Nutr Res Pract.  2023 Feb;17(1):1-12. 10.4162/nrp.2023.17.1.1.

Schisandrol A and gomisin N from Schisandra chinensis extract improve hypogonadism via anti-oxidative stress in TM3 Leydig cells

• Bak J
• Lee SJ
• Kim TW
• Hwang S
• Park MJ
• Arunachalam R
• Yoo E
• Park MH
• Choi YS
• Kim HK

• KMID: 2539450
• DOI: http://doi.org/10.4162/nrp.2023.17.1.1

Abstract

BACKGROUND/OBJECTIVES
Male hypogonadism is a condition where the body does not produce enough testosterone and significantly impacts health. Age, obesity, genetics, and oxidative stress are some physiological factors that may contribute to testosterone deficiency. Previous studies have shown many pharmacological benefits of Schisandra chinensis (S. chinensis) Baillon as an anti-inflammatory and antioxidant. However, the molecular mechanism of attenuating hypogonadism is yet to be well established. This research was undertaken to study the effects of S. chinensis extract (SCE) on testosterone deficiency.
MATERIALS/METHODS
S. chinensis fruit was pulverized and extracted using 60% aqueous ethanol. HPLC analysis was performed to analyze and quantify the lignans of the SCE.
RESULTS
The 2,2-diphenyl-2-picrylhydrazyl and 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) scavenging assays confirmed that the SCE and its major lignans (schisandrol A and gomisin N) inhibit oxidative stress. Effects of SCE analysis on the testosterone level under oxidative stress conditions revealed that both schisandrol A and gomisin N were able to recover the lowered testosterone levels. Through mRNA expression of TM3 Leydig cell, we observed that the SCE lignans were able to induce the enzymes involved in testosterone biosynthesis-related genes such as 3β-HSD4 (P < 0.01 for SCE, and P < 0.001 for schisandrol A and gomisin N), 17β-HSD3 (P < 0.001 for SCE, schisandrol A and gomisin N), and 17, 20-desmolase (P < 0.01 for schisandrol A, and P < 0.001 for SCE and gomisin N).
CONCLUSIONS
These results support that SCE and its active components could be potential therapeutic agents for regulating and increasing testosterone production.

Keyword

Hypogonadism; oxidative stress; Schisandra chinensis; lignan; Leydig cells

Figure

• 

  Fig. 1 HPLC chromatograms of 60% ethanolic extract of Schisandra chinensis fruits. (A) lignans standard, and (B) S. chinensis extract: Schisandrol A (1), Schisandrol B (2), Schisandrin A (3), Gomisin N (4) and Schisandrin C (5).HPLC, high performance liquid chromatography.

• 

  Fig. 2 Antioxidant effect of SCE. (A) DPPH assay and (B) ABTS assay. Data are presented as mean ± SEM, and statistical significance was analyzed by one-way ANOVA followed by Dunnett’s multiple comparisons test.SCE, Schisandra chinensis extract; DPPH, 2,2-diphenyl-2-picrylhydrazyl; ABTS, 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid); SEM, standard error of the mean; CON, control; AA, L-ascorbic acid.***P < 0.001 compared to control.

• 

  Fig. 3 Cell viability of SCE and its active compounds. (A) SCE, (B) schisandrol A, and (C) gomisin N. Data are presented as mean ± SEM, and statistical significance was analyzed by one-way ANOVA followed by Dunnett’s multiple comparisons test.SCE, Schisandra chinensis extract; SEM, standard error of the mean; CON, control.*P < 0.05 and ***P < 0.001.

• 

  Fig. 4 Effects of SCE and its active compounds on H2O2-induced oxidative stress in Leydig cells. (A) SCE, (B) schisandrol A, and (C) gomisin N. Data are presented as mean ± SEM, and statistical significance was analyzed by one-way ANOVA followed by Dunnett’s multiple comparisons test.SCE, Schisandra chinensis extract; H2O2, hydrogen peroxide; SEM, standard error of the mean.*P < 0.05 and ***P < 0.001 compared to control. #P < 0.05 and ###P < 0.001 compared to H2O2-treated group.

• 

  Fig. 5 Effect of SCE and its active compounds on testosterone level under oxidative stress condition. (A) SCE, (B) schisandrol A, and (C) gomisin N. Data are presented as mean ± SEM, and statistical significance was analyzed by one-way ANOVA followed by Dunnett’s multiple comparisons test.SCE, Schisandra chinensis extract; H2O2, hydrogen peroxide; SEM, standard error of the mean.*P < 0.05 and ***P < 0.001 compared to control. ###P < 0.001 compared to H2O2-treated group.

• 

  Fig. 6 Effect of SCE and its active compounds on mRNA expressions of 3β-HSD4, 17β-HSD3, and 17, 20-desmolase. (A-C) SCE, (D-F) schisandrol A, and (G-I) gomisin N. Data are presented as mean ± SEM, and statistical significance was analyzed by one-way ANOVA followed by Dunnett’s multiple comparisons test.SCE, Schisandra chinensis extract; SEM, standard error of the mean; H2O2, hydrogen peroxide.*P < 0.05 and ***P < 0.001 compared to control. ##P < 0.01 and ###P < 0.001 compared to H2O2-treated group.

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