Volume Natural energy-boosting remedies. Month: Total Views: July 1 September 1 February 2 July Reproructive. The expansive and extended externalization of PS in primary trophoblasts appears to require the combined effects of forskolin: the stimulation or inhibition of unknown transporters and increased intracellular cAMP.

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Forskolin and reproductive health -

The present study was needed to further investigate the effectiveness of CF. Aside from its potential health and therapeutic benefits, additional research was needed to assess its role in the management of body composition, and to determine the safety and efficacy of supplementation.

It was also of interest to the investigator how forskolin affects general markers of health i. heart rate, blood pressure, and blood variables. This study took a more comprehensive approach to explore the role that forskolin supplementation has on body composition, fat loss, and general markers of health.

Nineteen 19 moderately overweight BMI of 25 — 35 female subjects between the ages of 18 and 40 participated in the study. A general medical exam was given that included evaluating the medical history, performing a general physical examination, and evaluating whether the subjects met entry criteria to participate in the study.

Entry criteria were based on age, BMI, and the presence of any medical condition deemed unsuitable for participation by the examining physician. Subjects recorded all food intake on dietary record forms for four days 4-d prior to pre-supplementation testing.

Subjects were instructed to refrain from exercise for 48 hours and to fast for 8 hours prior to pre-supplementation testing. Subjects then reported for the initial battery of assessments, which included an appetite questionnaire, a psychological mood inventory, and the following measurements: body weight, total body water, body composition, resting heart rate, and blood pressure.

Subjects then donated approximately 30 milliliters 6 teaspoons of blood. Capsules were provided in a 2-piece hard shell capsule form, and delivered in blindly labeled bottles containing 60 capsules each. Participants were instructed to take one capsule in the morning and one in the evening, a half an hour before a meal for 12 weeks.

Subjects were instructed to provide weekly reports to the research nurse in order to monitor safety and side effects.

Following 4 and 8 weeks of supplementation, subjects returned to have the same initial battery of assessments performed minus the blood draw and dietary history.

After 12 weeks of supplementation, subjects returned to repeat all baseline tests including dietary history and blood draw. Subjects who met eligibility criteria were informed to report any unexpected problems or adverse events they encountered during the course of the study.

Subjects recorded all food and fluid intake on dietary record forms. Dietary intake was assessed using the Food Processor III Nutrition Software Version 7. Appetite was assessed using a visual analogue scale ranging from low to high [ 9 ]. This scale was used to record appetite, hunger, fullness, satisfaction, energy, and quality of food.

Mood changes were assessed by the Profile of Moods States POMS inventory San Diego, CA. The POMS is a validated, standardized self-rating scale consisting of 57 items that measures six identifiable mood states; Tension-Anxiety; Depression-Dejection; Anger-Hostility; Vigor-Activity; Fatigue-Inertia; Confusion-Bewilderment.

Prior to each assessment, height was measured with the shoes removed using standard anthropometrics. The scale was calibrated by placing certified kg weights and balancing the scale. Total body water was estimated using the Valhalla Scientific Bioelectrical Impedance Analyzer Model B, San Diego, CA , which measures bio-resistance of water and body tissues based on a minute low-energy, high frequency transmitted through the body.

The analyzer was calibrated internally to a standard electrical current by pressing the calibration key located on the unit. After calibration was completed, subjects were placed in a supine position with the arms slightly bent at the elbows and palms facing down.

The arms and hands were not to contact the body, and the legs were not allowed to touch each other. The subjects were instructed to remove the right shoe and sock.

Electrodes were placed on the posterior aspect of the hand and wrist, and on the anterior aspect of the foot and ankle. Body composition was determined using a calibrated Hologic W dual-energy x-ray absorptiometry Bedford, MA with the Hologic version V7, Rev F software Waltham, MA.

The dual-energy x-ray absorptiometry DEXA segments regions of the body right arm, left arm, trunk, right leg, and left leg into three compartments for determination of fat, soft tissue muscle , and bone mass. Percent body fat was calculated by dividing the amount of measured fat mass by total scanned mass.

