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THE POTENTIAL EFFECT OF RED DRAGON FRUIT (Hylocereus polyrhizus) PEEL ETHANOL EXTRACT ON ENDOMETRIOSIS PROGRESSIVITY IN ENDOMETRIOSIS MICE

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Anindya Hapsari at State University of Malang
Anindya Hapsari
Yanuar Eka Pujiastutik
Yanuar Eka Pujiastutik
Yanuar Eka Pujiastutik
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Abstract and Figures

The aim of this study was to know the effect of red dragon fruit (Hylocereus polyrhizus) peel ethanol extract at dose of 0.25, 0.5, and 1 mg/gbw on endometriosis progressivity, signed by granuloma, on mouse model of endometriosis. Twenty five female mice were used as samples anddivided into 5 groups: 1 positive control, 1 negative control, and 3 treatment groups. Positive control and treatment groups were induced as modelof endometriosis for 14 days. The next 14 days, placebo was given to both control groups, while red dragon fruit peel ethanol extract at dose of0.25, 0.5, and 1 mg/g bw were given to mice in treatment groups as much as 0.2 mL/25 g bw/day orally. Endometriotic lesion was examined.Result showed that there were significantly differences on granuloma among control groups and treatment groups. The conclusion was reddragon fruit peel ethanol extract could inhibit endometriosis progressivity, signed by granuloma, on mouse model of endometriosis.
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Jurnal Kedokteran Hewan June 2018, 12(2):53-56
P-ISSN : 1978-225X; E-ISSN : 2502-5600 DOI: https://doi.org/10.21157/ j.ked.hewan.v12i2.10497
53
THE POTENTIAL EFFECT OF RED DRAGON FRUIT (Hylocereus
polyrhizus) PEEL ETHANOL EXTRACT ON ENDOMETRIOSIS
PROGRESSIVITY IN ENDOMETRIOSIS MICE
Anindya Hapsari1* and Yanuar Eka Pujiastutik2
1Department of Public Health, Sport Science Faculty, Universitas Negeri Malang, Malang, East Java, Indonesia
2Department of Nursing, Faculty of Health Sciences, Institut Ilmu Kesehatan Bhakti Wiyata, Kediri, East Java, Indonesia
*Corresponding author: anindya.hapsari.fik@um.ac.id
ABSTRACT
The aim of this study was to know the effect of red dragon fruit (Hylocereus polyrhizus) peel ethanol extract at dose of 0.25, 0.5, and 1 mg/g
bw on endometriosis progressivity, signed by granuloma, on mouse model of endometriosis. Twenty five female mice were used as samples and
divided into 5 groups: 1 positive control, 1 negative control, and 3 treatment groups. Positive control and treatment groups were induced as model
of endometriosis for 14 days. The next 14 days, placebo was given to both control groups, while red dragon fruit peel ethanol extract at dose of
0.25, 0.5, and 1 mg/g bw were given to mice in treatment groups as much as 0.2 mL/25 g bw/day orally. Endometriotic lesion was examined.
Result showed that there were significantly differences on granuloma among control groups and treatment groups. The conclusion was red
dragon fruit peel ethanol extract could inhibit endometriosis progressivity, signed by granuloma, on mouse model of endometriosis.
____________________________________________________________________________________________________________________
Key words: endometriosis progressivity, granuloma, red dragon fruit peel ethanol extract
ABSTRAK
Penelitian ini bertujuan mempelajari pengaruh dari ekstrak etanol kulit buah naga merah (Hylocereus polyrhizus) dosis 0,25; 0,5; dan 1
mg/g bb terhadap progresivitas endometriosis yang ditandai dengan granuloma pada hewan coba mencit model endometriosis. Sampel
penelitian adalah 25 ekor mencit betina, yang dikelompokkan dalam 5 kelompok: 1 kelompok kontrol positif, 1 kelompok kontrol negatif, dan 3
kelompok perlakuan. Kelompok kontrol positif dan kelompok perlakuan dijadikan mencit model endometriosis selama 14 hari. Selanjutnya,
selama 14 hari berikutnya, kelompok kontrol negatif dan kelompok kontrol positif diberi plasebo, sedangkan kelompok perlakuan diterapi ekstrak
etanol kulit buah naga merah dosis 0,25; 0,5; dan 1 mg/g bb mencit sebanyak 0,2 ml/25 g bb/hari. Lesi endometriosis kemudian diperiksa. Hasil
penelitian menunjukkan terdapat perbedaan secara bermakna pada granuloma antara kelompok kontrol dan kelompok perlakuan. Kesimpulan
penelitian ini adalah ekstrak etanol kulit buah naga merah mampu menghambat progresivitas endometriosis, yang ditandai dengan granuloma
pada hewan coba mencit model endometriosis.
