Nutr Res Pract.  2021 Dec;15(6):715-731. 10.4162/nrp.2021.15.6.715.

Lomens-P0 (mixed extracts of Hordeum vulgare and Chrysanthemum zawadskii) regulate the expression of factors affecting premenstrual syndrome symptoms

Affiliations
  • 1Department of Oriental Medicine Biotechnology, College of Life Sciences, Kyung Hee University, Yongin 17104, Korea
  • 2BioMedical Research Institute, Kyung Hee University, Yongin 17104, Korea
  • 3Research Institute, Genencell Co. Ltd., Yongin 16950, Korea

Abstract

BACKGROUND/OBJECTIVES
Premenstrual syndrome (PMS) is a disorder characterized by repeated emotional, behavioral, and physical symptoms before menstruation, and the exact cause and mechanism are uncertain. Hyperprolactinemia interferes with the normal production of estrogen and progesterone, leading to PMS symptoms. Thus, we judged that the inhibition of prolactin hypersecretion could mitigate PMS symptoms.
MATERIALS/METHODS
Hordeum vulgare L. extract (HVE), Chrysanthemum zawadskii var. latilobum extract (CZE), and Lomens-P0 the mixture of these extracts were tested in subsequent experiments. The effect of extracts on prolactin secretion at the in vitro level was measured in GH3 cells. Nitric oxide and pro-inflammatory mediator expression were measured in RAW 264.7 cells to confirm the anti-inflammatory effect. Also, the hyperprolactinemic Institute for Cancer Research (ICR) mice model was used to measure extract effects on prolactin and hormone secretion and uterine inflammation.
RESULTS
Anti-inflammatory effects of and prolactin secretion suppress by HVE and CZE were confirmed through in vitro experiments (P < 0.05). Treatment with Lomens-P0 inhibited prolactin secretion (P < 0.05) and restored normal sex hormone secretion in the hyperprolactinemia mice model. In addition, extracts significantly inhibited the expression of pro-inflammatory biomarkers, including interleukin-1β, and -6, tumor necrosis factor-α, inducible nitric oxide synthase, and cyclooxygenase-2 (P < 0.01). We used high-performance liquid chromatography analyses to identify tricin and chlorogenic acid as the respective components of HVE and CZE that inhibit prolactin secretion. The Lomens-P0, which includes tricin and chlorogenic acid, is expected to be effective in improving PMS symptoms in the human body.
CONCLUSIONS
The Lomens-P0 suppressed the prolactin secretion in hyperprolactinemia mice, normalized the sex hormone imbalance, and significantly suppressed the expression of inflammatory markers in uterine tissue. This study suggests that Lomens-P0 may have the potential to prevent or remedy materials to PMS symptoms.

Keyword

Premenstrual syndrome; medicinal plants; prolactin; hormones; inflammation

Figure

  • Fig. 1 Inhibitory effect of HVE or CZE on PRL secretion in GH3 cells, the rat pituitary cell. (A) Effects of HVE on PRL secretion. (B) Effects of CZE on PRL secretion. Data are expressed as the mean ± standard error of mean (n = 3) and analyzed using a one-way analysis of variance.HVE, H. vulgare L. extract; CZE, C. zawadskii var. latilobum extract; PRL, prolactin.*P < 0.05 and **P < 0.01 vs. E2 control group; ## P < 0.01 vs. normal control group.

  • Fig. 2 Inhibitory effect of HVE, CZE or Lomens-P0 on NO production in RAW 264.7 cells. RAW 264.7 cells were incubated with various concentrations of HVE, CZE, or Lomens-P0 in the presence of LPS (1 μg/mL, 2 h) for 24 h. (A) Cytotoxic effects of HVE, CZE, or Lomens-P0. (B) Effects of HVE, CZE, or Lomens-P0 on the production of NO. Data were expressed as the mean ± standard error of mean (n = 3) and analyzed using a one-way analysis of variance.HVE, H. vulgare L. extract; CZE, C. zawadskii var. latilobum extract; Lomens-P0, 1:1 mixture of H. vulgare L. extract and C. zawadskii var. latilobum extract; NO, nitric oxide; LPS, lipopolysaccharide.*P < 0.05 and **P < 0.01 vs. LPS-treated group; ##P < 0.01 vs. normal control group.

