Odevixibat: A Review of a Bioactive Compound for the Treatment of Pruritus Approved by the FDA.

Odevixibat is synthesized through chemical modification of Benzothiazepine's structure. It is a tiny chemical that inhibits the ileal bile acid transporter and is used to treat a variety of cholestatic illnesses, including progressive familial intrahepatic cholestasis (PFIC). For cholestatic pruritus and liver disease development, bile acid transporter inhibition is a unique treatment strategy. Odevixibat reduces enteric bile acid reuptake. Oral odevixibat was also studied in children with cholestatic liver disease. Odevixibat received its first approval in the European Union (EU) in July 2021 for the treatment of PFIC in patients aged 6 months, followed by approval in the USA in August 2021 for the treatment of pruritus in PFIC patients aged 3 months. Bile acids in the distal ileum can be reabsorbed by the ileal sodium/bile acid cotransporter, a transport glycoprotein. Odevixibat is a sodium/bile acid co-transporter reversible inhibitor. An average 3 mg once-daily dose of odevixibat for a week resulted in a 56% reduction in the area under the curve of bile acid. A daily dose of 1.5 mg resulted in a 43% decrease in the area under the curve for bile acid. Odevixibat is also being evaluated in many countries for the treatment of other cholestatic illnesses, including Alagille syndrome and biliary atresia. This article reviews the updated information on odevixibat with respect to its clinical pharmacology, mechanism of action, pharmacokinetics, pharmacodynamics, metabolism, drug-drug interactions, pre-clinical studies, and clinical trials.

Evaluation of Acute and Subacute Oral Toxicity Induced by Ethanolic Extract of Marsdenia tenacissima Leaves in Experimental Rats.

The objective of this study is to evaluate the acute and subacute toxicity of the ethanolic extract of Marsdenia tenacissima (MTE) leaves (family: Asclepiadaceae) in albino rats. The acute toxicity was performed where the limit dose of 5000 mg/kg body weight used. Observations were made and recorded for 24 h, and once daily further for a period of 14 days. The rats were weighed and various observations, like mortality, behavior, injury, or any signs of illness were conducted once daily during the period. For subacute study, four groups of 10 animals (female rats) received 10% Tween 20 in distilled water (control), and 250, 500, and 1000 mg/kg of freshly-prepared extracts, respectively, every 24 h orally for 28 days. At the end of each study, hematological analysis and biochemical parameters were evaluated. Histopathological examination of vital organs of the animals were taken for gross findings, compared to controls. There was no significant difference (p > 0.05) observed in the relative organs, body weights, hematological, biochemical parameters, and gross abnormalities, compared to the control. No mortality was recorded. Therefore, analysis of results may lead to the conclusion that the medium-term oral administration of the MTE leaves for 28 days does not cause toxicity.

Reversible germ cell toxicity of sulphasalazine and ampicillin combination in male rats.

BACKGROUND: The antifertility effect of ampicillin (AMP, 40 mg/kg) and sulphasalazine or salicylazosulfapyridine (SASP, 300,450 and 600 mg/kg) in male rats has been reported earlier. The combination of AMP and SASP is generally used in certain pathological conditions, but the combined effect of these two drugs on the fertility is not clear. So, the aim of this study was to investigate the antifertility effect of ampicillin and sulphasalazine combination in male rats. METHODS: In the present study, forty rats were randomly divided into five groups (n=8). Group I served as the control, while Group II and III received AMP and SASP at the doses of 20 mg/kg and 200 mg/kg respectively. Moreover, group IV and V received the combination of SASP (100 mg/kg) and AMP (10 mg/kg). However, for evaluating the reversible effect of the combination, a washout period of 30 days was given in group V. After 45 days of drug treatment, each rat was sacrificed. The testes, seminal vesicles and epididymis were dissected & weighed. Furthermore, fertility tests, sperm characteristic analysis, histopathological studies, testosterone assay and tissue biochemistry were performed. The data were analyzed using ANOVA and in case ANOVA shows statistical differences, post hoc analysis was performed. RESULTS: A decrease in parameters related to fertility of males such as sperm count, sperm motility, fertility ratio, serum testosterone level, glycogen and protein content in sexual organs was observed. Although AMP and SASP significantly (p<0.001) reduced the reproductive activity separately, but their combination was found to be impairing the reproductive activity at a considerably lower dose. However, on withdrawing the treatment, all these parameters were restored which was confirmed by the histopathological analysis of the testis. CONCLUSION: The combination produces synergistic antifertility effect in male rats and the effect was reversible. The dose and efficacy of results could be extrapolated in future clinical trials.

Effects of Mangifera indica fruit extract on cognitive deficits in mice.

Mangos are a source of bioactive compounds with potential health-promoting activity. The present work was undertaken to evaluate the ethanolic extract of Mangifera indica L. fruit on cognitive performances. The models used to study the effect on cognitive performances are step down passive avoidance task and elevated plus maze task in mice. Chronic treatment (7 days) of extract and vitamin C significantly (p < 0.05) reversed the aging and scopolamine induced memory deficits in both paradigms. Preliminary phytochemical screening revealed the presence of free sugars, saponins, tannins, and flavonoids. The results suggestthe extract contained pharmacologically active principles that are memory-enhancing in nature.

Protective effects of Punica granatum seeds extract against aging and scopolamine induced cognitive impairments in mice.

Dementia is one of the age related mental problems and characteristic symptom of various neurodegenerative diseases including Alzheimer's disease. This impairment probably is due to the vulnerability of the brain cells to increased oxidative stress during aging process. Many studies have shown that certain phenolic antioxidants attenuate neuronal cell death induced by oxidative stress. The present work was undertaken to assess the effect of ethanolic extract of Punica granatum seeds on cognitive performance of aged and scopolamine treated young mice using one trial step-down type passive avoidance and elevated plus maze task. Aged or scopolamine treated mice showed poor retention of memory in step-down type passive avoidance and in elevated plus maze task. Chronic administration (21 days) of Punica granatum extract and vitamin C significantly (p < 0.05) reversed the age induced or scopolamine induced retention deficits in both the paradigms. Punica granatum extract also significantly lowered lipid peroxidation level and increased antioxidant glutathione level in brain tissues. Punica granatum preparations could be protective in the treatment of cognitive disorders such as dementia and Alzheimer's disease.

Central nervous system activity of acute administration of ethanol extract of Punica granatum L. seeds in mice.

Role of ethanolic extract of P. granatum seeds on central nervous system (CNS) in animal models of elevated plus maze test, barbiturate-induced sleeping time, tail suspension test, hot-plate and tail-flick test was studied. P. granatum (PG) extract was administered to young and aged mice at single doses of 100, 250 and 500 mg/kg, perorally while diazepam (1 mg/kg), morphine (5 mg/kg) and imipramine (30 mg/kg) were used intraperitoneally as standard drugs. The results showed that PG extract at all dose levels significantly exhibited the anxiolytic activity. In another study PG extract (250 and 500 mg/kg) significantly increased the sleeping latency and reduced the sleeping time. Tail suspension test showed that PG extract (250 and 500 mg/kg) was able to induce a significant decrease in the immobility time, similar to imipramine, a recognized antidepressant drug. Tail-flick and hot-plate tests exhibited antinociceptive property of PG extract, similar to morphine, a recognized antinociceptive agent. Phytochemical investigation of ethanol extract for the presence of phenolic compounds, flavonoids, tannins, anthocyanins, sugars and saponins was also carried out. Phytochemical screening and measurement of reducing power revealed the CNS activity of ethanol extract of PG seeds may be due to its antioxidative profile.