• Title/Summary/Keyword: Reverse pharmacology

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Effect of Astragali Radix on SPS-induced PTSD in Rats (황기(黃芪)가 흰쥐에서 SPS로 유도된 PTSD에 미치는 효과)

  • Min, Ye-Eun;Lee, Tae-Hee
    • Herbal Formula Science
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    • v.30 no.3
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    • pp.109-121
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    • 2022
  • Objective : This study is conducted to investigate the effect of Astragali Radix on Post Traumatic Stress Disorder(PTSD) induced by the Single Proposed Stress(SPS). Methods : The experiment was conducted with five groups; SAL groups with only saline treatment, SPS group, SPS + ARX25 group, SPS + ARX50 group, and SPS + ARX100 group. After applying SPS, saline and ARX were administered for 14 days to identify the change of body weight, sucrose intake amount, and behavioral changes through Open Field Test(OFT) and Forced Swimming Test(FST). After the behavioral experiment, plasma corticosterone levels, serotonin, norepinephrine and dopamine concentrations were measured by enzyme-linked immunoassay in medical prefrontal cortex, hippocampus, and amygdala. Brain-derived neurotrophic factor(BDNF) in the hippocampus was measured using Reverse Transcription Polymerase Chain Reaction. Results : Weight change has significantly decreased in the SPS group compared to the SAL group(p<0.05). On day 14, the sucrose intake of rats has significantly increased in the SPS + ARX100 group compared to the SPS group(p<0.05). In OFT, the number of staying in the central space has significantly increased in the SPS + ARX100 group(p<0.01). In FST, immobility has significantly decreased in SPS + ARX50 group and SPS + ARX100 group(p<0.05). The concentration of serotonine, dopamine and BDNF expression has increased significantly in SPS + ARX100 group compared to SPS group(p<0.05) Conclusions : In the SPS-induced PTSD experiment, ARX increased sucrose intake and the numbers of crossing in the central zone space in OFT, decreased immobility time in FST, and increased concentration of serotonin, dopamine, and BDNF. It can be postulated that the ARX could be effective for the treatment of PTSD.

Novel polymorphisms of dopa decarboxylase gene and their association with lamb quality traits in Indonesian sheep

  • Ratna Sholatia Harahap;Ronny Rachman Noor;Yuni Cahya Endrawati;Huda Shalahudin Darusman;Asep Gunawan
    • Animal Bioscience
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    • v.36 no.6
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    • pp.840-850
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    • 2023
  • Objective: This study aimed to investigate the polymorphisms of the dopa decarboxylase (DDC) gene and association analysis with lamb quality and expression quantification of the DDC gene in phenotypically divergent Indonesian sheep. Methods: The totals of 189 rams with an average body weight of 24.12 kg at 10 to 12 months were used to identify DDC gene polymorphism using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Among 189 rams, several rams representing various sheep genotypes were used for an association study between genotypes and phenotypic traits with proc general linear model (GLM) analysis. In addition, the gene expression analysis of the DDC mRNA in the phenotypically divergent sheep population was analyzed using quantitative reverse-transcription PCR. Results: The DDC gene (g. 5377439 G>A) showed polymorphisms that indicated three genotypes: AA, AG, and GG. The DDC gene polymorphism was significantly associated (p≤0.05) with carcass characteristics including carcass percentage, carcass length, hot and cold carcass; physical properties of lamb quality including pH value; retail cut carcass; fatty acid composition such as fat content, pentadecanoic acid (C15:0), tricosylic acid (C23:0), lignoceric acid (C24:0), oleic acid (C18:1n9c), elaidic acid (C18:1n9t), nervonic acid (C24:1), linoleic acid (C18:2n6c), arachidonic acid (C20:4n6), cervonic acid (C22:6n3); and mineral content including potassium (K). The GG genotype of the DDC gene had the best association with lamb quality traits. The DDC gene expression analysis mRNA showed no significant difference (p≥0.05) between lamb quality traits. Conclusion: The DDC gene could be used as a potential candidate gene to improve lamb quality.

