Effects Of Human Placental Extract Research Articles

Human Placental Extract Delays In Vitro Cellular Senescence through the Activation of NRF2-Mediated Antioxidant Pathway.

Senescent cells accumulate in the organs of aged animals and exacerbate organ dysfunction, resulting in age-related diseases. Oxidative stress accelerates cellular senescence. Placental extract, used in the alleviation of menopausal symptoms and promotion of wound healing and liver regeneration, reportedly protects against oxidative stress. In this study, we investigated the effects of human placental extract (HPE) on cellular senescence in normal human dermal fibroblasts (NHDFs) under oxidative stress conditions. We demonstrated that HPE delays the onset of cellular senescence. Next-generation sequencing analysis revealed that under oxidative stress conditions, HPE treatment enhanced the expression of the antioxidant genes CYGB, APOE, NQO1, and PTGS1. Further, HPE treatment under oxidative stress conditions increased the protein level of nuclear factor-erythroid factor 2-related factor 2 (NRF2)—a vital molecule in the antioxidant pathway—via post-transcriptional and/or post-translational regulations. These findings indicate that HPE treatment in NHDFs, under chronic oxidative stress, delays cellular senescence by mitigating oxidative stress via upregulation of the NRF2-mediated antioxidant pathway, and HPE treatment could potentially ameliorate skin-aging-associated damage, in vivo.

Possible ameliorative effect of human placental extract on methotrexate-induced nephrotoxicity in albino rats

BackgroundMethotrexate (MTX) is one of chemotherapeutic drugs that induce several side effects. The present study aimed to investigate the ameliorative effect of human placental extract (HPE) against MTX-induced nephrotoxicity in rats. In this study, forty adult male albino rats were equally divided into four groups. Control group: rats were daily injected intraperitoneally with physiological saline (0.5 ml for each rat) for 5 days, HPE group: rats were subcutaneously injected with HPE at a dose level of 10.08 mg/Kg b.w/day for 2 weeks, MTX group: rats were intraperitoneally injected with MTX at a dose level of 5 mg/Kg b.w/day for 5 consecutive days, MTX and HPE group: rats were intraperitoneally injected with MTX (at the same dosage of MTX group) for 5 days and at the same time they were subcutaneously injected with HPE (at an exact dosage of HPE group), daily for 2 weeks. Twenty-four hours after the last dose for each treatment, rats were killed and blood samples were collected for determination of urea, creatinine, sodium (Na+) and potassium (K+) levels. Kidney tissues were taken for histological examination and immunohistochemical staining of both cysteine-aspartic protease-3 (caspase-3) and proliferating antigen Ki-67 (Ki-67) expressions.ResultsFrom the obtained data, MTX induced nephrotoxicity through a highly significant increase in urea, creatinine, Na+ and K+ levels compared with the control group. In addition to massive histological alterations, a highly significant increase in caspase-3 expression and a significant decrease in Ki-67 expression were observed. On the other hand, injection with HPE ameliorated urea, creatinine, Na+ and K+ levels comparing to MTX group. Moreover, HPE markedly improved the histological and immunohistochemical changes resulted from MTX treatment.ConclusionsIt is concluded that HPE ameliorated the nephrotoxicity induced by MTX.

Human placental extract attenuates neurological symptoms in the experimental autoimmune encephalomyelitis model of multiple sclerosis-a putative approach in MS disease?

