Sphingolipid-Enriched Porcine Placental Extract Promotes the Expression of Structural Genes and Desquamation Enzyme Genes in Cultured Human Keratinocytes.

Porcine placental extract (PPE) is commonly used in various health foods and cosmetics. PPE use in cosmetics predominantly consist of the water-soluble fraction derived from the entire placenta. In this report, we examined the effect of the hydrophobic constituents of the PPE, specifically the sphingolipid-enriched fraction designated as the sphingolipid-enriched porcine placental extract (SLPPE), on the expression of genes associated with skin function in cultured normal human epidermal keratinocytes. Using quantitative RT-PCR (qRT-PCR) analysis, we found that SLPPE concentrations ranging from 25 to 100 µg/mL upregulated the gene expression of key components associated with the cornified envelope structure (filaggrin (FLG), involucrin (IVL) and loricrin (LOR)), cornification enzymes (transglutaminase 1 (TGM1) and TGM5) and the desquamation enzymes (kallikrein 5 (KLK5) and KLK7). Additionally, KLK5p and FLG protein (FLGp) were detected in the culture supernatants of keratinocytes treated with SLPPE at these concentrations. These findings suggest that SLPPE is possible to promote the cornification and desquamation in epidermal keratinocytes, and it may offer potential benefits in cosmetics.

Improvement of Aspects of Subjective Sleep Quality of Healthy Volunteers by Ingestion of Porcine Placental Extract: A Randomized Cross-Over Pilot Study.

Objectives: This study assessed the effects of oral porcine placental extract (PPE) on sleep quality of healthy volunteers not satisfied with their sleep. Design: This study used a randomized, placebo-controlled, double-blind, cross-over clinical pilot study. Setting: This study was conducted under an outpatient multicenter setting in Japan. Interventions: A total of 20 healthy Japanese volunteers aged between 28 and 73, whose Pittsburgh Sleep Quality Index global scores were between 6 and 10, successfully completed the study. At first, PPE at 300 mg/kg or placebo was ingested for 2 weeks. Then, after a 2-week washout period, each group ingested under a cross-over setting the opposite sample (placebo or PPE) for another 2 weeks. Main Outcome Measures: Objective measurement of the sleep made with an activity tracker and subjective measurements of sleep quality by use of St. Mary's Hospital Sleep Questionnaire were done just before and after the administration time slots. Results: No effect of PPE on the sleep length was observed. Several measures in the subjective St. Mary's Hospital Sleep Questionnaire, i.e., changes in Q5 (sleep depth) and Q9 (sleep wellness) between pre- and post-ingestions, were significantly different between groups in the direction of improvement of subjective sleep quality in the PPE group. Conclusions: Although oral PPE at 300 mg/day for 2 weeks did not affect the length of sleep itself, it significantly improved several measures of subjective sleep quality. These results suggest that PPE might be a way to improve sleep quality without hypnotic drugs. Clinical Trial Registration: www.umin.ac.jp/ctr/, identifier: UMIN000026468.

Effect of porcine placental extract on menopausal symptoms in postmenopausal women: A prospective, randomized, double-blind, placebo-controlled trial.

OBJECTIVES: To determine the effect of oral administration of porcine placental extract (PPE) on the menopausal symptoms of Korean women. MATERIALS AND METHODS: This study was a multicenter, randomized double-blind placebo-controlled trial. A hundred menopausal Korean women were randomly allocated either to the PPE 400 mg per day or the control group during 12 weeks of the study period. Menopausal symptoms were evaluated using the Kupperman Index (KMI). RESULTS: The KMI decreased after 12 weeks in both groups; however, the difference in the changes was not statistically significant. Among overweight or obese women whose body mass index (BMI) was 23 kg/m2 or higher, the KMI decreased more significantly in the PPE group than placebo group after 12 weeks (-18.52 ± 9.09 vs -11.40 ± 10.68, P < 0.05). Among 49 early menopausal women whose duration of menopause was less than 3 years, the KMI decreased more significantly in the PPE group after 12 weeks (-17.29 ± 9.07 vs -11.29 ± 10.68, P < 0.05). The baseline estradiol level was not statistically different between the two groups before trial, but the estradiol level of the PPE group was significantly increased at 12 weeks (11.13 ± 35.13 pg/m, P < 0.05). CONCLUSIONS: Oral administration of 400 mg PPE per day decreases menopausal symptoms in women with BMI 23 kg/m2 or higher or in early menopausal women. PPE may be considered as a short-term complementary treatment to reduce menopausal symptoms, especially in overweight or early menopausal women.

Effect of Single-Dose, Oral Enzymatic Porcine Placental Extract on Pharmacokinetics of Alcohol and Liver Function in Rats.

