Abstract
Objective To investigate the therapeutic potential and underlying mechanism of Lantana ca-mara ethanolic extract(LCEE)in ulcerative colitis(UC).
Methods Phytochemical analysis of LCEE was conducted using qualitative analysis,liquid chromatography-mass spectrometry(LC-MS),and high-performance thin-layer chromatog-raphy(HPTLC).The active constituents of LCEE were identified through network pharmacol-ogy analysis,followed by molecular docking.The therapeutic mechanism was validated in a UC rat model using 42 male Wistar rats(200-250 g)induced by 2,4,6-trinitrobenzene sulfon-ic acid(TNBS).Rats were randomly divided into seven groups(n=6 per group):normal con-trol(NC),ethanol control(EC),disease control(DC),three doses of LCEE treatment[low dose LCEE(100 mg/kg),medium dose LCEE(200 mg/kg),and high dose LCEE(400 mg/kg),p.o.],and dexamethasone(DEX,2 mg/kg,p.o.)groups.Following TNBS-induced UC(120 mg/kg,intrarectally),rats were treated orally for 28 d.Disease severity was assessed through body weight changes,disease activity index(DAI),colon weight,colon length,and morphological scores.Haematological parameters,enzymatic antioxidants,nitric oxide(NO),myeloperoxi-dase(MPO),and inflammatory cytokines were measured in the serum and colon tissues.Gene expressions of tumor necrosis factor(TNF)-α,epidermal growth factor receptor(EGFR),signal transducer and activator of transcription 3(STAT3),and B-cell lymphoma 2(Bcl-2)were analyzed by quantitative reverse transcription polymerase chain reaction(qRT-PCR).Histopathological alterations in the colon tissues were evaluated using hematoxylin and eosin(HE),Giemsa,and periodic acid-schiff staining(PAS).
Results LC-MS analysis identified 13 phytoconstituents in LCEE,and HPTLC analysis con-firmed the presence of ursolic acid,geniposide,and chlorogenic acid.Network pharmacologi-cal analysis identified 152 potential therapeutic targets with TNF,STAT3,Bcl-2,albumin(ALB),and EGFR as the top 5 hub targets.Molecular docking revealed strong binding affini-ties of LCEE phytoconstituents with key inflammatory and apoptotic targets:linaroside with TNF-α(-6.1 kcal/mol),ursolic acid with STAT3(-6.8 kcal/mol)and Bcl-2(-8.7 kcal/mol),and cirsiliol with EGFR(-8.2 kcal/mol),comparable to DEX.LCEE treatment significantly in-creased body weights and thymus weight,while significantly reducing colon weight,spleen weight,and DAI scores.Haematological parameters showed significant improvements with increased haemoglobin,red blood cells,and platelet count,and decreased white blood cells counts.Antioxidants markers were significantly improved with increased glutathione,superoxide dismutase,and catalase levels,and decreased malondialdehyde levels.LCEE significantly reduced NO and MPO levels and inflammatory cytokines including TNF-α,inter-leukin(IL)-1β,nuclear factor kappa-B(NF-κB),IL-6,and IL-12 compared with TNBS treated rats.LCEE downregulated the gene expression levels of TNF-α,EGFR,and STAT3,while up-regulating Bcl-2 expression level,indicating modulation of inflammation and apoptosis path-ways.Histological evaluation confirmed that after LECC treatment,mucosal ulcers and in-flammatory cell infiltration decreased.
Conclusion The findings suggest that Lantana camara may serve as a medicinal plant to alle-viate UC and offer an investigational basis for the clinical utilization of Lantana camara.关键词
溃疡性结肠炎/马缨丹/三硝基苯磺酸/网络药理学/分子对接/炎症细胞因子Key words
Ulcerative colitis/Lantana camara/Tri-nitrobenzene sulfonic acid/Network pharmacology/Molecular docking/Inflammatory cytokines
