Protective Effects of Many <i>Citrus</i>Flavonoids on Cartilage Degradation Process

The objective of this study was to investigate the effects of many citrus flavanones, such as neoeriocitrin, naringin and neohesperidin, in cartilage degradation. Degenerative joint disease involved degradation of joints, including articular cartilage and subchondral bone. When bone surfaces become less well protected by cartilage, bone may be exposed and damaged. The degradation cartilage is mediated by alteration of the balance between anabolic and catabolic processes, changes in proteolytic enzyme activity, mechanical disruption of the cartilage extracellular matrix (ECM), or a combination of these processes. We examine the capability of neoeriocitrin, naringin and neohesperidin, to inhibit metalloproteinase (MMP)-13, collagenase involved in degradation of cartilage matrix components. Also, we assay the flavonoids effect on reducing of Glycosaminoglycans (GAGs) release, and restore Nitric oxide (NO) levels in explant of human articular cartilage. Our results suggest that neoeriocitrin, naringin and neohesperidin are a potential therapeutic agent to protect cartilage tissue.

Naringin,neohesperidin and their corresponding dihydrochalcones as bioactive substances:a symphony of bitter–sweet

Bitter is generally undesirable,although it is an important part of flavor.Bitter substances exhibit diverse health-promoting activities,which is in line with the famous Chinese saying‘a good medicine tastes bitter’.Naringin(NAG)and neohesperidin(NHP),two important flavanones that give bitterness to citrus fruits,show various pharmacological activities.Interestingly,their hydrogenation products,i.e.naringin dihydrochalcone(NDC)and neohesperidin dihydrochalcone(NHDC),undergo a dramatic taste shift from bitter to intensely sweet,which can be 300 and 1000 times sweeter than sucrose,respectively.Such sweeteners not only provide a sweet taste without the burden of increased calorie intake and glycemia,but also may exert multiple bioactivities.This review summarizes common dietary bitter and sweet compounds with sensory scores.Taste conversions induced by structural changes from bitter NAG and NHP to sweet NDC and NHDC are particularly discussed.In addition,the taste-sensing mechanisms,pharmacological characteristics,dietary distribution,synthesis,and food industry applications of these bitter–sweet interchangeable compounds are outlined.In conclusion,the bitter NAG and NHP are promising therapeutic candidates for management of diverse etiologically complex diseases while their corresponding dihydrochalcones NDC and NHDC are promising sweeteners,which might be a blessing for those who need to control sugar intake.

Therapeutic effect of neohesperidin on TNF-α-stimulated human rheumatoid arthritis fibroblast-like synoviocytes

During the pathogensis of rheumatoid arthritis(RA),activated RA fibroblast-like synoviocytes(RA-FLSs)combines similar proliferative features as tumor and inflammatory features as osteoarthritis,which eventually leads to joint erosion.Therefore,it is imperative to research and develop new compounds,which can effectively inhibit abnormal activation of RA-FLSs and retard RA progression.Neohesperidin(Neo)is a major active component of flavonoid compounds with anti-inflammation and anti-oxidant properties.In this study,the anti-inflammation,anti-migration,anti-invasion,anti-oxidant and apoptosis-induced effects of Neo on RAFLSs were explored to investigate the underlying mechanism.The results suggested that Neo decreased the levels of interleukin IL-1β,IL-6,IL-8,TNF-α,MMP-3,MMP-9 and MMP-13 in FLSs.Moreover,Neo blocked the activation of the MAPK signaling pathway.Furthermore,treatment with Neo induced the apoptosis of FLSs,and inhibited the migration of FLSs.It was also found that Neo reduced the accumulation of reactive oxygen species(ROS)induced by TNF-α.Taken together,our results highlighted that Neo may act as a potential and promising therapeutic drug for the management of RA.

Comparative pharmacokinetics of naringin and neohesperidin after oral administration of flavonoid glycosides from Aurantii Fructus Immaturus in normal and gastrointestinal motility disorders mice

Objective: To compare the pharmacokinetics of naringin and neohesperidin after oral administration of Zhishi total flavonoid glycosides(ZSTFG) extracted from Aurantii Fructus Immaturus in normal and gastrointestinal motility disorders(GMD) mice.Methods: ZSTFG was orally given to normal and GMD mice induced by atropine or dopamine. The plasma samples were incubated with β-glucuronidase/sulfatase, the total(free + conjugated) naringenin and hesperitin were extracted with acetonitrile. The validated HPLC-MS/MS method was successfully applied to the pharmacokinetic study.Results: The results showed that, compared with the normal group, AUC0–∞, AUC0–tand Cmaxfor total naringenin and hesperitin were significantly higher(P < 0.01 or P < 0.05), while CLZ/F for total naringenin and hesperitin was significantly lower(P < 0.01) in the GMD group. Tmax, t1/2 z, MRT0-t, and MRT0-∞for naringenin were longer(P < 0.01) in the GMD group than those in the normal group.Conclusion: The results showed that there were significant differences in pharmacokinetic parameters of naringenin and hesperitin between normal and GMD groups. It was suggested that the absorption of naringenin and hesperitin was increased, and the elimination processes of naringenin and hesperitin were slower in the GMD group than the normal group. The data are of value for further pharmacological studies of ZSTFG and would be useful to provide a reference for improving the therapeutic regimen of ZSTFG in clinical trials.