Day-to-day reliability studies of hip, spine, and whole body scans on men and women show the DEXA used in this study to be a highly reliable and precise method for determining variations in body composition segments [ 11 ].

In addition, weekly calibration procedures were performed on a density step calibration phantom. Testing was performed by certified radiology technicians who properly positioned the subjects in a supine manner on the DEXA table and executed testing according to standard procedures.

Heart rate was determined by palpitation of the radial artery according to procedures outlined in the ACSM's Guidelines for Exercise Testing and Prescription [ 12 ].

Blood pressure was assessed in the supine position after resting for 5-min with a mercurial sphygmomanometer Trimline by PyMah Corporation, Somerville, NJ using standard procedures. Subjects observed an overnight eight [ 8 ] hour fast prior to reporting to the lab to donate blood.

Approximately 6 teaspoons of venous blood 30 milliliters were obtained through venipuncture of an antecubital vein in the forearm using standard phlebotomy procedures. Trained laboratory technicians centrifuged the blood samples at rev × min -1 for 10 minutes in a Biofuge 17R Centrifuge Heraeus Inc.

Serum from the remaining SST and EDTA tubes were transferred into two 2 separate 10 mL plain sterile tubes. The whole blood was diluted with 2 mL of saline solution. Both serum and whole blood samples were refrigerated and sent to Quest Diagnostic Labs Ann Arbor, MI for clinical analysis.

A complete panel clinical chemistry profile was run on serum samples using the Technicon DAX model automated chemistry analyzer Technicon Inc. Cell counts with percent differentials were run on whole blood samples using a Coulter STKS automated analyzer Coulter Inc.

Frozen serum samples were sent to the Department of Physiology at East Tennessee State University to assay thyroid stimulating hormone thyrotropin , thyroxin, total thyroxin, and fasting insulin.

A chemistry profile was run on these samples using an Immulite Mark 5 HSS chemiluminescence random access immunoassay analyzer Diagnostic Products Corporation, Los Angeles, CA following standard procedures. These analyzers were calibrated daily to controls according to manufacturer recommendations and federal guidelines for clinical diagnostic laboratories.

Analysis of these blood parameters helped determine the safety effects of this nutritional supplementation formulation on general markers of clinical health status and selected hormones. A 2 groups × 4 times analysis of variance ANOVA test with repeated measures on the second factor was performed on five variables: total body weight, total body water, body composition, appetite surveys, and psychological mood state inventories.

A 2 × 2 ANOVA test with repeated measures on the second factor was performed on the diet logs and the clinical profiles for the blood samples. Type I error was controlled at 0. Tukey least significant difference LSD post-hoc procedures were conducted when a significance level was observed. Delta values were calculated on body composition variables to further highlight significant changes that occurred during the study.

Table 2 presents four day total nutritional intake data for the CF and P groups. Table 3 presents significant blood markers obtained throughout the study. These hematological responses were measured for the analysis of the safety of the supplement on general markers of health.

A significant decrease was noted in all of the values except for total bilirubin, which significantly increased within both groups. All values remained within normal clinical parameters. Table 4 presents body composition data obtained during each of the four testing trials, and Figure 1 presents mean changes in body composition data from Week 0 to Week No other significant differences were observed.

Table 5 presents the appetite data obtained during each of the four testing trials. There were no significant changes observed in appetite, amount of energy, or overall quality of food.

The major findings of this study were: 1. CF supplementation did not adversely affect markers of health status. However, some interesting findings were observed that warrant additional research. The following discusses the results of this study in greater detail. The subjects involved in the study recorded all food and fluid intake during Week 0 and Week 12 of the testing sessions.

Significant decreases were seen in carbohydrate, fat, and energy intake for both groups over time. No significant differences were observed between CF and P, which suggest that supplementation had no significant effect on diet.

The changes over time could reflect subject efforts to decrease food intake in an attempt to assist in the weight loss process. It is possible that more group differences could have been observed if a specific diet were implemented into the study. This would allow for the effects of supplementation to be more closely monitored.