BackgroundDifferent studies have demonstrated the anti-inflammatory effects of human placental extract both in vivo and in vitro. Considering the chronic inflammatory nature of multiple sclerosis (MS) disease, we examined whether or not the administration of human placental extract is able to attenuate the neurological symptoms detected in experimental autoimmune encephalomyelitis (EAE) model of MS.MethodsThe injected myelin oligodendrocyte glycoprotein (MOG) induced EAE in mice, and treatment began from day 4 post-injection by intraperitoneal administration of 20 mg/kg human placental extract, repeated every other day up to day 31 post-injection. At the end of the treatment, luxol fast blue (LBS) staining and hematoxylin and eosin (H&E) staining were performed to evaluate the demyelination of neurons and inflammatory responses, respectively. Further assessed were the serum concentrations of IL-23 and IL-27.ResultsThe administration of human placental extract was able to significantly reduce the mean clinical score in EAE mice, decrease the pro-inflammatory process and attenuate neural demyelination. Moreover, while the serum concentration of IL-23 was significantly diminished in the EAE mice receiving human placental extract compared to the non-treated EAE group, IL-27 concentration was significantly increased.ConclusionsOur findings demonstrated the administration of human placental extract could significantly attenuate the neurological symptoms in the EAE model of MS in part through modulating the serum levels of IL-23 and IL-27 and enhancing neuroprotection and myelin repair.

Human placental extract: a potential therapeutic in treating osteoarthritis

Osteoarthritis (OA) is a degenerative joint disease marked by cartilage degradation and loss of function. Recently, there have been increased efforts to attenuate and reverse OA by stimulating cartilage regeneration and preventing cartilage degradation. Human placental extract (HPE) may be an option due to its anti-inflammatory, antioxidant, and growth stimulatory properties. These properties are useful in preventing cell death and senescence, which may optimize in-situ cartilage regeneration. In this review, we discuss the anatomy and physiology of the placenta, as well as explore in vivo and in vitro studies assessing its effects on tissue regeneration. Finally, we assess the potential role of HPE in cartilage regenerative medicine and OA. The Medline database was utilized for all studies that involved the use of HPE or human placenta hydrolysate. Exclusion criteria included articles not written in English, conference reviews, editorials, letters to the editor, surveys, case reports, and case series. HPE had significant anti-inflammatory and regenerative properties in vitro and in vivo . Furthermore, HPE had a role in attenuating cellular senescence and cell apoptosis via reduction of reactive oxidative species both in vitro and in vivo . One study explored the effects of HPE in OA and demonstrated reduction in cartilage catabolic gene expression, indicating HPE’s effect in attenuating OA. HPE houses favorable properties that can attenuate and reverse tissue damage. This may be a beneficial therapeutic in OA as it creates a more favorable environment for in-situ cartilage regeneration. More well designed in-vitro and in-vivo studies are needed to define the role of HPE in treating OA.

The Protective Effect of Sheep Placental Extract on Concanavalin A-induced Liver Injury in Mice.

Though the biological effects of human placental extract have been widely studied, it has limited availability and its use poses ethical problems. Thus, domestic animal placental extracts are suggested as alternatives. In this study, the protective effect of sheep placental extract (SPE) on concanavalin A (Con A)-induced liver injury was investigated. BALB/c mice were randomly divided into six groups, including one normal group and five experimental groups, which received different oral doses of SPE (0, 5, 10 and 50 mg/kg) or a mixture of amino acids for 3 days before Con A injection. Compared with Con A-induced model group, the SPE administration significantly decreased serum aminotransaminase activity, alleviated pathological changes, recovered liver antioxidant capacity and prevented the increase of nitric oxide. Secretion of pro-inflammatory cytokines in serum decreased and mRNA expression of hepatic intercellular adhesion molecule-1, interferon-inducible chemokine 10 and inducible nitric oxide synthase were downregulated, while B-cell lymphoma-2 expression increased. The administration of amino acids mixture had no significant effect in most measurements compared with the model group, which indicated proteins and peptides, rather than individual amino acid, were largely responsible for the bioactivity of SPE. The results indicate SPE has potential therapeutic effects against immune-mediated hepatitis.

