Pongamol from the seeds of Tephrosia purpurea exert anti-cancer activity against cervical cancer cell line

Tephrosia purpurea belongs to the family Fabaceae, is used for the treatment of inflammation, diabetes, cancer, elephantitis, haemmaroids, anaemia, dysmenorrhea, chronic fever, boils, gingivitis etc. In the present study, three compounds (TP-1, TP-3 and TP-5) were isolated from EETP. Quantity of TP-3 (6.05 %) in EETP was determined by HPLC. In-vitro anti-cancer activity of EETP and isolated compound TP-3 on SiHa cells (cervical cancer cell lines) as well as PBMCs (peripheral blood mononuclear cells) were evaluated by MTT (3-(4,5- di methyl thiazol -2-yl)-2,5-di phenyl tetrazolium bromide) assay. Spectroscopic analysis and physical properties, structure of isolated compounds TP-1, TP-3 and TP-5 were characterized as teclenone, pongamol and β-sitosterol respectively. Isolated compound TP-3 showed cytotoxicity against SiHa cells with the IC50 33.06 µgmL-1. TP-3 showed cytotoxicity at all the concentrations but significant activity was observed at the concentration range from 20-50 µgmL-1 as compared to control. Maximum cytotoxicity (72.75%) was observed at the concentration of 50 µgmL-1. TP-3 showed non-significant cytotoxicity against PBMCs cells at all the concentrations except at 50 µgmL-1 (cytotoxicity 24.19%). EETP showed significant cytotoxic activity (IC50 value 113.63 µgmL-1) against SiHa cells at the concentration range from 75-150 µgmL-1 as compared to control. Maximum cytotoxicity (75.34%) was observed at the concentration of 150 µgmL-1

Pongamol from the seeds of Tephrosia purpurea exert anti-cancer activity against cervical cancer cell line

182-188Tephrosia purpurea belongs to the family Fabaceae, is used for the treatment of inflammation, diabetes, cancer, chronic fever, boils, gingivitis etc. In the present study, three compounds (TP-1, TP-3 and TP-5) were isolated from ethyl acetate extract of the seeds of T. purpurea (EETP). Quantity of TP-3 (6.05%) in EETP was determined by HPLC. In-vitro anti-cancer activity of EETP and isolated compound TP-3 on SiHa cells as well as PBMCs (peripheral blood mononuclear cells) were evaluated by MTT (3-(4,5- di methyl thiazol -2-yl)-2,5-di phenyl tetrazolium bromide) assay. On the basis of spectroscopic analysis and physical properties, structure of isolated compounds TP-1, TP-3 and TP-5 were characterized as teclenone, pongamol and β-sitosterol respectively. Isolated compound TP-3 showed cytotoxicity against SiHa cells with the IC50 33.06 μgmL-1. TP-3 showed significant cytotoxicity at the concentration range from 20-50 μgmL-1 as compared to control. Maximum cytotoxicity (72.75%) was observed at the concentration of 50 μgmL-1. TP-3 showed non-significant cytotoxicity against PBMCs cells at all the concentrations except at 50 μgmL-1 (cytotoxicity 24.19%). EETP showed significant cytotoxicity (IC50 value 113.63 μgmL-1) against SiHa cells at the concentration range from 75-150 μgmL-1 as compared to control. Maximum cytotoxicity (75.34%) was observed at the concentration of 150 μgmL-1

Autoimmunity and clinical pathology amelioration in SLE by dexamethasone primed mesenchymal stem cell derived conditioned media

Abstract Background This study aimed to investigate the therapeutic potential of cell-free Dexamethasone (Dex) primed Wharton’s jelly Mesenchymal stem cells derived conditioned media (DW) in addressing complications associated with systemic lupus erythematosus (SLE), focusing on its immunomodulatory effects. Methods Peripheral blood mononuclear cells from 74 SLE patients were stimulated and treated with Dex, DW and W. Culture supernatant were evaluated for autoantibody levels, IL-10 and TGF-β by ELISA, Treg subtypes, Breg subtypes, TH17 cells Double negative T cells and inflammatory neutrophils by flow cytometry, IL-10 and IL-17A by qPCR. In vivo studies were performed on 60 pristane induced female BALB/c mice. Dex and DW treatments were evaluated for autoantibody production, proteinuria, immunomodulation of immune cells, organ function, and histopathology. In vivo imaging of internal organs was done using VevoLAZR-X photoacoustic imaging system. Results DW treatment significantly expanded different Treg and Bregs subtypes. DW suppressed pathogenic TH17, Double negative T cells and inflammatory neutrophils. Comparative analyses with hydroxychloroquine showed similar effects, with combined treatment enhancing efficacy. Inhibition studies implicated the TGF-β pathway in DW's mechanism. In vivo studies using the PIL mouse model showed that DW treatment reduced mortality, prevented proteinuria, and ameliorated symptoms such as limb inflammation, seizures, and alopecia. Detailed organ-specific evaluations through live imaging and histopathological analyses revealed DW’s protective effects on kidneys, liver, lungs, heart, and spleen. Conclusion DW shows promise as a cell-free biological therapy for SLE and related autoimmune disorders, capable of modulating immune responses effectively without the adverse effects of glucocorticoids

Exploration of Neuroprotective Properties of a Naturally Inspired Multifunctional Molecule (F24) against Oxidative Stress and Amyloid β Induced Neurotoxicity in Alzheimer’s Disease Models

The pathological hallmarks of Alzheimer’s disease (AD) are manifested as an increase in the level of oxidative stress and aggregation of the amyloid-β protein. In vitro, in vivo, and in silico experiments were designed and carried out with multifunctional cholinergic inhibitor, F24 (EJMC-7a) to explore its neuroprotective effects in AD models. The neuroprotection ability of F24 was tested in SH-SY5Y cells, a widely used neuronal cell line. The pretreatment and subsequent co-treatment of SH-SY5Y cells with different doses of F24 was effective in rescuing the cells from H2O2 induced neurotoxicity. F24 treated cells were found to be effective in the reduction of cellular reactive oxygen species, DNA damage, and Aβ1–42 induced neurotoxicity, which validated its neuroprotective effectiveness. F24 exhibited efficacy in an in vivo Drosophila model by rescuing eye phenotypes from degeneration caused by Aβ toxicity. Further, computational studies were carried out to monitor the interaction between F24 and Aβ1–42 aggregates. The computational studies corroborated our in vitro and in vivo studies suggesting Aβ1–42 aggregation modulation ability of F24. The brain entry ability of F24 was studied in the parallel artificial membrane permeability assay. Finally, F24 was tested at doses of 1 and 2.5 mg/kg in the Morris water maze AD model. The neuroprotective properties shown by F24 strongly suggest that multifunctional features of this molecule provide symptomatic relief and act as a disease-modifying agent in the treatment of AD. The results from our experiments strongly indicated that natural template-based F24 could serve as a lead molecule for further investigation to explore multifunctional therapeutic agents for AD management