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"Komplikasi penyakit perlemakan hati non-alkoholik (PHNA) ditemukan pada 67% populasi memenuhi kriteria sindrom metabolik. Acalypha indica L. (AI) adalah herbal yang telah diketahui memiliki efek anti-oksidan, dan anti-inflamasi. Penelitian ini bertujuan membuktikan efek AI terhadap mekanisme pertahanan imun yang dibawa. Penelitian dilakukan dengan molecular docking terhadap senyawa AI pada TLR9, NFκB, TNFα, dan perubahan histopatologik hati. Model hewan steatohepatitis pada tikus Sprague-Dawley didapat dari induksi diet tinggi fruktosa, dan kolesterol (DTFK) selama 12 minggu. Terapi diberikan selama 8 minggu. Dua puluh lima tikus dibagi ke dalam 5 kelompok: Normal (K1), DTFK (K2), DTFK+AI, 400 mg (K3), kombinasi AI, 400 mg +gemfibrozil (Gem) 31 mg (K4) dan Gem 31 mg (K5) masing-masing per kgBB. Molecular docking untuk mengidentifikasi interaksi antara molekul hidrogen senyawa AI dengan residu asam amino TLR9, NFκB, TNFα. Perubahan morfologi hati dinilai dengan cara skoring. Analisis statistik yang dilakukan adalah uji Kruskall Wallis post hoc Mann Whitney, dilanjutkan dengan uji korelasi Spearman. Hasil molecular docking menunjukkan, selain senyawa flavonoid, ditemukan senyawa alkaloid beta-sitosterol, dan stigmasterol yang dapat berikatan dengan ketiga marker inflamasi dengan nilai binding energy terbaik. Senyawa lain dasycarpidan-1-methanol, acetate (ester), fenofibrate, quinine. Pemberian AI menurunkan hipertrofi (p=0,031), steatosis makrovesikular (p=0,018), fokus inflamasi (p=0,005). Pemberian AI juga menurunkan ekspresi TLR9 (p=0,009), NFκB (p=0,009), TNFα (p=0,009), akan tetapi tidak sebaik pemberian kombinasi AI+Gem.

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Complications of non-alcoholic fatty liver disease (NAFLD) include 67% of the criteria for metabolic syndrome. Acalypha indica L., (AI) which is one of a herbal plant had been known as anti-oxidant and anti-inflammatory effects. The effect of AI for therapy investigated by looking of the immune defense mechanisms. This researched was assessed by molecular docking approached on TLR9, NFκB, TNFα expression and liver morphological changes. Animal models of steatohepatitis were collected from high- fructose and cholesterol diet (HFCD) of Sprague-Dawley rats for 12 weeks and followed by therapy for 8 weeks. There were 5 groups from twenty five researched rats, include normal group (K1), HFCD group (K2), HFCD group supplemented with 400 mg Acalypha indica L. (K3), combination between 400 mg AI.+gemfibrozil (Gem) 31 mg (K4) and Gem 31 mg/kg (K5) in kgBW, respectively. The results of molecular docking were carried out by assessing the interaction between hydrogen molecules of AI compounds and amino acid residues in TLR9, NFκB, TNFα. Morphological changes were assessed by scoring system. Statistical analyzed used Kruskall Wallis with post hoc Mann Whitney test continued by Spearman correlation test. The molecular docking analysis showed that, an alkaloid compounds were found besides the flavonoid compounds that can bind to the binding pocket of inflammatory markers with the best binding energies. Other compounds, there are dasycarpidan-1-methanol, acetate (ester), fenofibrate and quinine. Supplementation of AI would reduced hypertrophy (p=0.031), macrovesicular steatosis (p=0.018), inflammation foci (p=0.005) and also decreased of TLR9 (p=0.009), NFκB (p=0.009), TNFα (p=0.009) expression, but not as good as the combination of AI+Gem."