Effect of human placental extract in the management of biofilm mediated drug resistance – A focus on wound management

Management of infectious wounds, particularly chronic wounds and burn injuries, is a matter of global concern. Worldwide estimates reveal that, billions of dollars are being spent annually for the management of such chronic ailments. Evidently, bacterial biofilms pose a greater problem in the effective management of infection in chronic wounds, since most of the currently available antibiotics are unable to act on the microorganisms residing inside the protected environment of the biofilms. Accordingly, in the present study, we have attempted to evaluate the anti-biofilm properties of human placental extract (PLX) and also other virulence factors that are mediated via the quorum sensing (QS) signalling system. PLX is well known for its anti inflammatory action and it has been shown earlier some anti microbial and enzymatic activity also. PLX was found to produce significant inhibition of biofilm formation and also decreased the levels of pyoverdin and pyocyanin. The microscopic analysis (both light microscopy and atomic force microscopy) of biofilms was also used for substantiating the findings from spectrophotometric (crystal violet estimation) and fluorescence analysis (resazurin uptake). PLX pre-treatment decreased the hydrophobicity of gram-positive and gram negative cells, indicating the effect of placental extract on adherence property of planktonic cell, serving as an indicator for its antibiofilm effect on microorganisms. The reduced extracellular DNA (eDNA) content in biofilm matrix following treatment with PLX also indicates the effectiveness of placenta extract on bacterial adherence, which in turn serves as evidence substantiating the antibiofilm effects of the PLX. Furthermore, PLX was also found to be significantly effective in the in vitro wound biofilm model. Thus the present study, the first of its kind with PLX, establishes the therapeutic benefit of the same particularly in infected wounds, opening up newer avenue for further exploration.

Potential synergistic effects of human placental extract and minoxidil on hair growth-promoting activity in C57BL/6J mice.

Human placenta extract (HPE) has been used to alleviate tiredness and promote wound healing, and for its antiageing functions; however, it has not yet been studied for its effects on hair growth. In the present study, we evaluated the in vitro effect of HPE on hair growth by observing its actions on human dermal papilla cells (DPCs). To define how HPE promotes induction of anagen hair growth during the telogen phase, and to understand the synergistic molecular mechanisms of HPE and minoxidil (MXD) actions on hair growth. We examined the effects of HPE and MXD on C57BL6/J mice using haematoxylin and eosin staining, quantitative histomorphometry, hair growth scoring, immunohistochemistry and immunofluorescence on the dorsal skins of C57BL/6J mice. We found that HPE synergistically augmented the effects of MXD, a promoter of hair growth. In particular, histomorphometric analysis data indicated that subcutaneous injection of HPE induced an earlier anagen phase and prolonged the anagen phase. It also stimulated increases in both the number and size of hair follicles in groups treated with HPE alone and HPE+MXD. From our data, we conclude that HPE increases β-catenin and Wnt3a expression levels. Overall, our findings suggest that HPE in combination with MXD has hair growth-promoting activity and is a potential novel therapeutic treatment for alopecia or baldness in humans.

Experimental evaluation of anticonvulsant effect of human placental extract in pentylenetetrazole induced convulsions in mice

Background: Human placental extract (HPE) is used in different clinical conditions. Human placental extract (HPE), a folklore medicine, prepared from fresh, healthy human placenta has been in use, as single dose therapy in the treatment of epilepsy in some parts of India. Hence, present study was carried out to explore anticonvulsant property of Human placental extract (HPE) in Pentylenetetrazole (PTZ) induced convulsions in albino mice. Methods: Effects of human placental extract (HPE) (1.0, 1.2 and 1.4 ml / 100 gm body weight) as test drug, sodium valproate (150 mg / kg body weight) as standard and distilled water as control were studied in pentylenetetrazole (PTZ) induced convulsions in albino mouse model. Failure to observe even a single episode of tonic spasm for 5 sec. duration for 1 hour was taken as index of anticonvulsant activity. Onset, duration, complete recovery from convulsion and percent protection was calculated and statistical analysis was carried out using student ‘t’ test. Results: Pretreatment with human placental extract (HPE) administered in the dose of 1.0 ml / 100 gm body weight provided 33.33% and in the doses of 1.2 and 1.4 ml / 100 gm body weight and sodium valproate provided 100% protection from convulsions induced by Pentylenetetrazole in albino mice. Conclusion: Human placental extract (HPE) has shown promising anticonvulsant effect on Pentylenetetrazole induced mouse model.