One purpose of this study was to determine the safety effects of forskolin supplementation on general markers of health. This was measured by monitoring changes in heart rate and blood pressure taken during each testing session, and serum and whole blood samples collected during Week 0 and Week 12 of the study.

Previous research indicated that CF causes an increase in heart rate and a decrease in blood pressure [ 14 , 15 ]. However, the results of this analysis showed that supplementation had no significant effect on either variable. The blood samples collected were assayed for muscle and liver enzymes, lipid profile, electrolytes, protein status, thyroid hormones, fasting insulin, and whole blood cell counts.

Significant changes were observed from Week 0 to Week 12 in Group CF in white blood cell count, absolute lymphocyte count, absolute neutrophil count, calcium levels, ALT, and uric acid levels. Supplementation resulted in an increase in calcium, white blood cell, absolute lymphocyte, and absolute neutrophil counts.

Decreases were observed in ALT and uric acid levels. These variables contribute to muscle, immune, liver, and protein functions, respectively, in the body. Even though these changes occurred, the values remained within normal ranges and were relatively small.

As widespread PS externalization has previously been shown only in trophoblastic cell lines stimulated to fuse with forskolin after 72 hours [9] , [16] , [20] we went on to treat primary CT with forskolin. Since forskolin treatment and addition of cAMP stimulate trophoblast fusion through seemingly similar mechanisms increased intracellular cAMP concentrations but result in very different patterns of PS externalization, we went on to examine whether this may be due to pleiotropic effects of forskolin beyond adenylate cyclase activation.

An analog of forskolin, 1,9-dideoxyforskolin, does not stimulate adenylate cyclase activation but interacts with and modulates the above membrane transporters [25] — [27]. Thus we utilized 1,9-dideoxyforskolin to understand whether the non-adenylate cyclase effects of forskolin may be causing the observed increased proportion of cells with externalized PS.

Treatment with 1,9-dideoxyforskolin alone did not significantly stimulate cellular fusion or PS externalization. Again, as with forskolin treatment, a very high variability was observed in the proportion of cells with externalized PS with this treatment.

In this study we examined whether PS externalization was involved in primary villous CT differentiation into syncytium. We found that extensive PS externalization only occurs when differentiation is stimulated with the adenylate cyclase activator forskolin or the combination of cAMP and the forskolin analog 1,9-dideoxyforkolin, and that cAMP treatment alone and spontaneous trophoblast fusion do not result in significant extensive PS externalization in primary trophoblasts.

Therefore extensive PS externalization is likely due to modulation of membrane transporters by forskolin and its analog, which does not stimulate adenylate cyclase activity, and is also a process that requires increased intracellular cAMP concentrations.

Our data also demonstrated that extensive PS externalization is independent of trophoblast fusion in primary trophoblasts. We also assessed Bewo cells and found that the proportion of cells that were observed to have externalized PS was much lower than the proportion of fused cells observed and that extensive PS externalization was not consistently observed.

Previously, using data produced in trophoblastic cell lines stimulated to fuse with forskolin, it was established that PS externalization on the entire surface of syncytium occurred concomitant with cellular fusion and that a monoclonal anti-PS antibody was capable of inhibiting cellular fusion [9] , [16] , [20].

The authors concluded based on this work that PS externalization was required for trophoblast fusion. This conclusion is in contrast with ours but a direct comparison of the data are not available as the previous publications do not contain a summary of the proportion of cells that are positive for externalized PS.

Further, the authors also do not show an increase in PS externalization over a medium alone control after forskolin treatment [9] , [20]. Additionally images of positive staining are not presented or limited to clusters of fewer than 10 nuclei, thus making comparison to our experiments difficult [9] , [20].

Since the exact transporters responsible for PS externalization remain to be elucidated, it is possible that forskolin and 1,9-dideoxyforskolin stimulate one or more of these unidentified transporters directly or cause the inhibition of flippases, which maintain normal phosphlipid membrane asymmetry [21] — [23].

If a direct interaction is occurring it, appears to be insufficient to cause PS externalization without increased levels of intracellular cAMP. The expansive and extended externalization of PS in primary trophoblasts appears to require the combined effects of forskolin: the stimulation or inhibition of unknown transporters and increased intracellular cAMP.

