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"ABSTRAKKanker kolorektal merupakan salah satu jenis kanker yang paling banyakmenyebabkan kematian di dunia dan berada di peringkat tiga terbanyak setelahkanker paru dan kanker payudara. Inflamasi merupakan predisposisi kankerkolorektal melalui berbagai mediator proinflamasi dan antiinflamasi yang dihasilkansel-sel inflamasi. Pengobatan kanker kolorektal secara konvensional dengan terapibedah, kemoterapi maupun radioterapi belum dapat memberikan hasil yangmemuaskan karena angka kekambuhan kanker yang tinggi dan terjadinya inflamasiakibat terapi. Annona muricata Linn. (AML), atau sirsak memiliki zat aktifasetogenin,yang selain bersifat anti-oksidan, antiinflamasi juga memiliki efeksitotoksik karena mampu menginduksi apoptosis dengan mengurangi kadar cAMPdan cGMP pada sel-sel kanker manusia. Dua puluh lima subyek penderita kankerkolorektal yang sudah direseksi dibagi menjadi dua kelompok dan mendapatkantambahan terapi berupa ekstrak etanol daun AML atau maltosa selama 8 minggu, dandilakukan pemeriksaan kadar TNF-α, IL-10, IFN-γ, COX-2 serta cleaved caspaseCK18 melalui serum subyek sebelum dan setelah terapi selesai dilakukan. Pemberianekstrak etanol AML tidak menimbulkan perubahan signifikan dari kelima parameterdibandingkan antara kelompok perlakuan dan kontrol. Terdapat korelasi bersifatpositif yang signifikan antara mediator proinflamasi TNF-α dan IL-10 setelahperlakuan yaitu 0,641 (p = 0,009) dan juga korelasi positif antara TNF-α dan ccCK18yaitu 0,817 (p = 0,002). Berdasarkan hasil di atas ekstrak etanol AML memiliki peranuntuk meregulasi homeostasis proinflamasi dan antiinflamasi serta berperan dalamproses apoptosis.

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ABSTRACTColorectal cancer is one type of cancer which causes the most deaths in the world andis the third highest after lung cancer and breast cancer. Inflammation is one ofcolorectal cancer predispotition, mediated by a variety of inflammatory cytokineproduced by inflammatory cells. Treatment of colorectal cancer include surgicaltherapy, chemotherapy or radiotherapy had not given a satisfactory result for the highrecurrence rate of cancer, even resulted inflammation as a side effect of therapy.Annona muricata Linn. (AML), or soursop has asetogenin as one of its activesubstances, which have antioxidant potency, anti-inflammatory and cytotoxic effectbecause it can induce apoptosis by reducing levels of cAMP and cGMP in humancancer cells. Twenty-five post-resection colorectal cancer patients divided into twogroups and get ethanol fraction of leaves of AML or maltose as an additional therapyfor 8 weeks. Levels of TNF-α, IL-10, IFN-γ, COX-2 and caspase cleaved CK18serum subjects before and after treatment was examined. Ethanol fraction of AMLdid not make a significant change from the five parameters which were comparedbetween treatment and kontrol groups. TNF-α and IL-10 serum after treatment had apositive correlation with R= 0,641 (p = 0.009). TNF-α and ccCK18 also had positivecorrelation with R = 0.817 (p = 0.002). Based on results the ethanol fraction of AMLplays a role to homeostasis of proinflammatory and antiinflammatory as well asapoptosis regulation."

"[ABSTRAKKanker payudara adalah penyakit multifaktor yang mengakibatkan insiden kematian wanita tertinggi di dunia. Pengobatan kanker payudara berupa pembedahan, radioterapi, dan kemoterapi memiliki efek samping sehingga perlu pengobatan alternatif, salah satunya menggunakan bahan herbal. Daun sirsak (Annona muricata Linn) dilaporkan memiliki efek antitumor dan sitotoksik, tetapi penelitian in vivo terhadap kanker payudara masih sedikit, dibutuhkan penelitian lanjut mengenai efektivitas dan jalur penghambatan daun sirsak terhadap berbagai kanker. Penelitian ini bertujuan untuk mengetahui daya hambat dan dosis efektif ekstrak metanol daun sirsak (Annona muricata Linn) terhadap pertumbuhan tumor payudara mencit C3H secara in vivo. Sebanyak 30 ekor mencit galur C3H yang ditransplan dengan tumor payudara dari mencit C3H donor bertumor, dibagi dalam 5 kelompok perlakuan, yaitu kontrol negatif hanya diberi pelarut CMC 0,5%, kontrol positif diberi doksorubisin, kelompok pemberian ekstrak daun sirsak dosis 15, 30, dan 45 mg/kg BB. Setiap mencit dicekok ekstrak daun sirsak 0,2 cc per hari selama 21 hari, sedangkan kelompok kontrol positif diberikan doksorubisin secara intra vena 0,03 μg/20g BB seminggu sekali selama 21 hari. Panjang dan lebar tumor diukur di awal dan seminggu sekali selama perlakuan untuk mendapatkan data volume tumor. Pada akhir penelitian mencit dinekropsi, tumor mencit ditimbang dan dilakukan pewarnaan AgNOR untuk diukur aktivitas proliferasi sel. Hasil uji Anova menunjukkan perbedaan yang bermakna (p=0,007) antar perlakuan terhadap volume tumor akhir dan terhadap aktivitas proliferasi (p=0,001). Uji Kruskal Wallis terhadap berat tumor menunjukkan tidak ada perbedaan yang bermakna antar perlakuan (p=0,03). Hasil uji korelasi Spearman secara bermakna (p=0,03) menunjukkan ada korelasi positif antara aktivitas proliferasi sel dengan pertumbuhan volume tumor dengan kekuatan korelasi yang lemah (r=0,39). Disimpulkan bahwa ekstrak metanol daun sirsak (Annona muricata Linn) dapat menghambat laju pertumbuhan volume tumor dan aktivitas proliferasi sel kanker payudara mencit C3H dan optimum penghambatan pada dosis 30 mg/kg