____________________________________________________________________________________________________________________
Kata kunci: progresivitas endometriosis, granuloma, ekstrak etanol kulit buah naga merah
INTRODUCTION
Infertility is the inability of a sexually active, non-
contraception couple to achieve pregnancy in one year.
Infertility is a disease of the reproductive system
defined by the failure to achieve a clinical pregnancy
after 12 months or more of regular unprotected sexual
intercourse (Schmidt, 2006). The prevalence of
infertility in whole world is increasing, reaching 10-
15% among all reproductive-aged couples (Deka and
Sarma, 2010). Infertility can be caused by many
factors; one of them is endometriosis (Hendarto, 2015).
Endometriosis is the presence of endometriosis-like
tissue outside the uterus, which induces a chronic
inflammatory reaction (ESHRE, 2013). This chronic
inflammatory process make endometriosis as a
progressive disease that can destroy structures at
peritoneum cavity so that reproductive system,
functions, and processes can be disturbed (Schenken
and Guzick, 1997). The progressivity of endometriosis
on peritoneum cavity can be seen by seeing peritoneum
level of destruction or abdominal adhesion. This
destruction is signed by inflammation, granulomas,
abscess/necrosis, and fibrosis (Klopfleisch, 2013).
Granuloma or granulomatous inflammation is a
distinctive form of chronic inflammation produced in
response to various infectious, autoimmune, toxic,
allergic, and neoplastic conditions. Granuloma is
defined by the presence of mononuclear leucocytes,
particularly macrophages that respond to various
chemical mediators of cell injury. Granuloma can
occurs in all age groups and within all tissue sites (Shah
et al., 2017).
To prevent endometriosis progressivity, there are 2
common managements that can be done, empirical
treatments and surgery. However, the recurrence rate
after treatment is still high, reaching about 35% in mild
endometriosis and 74% in severe endometriosis
(Speroff and Fritz, 2005). The high recurrence rate due
to endometriosis is a progressive disease that needed
long-time treatment (Annas et al., 2014).
As an alternative therapy to overcome chronic
inflammation condition, endometriosis patients may
consume traditional drugs that have anti-inflammatory
effects. One of plants that has been known for its anti-
inflammatory effect and was able to inhibit carcinoma
mammae cells (MCF-7) in vitro is red dragon fruit
(Hylocereus polyrhizus) (Sarasmita and Laksmiani,
2015). Red dragon fruit is a plant that is included in
Cactaceae family dan Hylocereanea subfamily
(Wybraniec et al., 2007; Nurliyana et al., 2010).
Ethanolic extract of red dragon fruit peel contains
betalain that is able to inhibit transcription factor NF-
κB so that inflammatory genes expression, such as
TNF-α and IL-1β, will not be released (Sarasmita and
Laksmiani, 2015).
Amindya Hapsari and Yanuar Eka Pujiastutik
54
Recently, the information regarding the potential
effect of ethanolic extract of red dragon fruit peel on
endometriosis progressivity is not available. Therefore,
this study was conducted to know the potential effect of
ethanolic extract of red dragon fruit peel at dose of
0.25; 0.5; and 1 mg/g bw to endometriosis
progressivity, signed by granuloma, on mouse model of
endometriosis.
MATERIALS AND METHODS
This study has been received approval ethical
clearance letter of animal subjects from Faculty of
Veterinary Medicine, Universitas Airlangga with
number 710-KE. This study was a laboratory
experimental research. Twenty five female mice (Mus
musculus), aged 2-3 months and weighed 20-25 g, were
used as samples.
Female mice divided into 5 groups after adaptation
for a week. These groups consist of positive control
group (K1), negative control group (K2), treatment
group with ethanolic extract of red dragon fruit peel at
dose of 0,25 mg/g bw/day (K3), treatment group with
ethanolic extract of red dragon fruit peel at dose of 0.5
mg/g bw/day (K4), and treatment group with ethanolic
extract of red dragon fruit peel at dose of 1 mg/g
bw/day (K5). The mice in positive control and
treatment groups were induced endometriosis by this
following steps: 1) injection of cyclosporin A (0.2
mL/mice) intramuscularly on day one to make mice in
immunodeficiency state; 2) injection of ethinyl
estradiol 20.000 IU (0.1 mL/mice) on day one and five;
3) injection of implant tissue (0.1 mL/mice) in the
peritoneal cavity on day one. Implant tissue was
derived from the myometrium and endometrium of
gynecologic benign tumor patients who underwent
surgery procedure and did not use hormonal
contraception at least for last 3 months before surgery.
