Table of Content

31 May 2026, Volume 35 Issue 5

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Original articles

Molecular docking and dynamics simulations reveal phytosterol mechanisms in chronic kidney disease therapy

Rui Li, Ying Zhang, Yurong Chen, Yingjie Gao, Fan Yang

2026, 35(5):  407-419.  DOI: 10.5246/jcps.2026.05.029

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Chronic kidney disease (CKD) represents a growing global health challenge due to its high prevalence, multifactorial pathogenesis, and limited therapeutic options. Phytosterols, a class of naturally occurring bioactive compounds widely present in plants, have garnered increasing attention for their anti-inflammatory, antioxidant, and immunomodulatory properties. Among these, stigmasterol (Stig) and β-sitosterol (β-Sito) are the most abundant and biologically active representatives, previously reported to confer protective effects against cardiovascular, metabolic, and renal disorders. In the present study, we explored the potential molecular mechanisms of these phytosterols in a folic acid (FA)-induced CKD mouse model. Comprehensive transcriptomic analysis revealed that Sting1, a gene critically involved in innate immune responses, was markedly upregulated in CKD and significantly downregulated following phytosterol treatment. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses further implicated immune- and inflammation-related pathways, such as cytokine-cytokine receptor interaction and chemokine signaling, as potential mediators of the therapeutic effects. Molecular docking and molecular dynamics (MD) simulations demonstrated stable binding of both phytosterols to the Sting1 protein, with stigmasterol exhibiting higher binding affinity and greater conformational stability. Detailed analyses of root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), and radius of gyration (Rg) supported the structural integrity of the phytosterol-Sting1 complexes. MM-PBSA energy decomposition identified PHE-268 and PRO-208 as key residues mediating the interactions. Moreover, cellular thermal shift assays (CETSA) in HK-2 cells confirmed that both compounds enhanced the thermal stability of Sting1 under moderate heat stress (40–49 °C), providing additional evidence for a direct interaction. Taken together, these findings indicated that phytosterols might exert nephroprotective effects through direct modulation of Sting1, thereby attenuating immune and inflammatory dysregulation in CKD. This study offered novel mechanistic insights and established a theoretical foundation for the development of phytosterol-based therapeutic interventions for CKD.



Targeting TREM1: screening metabolically-active TCM compounds for TAM polarization and enhancing PD-1 inhibitor efficacy in HCC by alleviating immunosuppression

Ruiwei Yao, Ziyi Zeng, Yue He, Ying Zhang, Chong Zhong, Jinfang Zhang

2026, 35(5):  420-437.  DOI: 10.5246/jcps.2026.05.030

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Hepatocellular carcinoma (HCC), characterized by its high malignancy, poses a serious threat to patient survival and health. Immunotherapy has increasingly emerged as a key therapeutic strategy for HCC; however, the immunosuppressive tumor microenvironment (TME) frequently undermines its efficacy. Therefore, identifying molecular targets and therapeutic agents capable of alleviating this immunosuppression is of paramount importance. In this study, bioinformatics analyses revealed that triggering receptor expressed on myeloid cells-1 (TREM1) expression correlated positively with HCC progression, and elevated TREM1 levels were associated with poorer clinical outcomes. Notably, TREM1 was predominantly expressed in macrophages and exhibited the strongest interaction with these cells within the TME. Functional in vitro assays demonstrated that silencing TREM1 attenuated the immunosuppressive phenotype of tumor-associated macrophages (TAMs). In a subcutaneous mouse tumor model, TREM1 knockdown synergized with PD-1 blockade to enhance anti-tumor efficacy. RNA sequencing further indicated that TREM1 modulated metabolism-related pathways. Complementary literature review and molecular docking analyses suggested that specific bioactive compounds derived from traditional Chinese medicine (TCM) might exert anti-HCC effects by targeting TREM1 and regulating TAM metabolism. Collectively, these findings provided a novel mechanistic framework for understanding the immunomodulatory potential of TCM in HCC therapy.



Cyasterone alleviates collagen-induced arthritis in mice by activating autophagy and inhibiting inflammation via the TLR4/MyD88/NF-κB signaling pathway

Xinfang Tan, Yuan Liu, Pengbo Shi, Jiangtao Ma, Chengxi Huang, Zhifang Wu, Xiaoshen Hu, Liangliang Xu

2026, 35(5):  438-453.  DOI: 10.5246/jcps.2026.05.031

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Rheumatoid arthritis (RA) is a chronic autoimmune disease. Cyasterone, a phytoecdysteroid, demonstrates anti-inflammatory potential, but its mechanism in RA remains unclear. This study aims to investigate Cyasterone’s therapeutic effect and underlying mechanisms in collagen-induced arthritis (CIA) mice. Cell migration and cell invasion capabilities were measured by the transwell assay. Apoptosis was detected by TUNEL or flow cytometry. Tail vein injection of bovine type II collagen was used to establish the mouse CIA model. The enzyme-linked immunoassay was performed to measure inflammatory factor concentrations. Quantitative real-time PCR or WB analysis was performed to detect gene or protein expression. CIA was assessed by the arthritis index and claw thickness curve, etc. The results demonstrated that Cyasterone had dose-dependent inhibitory effects on the proliferation, migration, and invasion of rheumatoid arthritis-fibroblast like synoviocytes (RA-FLS). Cyasterone increased apoptosis and reduced inflammation in RA-FLS, indicating its protective effects in RA. Cyasterone inhibited TLR4/MyD88/NF-κB pathway and increased autophagy in RA-FLS, as demonstrated by reduced TLR4, MyD88, phosphorylated p65, and p-mTOR levels while increasing Beclin 1 expression and light chain 3 II/I ratio. The in vivo results further confirmed that Cyasterone reduced the arthritis index and paw swelling, significantly reduced the serum levels of inflammatory factors, alleviated synovial hyperplasia and destruction of cartilage structure, demonstrating an anti-cartilage damage effect. In conclusion, Cyasterone protected against CIA through the TLR4/MyD88/NF-κB signaling pathway, which might be a promising candidate for arthritis treatment.