Aim: Rhizophora mucronata, commonly called as 'red mangrove' grows in the tropical and subtropical regions and on the sheltered shores. The bioactive compounds from the plant have been used in the treatment of wide range of diseases. Though the beneficial effects have been reported, the safety and toxicological studies are not carried out. Hence, major bioactives have been identified by HPLC and then acute and sub-acute toxicity studies of (BERM) in Swiss Albino mice have been carried out. Main methods: HPLC fingerprinting was carried out of BERM for the characterization of bioactives. BERM as a single dose was given orally at 800, 1600 mg/kg and 3200 mg/kg by a stainless steel cannula to the mice. Then the mice were observed for 14 days for mortality and behavioural changes. Food, water intake and body weight changes were also observed throughout the study period. On the fifteenth day, the mice were anesthetized with isofluorane and blood was withdrawn for haematological and biochemical analysis. The animals were sacrificed by overdose of isofluorane and organs such as liver, kidney, lungs and spleen were dissected out for histopathological analysis. There was no mortality of the mice even in 3200 mg/kg dose, stating that the oral LD50 of BERM is more than 5000 mg/kg. In terms of Sub-acute toxicity, for a period of 28 days repeated dose of 400 mg/ kg and 800 mg/kg as an optimum dose and a control group was kept with only distilled water at 5 ml/kg against the treated groups. On 29 th day, the mice from all groups were sacrificed and blood was withdrawn and organs such as liver, kidney, lungs and spleen were dissected out for the assessment of internal tissues, wherein no abnormalities were observed in the treatment groups as compared to the control. The blood parameters, biochemical analysis of the treated groups were well within the range, histopathological confirmed the findings wherein the organs viz, liver, kidneys, lungs and spleen possessed normal architecture. Key findings: Based on HPLC results, prominent 5 major compounds viz: Diadzein, Epicatechin, Hesperidin, Diosmin and Quercitrin respectively were identified. Isolated changes observed in the haematological, biochemical and histopathological studies were not dose related and showed the safety of the bark extract. Similarly, the sub-acute toxicity of BERM has been conducted for 28 days, wherein repeated dose of 400 mg/kg and 800 mg/kg and control group was given orally. There were no abnormalities found both in external and internal parameters. Significance: Based on the study it is concluded that the bark extract of Rhizophora mucronata (BERM) is safe at 1000 mg/kg or less on repeated dosage can be considered as a safe dose for pharmacological efficacy studies.
The bark extract of Rhizophora mucronata (BERM) was recently reported for its prominent in vitro protective effects against liver cell line toxicity caused by various toxicants, including ethanol. Here, we aimed to verify the in vivo hepatoprotective effects of BERM against ethanol intoxication. An oral administration of different concentrations (100, 200, and 400 mg/kg) of BERM prior to high-dose ethanol via intraperitoneal injection was performed in mice. On the 7th day, liver and kidney sections were dissected out for histopathological examination. The ethanol intoxication caused large areas of liver necrosis while the kidneys were not affected. Pre-BERM administration decreased ethanol-induced liver injury, as compared to the mice treated with ethanol alone. In addition, the pre-BERM administration resulted in a decrement in the level of ethanol-induced oxidative stress, revealed by a concomitant increase of GSH and a decrease of MDA hepatic levels. The BERM extract also reversed the ethanol-induced liver injury and hepatotoxicity, characterized by the low detection of TNF-α gene expression level and fragmented DNA, respectively. Altogether, BERM extract exerts antioxidative activities and present promising hepatoprotective effects against ethanol intoxication. The identification of the related bioactive compounds will be of interest for future use at physiological concentrations in ethanol-intoxicated individuals.
The bark extract of Rhizophora mucronata (BERM) was recently reported for its prominent in vitro protective effects against liver cell line toxicity caused by various toxicants, including ethanol. Here, we aimed to verify the in vivo hepatoprotective effects of BERM against ethanol intoxication with the prediction of potential targets employing in silico studies. An oral administration of different concentrations (100, 200 and 400 mg/kg body weight) of BERM before high-dose ethanol via intraperitoneal injection was performed in mice. On day 7, liver sections were dissected for histopathological examination. The ethanol intoxication caused liver injury and large areas of necrosis. The pre-BERM administration decreased the ethanol-induced liver damage marker tumor necrosis factor-alpha (TNF-α) expression, reduced hepatotoxicity revealed by nuclear deoxyribonucleic acid (DNA) fragmentation and decreased oxidative stress indicated by malondialdehyde and glutathione contents. Our in silico studies have identified BERM-derived metabolites exhibiting the highest predicted antioxidant and free radical scavenger activities. Molecular docking studies showed that most of the metabolites were predicted to be enzyme inhibitors such as carbonic anhydrase inhibitors, which were reported to stimulate the antioxidant defense system. The metabolites predominantly presented acceptable pharmacokinetics and safety profiles, suggesting them as promising new antioxidant agents. Altogether, the BERM extract exerts antioxidative activities and shows promising hepatoprotective effects against ethanol intoxication. Identification of related bioactive compounds will be of interest for future use at physiological concentrations in ethanol-intoxicated individuals.
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