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ABSTRACTBB.;Breast cancer is a multifactor disease that has been a leading cause of woman?s mortality. Treatments for breast cancer such as surgery, radiotherapy, and chemotherapy have their own side effects, so that alternative treatments such as herbal medicine are needed. Soursop leaf (Annona muricata Linn) has been reported to have antitumor and cytotoxic effects, but only few conducted in vivo, an advanced research is needed to find the effectiveness and the inhibition pathway of the soursop leaf. The purpose of this research is to find out the inhibition capacity and the effective dose of soursop leaf methanol extract (Annona muricata Linn) against the development of C3H mice?s breast cancer in vivo. There were thirty mice of C3H strain which were transplanted with breast tumor and they were divided into five groups consisting of negative control group which was given only solvent CMC 0.5%, a positive control group which was given doxorubicin, a dose group of 15 mg/kg BB, a dose group of 30 mg/kg BB, and a dose group of 45 mg/kg BB. Each mouse was given 0,2 cc soursop leaf extract every day for 21 days while the positive control group was given doxorubicin 0,03 μg/20 gram BB once a week for 21 days intravenously. The length and the width of the tumor were measured at the beginning and also measured once a week during the experiment process to gain the data of the tumor volume. At the end of the research, the tumor of the mice was lifted and weighed and it was stained by AgNOR to measure the proliferation activity of the cell. The Anova result showed that there was a significant difference (p=0,007) between treatment against the development of tumor which was marked by the decrease of the tumor volume and proliferation activity (p=0,001). The Kruskal Wallis result showed that there was no significant difference (p<0,33) in the tumor weight. Spearman correlation study significantly (p=0,03) indicated that there was a positive correlation between the cell proliferation activity and the growth of the tumor but in a weak correlation (r=0,39). Therefore, it could be concluded that the methanol extract of soursop leaf (Annona muricata Linn) can inhibit the growth rate of tumor volume as well as the proliferation activity of the breast cancer cell of C3H mice and it worked optimally at 30 mg/kg BB dose.;Breast cancer is a multifactor disease that has been a leading cause of woman?s mortality. Treatments for breast cancer such as surgery, radiotherapy, and chemotherapy have their own side effects, so that alternative treatments such as herbal medicine are needed. Soursop leaf (Annona muricata Linn) has been reported to have antitumor and cytotoxic effects, but only few conducted in vivo, an advanced research is needed to find the effectiveness and the inhibition pathway of the soursop leaf. The purpose of this research is to find out the inhibition capacity and the effective dose of soursop leaf methanol extract (Annona muricata Linn) against the development of C3H mice?s breast cancer in vivo. There were thirty mice of C3H strain which were transplanted with breast tumor and they were divided into five groups consisting of negative control group which was given only solvent CMC 0.5%, a positive control group which was given doxorubicin, a dose group of 15 mg/kg BB, a dose group of 30 mg/kg BB, and a dose group of 45 mg/kg BB. Each mouse was given 0,2 cc soursop leaf extract every day for 21 days while the positive control group was given doxorubicin 0,03 μg/20 gram BB once a week for 21 days intravenously. The length and the width of the tumor were measured at the beginning and also measured once a week during the experiment process to gain the data of the tumor volume. At the end of the research, the tumor of the mice was lifted and weighed and it was stained by AgNOR to measure the proliferation activity of the cell. The Anova result showed that there was a significant difference (p=0,007) between treatment against the development of tumor which was marked by the decrease of the tumor volume and proliferation activity (p=0,001). The Kruskal Wallis result showed that there was no significant difference (p<0,33) in the tumor weight. Spearman correlation study significantly (p=0,03) indicated that there was a positive correlation between the cell proliferation activity and the growth of the tumor but in a weak correlation (r=0,39). Therefore, it could be concluded that the methanol extract of soursop leaf (Annona muricata Linn) can inhibit the growth rate of tumor volume as well as the proliferation activity of the breast cancer cell of C3H mice and it worked optimally at 30 mg/kg BB dose.;Breast cancer is a multifactor disease that has been a leading cause of woman?s mortality. Treatments for breast cancer such as surgery, radiotherapy, and chemotherapy have their own side effects, so that alternative treatments such as herbal medicine are needed. Soursop leaf (Annona muricata Linn) has been reported to have antitumor and cytotoxic effects, but only few conducted in vivo, an advanced research is needed to find the effectiveness and the inhibition pathway of the soursop leaf. The purpose of this research is to find out the inhibition capacity and the effective dose of soursop leaf methanol extract (Annona muricata Linn) against the development of C3H mice?s breast cancer in vivo. There were thirty mice of C3H strain which were transplanted with breast tumor and they were divided into five groups consisting of negative control group which was given only solvent CMC 0.5%, a positive control group which was given doxorubicin, a dose group of 15 mg/kg BB, a dose group of 30 mg/kg BB, and a dose group of 45 mg/kg BB. Each mouse was given 0,2 cc soursop leaf extract every day for 21 days while the positive control group was given doxorubicin 0,03 μg/20 gram BB once a week for 21 days intravenously. The length and the width of the tumor were measured at the beginning and also measured once a week during the experiment process to gain the data of the tumor volume. At the end of the research, the tumor of the mice was lifted and weighed and it was stained by AgNOR to measure the proliferation activity of the cell. The Anova result showed that there was a significant difference (p=0,007) between treatment against the development of tumor which was marked by the decrease of the tumor volume and proliferation activity (p=0,001). The Kruskal Wallis result showed that there was no significant difference (p<0,33) in the tumor weight. Spearman correlation study significantly (p=0,03) indicated that there was a positive correlation between the cell proliferation activity and the growth of the tumor but in a weak correlation (r=0,39). Therefore, it could be concluded that the methanol extract of soursop leaf (Annona muricata Linn) can inhibit the growth rate of tumor volume as well as the proliferation activity of the breast cancer cell of C3H mice and it worked optimally at 30 mg/kg BB dose.;Breast cancer is a multifactor disease that has been a leading cause of woman?s mortality. Treatments for breast cancer such as surgery, radiotherapy, and chemotherapy have their own side effects, so that alternative treatments such as herbal medicine are needed. Soursop leaf (Annona muricata Linn) has been reported to have antitumor and cytotoxic effects, but only few conducted in vivo, an advanced research is needed to find the effectiveness and the inhibition pathway of the soursop leaf. The purpose of this research is to find out the inhibition capacity and the effective dose of soursop leaf methanol extract (Annona muricata Linn) against the development of C3H mice?s breast cancer in vivo. There were thirty mice of C3H strain which were transplanted with breast tumor and they were divided into five groups consisting of negative control group which was given only solvent CMC 0.5%, a positive control group which was given doxorubicin, a dose group of 15 mg/kg BB, a dose group of 30 mg/kg BB, and a dose group of 45 mg/kg BB. Each mouse was given 0,2 cc soursop leaf extract every day for 21 days while the positive control group was given doxorubicin 0,03 μg/20 gram BB once a week for 21 days intravenously. The length and the width of the tumor were measured at the beginning and also measured once a week during the experiment process to gain the data of the tumor volume. At the end of the research, the tumor of the mice was lifted and weighed and it was stained by AgNOR to measure the proliferation activity of the cell. The Anova result showed that there was a significant difference (p=0,007) between treatment against the development of tumor which was marked by the decrease of the tumor volume and proliferation activity (p=0,001). The Kruskal Wallis result showed that there was no significant difference (p<0,33) in the tumor weight. Spearman correlation study significantly (p=0,03) indicated that there was a positive correlation between the cell proliferation activity and the growth of the tumor but in a weak correlation (r=0,39). Therefore, it could be concluded that the methanol extract of soursop leaf (Annona muricata Linn) can inhibit the growth rate of tumor volume as well as the proliferation activity of the breast cancer cell of C3H mice and it worked optimally at 30 mg/kg BB dose.;Breast cancer is a multifactor disease that has been a leading cause of woman’s mortality. Treatments for breast cancer such as surgery, radiotherapy, and chemotherapy have their own side effects, so that alternative treatments such as herbal medicine are needed. Soursop leaf (Annona muricata Linn) has been reported to have antitumor and cytotoxic effects, but only few conducted in vivo, an advanced research is needed to find the effectiveness and the inhibition pathway of the soursop leaf. The purpose of this research is to find out the inhibition capacity and the effective dose of soursop leaf methanol extract (Annona muricata Linn) against the development of C3H mice’s breast cancer in vivo. There were thirty mice of C3H strain which were transplanted with breast tumor and they were divided into five groups consisting of negative control group which was given only solvent CMC 0.5%, a positive control group which was given doxorubicin, a dose group of 15 mg/kg BB, a dose group of 30 mg/kg BB, and a dose group of 45 mg/kg BB. Each mouse was given 0,2 cc soursop leaf extract every day for 21 days while the positive control group was given doxorubicin 0,03 μg/20 gram BB once a week for 21 days intravenously. The length and the width of the tumor were measured at the beginning and also measured once a week during the experiment process to gain the data of the tumor volume. At the end of the research, the tumor of the mice was lifted and weighed and it was stained by AgNOR to measure the proliferation activity of the cell. The Anova result showed that there was a significant difference (p=0,007) between treatment against the development of tumor which was marked by the decrease of the tumor volume and proliferation activity (p=0,001). The Kruskal Wallis result showed that there was no significant difference (p<0,33) in the tumor weight. Spearman correlation study significantly (p=0,03) indicated that there was a positive correlation between the cell proliferation activity and the growth of the tumor but in a weak correlation (r=0,39). Therefore, it could be concluded that the methanol extract of soursop leaf (Annona muricata Linn) can inhibit the growth rate of tumor volume as well as the proliferation activity of the breast cancer cell of C3H mice and it worked optimally at 30 mg/kg BB dose.;Breast cancer is a multifactor disease that has been a leading cause of woman’s mortality. Treatments for breast cancer such as surgery, radiotherapy, and chemotherapy have their own side effects, so that alternative treatments such as herbal medicine are needed. Soursop leaf (Annona muricata Linn) has been reported to have antitumor and cytotoxic effects, but only few conducted in vivo, an advanced research is needed to find the effectiveness and the inhibition pathway of the soursop leaf. The purpose of this research is to find out the inhibition capacity and the effective dose of soursop leaf methanol extract (Annona muricata Linn) against the development of C3H mice’s breast cancer in vivo. There were thirty mice of C3H strain which were transplanted with breast tumor and they were divided into five groups consisting of negative control group which was given only solvent CMC 0.5%, a positive control group which was given doxorubicin, a dose group of 15 mg/kg BB, a dose group of 30 mg/kg BB, and a dose group of 45 mg/kg BB. Each mouse was given 0,2 cc soursop leaf extract every day for 21 days while the positive control group was given doxorubicin 0,03 μg/20 gram BB once a week for 21 days intravenously. The length and the width of the tumor were measured at the beginning and also measured once a week during the experiment process to gain the data of the tumor volume. At the end of the research, the tumor of the mice was lifted and weighed and it was stained by AgNOR to measure the proliferation activity of the cell. The Anova result showed that there was a significant difference (p=0,007) between treatment against the development of tumor which was marked by the decrease of the tumor volume and proliferation activity (p=0,001). The Kruskal Wallis result showed that there was no significant difference (p<0,33) in the tumor weight. Spearman correlation study significantly (p=0,03) indicated that there was a positive correlation between the cell proliferation activity and the growth of the tumor but in a weak correlation (r=0,39). Therefore, it could be concluded that the methanol extract of soursop leaf (Annona muricata Linn) can inhibit the growth rate of tumor volume as well as the proliferation activity of the breast cancer cell of C3H mice and it worked optimally at 30 mg/kg BB dose., Breast cancer is a multifactor disease that has been a leading cause of woman’s mortality. Treatments for breast cancer such as surgery, radiotherapy, and chemotherapy have their own side effects, so that alternative treatments such as herbal medicine are needed. Soursop leaf (Annona muricata Linn) has been reported to have antitumor and cytotoxic effects, but only few conducted in vivo, an advanced research is needed to find the effectiveness and the inhibition pathway of the soursop leaf. The purpose of this research is to find out the inhibition capacity and the effective dose of soursop leaf methanol extract (Annona muricata Linn) against the development of C3H mice’s breast cancer in vivo. There were thirty mice of C3H strain which were transplanted with breast tumor and they were divided into five groups consisting of negative control group which was given only solvent CMC 0.5%, a positive control group which was given doxorubicin, a dose group of 15 mg/kg BB, a dose group of 30 mg/kg BB, and a dose group of 45 mg/kg BB. Each mouse was given 0,2 cc soursop leaf extract every day for 21 days while the positive control group was given doxorubicin 0,03 μg/20 gram BB once a week for 21 days intravenously. The length and the width of the tumor were measured at the beginning and also measured once a week during the experiment process to gain the data of the tumor volume. At the end of the research, the tumor of the mice was lifted and weighed and it was stained by AgNOR to measure the proliferation activity of the cell. The Anova result showed that there was a significant difference (p=0,007) between treatment against the development of tumor which was marked by the decrease of the tumor volume and proliferation activity (p=0,001). The Kruskal Wallis result showed that there was no significant difference (p<0,33) in the tumor weight. Spearman correlation study significantly (p=0,03) indicated that there was a positive correlation between the cell proliferation activity and the growth of the tumor but in a weak correlation (r=0,39). Therefore, it could be concluded that the methanol extract of soursop leaf (Annona muricata Linn) can inhibit the growth rate of tumor volume as well as the proliferation activity of the breast cancer cell of C3H mice and it worked optimally at 30 mg/kg BB dose.]"

