Anti‐inflammatory effects of amarogentin on 2,4‐dinitrochlorobenzene‐induced atopic dermatitis–like mice and in HaCat cells

Abstract

Background Amarogentin (AMA) is a secoiridoid glycoside extracted from Swertia and Gentiana roots and exhibits many biological effects such as antioxidative, anti‐inflammatory, and antitumor activities. Atopic dermatitis (AD) is a chronic inflammatory skin disease caused by disorders in the regulation of multiple inflammatory cytokines. No effective cure has been found for AD now. Methods We constructed the HaCat and splenocyte model and tested the inhibitory effect of AMA on IL‐4, IL‐6, and IL‐13 secretions using enzyme‐linked immunosorbent assay (ELISA). The AD mouse model was constructed and treated with AMA, the severity of skin lesions was observed, epidermal tissue was collected, and epidermal thickness and mast cell infiltration were observed using hematoxylin and eosin and toluidine blue staining, respectively. The expression of kallikrein‐related peptidase 7 (KLK7) and filaggrin (FLG) was detected using immunostaining and Western blot analysis. The mRNA expression of KLK7 and FLG was detected using quantitative polymerase chain reaction (qPCR). Blood immunoglobulin E (IgE) secretion was detected. Results AMA inhibited IL‐6 secreted by tumor necrosis factor (TNF)‐α‐induced HaCaT cells and reduced IL‐4 and IL‐13 secreted by phytohemagglutinin (PHA)‐induced primary cells in the mice spleen. It was found that the treatment of AMA with 2,4‐dinitrochlorobenzene‐induced AD‐like mice could promote the recovery of dermatitis, reduce the score of dermatitis severity and the scratching frequency, treat the skin lesions, reduce the epidermal thickness, decrease the infiltration of mast cells, reduce the IgE level in serum, decrease the expression levels of AD‐related cytokines, increase protein and mRNA expression of FLG, and reduce the protein and mRNA expression of KLK7 in the skin tissues of AD‐like mice. Conclusion In conclusion, AMA inhibits inflammatory response at the cellular level, and AMA reduces the validation response of specific dermatitis mice, relieves pruritus, and repairs the damaged skin barrier.

Antioxidant, Antibacterial Properties of Novel Peptide CP by Enzymatic Hydrolysis of Chromis notata By-Products and Its Efficacy on Atopic Dermatitis

“…On the day of mouse sacrifice, skin tissue samples were collected from the four groups, fixed in 10% formalin solution, embedded in paraffin, and sliced into 4 µm thick sections. The sections were then subjected to Masson's trichrome and toluidine blue staining to observe changes in the thickness of the epidermis and dermis, as well as infiltration of inflammatory cells [78].…”

Bitter Phytochemicals as Novel Candidates for Skin Disease Treatment

“…Amarogentin, identified as an agonist of seven TAS2Rs (TAS2R1 [43], TAS2R4 [43], TAS2R39 [43], TAS2R43 [43], TAS2R46 [43], TAS2R47 [43], TAS2R50 [43]), is a secoiridoid glycoside that can be found in various plants from the Gentianaceae family and ranks among the most bitter natural substances [164][165][166]. In a mouse model of induced atopic dermatitis, amarogentin decreased IgE serum levels and demonstrated anti-inflammatory effects [167]. In another mouse model of skin carcinogenesis, the amarogentin-rich fraction from Swertia chirata exerted proapoptotic and antiproliferative actions [168].…”

“…TAS2R50 [43] Atopic dermatitis [167] Liver and renal toxicity [277] Amygdalin TAS2R16 [43,170] Psoriasis (amygdalin analogues) [174][175][176] Toxicity due to hydrogen cyanide (amygdalin) [173] Berberine TAS2R38 [177] TAS2R46 [178] Atopic dermatitis [179] Melanoma [181,182] Squamous cell carcinoma [180] Gut microbiota dysbiosis [278] Diarrhea [278] Chrysin TAS2R14 [132] TAS2R39 [132] Psoriasis [188] Atopic dermatitis [189] Melanoma [190][191][192][193][194][195][196][197] Alteration in hematological parameters [279] Hepatic toxicity [279] Poor bioavailability [280] Cucurbitacin B TAS2R10 [43] TAS2R14 [43] Psoriasis [199] Squamous cell carcinoma [200] Melanoma [201][202][203] Low oral bioavailability [281] Non-selective toxicity [282] Epigallocatechin gallate TAS2R14 [132,204] TAS2R31 [204] TAS...…”