A Double-blind, Randomized Controlled Trial of Ciplukan (Physalis angulata Linn) Extract on Skin Fibrosis, Inflammatory, Immunology, and Fibrosis Biomarkers in Scleroderma Patients

Background: scleroderma is an autoimmune disease characterized by organ fibrosis, resistant to standard treatment. It is suspected the addition of Physalis angulata Linn. (Ciplukan) extract as adjuvant therapy can improve the scleroderma skin fibrosis. The aim at this study is to evaluate the effect of ciplukan extract as adjuvant on scleroderma skin fibrosis in standard therapy, based on modified Rodnan skin scale (MRSS), inflammatory biomarkers, immunology and serum fibrosis. Methods: double-blind, randomized clinical trial was performed in scleroderma patients with stable disease at Cipto Mangunkusumo hospital and Hasan Sadikin hospital during November 2015−March 2017 who met the selection criteria and continued to receive standard therapy. The subjects were randomly allocated into two groups: the study group received the ciplukan  extract 3 x 250 mg / day for 12 weeks and the placebo group. Examination of MRSS, ESR, P1NP, BAFF and sCD40L was performed every 4 weeks until the end of the study. Results: fifty-nine subjects completed the study. They consisted of 29 subjects of the treatment group and 30 of the placebo group, with an average age of 41 (SD 9) years, the proportion of women: male = 9 : 1. There was a significant improvement of skin fibrosis in the study group with a highly significant decrease in MRSS (35.9% VS 6.3%, p <0.001) and a relative decrease in P1NP levels (17.8% VS 0.7%, p = 0.002). No decrease in ESR, BAFF and sCD40L levels in both groups. There was a weak but significant positive correlation between MRSS with P1NP levels (r = 0.236, p = 0.036). Conclusion: Ciplukan extract with dose 3 x 250 mg for 12 weeks as adjuvant on scleroderma standard therapy alleviates skin fibrosis significantly based on MRSS and P1NP levels

Perubahan Parameter Biokimia, Histopatologi Ginjal Tikus Spraque Dawley Pascahipoksia Oleh Ekstrak Akar Acalypha indica dan Herba Centella asiatica

Hipoksia kronik merupakan salah satu penyebab penyakit ginjal akibat peningkatan pembentukan Reactive Oxygen Species (ROS)  dalam sel. Kombinasi ekstrak akar Acalypha indica 250 mg/KgBB (AI250) dan Centella asiatica 150 mg/kgBB (CA150) memiliki efek neuroterapi pada tikus Spraque Dawley pascahipoksia. Penelitian dilakukan untuk membuktikan manfaat kombinasi ekstrak etanol dan/atau ekstrak tunggalnya dapat memperbaiki kerusakan ginjal tikus pascahipoksia melalui mekanisme antioksidan. 28 tikus jantan dikelompokkan dalam 7 kelompok: kontrol normal; kontrol hipoksia+air; hipoksia+(AI200+CA150); hipoksia+(AI250+CA100); hipoksia+AI250; hipoksia+CA150; hipoksia+vitamin C. Hipoksia selama 7 hari dalam hypoxic chamber berisi O2 10% dan N2 90%, 1 atm. Setiap kelompok diberi perlakuan selama 7 hari. Pada akhir studi hewan diterminasi. Darah dan organ ginjal diambil untuk pemeriksaan biokimia dan histopatologi.Kombinasi  (AI250+CA100) menurunkan kadar MDA ginjal dan plasma secara bermakna dibandingkan kontrol hipoksia (p=0,001 dan p=0,021) dan AI250 (p=0,003 dan 0,043). Kombinasi AI250+CA100 terjadi penurunan ekspresi relatif mRNA HIF-1α (p=0,014), kadar urea plasma (p=0,001) dan perbaikan lesi intra-glomerulus p=0,013.Kesimpulan: Kombinasi (AI250+CA100) dan tunggal AI250 memiliki aktivitas antioksidan terbaik dalam mencegah kerusakan ginjal pascahipoksia, secara biokimiawi dan histopatologinya

THE ROLE OF ACALYPHA INDICA LINN. EXTRACT ON HEART RATES WITH MYASTHENIA GRAVIS RAT MODEL

  Objective: Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction (NMJ) caused by antibodies that attack components of the postsynaptic membrane, impair neuromuscular transmission, and lead to weakness and fatigue of skeletal muscle. Acetylcholine is also used as a neurotransmitter in the autonomic nervous system. Striated cardiac muscle can be a target for immune attack manifesting as heart failure, arrhythmia, and sudden death. Involvement of the heart rate (HR) has been claimed and reported, but a causal connection between MG and altered cardiac function has not been found.Methods: For this study of experimental autoimmune MG (EAMG) is used rocuronium, prostigmine, and Acalypha indica (AI) Linn. compared with HR.Results: From the results, the study found that sympathetic activity of HR variability in EAMG injected with rocuronium 10 mg/kg body weight (BW) in 10 min significantly found increasing in measures of short-term variations in HR variability, indicating parasympathetic impairment.Conclusion: We conclude that in MG, cholinergic transmission is affected more diffusely than previously thought. Furthermore, AI was given orally 30 mg/kg BW has an effect similar to the injecting of prostigmine 10 mg/kg BW that can reduce HR. Driven by the fact that the pharmacological treatment of MG is unsatisfied, it needs the therapeutic development for MG using herbal ingredients of AI. This means that the AI compositions containing anti-MG whose composition should be investigated for the next research

