Phytochemical profiling and cytotoxic potential of Arnebia nobilis root extracts against hepatocellular carcinoma using in-vitro and in-silico approaches.

Hepatocellular carcinoma is the fifth most prevalent cancer worldwide. The emergence of drug resistance and other adverse effects in available anticancer options are challenging to explore natural sources. The current study was designed to decipher the Arnebia nobilis (A. nobilis) extracts for detecting phytochemicals, in-vitro evaluation of antioxidative and cytotoxic potentials, and in-silico prediction of potent anticancer compounds. The phytochemical analysis revealed the presence of flavonoids, phenols, tannins, alkaloids, quinones, and cardiac glycosides, in the ethanol (ANE) and n-hexane (ANH) extracts of A. nobilis. ANH extract exhibited a better antioxidant potential to scavenge DPPH, nitric oxide and superoxide anion radicals than ANE extract, which showed better potential only against H2O2 radicals. In 24 h treatment, ANH extract revealed higher cytotoxicity (IC50 value: 22.77 µg/mL) than ANH extract (IC50 value: 46.74 µg/mL) on cancer (HepG2) cells without intoxicating the normal (BHK) cells using MTT assay. A better apoptotic potential was observed in ANH extract (49.10%) compared to ANE extract (41.35%) on HepG2 cells using the annexin V/PI method. GCMS analysis of ANH extract identified 35 phytocompounds, from which only 14 bioactive compounds were selected for molecular docking based on druggability criteria and toxicity filters. Among the five top scorers, deoxyshikonin exhibited the best binding affinities of - 7.2, - 9.2, - 7.2 and - 9.2 kcal/mol against TNF-α, TGF-ßR1, Bcl-2 and iNOS, respectively, followed by ethyl cholate and 2-Methyl-6-(4-methylphenyl)hept-2-en-4-one along with their desirable ADMET properties. The phytochemicals of ANH extract could be used as a promising drug candidate for liver cancer after further validations.

Role of diagnostic factors associated with antioxidative status and expression of matrix metalloproteinases (MMPs) in patients with cancer therapy induced ocular disorders.

BACKGROUND: Cancer patients when treated with different chemotherapeutic drugs often develop mild to severe sight threatening diseases during or after chemotherapy. The mechanism involved in the pathogenesis of ocular toxicities is poorly understood. Oxidative stress, inflammation and MMPs (angiogenic factor) are involved in the progression of chemotherapy related ocular disorders. MATERIALS AND METHODS: The concentration of oxidative stress markers such as MDA, NO and levels of different antioxidant molecules such as SOD, CAT, GSH, GPx, GPr, VIT A, VIT E and VIT C present in the serum of chemotherapy treated patients (n = 50) and in normal persons (n = 20) were estimated by the direct spectrophotometric method while the concentration of TNF-α and MMP-9 activity were determined using human TNF-α and MMP-9 ELISA kits. RESULTS: The concentration of SOD and CAT (0.356 ±â€¯0.05 µg/dl and 1.26 ±â€¯0.01 µmol/mol of protein) was significantly lower as compared to that (1.09 ±â€¯0.03 µg/dl and 3.99 ±â€¯0.04 µmol/mol of protein) in controls. The levels of GPx (0.06 ±â€¯0.01 mmol/dl) in the cancer patients were much lower than those in the controls (0.78 ±â€¯0.06 mmol/dl). Lower level of GSH (0.96 ±â€¯0.003 µg/dl) in serum of the diseased group was observed as compared to healthy group (7.26 ±â€¯1.40 µg/dl). The level of Vit A, Vit C and Vit E was lower in systemic circulation of cancer patients (109.99 ±â€¯6.35 µg/ml, 1.26 ±â€¯0.36 µg/ml and 1.29 ±â€¯0.191 µg/ml) as compared to control subjects (166.35 ±â€¯14.26 µg/ml, 3.25 ±â€¯0.099 µg/ml and 6.354 ±â€¯2.26 µg/ml) respectively. The concentration of nitric oxide was significantly higher in the cancer patients (45.26 ±â€¯6.35 ng/ml) than that in the normal subjects (16.35 ±â€¯3.26 ng/ml). The higher concentration of MDA (8.65 ±â€¯3.26 nmol/ml) was observed in the patients than normal ones (1.254 ±â€¯0.065 nmol/ml). The quantity of TNF-α was significantly higher in chemotherapy treated patients (32.68 ±â€¯4.33 pg/ml) as compared to the control group (20.979 ±â€¯1.98 pg/ml). Significantly higher concentration of MMP-9 (40.26 ±â€¯3.26 ng/ml) was observed in the cancer patients than the controls (7.256 ±â€¯1.95 ng/ml). CONCLUSION: Lower levels of antioxidant enzymes and non-enzymatic small molecules and higher levels of oxidative stress and inflammatory clinical parameters such as NO, MDA, TNF-α and MMP-9 may be involved in the pathogenesis of systemic chemotherapy related ocular complications such as cataract, glaucoma, blepharitis, retinitis pigmentosa, macular degeneration, pterygium and retinal degeneration.