Maca (Lepidium meyenii Walp.) inhibits HIV-1 infection through the activity of thiadiazole alkaloids in viral integration

J Ethnopharmacol. 2024 Dec 5:335:118613. doi: 10.1016/j.jep.2024.118613. Epub 2024 Jul 23.

Abstract

Ethnopharmacology relevance: Lepidium meyenii Walp. (maca) has been traditionally used for centuries in the Central Andes region both as food and as medicine. In the last decades, its fertility enhancer properties have gained importance, with the majority of the scientific literature related to this topic. However, other traditional uses are less known as metabolic or infectious diseases.

Aim of the study: The main purpose of this study is to investigate the anti-infectious activity of L. meyenii, specifically in HIV-1 infection. There are previous reports of the transcriptional related activity of L. meyenii extracts in human T lymphocytes via transcription factors as NF-κB. Since T lymphocytes are the main target of HIV-1 infection and NF-κB is strongly involved in HIV-1 transcription, L. meyenii could display antiviral activity.

Material and methods: Chromatography and spectroscopy techniques were used to isolate and identify the compounds in the active extracts. An antiviral assay system based on recombinant viruses was used to evaluate the anti-HIV activity. Cell toxicity was tested for all the extracts and compounds. Viral entry was studied using VSV-HIV chimera viruses and reverse transcription and viral integration were studied by qPCR of viral DNA in infected cells. Finally, viral transcription was studied in primary lymphocytes transfected with HIV-1 or NF-κB luciferase reporter plasmids.

Results: n-Hexane extracts of purple maca displayed anti-HIV activity in an in vitro assay. A bioassay-guided fractionation led to the identification of three thiadiazole alkaloids with antiviral activity. All the compounds were able to inhibit HIV infection of MT-2 cell lines and primary lymphocytes (PBMCs) with IC50 values in the low micromolar range. The mechanism of action differs between the three compounds: one of them showed activity on viral entry, and all the three compounds inhibited viral integration at low concentrations. Remarkably, none of the compounds inhibited reverse transcription or viral transcription.

Conclusions: n-Hexane extracts of the purple ecotype of L. meyenii inhibit HIV-1 infection in vitro and three active thiadiazole alkaloids were isolated acting mainly on viral integration and viral entry.

Keywords: Antiviral; HIV; Integration; Lepidium; Maca: AIDS.

MeSH terms

  • Alkaloids* / isolation & purification
  • Alkaloids* / pharmacology
  • Anti-HIV Agents* / chemistry
  • Anti-HIV Agents* / isolation & purification
  • Anti-HIV Agents* / pharmacology
  • Cell Line
  • Ethnopharmacology
  • Gene Expression Regulation, Viral / drug effects
  • HIV Infections* / drug therapy
  • HIV Infections* / virology
  • HIV-1* / drug effects
  • HIV-1* / genetics
  • HIV-1* / growth & development
  • HIV-1* / physiology
  • Humans
  • Hypocotyl / chemistry
  • Lepidium* / chemistry
  • Lymphocytes / drug effects
  • Lymphocytes / virology
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology
  • Reverse Transcription / drug effects
  • Thiadiazoles* / isolation & purification
  • Thiadiazoles* / pharmacology
  • Transcription, Genetic / drug effects
  • Virus Integration* / drug effects
  • Virus Internalization / drug effects
  • Virus Replication / drug effects

Substances

  • Alkaloids
  • Plant Extracts
  • Thiadiazoles
  • Anti-HIV Agents