ABSTRACT
Aim In this study, a mouse model of psoriasis-like lesions induced by 62. 5 mg imiquimod was used to explore the effect and mechanism of Sophorae Flavescentis Radix and Rhizoma Smilacis Glabrae combination for the topical treatment of psoriasis. Methods Firstly, the topical administration of Sophorae Flavescentis Radix and Rhizoma Smilacis Glabrae combination for treating psoriasis in progressive and recurrent stages was evaluated by psoriatic mouse model and HE staining. Secondly, immunohistochemistry was used to study the regulatory effects of Sophorae Flavescentis Radix and Rhizoma Smilacis Glabrae combination on the pivotal pathological mechanism of psoriasis-the positive feedback loop between the abnormal proliferation of keratinocytes and skin immune microenvironment. Finally, metabolomics technology was used to explore whether Sophorae Flavescentis Radix and Rhizoma Smilacis Glabrae combination topically treat psoriasis by regulating inflammation-related metabolism and lipid metabolism pathways. Results The combination of Sophorae Flavescentis Radix and Rhizoma Smilacis Glabrae alleviated psoriasis-like lesions in mice. It effectively relieved the recurrence after the cure of psoriatic lesions in mice, and the efficacy is comparable to that of benweimod. The combination of Sophorae Flavescentis Radix and Rhizoma Smilacis Glabrae inhibited the proliferation of mouse epidermal keratinocytes and reduced the number of T cells in the skin. The potential molecular mechanism was that the combination of Sophorae Flavescentis Radix and Rhizoma Smilacis Glabrae regulated arachidonic acid metabolism, sphin- golipid metabolism, tryptophan metabolism and phenylalanine metabolism. Conclusions The combination of Sophora Flavescens Radix and Rhizoma Smilacis Glabrae can relieve psoriasis-like lesions in mice by inhibiting the proliferation of epidermal keratinocytes and reducing the number of T cells in the skin and regulating metabolism to intervene psoriasis recurrence. This study provides a potential topical drug of psoriasis for relieving psoriasis recurrence.
ABSTRACT
Total glucosides of Rhizoma Smilacis Glabrae (RSG) are selective immunosuppressants that exhibit primary efficacy in the treatment of rheumatoid arthritis through targeted inhibition of activated T cells. In this study, we aimed to investigate the potential application of RSG in the treatment of psoriasis and elucidate its mechanism of action and material basis. Our findings revealed significant improvements upon administration of RSG in an imiquimod (IMQ)-induced psoriasis model. These improvements were characterized by a remarkable increase in the number of tail scales in mice and a substantial amelioration of skin erythema, ulceration, and flaking. By transcriptome sequencing and T-cell flow sorting assay, we identified notable effects of RSG on the modulation of various cellular processes. Specifically, RSG prominently down-regulated the Th17/Treg ratio in damaged skin tissues and reduced the proportion of G2 phase cells. Furthermore, RSG exhibited a stimulatory effect on the proliferation and differentiation of epithelial cells. Of particular interest, we discovered that β-sitosterol, sitostenone, stigmasterol, smiglanin, and cinchonain Ib displayed potent inhibitory effects on the IL-17-mediated inflammatory response in HaCaT cells. In summary, our study highlights the therapeutic potential of RSG in the treatment of psoriasis, attributed to its ability to regulate the Th17/Treg balance. These findings contribute to the development of new indications for RSG and provide a solid theoretical foundation for further exploration in this field.
Subject(s)
Animals , Mice , T-Lymphocytes, Regulatory , Psoriasis/drug therapy , Arthritis, Rheumatoid , Biological Assay , Glucosides/pharmacologyABSTRACT
Objective To optimize the sulfated modification conditions for Rhizoma Smilacis Glabrae polysaccharides (RSGP),and to investigate the possibility of enhancing the activity of RSGP after sulfating modification.Methods RSGP was modified by cholorosulfonic acid-pyridine.With the yield,carbohydrate content and sulphate substitution degree as the observation indexes,L9 (34)orthogonal design was used to optimize reaction time,reaction temperature and reagent ratio.The degree of sulphate substitution was determined by barium chloride turbitimetry,and the carbohydrate content was detected by sulfuric acid-phenol method.Then the structures of the sulfated modified products were analyzed by infrared radiation (IR) spectrum.Methyl thiazolyl tetrazolim(MTT)assay was used to determine the anti-tumor activity of sulfated RSGP on HepG2 and MCF-7 cell lines.Results The optimized modification conditions of RSGP were sulfating RSGP with cholorosulfonic acid-pyridine in the ratio of 1:6 for 4.5 hours at 60 ℃.The MTT assay results showed that the sulfated RSGP could inhibit the growth and proliferation of human liver cancer HepG2 cell line and human mammary cancer MCF-7 cell line in concentrationdepending manner.Conclusion It is feasible for sulfating modification of RSGP with cholorosulfonic acid-pyridine,and sulfating modification can enhance the anti-tumor activitv of RSGP.
ABSTRACT
A remarkabale inhibitory activity was exhibited by the aqueous extract from Rhizoma smilacisglabrae(RSG) against both picryl chloride(PC)- induced contact dermatitis and sheep red bloodcells (SRBC)- induced footpad reaction.The effect of RSG was displayed more distinctlywheng given after than before the 2nd antigen challenge.RSG also showed a marked anti-in-flammatory activity against xylene- induced ear and egg whiteinduced footpad edema.Addi-tionally,RSG did not show a potable influence on IgM- and IgG-PFC counts against SRBC inmice.An increase but not decrease in serum hemolysin level,however,was observed in both groupsof RSG,peralleled with the finding that hemolytic plaques in PFC test were obviously biggerthan those in control.These results suggest that RSG has a selective activity to suppress the cellularimmune response without inhibiting the humoral immune response.The suppression to cellular im-munity by RSG may be presented mainly through affecting the inflammatory process after lym-phokine release.