Two triterpenoids from Rubus fraxinifolius leaves and their tyrosinase and elastase inhibitory activities.

Numerous therapeutic compounds have been isolated from naturally abundant organic resources, which may offer economical and sustainable sources of compounds with safe and efficacious biological activities. In the cosmetics industry, natural compounds with anti-aging activities are eagerly sought. Thus, we prepared various extracts from Rubus fraxinifolius leaves and used enzyme inhibition assays to isolate compounds with protective effects against skin aging. Two triterpenoids were isolated from Rubus fraxinifolius Poir. leaves. The structures were characterized by spectroscopic analyses (LC-ESI-MS, 1D/2D NMR) and comparison to reported data. Compound 1 and 2 were determined as 2,3-O-ethyleneglycol, 19-hydroxyurs-12-en-23,28-dioic acid and 2,3-O-propanediol,19-hydroxyurs-12-en-28-oic acid. Methanol extract and isolates were assessed for their inhibitory effects on elastase and tyrosinase. Compounds 1 and 2 inhibited elastase with IC50 122.199 µg/mL and 98.22 µg/mL, and also inhibited tyrosinase with IC50 207.79 µg/mL and 221.51 µg/mL, respectively. The molecular docking proved that both compounds have affinities toward the enzymes.

Sera Anti-P53 Antibody Provides New Information Which Explains the Link Between Diabetes and Cancer.

INTRODUCTION: Abnormalities in glucose metabolism in diabetic patients may lead to an increased risk of certain cancers. Epidemiological studies and meta-analysis have shown that factors such as gender, age, obesity, and insulin resistance are related to cancer incidence. The anti-p53 antibody is a known cancer marker due to tumor-associated p53 accumulation. Many studies have aimed to unravel the link between diabetes and cancer. Here, we aimed to elucidate the impact of diabetes on malignancies by analyzing anti-p53 antibody in sera of type 2 diabetes mellitus (T2DM) patients. MATERIALS AND METHODS: We conducted an observational study with a cross-sectional design. A total of 149 subjects comprised of 78 T2DM patients (32 with cancer risk and 46 subjects without cancer risk), 51 T2DM patients with cancer, and 20 healthy subjects as controls from multisites. The anti-p53 antibody was measured by enzyme-linked immunosorbent assay, while HbA1c was measured using the NGSP standardized method. RESULTS: We observed an 8.3-fold (p<0.05) increase of anti-p53 antibody in the sera of T2DM patients and a 24-fold increase (p<0.001) in T2DM patients with cancer compared to healthy subjects. The anti-p53 antibodies significantly increased almost three times (p<0.05) in T2DM patients with cancer (0.72 U/mL±0.20) compared to T2DM patients (0.25 U/mL±0.05). Meanwhile, this antibody was almost undetectable in healthy subjects as a control group (0.03 U/mL±0.03). The anti-p53 antibody level was higher in T2DM with cancer risk patients. However, we did not find a significant difference for it in T2DM without cancer risk patients (0.19 U/mL±0.03) and T2DM with cancer risk patients (0.29 U/mL±0.08). Multivariate regression analysis showed that T2DM with cancer was the only one independent factor (beta=0.218, p=0.019) that could predict the increase of anti-p53 antibody, controlled by age, gender, BMI, DM duration, and HbA1c. CONCLUSION: Our results showed that anti-p53 antibody almost not detected in healthy subjects, but 8.3-fold increase in the sera of T2DM patients and 24-fold increase in T2DM patients with cancer. Therefore, this biomarker provides new information which explains the link between diabetes and cancer.

In silico and in vitro identification of candidate SIRT1 activators from Indonesian medicinal plants compounds database.

