Garcinia species are widely used for their slimming effects via increased fat burning and suppression of satiety. However, scientific evidence for the biological effects of Garcinia atroviridis (GA) is lacking. We investigated the phytochemical composition, safety profiles, and antioxidant and antiobesity effects of methanolic extracts of Garcinia atroviridis (MeGa) in obese female rats. Repeated dose toxicity studies were conducted according to the OECD guidelines. Upon sacrifice, haematological, biochemical, lipid profile, and serum-based metabolomics analyses were performed to evaluate metabolic expression changes and their related pathways. MeGa contains several phytochemical groups and GA fruit acids. MeGa was found to be nontoxic in both male and female rats with an oral lethal dose (LD50) of 2000 mg/kg. After 9 weeks of treatment, MeGa-treated obese rats had lower weight gain and better lipid profiles (cholesterol and triglyceride), which correlated with the altered metabolic pathways involved in the metabolism of lipid (glycerophospholipid) and biosynthesis of unsaturated fatty acid. In addition, MeGa caused differential metabolism pathways of arachidonic acid and tryptophan that affect the inflammatory response and suppression of appetite. We concluded that MeGa is safe, and its slimming effects are due to the differential metabolism of lipids.
Stevia rebaudiana is a medicinal plant recommended to diabetic or obese patients as an alternative sweetener owing to its low-calorie property. Previous studies have found that the stevioside level is highest at the time of flower bud formation and lowest at the time of preceding and following flower bud formation. Hence, this study aims to identify the genes involved in the flowering of local S. rebaudiana accession MS007 by investigating the transcriptomic data of two stages of growth, before flowering (BF) and after flowering (AF) that were deposited under accession number SRX6362785 and SRX6362784 at the NCBI SRA database. The transcriptomic study managed to annotate 108299 unigenes of S. rebaudiana with 8871 and 9832 genes that were differentially expressed in BF and AF samples, respectively. These genes involved in various metabolic pathways related to flower development, response to stimulus as well as photosynthesis. Pheophorbide A oxygenase ( PAO ), eukaryotic translation initiation factor 3 subunit E ( TIF3E1 ), and jasmonate ZIM domain-containing protein 1 ( JAZ1 ) were found to be involved in the flower development. The outcome of this study will help further research in the manipulation of the flowering process, especially in the breeding programme to develop photo-insensitive Stevia plant.
In this study, transformation of BrCHS var 2 into B. rotunda cell suspension culture, followed by chalcone synthase enzymatic assay and HPLC analysis was conducted to investigate whether the substrate specificity for BrCHS var 2 is either cinnamoyl-CoA or p-coumaroyl-CoA. The HPLC profile showed an increase in the amount of pinocembrin chalcone when cinnamoyl-CoA and malonyl-CoA were added but not p-coumaroyl-CoA. Molecular docking was performed to explore the binding of cinnamoyl-CoA and p-coumaroyl-CoA to BrCHS var 2 receptor and the docking results showed that cinnamoyl-CoA formed numerous hydrogen bonds and more negative docked energy than p-coumaroyl-CoA. Cinnamoyl-CoA showed good interactions with Cys 164 to initiate the subsequent formation of pinocembrin chalcone, whereas the hydroxyl group of p-coumaroyl-CoA formed an unfavorable interaction with Gln 161 that caused steric hindrance to subsequent formation of naringenin chalcone. Docked conformation analysis results also showed that malonyl-CoA formed hydrogen bonding with Cys 164, His 303, and Asn 336 residues in BrCHS var 2. The results show that cinnamoyl-CoA is the preferred substrate for BrCHS var 2.
Moringa oleifera Lam. and Centella asiatica (L.) Urb. leaves have been previously reported to exhibit antioxidant activity. The objective of the present study is to determine the in vitro antioxidant activity of the combined extracts of M. oleifera and C. asiatica (TGT-PRIMAAGE) and its effect on hydrogen peroxide (H 2O2)-induced oxidative stress in human dermal fibroblasts. TGTPRIMAAGE acted on the mechanism of hydrogen transfer as it showed scavenging activity in the DPPH assay. This is due to the presence of phenolics and flavonoids in TGT-PRIMAAGE. TGT-PRIMAAGE effectively reduced cellular generation of reactive oxygen species induced by H O2. The activities of superoxide dismutase and catalase were also increased in cells treated with TGT-PRIMAAGE. 2 Treatment with TGT-PRIMAAGE showed significant reduction (P < 0.05) in the number of senescent cells. Significant reduction (P < 0.05) of malondialdehyde was also seen in cells treated with TGT-PRIMAAGE. The p53 protein level was reduced in TGT-PRIMAAGEtreated cells, which indicates its potential in protecting the cells from oxidative stress induced by H2O2.
