BACKGROUND: Traditionally, the plant Morinda longissima Y.Z.Ruan (Rubiaceae) is used by ethnic people in Vietnam for the treatment of liver diseases and hepatitis.
OBJECTIVE: The study was designed to assess the efficacy of the 95% ethanolic extract of Morinda longissima roots (MLE) in experimental immune inflammation. The phytochemical variation of root extract and the chemical structures of natural compounds were also investigated using HPLC-DAD-HR-MS analysis.
METHODS: Three different doses (100, 200, and 300 mg/kg b.w.) of MLE were chosen to determine anti-inflammatory activity. The mice were given orally extracts and monitored their behavior and mortality for 14 days to evaluate acute toxicity. The volume of the paw and the histopathological evaluation were carried out. The polyphenolic phytoconstituents of MLE extract were identified using LC/MS analysis. The anti-inflammatory efficacy in silico and molecular docking simulations of these natural products were evaluated based on their cyclooxygenase (COX)-1 and 2 inhibitory effects.
RESULTS: This investigation showed the 95% ethanolic extract of Morinda longissima roots was found non-toxic up to 2000 mg/kg dose level in an acute study, neither showed mortality nor treatment-related signs of toxicity in mice. Eight anthraquinones and anthraquinone glycosides of Morinda longissima roots were identified by HPLC-DAD-HR-MS analysis. In the in vivo experiments, MLE was found to possess powerful anti-inflammatory activities in comparison with diclofenac sodium. The highest anti-inflammatory activity of MLE in mice was observed at a dose of 300 mg/kg body weight. The in silico analysis showed that seven out the eight anthraquinones and anthraquinone glycosides possess a selectivity index RCOX-2/COX-1 lower than 1, indicating that these compounds are selective against the COX-2 enzyme in the following the order: rubiadin-3-methyl ether < morindone morindone-6-methyl ether < morindone-5-methyl ether < damnacanthol < rubiadin < damnacanthol-3-O-β-primeveroside. The natural compounds with the best selectivity against the COX-2 enzyme are quercetin (9), rubiadin-3-methyl ether (7), and morindone (4), with RCOX2/COX1 ratios of 0.02, 0.03, and 0.19, respectively. When combined with the COX-2 protein in the MD research, quercetin and rubiadin-3-methyl ether greatly stabilized the backbone proteins and ligands.
CONCLUSIONS: In conclusion, the anthraquinones and ethanolic extract of Morinda longissima roots may help fight COX-2 inflammation. To develop novel treatments for inflammatory disorders linked to this one, these chemicals should be investigated more in the future.

BACKGROUND: Remijia ferruginea DC. (Rubiaceae) (syn. Cinchona ferruginea A.St.-Hil.) is used in traditional medicine for the treatment of wounds, fever and malaria.
OBJECTIVE: This study investigated in vitro the proliferative and antioxidant effects of hydroalcoholic extract of leaves of R. ferruginea (HERF) and in vivo the healing effect of ointment based on HERF.
METHODS: The plant extract was characterized by liquid chromatography/mass spectrometry. Cell proliferation assays and in vitro antioxidant activity were performed. In in vivo assays, wound contraction ax was evaluated, as well as histological analyzes such as cellularity, proportion of blood vessels and collagen type I and III index. In addition, analyzes of the antioxidant enzymes SOD, CAT and GST were performed.
RESULTS: Our results showed in the chromatographic analysis that catechin, rutin and quercetin were the main phenolic compounds in the plant extract and may be responsible for the antioxidant and proliferative effects (p < 0.05). In addition, these compounds were found in higher concentration in leaves collected in spring. The ointment containing HERF was able to modulate tissue morphology, increasing cell proliferation, blood vessels, being able to stimulate the production of collagen fibers type I and III, (p < 0.05) contributing to scar tissue maturation and resistance.
CONCLUSIONS: Our findings indicated that the three doses of HERF tested (1%, 3% and 5%) can modulate the skin repair process, but the best effects were observed after exposure to the highest dose.

