Addition of iron does not ameliorate sulfide toxicity by sargassum influx to mangroves but dampens methane and nitrous oxide emissions.

Sargassum spp. strandings in the tropical Atlantic harm local ecosystems due to toxic sulfide levels. We conducted a mesocosm experiment to test the efficacy of iron(III) (hydr)oxides in (a) mitigating sulfide toxicity in mangroves resulting from Sargassum and (b) reducing potentially enhanced greenhouse gas emissions. Our results show that iron addition failed to prevent mangrove mortality caused by highly toxic sulfide concentrations, which reached up to 15,000 µmol l-1 in 14 days; timely removal may potentially prevent mangrove death. Sargassum-impacted mesocosms significantly increased methane, nitrous oxide, and carbon dioxide emissions, producing approximately 1 g CO2-equivalents m-2 h-1 during daylight hours, thereby shifting mangroves from sinks to sources of greenhouse gasses. However, iron addition decreased methane emissions by 62 % and nitrous oxide emissions by 57 %. This research reveals that Sargassum strandings have multiple adverse effects related to chemical and ecological dynamics in mangrove ecosystems, including greenhouse gas emissions.

Inhibitory Effects of the Polyphenols from the Root of Rhizophora apiculata Blume on Fatty Acid Synthase Activity and Human Colon Cancer Cells.

Marine mangrove vegetation has been traditionally employed in folk medicine to address various ailments. Notably, Rhizophora apiculata Blume has exhibited noteworthy properties, demonstrating efficacy against cancer, viruses, and bacteria. The enzyme fatty acid synthase (FAS) plays a pivotal role in de novo fatty acid synthesis, making it a promising target for combating colon cancer. Our study focused on evaluating the FAS inhibitory effects of both the crude extract and three isolated compounds from R. apiculata. The n-butanol fraction of R. apiculata extract (BFR) demonstrated a significant inhibition of FAS, with an IC50 value of 93.0 µg/mL. For inhibition via lyoniresinol-3α-O-ß-rhamnopyranoside (LR), the corresponding IC50 value was 20.1 µg/mL (35.5 µM). LR competitively inhibited the FAS reaction with acetyl-CoA, noncompetitively with malonyl-CoA, and in a mixed manner with NADPH. Our results also suggest that both BFR and LR reversibly bind to the KR domain of FAS, hindering the reduction of saturated acyl groups in fatty acid synthesis. Furthermore, BFR and LR displayed time-dependent inhibition for FAS, with kobs values of 0.0045 min-1 and 0.026 min-1, respectively. LR also exhibited time-dependent inhibition on the KR domain, with a kobs value of 0.019 min-1. In human colon cancer cells, LR demonstrated the ability to reduce viability and inhibit intracellular FAS activity. Notably, the effects of LR on human colon cancer cells could be reversed with the end product of FAS-catalyzed chemical reactions, affirming the specificity of LR on FAS. These findings underscore the potential of BFR and LR as potent FAS inhibitors, presenting novel avenues for the treatment of human colon cancer.

Multifarious plant growth-promoting traits of mangrove yeasts: growth enhancement in mangrove seedlings (Rhizophora mucronata) for conservation.

Plant Growth-Promoting Yeasts (PGPY) have garnered significant attention in recent years; however, research on PGPY from mangroves remains a largely unexplored frontier. This study, therefore, focused on exploring the multifaceted plant growth-promoting (PGP) capabilities of yeasts isolated from mangroves of Puthuvype and Kumbalam. The present work found that manglicolous yeasts exhibited diverse hydrolytic properties, with the predominance of lipolytic activity, in addition to other traits such as phosphate solubilization, and production of indole acetic acid, siderophore, ammonia, catalase, nitrate, and hydrogen cyanide. After screening for 15 PGP traits, three strains P 9, PV 23, and KV 35 were selected as the most potent ones. These strains also exhibited antagonistic activity against fungal phytopathogens and demonstrated resilience to abiotic stresses, making them not only promising biocontrol agents but also suited for field application. The potent strains P 9, PV 23, and KV 35 were molecularly identified as Candida tropicalis, Debaryomyces hansenii, and Aureobasidium melanogenum, respectively. The potential of these strains in enhancing the growth performance of mangrove seedlings of Rhizophora mucronata, was demonstrated using the pot-experiment. The results suggested that the consortium of three potent strains (P 9, PV 23, and KV 35) was more effective in increasing the number of shoot branches (89.2%), plant weight (87.5%), root length (83.3%), shoot height (57.9%) and total leaf area (35.1%) than the control seedlings. The findings of this study underscore the significant potential of manglicolous yeasts in contributing to mangrove conservation and restoration efforts, offering a comprehensive understanding of their diverse plant growth-promoting mechanisms and highlighting their valuable role in sustainable ecosystem management.

