Abstract:Objective: To explore the mechanism of the influence of D-pinitol on Th1/Th2 balance in psoriatic skin lesions in rats. Methods: The imiquimod (IMQ) rat model was constructed and randomly grouped into control group, IMQ group, low-dose D-pinitol group, medium-dose D-pinitol group, high-dose D-pinitol group and positive control group , 10 in each group. After successful modeling, the rats were given intragastric administration of D-pinitol low, medium and high dose groups ( 50 mg / kg, 100 mg / kg, 150 mg / kg ) and positive control group ( 1 mg / kg, methotrexate ). The control group and IMQ group were given the same dose of normal saline once a day for 7 days.On the 8th day of administration, different drug treatments were given to evaluate the psoriasis skin lesion symptoms and index (MPASI) of rats in each group; HE staining was used to observe the pathological changes of psoriatic skin lesions; ELISA was applied to detect serum levels of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), and interleukin-10 (IL-10); flow cytometry was used to measure the T helper 1 (Th1)/helper 2 (Th2) ratio; Western blot was applied to detect the protein expressions of T box transcription factor (T-bet), GATA-binding protein 3 (GATA-3), Notch 1 and hairy and enhancer of split 1 (Hes1). Results: Compared with the control group, the rats in the IMQ group had psoriasis-like lesions such as erythema, hyperkeratinization, inflammatory cell infiltration, etc. the levels of IFN-γ, TNF-α, Th1 cells, T-bet, Notch1 and Hes1 were obviously increased (P<0.05), the levels of IL-4, IL-10, Th2 cells, and GATA-3 were obviously reduced, the ratio of Th1/Th2 cells was unbalanced (P<0.05); after D-pinitol treatment, the psoriasis-like lesions in rats were alleviated or disappeared, and the skin lesion index decreased, the levels of IFN-γ, TNF-α, Th1 cells, T-bet, Notch1 and Hes1 decreased (P<0.05), the levels of IL-4, IL-10, Th2 cells, GATA-3 increased, Th1/Th2 ratio recovered somewhat (P<0.05). Conclusion: D-pinitol may inhibit Notch1/Hes1 signaling pathway to regulate Th1/Th2 balance, reduce the production of inflammatory factors, and alleviate psoriatic skin lesions in IMQ rats.
[1] Pradhan M,Alexander A,Singh MR,et al.Understanding the prospective of nano-formulations towards the treatment of psoriasis[J].Biomed Pharmacother,2018,107(1):447-463. [2] Sun P,Vu R,Dragan M,et al.OVOL1 regulates psoriasis-like skin inflammation and epidermal hyperplasia[J].Invest Dermatol,2021,141(6):1542-1552. [3] Ma J,Feng S,Ai D,et al.D-pinitol ameliorates imiquimod-induced psoriasis like skin inflammation in a mouse model via the NF-κB pathway[J].Environ Pathol Toxicol Oncol,2019,38(3):285-295. [4] Gratton R,Tricarico PM,Moltrasio C,et al.Pleiotropic role of notch signaling in human skin diseases[J].Int Mol Sci,2020,21(12):4214. [5] Lin YW,Li XX,Fu FH,et al.Notch1/Hes1-PTEN/AKT/IL-17A feedback loop regulates Th17 cell differentiation in mouse psoriasis-like skin inflammation[J].Mol Med Rep,2022,26(1):223. [6] Fukuda A,Kano S,Nakamaru Y,et al.Notch signaling in acquired middle ear cholesteatoma[J].Otol Neurotol,2021,42(9):e1389-e1395. [7] You X,Sun X,Kong J,et al.D-pinitol attenuated ovalbumin-induced allergic rhinitis in experimental mice via balancing Th1/Th2 response[J].Iran Allergy Asthma Immunol,2021,20(6):672-683. [8] Parmar KM,Jagtap CS,Katare NT,et al.Development of a psoriatic-like skin inflammation rat model using imiquimod as an inducing agent[J].Indian Pharmacol,2021,53(2):125-131. [9] 安月鹏,杨素清,周妍妍.基于miR-155调控SOCS1-JAK2/STAT3通路研究蜈蚣败毒饮治疗银屑病模型鼠的机制[J].中国皮肤性病学杂志,2021,35(4):405-412. [10] Rendon A,Schakel K.Psoriasis pathogenesis and treatment[J].Int Mol Sci,2019,20(6):1475. [11] Sharif K,Watad A,Bragazzi NL,et al.Physical activity and autoimmune diseases:get moving and manage the disease[J].Autoimmun Rev,2018,17(1):53-72. [12] Butcher MJ,Zhu J.Recent advances in understanding the Th1/Th2 effector choice[J].Fac Rev,2021,10(1):30. [13] 罗雅琴,黄伟.芪黄益气摄血方对ITP模型小鼠Th1/Th2细胞因子及转录因子T-bet/GATA3表达的影响[J].时珍国医国药,2022,33(1):48-51. [14] 杨鑫娜,刘晓菊,赵兰婷,等.Notch信号通路在慢性阻塞性肺疾病免疫失衡中的作用及机制研究[J].中华结核和呼吸杂志,2016,39(11):881-885. [15] Li Q,Zhang H,Yu L,et al.Down-regulation of Notch signaling pathway reverses the Th1/Th2 imbalance in tuberculosis patients[J].Int Immunopharmacol,2018,54(1):24-32.