"Pendahuluan: Kanker prostat merupakan penyebab utama kedua kematian kanker pada laki-laki di seluruh dunia, menyebabkan 258.000 kematian pada tahun 2008 dan saat ini terjadi kecenderungan peningkatan insiden kanker prostat. Dikhawatirkan insiden makin meningkat seiring dengan peningkatan populasi laki-laki berusia >50 tahun, penanganan dan terapi yang diberikan tidak tepat. Efek samping akibat pengobatan medis dan mahalnya biaya yang dibutuhkan menyebabkan banyak penderita beralih ke pengobatan alternatif seperti penggunaan obat herbal. Ekstrak daun Annona muricata Linn. mengandung annonaceous acetogenins yang potensi aktivitas sitotoksik dan mampu menekan viabilitas sel kanker. Tujuan dari penelitian ini adalah untuk mengetahui pengaruh ekstrak metanol daun sirsak terhadap viabilitas terhadap galur sel kanker independen hormonal ( sel PC3).Metode: Desain penelitian adalah eksperimental laboratorik in vitro menggunakan galur sel kanker prostat PC3 yang dibagi 5 kelompok yaitu kelompok sel tanpa perlakuan (kontrol negatif), kelompok perlakuan dengan ekstrak metanol daun sirsak konsentrasi 6,25; 12,5 dan 25 ug / mL dan kelompok doksorubisin dosis 15 µg/ml (sebagai kontrol positif). Untuk mengetahui viabilitas sel dilakukan pengujian MTT dan pengamatan morfologi terhadap kelompokkelompok perlakuan dengan waktu inkubasi 0 dan 24 jam. Viabilitas sel diketahui dengan menganalisis nilai OD yang merupakan nilai absorbansi dari hasil pembacaan menggunakan menggunakan ELISA reader dengan panjang gelombang (λ) 595 nm. Seluruh data dianalisis dengan uji statistik ANOVA.Hasil: Hasil analisis menunjukkan adanya kecenderungan penurunan nilai OD pada kelompok EMDS 6,25 dan 12,5 µg/ml dibandingkan kelompok kontrol (0,63 dan 0,63 vs 0,67). EMDS konsentrasi 12,5 µg/ml mempunyai kemampuan menghambat viabilitas paling tinggi dibandingkan kelompok perlakuan lainnya, walaupun secara statistik tidak berbeda bermakna. Adanya penurunan viabilitas ini didukung oleh perubahan morfologi sel yang menunjukkan peningkatan morfologi sel mati.Kesimpulan: Ekstrak metanol daun sirsak dapat menurunkan viabilitas galur sel kanker prostat PC3 dengan kemampuan daya hambat tertinggi pada konsentrasi 12,5 µg/ml.