Mangrove expansion on the low wooded islands of the Great Barrier Reef.

Mangrove forests are the dominant vegetation growing on low wooded islands, which occur in the Caribbean, Indian and Pacific Oceans. In the northern Great Barrier Reef, we map remarkable, undocumented mangrove forest extension on 10 low wooded islands in the Howick Group that collectively equates to an area of 667 000 m2 (66.7 ha). We combine extensive field survey with canopy height models derived from RPA imagery and allometric scaling to quantify above ground biomass in both old (pre-1973) and new (post-1973) forest areas. Forest expansion added approximately 10 233 tonnes of new biomass since the early 1970s. We suggest that such substantial expansion of mangrove forest has occurred within a short time span in response to changing environmental controls. These may include sea-level rise, sediment transport and deposition, cyclone impact and the development of associated reef flat sedimentary landforms including unconsolidated and lithified shingle ridges, which influence reef flat hydrodynamics. Our observations highlight the globally dynamic response of mangrove distribution and forest structure to environmental change and provide timely new estimates from understudied reef island settings.

Antimicrobial and Antioxidant Property of a True Mangrove Rhizophora apiculata Bl.

Mangroves are abundant in bioactive natural substances that fight off pathogenic diseases. Different parts of R. apiculata, an abundant mangrove found in Bhitarkanika National Park, India were extracted with methanol and a mixture of solvents methanol/ethanol/chloroform (60 : 20 : 20) to evaluate their antimicrobial properties. The combination solvent extract of bark had the highest zone of inhibition (ZOI) of 18.62 mm against Pseudomonas aeruginosa and a ZOI of 17.41 mm against Streptococcus mitis. Bark extracts had the highest DPPH (43 %) and FRAP (96 %) activities. The combination solvent bark extract of R. apiculata had the highest ZOI of 20.42 mm (lowest MIC of 2.12 µg/ml) against Candida albicans and ZOI of 15.33 mm (MIC of 3.02 µg/mL) against Penicillium chrysogenum. Combination bark extracts of R. apiculata contained flavanols than methanolic extracts. The crude extract of R. apiculata bark made with a mixture of solvents containing more active ingredients could be used in novel drug formulation.

Ethanol preservation and pretreatments facilitate quality DNA extractions in recalcitrant plant species.

Premise: The preservation of plant tissues in ethanol is conventionally viewed as problematic. Here, we show that leaf preservation in ethanol combined with proteinase digestion can provide high-quality DNA extracts. Additionally, as a pretreatment, ethanol can facilitate DNA extraction for recalcitrant samples. Methods: DNA was isolated from leaves preserved with 96% ethanol or from silica-desiccated leaf samples and herbarium fragments that were pretreated with ethanol. DNA was extracted from herbarium tissues using a special ethanol pretreatment protocol, and these extracts were compared with those obtained using the standard cetyltrimethylammonium bromide (CTAB) method. Results: DNA extracted from tissue preserved in, or pretreated with, ethanol was less fragmented than DNA from tissues without pretreatment. Adding proteinase digestion to the lysis step increased the amount of DNA obtained from the ethanol-pretreated tissues. The combination of the ethanol pretreatment with liquid nitrogen freezing and a sorbitol wash prior to cell lysis greatly improved the quality and yield of DNA from the herbarium tissue samples. Discussion: This study critically reevaluates the consequences of ethanol for plant tissue preservation and expands the utility of pretreatment methods for molecular and phylogenomic studies.

A modified method for efficient RNA isolation from mangrove root tissues rich in secondary metabolites.

Secondary metabolites in mangroves often interfere with RNA extraction yielding poor concentration and quality, which is unsuitable for downstream applications. As existing protocols yielded low-quality RNA from root tissues of Kandelia candel (L.) Druce and Rhizophora mucronata Lam., an optimized method was developed for improving the quality and yield of RNA. Compared with three other methods, this optimized protocol gave better RNA yield and purity for both species. The absorbance ratios were ≥1.9 for A260/280 and A260/230, while RNA integrity number values ranged from 7.5 to 9.6. Results show that our modified method is efficient in obtaining high-quality RNA from mangrove roots and is suitable for downstream experiments such as cDNA synthesis, real-time quantitative PCR and next-generation sequencing.