"Inflamasi memiliki peran penting dalam perkembangan berbagai kondisi patologis, yang dimediasi oleh aktivasi berbagai jalur pensinyalan, termasuk jalur IKK-NF-κB. Silybin, senyawa flavonolignan yang ditemukan dalam Milk Tistle (Silybum marianum L) telah digunakan secara tradisional untuk mengobati penyakit hati dan telah dilaporkan memiliki aktivitas anti-inflamasi, antifibrotik, dan imunomodulator. Namun, mekanisme molekuler silybin sebagai agen antiinflamasi potensial terhadap jalur pensinyalan IKKNF- κB masih belum jelas. Penelitian ini menggunakan simulasi penambatan molekuler menggunakan Autodock 4.0 untuk menyelidiki interaksi antara Silybin dan NF-κB. Hasil penelitian menunjukkan bahwa silybin menunjukkan inhibisi kompetitif-ATP dan memiliki afinitas pengikatan yang tinggi untuk makromolekul IkB kinase beta (IKKβ) dan NIK (NF-kB-inducing kinase), dengan energi pengikatan -9,73 kkal/mol pada rantai A dan -9,84 kkal/mol pada rantai B IkB kinase beta (IKKβ) serta -9,34 kkal/mol pada makromolekul NIK (NF-kB-inducing kinase). Konstanta Inhibisi (Ki) ditemukan masingmasing 74,14 nM pada rantai A dan 61,12 nM pada rantai B IkB kinase beta (IKKβ) serta 141,81 nM mol pada NIK (NF-kB-inducing kinase). Temuan ini menunjukkan bahwa silybin memiliki potensi untuk menghambat jalur pensinyalan IKK-NF-κB, sehingga memberikan efek anti-inflamasi. Selain itu, silybin menunjukkan afinitas pengikatan yang lebih tinggi jalur persinyalan kanonikal dibanding jalur perisnyalan alternatif. Studi ini memberikan wawasan tentang mekanisme molekuler silybin sebagai agen antiinflamasi potensial dan aplikasi terapeutiknya dalam terapi penyakit yang berhubungan dengan Inflamasi.

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Inflammation has a crucial role in the progression of various pathological conditions, mediated by the activation of multiple signaling pathways, including the IKK-NF-κB pathway. Silybin, a flavonolignan compound extracted from Milk thistle (Silybum marianum L.) has been traditionally used to treat liver disorders and exhibits pharmacological properties, including anti-inflammatory, antifibrotic, and immunomodulatory activities. However, the molecular mechanisms underlying Silybin's anti-inflammatory potential, particularly its interaction with the IKK-NF-κB signaling pathway, remain unclear. This study employed molecular docking simulations using Autodock 4.0 to investigate the interaction between Silybin and NF-κB. The results showed that silybin exhibited competitive-ATP inhibition and high binding affinity for IkB kinase beta (IKKβ) and NIK (NF-kB-inducing kinase) macormolecule, with binding energies of -9.73 kcal/mol on the A chain and -9.84 kcal/mol on the B chain of IkB kinase beta (IKKβ) and -9.34 kcal/mol on NIK (NF-kB-inducing kinase). Inhibition constants (Ki) were found to be 74.14 nM on chain A and 61.12 nM on chain B of IkB kinase beta (IKKβ) and 141.81 nM mol on NIK (NF-kB-inducing kinase), respectively. Notably, silybin displays higher binding affinity for the canonical pathway compared to the alternative pathway. These findings suggest that silybin has the potential to inhibit IKKNF- κB signaling, leading to anti-inflammatory effects. This study provides valuable insights into the molecular mechanism of silybin as a potential anti-inflammatory agent and its therapeutic applications in inflammation-related diseases."

"Pendahuluan: Saat ini, dunia secara global termasuk Indonesia tengah mengalami tren pesat peningkatan populasi lansia. Hal ini dapat menjadi tantangan kesehatan besar karena penuaan meningkatkan kerentanan terjadinya penyakit degeneratif. Sayangnya, agen antipenuaan seperti suplemen vitamin masih sulit terjangkau secara biaya atau diperoleh secara luas. Centella asiatica L. (CA) adalah tanaman herbal tradisional yang dilaporkan memiliki efek antiinflamasi dan antioksidan poten dalam banyak studi. Namun, studi yang meneliti efek CA dalam konteks penuaan masih sangat terbatas. Tujuan: Studi ini meneliti efek pemberian ekstrak etanol CA terhadap kadar TNF-α pada jantung dan ginjal tikus Sprague-Dawley tua Metode: Tikus Sprague Dawley jantan usia 8-12 minggu dan 20-24 bulan dibagi menjadi empat kelompok uji: kontrol positif (vitamin E 6 IU), kontrol negatif (air ad libitum), CA 300 (CA 300 mg/kgBB), dan kontrol muda (tikus usia 8-12 minggu dengan air ad libitum). Setelah 28 hari perlakuan, tikus diterminasi. Organ jantung dan ginjal setiap tikus diambil dan melewati pengukuran kadar TNF-α dengan metode enzyme-linked immunosorbent assay (ELISA). Hasil: Pada kelompok CA 300, terdapat penurunan kadar TNF-α jantung secara signifikan (p = 0,023) disertai penurunan kadar TNF-α ginjal secara tidak signifikan (p = 0,574). Namun, kadar TNF-α ginjal pada kelompok yang diberikan CA tetap paling rendah dibandingkan kelompok lainnya. Kesimpulan: Pemberian ekstrak etanol CA menurunkan kadar TNF- α jantung secara signifikan pada tikus Sprague-Dawley tua namun tidak berpengaruh terhadap kadar TNF-α ginjal. Diperlukan penelitian lebih lanjut untuk menyelidiki efek CA sebagai agen antipenuaan.