In particular, 1,9-dideoxyforskolin is not capable of stimulating expansive PS externalization without the addition of exogenous cAMP. Expansive PS externalization was inconsistently observed in the Bewo cell line but the trend towards increased PS efflux with forskolin and the combined treatment of 1,9-dideoxyforskolin plus cAMP was observed.

Importantly, Bewo required a cAMP concentration 25 times higher than primary cells for significant fusion to be observed; thus it appears Bewo are far less sensitive to exogenous cAMP treatment than primary cells. This decreased sensitivity of Bewo cells to cAMP in turn may be related to the inconsistent effects observed on Bewo externalization of PS.

Since it has been previously shown in trophoblastic cell lines that PS externalization during forskolin induced differentiation is not associated with increased levels of apoptosis, such externalization appears to be an apoptosis-independent event and forskolin may be useful in answering fundamental questions about what proteins and cellular pathways are involved in PS externalization under non-apoptotic conditions.

Forskolin is used extensively in the trophoblast literature as a differentiation agent of trophoblastic cell lines though, to our knowledge, the pleiotropic effects of forskolin beyond activation of adenylate cyclase have not been widely, if ever, acknowledged. Use of forskolin as a differentiating agent for Bewo was initially presented by Wice et al.

The data presented here demonstrates that forskolin can have pleiotropic effects on trophoblastic cells independent of adenylate cyclase activity.

Though it appears that extensive PS externalization is not involved in trophoblastic cell fusion, our experiments have not directly examined whether transient PS externalization at the site of membrane fusion is occurring in trophoblasts.

This pattern of PS externalization has been observed in myoblast and macrophage fusion [17] — [19]. Since the exposure of PS at the actual site of membrane fusion could be very short lived, the large disparity in the numbers between cells that will fuse either spontaneously or with cAMP treatment and those that were observed to bind annexin-V does not rule out that this may be occurring.

Additionally Adler et al. Similarly designed experiments using anti-PS antibodies and annexin-V have been shown to block myoblast formation [18] , [19].

Thus close examination of phosphlipid membrane localization warrants further investigation in trophoblasts to completely exclude the involvement of externalized PS in the fusion process. Ultimately the data presented in this communication suggest that PS externalization is unlikely to be involved in trophoblastic cell fusion and brings to the attention of the reader the pleiotropic effects of forskolin treatment on trophoblastic cells.

Representative images of annexin-V-FITC binding to trophoblastic cells after induction of apoptosis with staurosporine. A Primary trophoblasts 4 hours after staurosporine treatment; B Bewo cells 4 hours after staurosporine treatment. The present study would like to acknowledge our research nurse, Donna Dawson, for the collection of all samples.

Conceived and designed the experiments: MR STD LJG. Performed the experiments: MR BWL YJ. Analyzed the data: MR. Wrote the paper: MR STD LJG. Browse Subject Areas? Click through the PLOS taxonomy to find articles in your field. Article Authors Metrics Comments Media Coverage Reader Comments Figures.

Abstract Forskolin is an extract of the Coleus forskholii plant that is widely used in cell physiology to raise intracellular cAMP levels. van Veen, University of Cambridge, United Kingdom Received: July 9, ; Accepted: October 10, ; Published: December 5, Copyright: © Riddell et al.

Introduction A properly formed and well functioning placenta is essential for optimal growth of the fetus and aberrant formation and function of the placenta is associated with the common pregnancy conditions of preeclampsia and intrauterine growth restriction [1] — [3].

Materials and Methods Cells, Tissues and Ethical Approval The Bewo choriocarcinoma cell line was obtained from the American Type Culture Collection ATCC, Rockville, USA.

Assessment of Cell Fusion Primary trophoblasts were fixed after 24, 48, or 72 hours in culture with methanol and stained for the cellular junction protein desmoplakin as previously described [14] , [24]. Annexin-V Binding Both primary trophoblasts and Bewo were washed once in annexin-V binding buffer 10 mM HEPES, mM NaCl, 2.