Red Mangrove (Rhizophora stylosa Griff.)-A Review of Its Botany, Phytochemistry, Pharmacological Activities, and Prospects.

Mangroves are ecologically significant plants in marine habitats that inhabit the coastlines of many countries. Being a highly productive and diverse ecosystem, mangroves are rich in numerous classes of phytochemicals that are of great importance in the field of pharmaceutical industries. The red mangrove (Rhizophora stylosa Griff.) is a common member of the Rhizophoraceae family and the dominant species in the mangrove ecosystem of Indonesia. R. stylosa mangrove species are rich in alkaloids, flavonoids, phenolic acids, tannins, terpenoids, saponins, and steroids, and are widely used in traditional medicine for anti-inflammatory, antibacterial, antioxidant, and antipyretic effects. This review aims to provide a comprehensive understanding of the botanical description, phytochemical profiles, pharmacological activities, and medicinal potentials of R. stylosa.

Genome wide identification and characterization of MATE family genes in mangrove plants.

Multidrug and Toxic Compound Extrusion (MATE) proteins are essential transporters that extrude metabolites and participate in plant development and cellular detoxification. MATE transporters, which play crucial roles in the survival of mangrove plants under highly challenged environments, by specialized salt extrusion mechanisms, are mined from their genomes and reported here for the first time. Through homology search and domain prediction in the genome assemblies of Avicennia marina, Bruguiera sexangula, Ceriops zippeliana, Kandelia obovata, Rhizophora apiculata and Ceriops tagal, 74, 68, 66, 66, 63 and 64 MATE proteins, respectively were identified. The phylogenetic analysis divided the identified proteins into five major clusters and following the clustering pattern of the functionally characterized proteins, functions of the transporters in each cluster were predicted. Amino acid sequences, exon-intron structure, motif details and subcellular localization pattern for all the 401 proteins are described. The custom designed repeat masking libraries generated for each of these genomes, which will be of extensive use for the researchers worldwide, are also provided in this paper. This is the first study on the MATE genes in mangroves and the results provide comprehensive information on the molecular mechanisms enabling the survival of mangroves under hostile conditions.

Assessment of the Genetic Diversity and Population Structure of Rhizophora mucronata along Coastal Areas in Thailand.

Unique and biodiverse, mangrove ecosystems provide humans with benefits and contribute to coastal protection. Rhizophora mucronata, a member of the Rhizophoraceae family, is prevalent in the mangrove forests of Thailand. R. mucronata's population structure and genetic diversity have received scant attention. Here, we sequenced the entire genome of R. mucronata using 10× Genomics technology and obtained an assembly size of 219 Mb with the N50 length of 542,540 bases. Using 2857 single nucleotide polymorphism (SNP) markers, this study investigated the genetic diversity and population structure of 80 R. mucronata accessions obtained from the mangrove forests in Thailand. The genetic diversity of R. mucronata was moderate (I = 0.573, Ho = 0.619, He = 0.391). Two subpopulations were observed and confirmed from both population structure and principal component analysis (PCA). Analysis of molecular variance (AMOVA) showed that there was more variation within populations than between them. Mean pairwise genetic differentiation (FST = 0.09) showed that there was not much genetic difference between populations. Intriguingly, the predominant clustering pattern in the R. mucronata population did not correspond to the Gulf of Thailand and the Andaman Sea, which are separated by the Malay Peninsula. Several factors could have influenced the R. mucronata genetic pattern, such as hybridization and anthropogenic factors. This research will provide important information for the future conservation and management of R. mucronata in Thailand.

Sediment microbial community structure associated to different ecological types of mangroves in Celestún, a coastal lagoon in the Yucatan Peninsula, Mexico.