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Introduction: Prostate cancer is the second leading cause of death in men in the entire world. It caused 258,000 death in 2008 and have a tendency to keep increase until now. It is feared that the incidence is increasing along with the increase in the male population more than fifty years old, and unappropriate handling and tretament. Side effects due to the high cost of medical treatment caused many patients turn to alternative treatments such as herbal therapy. Soursop leaves contain Annonaceous Acetogenins active compounds that have a cytotoxic effect on cancer cells and have a potency to decrease the viability of cancer cell. The aim of this study is to determine the effect of soursop leaf extract on the viability and the increase in inhibitory rate on the hormonal-independent of prostate cancer cell line PC3.Methods: The study design was an experimental in vitro study. Subjects were 5 groups of PC3 cell line: cell control group, the group treated with methanol extract of soursop leaves with the concentrations of 6.25, 12.5 and 25 µg/ml and the doxorubicin group as a posotif control. The groups were tested using the MTT cell viability assay at 0 and 24 hours of incubation followed by PC3 cell morphology examination. Cell viability was determined by analyzing OD value which is the absorbance value obtained by using ELISA reader with λ 595 nm. Data were analyzed by ANOVA statistical test.Results: The OD value tend to decrease in 6.25 and 12.5 µg/ml soursop extracttreated group compared to control cell group (0.63, 0.63, and 0.67 respectivelly) even not different statistically (p < 0.05). The 12.5 mg / ml soursop extract-treated group showed the highest ability in inhibiting cell viability compared to the other groups, even not different statistically (p < 0.05). A decrease in viability is supported by morphological changes which indicate cell death.Conclusion: The methanol extract of soursop leaves may reduce the viability of PC3 prostate cancer cell lines with the highest inhibitory ability at a concentration of 12.5 µg/ml."

