Inhibitory effect of rosmarinic acid on IgE-trigged mast cell degranulation in vitro and in vivo.

BACKGROUND: Rosmarinic acid (RA), a polyphenol from edible-medical Lamiaceae herbs, is known to possess a variety of pharmacological activity, like anti-inflammatory, hepatoprotective and immunoregulation activities. METHODS AND RESULTS: Hereon, we investigated the anti-allergic activity of RA on immunoglobulin E (IgE)-mediated anaphylaxis responses in rat basophilic leukemia (RBL)-2H3 mast cell. RA hindered the morphological changes of IgE-induced degranulated RBL-2H3 cells. The release of two key biomarkers (ß-hexosaminidase (ß-HEX) and histamine) of IgE-induced degranulated mast cells was also remarkably down-regulated by RA intervention in a dose dependent manner. Moreover, RA inhibited IgE-induced ROS overproduction and flux of intracellular Ca2+ in IgE-mediated degranulated mast cells. The q-PCR analysis showed that the expressions of genes (COX 2, PGD 2, LTC 4, HDC, Nrf2, HO-1 and NQO1) involved in MAPK and oxidative stress signaling pathways were significantly regulated by RA intervention. Moreover, the degranulation inhibitory effect of rosmarinic acid was investigated on the anti-DNP IgE/DNP-HSA induced passive cutaneous anaphylaxis (PCA) mice model in vivo. It showed that RA significantly inhibited the PCA reaction and allergic edema of ears in anti-DNP IgE/DNP-HSA stimulated mice. CONCLUSION: These findings suggest that RA has the potential to be used as a therapeutic candidate for allergic diseases by inhibiting mast cell degranulation. This indicates a possible role for RA in managing allergic reactions and related conditions.

Effects of rosmarinic acid on immune response and intestinal microbiota in ovalbumin-induced intestinal allergy mice.

BACKGROUND: Rosmarinic acid (RA) is an active polyphenol that is widely found in various edible herbs. This study explored the potential anti-allergic activities and the underlying mechanisms of RA in ovalbumin (OVA)-induced intestinal allergic mice. RESULTS: Forty female BALB/c mice were randomly divided into five groups: control group, model group (OVA sensitized/challenged), RA-Low group (OVA sensitized/challenged, 30 mg kg-1 RA intervention), RA-Middle group (OVA sensitized/challenged, 90 mg kg-1 RA intervention) and RA-High group (OVA sensitized/challenged, 270 mg kg-1 RA intervention). RA effectively attenuated allergic reactions, including alleviating allergic symptoms and regulating the hypothermia of mice in the model group. Moreover, the anaphylactic mediator (OVA-specific IgE, histamine and mMCP-1) levels of OVA allergic mice were markedly decreased after RA intervention. Quantitative polymerase chain reaction analysis showed that RA significantly inhibited Th2 cytokine expression, while Th1 and Treg cytokines were markedly increased. 16S rRNA gene sequence analysis indicated that RA effectively regulated the richness and diversity of the intestinal microbiota in OVA allergic mice. At the phylum level, the relative abundance of Bacteroidetes and Firmicutes and the Firmicutes/Bacteroidetes ratio were altered by RA intervention. At the genus level, RA was found to regulate the disturbances in the relative abundance of Muribaculaceae, Lactobacillus and Prevotella. CONCLUSION: RA exhibited potential anti-allergic activity in OVA allergic mice by regulating hypersensitive immune responses and the intestinal microbiota structure. These results provide important evidence that RA can be developed into a novel functional food-derived ingredient against food allergy. © 2023 Society of Chemical Industry.

Hepatoprotective Effects of Rosmarinic Acid on Ovalbumin-Induced Intestinal Food Allergy Mouse Model.

Rosmarinic acid (RA) has been proven to exert antianaphylaxis in atopic dermatitis, asthma, and allergic rhinitis. The aim of this study was to determine the hepatoprotective effects of RA on ovalbumin (OVA) challenge-induced intestinal allergy. The results exhibited that RA could relieve anaphylactic symptoms, decrease diarrhea, and prevent hypothermia in allergic mice. Moreover, the elevation of OVA specific IgE (OVA-sIgE), histamine, and mouse mast cell proteinases (mMCP-1) in the serum of OVA challenged mice were remarkably inhibited by RA. OVA challenge resulted in notable increases in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) activities, liver malondialdehyde (MDA) and nitic oxide (NO) levels, and a remarkable decrease in liver superoxide dismutase (SOD) activity and glutathione (GSH) level. RA treatments succeeded in improving these biochemical parameters and promote the redox homeostasis. Cytokine expression evaluation showed that RA effectively enhanced the expression of anti-inflammatory cytokines (IL-10 and FOXP-3) in the liver of OVA-challenged mice. Meanwhile, the elevation of pro-inflammatory cytokines (TNF-α, IL-4, IL-6, mMCP-1, and iNOS) were remarkably inhibited by RA. These findings suggest that RA possesses hepatoprotective effects on OVA challenge-induced liver injury. The anti-oxidative and anti-inflammatory activities of RA potentially play vital roles in this process.