In-Silico Screening Compounds of Brassica rapa ssp. chinensis as Potential Inhibitor of Neutral Amino Acid Transporter B0AT1 as an Alternative Phenylketonuria Treatment

Phenylketonuria (PKU) is known as a severe autosomal recessive disease caused by mutations in the expression enzyme, namely the PAH (Phenylalanine Hydroxylase) enzyme that causes the build-up of phenylalanine in the body. Untreated PKU affected brain damage and developmental problems. One of the strategies to reduce phenylalanine in the body is inhibiting B0AT1 activity using carotenoid and terpenoids compounds from Bok choy (Brassica rapa ssp.chinensis). In this study, we evaluated the nine carotenoid and terpenoid compounds from Bok choy as B0AT1 inhibitors. Nine Bok choy compounds, including alpha-carotene, beta-carotene, dimethylallyl pyrophosphate, isopentenyl pyrophosphate, lutein, neoxanthin, violaxanthin, geranylgeranyl diphosphate, and zeaxanthin were downloaded from PubChem database, while the 3D structure of B0AT1 was retrieved from Protein Data Bank RCSB. The compounds and B0AT1 were prepared by PyRx 0.8 version and Discovery Studio ver 21.1.1, then docked with Hex 8.0.0 and analyzed using Discovery Studio ver 21.1.1. This screening implies that three terpenoid compounds dimethylallyl pyrophosphate, isopentenyl pyrophosphate, and geranylgeranyl diphosphate interacts in C domain of B0AT1 while six carotenoid compounds, alpha carotene, beta-carotene, lutein, neoxanthin, violaxanthin, and zeaxanthin interacts in A domain and have possibility to inhibit B0AT1, because it interact with same A domain and have a stronger binding energy than phenylalanine. Alpha carotene has a same residue with phenylalanine, Phe144, making it potentially greater than other compound as inhibitors. Brassica rapa ssp. chinensis is indeed good for consumption by people with phenylketonuria, but it is also necessary to do a further compound screening in other low-phenylalanine diet foods to know which one is better as alternative phenylketonuria treatment.

Spirulina platensis’s phycocyanobilin as an antiangiogenesis by inhibiting VEGFR2-VEGFA pathway in breast cancer: in silico study

Breast cancer is a cancer type that leads to many women deaths. The causes are from the primary tumour and other progressions such as metastatic and angiogenesis. Some therapy strategies have been developed to treat breast cancer, but they are not good enough for treating breast cancer progressions. Spirulina platensis has a phycocyanin and a phycocyanobilin, known as antioxidant and antiinflammatory bioactivities. This study identified anticancer activity of phycocyanobilin from Spirulina platensis. We also investigated the phycocyanobilin mechanism in breast cancer inhibition through VEGFR2-VEGFA pathway. In silico analysis was conducted the inhibition modelling of phycocyanobilin to the VEGF-VEGFR pathway. The VEGF and VEGFR proteins were taken out from Protein Data Bank (PDB) database and were prepared with BIOVIA Discovery Studio 2019. Phycocyanobilin as a ligand was obtained from PubChem and prepared with PyRx. The molecular docking was conducted using HEX 8.0.0 CUDA and the last step is the protein-ligand complexes were visualized and analyzed using BIOVIA Discovery Studio 2019. It results in five protein-ligand complexes in which the receptor-ligand complex VEGFR2-[VEGFA-phycocyanobilin] can inhibit the angiogenesis process by phycocyanobilin binds to VEGFA, and it prevents the angiogenesis process by blocks the VEGFR2 and stops VEGFA to bind with VEGFR2. Thus phycocyanobilin has potential as an anticancer agent especially in breast cancer as an antiangiogenesis.

In-Silico Analysis of Procyanidin Type-A Extracted From Cinnamon for Diabetes Mellitus Type 2 Treatment

Type 2 diabetes mellitus (T2DM) is the most common disease in developing countries. People with type-2 diabetes are at high risk of complications leading to disability and premature death. Procyanidin compounds in cinnamon have an insulin-like activity that can regulate normal blood sugar levels. This research aimed to investigate the interaction between α-glucosidase and α-amylase with procyanidin A and their potential for diabetes treatment therapy. Data mining receptor was downloaded from RCSB PDB and ligands from PubChem. Drug likeness properties were evaluated using SwissADME, while toxicity analysis was assessed using metatox. Molecular docking between α-glucosidase and α-amylase with procyanidin A was performed using HEX 8.0.0 and was visualized by Discovery Studio. Procyanidin A showed interaction with α-glucosidase by non-bonds interaction, including hydrogen, hydrostatic and hydrophobic bonds, while procyanidin A and α-amylase formed hydrogen and hydrophobic bonds. Procyanidin A is an alternative treatment for T2DM with a variety of supportive chemical bonds. Procyanidin A has an excellent ability to inhibit activity α-glucosidase and α-amylase in the process of breaking down glucose in the intestines.