Development of the Tentative Educational Objectives for the Nursing College (대학간호교육목표의 시안개발)

  • Lee Haw-Ja
    • The Journal of Korean Academic Society of Nursing Education
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    • v.1 no.1
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    • pp.32-45
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    • 1995
  • This thesis is a study to develop the tentative objectives and present the professional and courses for the nursing college. The conclusions conducted by the purpose of this study are as follows. First, on the basis of the concepts of the nursing and the view-points of nursing education, the tentative goals for the nursing education are set up as follows. 1. To understand human being's life, dignity and their physical, mental, and social aspects. 2. To understand the basic concepts and the principles of human sciences, social sciences, natural sciences, and medical sciences. To apply their knowledges to nursing practices. 3. To diagnose and assess the problems of individual, family and community in terms of nursing practice. To develop the ability of planning, negotiation, management, and evaluation for the nursing education. 4. To develop appropriate knowlege, attitudes, and skills to promote the clients' health and treat their illness. 5. To accomplish all tasks effectively as a trained and qualified professional nurse through the endless studies. Second, the nursing areas and courses for the nursing college in terms of validity, Importance, continuity, relationship, utility and appropriateness are listed as follows. 1. Fundamental courses of the nursing. (1) General courses communication human development, behavior science, biochemistry, microbiology, pharmacology (2) Medical courses physiology, anatomy, pathology 2. Basic courses in nursing (1) General nursing fundamental nursing, introduction of nursing, nursing history, nursing process, health education, health assessment, philosophy of nursing, nursing psychology (2) Maternal-Child nursing child-health nursing, child-disease nursing, adolescent nursing, obstetric nursing, post-partum nursing, gyneco-pathy nursing (3) Adult nursing adult health nursing, adult disease nursing I(fluid & electrotonic, shock, anoxia disorder), adult disease nursing II(nutrition-excretion disorder, sexual dysfunction), adult disease nursing III(sense-, control-, activity-, sleep disorder), adult disease nursing IV(operation, rehabilitation, emergency), gerontological nursing (4) Psychiatric nursing child-adolescent psychiatric nursing, adult psychiatric nursing, gerontological psychiatric nursing, spiritual nursing (5) Community health nursing community nursing, school nursing, industrial nursing, family nursing, nursing epidemiology 3. Nursing management and research skills (1) Nursing management nursing administration, nursing ethics, laws related to nursing (2) Research skills nursing statistics, nursing research methodology Finally, the principles of the statement of the specific objectives are the followings : 1. To state the specific objectives on the basis of the syllabus of each courses. 2. To match a content with a verb or gerund as the basic form of objectives. 3. To control the level of the objectives according to the rule 'the higher the level of a content, the lower the level of a verb or a gerund'. This rule applies in the reverse, as well. 4. To decide the number of the objectives in each course on the basis of the numbers of the syllabus and the level of its comprehensiveness, 5. To correct, supplement or eliminate the stated objectives by a professional or professional groups in that area.

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Spinosin, a C-Glucosylflavone, from Zizyphus jujuba var. spinosa Ameliorates Aβ1-42 Oligomer-Induced Memory Impairment in Mice

  • Ko, Sang Yoon;Lee, Hyung Eun;Park, Se Jin;Jeon, Se Jin;Kim, Boseong;Gao, Qingtao;Jang, Dae Sik;Ryu, Jong Hoon
    • Biomolecules & Therapeutics
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    • v.23 no.2
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    • pp.156-164
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    • 2015
  • Alzheimer's disease (AD) is a neurodegenerative disorder associated with progressive memory loss and neuronal cell death. Although numerous previous studies have been focused on disease progression or reverse pathological symptoms, therapeutic strategies for AD are limited. Alternatively, the identification of traditional herbal medicines or their active compounds has received much attention. The aims of the present study were to characterize the ameliorating effects of spinosin, a C-glucosylflavone isolated from Zizyphus jujuba var. spinosa, on memory impairment or the pathological changes induced through amyloid-${\beta}_{1-42}$ oligomer ($A{\beta}O$) in mice. Memory impairment was induced by intracerebroventricular injection of $A{\beta}O$ ($50{\mu}M$) and spinosin (5, 10, and 20 mg/kg) was administered for 7 days. In the behavioral tasks, the subchronic administration of spinosin (20 mg/kg, p.o.) significantly ameliorated $A{\beta}O$-induced cognitive impairment in the passive avoidance task or the Y-maze task. To identify the effects of spinosin on the pathological changes induced through $A{\beta}O$, immunohistochemistry and Western blot analyses were performed. Spinosin treatment also reduced the number of activated microglia and astrocytes observed after $A{\beta}O$ injection. In addition, spinosin rescued the $A{\beta}O$-induced decrease in choline acetyltransferase expression levels. These results suggest that spinosin ameliorated memory impairment induced through $A{\beta}O$, and these effects were regulated, in part, through neuroprotective activity via the anti-inflammatory effects of spinosin. Therefore, spinosin might be a useful agent against the amyloid ${\beta}$ protein-induced cognitive dysfunction observed in AD patients.

