Pharmaceutical Importance of Some Promising Plant Species with Special Reference to the Isolation and Extraction of Bioactive Compounds: A Review.

BACKGROUND: Active principles from natural sources, in the form of extracts and natural compounds, provide an infinite number of bioactive compounds with consummate disposal of chemical diversity. These compounds and active principles are of utmost importance in the discovery of drugs of biological origin particularly, from plants. OBJECTIVES: Development of resourceful technology for the isolation and extraction of bioactive compounds of medicinal importance is considered as an important task for researchers. There are a number of extraction, isolation, and characterization techniques currently utilized; however, most are laborious and use toxic chemicals and huge quantities of raw materials with a very low output. There are a number of abiotic and biotic factors that affects the quality and the quantity of plants bioactive compounds. Considering this, the objectives of the current review are to discuss the various extraction and characterization techniques used to isolate the essential bioactive compounds from three plant species and the biotic and abiotic factors that affect the quantity and quality of the plants secondary metabolites. METHODS: Many advanced technologies have been developed and tested for extraction, characterization, and their capacity for high yield products, and those requiring less application of toxic solvents are investigated continuously. CONCLUSION: In this context, the present review summarizes the different types of extraction and characterization techniques utilized commercially by the food, drug, and pharmaceutical industries for better output and environmentally- and health-benefiting products with special reference to three industrially important plants: Leonotis leonurus (L.) R.Br. (Lamiaceae) and Santalum album L. (Santalaceae) and Aloe vera (L.) Burm. f. (Aloaceae or Asphodelaceae).

Coffee Intake and Obesity: A Meta-Analysis.

Many studies have explored the relationship between coffee-one of the most commonly consumed beverages today-and obesity. Despite inconsistent results, the relationship has not been systematically summarized. Thus, we conducted a meta-analysis by compiling data from 12 epidemiologic studies identified from PubMed and Embase through February 2019. The included studies assessed obesity by body mass index (BMI, a measure of overall adiposity) or waist circumference (WC, a measure of central adiposity); analyzed the measure as a continuous outcome or binary outcome. Using random effects model, weighted mean difference (WMD) and 95% confidence interval (CI) were obtained for continuous outcomes; summary relative risk (RR) and 95% CI for the highest vs. lowest categories of coffee intake were estimated for binary outcome. For BMI, WMD was -0.08 (95% CI -0.14, -0.02); RR was 1.49 (95% CI 0.97, 2.29). For WC, WMD was -0.27 (95% CI -0.51, -0.02) and RR was 1.07 (95% CI 0.84, 1.36). In subgroup analysis by sex, evidence for an inverse association was more evident in men, specifically for continuous outcome, with WMD -0.05 (95% CI -0.09, -0.02) for BMI and -0.21 (95% CI -0.35, -0.08) for WC. Our meta-analysis suggests that higher coffee intake might be modestly associated with reduced adiposity, particularly in men.

Ecklonia cava Extract Containing Dieckol Suppresses RANKL-Induced Osteoclastogenesis via MAP Kinase/NF-κB Pathway Inhibition and Heme Oxygenase-1 Induction.

Ecklonia cava, an edible marine brown alga (Laminariaceae), is a rich source of bioactive compounds such as fucoidan and phlorotannins. Ecklonia cava extract (ECE) was prepared using 70% ethanol extraction and ECE contained 67% and 10.6% of total phlorotannins and dieckol, respectively. ECE treatment significantly inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation of RAW 264.7 cells and pit formation in bone resorption assay (p ＜0.05). Moreover, it suppressed RANKL-induced NF-κB and mitogen-activated protein kinase signaling in a dose dependent manner. Downregulated osteoclast-specific gene (tartrate-resistant acid phosphatase, cathepsin K, and matrix metalloproteinase-9) expression and osteoclast proliferative transcriptional factors (nuclear factor of activated T cells-1 and c-fos) confirmed ECE-mediated suppression of osteoclastogenesis. ECE treatment (100 µg/ml) increased heme oxygenase-1 expression by 2.5-fold and decreased intercellular reactive oxygen species production during osteoclastogenesis. The effective inhibition of RANKL-stimulated osteoclast differentiation and oxidative stress by ECE suggest that ECE has therapeutic potential in alleviating osteoclast-associated disorders.

Irradiation by gallium-aluminum-arsenate diode laser enhances the induction of nitric oxide by Porphyromonas gingivalis in RAW 264.7 cells.