The animal model was observed for 14 days to be the
mice model of endometriosis.
Starting from day 15, 0.5% Na-carboxymethyl
cellulose (Na-CMC) was given to both control groups
as placebo, while ethanolic extract of red dragon fruit
peel was given to 3 treatment groups (K3, K4, and K5)
at dose of 0.25, 0.5, and 1 mg/g bw/day, respectively.
These placebo and extract was administered orally (0.2
mL/25 g bw/day) for 14 days with an oral gavage.
At the end of experiment, mice were anesthetized
with ketamine and acepromazine, and then the
endometriosis lesions were collected. Formalin-fixed
and paraffin-embedded tissue sections from
endometriosis lesion were stained with hematoxillin
eosin (HE) to evaluate granulomas. Granulomas from 2
endometriosis lesions then were counted and evaluated
based on Klopfleisch scoring. The score criteria are:
0= no granuloma mass, 2= any granuloma mass and/or
11-50 macrophage infiltration observed, 4= granuloma
mass with abscess observed, 6= granuloma mass with
abscess and muscle necrosis observed and
8= granuloma mass with abscess, muscle necrosis, and
fibrosis observed (Klopfleisch, 2013).
Shapiro-Wilk test was used to know the normality
of data and Levene test was used to know the
homogeneity of data. If distribution and homogeneity
of data were normal (P>0.05), one way analysis of
variance (ANOVA) test was conducted, followed with
posthoc Bonferroni. But, if the data distribution or
homogeneity was not normal, Kruskall-Wallis test
followed with Mann-Whitney test, were conducted.
Table 1
. Granulomas on mice model endometriosis among control group and treatment groups using Mann-Whitney test
K1 K2 K3 K4 K5
K1 - 0,008* 0,032* 0,310 1,000
K2 0,008* - 0,016* 0,008* 0,008*
K3 0,032* 0,016* - 0,151 0,032*
K4 0,310 0,008* 0,151 - 0,310
K5 1,000 0,008* 0,032* 0,310 -
*P= 0.001. K1= Positive control group, K2= Negative control group, K3= Treatment group with ethanolic extract of red dragon fruit peel at
dose of 0,25 mg/g bw/day, K4= Treatment group with ethanolic extract of red dragon fruit peel at dose of 0.5 mg/g bw/day, K5= Treatment
group with ethanolic extract of red dragon fruit peel at dose of 1 mg/g bw/day
Figure 1. Chronic inflammation signed by fibrous formation and granuloma mass on peritoneum cavity of endometriosis mice.
A= Fibrous formation (arrow) among muscles, B= Granuloma mass (arrow) and massive infiltration of inflammatory cells on muscles (HE,
400x)
Amindya Hapsari and Yanuar Eka Pujiastutik
55
RESULTS AND DISCUSSION
Result showed that there were chronic inflammation
signed by fibrous formation and granuloma mass on
peritoneum cavity of endometriosis mice (Figure 1).
The granuloma mass was more pronounced in positive
control group (K2) than other groups (Figure 2). There
were mean differences among K1, K2, K3, K4, and K5
groups, as seen on Table 1. The endometriosis
progressivity, signed by granulomas formation, was
decreased on treatment groups. This reduction was
linear with the increasing dose of ethanolic extract of
red dragon fruit peel.
Shapiro-Wilk test showed that data in group 1, 2, 4,
and 5 were not normally distributed (P<0.05). Levene
test also showed that data were not homogenous,
therefore one way ANOVA test could not be
conducted. Statistical analysis was then conducted by
Kruskall-Wallis test with P= 0.001, that means there
was at least 1 significantly differences between 2
groups. Mann-Whitney test showed that there were
significantly differences between: K1 and K2, K1 and
K3, K2 and K3, K2 and K4, K2 and K5, and K3 and
K5 (Table 1).
The result of this study showed that ethanolic
extract of red dragon fruit peel was capable of reducing
endometriosis progressivity, signed by less granulomas
formation, on mice model endometriosis. Ethanolic
extract of red dragon fruit peel at dose of 0.5 and 1
mg/g bw had no significant differences with negative
control group, so it could be said that ethanolic extract
of red dragon fruit peel on dose 0.5 and 1 mg/g bw
could reduce granulomas on endometriosis mice
reaching levels to those comparable to healthy mice.