Mangroves are unique coastal ecosystems, which have many important ecological functions, as they are a reservoir of many marine species well adapted to saline conditions and are fundamental as sites of carbon storage. Although the microbial contribution to nutrient cycling in these ecosystems has been well recognized, there is a lack of information regarding the microbial composition and structure of different ecological types of mangrove forests. In this study, we characterized the microbial community (Bacteria and Archaea) in sediments associated with five ecological types of mangrove forests in a coastal lagoon dominated by Avicennia germinans and Rhizophora mangle, through 16S rRNA-V4 gene sequencing. Overall, Proteobacteria (51%), Chloroflexi (12%), Gemmatimonadetes (5%) and Planctomycetes (6%) were the most abundant bacterial phyla, while Thaumarchaeota (30%), Bathyarchaeota (21%) and Nanoarchaeaeota (18%) were the dominant archaeal phyla. The microbial composition associated with basin mangroves dominated by Avicennia germinans was significantly different from the other ecological types, which becomes relevant for restoration strategies.

Taxon Cycles in Neotropical Mangroves.

The concept of the taxon cycle involves successive range expansions and contractions over time, through which a species can indefinitely maintain its core distribution. Otherwise, it becomes extinct. Taxon cycles have been defined mostly for tropical island faunas; examples from continental areas are scarce, and similar case studies for plants remain unknown. Most taxon cycles have been identified on the basis of phylogeographic studies, and straightforward empirical evidence from fossils is lacking. Here, empirical fossil evidence is provided for the recurrent Eocene to the present expansion/contraction cycles in a mangrove taxon (Pelliciera) after a Neotropical-wide study of the available pollen records. This recurrent behavior is compatible with the concept of the taxon cycle from biogeographical, chronological and ecological perspectives. The biotic and abiotic drivers potentially involved in the initiation and maintenance of the Pelliciera expansion/contraction cycles are analyzed, and the ecological and evolutionary implications are discussed. Whether this could be a trend toward extinction is considered under the predictions of the taxon cycle theory. The recurrent expansion and contraction cycles identified for Pelliciera have strong potential for being the first empirically and unequivocally documented taxon cycles and likely the only taxon cycles documented to date for plants.

Physiology and proteomics analyses reveal the response mechanisms of Rhizophora mucronata seedlings to prolonged complete submergence.

Mangrove seedlings are subject to natural tidal inundation, while occasional flooding may lead to complete submergence. Complete submergence reduces light availability and limits gas exchange, affecting several plant metabolic processes. The present study focuses on Rhizophora mucronata, a common mangrove species found along the coasts of Thailand and the Malay Peninsula. To reveal response mechanisms of R. mucronata seedlings to submergence, a physiological investigation coupled with proteomic analyses of leaf and root tissues was carried out in plants subjected to 20 days of control (drained) or submerged conditions. Submerged seedlings showed decreased photosynthetic activity, lower stomatal conductance, higher total antioxidant capacity in leaves and higher lipid peroxidation in roots than control plants. At the same time, tissue nutrient ion content displayed organ-specific responses. Proteome analysis revealed a significant change in 240 proteins in the leaves and 212 proteins in the roots. In leaves, most differentially accumulated proteins (DAPs) are associated with nucleic acids, stress response, protein transport, signal transduction, development and photosynthesis. In roots, most DAPs are associated with protein metabolic process, response to abiotic stimulus, nucleic acid metabolism and transport. Our study provides a comprehensive understanding of submergence responses in R. mucronata seedlings. The results suggest that submergence induced multifaceted stresses related to light limitation, oxidative stress and osmotic stress, but the responses are organ specific. The results revealed many candidate proteins which may be essential for survival of R. mucronata under prolonged submergence.

Isolation, characterisation, anticancer and anti-oxidant activities of 2-methoxy mucic acid from Rhizophora apiculata: an in vitro and in silico studies.

The main objective of the present study is to isolate and characterise the novel bioactive molecule, 2-methoxy mucic acid (4) from Rhizophora apiculate Blume under the Rhizophoraceae family. In this study, the 2-methoxy mucic acid (4) was isolated for the first time from the methanolic extract of the leaves of R. apiculata. Anticancer activity of 2-methoxy mucic acid (4) was evaluated against HeLa and MDA-MB-231 cancer cell lines and they displayed promising activity with IC50 values of 22.88283 ± 0.72 µg/ml in HeLa and 2.91925 ± 0.52 µg/ml in the case of MDA-MB-231, respectively. Furthermore, the antioxidant property of 2-methoxy mucic acid (4) was found to be (IC50) 21.361 ± 0.41 µg/ml. Apart from in vitro studies, we also performed extensive in silico studies (molecular docking and molecular dynamics simulation) on four critical antiapoptotic Bcl-2 family members (Bcl-2, Bcl-w, Bcl-xL and Bcl-B) towards 2-methoxy mucic acid (4). The results revealed that this molecule showed higher binding affinity towards Bcl-B protein (ΔG = -5.8 kcal/mol) and the structural stability of this protein was significantly improved upon binding of this molecule. The present study affords vital insights into the importance of 2-methoxy mucic acid (4) from R. apiculata. Furthermore, it opens the therapeutic route for the discovery of anticancer drugs. Research HighlightsThis is a first report on a bioactive compound identified and characterised; a novel 2-methoxy mucic acid derived from methanolic crude extract from the leaves of R. apiculata from ANI.Estimated binding free energy of 2-methoxy mucic acid is found to be -5.8 kcal/mol to the anti-apoptotic Bcl-B protein.2-methoxy mucic acid showed both significant anti-cancer and anti-oxidant activity.Communicated by Ramaswamy H. Sarma.

