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The hepatoprotective properties of scopoletin have been explored in carbon tetrachloride (CCl4) induced liver injury but not in drug-induced liver injury (DILI) scenarios. Only N-acetyl-cysteine (NAC) has proven efficacy in DILI treatment. Accordingly, we conducted a study to assess the hepatoprotective action of scopoletin in the anti-tubercular treatment (ATT)-DILI model in Wistar rats, if any. A total of 36 rats were evaluated, with six in each group. A 36-day ATT at 100 mg/kg dose for isoniazid, 300 mg/kg for rifampicin and 700 mg/kg for pyrazinamide were fed to induce hepatotoxicity in rats. Group I and II–VI received normal saline and ATT, respectively. Oral scopoletin (1,5 and 10 mg/kg) and NAC 150 mg/kg were administered in groups III, IV, V and VI, respectively, once daily for the last 15 days of the experiment. LFT monitoring was performed at baseline, days 21, 28, and 36. Rats were sacrificed for the histopathology examination. Aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and bilirubin levels were significantly increased in group II (receiving ATT) compared to normal control on day 28 and day 36 (p<0.05). All three doses of scopoletin and NAC groups led to the resolution of AST, ALT, ALP, and bilirubin changes induced by ATT medications effect beginning by day 28 and persisting on day 36 (p<0.01). An insignificant effect was observed on albumin and total protein levels. The effect was confirmed with antioxidants and histopathology analysis. The study confirms the hepatoprotective efficacy of scopoletin in a more robust commonly encountered liver injury etiology. [ABSTRACT FROM AUTHOR]

Background: Several phyto-chemicals have been identified and suggested as potential therapeutic options for hepatotoxicity management. Objective: To assess the hepatoprotective effect of scopoletin, a pure phyto-chemical, in carbon tetrachloride (CCl4)-induced hepatotoxicity model in Wistar rats. Methods: Thirty-six rats in total, six in each group, were utilized in this study. Animals in group 1 received normal saline; those in group 2 received carbon tetrachloride in olive oil (0.5 ml/kg, i.p. in ratio 1:1); those in groups 3, 4, and 5 received oral scopoletin (1 mg/kg, 5 mg/kg, 10 mg/kg dose-wise groups); and those in group 6 received N-acetyl cysteine (NAC) 150 mg/kg. Blood sampling was performed on day - 3, day 1, and day 7 of the CCl4 administration. Rats were sacrificed on day 7 of the experiment for histological examination and oxidative stress measurement of the liver. Results: The 5 mg/kg scopoletin group showed a maximum reduction in AST levels [727.33 ± 29.15 in medium dose (MD) group vs 1526.66 ± 60.72 in the experimental control (EC) group (P < 0.001) and ALT levels of 532.66 ± 24.23 in MD group vs 894.83 ± 52.47 in EC (P < 0.01)]. The dose-dependent action was not observed with scopoletin doses. The protective effect of scopoletin was confirmed by MDA and GSH levels (P < 0.05) coupled with histo-pathological findings. In the present study, a reversible model of CCl4-induced hepatotoxicity was observed to get normalized in a week's time. Conclusion: The study confirms the hepatoprotective action of scopoletin in an acute model of hepatic injury with the putative anti-oxidant mechanism. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study was to evaluate the effect of Convolvulus pluricaulis (CP; C. pluricaulis) methanolic extract on Triton WR‐1339‐induced hyperlipidaemia in rats. Methods: The study comprised of six groups namely normal control, experimental control and treatment groups (100, 200 and 400 mg/kg of C. pluricaulis, and 65 mg/kg of Fenofibrate). Hyperlipidaemia was induced by a single intraperitoneal injection of Triton WR‐1339 400 mg/kg in rats. Parameters such as lipid profile, oxidative stress, histological analysis and atherogenic index were evaluated. The plant extract was further studied by HPLC and LCMS, for analyses of active phytochemicals. Key findings: The result of the study showed that C. pluricaulis significantly decreased total cholesterol, triglycerides, LDL‐c, MDA levels and atherogenic index while the levels of HDL‐c and GSH were found to be raised. Plant extract at the dose of 400 mg had a consistent effect on all lipid profile parameters. Lower doses (100 and 200 mg) did not produce a statistically significant reduction in LDL‐c. In addition, the protective effect of C. pluricaulis was confirmed by histological analysis. Further, the findings of the study were found to be comparable with fenofibrate. Conclusions: Therefore, the present study suggests that C. pluricaulis has the potential for the treatment of hyperlipidaemia. [ABSTRACT FROM AUTHOR]