"Hemoroid merupakan pembengkakan vena rektoanal yang menyebabkan peradangan, nyeri, dan pendarahan. Tanaman dengan senyawa fenolik diketahui memperbaiki tonus vena dan antiinflamasi. Daun sirsak mengandung senyawa fenolik, alkaloid, acetogenin dan megastigmanes. Penelitian ini bertujuan untuk memeriksa parameter spesifik, nonspesifik, kadar fenol total, flavonoid total dan antioksidan Ekstrak Etanol Daun Sirsak (EEDS), juga melihat efek EEDS terhadap gambaran histopatologi dan ekspresi COX-2 dan TNFα pada jaringan rektoanal mencit Swiss berusia 20 minggu yang diinduksi dengan kroton oil 12% melalui anus. EEDS dosis 100, 200, dan 400mg/KgBB diberikan peroral selama 7 hari. Hasilnya menunjukkan EEDS memenuhi standar mutu ekstrak spesifik dan nonspesifik, kadar total fenol 22,85% atau 228,5 mgGAE/g ekstrak, kadar total flavonoid 5,36% atau 53,6 mgQE/g ekstrak, dan memiliki aktivitas antioksidan sedang (IC50 123,325 μg/mL). Pemeriksaan histopatologi pada jaringan rektoanal mencit dinilai dengan menskor lesi nekrosis, inflamasi, vasodilatasi, dan oedema yang diwarnai Hematoksilin-Eosin. Pemberian EEDS pada semua dosis menunjukkan perbedaan pada jaringan inflamasi, nekrosis, vasodilatasi dan oedema P<0.00. Sel positif mengekspresikan COX-2 dan TNFα dihitung pada sel epitel terinflamasi. Hasil menunjukkan EEDS dosis 200, 400 mg/KgBB signifikan menurunkan COX-2 P<0,002 dibandingkan dengan kontrol negatif, dan EEDS dosis 100, 200, dan 400 mg/KgBB signifikan menurunkan TNFα P< 0,010 dibandingkan dengan kontrol negatif.

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Haemorrhoids are rectoanal swelling that causes inflammation, pain, and bleeding. Plants with phenolic compounds are known to improve venous tone and anti-inflammation. Soursop leaves contain phenolic compounds, alkaloids, acetogenin and megastigmanes. This study aims to examine specific, nonspecific parameters, and total phenol levels, total flavonoids and antioxidants of Soursop Leaf Ethanol Extract (SLEE), also see the effect of SLEE on the histopathological features and expression of COX-2 and TNFα in rectoanal tissue of 20-week Swiss mice that are induced with 12% croton oil through the anus. SLEE doses of 100, 200, and 400mg/Kg were given orally for 7 days.

The results show SLEE meets the quality standards of specific and nonspecific extracts, total phenol levels of 22.85% or 228.5 mgGAE/g extracts, total flavonoid levels of 5.36% or 53.6 mgQE/g extracts, and have moderate antioxidant activity (IC50 123,325 μg/mL). Histopathological examination of the rectoanal tissue of mice was assessed by scoring necrotizing, inflammatory, vasodilatation, and oedema lesions hematoxylin-eosin. Administration of SLEE at all doses showed differences in inflammatory tissue, necrosis, vasodilation and oedema P<0.00. Positive cells expressing COX-2 and TNFα were counted on inflammatory epithelial cells. The results showed SLEE dosages of 200, 400 mg/Kg significantly decreased COX-2 P<0.002 compared to negative controls, and SLEE doses of 100, 200, and 400 mg/Kg significantly reduced TNFα P<0.010 compared with negative controls."

"Latar Belakang: Kanker kolorektal merupakan perubahan patologis jaringan epitel kolon dan rektum normal menjadi massa jaringan yang abnormal, salah satunya disebabkan ekspresi berlebih pada protein siklin D1 sehingga menyebabkan proliferasi sel di kolorektal yang berlebihan. Upaya pencegahan dan pengobatan penyakit kanker kolorektal dapat dilakukan secara alami salah satunya dengan mengonsumsi ekstrak daun Annona muricata L. (sirsak). Sirsak diketahui banyak mengandung komponen fitokimia yang berperan sebagai anti-kanker. Metode: Penelitian ini menggunakan sel kultur kanker kolorektal HT-29 yang diberi paparan ekstrak etanol daun sirsak dan 5-Fluorourasil (5-FU) sebagai kontrol positif, kontrol pelarut, kontrol sel sebagai kontrol negatif untuk dicari konsentrasi optimumnya (CC50) dan dilanjutkan dengan konsentrasi ½ x CC50,1 x CC50, dan 2 x CC50. Parameter yang dinilai adalah viabilitas sel dengan MTT Assay dan analisis penambatan molekuler dari ekstrak etanol daun sirsak terhadap protein siklin D1 dengan molecular operating environment (MOE) 2013.08 software. Hasil: Konsentrasi optimum (CC50) ekstrak etanol daun sirsak sebesar 278 µg/mL dan 5-FU sebesar 88 µg/mL. Pemeriksaan viabilitas sel menunjukkan persentase sel HT-29 hidup menurun seiring dengan bertambahnya konsentrasi dan persentase terendah di konsentrasi 2 x dari cytotoxicity concentration 50 (CC50) setelah pemberian ekstrak etanol daun sirsak (40,4±1,3%) dibandingkan dengan 5-FU (52,8±4,3%), kontrol pelarut (97,2±1,4%) dan kontrol sel (100%). Analisis penambatan molekuler terhadap protein siklin D1 didapatkan molekul N-hexadecanoic acid dan phytol yang mempunyai energi bebas (ΔG) terendah, yaitu 9,7755 kkal/mol dan -7,2147 kkal/mol. Kesimpulan: Konsentrasi 5-FU memiliki CC50 tiga kali lebih rendah dibandingkan ekstrak etanol daun sirsak. Molekul N-hexadecanoic acid dan phytol mempunyai kemampuan berikatan dengan protein siklin D1.

