Lupus nephritis (LN) is a common and serious symptom in patients with systemic lupus erythematosus (SLE). Tubular interstitial fibrosis is a common underlying mechanism in the development of lupus nephritis to end-stage renal failure (ESRD). Quercetin is widely proven to prevent tissue fibrosis. Therefore, the purpose of this study is to investigate the beneficial effects of quercetin on the inhibition of fibrosis and inflammation pathways in in vitro and in vivo lupus nephritis models. In the current study, MRL/lpr mice as animal models, and HK-2 human renal tubular epithelial cells were stimulated by interleukin-33 (IL-33) to mimic the cellular model of lupus nephritis. Immunohistochemical staining, immunoblotting assay, immunofluorescence staining, and quantitative real-time polymerase chain reaction assay were used. The in vivo results showed that quercetin improved the renal function and inhibited both fibrosis- and inflammation-related markers in MRL/lpr mice animal models. The in vitro results indicated that quercetin ameliorated the accumulation of fibrosis- and inflammation-related proteins in IL-33-induced HK-2 cells and improved renal cell pyroptosis via the IL33/ST2 pathway. Overall, quercetin can improve LN-related renal fibrosis and inflammation, which may offer an effective potential therapeutic strategy for lupus nephritis.

Banana peel (BP) has potent antioxidative properties; however, the anti-inflammatory potential of BP and its related bioactive components remain unclear. This study used solvent extraction and gas chromatography–mass spectrometry (GC–MS) to isolate and identify the active fractions and compounds in BP. BP was extracted with 95% ethanol (BP-95E) and partitioned with an ethyl acetate (EA) and water mixture to obtain the BP-95E-EA and BP-95E-H₂O fractions. The BP-95E-EA fractions were further partitioned with n-hexane (Hex) and methanol (MeOH) mixtures to obtain BP-95E-EA-Hex and BP-95E-EA-MeOH subfractions, and the BP-95E-H₂O fractions were partitioned with n-butanol (BuOH) to obtain BP-95E-H₂O-BuOH subfractions and the H₂O residual. The results show that the BP-95E-H₂O-BuOH subfractions exhibited the most potent inhibition of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) secretion while down-regulating inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. In this active subfraction, five non-polyphenol compounds were identified, namely, 5-hydroxyethyl furfural (5-HMF), guaiol, oleic acid, linoleic acid, and oleamide. 5-HMF, guaiol, and oleamide were the most effective at suppressing IL-6 and TNF-α secretion. The in vivo immunomodulatory action of BP was evaluated in an LPS-induced endotoxemia model of BALB/c mice. Oral administration of BP-95E-H₂O-BuOH extracts (42 and 166 mg/kg b.w.) for two weeks lowered the serum levels of IL-6 and TNF-α and normalized the activated T-cell population, as evidenced by an increase in CD₃CD₆₉ and decrease in IFN-γ/IL-4 (Th1/Th2) in mice with systemic inflammation. Our findings reveal that BP exhibits anti-inflammatory and T-cell immunomodulatory effects that may contribute to delaying endotoxemia-associated disorders.

Type 2 diabetes mellitus is a complex multifactorial disease characterized by poor glucose tolerance and insulin resistance. Rice-husk silica liquid (RHSL) derived from rice husk has the ability to improve the dysfunction of pancreatic β-cells. This study aimed to confirm the potential protective effects of RHSL in streptozotocin (STZ)-induced diabetic mice. Diabetes was induced in male C57BL/6J mice by intraperitoneal administration of STZ (200 mg/kg BW). RHSL, food-grade silica liquid (FDSL), and rosiglitazone (RSG) were administered to diabetic mice for 12 weeks after successful induction of diabetes. During the experiment, fasting blood glucose, serum insulin, and organ weights were measured. The histopathology of liver tissue was evaluated by H&E staining. Western blotting was performed to assess protein expression levels. The results showed that RHSL significantly reversed the serum insulin levels and improved oral glucose tolerance test (OGTT) results (p < 0.05). In addition, liver sections of STZ-induced diabetic mice after RHSL treatment showed neatly arranged and intact hepatocytes. Furthermore, RHSL was more effective than FDSL in increasing the expression of SIRT1 and decreasing the expression of the PPAR-γ and p-NF-κB proteins. Taken together, this study demonstrated that RHSL ameliorated STZ-induced insulin resistance and liver tissue damage in C57BL/6J mice.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by widespread inflammation and multi-organ damage. Toll-like receptor 7 (TLR-7) and autophagy have been implicated in SLE pathogenesis. Rice husk silica liquid (RHSL) has shown potential for modulating inflammatory responses, but its effects on SLE have not been thoroughly investigated. This study aims to evaluate the impact of RHSL on immune responses and autophagy in cell culture experiments, focusing on its effects on TLR-7 signaling, cytokine production, and autophagy modulation. RAW264.7 cells and human peripheral blood mononuclear cells (PBMCs) from healthy donors and SLE patients were used. Cells were stimulated with LPS or TLR-7 agonists and treated with RHSL. Cell viability was assessed, and cytokine levels (TNF-α and IL-6) were measured by ELISA. Autophagy-related proteins (LC3II, ATG5-ATG12) were analyzed by Western blotting. The effect of autophagy inhibition was studied using 3-methyladenine (3-MA). A concentration of 100 μg/mL RHSL did not affect cell viability but significantly reduced the TNF-α production in TLR-7 agonist-stimulated RAW264.7 cells (compared to TLR-7 alone, 3.41 ± 0.54 vs. 6.72 ± 0.07 folds) and PBMCs (compared to TLR-7 alone, 0.97 ± 0.19 vs. 1.40 ± 0.33 folds). RHSL enhanced autophagy, as evidenced by increased LC3II (4.35 ± 1.08 folds) and ATG5-ATG12 (7.07 ± 1.30 folds) conjugation in both RAW264.7 cells and SLE patient-derived PBMCs. The reduction in TNF-α production by RHSL was attenuated by 3-MA, indicating that autophagy plays a role in this process. RHSL also inhibited the translocation of phosphorylated NF-κB into the nucleus, suggesting a mechanism for its anti-inflammatory effects. RHSL exhibits potential as an immunomodulatory agent in SLE by enhancing autophagy and modulating TLR-7 signaling pathways. These findings suggest that RHSL could offer therapeutic benefits for managing inflammatory responses in SLE and warrant further investigation into its clinical applications.