Granuloma is defined by the presence of
mononuclear leucocytes, specifically macrophages
Figure 2. The granuloma mass (arrow) on peritoneum cavity of endometriosis mice in different groups. K1= Positive control group,
K= Negative control group, K3= Treatment group with ethanolic extract of red dragon fruit peel at dose of 0,25 mg/g bw/day, K4= Treatment
group with ethanolic extract of red dragon fruit peel at dose of 0.5 mg/g bw/day, K5= Treatment group with ethanolic extract of red dragon fruit
peel of 1 mg/g bw/day (HE, 400x)
Amindya Hapsari and Yanuar Eka Pujiastutik
56
(Shah et al., 2017). On endometriosis, peritoneal
macrophages are first cells that are activated. These
macrophages play role as secretors for pro-
inflammatory cytokines which create ideal micro
environment for endometriosis cells to progress
(Sourial et al., 2014). One of these pro-inflammatory
cytokines is tumor necrosis factor-α. Tumor necrosis
factor-α plays its role through NF-κB pathway. It can
stimulate endometriosis cells to express monocyte
chemotactic protein 1 (MCP-1) which roles as chemo-
attractor to attract more macrophages to the lesions. So
we can find a large number of macrophages that form
granulomatous inflammation on endometriosis lesions
and peritoneal fluid (Grund et al., 2008; Gonzalez-
Ramos et al., 2012; Zheng et al., 2012).
Ethanolic extract of red dragon fruit peel were
given to mice model endometriosis to inhibit NF-κB
pathway which is activated by macrophage and
endometriosis cells when these cells bind to their
receptors (Martinez et al., 2014). By blocking NF-κB
pathway, it was supposed that the genes expression of
TNF-α and MCP-1 reduced, so that macrophage
migration to endometriosis lesion would also be
decreased and there would be less granuloma
formation.
CONCLUSION
Ethanolic extract of red dragon fruit peel could
inhibit endometriosis progressivity, signed by less
granuloma formation, on mouse model of
endometriosis.
ACKNOWLEDGEMENT
The authors wish to thank Djoko Legowo, DVM,
M.Sc for help with the interpretation of histology.
REFERENCES
Annas, J.Y., Hendarto, and H. Widjiati. 2014. Khasiat berbagai dosis
suplementasi kurkumin pada progresivitas endometriosis di
hewan coba mencit. Majalah Obstetri dan Ginekologi.
22(3):118-125.
Deka, P.K. and S. Sarma. 2010. Psychological aspects of infertility.
Br. J. Med. Pract. 3(3):a336.
ESHRE. European Society of Human Reproduction and Embriology.
2013. Management of Women with Endometriosis: Guideline
of the European Society of Human Reproduction and
Embriology. ESHRE Endometriosis Guideline Development
Group, Barcelona.
Gonzalez-Ramos, R., S. Defrere, and L. Devoto. 2012. Nuclear
factor-kappaB: A main regulator of inflammation and cell
survival in endometriosis pathophysiology. Fertil. Steril.
98(3):520-528.
Grund, E.M., D. Kagan, C.A. Tran, A. Zeitvogel, A. Starzinski-
Powit, S. Nataraja, and S.S. Palmer. 2008. Tumor necrosis
factor-α regulates i nflammatory and mesenchymal responses via
mitogen-activated protein kinase, p38, and nuclear factor-κb in
human endometriotic epithelial cells. Mol. Pharmacol.
73(5):1394-1404.
Hendarto, H. 2015. Endometriosis dari Aspek Teori Sampai
Penangangan Klinis. Airlangga University Press, Surabaya.
Klopfleisch, R. 2013. Multiparametric and semiquantitative scoring
systems for the evaluation of mouse model histopathology - a
systematic review. BMC Vet. Re. Doi.org/10.1186/1746-6148-
9-123.
Martinez, R.M., D.T. Longhi-Balbinot, A.C. Zarpelon, L. Staurengo-
Ferrari, M.M. Baracat, S.R. Georgetti, R.C. Sassonia, W.A.
Verri, and R. Casagrande. 2014. Anti-inflammatory activity of
betalain-rich dye of Beta vulgaris: Effect on edema, leucocyte
recruitment, superoxide anion, and cytokine production. Arch.
Pharm. Res. 38:494-504.
Nurliyana, S.Z., I.M.K. Suleiman, M.R. Aisyah, and K.R. Rahim.
2010. Antioxydant study of pulp and peels of dragon fruits: A
Comparative Study. Int. Food Res. 17:367-375.
Sarasmita, M.A. and N.P.L. Laksmiani. 2015. Uji sitotoksisitas
ekstrak etanol limah kulit buah naga merah (Hylocereus
polyrhizus) pada sel kanker payudara secara invitro dan in silico.