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Introduction: Colorectal cancer is a pathological transformation of normal colon and rectum epithelial that becomes an abnormal tissue mass, due to the overexpression of cyclin D1 protein that inducing the high/excessive proliferation of colorectal cell. It accounted for about 1 million new cancer cases in 2002 (9.4% of the world total). The treatment and prevention of colorectal cancer could be done naturally by consuming leave extract of Annona muricata L. (soursop). Soursop is known for many phytochemical components that serve as an anti-cancer such as alkaloid, annonaceous acetogenin, megastigman, flavonoid glycosides, phenolic, and cyclopeptide.

Methods: The study was used HT-29 colorectal cancer cell that treated with ethanolic leave extract of soursop and 5-Fluorourasil (5-FU) as positive control to find the cytotoxicity concentration that can inhibit 50% of HT-29 cell population (CC50) and the ½ x CC50,1 x CC50, and 2 x CC50 concentrations of them were treated for next treatment with MTT assay. Analysis of molecular docking of ethanolic leave extract of soursop to cyclin D1 protein used molecular operating environment (MOE) 2013.08 software.

Results : Optimum concentration (CC50) of ethanolic leave extract of soursop is 278 μg/mL dan 5-FU is 88 μg/mL. Percentage of viable HT-29 cell line decrease in accordance with increasing concentration and the lowest percentage of viable cell is 2 x cytotoxicity concentration 50 (CC50) after ethanolic leave extract of soursop treatment (40,4±1,3%) was compared to 5-FU (30,68±0,93%), solvent control (97,2±1,4%), and cells control (100%). Analysis of molecular docking to cyclin D1 protein was obtained N-hexadecanoic acid and phytol molecules that have the lowest free energy (ΔG), that are 9,7755 kkal/mol and -7,2147 kkal/mol.

Conclusions 5-FU concentration is 3-fold lower than ethanolic leave extract of soursop. N-hexadecanoic acid and phytol molecules have ability to inhibit cyclin D1 protein."

"Inhibitor ramah lingkungan saat ini diperlukan untuk mengurangi dampak pencemaran dari inhibitor anorganik. Penelitian ini mempelajari pengaruh injeksi ekstrak daun sirsak dengan pelarut tiga tingkat sebagai inhibitor organik terhadap baja karbon rendah API 5L grade A dalam larutan air terproduksi. Berdasarkan pengujian weight loss dari seluruh sampel uji, sampel 8 hari dengan penambahan inhibitor 2 ml menunjukan nilai efisiensi paling tinggi yakni sebesar 52.62 %. Hasil uji polarisasi dan EIS dengan pelarut tiga tingkat didapatkan pelarut etanol mempunyai nilai efisiensi paling besar: 88.52%, sedangkan pelarut semi polar dan non polar nilai efisiensi nya hampir sama. Data dari EIS menunjukkan tahanan larutan menjadi turun dengan semakin meningkat nya penambahan inhibitor ekstrak daun sirsak. Uji FTIR memperlihatkan bahwa terdapat gugus fungsi dari ekstrak daun sirsak dan senyawa aktif nya adalah tipe polifenol.

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Green inhibitors are now increasingly needed to reduce the adverse environmental impacts of the inorganic inhibitor. This research studied the effects of injection of soursop leaves extract in three-level solvents (polar, semi polar and non polar) as an organic inhibitor for the low-carbon steel API 5L of grade A in produced water solution. Based on weight loss test of the entire sample, the 8 days's sample with addition of 2 ml inhibitor from soupsop leaves extract showed the highest efficiency value which amounted to 52.62%. The polarization and EIS tests for three levels's solvents show that the ethanol solvent (type of polar) has the greatest efficiency values: 88.52%, while the efficiency value of non-polar and semi-polar solvent is almost without difference. EIS data showed that inhibiting power of the solution decreases when the inhibitor of soursop leaves extract is increasingly added. FTIR test showed that there is a functional group in the soursop leaves's extract and the active compound is a kind of polyphenol."

"Prevalensinya terus meningkat dari tahun ke tahun baik di negara maju juga tidak berkembang. Di Indonesia diperkirakan ada 12 juta orang berusia 15 tahun yang menderita diabetes mellitus pada tahun 2013. Pengobatan diabetes mellitus menggunakan ekstrak tumbuhan dilaporkan memiliki hasil yang baik cukup bagus. Salah satu tanaman yang memiliki efek antidiabetes adalah Annona muricata. Ekstrak daun Annona muricata ditemukan meningkat regenerasi sel beta pankreas. Penelitian ini bertujuan untuk mengetahui pengaruh pemberian ekstrak etanol daun sirsak (EEDS) pada diameter pulau Langerhans, ekspresi insulin, dan kadar plasma glukagon-like peptide-1 (GLP-1) pada tikus diinduksi aloksan. Metode: Penelitian ini menggunakan desain eksperimental. Sampel yang digunakan adalah mencit Swiss Webster sebanyak 30 ekor jantan dengan umur 12-14 minggu dan berat badan 20-30 gram. Sampel dibagi dengan diacak menjadi 5 kelompok, diinduksi dengan aloksan, dan diberi perlakuan 14 hari. Kelompok terdiri dari: kontrol negatif, kontrol positif yang diberi perlakuan glibenklamid 0,65 mg/kgBB, pengobatan dengan EEDS 150 mg/kgBB (P1), 300 mg/kgBB (P2), dan 600 mg/kgBB (P3). Diameter pulau-pulau Langerhans dan Ekspresi insulin diukur dengan pemeriksaan histopatologi dengan pewarnaan hematoxylin-eosin (HE) dan imunohistokimia (CPI), sedangkan GLP-1. level plasma diukur dengan ELISA. Data yang berdistribusi normal dianalisis dengan uji ANOVA satu arah, diikuti oleh Tukey HSD post hoc. Data dengan distribusi. Kelainan dianalisis dengan uji Kruskal-Wallis. Hasil: Analisis bivariat menunjukkan perbedaan yang signifikan antara pemberian EEDS dengan diameter Pulau Langerhans (p = 0,001) tetapi perbedaannya tidak signifikan dengan ekspresi insulin (p = 0,539) dan kadar GLP-1 plasma (p = 0,122). Kesimpulan: EEDS yang diberikan dalam dosis 300 mg/kgBB paling efektif dalam memperbesar diameter pulau langerhans. Sebaliknya, ketiga dosis ekstrak tidak dapat meningkatkan ekspresi insulin dan kadar GLP-1 plasma.

