Total RNA was extracted using TRI reagent (Molecular Research Center, Cincinnati, OH, United States) following the manufacturer’s instructions. In Vitro 24, 375–381. In this study, we investigated the effects of E. cava extract in rats with PCOS. Overview. After 2 weeks, E. cava extract was administered via P.O. Data are representative of three independent experiments and are expressed as the mean ± SD; ap < 0.05 vs. control; bp < 0.05 vs. forskolin. Ecklonia cava, collected from Jeju island of South Korea, was purchased from a comprehensive herbal medicinal shopping mall at Jungwoo-Dang (South Korea). High levels of LH and increased LH:FSH ratios can serve as biomarkers to diagnose PCOS in women (Bednarska and Siejka, 2017). Endocrinol.  https://www.ncbi.nlm.nih.gov/pubmed/19913068,  https://www.ncbi.nlm.nih.gov/pubmed/22878185,  https://www.ncbi.nlm.nih.gov/pubmed/25261704,  https://www.ncbi.nlm.nih.gov/pubmed/17887942,  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4737831/,  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4737831/. Values represent the means ± SEM. doi: 10.1016/j.imr.2018.05.003, Keywords: Ecklonia cava, polycystic ovary syndrome, follicle stimulating hormone, luteinizing hormone, androgen, testosterone, dehydroepiandrosterone, Citation: Yang H, Lee SY, Lee SR, Pyun B-J, Kim HJ, Lee YH, Kwon SW, Suh DH, Lee CH, Hong E-J and Lee HW (2018) Therapeutic Effect of Ecklonia cava Extract in Letrozole-Induced Polycystic Ovary Syndrome Rats. In addition, the mRNA levels of Bmp, Cyp11a1, and Has2 were significantly elevated by EC500 treatment compared to the levels in the non-treated group (PCOS group). ap < 0.05 vs. placebo group, bp < 0.05 vs. PCOS group. Aromatase, encoded by the Cyp19 gene, is a member of the cytochrome P450 family (Bulun et al., 2003) and is a rate-limiting enzyme that catalyzes the conversion of androgen to estrogens during steroidogenesis (Mills et al., 2014). The absorbance was measured with a microtiter plate reader (BIO-TEK, Synergy HT, Winooski, VT, United States) at 570 nm. Recently, natural substances have been used for PCOS therapy. Its scientific name is Morinda officinalis. (2015). Ecklonia cava is a brown alga that found on Jeju island, Korea, and in Japan (Kim et al.,2006). While significantly elevated in rats with PCOS, Cyp19a1 mRNA levels were significantly decreased in PCOS + EC500-treated rats (Figure 6A). 261 for dieckol, 741 → 477 for 6,6′-bieckol, 741 → 723 for 8,8′-bieckol, and 125 → 57 for phloroglucinol. The eluent consisted of water containing 0.1% formic acid (solvent A) and acetonitrile containing 0.1% formic acid (solvent B), and the flow rate used was 300 μL/min. As assessed by the LH/FSH ratio of plasma hormones, only rats in the EC500 treatment group exhibited a response in the LH/FSH ratio, unlike the corresponding rats with PCOS (Figure 3C). Serum testosterone levels were measured using a Testosterone ELISA Kit (Abcam, Cambridge, United Kingdom). Endocrinology 140, 2581–2591. https://www.ncbi.nlm.nih.gov/pubmed/19913068, https://www.ncbi.nlm.nih.gov/pubmed/22878185, https://www.ncbi.nlm.nih.gov/pubmed/25261704, https://www.ncbi.nlm.nih.gov/pubmed/17887942, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4737831/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3382810/, https://journals.humankinetics.com/view/journals/ijsnem/20/1/article-p72.xml, https://pdfs.semanticscholar.org/1c0d/58e585ecb12cef1fa7d09b8bc40504d365a9.pdf, https://pdfs.semanticscholar.org/04bc/6ae0d6af71a86e69c20da7e1c2cbb2be8de8.pdf, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983271/. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Sex Med. Impact Factor 4.225 | CiteScore 5.0More on impact ›, Department of Biological Sciences, College of Science, Sungkyunkwan University, South Korea. The scientific research is just coming out, but it already shows that ecklonia cava is â¦ Whilst a lot of the research is still in its infancy, the benefits of Ecklonia Cava are undeniable. But more than just a food, it has been proven to â¦ When rats with PCOS were first exposed to letrozole for 2 weeks (0.1 mg/kg/day), followed by 2 weeks of exposure to placebo pellets, the body weights of these PCOS + rats were not significantly different compared to those of the corresponding rats with PCOS exposed to letrozole for 4 weeks. When the ovaries of rats with PCOS had numerous subcapsular cysts and thin granulosa cell layers, we observed numerous corpora lutea and antral follicles in the granulosa cell layer of PCOS + EC500-treated rats. However, excessive DHT in the body can lead to this enzyme interacting with hair follicles, making them weaker over time and eventually leading to hair loss in men (alopecia). Required fields are marked *. From reducing inflammation, diabetic symptoms and reversing hair loss as well as assisting athletic performance by boosting endurance and testosterone and promoting better sleep and reducing pain, Ecklonia Cava is certainly something worth taking on a daily basis to help you live a better life and move you one step closer towards your goals. In parallel with the transcription levels, Ar and Erβ expression increased in the follicles of PCOS + EC500-treated rats compared to the corresponding rats with PCOS (Figure 7). Exp. 13, 169–173. doi: 10.1016/0014-5793(96)00782-X, Rajan, R. K., M, S. S., and Balaji, B. Other studies have also confirmed seaweed extracts have good antioxidant activities that can benefit your overall health and well-being.. To validate the effect of the E. cava extract on hormonal changes, we examined the plasma hormone levels. Effect of E. cava treatment on aromatase, androgen receptor, and estrogen receptor β localization. Topical application of E. cava is known to enhance hair growth; this is a novel application that also leads to inhibition of androgen-induced hair loss (Kang et al., 2012). In the 2012 study, Korean researchers used an ecklonia cava â¦ Toxicol. As expected, rats with PCOS exhibited a prolonged diestrus phase (Figure 2C). Ecklonia Cava is an edible marine alga common in Asia off the coasts of Korea, Japan, and China. Modulation of aromatase activity as a mode of action for endocrine disrupting chemicals in a marine fish. FIGURE 7. Also known as brown algae or brown seaweed, ecklonia cava has been linked to some powerful â¦ EC, E. cava extract; PCOS, polycystic ovary syndrome. Dieckol is the most active component in Ecklonia cava for the reduction of 5Î±-reductase (Kang et al., 2012). The pathogenesis and treatment of polycystic ovary syndrome: what’s new? treatment every day for 2 weeks. Interestingly, while the Cyp19a1 mRNA levels significantly increased in the rats with PCOS, aromatase completely disappeared from the follicles. How does the Cava Forte work? They then go on to compare how that value is double that of blueberries, etc. Moreover, the transcriptional levels of Fshr, Fshβ, and Lhr were altered in the ovaries of PCOS rats, and these levels were restored to the normal range by E. cava extract treatment. Clinical review: hyperandrogenism and polycystic ovary syndrome in women with type 1 diabetes mellitus. FIGURE 5. In addition to Cyp19a1 mRNA, Ar, and Esr2 receptor mRNAs were substantially and significantly suppressed in the PCOS ovaries (p < 0.05 vs. placebo). Each group performed 2 endurance-based exercises with a 1 week break in between with the participants required to drink the ECS or the placebo 30 minutes prior. Next, we investigated the effects of EC500 on the mRNA expression of ovarian Kitl, Bmp, Cyp11a1, and Has2, which are associated with follicle development; these genes can serve as biomarkers to diagnose the follicular stage of the ovarian cycle, such as