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Introduction: Currently, the world including Indonesia are experiencing a trend of rapid growth in aging population. This poses a major challenge to healthcare due to increasing incidence of degenerative diseases. In spite of this, preventive antiaging agents such as vitamin supplements are not widely available nor affordable. Centella asiatica L. (CA), a traditional herbal plant native to Southeast Asia, has been widely studied and demonstrated potent anti-inflammatory and antioxidant effects in clinical studies. However, studies examining effects of CA in aging population are very limited. Objective: This study investigates effects of CA treatment on aged Sprague-Dawley rats. Methods: Male Sprague-Dawley rats aged 8-12 weeks and 20-24 months were split into four experimental groups: positive control (vitamin E 6 IU), negative control (water ad libitum), CA 300 (CA 300 mg/kgBW), and young control (young rats given water ad libitum). After 28 days of treatment, the rats underwent termination with kidneys and hearts harvested. TNF-α concentration were determined using enzyme-linked immunosorbent assay (ELISA) method. Results: In the CA 300 group, there was a significant decrease in heart TNF-α levels (p = 0,023) accompanied by an insignificant decrease in kidney TNF-α levels (p = 0,574). However, renal TNF-α levels in the group given with CA is still the lowest among all groups. Conclusion: The administration of CA ethanolic extract on aged Sprague-Dawley rats significantly reduced heart TNF-α level and had no effect on the kidney TNF-α level. Further research and exploration needs to be made to investigate the effects of CA as an antiaging agent"

"Jumlah penduduk lanjut usia di dunia mengalami peningkatan setiap tahunnya. Hal ini diikuti dengan semakin naiknya insidensi penyakit tidak menular yang kerap menyerang di usia tua. Penggunaan antioksidan dapat mencegah insidensi penyakit-penyakit tersebut melalui kapasitasnya menangkal peningkatan radikal bebas, inflammaging, dan markamarka inflamasi, seperti TNF-α. Salah satu sumber antioksidan yang paling baik dan banyak tersedia adalah dari tanaman-tanaman herbal, seperti Acalypha indica L. (AI). Tidak hanya banyak tersedia, tanaman ini juga telah dipakai secara empiris oleh berbagai peradaban dunia dan ditemukan memiliki sifat antioksidan. Metode: Penelitian dilaksanakan pada tikus Sprague-Dawley yang dibagi menjadi empat kelompok, yaitu kelompok kontrol negatif (plasebo), kontrol positif (6 IU vitamin E), perlakuan (250 mg/kg berat badan (mg/kgBB) ekstrak AI), dan kontrol pembanding (tikus muda). Setelah 28 hari, tikus diterminasi dan diambil organ ginjal dan jantungnya untuk dilakukan pengecekan kadar TNF-α menggunakan metode ELISA. Data yang didapatkan dianalisis menggunakan tes Saphiro-Wilk dan one-way ANOVA. Hasil: Pemberian AI menghasilkan penurunan kadar TNF-α in pada ginjal (0,95 ± 0,76 pg/mg pada kelompok perlakuan vs 1,37 ± 0,41 pg/mg pada kelompok kontrol negatif) dan jantung (15,43 pg/mg ± 2,33 pada kelompok perlakuan vs 16,50 ± 1,33 pg/mg pada kelompok kontrol negatif) tikus tua meski tidak signifikan (p = 0,645 pada ginjal dan p = 0,973 pada jantung). Kesimpulan: Penemuan penurunan TNF-α dalam studi ini menunjukkan potensi penggunaan AI sebagai agen antiinflamasi dan anti penuaan. Penelitian dan investigasi lebih lanjut perlu dilakukan pada AI dengan menggunakan durasi perlakuan, dosis, dan parameter inflammaging yang berbeda.