Jurnal Farmasi Udayana. 4(2):91-97.
Schenken, R.S. and D.S. Guzick. 1997. Revised endometriosis
classification american fertility society. Fertil. Steril. 67(5):815-
816.
Schmidt, L. 2006. Infertility and assisted reproduction in Denmark
epidemiology and psychosicial consequences. Dan. Med. Bull.
53(4):390-417.
Shah, K.K., B.S. Prit, and M.P. Alexander. 2017. Histopathologic
review of granulomatous inflammation. J. Clin. Tuberc. Other
Mycobac. Dis. 7:1-12.
Sourial, S., N. Tempest, and D.K. Hapangama. 2014. Theories on the
pathogenesis of endometriosis. Int. J. Reprod. Med.
Dx.doi.org/10.1155/2014/179515.
Speroff, L. and M.A. Fritz. 2005. Endometriosis. In Clinical
Gynecologic Endocrinology and Infertility. Speroff, L. and
M.A. Fritz (Eds.). 7th ed. Lippincott William & Wilkins,
Philadelphia.
Wybraniec, S., B. Nowak-Wydra, and K. Mitka. 2007. Minor
betalain in fruit of hylocereus species. J. Phytochem. 68:251-
259.
Zheng, Y., X. Liu, and S.W. Guo. 2012. Therapeutic potential of
andrographolide for treating endometriosis. Hum. Reprod.
27(5):1300-1313.
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Full-text available
  • Feb 2017
Granulomatous inflammation is a histologic pattern of tissue reaction which appears following cell injury. Granulomatous inflammation is caused by a variety of conditions including infection, autoimmune, toxic, allergic, drug, and neoplastic conditions. The tissue reaction pattern narrows the pathologic and clinical differential diagnosis and subsequent clinical management. Common reaction patterns include necrotizing granulomas, non necrotizing granulomas, suppurative granulomas, diffuse granulomatous inflammation, and foreign body giant cell reaction. Prototypical examples of necrotizing granulomas are seen with mycobacterial infections and non-necrotizing granulomas with sarcoidosis. However, broad differential diagnoses exist within each category. Using a pattern based algorithmic approach, identification of the etiology becomes apparent when taken with clinical context. The pulmonary system is one of the most commonly affected sites to encounter granulomatous inflammation. Infectious causes of granuloma are most prevalent with mycobacteria and dimorphic fungi leading the differential diagnoses. Unlike the lung, skin can be affected by several routes, including direct inoculation, endogenous sources, and hematogenous spread. This broad basis of involvement introduces a variety of infectious agents, which can present as necrotizing or non-necrotizing granulomatous inflammation. Non-infectious etiologies require a thorough clinicopathologic review to narrow the scope of the pathogenesis which include: foreign body reaction, autoimmune, neoplastic, and drug related etiologies. Granulomatous inflammation of the kidney, often referred to as granulomatous interstitial nephritis (GIN) is unlike organ systems such as the skin or lungs. The differential diagnosis of GIN is more frequently due to drugs and sarcoidosis as compared to infections (fungal and mycobacterial). Herein we discuss the pathogenesis and histologic patterns seen in a variety of organ systems and clinical conditions.
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Antioxidant study of pulps and peels of dragon fruits: A comparative study
Article
Full-text available
  • Jan 2010
The aim of this study is to compare antioxidant level and activities (i.e. primary and secondary) in pulps and peels of two species of dragon fruits, Hylocereus undatus (white dragon fruit) and Hylocereus polyrhizus (red dragon fruit). Total phenolic content (TPC) assay demonstrated that peels of both Hylocereus species contained higher phenolic content than the pulps. The phenolic content in peels of H. undatus was higher than H. polyrhizus, but the phenolic content in pulps of H. undatus was much lower than H. polyrhizus. 2, 2, diphenyl-1-picrylhydrazyl (DPPH) assay showed that radical scavenging activities of peels for both species were higher than the pulps. For ferrous ion chelating (FIC) assay, peels and pulps of both Hylocereus species showed moderate metal ion chelating effect as compared to EDTA. Overall, the results suggested that the TPC showed good relationship with the primary antioxidant activities for general comparison between the peels and the pulps.
