Periodontitis is a chronic inflammatory condition that causes tooth loss by destroying the supporting components of the teeth. In most cases, it is difficult to diagnose early and results in severe phases of the disease. Given their endogenous origins, exosomes, which are rich in peptides, lipids, and nucleic acids, have emerged as a cell-free therapeutic approach with low immunogenicity and increased safety. Because the constituents of exosomes can be reprogrammed depending on disease states, exosomes are increasingly being evaluated to act as potential diagnostic biomarkers for dental disease, including periodontitis. Exosomes also have been demonstrated to be involved in inflammatory signal transmission and periodontitis progression in vitro, indicating that they could be used as therapeutic targets for periodontal regeneration. Nevertheless, a review on the involvement of salivary exosomes in periodontitis in impacting the successful diagnosis and treatment of periodontitis is still lacking in the literature. Thus, this review is intended to scrutinize recent advancements of salivary exosomes in periodontitis treatment. We summarize recent research reports on the emerging roles and characteristics of salivary exosomes, emphasizing the different expressions and changed biological roles of exosomes in periodontitis.
Chronic periodontitis (CP) is an oral cavity disease arising from chronic inflammation of the periodontal tissues. Exosomes are lipid vesicles that are enriched in specific microRNAs (miRNAs), potentially providing a disease-specific diagnostic signature. To assess the value of exosomal miRNAs as biomarkers for CP, 8 plasma- and 8 salivary-exosomal miRNAs samples were profiled using Agilent platform (comparative study). From 2,549 probed miRNAs, 33 miRNAs were significantly down-regulated in CP as compared to healthy plasma samples. Whereas, 1,995 miRNAs (1,985 down-regulated and 10 up-regulated) were differentially expressed in the CP as compared to healthy saliva samples. hsa-miR-let-7d [FC = -26.76; AUC = 1; r = -0.728 [p-value = 0.04]), hsa-miR-126-3p (FC = -24.02; AUC = 1; r = -0.723 [p-value = 0.043]) and hsa-miR-199a-3p (FC = -22.94; AUC = 1; r = -0.731 [p-value = 0.039]) are worth to be furthered studied for plasma-exosomal samples. Meanwhile, for salivary-exosomal samples, hsa-miR-125a-3p (FC = 2.03; AUC = 1; r = 0.91 [p-value = 0.02]) is worth to be furthered studied. These miRNAs are the reliable candidates for the development of periodontitis biomarker, as they were significantly expressed differently between CP and healthy samples, have a good discriminatory value and strongly correlate with the mean of PPD. These findings highlight the potential of exosomal miRNAs profiling in the diagnosis from both sourced as well as provide new insights into the molecular mechanisms involved in CP.
Pancreatic cancer is an aggressive disease that progresses in a relatively symptom-free manner; thus, is difficult to detect and treat. Essential oil is reported to exhibit pharmacological properties, besides its common and well-known function as aromatherapy. Therefore, this study herein aimed to investigate the anti-proliferative effect of essential oil extracted from leaves of Garcinia atroviridis (EO-L) against PANC-1 human pancreatic cancer cell line. The cell growth inhibitory concentration at 50% (IC50) and selective index (SI) values of EO-L analyses were determined as 78 µg/mL and 1.23, respectively. Combination index (CI) analysis revealed moderate synergism (CI values of 0.36 to 0.75) between EO-L and 2 deoxy-d-glucose (2-DG) treatments. The treatments of PANC-1 cells with EO-L, 2-DG and EOL+2DG showed evidence of depolarization of mitochondrial membrane potential, cell growth arrest and apoptosis. The molecular mechanism causing the anti-proliferative effect between EO-L and 2-DG is potentially through pronounced up-regulation of P53 (4.40-fold), HIF1α (1.92-fold), HK2 (2.88-fold) and down-regulation of CYP3A5 (0.11-fold), as supported by quantitative mRNA expression analysis. Collectively, the current data suggest that the combination of two anti-proliferative agents, EO-L and 2-DG, can potentially be explored as therapeutic treatments and as potentiating agents to conventional therapy against human pancreatic cancer.
Clinacanthus nutans is a well-known herb that has been used as an alternative and therapeutic medicine, however more selective C. nutans extracts are needed. In this study, leaves were extracted with 80% methanol and further fractionated with n-hexane, dichloromethane, chloroform, n-butanol, and aqueous residue. Subsequently, the total phenolic content (TPC), total flavonoid content (TFC), antioxidant scavenging activity, and antiproliferative effects on breast cancer (Michigan Cancer Foundation-7 [MCF7]) and normal breast (Michigan Cancer Foundation-10A [MCF 10A]) cells of the extracts were measured. Additionally, molecular docking simulation of the major compounds from C. nutans extracts was conducted. The aqueous residue had the highest TPC and TFC, whereas the crude extract had the highest scavenging activity. Among the extracts, dichloromethane extract (CN-Dcm) was selected as it had the highest selectivity index (SI) (1.48). Then, the chosen extract (CN-Dcm) was proceed for further analysis. The compounds from CN-Dcm were identified using gas chromatography-mass spectrometry (GC-MS). The major compounds from CN-Dcm were further investigated through molecular docking studies. Palmitic acid and linolenyl alcohol were the compounds found in the CN-Dcm extract that exhibited the highest binding affinities with p53-binding protein Mdm-2. These results highlight the potential of C. nutans as a source of anticancer activities.