Anti-Obesity Properties of Black Pepper (Piper nigrum): Completing Puzzle using Computational Analysis

Pepper (Piper nigrum) is one of the most common spices found in almost every food. Current knowledge informed that pepper regulates physiological activity in obesity. However, the exact mechanism is still poorly understood. This study determined the potential of piperine and piperidine as major compounds in pepper as GHSR-Ghrelin inhibitors due to over-activity of Ghrelin as appetite hormone in obesity. Molecular docking was performed to simulate the binding pattern of piperine and piperidine as GHSR-Ghrelin antagonist. The result showed that piperidine has a lower potential as GHSR-Ghrelin antagonist than piperine based on binding energy calculation and amino acid interaction. Further, piperine binding to GHSR could shift the Ghrelin binding site to the GHSR. In conclusion, piperine may act as an inhibitor of GHSR-Ghrelin interaction to prevent appetite behavior resulting in bodyweight loss in obesity.

In Silico Study of Vacuolin-1 as an Inhibitor of HSP27 for Precancerous Treatment of Breast Cancer

Breast cancer has a great chance of being cured if it is diagnosed and treated properly in its early stage. The pre-cancer stage is an early stage of cancer development characterized by the overexpression of HSP27. Therefore, HSP27 can be a therapeutic target of cancer. This study aims to analyze whether vacuolin-1, a small drug compound known for its ability to inhibit metastasis, can inhibit HSP27 to prevent precancerous development in breast cancer, as well as its ADME and biosafety aspects. Protein & ligand structures were obtained from RCSB PDB and PubChem database. Preparation was performed with Discovery Studio and PyRx. Drug-likeness/ADME analysis was performed in Swiss-ADME web server. Biosafety analysis was performed in MetaTox web server. Molecular docking was performed using PyRx. The visualization of docking results was performed using Discovery Studio. The docking result between vacuolin-1 and HSP27 showed that vacuolin-1 can act as an HSP27 inhibitor by interacting with S78 residue of HSP27 and blocking its phosphorylation as well as depolymerization process. The drug-likeness characterization result of this compound showed that vacuolin-1 violates one of the four Lipinski's Rule of Five. Biosafety analysis showed that vacuolin-1 has a low toxicity level with an estimated LD50 around 13,016.65 mg/kg.

Virtual Screening of Mimosa pudica Secondary Metabolites as Hyaluronidase B Potential Inhibitor to Prevent Vespa velutina Venom Spreading

Vespa velutina, also known as the Yellow-legged hornet, is a wasp species native to Asia with a large distribution area in Indonesia. Hyaluronidase B in a wasp venom acts as a "spreading factor", which is the key at the beginning of envenomation. Shameplant (Mimosa pudica), a common plant in Indonesia, has shown the potential to be a hyaluronidase B inhibitor. This study aimed to analyze the potential of secondary metabolites in Shameplant as an inhibitor of V. velutina Hyaluronidase B base on their molecular interactions and as a topical drug base on physicochemical characteristics. In silico computational studies is performed to predict the binding modes of M. pudica compounds and hyaluronidase B enzyme. The secondary metabolites were retrieved from the PubChem database and screened using SwissADME. The seven metabolite compounds were docked with Hyaluronidase B and hyaluronan by HEX Cuda 8.0.0 program. Hyaluronidase B was also docked with its native ligand (hyaluronan) to validate the docking study. Three dimensional and 2D views were then evaluated using Discovery Studio 2016. Results of this study are all compounds do not have the same molecular interaction with the control. It defines no inhibition of the interaction on the active side. Mimopudine is the most potent inhibitor of hyaluronidase B based on its binding energy. While, jasmonic acid is the only compound that meets the physicochemical parameter of the topical drug.

Effects of Mango Mistletoe (Dendrophthoe pentandra L. Miq) Extracts on Brain in Hypertensive Rats Treated with Deoxycorticosterone Acetate (DOCA)-Salt