Colorectal cancer (CRC) is a malignant tumor arising from a human inner colon lining that may spread to other organs such as the liver and lungs. Per ARNT Sim domain containing 1 (PASD1) is a cancer-testis antigen expressed in cancers including CRC but not in normal tissues except for normal testes. This study aims to study PASD1 protein as a potential target for CRC immunotherapy. A total of 90 CRC and polyps tissue samples were investigated for PASD1 RNA and protein expression using a real-time polymerase chain reaction and immunohistochemical staining, respectively. Matched patients' peripheral blood mononuclear cells were pulsed with PASD1 peptides and measured for immunogenicity, cell cytotoxicity, and cytokine assays. The clinical data were collected and analyzed accordingly. Our results show that PASD1_v2 mRNA expression was highly expressed in CRC (46.0%) and polyps samples (33.3%). Both PASD1-1 and PASD1-2 proteins were expressed in 31.7% of CRC and 29.4% of polyps samples. Protein expression was weak to moderate positive in the cytoplasm and/or nucleus of the tissues. Immune responses towards CD4-specific PASD1 peptides were detected in 21.7% of CRC and 23.5% of polyps patients. The most immunogenic peptide was PASD1 (1) in CRC while PASD1 (3) in polyps. Cytotoxicity effects were detected up to 57.20% observed in CRC samples while IL-17A and IL-6 cytokines were highly expressed. The demographic data suggest that Chinese female patients more than 60 years old, diagnosed with late-stage rectosigmoid tumors may benefit from the PASD1 peptide immunotherapy approach. This is the first report describing CD4-positive T-helper response to the PASD1 positive CRC patients and its cytotoxicity.
A skin wound or perforation triggers a series of homeostatic reactions to safeguard internal organs from invasion by pathogens or other substances that could damage body tissues. An injury may occasionally heal quickly, leading to the closure of the skin's structure. Healing from chronic wounds takes a long time. Although many treatment options are available to manage wound healing, an unmet therapy need remains because of the complexity of the processes and the other factors involved. It is crucial to conduct consistent research on novel therapeutic approaches to find an effective healing agent. Therefore, this work aims to cover various in vitro and in vivo methodologies that could be utilised to examine wound recovery. Before deciding on the optimal course of action, several techniques' benefits, drawbacks, and factors need to be reviewed.
The nsp3 macrodomain is implicated in the viral replication, pathogenesis and host immune responses through the removal of ADP-ribosylation sites during infections of coronaviruses including the SARS-CoV-2. It has ever been modulated by macromolecules including the ADP-ribose until Ni and co-workers recently reported its inhibition and plasticity enhancement unprecedentedly by remdesivir metabolite, GS-441524, creating an opportunity for investigating other biodiverse small molecules such as β-Carboline (βC) alkaloids. In this study, 1497 βC analogues from the HiT2LEAD chemical database were screened, using computational approaches of Glide XP docking, molecular dynamics simulation and pk-CSM ADMET predictions. Selectively, βC ligands, 129, 584, 1303 and 1323 demonstrated higher binding affinities to the receptor, indicated by XP docking scores of -10.72, -10.01, -9.63 and -9.48 kcal/mol respectively than remdesivir and GS-441524 with -4.68 and -9.41 kcal/mol respectively. Consistently, their binding free energies were -36.07, -23.77, -24.07 and -17.76 kcal/mol respectively, while remdesivir and GS-441524 showed -21.22 and -24.20 kcal/mol respectively. Interestingly, the selected βC ligands displayed better stability and flexibility for enhancing the plasticity of the receptor than GS-441524, especially 129 and 1303. Their predicted ADMET parameters favour druggability and low expressions for toxicity. Thus, they are recommended as promising adjuvant/standalone anti-SARS-CoV-2 candidates for further study.Key words: SARS-CoV-2, nsp3 macrodomain, ADP-ribose, β-carboline, bioinformatics, drug design.