Effect of Human Placental Extract on Health Status in Elderly Koreans

Objectives. Human placental extract (HPE) has begun to be used in Korea in various ways to improve health, even though evidence-based data is insufficient. This study investigated the effects of HPE on health status in elderly Koreans. Design. Randomized, single-blind, and case-control study design. Setting and Participants. Thirty-nine community-dwelling healthy Koreans ≥65 years of age. Intervention. The participants were randomly categorized into a placebo group (n = 17) and HPE group (n = 22). The HPE group received abdominal subcutaneous injections of HPE for 8 weeks. The placebo group was injected with normal saline. Measurements. The degree of health status was surveyed by the Korean health status measure for the elderly (KoHSME V1.0) at baseline and the end of the study. Results. In the HPE group, the scores of physical function, sexual life, and general heath perception at the end of the study period were significantly improved from baseline (P = .007, .020, and .005, resp.), while the health status of the placebo group remained unchanged during the study period. There was a significant difference over the study period between the two groups in the mean change of the physical function score (P = .036). Conclusion. A HPE injection regimen can improve the health status in elderly Koreans.

The Effect of Human Placental Extract on Rheumatoid Arthritis in an Animal Model

ObjectiveTo assess the efficacy of human placental extract (HPE) in an animal model of rheumatoid arthritis (RA).MethodWe used (i) KRN C57BL/6 TCR transgenic x NOD mice (KBx/N) serum transfer arthritis and (ii) collagen-induced arthritis (CIA) mice to evaluate the effi cacy of HPE (1 ul or 100 ul, intra-peritoneal, three times per week) on RA. Incidence, severity of arthritis, and hind-paw thickness were quantifi ed. Joint destruction was analyzed using modifi ed mammographic imaging. Histopathological analysis for inflammation, cartilage, and osteoclasts was performed using Hematoxylin-eosin (H-E), safranin-O, and tartrate-resistant acidic phosphatase (TRAP). ELISAs were used for detection of various cytokines in serum and joint tissue.ResultsThere were no significant differences in incidence of arthritis, clinical scores of arthritis, and hind-paw thickness between HPE-treated and vehicle-treated groups for up to 2 weeks in the KBx/N serum transfer arthritis model. Histopathological analysis also showed no differences 2 weeks after treatment. Levels of TNF-α, IL-1β, IL-6, IL-10, and RANKL in serum and joint tissues were similar in all groups. Furthermore, there were no differences in clinical, radiological, and histological parameters between HPE-treated and vehicle-treated group for 3 weeks in the CIA model.ConclusionSystemic treatment with HPE has no beneficial effects on arthritis in animal models of RA. Therefore, indiscreet use of HPE in RA should be forbidden.

Effect of human placental extract on menopausal symptoms, fatigue, and risk factors for cardiovascular disease in middle-aged Korean women

In Korea, human placental extract (HPE) has recently been used to treat various diseases (chronic liver diseases, menopause syndrome, chronic fatigue, skin pigment diseases, etc.), but evidence-based studies are not yet sufficient. The aim of this study was to examine the effects of HPE on menopausal symptoms, fatigue, and risk factors for cardiovascular disease in middle-aged Korean women in a randomized controlled trial. Korean women, aged 40 to 64 years, with menopausal symptoms and fatigue were recruited as participants. The women were randomly assigned to a placebo group or an HPE group. The HPE group received subcutaneous injections of HPE in the abdomen for 8 weeks, whereas the placebo group received normal saline. Then, the Menopause Rating Scale, and Fatigue Severity Scale, and Visual Analog Scale were administered, and risk factors for cardiovascular disease were assessed. The Menopause Rating Scale total baseline score was not different between the two groups; however, the score of the HPE group decreased significantly at 8 weeks compared with that of the placebo group (P = 0.033). Fatigue Severity Scale and Visual Analog Scale scores of the placebo group did not change, whereas the scores of the HPE group decreased significantly during the study period (Fatigue Severity Scale, P = 0.002; Visual Analog Scale, P = 0.001). The baseline 17beta-estradiol level was not significantly different between the two groups, but the 17beta-estradiol level of the HPE group was significantly increased at 8 weeks compared with that of the placebo group (P = 0.031). No changes in risk factors for cardiovascular disease were observed in either group. Menopausal symptoms and fatigue in middle-aged Korean women improved after 8 weeks of HPE treatment, whereas risk factors for cardiovascular disease did not change during the study period.

