Crocin, an active constituent of Crocus sativus ameliorates cerulein induced pancreatic inflammation and oxidative stress.

Acute pancreatitis (AP) is a disorder of the pancreas marked by profound inflammation and oxidative stress. Phytoconstituents presents an important toolbox of preventive strategies to combat inflammatory disorders. To this end, we selected the active constituent of Crocus sativus, crocin for evaluation against cerulein-induced AP, owing to its promising antiinflammatory activity in acute as well as chronic inflammatory conditions. The animals were randomly divided into five groups comprising of normal control, cerulein control, crocin low dose (30 mg/kg), crocin high dose (100 mg/kg), and crocin control (100 mg/kg). Various biochemical parameters and the levels of inflammatory cytokines and p65-NFκB were measured. The mechanism was investigated by histology and immunohistochemistry. We found that crocin significantly reduced the pancreatic edema, amylase, and lipase levels. It abrogated the oxidative stress incurred by cerulein challenge. We found that crocin modulated the pancreatic inflammatory cytokine levels. Crocin perturbed the nuclear translocation of p65-NFκB. Crocin reverted the pancreatic histology associated with AP. Furthermore, it upregulated the expression of Nrf-2 and downregulated the expression of IL-6, TNF-α, nitrotyrosine, and NFκB. Cumulatively, these results indicate that crocin has promising potential to prevent cerulein induced AP and regular intake of saffron can prove beneficial for the pancreatic health.

Synthesis of Substituted Cinnamido Linked Quinazolinone Congeners as Potential Anticancer Agents via Mitochondrial Dependent Intrinsic Apoptotic Pathway.

BACKGROUND: The synthesis of novel heterocyclic scaffolds with amide functionality is a key research area due to their plethora of medicinal applications. The present study aims to explore the synthesis of new cinnamido linked quinazolinone congeners and their potential as anticancer agents. METHODS: Cytotoxicity evaluation, Cell cycle analysis, JC-1 staining, ROS, Annexin V assays, AO/EB, DAPI nuclear staining, Colony-forming assay and Western blot analysis. RESULTS: Among the synthesized compounds, 5eb and 5fc have shown promising cytotoxic activity with an IC50 value of 3.89±1.01µM and 4.05±0.62µM against HeLa cell lines. The flow-cytometry analysis demonstrated that the compound 5eb arrested the sub-G1 phase of the cell cycle and induced apoptosis. Furthermore, the compound 5eb triggered the collapse of mitochondrial membrane potential (ΔΨm), which was assessed by JC-1 staining and also induced the generation of Reactive Oxygen Species. An increase in the expression of proapoptotic proteins such as Bax, p53, cleaved PARP and cleaved caspase-3 by 5eb confirmed the activation of the mitochondrial-dependent intrinsic apoptosis pathway. CONCLUSION: Our results suggest that compound 5eb and 5fc of cinnamido linked quinazolinone derivatives could serve as potential leads in the development of novel chemotherapeutic agents.

Withaferin A ameliorates renal injury due to its potent effect on inflammatory signaling.

Chronic kidney disease (CKD) is one of the major global health concerns and is responsible for end-stage renal disease (ESRD) complications. Inflammation plays a pivotal role in the progression of CKD. In the present study, we evaluated the renoprotective effects of a potent immunomodulator steroidal lactone, Withaferin A (WfA), in an animal model of renal injury (unilateral ureteral obstruction, UUO) and further investigated if the inhibition of inflammatory signaling can be a useful approach to reduce renal injury. Animals were randomly divided into five groups: Sham control, UUO control, WfA control, WfA low dose (1 mg/kg), and WfA high dose (3 mg/kg). Oxidative stress was measured by the estimation of reduced glutathione and lipid peroxidation levels. H&E and Picrosirius Red staining were performed to assess the extent of histological damage and collagen deposition. Furthermore, the molecular mechanism of the WfA effects was explored by immunohistochemistry, enzyme-linked immunosorbent assay, multiplex analysis of transforming growth factor ß (TGF-ß) pathway, and an array of inflammatory cytokines/chemokines. Interestingly, our pharmacological intervention significantly attenuated tissue collagen, inflammatory signaling, and macrophage signaling. WfA intervention abrogated the inflammatory signaling as evident from the modulated levels of chemokines and cytokines. The levels of TGF-ß along with downstream signaling molecules were also attenuated by WfA treatment as revealed by inhibition in the expression of TGF-ß1, TGF-ß2, p-Smad2, p-Smad3, total Smad4, p-Akt, and p-ERK. We, to the best of our knowledge, prove for the first time that WfA has potential renoprotective activity against UUO-induced nephropathy due to its outstanding anti-inflammatory properties.