The putative hypolipidemic properties of scopoletin have not been fully confirmed due to a lack of validation in an irreversible chronic hyperlipidemia animal model. The druggability also needs to be studied in terms of bioavailability in the vascular compartment. Accordingly, we conducted a study to assess the hypolipidemic and pharmacokinetic behavior of scopoletin in the high-fructose high-fat diet (HFHFD)-induced dyslipidemia model in Wistar rats. A total of 42 rats were studied, with 6 in each of the 7 groups. A 60-day HFHFD opted for induction of dyslipidemia. Group I and groups II–VII received normal rat chow diet and HFHFD, respectively. Oral scopoletin (1, 5, 10 mg/kg) and atorvastatin 5 mg/kg were administered in groups III–VI, respectively, once daily for the next 15 days. A separate group, group VII, was used for the pharmacokinetic assessment comparing the scopoletin 10 mg/kg intraperitoneally (IP) in group VII versus the oral (group V). Pharmacokinetic blood sampling was performed on the 10th day of continuous once-daily therapy. Rats were sacrificed for the histological examination. All three scopoletin dosages significantly decreased the total cholesterol, low-density lipoproteins, and triglycerides (P < .05 for all), but not in a dose-dependent manner. Atherogenic Index of plasma, Castelli's risk indices, and histopathological findings confirmed the protective effect of scopoletin. The IP administration showed a 23.18% higher exposure than the oral route (P < .001 for area under the curve and P < .05 for concentration-maximum). This study confirms the hypolipidemic efficacy of scopoletin in a more robust irreversible model of dyslipidemia. Scopoletin's gut absorption in the disease state may also boost the initial phase exploratory clinical trial. [ABSTRACT FROM AUTHOR]

Antihyperglycemic action of scopoletin needs to be validated before considering it for clinical trials. The present study explored antihyperglycemic action of scopoletin in high-fructose high-fat diet (HFHFD)–induced diabetes in rats. The animal study was performed using 48 rats, 6 in each group. HFHFD was administered for model induction for 74 days. Rats in Group I (normal control [NC]) and group II (experimental control [EC]) received normal saline and HFHFD, respectively, throughout the study. Groups III, IV, V, and VI received oral scopoletin (1 mg/kg [low dose, LD], 5 mg/kg [medium dose, MD], 10 mg/kg [high dose, HD]), and metformin (250 mg/kg; positive control [PC] for efficacy), respectively, once daily from day 60 to 74, in addition to HFHFD. Group VII (10 mg/kg oral scopoletin safety group) and VIII (0.1 mg/kg oral warfarin; PC for safety) were separately used for bleeding time-clotting time (BTCT) assessment on days 60, 68, and 74. Groups I, VII, and VIII rats were studied for safety assessment. Later, animals were sacrificed for histological examination. Scopoletin-treated groups showed a significant decline in glucose levels, especially in the MD (5.18 ± 0.12) and HD group (5.271 ± 0.11) in comparison to the EC (6.37 ± 0.05) on day 74 (P < .05). Two weeks after scopoletin treatment, β-cell function significantly improved (53.073 ± 4.67) in the MD group versus 29.323 ± 8.505 in the NC group (P < .05). A statistically significant difference was observed when the MD group (53.07 ± 4.67) was compared to the metformin-treated group (24.80 ± 3.24; P < .05). The safety assessment in the form of BTCT findings did not observe a difference among groups I, VII, and VIII (P > .05). The study showed that scopoletin dose-independently reversed insulin resistance. Consequently, scopoletin can be a potential candidate for antidiabetic drug development. [ABSTRACT FROM AUTHOR]