The use of deuterium-incorporated bioactive compounds is an efficient method for tracing their metabolic fate and for quantitative analysis by mass spectrometry without complicated HPLC separation even if their amounts are extremely small. Plant sphingolipids and their metabolites, which have C4, 8-olefins on a common backbone as a sphingoid base, show unique and fascinating bioactivities compared to those of sphingolipids in mammals. However, the functional and metabolic mechanisms of exogenous plant sphingolipids have not been elucidated due to the difficulty in distinguishing exogenous sphingolipids from endogenous sphingolipids having the same polarity and same molecular weight by mass spectrometric analysis. Their roles might be elucidated by the use of deuterated probes with original biological and physicochemical properties. In this study, we designed (2S,3R,4E,8Z)-2-aminooctadeca-4,8-diene-17,17,18,18,18-d5-1,3-diol (penta-deuterium-labeled 4E, 8Z-sphingadienine) as a tracer for exogenous metabolic studies. In addition, the sphingadienine was confirmed to be metabolized in HEK293 cells and showed distinct peaks in mass spectrometric analysis.

Micromorphological features of vegetative and reproductive organs in plants are considered important because they can be used as taxonomic characters. Asperula cankiriense B. Şahin & Sağıroğlu, commonly known as “Çankırı belumu”, belongs to the family Rubiaceae and generally occurs in gypsum steppes. This research reports for the first time the micromorphological characteristics of the vegetative and reproductive organs of A. cankiriense using light and scanning electron microscopy. Taxonomically critical diagnostic features, such as raphide crystals, presence and shape of trichomes, leaf cross-section shape, flower structure, and epidermal ornamentation, were described in detail. This study provided up-to-date information on the micromorphology of this newly described species and provided additional systematic information on A. cankiriense. New data about the species are reported here and will contribute to the knowledge about the family Rubiaceae.

BACKGROUND: antibiotic resistance encourages the development of new therapies, or the discovery of novel antibacterial agents. Previous research revealed that Myrmecodia pendans (Sarang Semut) contain potential antibacterial agents. However, specific proteins inhibited by them have not yet been identified as either proteins targeted by antibiotics or proteins that have a role in the quorum-sensing system. This study aims to investigate and predict the action mode of antibacterial compounds with specific proteins by following the molecular docking approach.
METHODS: butein (1), biflavonoid (2), 3″-methoxyepicatechin-3-O-epicatechin (3), 2-dodecyl-4-hydroxylbenzaldehyde (4), 2-dodecyl-4-hydroxylbenzaldehyde (5), pomolic acid (6), betulin (7), and sitosterol-(6\'-O-tridecanoil)-3-O-β-D-glucopyranoside (8) from M. pendans act as the ligand. Antibiotics or substrates in each protein were used as a positive control. To screen the bioactivity of compounds, ligands were analyzed by Prediction of Activity Spectra for Substances (PASS) program. They were docked with 12 proteins by AutoDock Vina in the PyRx 0.8 software application. Those proteins are penicillin-binding protein (PBP), MurB, Sortase A (SrtA), deoxyribonucleic acid (DNA) gyrase, ribonucleic acid (RNA) polymerase, ribosomal protein, Cytolysin M (ClyM), FsrB, gelatinase binding-activating pheromone (GBAP), and PgrX retrieved from UniProt. The docking results were analyzed by the ProteinsPlus and Discovery Studio software applications.
RESULTS: most compounds have Pa value over 0.5 against proteins in the cell wall. In nearly all proteins, biflavonoid (2) has the strongest binding affinity. However, compound 2 binds only three residues, so that 2 is the non-competitive inhibitor.
CONCLUSIONS: compound 2 can be a lead compound for an antibacterial agent in each pathway.