Exploration of the main active metabolites from Tinospora crispa (L.) Hook. f. & Thomson stem as insulin sensitizer in L6.C11 skeletal muscle cell by integrating in vitro, metabolomics, and molecular docking

Ethnopharmacological relevance: Tinospora crispa (L.) Hook. f. & Thomson stem (TCS) has long been used as folk medicine for the treatment of diabetes mellitus. Previous study revealed that TCS possesses multi-ingredients and multi-targets characteristic potential as insulin sensitizer activity. However, its mechanisms of action and molecular targets are still obscure. Aim of the study: In the present study, we investigated the effects of TCS against insulin resistance in muscle cells through integrating in vitro experiment and identifying its active biomarker using metabolomics and in molecular docking validation. Materials and methods: We used centrifugal partition chromatography (CPC) to isolate 33 fractions from methanolic extract of TCS, and then used UHPLC-Orbitrap-HRMS to identify the detectable metabolites in each fraction. We assessed the insulin sensitization activity of each fraction using enzyme-linked immunosorbent assay (ELISA), and then used confocal immunocytochemistry microscopy to measure the translocation of glucose transporter 4 (GLUT4) to the cell membrane. The identified active metabolites were further simulated for its molecular docking interaction using Autodock Tools. Results: The polar fractions of TCS significantly increased insulin sensitivity, as measured by the inhibition of phosphorylated insulin receptor substrate-1 (pIRS1) at serine-312 residue (ser312) also the increasing number of translocated GLUT4 and glycogen content. We identified 58 metabolites of TCS, including glycosides, flavonoids, alkaloids, coumarins, and nucleotides groups. The metabolomics and molecular docking simulations showed the presence of minor metabolites consisting of tinoscorside D, higenamine, and tinoscorside A as the active compounds. Conclusions: Our findings suggest that TCS is a promising new treatment for insulin resistance and the identification of the active metabolites in TCS could lead to the development of new drugs therapies for diabetes that target these pathways

The Preparation of Liposomes derived from Mixed Micelles of Lecithin added by Sodium Cholate, followed by Dialysing using Hemoflow High Flux F60S

Liposomes are used for drug carriers meaning that drugs are incorporated in the membrane or the vesicle of the&nbsp;liposomes. In this study, liposomes were prepared from mixed micelles, consisting of phosphatidylcholine, without or&nbsp;with cholesterol and sodium cholate was added in several ratios namely 0.44; 0.55; 0.63; 0.70; 0.90 and 1.10. After the&nbsp;preparation, the sodium cholate has been removed by a dialysis membrane, using the Hemoflow High Flux, which is&nbsp;generally used for haemodialysis. The Hemoflow High Flux is a tool in an effort to obtain a simple, quick, effective&nbsp;method for removing sodium cholate in the process of preparing liposomes. The effectiveness of this tool was proved&nbsp;by the particle size of the liposome which was measured by the Malvern Particle Sizer. The particle size of the liposome&nbsp;consisting of phosphatidylcholine (PC) without cholesterol and with cholesterol was 63-68 nm at all ratios and&nbsp;approximately 125 nm at the ratio of 0.55; 0.63; 0.70, respectively. The particle size of the liposome tended to be&nbsp;smaller after dialyzing, although the concentration of lipids tended to increase. However, a large amount of buffer&nbsp;solution has to be used with this method

