[Objective]: To investigate the therapeutic potential and underlying mechanism of Lantana camara 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 chromatography (HPTLC). The active constituents of LCEE were identified through network pharmacology 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 sulfonic acid (TNBS). Rats were randomly divided into seven groups (n = 6 per group): normal control (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), myeloperoxidase (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 confirmed the presence of ursolic acid, geniposide, and chlorogenic acid. Network pharmacological 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 affinities 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 increased 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, interleukin (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 upregulating Bcl-2 expression level, indicating modulation of inflammation and apoptosis pathways. Histological evaluation confirmed that after LECC treatment, mucosal ulcers and inflammatory cell infiltration decreased. [Conclusion] The findings suggest that Lantana camara may serve as a medicinal plant to alleviate UC and offer an investigational basis for the clinical utilization of Lantana camara.

Objective: To investigate the bone-protective potential of Nelumbo nucifera Gaertn. seed hydroalcoholic extract (NNHE) in an ovariectomized (OVX) rat model by modulating the estrogen receptor/osteoprotegerin/receptor activator of nuclear factor (NF)-κB (ER/OPG/RANKL) signaling pathway. Methods: Network pharmacology was employed with the databases of PubChem, BindingDB, DisGeNET, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG), along with Cytoscape 3.10.2 for identifying the targets and pathways of NNHE relevant to OP. A total of 48 specific pathogen-free (SPF) grade female Wistar rats were randomly divided into six groups (n = 8 per group): sham control, OVX control, OVX + NNHE [100, 200, 400 mg/(kg·d)], and OVX + alendronate [3 mg/(kg·week)]. The treatment lasted for 16 weeks. Post-treatment assessment included bone parameters (weight, thickness, density, volume, and length), serum biochemical markers [parathyroid hormone (PTH), estrogen, OPG, RANKL, tartrate-resistant acid phosphatase (TRAP), osteocalcin (OC), calcitonin (CT), calcium (Ca), phosphorus (P), and alkaline phosphatase (ALP)], pro-inflammatory cytokines [tumour necrosis factor (TNF)-α, NF-κB, interleukin (IL)-1β, and IL-6], lipid profiles [total cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL), and high density lipoprotein (HDL)], oxidative stress markers [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH), and malondialdehyde (MDA)], and histopathological analyses of femur, uterus, and vaginal tissues. Results: Network pharmacology analysis revealed 61 overlapping targets between NNHE and osteoporosis-related genes, including signal transducer and activator of transcription 3 (STAT3), NF-κB subunit 1 (NFKB1), dopamine receptor D2 (DRD2), matrix metalloproteinase 9 (MMP9), and caspase-3. GO and KEGG enrichment suggested involvement in the ER/OPG/RANKL signaling pathway. In vivo studies demonstrated that NNHE treatment (400 mg/kg) significantly reduced OVX-induced body weight gain and exhibited estrogenic activity in the vaginal cornification assay. NNHE at 200 and 400 mg/kg significantly increased serum estrogen levels compared with OVX control group, while uterine weight remained unaffected. NNHE significantly improved the lipid profile compared with OVX group, with TC, TG, and LDL decreased, while HDL levels were increased at 200 and 400 mg/kg. Bone metabolism markers were significantly improved compared with OVX group, with serum Ca and P levels restored at all NNHE doses and ALP activity reduced. NNHE effectively modulated bone turnover markers compared with OVX group by reducing levels of OC, TRAP, and PTH, and increasing level of CT. In addition, NNHE decreased RANKL level while increasing OPG level at 200 and 400 mg/kg. Bone mineral density (BMD) was significantly enhanced compared with OVX group. Serum oxidative stress was significantly mitigated compared with OVX group through increased levels of antioxidant enzymes (SOD, CAT, and GSH) and reduced MDA, with the most pronounced effects observed at 400 mg/kg. Pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, and NF-κB) were significantly reduced in all NNHE treatment groups compared with OVX group. Histopathological analysis confirmed restoration of trabecular bone structure and normalization of reproductive tissue morphology in OVX rats after NNHE treatment. Conclusion NNHE demonstrated significant protective effects against OVX-induced osteoporosis through ER/OPG/RANKL signaling pathway modulation, oxidative stress, and inflammation suppression, resulting in improved BMD and structural integrity. These findings indicate that NNHE may represent a promising therapeutic candidate for postmenopausal osteoporosis management and merits further clinical investigation.