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The world’s elderly are currently rising in numbers every year. This is followed by an increase of noncommunicable diseases which are often found in the elderly. Antioxidants could prevent occurrences of such diseases because of their capacity to counter rising free radicals, inflammaging, and inflammatory markers, such as TNF-α. One of the main abundant sources of antioxidants are herbal plants, such as Acalypha indica L. (AI). AI has been used empirically by different cultures and is found to have antioxidant properties. Method: Research was conducted on Sprague-Dawley rats which were divided into four groups, the negative control (placebo), positive control (6 IU vitamin E), treatment group (250 mg/kg of body weight (mg/kgBW) AI extract), and comparison control (young rats). The rats were terminated after 28 days with their organs, kidneys and hearts examined using ELISA to look for TNF-α concentration. Data were analysed using the Saphiro-Wilk test and one-way ANOVA. Results: AI administration yielded decrease of TNF-α in both the kidneys (0.95 ± 0.76 pg/mg in treatment group vs 1.37 ± 0.41 pg/mg in negative control) and hearts (15.43 pg/mg ± 2.33 in treatment group vs 16.50 ± 1.33 pg/mg in negative control) of aged SD rats, albeit insignificantly (p value for the kidney = 0.645 and p value for the heart = 0.973). Conclusion: This finding of decreased TNF-α suggests a potential anti-inflammatory and anti-aging effect of AI. Further research and investigation need to be made on AI, such as by using different dosages, time, and inflammaging parameters."

"Latar Belakang Obesitas merupakan masalah kesehatan pada abad ke-21 dan berkaitan erat dengan peningkatan masalah kesehatan seperti non-alcoholic fatty liver disease (NAFLD). Patofisiologi obesitas tersebut melibatkan makrofag proinflamatori M1 (salah satu marker adalah Itgax atau CD11c) dalam perkembangan NAFLD. Dalam kasus yang lebih berat, NAFLD dapat berkembang menjadi fibrosis liver yang melibatkan TGF-β1. Meskipun pengobatan antiobesitas telah beredar dimasyarakat, namun obat tersebut dapat memiliki kontraindikasi dan efek samping masing-masing. Acalypha indica (Ai) merupakan salah satu tanaman herbal yang memiliki efek antihiperlipidemia dan antiobesitas. Penelitian ini akan menganalisis efek Ai terhadap perkembangan kerusakan liver melalui Itgax sebagai marker makrofag proinflamatori, TGF-β1 dan histopatologi liver pada tikus obesitas. Metode Uji reverse transcription-quantitative polymerase chain reaction (RT-qPCR) dilakukan untuk mengukur ekspresi Itgax dan TGF- β1 serta pemeriksaan histologi untuk menilai ada/tidaknya inflamasi dan persentase rerata luas area sinusoid pada organ liver tersimpan tikus obesitas dengan perlakuan: (1) diet normal (kontrol normal), (2) diet tinggi fruktosa dan kolesterol (DTFK) (kontrol negatif), (3) DTFK + Gemfibrozil (kontrol positif), serta (4) DTFK + ekstrak Ai (DTFK + Ai). HasilEkspresi Itgax pada kelompok tikus DTFK+Ai (1,580 + 0,836) terbukti lebih rendah dibanding dengan kelompok kontrol negatif (1,880 + 1,293), ekspresi TGF-β1 pada kelompok tikus DTFK+Ai (1,340 + 0,706) terbukti lebih rendah dibanding dengan kelompok kontrol negatif (1,850 + 1,358), walaupun tidak berbeda bermakna secara statistik. Di lain pihak, terjadi perbaikan inflamasi pada kelompok tikus DTFK+Ai dibanding dengan kontrol negatif, dan persentase rerata luas area sinusoid pada kelompok tikus DTFK+Ai (3,286 + 0,138) terbukti lebih tinggi dibanding dengan kontrol negatif (2,654 + 0,165).KesimpulanPemberian ekstrak akar Ai dapat menurunkan ekspresi Itgax dan TGF-β1, memperbaiki inflamasi pada liver serta meningkatkan persentase luas rerata sinusoid liver tikus obesitas, walaupun memerlukan penelitian lebih lanjut.