Duration of watching TV and child language development in young children

Background Many factors contribute to language development in children. About 5-8% of children in Indonesia experience delayed language skills. Young children need appropriate stimulation for optimal development. Children who watch television (TV) for long periods of time may receive less two-way interaction, the appropriate stimulation for learning. As such, shorter duration of the appropriate stimulation may impede language development in small children. Objective To assess for an association between duration of watching TV and language development in young children. Methods This cross-sectional study was done with primary data collected from questionnaires. Subjects, aged 18 months to 3 years, were from a Jakarta-area community health center (Puskesmas) Jatinegara and the Pediatric Growth and Development Clinic, Cipto Mangunkusumo Hospital, Jakarta. Their language development was tested using the Developmental Pre-screening Questionnaire (Kuesioner Pra Skrining Perkembangan, KPSP) and the Early Language Milestone (ELM Scale 2) test. Results From a total of 84 subjects, 47 (56%) had normal and 37 (44%) had delayed language development. Duration of watching TV was categorized as 4 hours per day. Children who watched TV >4 hours/day (OR 4.4; 95%CI 1.68 to 11.7; P=0.002), and children who watched both Indonesian and English language TV programs (OR 14.7; 95%CI 1.77 to 123.0; P=0.004) had higher risk of language delay. Other variables such as sex, first age exposed to TV, use of gadgets, and TV in the bedroom had no significant associations with delayed language development. Conclusion Children who watch TV >4 hours/day had four times higher risk of developing language delay. In addition, those who watch TV programs in both Indonesian and English, also have a 14.7 higher risk of delayed language development

IN SILICO STUDY OF ARYL EUGENOL DERIVATIVES AS ANTI-COLORECTAL CANCER BY INDUCING OF APOPTOSIS

Objective: Apoptosis is one method the body uses to get rid of unneeded or abnormal cells, but cancer cells have strategies to avoid apoptosis. Apoptosis inducers can get around these strategies to cause the death of cancer cells.Methods: We screened some derivatives aryl eugenol based on their interactions with Bcl-2 in many cancer tissues, using computer software applications (in silico method) to determine the best compounds. The docking experiment on Bcl-2 (Protein Data Bank ID 4LXD) was carried out by suitably positioning the energy-minimized ligand in the active site while carefully monitoring non-bonded interactions of the ligand enzyme.Results: The resulting ligand-receptor complex was docked using the Autodock Vina software. Docking results based free binding energy, EUGACl (21), EUASABr (17), EUGEABr (19), and EUASACL (17), has the lowest binding energy than navitoclax and binds significantly to BCL 2. In silico ADMET predictions revealed that except SA, ASA, and GEA, all other compounds had minimal toxic effects and had good absorption as well as solubility characteristics.Conclusion: These compounds of aryl eugenol (17, 19, and 21) may serve as a potential lead compound for developing new anticancer as apoptosis inducers

The Distribution of Liposomal-Methylprednisolone Palmitate (L-MPLP) in Several Organs in Mice after Intra-Peritoneal Injection

This study was to analyze the distribution of liposomal-methylprednisolone palmitate (L-MPLP)&nbsp;as a new drug formulation, in several organs of mice after intra-peritoneal injection. In a previous study, in vitro, the&nbsp;stability and the incorporation of methylprednisolone palmitate into liposome membranes were increased, from 70% to approximately 95% using tetra-ether lipid as a stabilizer of the liposome membrane. Based on this result, the stability of&nbsp;L-MPLP should also be proved, in vivo, that the drug, methylprednisolone palmitate, could be distributed into several&nbsp;organs more effective than in a control group (methylprednisolone palmitate and methylprednisolone as a standard of&nbsp;drug and liposome). Forty-two mice of C3H were divided into 5 study groups. Each group of animals was divided into&nbsp;6 sub-groups of time from 10 minutes to 48 hours. Each drug was injected intra-peritoneal, blood was drawn from the&nbsp;vein of the tail and the organs i.e. liver, kidneys, spleen, thymus, and bone marrow were extirpated after sacrificing the&nbsp;mice using ether. The distribution of the drug or their metabolites was higher at the minute of 180 and tended to&nbsp;decrease at the time of 48 hours after injection. The higher distribution was shown in the liver and rather high in the&nbsp;spleen, thymus, kidney, and bone-marrow respectively

The Distribution of Liposomal-Methylprednisolone Palmitate (L-MPLP) in Several Organs in Mice after Intra-Peritoneal Injection

This study was to analyze the distribution of liposomal-methylprednisolone palmitate (L-MPLP) as a new drug formulation, in several organs of mice after intra-peritoneal injection. In a previous study, in vitro, the stability and the incorporation of methylprednisolone palmitate into liposome membranes were increased, from 70% to approximately 95% using tetra-ether lipid as a stabilizer of the liposome membrane. Based on this result, the stability of L-MPLP should also be proved, in vivo, that the drug, methylprednisolone palmitate, could be distributed into several organs more effective than in a control group (methylprednisolone palmitate and methylprednisolone as a standard of drug and liposome). Forty-two mice of C3H were divided into 5 study groups. Each group of animals was divided into 6 sub-groups of time from 10 minutes to 48 hours. Each drug was injected intra-peritoneal, blood was drawn from the vein of the tail and the organs i.e. liver, kidneys, spleen, thymus, and bone marrow were extirpated after sacrificing the mice using ether. The distribution of the drug or their metabolites was higher at the minute of 180 and tended to decrease at the time of 48 hours after injection. The higher distribution was shown in the liver and rather high in the spleen, thymus, kidney, and bone-marrow respectively