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Its prevalence continues to increase from year to year both in developed countries also not growing. In Indonesia, it is estimated that there are 12 million people aged 15 years who suffer from diabetes mellitus in 2013. Treatment of diabetes mellitus using plant extracts is reported to have good results. One of the plants that have an antidiabetic effect is Annona muricata. Annona muricata leaf extract was found to increase pancreatic beta cell regeneration. This study aimed to determine the effect of soursop leaf ethanol extract (EEDS) on the diameter of the islets of Langerhans, insulin expression, and plasma levels of glucagon-like peptide-1 (GLP-1) in rats. alloxan induced. Methods: This study used an experimental design. The samples used were 30 male Swiss Webster mice, aged 12-14 weeks and weighing 20-30 grams. Samples were divided randomly into 5 groups, induced with alloxan, and treated for 14 days. The group consisted of: negative control, positive control that was given treatment glibenclamide 0.65 mg/kgBW, treatment with EEDS 150 mg/kgBW (P1), 300 mg/kgBW (P2), and 600 mg/kgBW (P3). The diameter of the islets of Langerhans and insulin expression were measured by histopathological examination with hematoxylin-eosin (HE) and immunohistochemical (CPI) staining, while GLP-1 . plasma levels were measured by ELISA. Data that were normally distributed were analyzed by one-way ANOVA test, followed by Tukey HSD post hoc. Data with a distribution that Abnormalities were analyzed by the Kruskal-Wallis test. Result: Bivariate analysis showed a significant difference between the administration of EEDS and the diameter of the Islets of Langerhans (p = 0.001) but the difference was not significant with insulin expression (p = 0.539) and plasma GLP-1 levels (p = 0.122). Conclusion: EEDS given in a dose of 300 mg/kgBW was most effective in increasing the diameter of the islets of Langerhans. In contrast, the three extract doses did not increase insulin expression and plasma GLP-1 levels."

"ABSTRACTKanker kolorektal saat ini merupakan kanker tersering ketiga di Indonesia dunia. Perawatan yang tersedia untuk penyakit ini masih memiliki banyak pengaruh sisi sehingga peneliti mencoba mengembangkan terapi antikanker baru dengan efek samping minimal. Manggis (Garcinia mangostana Linn.), Yang mengandung α-mangostin yang diketahui memiliki aktivitas antikanker. Fraksi etil asetat digunakan untuk mendapatkan kadar α-mangostin tertinggi dari ekstraksi manggis. Namun, hal itu berpengaruh pada lambung, usus, hati, dan ginjal sebagai organ yang terlibat dalam proses absorpsi, metabolisme, dan ekskresi obat belum dievaluasi. Penelitian ini bertujuan untuk menilai pengaruh fraksi etil asetat dari Garcinia mangostana Linn. (FGM) tentang perubahan histopatologis organ ini pada tikus. Penelitian ini menggunakan mencit betina berumur 6-8 minggu dengan berat 25-30 g dan diperoleh dari Balitbangkes Kemenkes RI yang terbagi dalam lima kelompok: kelompok kontrol negatif, kelompok pelarut, dan tiga kelompok uji yang menerimaFGM per oral dengan dosis tunggal 2, 4, dan 6 g / kg berat badan dengan masing-masing kelompok berisi lima tikus. Mencit diamati selama 14 hari. Selanjutnya, organ diambil untuk diperiksa secara histopatologi. Penelitian ini menunjukkan bahwa tidak ada perbedaan yang signifikan pada lambung. ginjal, dan usus antara lima kelompok. Namun, memberikan fGM dengan dosis 6 g / kgBW menunjukkan peningkatan derajat kerusakan jaringan hati. Riset lebih lanjut Pengembangan lebih lanjut diperlukan untuk pengembangan Garcinia mangostana Linn. sebagai terapi antikanker di masa depan.ABSTRACT Colorectal cancer is currently the third most common cancer in Indonesia in the world. The treatments available for this disease still have many side effects, so researchers are trying to develop new anticancer therapies with minimal side effects. Mangosteen (Garcinia mangostana Linn.), Which contains α-mangostin which is known to have anticancer activity. Ethyl acetate fraction was used to obtain the highest α-mangostin levels from mangosteen extraction. However, its effect on the stomach, intestines, liver, and kidneys as organs involved in the absorption, metabolism and excretion of drugs has not been evaluated. This study aims to assess the effect of the ethyl acetate fraction of Garcinia mangostana Linn. (FGM) regarding the histopathological changes of this organ in mice. This study used female mice aged 6-8 weeks weighing 25-30 g and were obtained from Balitbangkes Kemenkes RI which were divided into five groups: a negative control group, a solvent group, and three test groups that received FGM orally with a single dose of 2, 4, and 6 g / kg body weight with each group containing five mice. Mice were observed for 14 days. Next, the organs are removed for histopathological examination. This study shows that there are no significant differences in the stomach. kidney, and intestines among the five groups. However, giving fGM at a dose of 6 g / kgBW showed an increased degree of liver tissue damage. Further research Further development is required for the development of Garcinia mangostana Linn. as anticancer therapy in the future."