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Theories on the Pathogenesis of Endometriosis
Article
Full-text available
  • Feb 2014
Endometriosis is a common, chronic inflammatory disease defined by the presence of extrauterine endometrial tissue. The aetiology of endometriosis is complex and multifactorial, where several not fully confirmed theories describe its pathogenesis. This review examines existing theories on the initiation and propagation of different types of endometriotic lesions, as well as critically appraises the myriad of biologically relevant evidence that support or oppose each of the proposed theories. The current literature suggests that stem cells, dysfunctional immune response, genetic predisposition, and aberrant peritoneal environment may all be involved in the establishment and propagation of endometriotic lesions. An orchestrated scientific and clinical effort is needed to consider all factors involved in the pathogenesis of this multifaceted disease and to propose novel therapeutic targets to reach effective treatments for this distressing condition.
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Nuclear factor-kappaB: A main regulator of inflammation and cell survival in endometriosis pathophysiology
Article
Full-text available
  • Jul 2012
To update, analyze, and summarize the literature concerning nuclear factor-kappaB (NF-κB) participation in endometriosis pathophysiology. Review. Nuclear factor-kappaB is physiologically activated in the human endometrium, showing variable activity. A cyclic p65-DNA binding pattern was shown in the endometrium of healthy women. This cyclic pattern was altered in the endometrium of patients with endometriosis. Nuclear factor-kappaB is basally activated in peritoneal endometriotic lesions, showing higher p65 activity in red endometriotic lesions than in black lesions. In vivo and in vitro studies show up-regulation of inflammation and cell proliferation and down-regulation of apoptosis by NF-κB activity. Iron overload has been shown in the pelvic cavity of endometriosis patients, and iron overload and oxidative stress activate NF-κB in macrophages, which have been shown to participate in the endometriosis-associated inflammatory reaction. Nuclear factor-kappaB activation dysregulation in the endometrium of endometriosis patients may explain some endometrial biological alterations associated with endometriosis. The scientific evidence strongly suggests that NF-κB activity in endometriotic cells stimulates inflammation and cell proliferation and inhibits apoptosis, favoring the development and maintenance of endometriosis. Iron overload in the pelvic cavity of endometriosis patients could be a main factor enhancing oxidative stress and activating NF-κB in a chronic manner, contributing to endometriosis establishment and growth.
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Therapeutic potential of andrographolide for treating endometriosis
Article
Full-text available
  • Mar 2012
  • HUM REPROD
Mounting evidence shows that nuclear factor-κB (NF-κB) plays an important role in endometriosis. We therefore evaluated the therapeutic potential of andrographolide, an NF-κB inhibitor. Primary cell cultures were performed using ectopic endometrial tissue specimens and their homologous eutopic endometrial specimens from 16 women with endometriosis, as well as control samples from 4 women without endometriosis. Andrographolide was evaluated for an effect on cell proliferation and cell cycle, DNA-binding activity of NF-κB and expression of cyclooxygenase-2 (COX-2) and tissue factor (TF). In a rat model of endometriosis, andrographolide treatment was evaluated for an effect on lesion size, hotplate response latency and expression of phosphorylated p50 and p65, COX-2 and nerve growth factor (NGF) in ectopic endometrium. Andrographolide dose dependently suppressed proliferation and cell cycle progression, attenuated DNA-binding activity of NF-κB in endometriotic stromal cells and inhibited COX-2 and TF expression. In the rat experiment, induced endometriosis resulted in reduced response latency. Andrographolide treatment significantly reduced lesion size in a dose-dependent manner and significantly increased response latency. Andrographolide treatment also significantly reduced immunoreactivity of COX-2, phosphorylated p50 and p65, and NGF in ectopic endometrium. Treatment with andrographolide significantly suppresses the growth of ectopic endometrium in vitro and in vivo, and results in a significant improvement in generalized hyperalgesia in rats with induced endometriosis. Therefore, andrographolide may be cytoreductive and may relieve pain symptoms in women with endometriosis. With excellent safety and cost profiles, andrographolide could be a promising therapeutic agent for endometriosis.
