Discovery and development of new potentially selective anticancer agents are necessary to prevent a global cancer health crisis. Currently, alternative medicinal agents derived from plants have been extensively investigated to develop anticancer drugs with fewer adverse effects. Among them, steroidal alkaloids are conventional secondary metabolites that comprise an important class of natural products found in plants, marine organisms and invertebrates, and constitute a judicious choice as potential anti‐cancer leads. Traditional medicine and modern science have shown that representatives from this compound group possess potential antimicrobial, analgesic, anticancer and anti‐inflammatory effects. Therefore, systematic and recapitulated information about the bioactivity of these compounds, with special emphasis on the molecular or cellular mechanisms, is of high interest. In this review, we methodically discuss thein vitroandin vivopotential of the anticancer activity of natural steroidal alkaloids and their synthetic and semi‐synthetic derivatives. This review focuses on cumulative and comprehensive molecular mechanisms, which will help researchers understand the molecular pathways involving steroid alkaloids to generate a selective and safe new lead compound with improved therapeutic applications for cancer prevention and therapy.In vitroandin vivostudies provide evidence about the promising therapeutic potential of steroidal alkaloids in various cancer cell lines, but advanced pharmacokinetic and clinical experiments are required to develop more selective and safe drugs for cancer treatment.

Curcumin, used as a spice and traditional medicine in India, exerts beneficial effects against several diseases, owing to its antioxidant, analgesic, and anti-inflammatory properties. Evidence indicates that curcumin might protect against heavy metal-induced organ toxicity by targeting biological pathways involved in anti-oxidation, anti-inflammation, and anti-tumorigenesis. Curcumin has received considerable attention owing to its therapeutic properties, and the mechanisms underlying some of its actions have been recently investigated. Cadmium (Cd) is a heavy metal found in the environment and used extensively in industries. Chronic Cd exposure induces damage to bones, liver, kidneys, lungs, testes, and the immune and cardiovascular systems. Because of its long half-life, exposure to even low Cd levels might be harmful. Cd-induced toxicity involves the overproduction of reactive oxygen species (ROS), resulting in oxidative stress and damage to essential biomolecules. Dietary antioxidants, such as chelating agents, display the potential to reduce Cd accumulation and metal-induced toxicity. Curcumin scavenges ROS and inhibits oxidative damage, thus resulting in many therapeutic properties. This review aims to address the effectiveness of curcumin against Cd-induced organ toxicity and presents evidence supporting the use of curcumin as a protective antioxidant.

The discovery of new biomarkers for early detection of drug-induced acute kidney injury (AKI) is clinically important. In this study, sensitive metabolomic biomarkers identified in the urine of rats were used to detect cisplatin-induced AKI. Cisplatin (10 mg kg⁻¹, i.p.) was administered to Sprague-Dawley rats, which were subsequently euthanized after 1, 3 or 5 days. In cisplatin-treated rats, mild histopathological alterations were noted at day 1, and these changes were severe at days 3 and 5. Blood urea nitrogen (BUN) and serum creatinine (SCr) levels were significantly increased at days 3 and 5. The levels of new urinary protein-based biomarkers, including kidney injury molecule-1 (KIM-1), glutathione S-transferase-α (GST-α), tissue inhibitor of metalloproteinase-1 (TIMP-1), vascular endothelial growth factor (VEGF), calbindin, clusterin, neutrophil, neutrophil gelatinase-associated lipocalin (NGAL), and osteopontin, were significantly elevated at days 3 and 5. Among urinary metabolites, trigonelline and 3-indoxylsulfate (3-IS) levels were significantly decreased in urine collected from cisplatin-treated rats prior to histological kidney damage. However, carbon tetrachloride (CCl₄), a hepatotoxicant, did not affect these urinary biomarkers. Trigonelline is closely associated with GSH depletion and results in insufficient antioxidant capacity against cisplatin-induced AKI. The predominant cisplatin-induced AKI marker appeared to be reduced in urinary 3-IS levels. Because 3-IS is predominantly excreted via active secretion in proximal tubules, a decrease is indicative of tubular damage. Further, urinary excretion of 3-IS levels was markedly reduced in patients with AKI compared to normal subjects. The area under the curve receiver operating characteristics (AUC-ROC) for 3-IS was higher than for SCr, BUN, lactate dehydrogenase (LDH), total protein, and glucose. Therefore, low urinary or high serum 3-IS levels may be more useful for early detection of AKI than conventional biomarkers.