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Introduction

Obesity is a health problem in the 21st century and is closely related to an increase in health problems such as non-alcoholic fatty liver disease (NAFLD). The pathophysiology of obesity involves proinflammatory M1 macrophages (one of the markers is Itgax or CD11c) in the development of NAFLD. In more severe cases, NAFLD can progress to liver fibrosis involving TGF-β1. Even though anti-obesity treatments have been circulating in the community, these drugs can have their own contraindications and side effects. Acalypha indica (Ai) is a herbal plant that has antihyperlipidemia and antiobesity effects. This study will analyze the effect of Ai on the development of liver damage through Itgax as a marker for proinflammatory macrophages, TGF-β1 and liver histopathology in obese mice.

Method

The reverse transcription-quantitative polymerase chain reaction (RT-qPCR) test was carried out to measure the expression of Itgax and TGF-β1 as well as histology examination to assess the presence/absence of inflammation and the average percentage of sinusoid area in the stored liver organ of obese mice treated with: (1) diet normal (normal control), (2) high fructose and cholesterol diet (DTFK) (negative control), (3) DTFK + Gemfibrozil (positive control), and (4) DTFK + Ai extract (DTFK + Ai).

Results

Itgax expression in the DTFK+Ai group of mice (1.580 + 0.836) was proven to be lower than the negative control group (1.880 + 1.293), TGF- β1 expression in the DTFK+Ai group of mice (1.340 + 0.706) was proven to be lower than the negative control group. (1.850 + 1.358), although it is not statistically significantly different. On the other hand, there was an improvement in inflammation in the DTFK+Ai mice group compared to the negative control, and the average percentage of sinusoid area in the DTFK+Ai mice group (3.286 + 0.138) was proven to be higher than the negative control (2.654 + 0.165). Conclusion

Administration of Ai root extract can reduce the expression of Itgax and TGF-β1, improve inflammation in the liver and increase the percentage of the average area of liver sinusoids in obese mice, although further research is needed."

"Radikal bebas, dalam kadar rendah atau menengah, mempunyai peran fisiologis bagi kehidupan sel tubuh. Pada konsentrasi tinggi, radikal-bebas dapat memicu stres oksidatif yang menjadi dasar patogenesis berbagai penyakit. Suplai antioksidan eksogen dibutuhkan untuk membantu kinerja antioksidan endogen dalam menangkal stres oksidatif. Ekstrak-etanol Acalypha indica dan Centella asiatica masing-masing diketahui memiliki aktivitas antioksidan. Penelitian ini bertujuan untuk mengetahui perbandingan aktivitas antioksidan campuran ekstrak-etanol Acalypha indica dan Centella asiatica terhadap ekstrak-etanol Acalypha indica. Kombinasi ekstrak diharapkan mampu meningkatkan aktivitas antioksidan yang dihasilkan dan menurunkan dosis yang digunakan. Aktivitas antioksidan ekstrak diukur dengan metode spektrofotometri melalui uji DPPH. Kandungan fitokimia ekstrak juga diuji secara kualitatif. Hasil uji kualitatif menunjukkan bahwa ekstrak-etanol Acalypha indica maupun campuran ekstrak-etanol Acalypha indica dan Centella asiatica positif mengandung fitokimia berupa flavonoid dan steroid. Hasil pengukuran aktivitas antioksidan menunjukkan bahwa Vitamin C yang menjadi kontrol positif menunjukkan nilai EC50 sebesar 0,012 mg/mL. Nilai EC50 ekstrak-etanol Acalypha indica adalah 13,68 mg/mL, sedangkan nilai EC50 campuran ekstrak-etanol Acalypha indica dan Centella asiatica adalah 39,65 mg/mL. Nilai EC50 yang lebih kecil mengindikasikan aktivitas antioksidan yang lebih tinggi. Dengan demikian, aktivitas antioksidan campuran ekstrak-etanol Acalypha indica dan Centella asiatica lebih rendah dibandingkan dengan ekstrak-etanol Acalypha indica.