Enhanced Expression of TREK-1 Is Related with Chronic Constriction Injury of Neuropathic Pain Mouse Model in Dorsal Root Ganglion

  • Han, Hyo Jo;Lee, Seung Wook;Kim, Gyu-Tae;Kim, Eun-Jin;Kwon, Byeonghun;Kang, Dawon;Kim, Hyun Jeong;Seo, Kwang-Suk
    • Biomolecules & Therapeutics
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    • v.24 no.3
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    • pp.252-259
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    • 2016
  • Neuropathic pain is a complex state showing increased pain response with dysfunctional inhibitory neurotransmission. The TREK family, one of the two pore domain $K^+$ (K2P) channel subgroups were focused among various mechanisms of neuropathic pain. These channels influence neuronal excitability and are thought to be related in mechano/thermosensation. However, only a little is known about the expression and role of TREK-1 and TREK-2, in neuropathic pain. It is performed to know whether TREK-1 and/or 2 are positively related in dorsal root ganglion (DRG) of a mouse neuropathic pain model, the chronic constriction injury (CCI) model. Following this purpose, Reverse Transcription Polymerase Chain Reaction (RT-PCR) and western blot analyses were performed using mouse DRG of CCI model and compared to the sham surgery group. Immunofluorescence staining of isolectin-B4 (IB4) and TREK were performed. Electrophysiological recordings of single channel currents were analyzed to obtain the information about the channel. Interactions with known TREK activators were tested to confirm the expression. While both TREK-1 and TREK-2 mRNA were significantly overexpressed in DRG of CCI mice, only TREK-1 showed significant increase (~9 fold) in western blot analysis. The TREK-1-like channel recorded in DRG neurons of the CCI mouse showed similar current-voltage relationship and conductance to TREK-1. It was easily activated by low pH solution (pH 6.3), negative pressure, and riluzole. Immunofluorescence images showed the expression of TREK-1 was stronger compared to TREK-2 on IB4 positive neurons. These results suggest that modulation of the TREK-1 channel may have beneficial analgesic effects in neuropathic pain patients.

Effect of Various Divalent Ions on the Calcium Current of Adrenal Medullary Chromaffin Cells in the Rat

  • Kim, Jun;Leem, Chae-Hun;Kim, Sang-Jeong
    • The Korean Journal of Physiology
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    • v.26 no.2
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    • pp.113-122
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    • 1992
  • It is well known that chromaffin cells of adrenal medulla secrete catecholamine in response to sympathetic nerve activation and the influx of $Ca^{2+}$ through the voltage dependent $Ca^{2+}$ channels (VDCC) in the cell membrane do a major role in this secretory process. In this study, we explored the effect of divalent cations on VDCC of rat chromaffin cells. Rat (Sprague-Dawley rat, 150-250 gm) chromaffin cells were isolated and cultured. Standard giga seal, whole cell recording techniques were employed to study $Ca^{2+}$ current with external and internal solutions that could effectively isolate VDCC currents $(NMG\;in\;external\;and\;TEA\;and\;Cs^{2+}\;in\;internal\;solution)$. The voltage dependence and the inactivation time course of VDCC in our cells were identical to those of bovine chromaffin cells. A persistent inward current was first activated by depolarizing step pulse from the holding potential (H.P.) of -80 mV to -40 mV, increased to maximum amplitude at around +10 mV, and became smaller with progressively higher depolarizing pulses to reverse at around +60 mV. The inactivation time constant $(\tau)$, fitted from the long duration test potential (2 sec) was $1295.2{\pm}126.8$ msec $(n=20,\;1\;day\;of\;culture,\;mean\;{\pm}S.E.M.)$ and the kinetic parameters were not altered along the culture duration. Nicardipine $(10\;{\mu}M)$ blocked the current almost completely. Among treated divalent cations such as $Cd^{2+},\;Co^{2+},\;Ni^{2+},\;Zn^{2+}\;and\;,Mn^{2+},\;Cd^{2+}$ was the most potent blocker on VDCC. When the depolarizing step pulse from -80 mV to 10 mV was applied, the equilibrium dissociation constant $(K_d)$ of $Cd^{2+}\;was\;39\;{\mu}M,\;K_d\;of\;Co^{2+}\;was\;100\;{\mu}M\;and\;K_d\;of\;Ni^{2+}];was];780{\mu}M.$ The principal findings of this study are as follows. First, the majority of $Ca^{2+}$ channels in rat chromaffin cells are well classified to L-type $Ca^{2+}$ channel in the view of kinetics and pharmacology. Second, all divalent cations tested could block the $Ca^{2+}$ current and the most potent blocker among the tested was $Cd^{2+}$.

