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INTRODUCTION: Ceriops decandra (CD) and Ceriops tagal (CT) are two traditionally used mangrove plants widely distributed along the coastal areas of South Asia, Africa, South Pacific. In this study, we evaluated the diuretic potential of aerial roots of CD, CT and assessed the effectiveness of the plants' terpenoids enriched bioactive constituents against human carbonic anhydrase (hCA) enzyme through molecular docking. MATERIALS AND METHODS: Firstly, the acute toxicity of CD and CT was evaluated in mice. In vivo diuretic activity was then studied in mice and the volume of excreted urine was measured. The urine was further examined for pH, density and Na+, K+, Cl- concentrations. From this, the saluretic, natriuretic, kaliuretic and CAI (carbonic anhydrase inhibitory) activities were calculated. Finally, total terpenoid contents (TTC) of the plant extracts were quantified and the terpenoids previously reported from both CD and CT were docked against four hCA isoforms - hCAII, hCAIV, hCAXII and hCAXIV. RESULTS: In the acute toxicity assessment, no sign of toxicity was found. In diuretic activity evaluation, both extracts displayed substantial increase in urine volume, with CD being at top. Concentrations of Na+, K+ and Cl- were also upsurged at a high dose of treatment (500 mg/kg). Both extracts at 500 mg/kg dose demonstrated potent saluretic, natriuretic and CAI activity. The TTC of CD was significantly higher than CT. In molecular docking analysis, greater binding affinity against hCA isoforms was demonstrated by the terpenoids reported from CD. CONCLUSION: Aerial roots of both CD and CT possess substantial diuretic activity with an inhibitory effect on CA. Here, diuretic potential as well as the total terpenoid content of CD were much greater between the two.
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ETHNOPHARMACOLOGICAL RELEVANCE: Phragmites karka (Retz.) of family Poaceae is a pristine tropical plant that is well known to the local healers for ailments of diabetes, fever, diarrhea and CNS depression but lacks the scientific evidence behind its traditional usage. Hence, we explicated this plant to find the scientific basis of its traditional utilization. AIM OF THE STUDY: The current study aims to find out the antidiabetic potential, toxicity after oral administration and in vitro cytotoxic activity of aerial parts of the plant on HeLa cells. METHODS: The plant was extracted with methanol by maceration and the crude extract was then subjected to solvent partitioning with modified Kupchan method for preparing several fractions. Phytochemical screening and total phenolic content of the plant was first determined through established procedures. Acute toxicity of the plant was studied by orally administering a single high dose (5000 mg/kg) of drug. Cytotoxicity of the methanolic plant extract was determined by measuring the percentage of cell viability on human cervical cancer cell lines, HeLa. In vitro antidiabetic activity was determined through iodine starch and DNSA (3,5-dinitrosalicylic acid) method of α-amylase inhibition. Finally, in vivo oral glucose tolerance test and alloxan induced antidiabetic activity test was performed at 150 and 300 mg/kg body weight doses of plant extract to confirm the in vivo antidiabetic activity. RESULTS: No mortality was demonstrated by Phragmites karka in the acute toxicity test. However, signs of cellular toxicity was observed and histopathological studies on major organs exhibited necrosis in liver and kidney. In vitro cytotoxicity assay revealed the death of HeLa cells by DCM (dichloromethane) and n-hexane fractions of plant extract at 100 and 10 µg/mL concentrations. The IC50 value of the fractions were later evaluated by MTT assay (316.1 and 96.7 µg/mL for n-hexane and DCM fractions, respectively). In the iodine starch and DNSA method of α-amylase enzyme inhibitory activity test, substantial inhibition of enzyme was observed with the IC50 values of 2.05 and 2.08 mg/mL, respectively. In the in vivo antidiabetic activity test, considerable reduction in blood glucose level of diabetic mice was detected in both oral glucose tolerance test and alloxan induced antidiabetic activity test. In addition, the microscopic examination of pancreas showed noticeable recovery of pancreatic ß cells and the blood lipid profile analysis represented a significant (p < 0.05) reduction of total cholesterol, LDL (low density lipoprotein) and triglyceride level in plant extract treated mice. CONCLUSION: Results of this study reveals that the Phragmites karka extract is toxic at cellular level after oral administration and cytotoxic when tested on HeLa cells. The plant also evidenced hypoglycemic property, possibly through the inhibition of α-amylase enzyme and recovered the pancreatic beta cells along with the improvement of lipid profile of diabetic mice. However, robust studies on this plant is required to isolate the bioactive compounds, elucidate structures and evaluate their mechanism of actions in support of our findings. CLASSIFICATION: Toxicology and Safety, Quality Traditional Medicine.