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In low or moderate concentration, free-radicals have physiological role for cellular functions. Excessive production of free-radicals may induce oxidative stress, which is the pathogenesis basis of many diseases. Exogenous antioxidants supply is needed to support the function of endogenous antioxidants in preventing oxidative stress. The ethanolic-extract of Acalypha indica and Centella asiatica possess antioxidant activity. This study was managed to know the antioxidant activity of ethanolic-extract mixture of Acalypha indica and Centella asiatica in comparison with ethanolic-extract of Acalypha indica. The combination of extract was expected to improve the antioxidant activity and to reduce the dosage. The DPPH assay test with spectrophotometry was performed to measure the antioxidant activity. This study involved qualitative examination of phytochemical content in the extracts. In the qualitative-examination, both the extracts had flavonoids and steroids. Vitamin C as the positive control exhibited EC50 value as much as 0.012 mg/mL. The EC50 score of the ethanolic-extract mixture was 13.68 mg/mL, while the ethanolic-extract of Acalypha indica’s was 39.65 mg/mL. The lower EC50 score indicates the higher antioxidant activity. Thus, the ethanolic-extract mixture of Acalypha indica and Centella asiatica has lower antioxidant activity compared to the ethanolic-extract of Acalypha indica."

"Latar Belakang Peningkatan konsumsi diet tinggi fruktosa kolesterol (DTFK) pada masa ini telah memicu obesitas yang menyebabkan berbagai gangguan kesehatan. Pada kondisi obesitas, Interleukin-10 (IL-10) merupakan mediator inflamasi yang akan mengalami penurunan di jaringan adiposa. Tanaman Acalypha indica (Ai) merupakan salah satu tanaman yang terbukti memiliki beberapa senyawa yang menghambat inflamasi yang terjadi dalam kondisi obesitas. Penelitian ini menganalisis senyawa dalam akar Ai yang memiliki ikatan dengan IL-10 menggunakan metode molecular docking dan mengukur kadar IL-10 di jaringan adiposa viseral tikus obesitas. Metode Studi molecular docking dilakukan pada 17 senyawa ekstrak akar Ai untuk membuktikan afinitasnya dengan IL-10 (PDB: 2H24) sebagai protein target. Kemudian, studi eksperimental dilakukan pada 23 ekor tikus Sprague-Dawley jantan yang dibagi ke dalam empat kelompok, yakni kelompok diet normal, kelompok DTFK (kontrol negatif), DTFK+Ai, dan kelompok DTFK+Gemfibrozil (kontrol positif). Setelah 28 hari, tikustikus tersebut diterminasi dan diukur kadar IL-10 pada jaringan adiposa viseral menggunakan ELISA dan Bradford Protein Assay. Hasil Hasil studi molecular docking menunjukkan bahwa keseluruhan senyawa memiliki ikatan terhadap IL-10 dengan afinitas tertinggi dimiliki oleh stigmasterol (ΔG: -7,95 kkal/mol; Ki: 1,49 mikromolar) dan stigmast-5-en-3-ol (ΔG: -6,86 kkal/mol; Ki: 9,31 milimolar). Pemberian Ai terbukti memberikan hasil peningkatan kadar IL-10 sebesar 3x terhadap kelompok DTFK (DTFK = 0,157+0,041; DTFK+Ai = 0,485+0,021) yang berbeda bermakna (p<0,05). Kesimpulan Pemberian ekstrak akar Ai dapat meningkatkan kadar IL-10 pada jaringan adiposa viseral tikus obesitas yang diperkirakan melalui interaksi utama ligan stigmasterol dan stigmast- 5-en-3-ol dalam senyawa Ai.

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Introduction Increasing consumption of a high fructose corn syrup (DTFK) diet during this period has triggered obesity, which causes various health problems. In obesity-related diseases, Interleukin-10 (IL-10) is an inflammatory mediator that decreases in adipose tissue. The Acalypha indica (Ai) plant is one that has been proven to have several compounds that inhibit inflammation that occurs in obesity-related conditions. This study analyzed compounds in Ai roots that bind to IL-10 using the molecular docking method and measured IL-10 levels in the visceral adipose tissue of obese mice. Method Molecular docking was performed on 17 ligands of Ai root extract to prove their affinity with IL-10 (PDB: 2H24) as a target protein. Then, an experimental study was conducted on 23 male Sprague-Dawley rats, which were divided into four groups: normal diet, DTFK (negative control), DTFK+Ai, and DTFK+ Gemfibrozil (positive control). After 28 days, these rats were terminated and IL-10 levels were measured using ELISA and Bradford Protein Assay. Results The results of molecular docking studies show that all compounds bind to IL-10 with the highest affinity in stigmasterol (ΔG: -7.95 kcal/mol; Ki: 1.49 micromolar) and stigmast- 5-en-3-ol (ΔG: -6.86 kcal/mol; Ki: 9.31 millimolar). The administration of Ai was proven to increase 3x IL-10 levels in the DTFK group (DTFK = 0.157+0.041; DTFK+Ai = 0.485+0.021), which was significantly different (p<0.05). Conclusion Administration of Ai root extract can increase IL-10 levels in visceral adipose tissue of obese mice which is thought to be through the main interaction of the stigmasterol and stigmast-5-en-3-ol ligands in the Ai compound."