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Sex Differences in Autism-Like Behavioral Phenotypes and Postsynaptic Receptors Expression in the Prefrontal Cortex of TERT Transgenic Mice

  • Kim, Ki Chan;Cho, Kyu Suk;Yang, Sung Min;Gonzales, Edson Luck;Valencia, Schley;Eun, Pyeong Hwa;Choi, Chang Soon;Mabunga, Darine Froy;Kim, Ji-Woon;Noh, Judy Kyoungju;Kim, Hee Jin;Jeon, Se Jin;Han, Seol-Heui;Bahn, Geon Ho;Shin, Chan Young
    • Biomolecules & Therapeutics
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    • v.25 no.4
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    • pp.374-382
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    • 2017
  • Autism spectrum disorder (ASD) remains unexplained and untreated despite the high attention of research in recent years. Aside from its various characteristics is the baffling male preponderance over the female population. Using a validated animal model of ASD which is the telomerase reverse transcriptase overexpressing mice (TERT-tg), we conducted ASD-related behavioral assessments and protein expression experiments to mark the difference between male and females of this animal model. After statistically analyzing the results, we found significant effects of TERT overexpression in sociability, social novelty preference, anxiety, nest building, and electroseizure threshold in the males but not their female littermates. Along these differences are the male-specific increased expressions of postsynaptic proteins which are the NMDA and AMPA receptors in the prefrontal cortex. The vGluT1 presynaptic proteins, but not GAD, were upregulated in both sexes of TERT-tg mice, although it is more significantly pronounced in the male group. Here, we confirmed that the behavioral effect of TERT overexpression in mice was male-specific, suggesting that the aberration of this gene and its downstream pathways preferentially affect the functional development of the male brain, consistent with the male preponderance in ASD.

Anti-Proliferation Effects and Molecular Mechanisms of Action of Tetramethypyrazine on Human SGC-7901 Gastric Carcinoma Cells

  • Ji, Ai-Jun;Liu, Sheng-Lin;Ju, Wen-Zheng;Huang, Xin-En
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.8
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    • pp.3581-3586
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    • 2014
  • Aim: To investigate the effects of tetramethypyrazine (TMP) on proliferation and apoptosis of the human gastric carcinoma cell line 7901 and its possible mechanism of action. Methods: The viability of TMP-treated 7901 cells was measured with a 3-(4, 5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MTT) and cell apoptosis was analyzed by flow cytometry. The distribution of cells in different phases of cell cycle after exposure of TMPs was analyzed with flow cytometry. To investigate the molecular mechanisms of TMP-mediated apoptosis, the expression of NF-${\kappa}Bp65$, cyclinD1 and p16 in SGC-7901 cells was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting. Results: TMP inhibited the proliferation of human gastric carcinoma cell line 7901 in dose and time dependent manners. Cell growth was suppressed by TMP at different concentrations (0.25, 0.5, 1.0, 2.0 mg/ml), the inhibition rate is 0.46%, 4.36%, 14.8%, 76.1% (48h) and 15.5%, 18.5%, 41.2%, 89.8% (72h) respectively. When the concentration of TMPs was 2.0mg/ml, G1-phase arrest in the SGC-7901 cells was significant based on the data for cell cycle distribution. RT-PCR demonstrated that NF-${\kappa}Bp65$ and cyclin D1 mRNA expression was significantly down-regulated in 7901 cells treated with 2.0 mg/ml TMP for 72h (p<0.05), while the p16 mRNA level was up-regulated (p<0.05). The protein expression of NF-${\kappa}Bp65$ and cyclin D1 decreased gradually with the increase in TMP concentration, compared with control cells (p<0.05), while expression of protein p16 was up-regulated (p<0.01). Conclusion: TMP exhibits significant anti-proliferative and pro-apoptotic effects on the human gastric carcinoma cell line SGC-7901. NF-${\kappa}Bp65$, cyclinD1 and p16 may also play important roles in the regulation mechanisms.