Temperature dependence of O2 respiration in mangrove leaves and roots: implications for seedling dispersal phenology.

Seasonal differences in diaspore dispersal of three mangrove species, Kandelia obovata, Bruguiera gymnorrhiza and Rhizophora stylosa, suggest that respiratory energy production and demand may differ as a result of interspecific differences in temperature dependence of growth and maintenance processes during seedling establishment. We analyzed growth, temperature dependencies of respiratory O2 consumption and amounts of respiratory chain enzymes in seedlings of these species grown at various temperatures. Respiration rates measured at the low reference temperature, RREF , were highest in leaves of 15°C-grown K. obovata, whose dispersal occurs in the cold season, while root RREF of 15°C-grown R. stylosa was 60% those of the other species, possibly because of warm conditions during its establishment phase. In leaves and roots of K. obovata and leaves of R. stylosa, the overall activation energy, Eo , changed with growth temperature associated with changes in the ratios of the amount of protein in the two respiratory pathways. However, Eo of seedlings of B. gymnorrhiza, which has a long dispersal phase, were constant and independent of growth temperature. The different temperature responses of seedling respiration and growth among these three species may reflect the seasonal temperature range of seedling dispersal and establishment in each species.

Red Mangrove Propagule Bacterial Communities Vary With Geographic, But Not Genetic Distance.

Bacterial communities associated with plant propagules remain understudied, despite the opportunities that propagules represent as dispersal vectors for bacteria to new sites. These communities may be the product of a combination of environmental influence and inheritance from parent to offspring. The relative role of these mechanisms could have significant implications for our understanding of plant-microbe interactions. We studied the correlates of microbiome community similarities across an invasion front of red mangroves (Rhizophora mangle L.) in Florida, where the species is expanding northward. We collected georeferenced propagule samples from 110 individuals of red mangroves across 11 populations in Florida and used 16S rRNA gene (iTag) sequencing to describe their bacterial communities. We found no core community of bacterial amplicon sequence variants (ASVs) across the Florida range of red mangroves, though there were some ASVs shared among individuals within most populations. Populations differed significantly as measured by Bray-Curtis dissimilarity, but not Unifrac distance. We generated data from 6 microsatellite loci from 60 individuals across 9 of the 11 populations. Geographic distance was correlated with beta diversity, but genetic distance was not. We conclude that red mangrove propagule bacterial communities are likely influenced more by local environmental acquisition than by inheritance.

Association of Rhizophora mangle and ascorbic acid in hydrogels: Evaluation of cytotoxic and immunomodulatory effects

Abstract Polyphenolics from Rhizophora mangle (R. mangle) have shown wound healing and anti- inflammatory effects that may be potentiated by being associated with ascorbic acid, an important substance for collagen and elastin synthesis that plays a role in tissue repair. In our study, we aimed to formulate an association of R. mangle and ascorbic acid in hydrogels and evaluate the association's cytotoxic and immunomodulatory effects. In a pre-formulation study, three gelling polymers (i.e.xanthan gum, poloxamer and hydroxyethyl cellulose) were tested. The selected polymer (i.e. xanthan gum) was used to evaluate cytotoxic and immunomodulatory effects using flow cytometry. Xanthan gum (1.5%) had a homogeneous appearance, an orange colour, a smooth surface, intense brightness and the typical odour, as well as non-Newtonian pseudoplastic behaviour. With a pH of 5.0-5.3 and a non-cytotoxic profile, xanthan gum induced the proliferation and activation of CD4 +, CD8+ and NK T lymphocytes and the production of IL- 2, IL-4, IL-10, IL-17 and TNF-α cytokines in stimulated splenocytes. The results suggest that the association of R. mangle and ascorbic acid in 1.5% xanthan gum hydrogel may be promising in preparations for wound-healing processes.