BACKGROUND: Human placenta extract (HPE) has been used to treat a number of liver diseases. Porcine placenta is relatively safe and has been reported to have similar immune effects to HPE and used as its alternative. This study evaluates the effect of enzymatic porcine placental extract (EPPE, Uni-Placenta®) on alcohol pharmacokinetics in rat. METHODS: This study was designed to determine the effect of single-dose EPPE on the pharmacokinetics of alcohol and liver function. Results were based on serum alcohol and acetaldehyde concentrations and activities of hepatic and gastric ADH and ALDH in rats. RESULTS: The hepatic ADH in alcohol group was significantly increased and it may be enzyme-induction by alcohol. The hepatic ALDH and gastric ADH were not changed, but gastric ALDH was significantly decreased only in the high-dose EPPE group. In the alcohol pharmacokinetics parameters, the AUC was 44.5 mM∙h in the alcohol group. Otherwise, AUCs of low, middle, high, and silymarin groups were significantly decreased. Cmax was reached at 1 hour and then gradually decreased to 63% and 43% in the middle and high groups at 3 hours, respectively, and to 92% in the low groups. The pharmacokinetics and serum concentrations of acetaldehyde showed no differences between EPPE groups except the silymarin group. No histologic changes were seen in any group. CONCLUSIONS: The single-dose EPPE (0.5 to 2.5 g/kg) suppressed absorption of alcohol in the gastrointestinal tract. This may be useful in preventing hangover effects and toxicity after drinking alcohol and may also preserve liver health after alcohol ingestion.

Functional Food: Placental Extract / 日本補完代替医療学会誌

Placental extract has been attracting attention as a functional food. In this review, I specifically described the effects of porcine placenta extract on beauty, menopausal symptom, Late-Onset Hypogonadism syndrome (LOH syndrome), shoulder stiffness, knee pain, cognition and osteoporosis. The excellent actions of porcine placental extract are considered to bring light to men as well as middle-aged women.

Effects of Placental Extract on Healthy Women’s Body Constitution in Traditional Chinese Medicine: an Open-label Clinical Trial / 日本補完代替医療学会誌

We conducted a clinical trial in 26 healthy adult women to evaluate the effect of foods containing placental extract ingested for 12 consecutive weeks on 9 constitutional types in Traditional Chinese Medicine.The body constitution analysis set consisted of 23 subjects (excluding 3 dropouts). Twelve-week ingestion of placental extract-containing foods improved individual scores for “Gentleness” type, a healthy constitution, and “Qi-deficiency,” “Yang-deficiency,” “Yin-deficiency,” “Wet-heat” and “Qi-depression” types, which are all mibyou constitution.The safety analysis set consisted of 25 subjects (excluding 1 dropout). Only one subject experienced an adverse event (exacerbation of urticaria, an underlying disease). No other safety concerns arose.

Porcine placental extract facilitates memory and learning in aged mice.

Aging induces a decline in both memory and learning ability without predisposing an individual to diseases of the central nervous system, such as dementia. This decline can have a variety of adverse effects on daily life, and it can also gradually affect the individual and the people they are surrounded by. Since recent evidence indicated that placental extract has effects on brain function such as memory, we hypothesized that placental extract could ameliorate the age-associated reduction in cognitive function in aging. Here, we investigated the effect of new modified porcine placental extract (SD-F) on memory ability in aged mice at both the behavioral and molecular levels. Our results revealed that SD-F significantly enhanced memory ability in the object recognition and object location tasks in a dose-dependent manner in aged mice relative to controls. The numbers of Nissl-positive cells in the hippocampal cornu ammonis 3 (CA3) and dentate gyrus (DG) regions were increased in SD-F-treated aged mice relative to controls. RNA-seq analysis of the hippocampus of aged mice identified 542 differentially expressed genes, of which 216 were up-regulated and 326 were down-regulated in SD-F-treated mice relative to controls. Of the 216 up-regulated genes, we identified four characteristic genes directly related to memory, including early growth response protein 1 (Egr1), growth arrest and DNA-damage-inducible, beta (Gadd45b), NGFI-A binding protein 2 (Nab2), and vascular endothelial growth factor a (Vegfa). These results suggest that the efficacy of SD-F involves upregulation of these genes.

Study on the Effect of Porcine Placental Extract Ingestion on Symptoms of Late-onset Hypogonadism Syndrome in Middle-aged and Elderly Men / 日本補完代替医療学会誌

