curcumin and Mastitis

Curcumin is a naturally occurring polyphenol found in Curcuma longa with multiple therapeutic properties, such as anti-inflammatory, wound healing and anti-cancer effects. Curcuma longa is also used as a galactagogue to improve milk production during lactation.. To assess curcumin could have therapeutic potential for breastfeeding mothers, we investigated whether and how curcumin influences milk production in lactating mammary epithelial cells (MECs) at the cellular and molecular levels.. We prepared a lactating MEC culture model that produced milk components and formed less-permeable tight junctions (TJs) to investigate the molecular mechanism of curcumin on milk production, TJs, and inflammation in vitro.. Curcumin downregulated milk production in lactation MECs concurrently with inactivation of lactogenesis-relating signaling (STAT5 and glucocorticoid receptor). The maintenance of a less-permeable TJ barrier was also confirmed, although the TJ protein claudin-4 increased. Curcumin inactivated NFκB and STAT3 signaling, which are closely involved in inflammatory responses in weaning and mastitis mammary glands. The expression levels of IL-1β and TNF-α were also decreased by curcumin treatment. Furthermore, curcumin blocked activation of inflammatory signaling by lipopolysaccharide treatment in MECs, similar to those in MECs that were treated with diclofenac sodium. The drastic phosphorylation of ERK was induced by curcumin treatment in the absence of EGF. U0126, an inhibitor of ERK phosphorylation, attenuated the adverse effects of curcumin on lactating MECs.. The results of the present study suggests that curcumin downregulates milk production via inactivation of STAT5 and GR signaling with concurrent suppression of inflammatory responses via STAT3 and NFκB signaling in MECs. These findings provide new insights into the role of curcumin as a mild suppressor of milk production without inflammatory damages in breastfeeding mothers.

Topics: Animals; Caseins; Cells, Cultured; Curcumin; Epithelial Cells; Female; Glucocorticoids; Lactation; Lipopolysaccharides; Mammary Glands, Animal; Mastitis; Mice, Inbred ICR; Milk; NF-kappa B; Signal Transduction; STAT3 Transcription Factor; Tight Junctions

Mastitis is the inflammation of the mammary glands caused by bacteria. It causes severe economic loss to dairy industry. Curcumin, a polyphenol obtained from turmeric, has considerable anti-inflammatory effect. Since it is rapidly eliminated from the body, its oral bioavailability is low. However, nanoformulation of curcumin significantly enhances its therapeutic efficiency by improving its oral bioavailability. We evaluated whether nanocurcumin could be more effective than normal curcumin against bovine Staphylococcus aureus mastitis in mouse model. Curcumin-loaded PLGA nanoparticles (CUR-NP) were prepared by solid-in-oil-in-water emulsion method. The mouse model of mastitis was induced by inoculation of a field strain of S. aureus (bovine mastitis isolate) on the 9th day of parturition through the duct of the mammary gland. CUR-NP and curcumin were given orally for 7 days (day 2 to day 8 of parturition) prior to S. aureus inoculation. We determined the levels of inflammatory cytokines and the mRNA expression of NF‑κB. S. aureus infection increased the levels of tumor necrosis factor‑α, interleukin‑1β and myeloperoxidase in mammary tissues and C-reactive protein in serum. Both CUR-NP and curcumin significantly attenuated the levels of these cytokines. However, comparatively, the ameliorative efficiency of CUR-NP was better than normal curcumin. S. aureus infection-induced NF‑κB mRNA expression was significantly reduced to the healthy control level by CUR-NP. Our study demonstrates that the nanoformulation of curcumin can reduce pro-inflammatory mediators in S. aureus-infected mammary tissues by improving NF‑κB signaling. Besides, compared to normal curcumin, this nanoformulation appears to be a better alternative against murine mastitis.

Topics: Animals; C-Reactive Protein; Cattle; Curcumin; Disease Models, Animal; Female; Interleukin-1beta; Mammary Glands, Animal; Mastitis; Mice; Nanoparticles; NF-kappa B; Peroxidase; Polylactic Acid-Polyglycolic Acid Copolymer; Signal Transduction; Staphylococcal Infections; Staphylococcus aureus; Tumor Necrosis Factor-alpha

Curcumin, the main constituent of the spice turmeric, has been reported to have potent anti-inflammatory properties. However, the effect of curcumin on lipopolysaccharide (LPS)-induced mice mastitis has not been investigated. The aim of this study was to investigate whether curcumin could ameliorate the inflammation response in LPS-induced mice mastitis and to clarify the possible mechanism. The mouse model of mastitis was induced by injection of LPS through the duct of the mammary gland. Curcumin was applied 1h before and 12h after LPS treatment. The results showed that curcumin attenuated the infiltration of inflammatory cells, the activity of myeloperoxidase (MPO), and the expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in a dose-dependent manner. Additionally, Western blotting results showed that curcumin inhibited the phosphorylation of IκB-α and NF-κB p65 and the expression of TLR4. These results indicated that curcumin has protective effect on mice mastitis and the anti-inflammatory mechanism of curcumin on LPS-induced mastitis in mice may be due to its ability to inhibit TLR4-mediated NF-κB signaling pathways. Curcumin may be a potential therapeutic agent against mastitis.

Topics: Animals; Anti-Inflammatory Agents; Curcumin; Cytokines; Female; Lipopolysaccharides; Male; Mammary Glands, Animal; Mastitis; Mice, Inbred BALB C; NF-kappa B; Peroxidase; Signal Transduction; Toll-Like Receptor 4