Sirtuin 1 (SIRT1) is a class III family of protein histone deacetylases involved in NAD+-dependent deacetylation reactions. It has been suggested that SIRT1 activators may have a protective role against type 2 diabetes, the aging process, and inflammation. This study aimed to explore and identify medicinal plant compounds from Indonesian Herbal Database (HerbalDB) that might potentially become a candidate for SIRT1 activators through a combination of in silico and in vitro methods. Two pharmacophore models were developed using co-crystalized ligands that allosterically bind with SIRT1 similar to the putative ligands used by SIRT1 activators. Then, these were used for the virtual screening of HerbalDB. The identified compounds were subjected to molecular docking and 50 ns molecular dynamics simulation. Molecular dynamics simulation was analyzed using MM-GB(PB)SA methods. The compounds identified by these methods were tested in an in vitro study using a SIRT-Glo™ luminescence assay. Virtual screening using structure-based pharmacophores predicted that mulberrin as the best candidate SIRT1 activator. Virtual screening using ligand-based pharmacophores predicted that gartanin, quinidine, and quinine to be the best candidates as SIRT1 activators. The molecular docking studies showed the important residues involved were Ile223 and Ile227 at the allosteric region. The MM-GB(PB)SA calculations confirmed that mulberrin, gartanin, quinidine, quinine showed activity at allosteric region and their EC50 in vitro values are 2.10; 1.79; 1.71; 1.14 µM, respectively. Based on in silico and in vitro study results, mulberin, gartanin, quinidine, and quinine had good activity as SIRT1 activators.

In Silico Approach to Finding New Active Compounds from Histone Deacetylase (HDAC) Family.

BACKGROUND: Histone Deacetylase (HDAC) enzymes in the human body play an important role in the transcriptional regulation of gene expression. In the last decade, HDAC inhibitors and activators have been explored and have become known as therapeutic agents for many diseases such as osteodystrophy, neurogenerative disorders, cardiomyopathy, cancer, and diabetes. In recent years, the development of HDAC inhibitors or activators to obtain new potent lead compounds has been conducted using in vitro, in vivo, and in silico methods. Some HDAC family inhibitors and activators have been discovered. But some compounds have limitations such as not selectively binding to one of the HDAC variants. METHODS: At present, through bioinformation, HDAC family sequences have been revealed, and some in silico methods such as molecular modelling (homology modelling and pharmacophore modelling), virtual screening, and molecular dynamics are widely used to find and develop new potent and selective compounds. RESULTS: The main utilization of molecular modelling in this work is intended to complete the HDAC structure that partially lacks data regarding its amino acid monomer. Virtual screening methods are helpful in finding the best binding affinity of the test compounds. By molecular dynamic simulation, the temperature, time, and pressure can be adjusted to analyze the hydrogen bond. CONCLUSION: Combining these in silico approaches will be a more effective and efficient solution in finding new lead compounds for HDAC drug discovery research in the future.

Virtual Screening of Indonesian Herbal Database as HIV-1 Protease Inhibitor.

HIV-1 (Human immunodeficiency virus type 1)׳s infection is considered as one of most harmful disease known by human, the survivability rate of the host reduced significantly when it developed into AIDS. HIV drug resistance is one of the main problems of its treatment and several drug designs have been done to find new leads compound as the cure. In this study, in silico virtual screening approach was used to find lead molecules from the library or database of natural compounds as HIV-1 protease inhibitor. Virtual screening against Indonesian Herbal Database with AutoDock was performed on HIV-1 protease. From the virtual screening, top ten compounds obtained were 8-Hydroxyapigenin 8-(2",4"-disulfatoglucuronide), Isoscutellarein 4'-methyl ether, Amaranthin, Torvanol A, Ursonic acid, 5-Carboxypyranocyanidin 3-O-(6"-O-malonyl-beta-glucopyranoside), Oleoside, Jacoumaric acid, Platanic acid and 5-Carboxypyranocyanidin 3-O-beta-glucopyranoside.

Virtual screening of Indonesian herbal database as HIV-1 reverse transcriptase inhibitor.

HIV-1 (Human immunodeficiency virus type 1) is a member of retrovirus family that could infect human and causing AIDS disease. AIDS epidemic is one of most destructive diseases in modern era. There were more than 33 million people infected by HIV until 2010. Various studies have been widely employed to design drugs that target the essential enzymes of HIV-1 that is, reverse transcriptase, protease and integrase. In this study, in silico virtual screening approach is used to find lead molecules from the library or database of natural compounds as HIV-1 reverse transcriptase inhibitor. Virtual screening against Indonesian Herbal Database using AutoDock4 performed on HIV-1 reverse transcriptase. From the virtual screening, top ten compounds were mulberrin, plucheoside A, vitexilactone, brucine N-oxide, cyanidin 3-arabinoside, alpha-mangostin, guaijaverin, erycristagallin, morusin and sanggenol N.