Mango mistletoe (Dendrophthoe pentandra) is a plant that has the potential as a medicinal plant. Mango mistletoe is reported to contain the flavonoids quercetin, mesoinositol, rutin, and tannins. Hypertension as a non-communicable disease is a very serious health problem experienced by people in developing countries. Hypertension can be caused by high ROS (reactive oxygen species) which can inhibit oxygen flow to the heart and brain. Antioxidants can reduce the risk of hypertension. Damage to the brain due to hypertension is manifest in the white matter area. This study aimed to see how the histopathological profile of the brain in hypertensive rats (DOCA-Salt) which were given mango mistletoe methanolic extract (MMME) by experimental method. The number of tested animals was 25 male Wistar rats divided into 5 groups, each group contained 5 rats, they were negative control (Control-) as normotension, positive control (Control+) as inducer, and the treatment group with the provision of MMME at a dose of 50 mg / kgBW, 100 mg / kgBW, and 200 mg / kgBW. Data were analyzed using JAMOVI 1.1.9.0. Based on the results of the study showed that the difference in significant values between all groups was p<0.05. So, that giving EMBM to male rat significantly can decrease the number of cell necrosis and affect the width of the white matter area of the brain. The three dose variations did not show a significant difference, so this effect was controlled by the MMME dose of 50 mg / KgBW which was the optimum dose in reducing the amount of cell necrosis in the white matter area of the male Wistar rat brain.

Histopathological Profile of Therapeutic Doses of Mango Mistletoe Methanolic Extract (MMME) in Cardiac of Hypertensive Rats (DOCA-Salt)

This study determined the effect of Mango mistletoe Methanolic Extract (MMME) on the cardiac's histopathological profile of hypertensive rats (DOCA-Salt) treated. The MMME was treated on fifty rats for 14 days, divided into five treatments: negative control, positive control, doses 50, 100, and 200 mg/kg BW with five replications. One-way ANOVA analysis was used, namely JAMOVI with version 1.1.9.0, and for cell calculation, diameter using the IMAGE J application. Results showed that there were no significant differences in the histopathological profile of the cardiac in hypertensive rats (DOCA-Salt) treated with MMME for 14 days on the diameter of the heart muscle cells between the control (+) and control groups (-), treatments 1, 2, and 3. This is evidenced by the analysis of p-value> 0.05, namely 0.187 millimeters. Therefore, we concluded that MMME does not affect the diameter of heart/cardiac organ muscle cells. However, there was a significant difference in the amount of necrosis in the cardiac of hypertensive rats between control (+) and control (-) groups, treatments 1, 2, and 3. Based on the results, MMME reduces the number of necrosis in the heart/cardiac organ.

In silico study: Potential prediction of Curcuma longa and Cymbopogon citratus essential oil as Lipoxygenase inhibitor

Inflammation is the human body response by the injure as a results the inflammation will release LOX. To curve the conditions we use the bioactive from the nature are essential oil from Curcuma longa and Cymbopogon citratus because has a potential has pharmacologist activity. The purpose of this research to investigate the role essential oil from Curcuma longa and Cymbopogon citratus through LOX gene. Several chemical substances, including 3,7-dimethyl-1,3,6-octatriene, camphor, eugenol, curzerene and isoborneol were retrivied from PubChem database. The PyRx 0.8 was used to minimize and convert the sdf file to pdb format file of ligands. Those compounds were predicted their interaction using STITCH online server. Ligands and protein were docked by HEX Cuda 8.0.0 program, 3D and 2D views were evaluated using Discovery studio ver.19.0.0 and LigPlot+ ver 2.2, respectively. We found fourteen amino acid residues from LOX which bound the chemical compounds. Those interaction was supported by hydrogen bond with variety energy binding. To sum up, the essential oil from Curcuma longa and Cymbopogon citratus has a potential function as inhibitor LOX by inhibiting fourteen active side of the LOX gene.

Role of Superoxide Dismutases (SODs) in Hypertensive Rats After Administration of Mango Mistletoe Methanolic Extract

Hypertension is a condition where there is an abnormal rise in blood pressure that may be the primary cause of cardiovascular disease. Hypertension induces the production of free radicals known as reactive oxygen species (ROS) and oxidative stress. The purpose of this study is to further examine the function of Dendropthoe pentandra as an endogenous antioxidant modulator in this case superoxide dismutase (SOD) in hypertensive rats.The testing approach used is experimental. Data were analyzed using the one-way ANOVA test and the Post Hoc test to see variations in SOD levels in different treatments. This research used a hypertensive rat model induced by deoxycorticosterone acetate (DOCA) and salt. The number of animals tested was 25 white male rats divided into 5 groups, each containing 5 rats.The group consisted of a control group, a group of non- Extract methanolic of mango mistletoe hypertensive rats, and three groups of hypertensive rats receiving mango mistletoe methanolic extract (EMBM) at dosages of 50 mg/kg, 100 mg/kg, and 200 mg/kg body weight. Based on the results of the study, it is known that the levels of increased lung SOD with extract methanolic of mango mistletoe dosage variations in all treatment groups were not different. The administration of mango parasite methanolic extract at a dose of 50 mg / kgBW was optimum in increasing lung SOD levels in hypertensive rats.