A bottom-up approach for synthesizing silver nanoparticles (AgNPs-GA) phytomediated by Garcinia atroviridis leaf extract is described. Under optimized conditions, the AgNPs-GA were synthesized at a concentration of 0.1 M silver salt and 10% (w/v) leaf extract, 1:4 mixing ratio of reactants, pH 3, temperature 32 °C and 72 h reaction time. The AgNPs-GA were characterized by various analytical techniques and their size was determined to be 5-30 nm. FTIR spectroscopy indicates the role of phenolic functional groups in the reduction of silver ions into AgNPs-GA and in supporting their subsequent stability. The UV-Visible spectrum showed an absorption peak at 450 nm which reflects the surface plasmon resonance (SPR) of AgNPs-GA and further supports the stability of these biosynthesized nanoparticles. SEM, TEM and XRD diffractogram analyses indicate that AgNPs-GA were spherical and face-centered-cubic in shape. This study also describes the efficacy of biosynthesized AgNPs-GA as anti-proliferative agent against human breast cancer cell lines, MCF-7 and MCF-7/TAMR-1. Our findings indicate that AgNPs-GA possess significant anti-proliferative effects against both the MCF-7 and MCF-7/TAMR-1 cell lines, with inhibitory concentration at 50% (IC50 values) of 2.0 and 34.0 µg/mL, respectively, after 72 h of treatment. An induction of apoptosis was evidenced by flow cytometry using Annexin V-FITC and propidium iodide staining. Therefore, AgNPs-GA exhibited its anti-proliferative activity via apoptosis on MCF-7 and MCF-7/TAMR-1 breast cancer cells in vitro. Taken together, the leaf extract from Garcinia atroviridis was found to be highly capable of producing AgNPs-GA with favourable physicochemical and biological properties.
Garcinia celebica L., locally known as "manggis hutan" in Malaysia is widely used in folkloric medicine to treat various diseases. The present study was aimed to examine the chemical composition of the essential oil from the leaves of G. celebica L. (EO-GC) and its cytotoxic and antimicrobial potential. EO-GC obtained by hydrodistillation was analysed using capillary GC and GC-MS. Twenty-two compounds were identified, dominated by α-copaene (61.25%), germacrene D (6.72%) and β-caryophyllene (5.85%). In the in vitro MTT assay, EO-GC exhibited significant anti-proliferative effects towards MCF-7 human breast cancer cells with IC50 value of 45.2 μg/mL. Regarding the antimicrobial activity, it showed better inhibitory effects on Gram-positive bacteria than Gram-negative bacteria and none on the fungi and yeasts tested.
Garcinia atroviridis Griff. ex T. Anders. is used as a medication agent in folkloric medicine. The present study was to examine the chemical composition of the stem bark and leaf of G. atroviridis as well as their cytotoxic effects against MCF-7 cells. The constituents obtained by hydrodistillation were identified using GC-MS. The stem bark oil (EO-SB) composed mainly the palmitoleic acid (51.9%) and palmitic acid (21.9%), while the leaf oil (EO-L) was dominated by (E)-β-farnesene (58.5%) and β-caryophyllene (16.9%). Treatment of MCF-7 cells using EO-L (100 μg/mL) caused more than 50% cell death while EO-SB did not induce cytotoxic effect. EO-L has stimulated the growth of BEAS-2B normal cells, but not in MCF-7 cancerous cells. The IC50 of EO-L in MCF-7 and BEAS-2B cells were 71 and 95 μg/mL, respectively. A combination treatment of EO-L and tamoxifen induced more cell death than the treatment with drug alone at lower doses.
The Heck cross-coupling reaction is a well-established chemical tool for the synthesis of unsaturated compounds by formation of a new C-C bond. In this study, 1,3-diarylpropene derivatives, designed as structural analogues of stilbenoids and dihydrostilbenoids, were synthesised by the palladium-catalysed reactions of 2-amidoiodobenzene derivatives with either estragole or eugenol. The products were obtained with high (E) stereoselectivity but as two regioisomers. The ratios of isomers were found to be dependent on the nature of the allylbenzene partner and were rationalised by electronic effects exercising a determining influence in the β-hydride elimination step. In addition, the cytotoxic effects of all the Heck reaction products were evaluated against MCF-7 and MDA-MB-231 human breast cancer cells, with unpromising results. Among all, compound 7d exhibited weak cytotoxic activity towards MCF-7 cell lines with IC50 values of 47.92 µM in comparison with tamoxifen and was considered to have general toxicity (SI value < 2).
Silver nanoparticles (AgNPs) previously synthesised using leaf (AgNP-L) and stem (AgNP-S) extracts of Clinacanthus nutans (C. nutans) were tested to evaluate antimicrobial, antioxidant, and cytotoxicity activities. The AgNPs showed good inhibition against bacteria, but not fungi. The inhibition results showed the highest activity against Staphylococcus aureus (S. aureus) with 11.35 mm (AgNP-L) and 11.52 mm (AgNP-S), while the lowest inhibition was against Escherichia coli (E. coli) with 9.22 mm (AgNP-L) and 9.25 mm (AgNP-S) in the disc diffusion method. The same trend of results was noted in the well diffusion method. The IC50 of AgNP-L and AgNP-S in 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays was 417.05 μg/mL and 434.60 μg/mL, as well as 304.31 μg/mL and 326.83 μg/mL, respectively. Ferric reducing power (FRAP) assay showed that AgNP-L [872.389 μmol/L Fe(II)] and AgNP-S [612.770 μmol/L Fe(II)] exhibited significantly (p