The Effect of Aqueous Lessertia frutescens Extract on TM3 Leydig Cells Exposed to TNF-α in vitro

Kristian Leisegang; Renata Finelli; Ralf Henkel; Cătălina Zenoaga-Barbăroșie

doi:10.31083/j.fbl2809213

The Effect of Aqueous Lessertia frutescens Extract on TM3 Leydig Cells Exposed to TNF-α in vitro

Front Biosci (Landmark Ed). 2023 Sep 24;28(9):213. doi: 10.31083/j.fbl2809213.

Authors

Kristian Leisegang¹, Renata Finelli², Ralf Henkel^{3

4

5}, Cătălina Zenoaga-Barbăroșie⁶

Affiliations

¹ School of Natural Medicine, University of the Western Cape, 7535 Bellville, South Africa.
² CREATE Fertility, 150 Cheapside, EC2V 6ET London, UK.
³ Department of Metabolism, Digestion and Reproduction, Imperial College London, SW7 2AC London, UK.
⁴ Department of Medical Bioscience, University of the Western Cape, 7535 Bellville, South Africa.
⁵ Logixx Pharma, Theale, RG7 4AB Reading, UK.
⁶ Department of Genetics, Faculty of Biology, University of Bucharest, 060011 Bucharest, Romania.

PMID: 37796713
DOI: 10.31083/j.fbl2809213

Abstract

Background: Extractions of Lessertia frutescens (Lf) are shown to have immune modulation, anti-inflammatory and antioxidant properties. However, Lf is also cytotoxic, antiproliferative, and pro-apoptotic in vitro. Furthermore, Lf extractions may influence steroidogenesis. Nevertheless, the impact on Leydig cell function has not previously been investigated. As tumor necrosis factor-alpha (TNF-α) is known to cause Leydig cell dysfunction under inflammatory conditions, it is further proposed that Lf extracts may protect against the negative impact of TNF-α on Leydig cells. The aim of the study was to investigate the effect of an aqueous Lessertia frutescens extract (LFE) on Leydig cells exposed to TNF-αin vitro.

Methods: Human chorionic gonadotrophin-stimulated TM3 Leydig cells were exposed for 24 h to (a) TNF-α (0.1, 1, 10, 100 ng/mL), (b) LFE (0.01, 0.1, 1, 10, 100 ng/mL), and (c) co-exposure to 10 ng/mL TNF-α and LFE (0.01, 0.1, 1, 10, 100 ng/mL). We analyzed cell viability, cytotoxicity, caspase 3/7 activation, testosterone concentration, and intracellular superoxide.

Results: TNF-α exposure decreased cell viability, increased cytotoxicity, and caspase 3/7, with no significant effect on intracellular superoxide in TM3 Leydig cells. When LFE concentrations of 0.01-10 ng/mL were tested, we observed improved vitality and reduced levels of caspase 3/7. At 100 ng/mL, LFE decreased viability and increased cytotoxicity and caspase 3/7. However, LFE did not affect intracellular superoxide. Furthermore, LFE protected against 10 ng/mL TNF-α-induced cytotoxicity and apoptosis, except at the highest concentration. LFE alone and in co-culture with 10 ng/mL TNF-α increased testosterone at high concentrations.

Conclusions: In our TM3 Leydig cell model, LFE protected against TNF-α-induced cytotoxicity and early apoptosis, except at the highest experimental concentrations, where it was cytotoxic. These effects were not mediated through a change in intracellular superoxide. Although further investigations are warranted, aqueous LFE may protect against TNF-α-induced Leydig cell dysfunction.

Keywords: Lessertia frutescens; Leydig cells; Sutherlandia; apoptosis; inflammation; tumor necrosis factor-alpha.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Caspase 3
Humans
Leydig Cells* / physiology
Male
Superoxides
Testosterone / pharmacology
Tumor Necrosis Factor-alpha* / pharmacology

Substances

Tumor Necrosis Factor-alpha
Superoxides
Caspase 3
Testosterone