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Infertility and assisted reproduction in Denmark. Epidemiology and psychosocial consequences
Article
Full-text available
  • Dec 2006
  • Dan Med Bull
Clinically a couple is considered to be infertile after at least one year without contraception and without pregnancy. There was scant knowledge about the prevalences of infertility, involuntary childlessness and the seeking of fertility treatment and only few longitudinal studies about the psychosocial consequences of infertility and its treatment. This thesis is about the epidemiological aspects of infertility; the conceptualization and measurement of important psychosocial aspects of infertility; and a medical sociological analysis of the associations between these psychosocial variables among Danish women and men in fertility treatment. The thesis is based on nine papers. The three main purposes were: (i) to review critically, population based studies of infertility and medical care seeking in industrialised countries. Further, to examine these prevalences and subsequent motherhood among women in former assisted reproduction in a Danish population. (ii) To develop measures of psychosocial consequences of infertility: fertility problem stress, marital benefit, communication, coping strategies, attitudes to and evaluation of fertility treatment. (iii) To examine these phenomena and to analyse their interrelations among Danish women and men in fertility treatment. The thesis is based on four empirical studies: (i) The Women and Health Survey, a cross-sectional population-based study among 15-44 year old women (n=907, 25-44 year old) in Copenhagen County, 1989. (ii) The Psychosocial Infertility Interview Study, a qualitative interview study among 16 couples (n=2 participants) infertility treatment at The Fertility Clinic, Herlev University Hospital,1992. (iii) The Infertility Cohort, a longitudinal cohort study consecutively including all couples (n=250 participants) beginning anew fertility treatment period at one of four public (Braedstrup, Herlev, Odense, Rigshospitalet) and one private fertility clinic (Trianglen),2000-2002. (iv) The Communication and Stress Management Training Programme, an intervention study among couples(n=74 participants) in fertility treatment at The Fertility Clinic, The Juliane Marie Centre, Rigshospitalet, 2001-2003. Included is also a literature review of population-based infertility studies from industrialised countries. Data from (iii) and (iv) are studies from The Copenhagen Multi-centre Psychosocial Infertility (COMPI) Research Programme (www.compipro.dk). Epidemiological and demographic studies investigating the prevalences of infertility differed in how they defined the numerator (the infertile participants) and the denominator (the population at risk). It was important to calculate reliable estimates of the infertility prevalence by including only women who had tried to have at least one child in the population at risk, as a notable proportion of women in the fertile ages had not (yet) attempted to become a mother. The lifetime prevalence of infertility in the representative population-based study was 26.4%. In the age group 35 to 44 years 5.8% were primarily involuntarily in fecund (involuntarily childless). Even in a country with access to fertility treatment in a public health-care system without self-payment lower education was a predictor of lower treatment seeking. In the cohort study (2000-2002)of couples starting a new period of assisted reproduction treatment 62.6% reported a treatment-related pregnancy at the one-year follow-up. In total 32.4% reported a treatment-related delivery. In total 24.2% reported a current continuing pregnancy and spontaneous pregnancies accounted for 2.7% of these. We developed measures of fertility problem stress, marital benefit(that infertility has brought the partners closer together and strengthened their marriage), partner communication, infertility related communication, coping strategies, attitudes to fertility treatment and evaluation of care. The medical sociological analyses showed that the variables of psychosocial consequences of infertility and treatment are interwoven with each others in a complex pattern, a pattern that both differed and was similar when comparing women and men. The infertility-related communication strategy (secrecy, formal, open-minded)identified in the qualitative interviews was later confirmed in the COMPI Infertility Cohort. Using the formal strategy and not talking about the emotional aspects of infertility and its treatment suggested high fertility problem stress. The coping strategies studied showed significant social differences and active-avoidance coping was a significant predictor of high fertility problem stress. A positive effect of infertility on the marriage, marital benefit was common. Men using the secrecy communication strategy had increased risk of low marital benefit. Difficult partner communication was a significant predictor of high fertility problem stress and among men, of low marital benefit. The intervention study showed that it was possible for the participants to change their communication with partner and other people close to them and that participants achieved an increased awareness of what, how much and when to discuss with others. High fertility problem stress and high marital benefit were associated with high importance ratings of patient-centred care and intentions to use professional psychosocial services. Among women, high fertility problem stress was a predictor of lower satisfaction ratings with fertility treatment. High marital benefit was a predictor of high satisfaction ratings of both medical and patient-centred care. In conclusion, infertility is a common experience among couples attempting to become parents. Assisted reproduction in the public health-care system in Denmark has high success rates, i.e. pregnancies,deliveries and high patient satisfaction. A large minority of people in fertility treatment experience high fertility problem stress,and some use communication and coping strategies that predicts high stress. Developing and evaluating different psychosocial interventions are necessary to offer the psychosocial support needed for this minority of fertility patients.