Statistical Analysis All experiments were performed a minimum of three times with experiments utilizing primary trophoblasts carried out on cells isolated from at least 3 different pregnancies.

Results In order to examine whether expansive PS externalization was occurring in primary trophoblasts during the differentiation process, as was observed in Bewo cell line, cells were probed with annexin-V-FITC.

Download: PPT. Figure 1. PS externalization and cellular fusion in primary trophoblasts treated with cAMP. Figure 2. PS externalization and cellular fusion in primary trophoblasts treated with cAMP, forskolin or 1,9-dideoxyforskolin.

Figure 3. Representative images of desmoplakin staining after 72 hours in culture used to determine fusion levels in primary trophoblasts. Figure 4. Externalized PS levels are low in Bewo despite high amounts of cellular fusion. Figure 5. Representative images of E-cadherin staining after 72 hours in culture used to determine fusion levels in Bewo.

Discussion In this study we examined whether PS externalization was involved in primary villous CT differentiation into syncytium. To establish that the product manufacturers addressed safety and efficacy standards, we: Evaluate ingredients and composition: Do they have the potential to cause harm?

Fact-check all health claims: Do they align with the current body of scientific evidence? Assess the brand: Does it operate with integrity and adhere to industry best practices? We do the research so you can find trusted products for your health and wellness.

Read more about our vetting process. Was this helpful? Fast facts on forskolin: Forskolin is a supplement made popular for its possible use in weight loss. Forskolin comes from a plant called Coleus forskohlii. In theory, forskolin aids weight loss by helping create enzymes called lipase and adenylate cyclase.

Share on Pinterest Forskolin is a weight loss supplement derived from a plant. Share on Pinterest Studies on the weight loss benefits of forskalin have produced mixed results. Risks and benefits. Share on Pinterest Although forskolin is not known to interact with any existing conditions, caution is still advised.

Those taking blood thinners or medication for low blood pressure should avoid forskalin. How we reviewed this article: Sources. Medical News Today has strict sourcing guidelines and draws only from peer-reviewed studies, academic research institutions, and medical journals and associations.

We avoid using tertiary references. We link primary sources — including studies, scientific references, and statistics — within each article and also list them in the resources section at the bottom of our articles. You can learn more about how we ensure our content is accurate and current by reading our editorial policy.

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In an attempt to allow for acquisition of Forskolin and reproductive health reproeuctive maturation, Fosrkolin specific inhibitor, cilostamide and adenylate cyclase activator, forskolin were used to extend pre-maturation ane of adn human Forkolin. Cumulus—oocyte complexes retrieved from Body cleanse benefits ovaries were Healtb cultured under 20 µM cilostamide or 50 rerpoductive Forskolin and reproductive health, ajd or in Android vs gynoid fat distribution disparities for 6, 12, 24 or 48 h, respectively. Levels of intercellular gap junction communication GJC and maturational status were examined at these designated time points. Metaphase II oocytes obtained following 54 h biphasic culture with meiotic inhibitors from 0 to 24 h, no meiotic inhibitors from 24 to 54 h were subject to intracytoplasmic sperm injection and embryos were cultured for five more days. Both cilostamide and forskolin delayed spontaneous meiotic progression after continuous culture with immature human oocytes. A delay of 6 h for the loss of GJC was also observed under the combined treatment of cilostamide and forskolin. The fertilization rate was significantly higher under the combined treatment of cilostamide and forskolin than that of the control. Linda Forskolin and reproductive health, Craig C. We have previously demonstrated that the Forskolin and reproductive health activity in human endometrial stromal cells is stimulated by progestin and enhanced Forskoiln oestrogen. In reproductjve study, we have investigated reprpductive effect of forskolin Fitan agent that stimulates the hormone-sensitive adenylate cydase in mammalian cells, on the intracellular cAMP content and aromatase activity in endometrial stromal cells in primary culture. Stromal cells were isolated from proliferative and secretory endometria and were individually cultured in nutrient medium or medium supplemented with medroxyprogesterone acetate MPAoestradiol E2 and Fk, separately or in combination. The intracellular cAMP content of stromal cells was increased after incubation with Fk.