Purpose: An open-label, single-arm study was conducted to evaluate the effectiveness of porcine placental extract (PPE) ingestion to improve late-onset hypogonadism (LOH) syndrome symptoms. In addition, we reported the safety of continuous PPE ingestion in biochemistry tests.Materials and Methods: Test food containing PPE was given daily to healthy male subjects with an Aging Males’ Symptoms (AMS) score of ≥27, who were assessed as having LOH syndrome. AMS score, blood hormone level, and other parameters were measured before the start of PPE ingestion, Week 4, and Week 8. And adverse events that occurred during the ingestion period were accumulated.Results: Excluding one subject who withdrew from the study due to an adverse event unrelated to the test food, 14 subjects were included in the analysis. In terms of AMS score, no improvement was observed at Week 4, whereas a significant improvement was observed at Week 8. AMS scores were further categorized into three subscales (psychological, somatic, and sexual) and analyzed. The results showed a significant improvement from baseline in somatic scores at Week 8. Meanwhile, no significant change in sexual hormone levels was observed. At Week 8, improvements from baseline were observed in renal function and LDL cholesterol level. There were no adverse events related to the test food.Conclusion: The study demonstrated that 8-week PPE ingestion in middle-aged and elderly men can improve LOH syndrome symptoms while having little effect on sexual hormone secretion.

Anti-inflammatory Effect of the Water-Soluble Portion of Porcine Placental Extract in Lipopolysaccharide-Stimulated RAW264.7 Murine Macrophage Cells.

Porcine placental extract (PPE) is used as a nonprescription drug for analeptics and in health foods and cosmetics in Japan, Korea and China. It was reported that PPE has anti-oxidative and anti-inflammatory activities; however, the mechanisms and the responsible molecules involved in these activities are still unclear. Here, we investigated how enzymatically prepared PPE affects proinflammatory factors such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α in a cultured macrophage cell line, RAW264.7, when co-stimulated with lipopolysaccharide (LPS). Enhanced production of IL-1ß, IL-6 and TNF-α by LPS was significantly reduced by the addition of PPE and these effects were dose dependent. Nitric oxide (NO) production induced in cultured macrophages by LPS was also inhibited by PPE. Real-time PCR after the reverse transcription of total RNAs isolated from cells treated with PPE revealed that the mRNA expressions of IL-1ß, IL-6, TNFα, and NO synthase (NOS)-2 were reduced. The necessary concentration of PPE prepared by enzymatic digestion to mediate anti-inflammatory effects compared with the reported value of that extracted by phosphate buffered saline without digestion was proportional to the amount of extracted materials from the same amount of placenta (about 10-fold). This suggests that the molecules responsible for the anti-inflammatory activity exists in the placenta and can be extracted by phosphate buffered saline, and thus might survive enzymatic digestion.

Effect of porcine placental extract on the mild menopausal symptoms of climacteric women.

OBJECTIVES: This study assessed the effects of oral porcine placental extract (PPE) on the mild menopausal symptoms of climacteric women. METHODS: In this 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study, 50 climacteric Japanese women were randomized 1 : 1 to oral PPE (300 mg/day) or placebo. Menopausal symptoms were evaluated by using the Simplified Menopausal Index (SMI), as were serum estradiol (E2) and follicle stimulating hormone (FSH) levels. Blood biochemical and cellular and urinary tests were done to evaluate safety aspects of repeated oral administration of PPE. RESULTS: The total SMI score of the PPE group was significantly more improved after 12 weeks than that of the placebo group (p = 0.031). This score and three subscores (vasomotor, psychological, and somatic symptoms) were significantly improved at 8 and/or 12 weeks compared with the initial values in the PPE group (p < 0.05). E2 and FSH levels were not improved in either group. No adverse events were observed. CONCLUSIONS: Oral PPE at 300 mg/day improved the mild menopausal symptoms of climacteric women. Since oral PPE did not improve serum E2 and FSH levels, PPE is thought not to ameliorate hormonal balance itself but to improve subjective feelings of climacteric women.

Efficacy of porcine placental extract on wrinkle widths below the eye in climacteric women.

OBJECTIVE: Injections of human placental extract, which is known to play a role in skin regulation, have long been used for the treatment of skin wrinkles and non-healing wounds. Porcine placental extract (PPE), an oral supplement, was recently developed for this purpose. The aim of this study was to assess whether PPE has a positive effect on the improvement of fine wrinkles below the eye in climacteric women. METHODS: We first non-invasively measured wrinkle widths with a skin analyzer in a cross-section of 185 healthy adult Japanese women. Next, 44 climacteric women with mild or few climacteric symptoms were enrolled into an open-label, randomized, controlled study of the effect of PPE on wrinkle widths. A retrospective comparison of wrinkle widths in 123 climacteric women with climacteric symptoms with or without PPE treatment was also performed. RESULTS: Wrinkle widths below the eye in women ≥ 30 years of age were significantly higher than in women 20-29 years of age. Treatment with three capsules of PPE per day was significantly (p < 0.05) effective in reducing wrinkle widths at 24 weeks compared with control subjects. Retrospective analysis showed that subjects treated with three (p < 0.05) and six (p < 0.01) capsules of PPE per day observed a significant reduction in wrinkle widths compared with untreated subjects. CONCLUSION: Oral PPE treatment is a possible option for improving the appearance of fine wrinkles below the eye in climacteric women.