In our previous work, the partitions (1 mg/mL) of Ageratum conyzoides (AC) aerial parts and Ixora coccinea (IC) leaves showed inhibitions of 94% and 96%, respectively, whereas their fractions showed IC50 43 and 116 µg/mL, respectively, toward Matrix Metalloproteinase9 (MMP9), an enzyme that catalyzes a proteolysis of extracellular matrix. In this present study, we performed IC50 determinations for AC n-hexane, IC n-hexane, and IC ethylacetate partitions, followed by the cytotoxicity study of individual partitions against MDA-MB-231, 4T1, T47D, MCF7, and Vero cell lines. Successive fractionations from AC n-hexane and IC ethylacetate partitions led to the isolation of two compounds, oxytetracycline (OTC) and dioctyl phthalate (DOP). The result showed that AC n-hexane, IC n-hexane, and IC ethylacetate partitions inhibit MMP9 with their respective IC50 as follows: 246.1 µg/mL, 5.66 µg/mL, and 2.75 × 10-2 µg/mL. Toward MDA-MB-231, 4T1, T47D, and MCF7, AC n-hexane demonstrated IC50 2.05, 265, 109.70, and 2.11 µg/mL, respectively, whereas IC ethylacetate showed IC50 1.92, 57.5, 371.5, and 2.01 µg/mL, respectively. The inhibitions toward MMP9 by OTC were indicated by its IC50 18.69 µM, whereas DOP was inactive. A molecular docking study suggested that OTC prefers to bind to PEX9 rather than its catalytic domain. Against 4T1, OTC showed inhibition with IC50 414.20 µM. In conclusion, this study furtherly supports the previous finding that AC and IC are two herbals with potential to be developed as triple-negative anti-breast cancer agents.

All the specimens of Asterochiton species (Hemiptera: Aleyrodidae) on slides in the New Zealand Arthropod Collection, Auckland, were examined. The study reveals that the genus is currently restricted to New Zealand and is redescribed here. Obvious generic characters are the sub-elliptical to sub-circular puparium with distinct invaginations at the thoracic and caudal pores. Seven species are described: Asterochiton asteliae sp. n. from Astelia trinervia (Asteliaceae), and A. arboreae sp. n., A. areolatae sp. n., A. foetidissimae sp. n., A. propinqua sp. n., A. rhamnoidis sp. n., and A. rotundifoliae sp. n. from small-leaved Coprosma spp. (Rubiaceae). There are now 12 named species of Asterochiton, but the Brazilian species, Asterochiton auricolor (Bondar, 1923), does not belong in the genus. Details of minute setae, previously overlooked in described species, are provided. The setae length was found to vary at specific positions. Two species infesting three species of Pittosporum (Pittosporaceae) were observed having long and short setae on the abdomen, sometimes varying within a population from a single tree/host. Asterochiton pittospori Dumbleton is therefore synonymized with A. simplex. Additionally, the location of some setae varied on the subdorsal/submarginal area within a puparium. Chaetotaxy for Asterochiton species is proposed. A key to the puparia of Asterochiton species is provided.

BACKGROUND: Recently, it has emerged from the international scientific literature that quorum sensing (QS) is a promising way for the effective treatment of diseases caused by pathogenic bacteria. One of the crucial proteins in the QS system of Gram-positive bacteria is the pheromone. Some research has reported secondary metabolites from natural products capable of attenuating bacteria through the interruption of the quorum sensing system. One of the Indonesian herbal plants containing bioactive compounds is Sarang Semut (Myrmecodia pendans). A phenolic compound, dibenzo-p-dioxin-2,8-dicarboxylic acid, has been isolated from this plant which had antibacterial activity against Enterococcus faecalis. However, the molecular mechanism of it has not been known.
OBJECTIVE: The study in question aimed to predict the molecular action of the compound M. pendans against some proteins that act as a signal in the mediated QS of Gram-positive bacteria, called pheromones, including PrgQ, PrgX, PrgZ, and CcfA.
METHODS: The methods used in this in silico study were ligand-protein docking and virtual screening that were performed by some software and programs. The compound 1 and some positive controls act as ligand were subject binding to PrgQ, PrgX, PrgZ, and CcfA as proteins target, the ligands were free for blind docking. A framework was presented potency of phenolic compounds to inhibit the protein\'s target from its affinity binding scores.
RESULTS: It was found thatcompound 1 was potential to inhibit all of the tested protein and gave the highest binding affinity to PrgX (-9.2 kcal.mol-1; the site at Phe59B, Phe59B, Asn63A, and Asn63B residue) and PrgZ (-7.4 kcal.mol-1; the site at Leu4B, Thr65A, Thr82A. Gln81A, and Val5B residue).
CONCLUSIONS: It is proposed that compound 1 has a good activity to inhibit E. faecalis through its peptide pheromones in the QS system.

