rhoifolin and Inflammation

The consumption of plant-based food is important for health promotion, especially concerning the prevention and management of chronic diseases. Flavonoids are the main bioactive compounds in citrus fruits, with multiple beneficial effects, especially antidiabetic effects. We systematically review the potential antidiabetic action and molecular mechanisms of citrus flavonoids based on in vitro and in vivo studies. A search of the PubMed, EMBASE, Scopus, and Web of Science Core Collection databases for articles published since 2010 was carried out using the keywords citrus, flavonoid, and diabetes. All articles identified were analyzed, and data were extracted using a standardized form. The search identified 38 articles, which reported that 19 citrus flavonoids, including 8-prenylnaringenin, cosmosiin, didymin, diosmin, hesperetin, hesperidin, isosiennsetin, naringenin, naringin, neohesperidin, nobiletin, poncirin, quercetin, rhoifolin, rutin, sineesytin, sudachitin, tangeretin, and xanthohumol, have antidiabetic potential. These flavonoids regulated biomarkers of glycemic control, lipid profiles, renal function, hepatic enzymes, and antioxidant enzymes, and modulated signaling pathways related to glucose uptake and insulin sensitivity that are involved in the pathogenesis of diabetes and its related complications. Citrus flavonoids, therefore, are promising antidiabetic candidates, while their antidiabetic effects remain to be verified in forthcoming human studies.

Topics: Animals; Antioxidants; Citrus; Diabetes Mellitus; Disaccharides; Flavanones; Flavones; Flavonoids; Glycosides; Hesperidin; Humans; Inflammation; Phytochemicals; Polyphenols; Propiophenones

Sepsis is a systemic infection affects several organs, which needs novel therapy for the management of it, thus protective effect of Rhoifolin was estimated against sepsis. Cecal ligation and puncture (CLP) method was used to induce sepsis and thereafter mice were treated with rhoifolin (20 and 40 mg/kg, i.p.) for one week. Food intake and survival rate was determined sepsis mice, moreover liver function test and cytokines was estimated in the serum of sepsis mice. In the lung tissue homogenate, oxidative stress parameters were determined, histopathological analysis was performed in liver and lung tissue of sepsis mice. Food intake and percentage of survival was improved in rhoifolin treated group than sham group. Level of liver function enzyme and cytokine was reduced significantly in the serum of rhoifolin treated sepsis mice. Treatment with rhoifolin ameliorates the altered oxidative stress parameters, and mRNA expression of Toll-like receptor 4 (TLR-4) in lung tissue of sepsis mice. Histopathological changes were also reverse in rhoifolin treated group than sham group of mice. In conclusion, result of report indicates Rhoifolin treatment reduces oxidative stress and inflammation in CLP induced sepsis mice, as it regulates TLR4/MyD88/NF-κB pathway.

Topics: Animals; Cecum; Cytokines; Disease Models, Animal; Flavonoids; Inflammation; Liver; Mice; Punctures; Sepsis

Osteoarthritis (OA) is an age-related degenerative disease accompanied by an increasing number of senescent cells and chronic low-grade inflammation. Rhoifolin (ROF) showed considerable inhibition to inflammation, but its role in chondrocyte senescence and OA progress has not been fully characterized. We aimed to evaluate the protective effects of ROF on OA through a series of in vitro and in vivo experiments.. The role of ROF in the expression of senescence-associated secretory phenotype (SASP) factors was investigated using RT-qPCR, western blotting, and ELISA. Chondrocyte senescence was assessed by SA-β-gal staining. We applied molecular docking to screen candidate proteins regulated by ROF. Meanwhile, SASP factors and cellular senescence were further assessed after the transfection of Nrf2 siRNA. In the anterior cruciate ligament transection (ACLT) rat model, X-ray, hematoxylin-eosin (HE), and Masson's staining were performed to evaluate the therapeutic effects of ROF on OA.. We found that ROF inhibited SASP factors expression and senescence phenotype in IL-1β-treated chondrocytes. Furthermore, ROF suppressed IL-1β-induced activation of the NF-κB pathway cascades. Also, molecular docking and knock-down studies demonstrated that ROF might bind to Nrf2 to suppress the NF-κB pathway. In vivo, ROF ameliorated the OA process in the ACLT rat model.. ROF inhibits SASP factors expression and senescence phenotype in chondrocytes and ameliorates the progression of OA via the Nrf2/NF-κB axis, which supports ROF as a potential therapeutic agent for the treatment of OA.

Topics: Animals; Cells, Cultured; Chondrocytes; Disaccharides; Flavonoids; Glycosides; Inflammation; Molecular Docking Simulation; NF-E2-Related Factor 2; NF-kappa B; Osteoarthritis; Rats

Rhoifolin (ROF) is a main effective component in Citrus grandis 'Tomentosa'. ROF has a potential anti-inflammatory activity, but its specific effects and mechanisms have not been studied. This study investigated the anti-inflammatory activity of ROF and searched for its possible molecular mechanisms. A mouse model of acute inflammation was induced by lipopolysaccharide, and the effects of ROF on pathological damages of the lung and liver were observed. Carrageenan-induced paw edema rat model was used to evaluate the effect of ROF on the volume of swelling paw. In LPS-induced RAW264.7 macrophages, the expression levels of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α were measured using ELISA. Real-time PCR was used to measure the mRNA levels of iNOS and CCL2. Western blot was used to detect the activation of IκBα and IKKβ in NF-κB signaling pathways. The results showed that ROF accelerated the recoveries of liver and lung tissue damages in acute inflammation mice and inhibited carrageenan-induced paw edema in rats; in addition, ROF significantly suppressed the secretion of TNF-α, IL-1β, and IL-6 in the serum of rats and mouse model. In LPS-induced RAW264.7 cells, 100 μmol/L ROF enhanced cell viability and suppressed the production of TNF-α, IL-6, and IL-1β significantly. ROF also decreased the mRNA expression of iNOS and CCL2 and inhibited IκBα and IKKβ phosphorylation. In summary, ROF had a potential therapeutic value for inflammation. Our research provided experimental basis for the further development of ROF as an anti-inflammatory drug and for clarifying the anti-inflammatory substance basis of Citrus grandis 'Tomentosa'. Graphical Abstract.

Topics: Animals; Carrageenan; Cell Survival; Citrus; Cytokines; Disaccharides; Edema; Flavonoids; Glycosides; I-kappa B Kinase; Inflammation; Lipopolysaccharides; Mice; NF-kappa B; Phosphorylation; Rats; Rats, Sprague-Dawley; RAW 264.7 Cells; Signal Transduction