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Major objective of this study was to explore the protective effect of the methanolic extract of Chenopodium album against carbon tetrachloride induced hepatotoxicity in rats. Chenopodium album has locally been used for multiple medicinal proposes. Methanolic extract of Chenopodium album (whole plant) was prepared with Soxhlet extractor and rotatory evaporator. Antioxidant activity of Chenopodium album was determined by DPPH free radical scavenging assay. Thirty Wister (albino) rats (150-200 g) were divided into six groups for the evaluation of hepatoprotective potential of different concentrations of Chenopodium album against carbon tetrachloride (1:1 CCl4: Olive oil) under the controlled laboratory conditions. Group-I rats were administrated with olive oil (Normal control), Group-II with CCl4 only, Group-III with Silymarin (positive control), Group-IV with Chenopodium album (100 mg/kg), Group-V with Chenopodium album (200 mg/kg) and Group-VI rats with Chenopodium album (300 mg/kg) for the period of 28 days. Serum was taken to determine the levels of alanine transaminase, aspartate transaminase, alkaline phosphatase, cholesterol, triglyceride, creatinine and urea in the blood. Formalin stored tissues were examined for histopathological analysis. DPPH assay showed that Chenopodium album has the potential for reduction of oxidative stress. Chenopodium album minimized the levels of ALT (70 ± 8.68 U/L, 68.75 ± 8.38 U/L & 73.5 ± 10.28 U/L), AST (219.5 ± 19.16 U/L, 140.75 ± 13.35 U/L & 221.25 ± 13.33 U/L) and ALP (289.5 ± 28.21 U/L, 258 ± 11.12 U/L & 248.25 ± 4.03 U/L) at different concentrations (100 mg/kg, 200 mg/kg, 300 mg/kg respectively). Chenopodium album enhanced triglyceride level (64.75 ± 12.66 mg/dl at 200 mg/kg) as compared to CCl4 treated group (33.25 ± 1.26 mg/dl). Carbon tetrachloride elevated urea level (43.25 ± 6.6) was decreased by high dose of Chenopodium album (18 ± 8.17). Moreover, Chenopodium album also improved WBC level (9.69 × 103 /Cu.mr & 10.59 × 103 /Cu.mr at low and medium doses respectively), RBCs level (6.97 × 103 /Cu.mr) and hemoglobin level (13.95 G/dL, 13.467 G/dL & 14.05 G/dL at low, medium and high doses). In vivo study of Chenopodium album methanolic extract demonstrates the potential for protection of liver and after pre-clinical studies the plant can be used as a safe alternative of commercially available hepatoprotective medicines.
RESUMO
This corrects the article DOI: 10.1038/ncomms14338.
RESUMO
Neurodegenerative diseases characterized by aberrant accumulation of undigested cellular components represent unmet medical conditions for which the identification of actionable targets is urgently needed. Here we identify a pharmacologically actionable pathway that controls cellular clearance via Akt modulation of transcription factor EB (TFEB), a master regulator of lysosomal pathways. We show that Akt phosphorylates TFEB at Ser467 and represses TFEB nuclear translocation independently of mechanistic target of rapamycin complex 1 (mTORC1), a known TFEB inhibitor. The autophagy enhancer trehalose activates TFEB by diminishing Akt activity. Administration of trehalose to a mouse model of Batten disease, a prototypical neurodegenerative disease presenting with intralysosomal storage, enhances clearance of proteolipid aggregates, reduces neuropathology and prolongs survival of diseased mice. Pharmacological inhibition of Akt promotes cellular clearance in cells from patients with a variety of lysosomal diseases, thus suggesting broad applicability of this approach. These findings open new perspectives for the clinical translation of TFEB-mediated enhancement of cellular clearance in neurodegenerative storage diseases.