BACKGROUND: Low-level laser irradiation promotes cell viability and wound healing in periodontal tissue. However, its effect on periodontal pathogenic bacteria is unknown. The purpose of this study is to investigate the biologic effect of low-level laser irradiation on Porphyromonas gingivalis. METHODS: A murine macrophage cell line (RAW 264.7) was cultured and treated with gallium-aluminum-arsenate (GaAlAs) laser-irradiated P. gingivalis with varying levels of energy fluency. Gene expression of monocyte chemotactic protein-1 (MCP-1), interleukin-6 (IL-6), interferon-ß (IFN-ß), and inducible nitric oxide synthase (iNOS) was examined by reverse transcription-polymerase chain reaction. Production of iNOS was determined by Western blot analysis, and nitric oxide (NO) release was assessed using Griess reagent. Flow cytometric analysis was performed to determine the activation of Toll-like receptors (TLRs) in response to P. gingivalis. RESULTS: The laser-irradiated P. gingivalis significantly enhanced messenger RNA and protein levels of iNOS in RAW 264.7. Although the laser irradiation on P. gingivalis did not alter the expression level of MCP-1, IL-6, and IFN-ß, it showed a noticeable effect on NO production in RAW 264.7. Furthermore, the laser-irradiated P. gingivalis accelerated TLR2 activation, but not TLR4 activation. CONCLUSIONS: This study reveals that GaAlAs laser irradiation on P. gingivalis induced iNOS expression at the transcriptional and translation levels and increased NO release in macrophages. Moreover, it is confirmed that this process was mediated specifically by TLR2 activation. These findings suggest that low-level laser irradiation to periodontal pathogenic bacteria could be detrimental to periodontal treatments.

Induction of intercellular adhesion molecule-1 by water-soluble components of Hericium erinaceum in human monocytes.

AIM OF THE STUDY: Hericium erinaceum is a medicinal mushroom that has been traditionally used in Asian countries for the treatment of cancers and infectious diseases. Although the immunomodulating activity of H. erinaceum is considered to be responsible for its medicinal activity, its action mechanisms are poorly understood. In the present study, we investigated the capability of water-extracted H. erinaceum (WEHE) to induce the expression of intercellular adhesion molecule-1 (ICAM-1), which regulates the migration of immune cells. MATERIALS AND METHODS: THP-1, a human monocytic cell-line, or human peripheral blood mononuclear cells (PBMC) were stimulated with WEHE (0-30 µg/mL) and subsequently analyzed using flow cytometry to examine the surface expression of ICAM-1 protein. Steady-state levels of ICAM-1 mRNA were estimated using real-time reverse transcription-polymerase chain reaction analysis. Electrophoretic mobility shift assay was conducted to examine transcription factors involved in ICAM-1 transcription. RESULTS: WEHE induced ICAM-1 expression at both protein and mRNA levels in THP-1 cells in a dose- and time-dependent fashion. A similar pattern of ICAM-1 induction was also observed in CD14(+) monocytes in human PBMC that were stimulated with WEHE. The ICAM-1 expression on THP-1 cells stimulated with WEHE was suppressed by specific inhibitors for extracellular signal-regulated kinases (ERK) and reactive oxygen species (ROS). Additionally, exposure of THP-1 cells to WEHE increased the DNA binding activities of NF-κB, AP-1, SP-1 and STAT-1 transcription factors, all of which are known to be required for ICAM-1 gene expression. CONCLUSIONS: These results suggest that WEHE induces ICAM-1 expression in human monocytes through ERK- and ROS-dependent signaling pathways, resulting in the subsequent activations of NF-κB, AP-1, SP-1, and STAT-1 transcription factors.

Induction of ICAM-1 by Armillariella mellea is mediated through generation of reactive oxygen species and JNK activation.