"Hipoksia merupakan kondisi inadekuat suplai oksigen menyebabkan peningkatan radikal bebas perusak organ, contohnya otak. Radikal bebas dinetralisir antioksidan endogen dan eksogen. Acalypha indica dan Centella asiatica memiliki efek antioksidan. Pewarnaan AgNOR mengukur derajat kerusakan sel. Penelitian bertujuan membuktikan efek pemberian kombinasi ekstrak etanol akar Acalypha indica dan Centella asiatica pada histopatologi neuron korteks serebrum tikus pascahipoksia pewarnaan AgNOR. Penelitian mendapat sediaan dari 26 ekor tikus Spraque-Dawley, terbagi dalam 6 kelompok: kontrol normal; kontrol negatif (hipoksia+aquades); hipoksia+kombinasi 1; hipoksia+kombinasi 2; hipoksia+tunggal 2; kontrol positif (hipoksia+vit C). Induksi hipoksia selama 7 hari dengan mengalirkan O2 10% dan N2 90% bertekanan 1 atm. Setelah 7 hari, dilakukan Analisis Gas Darah, reoksigenasi 1 jam, dilanjutkan pemberian perlakuan aquades; (AI200+CA150); (AI250+CA100); CA150 dan vitamin C selama 7 hari. Pada akhir studi dilakukan euthanasia, organ otak diambil untuk pemeriksaan histopatologi dengan pewarnaan AgNOR. Hasil: Pemberian esktrak kombinasi 2, tunggal 2, dan kombinasi 1 berbeda bermakna dibandingkan kontrol negatif (p=0,000; p=0,005; p=0,023). Kesimpulan: Kombinasi ekstrak etanol (AI250+CA100) memiliki efek terbaik untuk mengurangi kerusakan neuron korteks serebrum secara histopatologi.

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Hypoxia is inadequate conditions of oxygen causes increasing free radicals destroying organs, e.g. brain. Free radicals neutralized by endogenous and exogenous antioxidants. Acalypha indica and Centella asiatica have antioxidant effects. AgNOR staining measures degree of damaged cell. The aim of this study was to prove the effect of the combination of ethanol extract on the roots of Acalypha indica and Centella asiatica on the histopathology of cortical neurons in cerebrum of rats after hypoxia in AgNOR staining. The study of 26 Spraque-Dawley rats, divided into 6 groups: normal control; negative control (hypoxia + aquades); hypoxia + combination 1; hypoxia + combination 2; hypoxia + single 2; positive control (hypoxia + vit C). Induction of hypoxia for 7 days by flowing 10% O2 and 90% N2 with 1 atm pressure. After 7 days, Blood Gas Analysis, 1 hour re-oxygenation, followed by treatments; distilled water; (AI200 + CA150); (AI250 + CA100); CA150 and vitamin C for 7 days. At the end of study, euthanasia was carried out, brain organs were taken for histopathology examination with AgNOR staining. The combination 2, single 2 and combination 1 extracts were significantly different compared to negative control (p = 0,000; p = 0.005; p = 0.023). The combination of ethanol extract (AI250 + CA100) has the best effect to reduce damage to cerebral cortical neurons histopathologically."