  • Fig. 3 Effects of HVE, CZE or Lomens-P0 on inflammatory markers and mRNA expression of RAW 264.7 cells. RAW 264.7 cells were incubated with various concentrations of HVE, CZE, and Lomens-P0 in the presence of LPS (1 μg/mL, 2 h) for 24 h. The changes in the expression of mRNA levels for (A) IL-1β, (B) IL-6, (C) TNF-α, (D) iNOS, and (E) COX-2 were determined by quantitative real-time PCR. All values were normalized to β-actin expression. Data were expressed as the mean ± standard error of mean (n = 3) and analyzed using a one-way analysis of variance.PF, prefemin; HVE, H. vulgare L. extract; CZE, C. zawadskii var. latilobum extract; Lomens-P0, 1:1 mixture of H. vulgare L. extract and C. zawadskii var. latilobum extract; LPS, lipopolysaccharide; IL, interleukin; TNF, tumor necrosis factor; iNOS, inducible nitric oxide synthase; COX, cyclooxygenase; PCR, polymerase chain reaction.*P < 0.05 and **P < 0.01 vs. LPS-treated group; ##P < 0.01 vs. normal control group.

  • Fig. 4 Effects of HVE, CZE or Lomens-P0 on sex hormones and inflammatory mediators in the serum of hyperprolactinemic mice. The hyperprolactinemia mouse model was prepared by intraperitoneal injection of MCP (20 mg/kg). Untreated animals served as normal controls. (A) Serum progesterone/estrogen ratio, (B) Serum PRL, (C) Serum LH, (D) Serum FSH, and (E) Serum PGE2. Data were expressed as the mean ± standard error of mean (n = 6) and analyzed using a one-way analysis of variance.PF, prefemin; HVE, H. vulgare L. extract; CZE, C. zawadskii var. latilobum extract; Lomens-P0, 1:1 mixture of H. vulgare L. extract and C. zawadskii var. latilobum extract; MCP, metoclopramide; PRL, prolactin; LH, luteinizing hormone; FSH, follicle-stimulating hormone; PGE2, prostaglandin E2.*P < 0.05 and **P < 0.01 vs. MCP-treated group; #P < 0.05 and ##P < 0.01 vs. normal control group.

  • Fig. 5 Effects of HVE, CZE or Lomens-P0 on uterine inflammation in hyperprolactinemic mice. The hyperprolactinemia mouse model was prepared by intraperitoneal injection of MCP (20 mg/kg). Untreated animals served as controls. Changes in the expression of mRNA for (A) IL-1β, (B) IL-6, (C) TNF-α, (D) iNOS, and (E) COX-2 were determined by quantitative real-time PCR. All values were normalized to β-actin expression. Data were expressed as the mean ± standard error of mean (n = 6) and analyzed using a one-way analysis of variance.PF, prefemin; HVE, H. vulgare L. extract; CZE, C. zawadskii var. latilobum extract; Lomens-P0, 1:1 mixture of H. vulgare L. extract and C. zawadskii var. latilobum extract; MCP, metoclopramide; IL, interleukin; TNF, tumor necrosis factor; iNOS, inducible nitric oxide synthase; COX, cyclooxygenase; PCR, polymerase chain reaction.*P < 0.05 and **P < 0.01 vs. MCP-treated group; #P < 0.05 and ##P < 0.01 vs. normal control group.

  • Fig. 6 HPLC analyses. (A) Chromatogram of the tricin standard; (B) Chromatogram of the chlorogenic acid standard; (C) Chromatogram of tricin in Lomens-P0; and (D) Chromatogram of chlorogenic acid in Lomens-P0. All experiments were performed in triplicate.HPLC, high-performance liquid chromatography; Lomens-P0, 1:1 mixture of H. vulgare L. extract and C. zawadskii var. latilobum extract.

  • Fig. 7 Inhibition of PRL secretion by active components identified in HVE or CZE. GH3 cells were treated with various concentrations of the active compounds. PRL secretion and cell viability were assessed using an ELISA assay. (A) Effects of HVE and tricin on cytotoxicity and PRL secretion, (B) Effects of CZE and chlorogenic acid on cytotoxicity and PRL secretion. Data were expressed as the mean ± standard error of mean (n = 3) and analyzed using a one-way analysis of variance.PF, prefemin; HVE, H. vulgare L. extract; CZE, C. zawadskii var. latilobum extract; ELISA, enzyme-linked immunosorbent assay; PRL, prolactin.*P < 0.05 and **P < 0.01 vs. MCP-treated group; #P < 0.05 and ##P < 0.01 vs. normal control group.

  • Fig. 8 Summary of this paper. Lomens-P0 normalizes the hormone imbalance and suppresses the expression of inflammatory cytokines and mediators involved in PMS symptoms. These results are due to the prolactin secretion inhibitory effect of Lomens-P0 (especially tricin and chlorogenic acid).Lomens-P0, 1:1 mixture of H. vulgare L. extract and C. zawadskii var. latilobum extract; PMS, premenstrual syndrome; PRL, prolactin; LH, luteinizing hormone; FSH, follicle-stimulating hormone; IL, interleukin; TNF, tumor necrosis factor; iNOS, inducible nitric oxide synthase; COX, cyclooxygenase; NO, nitric oxide; PGE2, prostaglandin E2.


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