the primary (Kitl), preantral (Bmp), early antral (Cyp11a1), and late antral (Has2) stages of the ovary (Epifano and Dean, 2002). Lhr is also located on the surfaces of theca cells and granulosa cells, and Lhr transcript levels also influence ovulation, corpus luteum formation and the production of other steroids, i.e., estrogen, progesterone and androgen (Edson et al., 2009). Gapdh mRNA was used as an internal control. Arthritis 2. Genetic control of early folliculogenesis in mice. 35, 103–108. Effects of E. cava on the mRNA expression of folliculogenesis-related genes and sex steroid hormone receptors in the ovaries of rats. Letrozole has been administered to female rats that were used as animal models of PCOS (Caldwell et al., 2014). ap < 0.05 vs. placebo group, bp < 0.05 vs. PCOS group. Adv. 26, 93–100. , When combined with Tribulus terrestris and water-soluble Chitosan, Ecklonia Cava can help improve erectile dysfunction and liido in men suffering from low testoserone,  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3382810/,  https://journals.humankinetics.com/view/journals/ijsnem/20/1/article-p72.xml,  https://pdfs.semanticscholar.org/1c0d/58e585ecb12cef1fa7d09b8bc40504d365a9.pdf,  https://pdfs.semanticscholar.org/1c0d/58e585ecb12cef1fa7d09b8bc40504d365a9.pdf, For instance, a study which looked at three groups of men aged between 18 – 45 years old (group A), 45 – 59 years old (group B) and 60 years + (group C) were treated with a combination of Ecklonia. Interestingly, some EC500-treated rats with PCOS were observed to have regular cycles, similar to the placebo rats (Figure 2C). ap < 0.05 vs. placebo group, bp < 0.05 vs. PCOS group. cDNA was synthesized from 1 μg of total RNA using a Thermo Scientific RevertAid First Strand cDNA Synthesis Kit (Thermo Corporation, MA, United States). Blood samples were collected directly from the inferior vena cava using a 1-mL syringe at the end of the experiment. Trends Endocrinol. 86, 219–224. Arch. doi: 10.1016/j.arcmed.2006.04.006, PubMed Abstract | CrossRef Full Text | Google Scholar, Bednarska, S., and Siejka, A. doi: 10.1016/j.lfs.2006.04.022, Lazaros, L., Xita, N., Hatzi, E., Takenaka, A., Kaponis, A., Makrydimas, G., et al. (2017). This was down to isolating the compound dieckol which increases antioxidative enzyme activity in insulinoma cells.. treatment every day for 2 weeks. EC, E. cava extract; PCOS, polycystic ovary syndrome. After treatment, MTT solutions (0.5 mg/mL) were added to each well, and the plates were incubated for 4 h at 37°C. doi: 10.1210/jc.2006-2641. 4, e104–e112. FIGURE 4. All samples aliquots (5 μL) were injected into a liquid chromatography (LC)-mass spectrometry (MS) system. EC, E. cava extract; PCOS, polycystic ovary syndrome. FEBS Lett. Experiments were carried out in triplicate, and the data are expressed as the means ± SEM (n = 5–8). Ecklonia Cava is a type of seaweed which is known to be one of the highest sources of phloroglucinols, a type of antioxidant compound that appears to be unique to sea plants. Effect of Dieckol, a component of Ecklonia cava, on the promotion of hair growth. doi: 10.1371/journal.pone.0079382, Venkatesan, J., Kim, S. K., and Shim, M. S. (2016).  https://pdfs.semanticscholar.org/04bc/6ae0d6af71a86e69c20da7e1c2cbb2be8de8.pdf,  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983271/,  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983271/, Your email address will not be published. doi: 10.1016/j.esxm.2015.12.002, Hasegawa, T., Kamada, Y., Hosoya, T., Fujita, S., Nishiyama, Y., Iwata, N., et al. Nevertheless, when it comes to hair loss, 5-alpha reductase is an important enzyme to consider which is predominantly involved in steroid metabolism. All hormone levels were measured according to the manufacturer’s instructions. Reprod. Psychological side-effects of clomiphene citrate and human