In this study, three distinct hydrolysates, which are designated Dur-I, Dur-II, and Dur-III, were generated from extrusion-pretreated Durvillaea antarctica biomass by applying viscozyme, cellulase, and α-amylase, respectively. Chemical analyses demonstrated distinct compositional differences among the extracts, whereas FTIR spectra verified the presence of fucose-containing sulfated polysaccharides. Furthermore, NMR analyses revealed pronounced structural variations among the extracts. To investigate neuroprotective properties of Dur-I, Dur-II, and Dur-III, rotenone (Rot) was added to SH-SY5Y cells that had been pretreated with Dur-I/II/III. Here, flow cytometry was employed to assess changes in mitochondrial membrane potential (MMP), Bcl-2 expression, cytochrome c release, caspase-9, -8, and -3 activation, as well as DNA fragmentation. The protective effect of Dur-I/II/III pretreatment of SH-SY5Y cells on the Rot-induced death process was further investigated using cell cycle and annexin V-fluorescein isothiocyanate (FITC)/PI (propidium iodide) double staining analyses. The results reveal that the Rot-induced apoptotic factors were all recovered by the pretreatment of Dur-I/II/III. Moreover, cell cycle and annexin V-FITC/PI double staining analyses also indicated that Dur-I/II/III were capable of protecting SH-SY5Y cells from Rot-induced cytotoxicity. Therefore, these Dur extracts are considered as good candidates for the prevention and treatment of neurodegeneration induced by oxidative stress.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by widespread inflammation and multi-organ damage. Toll-like receptor 7 (TLR-7) and autophagy have been implicated in SLE pathogenesis. Rice husk silica liquid (RHSL) has shown potential for modulating inflammatory responses, but its effects on SLE have not been thoroughly investigated. This study aims to evaluate the impact of RHSL on immune responses and autophagy in an in vitro model of SLE, focusing on its effects on TLR-7 signaling, cytokine production, and autophagy modulation. RAW264.7 cells and human peripheral blood mononuclear cells (PBMCs) from healthy donors and SLE patients were used. Cells were stimulated with LPS or TLR-7 agonists and treated with RHSL. Cell viability was assessed, and cytokine levels (TNF-α and IL-6) were measured by ELISA. Autophagy-related proteins (LC3II, ATG5-ATG12) were analyzed by Western blotting. The effect of autophagy inhibition was studied using 3-methyladenine (3-MA). RHSL did not affect cell viability but significantly reduced TNF-α production in LPS- and TLR-7 agonist-stimulated RAW264.7 cells and PBMCs. RHSL enhanced autophagy, as evidenced by increased LC3II and ATG5-ATG12 conjugation in both RAW264.7 cells and SLE patient-derived PBMCs. The reduction in TNF-α production by RHSL was attenuated by 3-MA, indicating that autophagy plays a role in this process. RHSL also inhibited the translocation of phosphorylated NF-κB into the nucleus, suggesting a mechanism for its anti-inflammatory effects. RHSL exhibits potential as an immunomodulatory agent in SLE by enhancing autophagy and modulating TLR-7 signaling pathways. These findings suggest that RHSL could offer therapeutic benefits for managing inflammatory responses in SLE and warrant further investigation into its clinical applications.