This study aimed to assess the protective effect of hesperidin (HES) and rutin (RUT) against cisplatin-induced nephrotoxicity in male rats. Cisplatin (5 mg/kg, intraperitoneal) caused significant increases in serum sodium, blood urea nitrogen, serum creatinine, total sodium and potassium excreted in urine, urine volume, and lipid peroxides measured as the malondialdehyde content of kidney, with significant decreases in serum total protein, creatinine clearance, reduced glutathione content of kidney, and kidney superoxide dismutase activity as compared with the control group. On the other hand, administration of HES (200 mg/kg, per oral [p.o.]) or RUT (30 mg/kg, p.o.) for 14 days with a single cisplatin dose on the tenth day ameliorated the cisplatin-induced nephrotoxicity as indicated by the restoration of kidney function and oxidative stress biomarkers. Furthermore, the test drugs reduced the histopathological changes induced by cisplatin. In conclusion, HES and RUT showed protective effects against cisplatin-induced nephrotoxicity.

Articular manifestations are the main hall mark for rheumatoid arthritis; inflammation and oxidative stress are involved in its pathogenesis. This study was designed to figure out the possible therapeutic potential of polydatin on experimentally induced arthritis in rats. Polydatin (POLY) was administered (200 mg/kg, p.o.) for 21 days to complete Freund's adjuvant (CFA; 0.1 ml, s.c.)-induced arthritic rats. Meanwhile, methotrexate (MTX; 0.75 mg/kg, i.p.) was given as a reference standard disease-modifying anti-rheumatic drug (DMARD). Both POLY and MTX significantly attenuated articular damage associated with CFA-induced arthritis. This was manifested by reducing levels of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), interleukin-17 (IL-17), and matrix metalloproteinase-3 (MMP-3), paralleled with marked decrease in hind paw and ankle diameters. Moreover, POLY and MTX downregulated gene expressions of receptor activator of nuclear factor kappa-B ligand (RANKL) as well as signal transducer and activator of transcription-3 (STAT3) besides hampering immunohistochemical staining of vascular endothelial growth factor (VEGF) and nuclear factor kappa-B (NF-κB). Furthermore, substantial decline in myeloperoxidase (MPO) activity and malondialdehyde (MDA) level associated with significant rise in reduced glutathione content (GSH) was observed. These findings provide an innovative therapeutic approach of POLY as a natural anti-arthritic drug through modulating IL-6/STAT-3/IL-17/NF-кB cascade. Graphical Abstract ᅟ.

This study aimed to coat lipid-based nanocarriers with chitosan to encapsulate nutraceuticals, minimize opsonization, and facilitate passive-targeting. Phase one was concerned with standardization according to the World Health Organization. Qualitative analysis using liquid chromatography-high-resolution mass spectrometry (LC-HRMS/MS) investigated the active constituents, especially reported cytotoxic agents. Cinnamaldehyde and rosmarinic acid were selected to be quantified using high-performance liquid chromatography. Phase two was aimed to encapsulate both extracts in solid lipid nanoparticles (core) and chitosan (shell) to gain the advantages of both materials properties. The developed experimental model suggested an optimum formulation with 2% lipid, 2.3% surfactant, and 0.4% chitosan to achieve a particle size of 254.77 nm, polydispersity index of 0.28, zeta potential of +15.26, and entrapment efficiency percentage of 77.3% and 69.1% for cinnamon and oregano, respectively. Phase three was focused on the evaluation of cytotoxic activity unencapsulated/encapsulated cinnamon and oregano extracts with/without 5-fluorouracil on HCT-116 cells. This study confirmed the success of the suggested combination with 5-fluorouracil for treating human colon carcinoma with a low dose leading to decreasing side effects and allowing uninterrupted therapy.

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