Human placental extract stimulates liver regeneration in rats.

The effect of human placental extract (HPE) on liver regeneration in rats was investigated. After intravenous administration of HPE to a-naphthylisothiocyanate (ANIT)-intoxicated rats, the labeling index in hepatocytes was significantly increased to a level 16.5 times higher than that of the control. A 1/500 dilution of HPE directly stimulated DNA synthesis of the hepatocytes in primary culture. HPE heated at 121 degrees C did not stimulate the labeling index in vivo or hepatocyte DNA synthesis in primary culture, suggesting that HPE contains heat-unstable but potent mitogens for hepatocytes. HPE contains hepatocyte growth factor (HGF), but the mitogenic effect of HPE cannot be explained by the effect exerted by HGF alone, since both the labeling index in vivo and hepatocellular DNA synthesis in vitro stimulated by HPE were much higher than those stimulated by HGF alone when the applied doses of HGF were set to be almost the same level between each case. When HPE was fractionated on a heparin-sepharose column, the mitogenic effect of HPE was found to be located mainly in the heparin-bound fraction. Hepatocyte DNA synthesis induced by this fraction was enhanced cooperatively by the heparin-unbound fraction, suggesting that there are some modulators in the heparin-unbound fraction which enhance the proliferative activity of the heparin-bound fraction by a synergetic mechanism. Both HPE and heated HPE completely recovered the biochemical marker activity for liver function (glutamic-pyruvic transaminase, GPT; alkaline phosphatase, ALP; lactate dehydrogenase, LAP; gamma-glutamyltransferase, gamma-GTP activities and the bilirubin concentration) almost to the control level in the serum of ANIT-intoxicated rats, indicating that HPE also contains a heat-stable fraction which repairs liver function.

Effects of human placental extract on brain monoamines and monoamine oxidase activity in rats.

Human placental extract, an agent clinically used world-wide in a number of physiological anomalies, has been claimed to be effective in children of slow learners. Since the monoaminergic neurotransmitter systems in the brain play an important role in the processes of learning and memory, we examined the effects of human placental extract on the levels of norepinephrine, dopamine and serotonine in rat brain as an attempt to evaluate the possible underlying biochemical mechanism of action of the extract. We also determined the changes of brain monoamine oxidase (MAO) activity following placental extract treatment. The results showed that subchronic (5, 10, 15 or 20) administration of placental extract (2-4 ml/kg/day) had the effect of increasing all the monoamines and decreasing the MAO activity which could be the possible mode of action of the extract in slow learners.

Elevated lipid peroxidation, decreased glutathione levels and changes in glutathione-related enzymes in rats treated with human placental extract.

The in vivo effects of human placental extract (1-4 ml/kg) on hepatic lipid peroxidation, blood and liver glutathione (GSH) levels and several enzymes associated with the antioxidant defence mechanism; i.e., catalase, glutathione peroxidase, glutathione reductase and glutathione S-transferase, together with some blood biochemical responses were investigated in rats. At an optimal dose level (4 ml/kg), a single acute intraperitoneal administration of the extract caused a significant enhancement (49.9%; p < 0.001) of lipid peroxidation with a decline in GSH level both in blood (45.1%; p < 0.001) and liver (61.0%; p < 0.001) in comparison to control animals. Activities of catalase, glutathione peroxidase and glutathione reductase were inhibited in a dose-responsive way by the treatment with the extract which also increased the activity of glutathione S-transferase in a dose-dependent manner. The extract was found to be hepatotoxic in terms of elevation of serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, serum lactate dehydrogenase and blood methemoglobin concentration. Results of this study suggest the adverse consequences of the administration of the extract due to its substantial ability to alter normal cellular processes.