The present investigation was executed to reveal the protective mechanism of rosmarinic acid (RA) against cadmium (Cd)-induced nephrotoxicity. RA exhibited a concentration-dependent anti-apoptotic effect against CdCl₂ in isolated mouse proximal tubular epithelial cells. Cd treatment significantly (p < 0.01) imparted oxidative stress to the renal cells via excessive ROS production, triggering NO level, NADPH oxidase activation, and impairment of cellular redox defense system. Cd-mediated oxidative stress significantly (p < 0.01) endorsed apoptosis to the murine kidney cells by triggering NF-κB/PKC-δ/TNFR2 activation. In addition, CdCl₂ induced renal fibrosis by triggering TGF-β1/SMAD3/α-SMA/collagen signaling within renal cells. On the other hand, RA significantly (p < 0.05–0.01) attenuated Cd-provoked oxidative stress and associated pathological signal transduction in murine renal cells. RA treatment also could significantly (p < 0.05–0.01) reciprocate Cd-mediated pathological changes in blood and urine parameters in mice. In addition, histological data supported the pharmacological findings. In silico chemometric analyses predicted the possible interactions between RA and different signal proteins and anticipated drug-likeness characteristics of RA. Hence, RA can potentially be applied as a therapeutic agent to treat Cd-mediated nephrotoxicity in future.

Cadmium (Cd) imparts nephrotoxicity via triggering oxidative stress and pathological signal transductions in renal cells. The present study was performed to explore the protective mechanism of carnosic acid (CA), a naturally occurring antioxidant compound, against cadmium chloride (CdCl₂)-provoked nephrotoxicity employing suitable in vitro and in vivo assays. CA (5 µM) exhibited an anti-apoptotic effect against CdCl₂ (40 µM) in normal kidney epithelial (NKE) cells evidenced from cell viability, image, and flow cytometry assays. In this study, CdCl₂ treatment enhanced oxidative stress by triggering free radical production, suppressing the endogenous redox defence system, and inhibiting nuclear factor erythroid 2-related factor 2 (Nrf2) activation in NKE cells and mouse kidneys. Moreover, CdCl₂ treatment significantly endorsed apoptosis and fibrosis via activation of apoptotic and transforming growth factor (TGF)-β1/mothers against decapentaplegic homolog (Smad)/collagen IV signalling pathways, respectively. In contrast, CA treatment significantly attenuated Cd-provoked nephrotoxicity via inhibiting free radicals, endorsing redox defence, suppressing apoptosis, and inhibiting fibrosis in renal cells in both in vitro and in vivo systems. In addition, CA treatment significantly (p < 0.05–0.01) restored blood and urine parameters to near-normal levels in mice. Histological findings further confirmed the protective role of CA against Cd-mediated nephrotoxicity. Molecular docking predicted possible interactions between CA and Nrf2/TGF-β1/Smad/collagen IV. Hence, CA was found to be a potential therapeutic agent to treat Cd-mediated nephrotoxicity.

The present studies have been executed to explore the protective mechanism of carnosic acid (CA) against NaAsO₂‐induced hepatic injury. CA exhibited a concentration dependent (1–4 μM) increase in cell viability against NaAsO₂(12 μM) in murine hepatocytes. NaAsO₂treatment significantly enhanced the ROS‐mediated oxidative stress in the hepatic cells both inin vitroandin vivosystems. Significant activation of MAPK, NF‐κB, p53, and intrinsic and extrinsic apoptotic signaling was observed in NaAsO₂‐exposed hepatic cells. CA could significantly counteract with redox stress and ROS‐mediated signaling and thereby attenuated NaAsO₂‐mediated hepatotoxicity. NaAsO₂(10 mg/kg) treatment caused significant increment in the As bioaccumulation, cytosolic ATP level, DNA fragmentation, and oxidation in the liver of experimental mice (n= 6). The serum biochemical and haematological parameters were significantly altered in the NaAsO₂‐exposed mice (n= 6). Simultaneous treatment with CA (10 and 20 mg/kg) could significantly reinstate the NaAsO₂‐mediated toxicological effects in the liver. Molecular docking and dynamics predicted the possible interaction patterns and the stability of interactions between CA and signal proteins. ADME prediction anticipated the drug‐likeness characteristics of CA. Hence, there would be an option to employ CA as a new therapeutic agent against As‐mediated toxic manifestations in future.

Sterculia foetida is a subject of interest in many scientific fields as researchers look for novel treatments because of its varied medicinal qualities and chemical richness. Terpenoids are aromatic and aliphatic chemicals with anti-bacterial properties and can prevent free radical damage. They are present in S. foetida extract. Moreover, it possesses immunomodulatory, hepatoprotective, antiviral, antioxidant, anti-inflammatory, antifungal properties. This work aims to green synthesize, characterize, and evaluate the anti-bacterial activity of Sterculia foetida bark extract-loaded silver nanoparticles. Chemicals like Methanol, Petroleum Ether, and water have been used to extract the phytoconstituents from the plant bark. AgNO3 and Silver have been used to synthesize the nanoparticles. Instruments like ATR-IR Spectrophotometer, UV- spectrophotometer, DLS, and SEM instruments have been used to characterize the nanoparticles. Bacterial strains like Staphylococcus aureus (ATCC-6538), Escherichia coli (ATCC 25922), saline water, AMX30, swab stick, inoculation loop, susceptibility scale have been used for studying the anti-bacterial activity. DLS and zeta potential analysis demonstrated the creation of stable nanoparticles with a particle size of 79 nm. The anti-bacterial activity of AgNPs with the methanolic bark extract showed significant anti-bacterial activity compared to the standard marketed drug AMX30. The highest zone of inhibition was observed against gram-positive bacteria S.aureus (1.68 cm) and gram-negative bacteria E.coli (1.74 cm), respectively, at 500 μg/ml concentration. The study concludes that greenly synthesized S. foetida bark extract containing nanoparticles is a potential anti-bacterial agent, especially against gram-negative bacteria. Further, in vivo studies are needed to establish its potential.