Unravelling the complexities of non-alcoholic steatohepatitis: The role of metabolism, transporters, and herb-drug interactions.

Nonalcoholic fatty liver disease (NAFLD) is a mainstream halting liver disease with high prevalence in North America, Europe, and other world regions. It is an advanced form of NAFLD caused by the amassing of fat in the liver and can progress to the more severe form known as non-alcoholic steatohepatitis (NASH). Until recently, there was no authorized pharmacotherapy reported for NASH, and to improve the patient's metabolic syndrome, the focus is mainly on lifestyle modification, weight loss, ensuring a healthy diet, and increased physical activity; however, the recent approval of Rezdiffra (Resmetirom) by the US FDA may change this narrative. As per the reported studies, there is an increased articulation of uptake and efflux transporters of the liver, including OATP and MRP, in NASH, leading to changes in the drug's pharmacokinetic properties. This increase leads to alterations in the pharmacokinetic properties of drugs. Furthermore, modifications in Cytochrome P450 (CYP) enzymes can have a significant impact on these properties. Xenobiotics are metabolized primarily in the liver and constitute liver enzymes and transporters. This review aims to delve into the role of metabolism, transport, and potential herb-drug interactions in the context of NASH.

Network pharmacology and bioinformatics based investigation of Phyllanthus fraternus: herb-drug interaction study.

Phyllanthus fraternus (PF), a plant from the Euphorbiaceae family, is used extensively in ayurvedic formulations for its significant medicinal properties. When PF is administered alongside conventional drugs, there could be potential herb-drug interactions between the active compounds and the genes involved in drug transport and metabolism. Hence, this study was designed to investigate potential herb-drug interactions, focusing on elucidating their functional and pharmacological mechanisms, using an integrated approach of metabolite profiling and network pharmacology. We utilized LC-MS to generate metabolite profiling of PF and network pharmacology for predicting key targets and pathways. This comprehensive analysis involved the construction of networks illustrating the relationships among compounds, targets, and pathways and the exploration of protein-protein interactions and protein-ligand interactions. In this study, a total of 79 compounds were identified in LC-MS, such as alkaloids, steroids, saponins, flavonoids, lignans, phenolic acids, tannins, terpenoids, and fatty acids. The identified compound's physicochemical properties were predicted using SwissADME. Network analysis predicted 1076 PF-related genes and 1497 genes associated with drug transport and metabolism, identifying 417 overlapping genes, including 51 related to drug transport and metabolism. Based on the degree of interaction the hub targets like ABCB1, CYP1A1, CYP1A2, CYP2C9, and CYP3A4 were identified. In the compound-target-pathway network, 2,4-bis(1,1-dimethyl ethyl)-phenol; 5-Methoxy-N-[(5-Methylpyridin-2-yl) sulfonyl]-1h-Indole-2-Carboxamide; and E,E,Z-1,3,12-Nonadecatriene-5,14-diol possessed more interactions with the targets. This study helps identify bioactive compounds, essential targets, and pathways potentially implicated in these interactions, laying the foundation for future studies (in vitro and in vivo) to verify their potential to explore their clinical implications.Communicated by Ramaswamy H. Sarma.

Investigation of the effect of Acai berry on the pharmacokinetics of Atorvastatin, Alogliptin and Empagliflozin: a herb-drug interaction study.

OBJECTIVES: To explore the effect of Acai berry on the pharmacokinetics of Atorvastatin (ATR), Alogliptin (ALO) and Empagliflozin (EMPA) in SD rats. METHOD: Thirty-six rats were divided into six groups (n = 6). First three groups were treated with Acai berry (PO; 250 mg/kg); fourth, fifth and sixth groups received sodium CMC (vehicle) for 10 days and on eleventh day, first and fourth groups were administered with ATR (PO; 10 mg/kg); second and fifth groups with ALO (PO; 25 mg/kg) and third and sixth groups received EMPA (PO; 25 mg/kg). KEY FINDINGS: Co-intake of ATR with Acai berry resulted in slight decrease in Cmax from 41.78 to 34.65 ng/ml and AUC from 227.66 to 136.31 (µg/ml) *h, while there was an increase in the Cmax from 43.43 to 68.71 ng/ml and AUC from 117.6 to 207.1 (µg/ml) *h in ALO treated groups and Cmax from 173.99 to 250.1 ng/ml and AUC from 400.37 to 518.35 (µg/ml) *h in the EMPA-treated groups. CONCLUSION: There was a significant change in the AUC0-t and Cmax of ATR, ALO and EMPA after co-administration with Acai berry. Further studies are recommended to confirm the clinical significance of these interactions.