menopausal gonadotrophin. To assess the localization and expression of CYP19A1 (an aromatase), Ar and Erβ, immunohistochemistry was performed using specific antibodies. However, because the etiology is unclear, management and treatment methods for PCOS are not well established. For quantification, the following MRM transitions were used in this study: 371 → 263 for eckol, 741 ? , The study concluded that Ecklonia Cava extracts have potential analgesic effects in the case of post-operative and neuropathic pain. The E. cava extract and five major reference compounds (eckol, dieckol, 6,6′-dieckol, 8,8′-dieckol, and phloroglucinol) were subjected to UHPLC-Triple-Q-MS/MS analysis. (C) MCF-7 cell proliferation and (D) pS2 gene expression were examined after treatment with estrogen and E. cava extract in estrogen-free medium (phenol red-free DMEM with 2% charcoal:dextran-stripped bovine serum) for 48 h. Data are representative of three independent experiments and expressed as the mean ± SD; ap < 0.05 vs. control. The MS was operated under the following conditions: capillary voltage, -3000 V; capillary temperature, 350°C; vaporizer temperature, 300°C; sheath gas, 3 L/min; ion sweep gas, 2.0 arb; aux gas, 10 arb, and drying gas, 8 L/min. Toxicol. Ecklonia's polyphenols are very effective at combating multiple pathologies of â¦ After 2 weeks, the rats were administered E. cava extract per os (P.O.) Gynaecol. Effect of E. cava treatment on physiological changes. Ecklonia cava polyphenols, however, have been shown to reduce reactive oxygen species, specifically those found in the hair follicles of those with Androgenetic Alopecia (AGA). As shown here, consistent with the Cyp19a1 mRNA levels, the immune-reactive aromatase of rats with PCOS was not detected in the granulosa cells or in degenerated follicles. Treatment of rats in the PCOS+positive groups with pellets was removed 14 d after insertion. After 2 weeks, E. cava extract was administered via P.O. Millions of dollars has been spent looking at this stuff for all kinds of purposes. In rats with PCOS, most of the follicles were degenerated, and ovarian aromatase, Ar and Erβ were not detected in the granulosa cells of the degenerated follicles (Figure 7). In the present study, treatment with E. cava extract increased Cyp19a1 mRNA expression in the ovaries of rats with PCOS. Received: 21 December 2017; Accepted: 29 October 2018;Published: 19 November 2018. The percentage of viable cells in each treatment group was determined by the experimental optical density (OD) value of the control. (2012). Each group was treated over a 30 day period. Paraffin-embedded tissue sections were dewaxed, rehydrated and stained with hematoxylin and eosin (H&E; Sigma-Aldrich). Algae 25, 155–171. The plants were deposited in the Herbal Medicine Research Division of Korea Institute of Oriental Medicine (KIOM) in Daejeon, Korea (voucher specimen KIOM H 160150). EC, E. cava extract; PCOS, polycystic ovary syndrome. Other beneficial effects include anticancer properties. In this study, we investigated the effects of E. cava extract in rats with PCOS. In particular, Ecklonia Cava can reduce the symptoms of type 1 diabetes by activating AMP-activated protein kinase (AMPK) and Protein Kinase B (Akt) pathways, where both play a key role in cellular energy homeostasis. The stained slides were examined using a VM600 digital slide scanning system (Motic, CA, United States). Nanomaterials 6:235. doi: 10.3390/nano6120235, Weng, J. R., Tsao, L. T., Wang, J. P., Wu, R. R., and Lin, C. N. (2004). Med. Rev. FIBROMYALGIA Fibromyalgia patients underwent a 2 â¦ (2017). 92, 1209–1216. After 2 weeks, E. cava extract was administered via P.O. The LC-MS MRM chromatograms of the 5 metabolites are summarized in Supplementary Figure S1. Cava Forte Claims. 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