"Kanker payudara merupakan salah satu penyebab kematian pada perempuan di seluruh dunia. Pengobatan menggunakan bahan alam banyak dikembangkan karena toksisitasnya rendah. Daun sirsak (Annona muricata L.) terbukti memiliki potensi aktivitas antiproliferasi pada sel kanker payudara.Penelitian ini bertujuan untuk memperoleh pengaruh enkapsulasi ekstrak etanol daun sirsak terhadap aktivitas antiproliferasi sel kanker payudara T47D. Liposom adalah mikropartikulat berbentuk sferis yang mampu menghantarkan obat antikanker.Pada penelitian ini ekstrak etanol daun sirsak dienkapsulasi dalam liposom menggunakan metode hidrasi lapis tipis dan diekstrusi dengan membran polikarbonat 0,4 μm dan 0,1 μm masing-masing sebanyak 10 siklus. Selanjutnya, formula liposom yang memiliki enkapsulasi terbaik dilihat dari waktu pemisahan yang lebih lama dan dispersi partikel yang paling kecil kemudian dibandingkan aktivitas antiproliferasinya dengan ekstrak yang tidak dienkapsulasi menggunakan metode MTT.Pada penelitian ini diperoleh bahwa liposom formula 1 memiliki dispersi partikel lebih kecil dan waktu pemisahan lebih lama dengan morfologi multi vesicular vesicle dan large unilamelar vesicle. Efisiensi penjerapan liposom formula 1 adalah 96,93%. IC50 ekstrak yang tidak dienkapsulasi adalah 64,53 μg/ml dan IC50 ekstrak yang dienkapsulasi liposom adalah 389,29 μg/ml.

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Breast cancer is one the leading cause of cancer death in women worldwide. Treatment using natural materials has been developed because it has low toxicity. Soursop leaves (Annona muricata L.) proved to have the potential antiproliferative activity in breast cancer cells. Liposomes are spherical microparticulate which capable of delivering anticancer drugs.This study aimed to obtain the effect of encapsulation soursop leaves ethanolic extract in liposome against antiproliferative activity in T47D breast cancer cell.In this study, ethanolic extract of soursop leaf encapsulated in liposomes using thin layer hydration method and extruded with a polycarbonate membrane of 0,4 μm and 0,1 μm respectively as many as 10 cycles. Furthermore, liposome?s formula which shown the best encapsulation from longer separation time and smallest particle dispersion compared its antiproliferative activity with extracts not encapsulated using MTT method.In this study showed that liposomes formula 1 has smaller particle dispersion and longer separation time whose multi vesicular vesicle and large unilamelar vesicle morphology. Entrapment efficiency of liposome formula 1 is 96,93%. IC50 value for not encapsulated extract was 64,53 μg/ml and IC50 value for extract encapsulated liposomes was 389,29 μg/ml."

"Tanaman Annona muricata Linn., termasuk kedalam suku Annonaceae. Berdasarkan penelitian terdahulu diketahui bahwa beberapa tanaman dari suku Annonaceae memiliki aktivitas antioksidan dengan berbagai metode uji antioksidan, namun informasi mengenai metode pengekstraksiannya hanya terbatas pada metode Soxhlet. Berdasarkan data tersebut dilakukan penelitian dengan berbagai metode ekstraksi. Penelitian ini dilakukan untuk mengetahui aktivitas antioksidan dari ekstrak etanol pada semua metode ekstraksi, serta mengetahui golongan senyawa kimia dari fraksi teraktif. Pada penelitian ini, daun Annona muricata Linn. diekstrak dengan metode yang berbeda dengan pelarut etanol menggunakan metode dingin dan metode panas, meliputi maserasi, perkolasi, refluks, Soxhlet, digesti, infusa, dan dekokta. Ekstrak yang paling aktif, yaitu ekstrak pada metode Soxhlet, kemudian difraksinasi dengan cara pengocokan menggunakan pelarut n-heksan, etil asetat, n-butanol, dan metanol. Masing-maing diperoleh empat fraksi, lalu seluruh fraksi diuji aktivitas antioksidannya dengan menggunakan metode DPPH. Hasil uji menunjukkan, ekstrak dari metode Soxhlet memiliki aktivitas antioksidan terbesar dengan nilai IC50 19,13 μg/mL, dan fraksi teraktif yaitu fraksi etil asetat yang mempunyai nilai IC50 12,53 μg/mL. Hasil identifikasi kimia fraksi etil asetat menunjukkan adanya flavonoid, alkaloid, tanin, saponin, terpen, dan glikosida.

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Annona muricata Linn., from Annonaceae family which have antioxidant activity. Based on previous research showed that the Annonaceae family had antioxidant activity with various test methods, however there was a few information and investigation about extraction methods, just limitted in Soxhlet methods. Based on these data, the research conducted by various extraction methods.

This research present, were extracted with ethanol 70% using cold and hot methods, including maceration, percolation, reflux, Soxhlet, digestion, infusion, and decoct from Annona muricata Linn leave. The research to determine the antioxidant activity in ethanol extracts of all methods extraction, and to know the chemical compounds most active fraction. The most active extracts then fractionated by using n-hexane, ethyl acetate, n-butanol, and methanol solvent, obtained four fractions and tested antioxidant activity using DPPH methods. The result showed that all of the extracts had antioxidant activity were indicated by IC50 values ​​.

Test results showed that extracts from Soxhlet method has the greatest antioxidant activity which has a value of IC50 16.05 µg/ mL, and the most active fractions of ethyl acetate fraction which has a value of IC50 10.94 µg/ mL. The chemical identification of ethyl acetate fraction showed containing flavonoids, alkaloids, tannins, saponnin, terpenes, and glycosides."