"Sepsis dikenal secara luas sebagai sindrom klinis yang merupakan hasil dari respon sistemik yang hebat terhadap infeksi dan melibatkan gangguan pada berbagai organ penderitanya Sepsis merupakan penyebab kematian tersering pada pasien yang dirawat di unit perawatan intensif Proses inflamasi dengan respon maladaptif terhadap proses tersebut merupakan mekanisme terjadinya disfungsi organ multipel dan kematian pada sepsis. Heparin juga diketahui dapat memodulasi proses inflamasi, namun belum banyak penelitian yang menjelaskan dosis heparin sebagai antiinflamasi. Penelitian ini ingin mengkaji lebih jauh pengaruh dosis heparin terhadap aktivasi faktor transkripsi Nuclear Factor Kappa Beta (NFkB) melalui pengukuran terhadap kadar NFkB sub unit p65 dan produksi sitokin proinflamasi Tumor Necrosis Factor Alpha (TNF-?) untuk memberikan dasar ilmiah mengenai penggunaan dosis heparin sebagai antiinflamasi pada pasien dengan sepsis berat. Penelitian ini merupakan eksperimental laboratorik dengan menggunakan sampel dari 5 orang sukarelawan sehat dan 10 orang pasien sepsis berat. Sel mononuklear darah tepi (peripheral blood mononuclear cells/PBMC) dari darah vena diperoleh dengan teknik Ficoll-hypaque. Fraksi non-monosit dari PBMC menggunakan Monoclonal Antibody Cell Sorter (MACS) microbeads. Isolasi monosit diresuspensi pada medium Roswell Park Memorial Institute (RPMI) yang disuplementasi dengan 10% fetal bovine serum (FBS). Sel kemudian dipaparkan dengan heparin 0.1 IU/ml (1?g/ml), 1 IU/ml (10 ?g/ml), dan 10 IU/ml (100 ?g/ml), sedangkan kontrol tidak diberi perlakuan. Setelah diinkubasi pada 37°C dan 5% CO2 selama 6 jam dan 24 jam, pelet sel diukur NFkB sedangkan supernatan diukur TNF-? dengan metode ELISA. Hasil penelitian menunjukkan kadar NFkB sub unit 65 dan produksi TNF-? pada kultur monosit pasien sepsis berat yang mendapat heparin ditemukan secara signifikan lebih rendah daripada kontrol. Heparin dosis rendah 0.1 IU/ml (1?g/ml), secara signifikan menurunkan aktivasi NF?B dan produksi TNF-? lebih besar. Penelitian ini menunjukkan bahwa heparin menghambat aktivasi NFkB sehingga menurunkan produksi sitokin TNF-?. Heparin dengan dosis rendah menunjukkan pengaruh sebagai antiinflamasi lebih besar. Hasil yang diperoleh diharapkan memberikan pemahaman baru mengenai pengaruh dosis heparin sebagai anti-inflamasi pada pasien sepsis berat.

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Sepsis is a severe systemic response to infection, based on the Systemic Inflammatory Response Syndrome (SIRS) plus infection proven or clinically suspected infection, with evidence of organ failure due to hypo-perfusion. Anti-inflammatory therapy is one of the important therapeutic modality and applied potential as sepsis therapy. Inflammatory process with a maladaptive response to this process is the mechanism for the occurrence of multiple organ dysfunction and mortality in sepsis. Bacterial lipopolysaccharide binds to CD14 receptors and toll-like receptor (TLR) on the surface of monocytes and activates intracellular signal transduction involving beta-Kinase Inhibitor Kappa/IKKB that activates Nuclear Factor Kappa-Beta (NFkB) enter the nucleus and initiate transcription of RNA that encodes the production of cytokines TNF-?. Heparin has long been known as an anticoagulant, but also known to modulate the inflammatory process. This study want to examine further role of heparin as an anti-inflammatory to provide a scientific basis for the use of heparin in sepsis. Peripheral blood mononuclear cells (peripheral blood mononuclear cells/PBMC) of patients with severe sepsis obtained by Ficoll-Hypaque technique. Non-monocyte fraction of PBMC were removed using a Monoclonal Antibody Cell Sorter (MACS) microbeads. Isolation of monocytes resuspended in Roswell Park Memorial Institute medium (RPMI) supplemented with 10% fetal bovine serum (FBS). Cells then exposed to 0.1 IU heparin (1 ?g/ml), 1 IU (10 ug/ml), and 10 IU (100 ?g/ml), whereas controls did not. After incubation at 37°C and 5% CO2 for 6 hours and 24 hours, each sample is aspirated into micro centrifuge tube and rotated at a speed of 400 g for 5 min. Cell pellet was measured for NFkB and supernatant measured for TNF-?. Both were measured by ELISA. The results showed NFkB activation and TNF-? production in cultured monocytes severe sepsis patients who received heparin found to be significantly lower than controls. Low-dose heparin 0.1 IU (1?g/ml), significantly decreased the activation of NFkB and TNF-? production a lot more. This study demonstrates how heparin interfere an inflammatory response in severe sepsis patients monocytes through interrupt NFkB activation that decrease the production of cytokines TNF-?. The results are expected to provide new insights into the role of heparin as an anti-inflammatory in patients with severe sepsis."