Ethyl acetate extract of Ceiba pentandra (L.) Gaertn. reduces methotrexate-induced renal damage in rats via antioxidant, anti-inflammatory, and antiapoptotic actions.

Methotrexate (MTX) is a chemotherapeutic agent and an immunosuppressant used to treat cancer and autoimmune diseases. However, its use is limited by its multi-organ toxicity, including nephrotoxicity, which is related to MTX-driven oxidative stress. Silencing oxidative stressors is therefore an important strategy in minimizing MTX adverse effects.Medicinal plants rich in phenolic compounds are probable candidates to overcome these oxidants. Herein, C. pentandra ethyl acetate extract showed powerful in vitro radical-scavenging potential (IC50 = 0.0716) comparable to those of the standard natural (ascorbic acid, IC50 = 0.045) and synthetic (BHA, IC50 = 0.056) antioxidants. The effect of C. pentandra ethyl acetate extract against MTX-induced nephrotoxicity in rats was evaluated by administering the extract (400 mg/kg/day) or the standard antioxidant silymarin (100 mg/kg/day) orally for 5 days before and 5 days after a single MTX injection (20 mg/kg, i.p.).C. pentandra showed slight superiorities over silymarin in restoring the MTX-impaired renal functions, with approximately twofold decreases in overall kidney function tests. C. pentandra also improved renal antioxidant capacity and reduced the MTX-induced oxidative stress. Moreover, C. pentandra inhibited MTX-initiated apoptotic and inflammatory cascades, and attenuated MTX-induced histopathological changes in renal tissue architecture.Phytochemical investigation of the extract led to the purification of the phenolics quercitrin (1), cinchonains 1a (2) and 1b (3), cis-clovamide (4), trans-clovamide (5), and glochidioboside (6); a structurally similar with many of the reported antioxidant and nephroprotective agents. In conclusion, these data demonstrate that C. pentandra exhibits nephroprotective effect against MTX-induced kidney damage via its antioxidant, antiapoptotic and anti-inflammatory mechanisms. TAXONOMY: Functional Disorder, Traditional Medicine, Herbal Medicine.

Development and optimization of a novel drug free nanolipid vesicular system for treatment of osteoarthritis.

OBJECTIVE: The goal of this study is to improve the transdermal delivery of phosphatidylcholine (PC) via constructing a novel nanolipid vesicular system (NLVS) with high level of permeability through the stratum corneum (SC). SIGNIFICANCE: In our study, a novel drug free NLVS was developed. The system depends on PC boundary cartilage lubrication to relieve osteoarthritic pain without developing gastrointestinal problems associated with anti-inflammatory drug. MATERIALS AND METHODS: A full two-level (23) factorial design is applied to optimize the quality of the prepared NLVS. The selected independent variables are the concentration of PC, the concentration of edge activator (EA), and EA type. The developed NLVS was evaluated for in-vitro, ex-vivo as well as in-vivo efficacy in rat animal model. RESULTS: Based on the factorial design, the selected formulation variables significantly affect the tested responses. The prepared NLV formulations have a particle size (PS)in the range of 10.34 to 496.3 nm, polydispersity index (PdI) values less than one, and negative zeta potential (ZP) range of -1.42 to -32.01 mV. In-vitro and ex-vivo study results reveal that the designed NLVS is effective in sustaining PC release and enhancing its transdermal permeation over 24 h. The optimal permeation flux through ex-vivo study is 0.415 mg/cm2/h following zero-order kinetics. Moreover, in-vivo study of the optimized formulations demonstrated remarkable reduction in inflammatory mediators associated with osteoarthritis (OA). CONCLUSION: The results indicate that the optimized drug free NLVS significantly augment transdermal delivery of PC and have a potential role in treatment of OA without the risk of systemic side effects.