ETHNOPHARMACOLOGICAL RELEVANCE: Armillariella mellea is an edible mushroom that has been traditionally used as an alternative medicine in many countries because of its anti-microbial and anti-cancer effects. AIM OF THE STUDY: In this study, we examined the ability of Armillariella mellea to induce the expression of intercellular adhesion molecule (ICAM)-1, an important cellular adhesion molecule for the recruitment of immune cells to regional inflammatory sites. MATERIALS AND METHODS: A human monocytic cell line, THP-1 or human peripheral blood mononuclear cells (PBMC) were stimulated with Armillariella mellea extract (AME) and subjected to flow cytometry to examine the expression of ICAM-1 protein on the cell surface. Steady-state mRNA level of ICAM-1 was determined by real-time reverse transcription-polymerase chain reaction. The phosphorylation of JNK protein was examined by Western blot analysis using antibodies specific for non-phosphorylated and phosphorylated forms of JNK. For the analysis of transcription factors regulating ICAM-1 transcription, the nuclear fraction was extracted from AME-treated THP-1 cells and subjected to electrophoretic mobility shift assay. RESULTS: AME induced expression of ICAM-1 and its mRNA in THP-1 cells in dose- and time-dependent manners. AME-induced ICAM-1 expression was also observed on CD14-positive monocytes in human PBMC. Interestingly, AME-induced ICAM-1 production was inhibited by the specific inhibitors of reactive oxygen species (ROS) and JNK, whereas no inhibitory effect was observed when inhibitors of ERK, p38 kinase, phosphatidylinositol 3-kinase, or protein kinase C were used. Concomitantly, AME increased phosphorylation of JNK in a time-dependent fashion. DNA binding activities of NF-kappaB, AP-1, SP-1, and STAT-1 were increased by AME treatment. CONCLUSION: These results suggest that AME induces ICAM-1 expression in human monocytic cells through ROS/JNK-dependent signaling pathways leading to the activation of NF-kappaB, AP-1, SP-1, and STAT-1 transcription factors.

Peptidoglycan-mediated IL-8 expression in human alveolar type II epithelial cells requires lipid raft formation and MAPK activation.

Staphylococcus aureus, a major sepsis-causing Gram-positive bacterium, invades pulmonary epithelial cells and causes lung diseases. In the lung, alveolar type II epithelial cells play an important role in innate immunity by secreting chemokines and antimicrobial peptides upon bacterial infection whereas type I cells mainly function in gas-exchange. In this study, we investigated the ability of S. aureus peptidoglycan (PGN) to induce expression of a chemokine, IL-8, in a human alveolar type II epithelial cell line, A549. PGN induces IL-8 mRNA and protein expression in a dose- and time-dependent manner. Supplementation of soluble CD14 further enhanced the PGN-induced IL-8 expression. Interestingly, PGN-induced IL-8 expression was inhibited by nystatin, a specific inhibitor for lipid rafts, but not by chlorpromazine, a specific inhibitor for clathrin-coated pits. Furthermore, PGN-induced IL-8 expression was attenuated by inhibitors for MAP kinases such as ERK, p38 kinase, and JNK/SAPK, whereas no inhibitory effect was observed by inhibitors for reactive oxygen species or protein kinase C. Electrophoretic mobility shift assay demonstrates that PGN increased the DNA binding of the transcription factors, AP-1 and NF-kappaB while minimally, NF-IL6, all of which are involved in the transcription of IL-8. Taken together, these results suggest that PGN induces IL-8 expression in a CD14-enhanced manner in human alveolar type II epithelial cells, through the formation of lipid rafts and the activation of MAP kinases, which ultimately leads to activation of AP-1, NF-kappaB, and NF-IL6.

NF-kappaB signaling pathway, not IFN-beta/STAT1, is responsible for the selenium suppression of LPS-induced nitric oxide production.

Upon stimulation of macrophages with lipopolysaccharide (LPS), Toll-like receptor 4 recognizes LPS, leading to expression of inducible nitric oxide synthase (iNOS), via MyD88/NF-kappaB and TRIF/IFN-beta/STAT pathways. Although selenium (Se) was reported to inhibit nitric oxide (NO) production, it is unclear which signaling pathway is inhibited by Se. Here, we investigated how Se inhibits NO production in LPS-stimulated RAW 264.7 cells. When the cells were pretreated with Se for 1 h followed by LPS treatment, iNOS mRNA expression and subsequent NO production declined significantly in a dose-dependent manner. Se inhibited IkappaBalpha degradation in the cytosol and NF-kappaB binding to its recognition site in the nucleus of the LPS-stimulated cells. Meanwhile, Se did not inhibit IFN-beta mRNA induction or STAT1 phosphorylation in the LPS-stimulated cells. These results suggest that Se down-regulates iNOS gene expression and NO production in the LPS-stimulated macrophages through inhibition of the NF-kappaB activation pathway but not the IFN-beta/STAT1 signaling pathway.