Increasing the resistance issue has become the reason for the development of new antibacterial in crucial condition. Many ways are tracked to determine the most effective antibacterial agent. Some proteins that are a key role in bacteria metabolism are targeted, including MurA in cell wall biosynthesis and gelatinase biosynthesis-activating pheromone (GBAP) in Fsr Quorum Sensing (QS) system.
The objective of this research is the analysis of compounds 1-4 from M. pendans as antibacterial and anti-QS activity trough protein inhibition by in silico study; focus on the structure-activity relationships, to appraise their role as an antibacterial and anti-QS agent in the molecular level.
Both activities of M. pendans compounds (1-4) were analyzed by in silico, compared to Fosfomycin, Ambuic acid, Quercetin, and Taxifolin as a standard. Chemical structures of M. pendans compounds were converted using an online program molview. The compounds were docked to MurA, GBAP, gelatinase and serine protease using Autodock Vina in Pyrx 0.8 followed PYMOL to visualization and proteis.plus program to analyze of the complex.
All compounds from M. pendans bound on MurA, GBAP, gelatinase and serine protease except compound 2. This biflavonoid did not attach to MurA and serine protease yet is the favorable ligand for GBAP and gelatinase with the binding affinity of -6.9 and -9.4 Kcal/mol respectively. Meanwhile, for MurA and serine protease, compound 4 is the highest of bonding energy with values of -8.7 and -6.4 Kcal/mol before quercetin (MurA, -8.9 Kcal/mol) and taxifolin (serine protease, -6.6 Kcal/mol).
Based on the data, biflavonoid acts better as anti-QS than an inhibitor of MurA enzyme while the others can be acted into both of them either the therapeutic agent of anti-QS or antibacterial agent of MurA inhibitor.

Diphtheria-tetanus-pertussis (DTP) vaccine may be associated with excess female deaths. There are few studies of possible nonspecific effects of the DTP-containing vaccine Penta (DTP-hepatitis B-Haemophilus influenzae type b). We therefore investigated whether Penta vaccinations were associated with excess female deaths in rural Bangladesh. Between June 29, 2011 and April 20, 2016, we examined the mortality rates of 7644 children followed between 6 weeks and 9 months of age. We analyzed mortality using crude mortality rate ratio (MRR) and age-adjusted MRR (aMRR) from a Cox proportional hazards model. Mortality was analyzed according to sex, number of doses of Penta, and the order in which BCG and Penta were administered. During follow-up, 43 children died. For children who were only BCG vaccinated (BCG-only), the adjusted F/M MRR was 0.47 (0.09-2.48). However, among children who had Penta as their most recent vaccination, the adjusted F/M MRR was 9.91 (1.16-84.44). Hence, the adjusted F/M MRR differed significantly for BCG-only and for Penta as the most recent administered vaccination. Although the mortality rate was low in rural Bangladesh, there was a marked difference between adjusted F/M MRR\'s for children vaccinated with BCG-only compared with children where Penta was the most recent administered vaccination. Although usually ascribed to differential treatment and access to care, DTP-containing vaccines may be part of the explanation for the excessive female mortality reported in some regions.