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Tumor Necrosis Factor- Regulates Inflammatory and Mesenchymal Responses via Mitogen-Activated Protein Kinase Kinase, p38, and Nuclear Factor B in Human Endometriotic Epithelial Cells
Article
Full-text available
  • May 2008
  • MOL PHARMACOL
Tumor necrosis factor (TNF)-alpha is central to the endometriotic disease process. TNF-alpha receptor signaling regulates epithelial cell secretion of inflammation and invasion mediators. Because epithelial cells are a disease-inducing component of the endometriotic lesion, we explored the response of 12Z immortalized human epithelial endometriotic cells to TNF-alpha. This report reveals the impact of disruption of established TNF-alpha-induced signaling cascades on the expression of biomarkers of inflammation and epithelial-mesenchymal transition (EMT) from endometriotic epithelial cells. Note that we show the molecular potential of soluble TNF-R1 [TNF binding protein (TBP)] and a panel of small molecule kinase inhibitors to block endometriotic gene expression directly. The TNF-alpha receptor is demonstrated to signal through IkappaB kinase complex (IKK) 2 > IkappaB > nuclear factor kappaB, extracellular signal-regulated kinase > mitogen-activated protein kinase kinase (MEK), p38, and phosphatidylinositol 3-kinase (PI3K) > Akt1/2. TNF-alpha induces the expression of transcripts for inflammatory mediators interleukin (IL)-6, IL-8, regulated on activation normal T cell expressed and secreted, TNF-alpha, granulocyte macrophage-colony-stimulating factor (GM-CSF), and monocyte chemoattractant protein (MCP)-1 and also invasion mediators matrix metalloproteinase (MMP)-7, MMP-9, and intracellular adhesion molecule-1. Indeed, TBP inhibits the TNF-alpha-induced expression of all the above endometriotic genes in 12Z endometriotic epithelial cells. The secretion of IL-6, IL-8, GMCSF, and MCP-1 by TNF-alpha is blocked by TBP. Interestingly, MEK, p38, and IKK inhibitors block TNF-alpha-induced IL-8, IL-6, and GM-CSF secretion and 12z invasion, whereas the PI3K inhibitors do not. The only inhibitor to block MCP-1 expression is the p38 inhibitor. Last, TBP, MEK inhibitor, or p38 inhibitor also block cell surface expression of N-cadherin, a marker of mesenchymal cells. Taken together, these results demonstrate that interruption of TNF-alpha-induced signaling pathways in human endometriotic epithelial cells results in decreased expression and secretion of biomarkers for inflammation, EMT, and disease progression.
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Anti-inflammatory activity of betalain-rich dye of Beta vulgaris: Effect on edema, leukocyte recruitment, superoxide anion and cytokine production
Article
  • Aug 2014
  • ARCH PHARM RES
We have recently developed betalain-rich beetroot (Beta vulgaris) dye (betalain) to be used in food products. Betalain (30-300 mg/kg) intraperitoneal (i.p.) treatment diminished carrageenan (100 µg/paw)-induced paw edema and neutrophil migration to the paw skin tissue. Betalain (100 mg/kg) treatment by subcutaneous or per oral routes also inhibited the carrageenan-induced paw edema. Importantly, the post-treatment with betalain (100 mg/kg, i.p.) significantly inhibited carrageenan- and complete Freund's adjuvant (10 µl/paw)-induced paw edema. Betalain (100 mg/kg) also reduced carrageenan (500 µg/cavity)-induced recruitment of total leukocytes, including mononuclear cells and neutrophils, as well as increasing vascular permeability in the peritoneal cavity. Furthermore, betalain significantly reduced carrageenan-induced superoxide anion, tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-1β levels in the peritoneal fluid, as well as augmenting IL-10 levels. Therefore, this compound presents prominent anti-inflammatory effect on carrageenan-induced paw edema and peritonitis by reducing the production of superoxide anion and the cytokines TNF-α and IL-1β, in addition to increasing IL-10 levels. These results suggest that betalain shows therapeutic potential that could be utilized in the treatment of inflammation-associated diseases.
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Minor betalains in fruits of Hylocereus species
Article
  • Feb 2007
  • PHYTOCHEMISTRY
Betacyanins in peel and flesh of fruits of different Hylocereus species were identified by means of GC/MS, electrospray MS/MS, HPLC as well as (1)H and (13)C NMR techniques. As hitherto unknown pigments: betanidin 5-O-(2'-O-beta-D-apiofuranosyl)-beta-D-glucopyranoside, betanidin 5-O-(4'-O-malonyl)-beta-D-glucopyranoside and betanidin 5-O-[(5''-O-E-sinapoyl)-2'-O-beta-D-apiofuranosyl]-beta-D-glucopyranoside were elucidated. The sinapoyl moiety attachment position in the structure of betacyanins was established for the first time. The peel contained a more complex pattern of betacyanins with apiofuranosyl moiety. Other recently identified pigments were also present in the samples and their (1)H or (13)C NMR spectra were recorded. In the case of phyllocactin and its 4'-isomer the migration of the malonyl group was noticed.
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