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Ameloblastoma is a non-cancerous but aggressive oral tumor emerging from odontogenic epithelial tissue involved during odontogenesis. Since there is lack in unravelling the complete molecular pathogenesis of ameloblastoma, chemotherapy is less attempted and a lot of disagreement over the optimal treatment option. Hence, till date, wide surgical resection is considered to be the reliable treatment for ameloblastoma. The Neurotrophin Signaling pathway plays an important role in neuron signaling and it is closely related with the MAPK pathway, which on the other hand regulated cell differentiation, apoptosis, proliferation, plasticity and survival. Protein- Protein Interaction analysis was analysed with STRING tool using WNL value, identified that CTNNB1, HRAS, NGFR, NGFR, and SORT1 having high interacting with BDNF, NT4, p75NTR, NGF, and NT3. The results of ontology analysis revealed that Neurotrophin signaling pathway is associated with Cell surface receptor signaling pathway, regulation of cell differentiation, regulation of development process, EGFR tyrosine kinase inhibitor resistance, MAPK signaling pathway, PI3K-Akt signaling pathway and Ras signaling pathway leading to pathogenesis involving genes. Further, clustering coefficient values of proteins BDNF, NT4, p75NTR, NGF & NT3 were identified as 0.627, 0.708, 0.367, 0.644 & 0.415 . The results of molecular docking studies revealed among the selected ligands Methyl-ɣ-oresellinate, N-(4-Hydroxy-phenyl)-2-phenyl-N-phenylacetyl-acetamide, Atranorin and Oresellinate exhibited high binding affinity with selected protein. The key genes involved in Neurotrophin signaling pathway leading to ameloblastoma pathogenesis is revealed, which are closely associated with cell differentiation, cell proliferation, pro-apoptosis, and pro-survival regulations. Further it can be concluded that Neurotrophin signaling pathway could be one of the promising pathway to tailor the targeted drug therapy for Ameloblastoma treatment., Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-024-00223-2., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

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Multiple drug resistance and increased side effects due to allopathic drugs has warned scientific community with a global alarm to identify molecules from natural sources to combat diseases with minimum or no side effects. The present investigation was aimed to identify and isolate secondary metabolites from traditionally used Nerium indicum using conventional column chromatography which led to the isolation of two compounds, C-I (fractions NB4f1) and C-II (fractions NC13b1). Further characterized, it is elucidated using spectral data and identified as N-(4-hydroxy-phenyl)-2-methoxy-2-phenyl-acetamide, molecular formula C 15 H 15 NO 3 , and molecular weight 257.3 (C-I) and N-(4-hydroxy-phenyl)-2-phenyl-N-phenylacetyl-acetamide, molecular formula C 22 H 19 NO 3 , and molecular weight 345.4 (C-II). Further, the isolated compounds were investigated using in silico approach by Autodock tool with four different proteins specific for cancer and in vitro assessed cell proliferation, and apoptosis against human breast cancer MCF 7 cell line. The results of the in silico model demonstrated potent binding affinity of both compounds with the proteins representing that the isolated molecules could be a drug of choice for cancer. Further, the isolated compounds revealed significant inhibition of cell proliferation (IC 50 values 21 μg/mL for C-I, 19 μg/mL for C-II) with induced apoptosis with nuclear condensation effect on the MCF 7 cells in in vitro condition even at very low concentration. Compound treatment to MCF-7 cell line represented bright fetches indicating condensed chromatins and higher level of nuclear fragmentation with DAPI staining, indicating higher cell death due to induced apoptosis and confirmed using flow cytometry analysis representing inhibition of cell proliferation at S phase. Graphical abstract.

The present study deals with the synthesis of silver nanoparticles (AgNPs) from Rhynchosia rufescens and to evaluate its cytotoxic effect mediated through induced apoptosis. The reduction and capping of phytoconstituents was confirmed using FTIR demonstrating O-H and C-H stretching at different peaks. The size and the shape of the particle were determined using scanning electron microscopy (SEM) illustrating 1 μm to 100 nm in size and the composition of compounds in the AgNPs were revealed using XRD and EDX. The results of the antioxidant assays revealed that the synthesized AgNPs had significant radical scavenging potential in dose-dependent inhibition with 22-64% for DPPH and 25-41% for ferric reducing antioxidant power assay at the concentrations of 20-100 μg/ml. Further, the synthesized AgNPs demonstrated potent cytotoxic activity against human breast cancer (MCF-7) cell line with an IC 50 value of 26 ± 1.0 μg/ml by the MTT assay. Cytotoxicity was confirmed using AO/EtBr and DAPI staining method where nuclear condensation and fragmentation of cancer cells was observed after treatment with nanoparticle. The results were further confirmed by flow cytometry analysis which revealed the occurrence of apoptosis during the S phase in cell cycle exposing the potential of the AgNPs against MCF-7 cancer cell. From the results, we conclude that the synthesized AgNPs from Rhynchosia rufescens exhibited multifunctional properties. Graphical abstract.

Background: Diabetes is rapidly rising all over the world at an alarming rate and has changed from a mild disorder to major causes of mortality and morbidity in the youth and middle-aged people, and the prevalence is seen especially in six inhabited continents of the globe. The present study aims to explore the antidiabetic, lipid lowering effect of Cassia auriculata L. flowers in alloxan-induced diabetes., Methods: Diabetes was induced using alloxan monohydrate in experimental rats and subsequent therapeutic effects of C. auriculata extract and standard drug glibenclamide were monitored. Bioassay-directed fractionation using silica gel column chromatography was performed until pure fractions were isolated. The effect of the treatment was analyzed by hematological parameters and enzyme assays. The pure compounds were confirmed with thin layer chromatography and high performance liquid chromatography pattern and further subjected for characterization., Results: The alterations in blood glucose were monitored throughout the study. There was a gradual fall in blood glucose and significant changes were observed in lipid profile and metabolic enzyme after treatment with C. auriculata . Bioassay fractionation represented that the C2 subfraction produced a dose-dependent fall in blood glucose and lipid profile and upon further purification yielded two pure compounds. The structure of the pure compound was elucidated using Fourier transform infrared, 1 H nuclear magnetic resonance, 13 C nuclear magnetic resonance, and mass spectral data., Conclusion: The present study clearly indicated the significant antidiabetic effect of C. auriculata and lends support for its traditional usage without evident toxic effects.