Role of diosgenin extracted from Helicteres isora L in suppression of HIV-1 replication: An in vitro preclinical study

Abstract

Background: Diosgenin, an essential sapogenin steroid with significant biological implications, is composed of a hydrophilic sugar moiety intricately linked to a hydrophobic steroid aglycone. While the antiviral properties of diosgenin against numerous RNA viruses have been extensively documented, its potential in combating Human Immunodeficiency Virus infections remains unexplored. Experimental procedure: This current investigation presents a comprehensive and systematic analysis of extracts derived from the leaves of Helicteres isora, which are notably enriched with diosgenin. Rigorous methodologies, including established chromatographic techniques and Fourier-transform infrared spectroscopy were employed for the characterization of the active diosgenin compound followed by molecular interaction analyses with the key HIV enzymes and mechanistic validation of HIV inhibition. Key results: The inhibitory effects of extracted diosgenin on the replication of HIV-1 were demonstrated using a permissive cellular system, encompassing two distinct subtypes of HIV-1 strains. Computational analyses involving molecular interactions highlighted the substantial occupancy of critical active site pocket residues within the key HIV-1 proteins by diosgenin. Additionally, the mechanistic underpinnings of diosgenin activity in conjunction with standard controls were elucidated through specialized colorimetric assays, evaluating its impact on HIV-1 Reverse Transcriptase and Integrase enzymes. Conclusions: To our current state of knowledge, this study represents the inaugural demonstration of the anti-HIV efficacy inherent to diosgenin found in the leaves of Helicteres isora, and can be taken further for drug design and development for the management of HIV infection.

Keywords

• Helicteres isora
• Diosgenin
• Phytoconstituents
• Anti-HIV activity
• Preclinical
• Drug discovery