 36.8% receiving olfactory training with placebo, 40% receiving twice daily um-PEA–LUT alone, and 41.6% receiving once daily um-PEA–LUT alone ( p  < 0.00001). Patients receiving treatment with um-PEA–LUT alone demonstrated subclinical improvement (< 3 point odor identification improvement) more often than patients receiving olfactory training with placebo ( p  < 0.0001.) Conclusions Olfactory training plus once daily um-PEA–LUT resulted in greater olfactory recovery than either therapy alone in patients with long-term olfactory function due to COVID-19. Trial registration 20112020PGFN on clinicaltrials.gov. Level of evidence 1b (Individual Randomized Clinical Trial).