Induction of DNA Damage in L5178Y Cells Treated with Gold Nanoparticle

  • Kang, Jin-Seok;Yum, Young-Na;Kim, Joo-Hwan;Song, Hyun-A;Jeong, Jin-Young;Lim, Yong-Taik;Chung, Bong-Hyun;Park, Sue-Nie
    • Biomolecules & Therapeutics
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    • v.17 no.1
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    • pp.92-97
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    • 2009
  • As nanomaterials might enter into cells and have high reactivity with intracellular structures, it is necessary to assay possible genotoxic risk of them. One of these approaches, we investigated possible genotoxic potential of gold nanoparticle (AuNP) using L5178Y cells. Four different sizes of AuNP (4, 15, 100 or 200 nm) were synthesized and the sizes and structures of AuNP were analyzed using transmission electron microscopy (TEM), scanning electron microscopy (SEM) and stability was analyzed by a UV/Vis. Spectrophotometer. Cytotoxicity was assessed by direct cell counting, and cellular location was detected by dark field microscope at 6, 24 and 48 h after treatment of AuNP. Comet assay was conducted to examine DNA damage and tumor necrosis factor (TNF)-${\alpha}$ mRNA level was assay by real-time reverse transcription polymerase chain reaction. Synthetic AuNP (4, 50, 100 and 200 nm size) had constant characteristics and stability confirmed by TEM, SEM and spectrophotometer for 10 days, respectively. Dark field microscope revealed the location of AuNP in the cytoplasm at 6, 24 and 48 h. Treatment of 4 nm AuNP induced dose and time dependent cytotoxicity, while other sizes of AuNP did not. However, Comet assay represented that treatment of 100 nm and 200 nm AuNP significantly increased DNA damage compared to vehicle control (p <0.01). Treatment of 100 nm and 200 nm AuNP significantly increased TNF-${\alpha}$ mRNA expression compared to vehicle control (p<0.05, p<0.01, respectively). Taken together, AuNP induced DNA damage in L5178Y cell, associated with induction of oxidative stress.

The Antiapoptic Effects of Hominis Placenta Extract

  • Seo, Jung-Chul;Chung, Joo-Ho;Ahn, Byoung-Choul
    • Journal of Pharmacopuncture
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    • v.4 no.1
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    • pp.123-124
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    • 2001
  • Purpose. Free radicals are implicated in the pathophysiology of aging, ischemic injury and neurodegenerative disorders. To deform]no whether Hominis Placenta extract prevents $H_2O_2$-induced apoptosis, we have performed morphological and biochemical analyses for the detection of apoptotic phenomena in the pineal tumor cell line $PGT-{\beta}$ We have also peformed cytochemical and immunocytochemical analyses for the detection of changes in nitric oxide synthase (NOS) activity and estimated the expression . of apoptotic genes using reverse transcription-polymerase chain reaction (RT-PCR) Methods. $PGT-{\beta}\;cells$ were pretreated with Hominis Placenta extracts $(0,\;10^{-2}\;{\mu}g/ml)$ for 2 hours and then exposed to $H_2O_2\;(0,\;50\;{\mu}M)$ for 3 hours. Appearance of apoptotic characteristics were monitored using 4, 6-diamidino-2-phenylindole dihydrochloride (DAPI) staining assay, terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay and flow cytometric analysis. NOS activity was measured by NADPH-diaphorase cytochemistry. Expression of inducible NOS (iNOS) and nuclear factor kappa B (NF k B) was assessed via immunocytochemistry. The expression of apoptotic genes was examined by RT-PCR. Results. After 3 flours of exposure to $H_2O_2$, it was shown that $PGT-{\beta}\;cells$ treated with $H_2O_2(50\;{\mu}M)$ exhibit classical apoptotic features and increases in NOS activity and caspase-3 expression. Treatment with Hominis Placenta extract resulted in a reduced occurrence of apoptotic features. DAPI staining, TUNEL and flow cytometric assays revealed decreases in the occurrence of nuclear fragmentation and in the sub-Gl fraction in the $PGT-{\beta}\;cells$ treated with Hominis Placenta extract. Cells treated with Hominis Placenta extract also showed lower activity of NADPH-diaphorase and immunoreactivities of both iNOS and NF k B than those of $H_2O_2$-treated cells which were not treated with Hominis Placenta extract. By RT-PCR, it was shown that the level of caspase-3 mRNA was derreased In the cells treated with Hominis Placenta . extract. Conclusions. This study shows that Hominis Placenta extract prevents $H_2O_2$-induced apoptosis in $PGT-{\beta}\;cells$; inhibitions of iNOS and caspnse-3 are possible mechanisms of the protection against apoptosis.