Stress is a mode of adaptive response towards external demands, and prolonged exposure to stress is known to promote aging and neurodegeneration. Several therapies promote neuroprotection but are usually accompanied by adverse consequences. Traditional medicine has been proven as an effective alternative for promoting pharmacological health benefits such as wound healing, boosting memory function and reducing oxidative stress. Centella asiatica (CeA) has also gaining attention as an alternative option in promoting neuroprotective activities against neurodegenerative disorders and neuronal injuries. In this study, the neurodegenerative condition of rats was achieved using chronic stress through movement restraint and forced swimming for 21 consecutive days. Here, the neuroprotective properties of three different dosage of CeA (200 mg/kg/day, 400 mg/kg/day and 800 mg/kg/day) was evaluated using metabolomics approach. The administration of CeA shown distinction between untreated group and treated group; and reducing the effect of chronic stress in rats. The extract also demonstrated a significant elevation in several metabolites (lactate, isoleucine, proline, methionine, valine, leucine and glutamine) in rats treated with CeA, particularly in rats administered with 800 mg/kg of CeA. These significant metabolites play important roles in variety of biochemical function of the brain such as the synthesis of protein, energy metabolism, synthesis of neurotransmitter, protection against oxidative stress and compartmentalisation of glutamate. The results of this study may contribute towards greater understanding of molecular mechanism of CeA in promoting neuroprotective properties against neurodegeneration from exposure to chronic stress.
Keywords: Centella asiatica, Chronic Stress, NMR-based metabolomics, Serum Metabolites
Curcuma mangga belongs to the family Zingibereae locally known as "mango ginger" or "manggo turmeric". Medicinally, the rhizomes of Curcuma mangga are used for treatment of stomach and chest pains, fever, stomach ulcer and general weakness. It is also used in postpartum treatment, particularly to help in the healing of the womb. The various medicinal purpose of this species inspired further phytochemical studies and potential biological activities. Phytochemical studies reported the isolation of six compounds identifies as curcumin (1), demethoxycurcumin (2), curcumol (3), curdione (4), zederone (5) and β-Sitosterol (6). Curcumol (3), curdione (4) and zederone ( 5) are reported to be first isolated from this species. Crude extracts and isolated constituents possessed potential cytotoxic activities against five human cancerous cell lines; promyelocytic leukemia (HL-60), breast cancer (MCF-7), colonic cancer (HT-29), cervical cancer (HeLa) and T-lymphoblastic (CEM-SS). Promising antioxidant activities and remarkable antimicrobial properties are recorded against Methicillin-resistant Staphylococcus aureus (MRSA), Bacillus subtillis and Pseudomonas aeruginosa.
Annona muricata is a common plant used in Africa and South America to manage various types of disease. However, there is insufficient toxicological information or published standard available regarding repeated dose animal toxicity data. As part of the safety assessment, we exposed Sprague Dawley rats to an acute oral toxicity of A. muricata. The intent of the current study was to use advanced proton nuclear magnetic resonance (1H NMR) in serum and urinary metabolomics evaluation techniques to provide the in vivo acute toxicological profile of A. muricata leaf ethanol extract in accordance with the Organization for Economic Co-operation and Development’s (OECD) 423 guidelines. A single 2000 mg/kg dose of A. muricata leaf ethanol extract was administered to Sprague Dawley rats over an observational period of 14 days. The toxicity evaluation (physical and behavior observation, body weight, renal function test, liver function test and 1H NMR analysis) showed no abnormal toxicity. Histopathological analysis manifested mild changes, i.e., the treated kidney manifested mild hypercellularity of mesangial cells and mild red blood cell congestion. In addition, there was mild hemorrhage into tissue with scattered inflammatory cells and mild dilated central vein with fibrosis in the liver. However, the changes were very mild and not significant which correlate with other analyses conducted in this study (biochemical test and 1H NMR metabolomic analysis). On the other hand, urinary 1H NMR analysis collected on day 15 revealed high similarity on the metabolite variations for both untreated and treated groups. Importantly, the outcomes suggest that A. muricata leaf ethanol extract can be safely consumed at a dose of 2000 mg/kg and the LD50 must be more than 2000 mg/kg.
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