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Published on: October 8, 2021
Nitrogen-Containing Steroidal Alkaloids and the Gut Microbiome: A Steroid-Xenobiotic Axis Perspective for Drug
Nila Ganamurali1, Sarvesh Sabarathinam1, N Manojkumar2
1Helix Research Lab, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University, 602105 Chennai, Tamil Nadu, India.
Abstract:
Drug metabolism has traditionally emphasized hepatic pathways; however, the gut microbiome introduces a parallel system of biochemical modification that profoundly affects drug efficacy, safety, and variability. This review integrates the emerging steroid-xenobiotic-microbiome axis, emphasizing nitrogen-containing steroidal alkaloids (NSAs) as pivotal modulators. These compounds, combining a hydrophobic steroidal scaffold with nitrogen-based polarity, exhibit unique bioactivities through microbial biotransformation. Gut microbes enzymatically modify steroids and xenobiotics via reduction, deconjugation, and oxidation, shaping pharmacokinetics and receptor signaling. Conversely, steroidal scaffolds regulate microbial enzyme expression, forming reciprocal metabolic feedback. Case studies on digoxin, solanine, and veratramine illustrate this interplay. Understanding how nitrogen incorporation governs structure activity relationships and microbial interactions offers a new avenues for precision pharmacology, biomarker discovery, and rational drug design. This integrated perspective bridges medicinal chemistry, microbiome science, and steroid pharmacology to develop next generation therapeutics guided by host-microbe metabolic crosstalk.
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