Dosimetric Analysis of Rhizophora-based Phantom Material in Radiation Therapy Applications Using Monte Carlo GATE Simulation.

Purpose: This study aims to determine the percentage depth dose (PDD) of a phantom material made from soy-lignin bonded Rhizophora spp. particleboard coated with a gloss finish by using Monte Carlo Geant4 Application for Tomographic Emission (GATE) simulation. Materials and Methods: The particleboard was fabricated using a hot pressing technique at target density of 1.0 g·cm-3 and the elemental fraction was recorded for the simulation. The PDD was simulated in the GATE simulation using the linear accelerator Elekta Synergy model for the water phantom and Rhizophora phantom, and the results were compared with the experimental PDD performed by several studies. Beam flatness and beam symmetry were also measured in this study. Results: The simulated PDD for Rhizophora and water was in agreement with the experimental PDD of water with overall discrepancies of 0% to 8.7% at depth ranging from 1.0 to 15.0 cm. In the GATE simulation, all the points passed the clinical 3%/3 mm criterion in comparison with water, with the final percentage of 2.34% for Rhizophora phantom and 2.49% for the water phantom simulated in GATE. Both the symmetries are all within the range of an acceptable value of 2.0% according to the recommendation, with the beam symmetry of the water phantom and Rhizophora phantom at 0.58% and 0.28%, respectively. Conclusions: The findings of this study provide the necessary foundation to confidently use the phantom for radiotherapy purposes, especially in treatment planning.

Elemental Composition of Above and Belowground Mangrove Tissue and Sediment in Managed and Unmanaged Compartments of the Matang Mangrove Forest Reserve.

Mangrove productivity depends on the storage of nutrients and elements. Elemental concentrations were examined in leaves, roots, and sediments for three age stands (15, 25 years, and VJR) of Rhizophora apiculata in the Matang Mangrove Forest Reserve (MMFR). Six compartments with two compartments each for each age group were used to analyze sixteen elements. Four types of elemental patterns were examined with decreasing order during analysis: (1) Cd < Cu < Pb < Zn < Mg < Mn < Fe < K < Na < Ca and P% < S% < N% < C% in leaves, (2) Cd < Pb < Cu < Zn < Mg < Mn < Fe < K < Na < Ca and P% < S% < N% < C% in roots, (3) Cd < Pb < Cu < Zn < Mg < Mn < K < Fe < Na < Ca and P% < N% < S% < C% in sediment samples and (4) Cd(S) < Pb(S) < Cu(S) < Zn(S) < Mg(S) < Mn(L) < K(L) < Fe(S) < Na(R) < Ca(R) and P%(S) < S%(S) < N%(L) < C%(R) collectively for all samples. Evidence that elements do not store primarily in above-ground biomass can be found in the observation that elements are stored more in sediment and roots. The outcome of the present study shows that the rate of increase of elements in trees (leaves and roots) was less as compared to sediments, where the elemental concentration increased considerably with time. Elemental concentration comparison within three age classes showed that C, N, and S were significantly different in all three types of samples. The δ15N ratios showed positive values in all six compartments which supported the concept that the δ15N ratio could not be observed in N concentration in this study. The δ13C values showed more negative values in all six compartments which represented less salinity and a freshwater intake. The S, P, and heavy metals concentrations were high. The concentrations of Cd, P, N, C, and S in the sediment influenced variations in four compartments in accordance with the three mangrove age groups. The results of this study can be utilized to create management plans for MMFR and conduct risk assessments of the elements' concentration in sediment.

Rhizophora mucronata Lam. (Mangrove) Bark Extract Reduces Ethanol-Induced Liver Cell Death and Oxidative Stress in Swiss Albino Mice: In Vivo and In Silico Studies.

The bark extract of Rhizophora mucronata (BERM) was recently reported for its prominent in vitro protective effects against liver cell line toxicity caused by various toxicants, including ethanol. Here, we aimed to verify the in vivo hepatoprotective effects of BERM against ethanol intoxication with the prediction of potential targets employing in silico studies. An oral administration of different concentrations (100, 200 and 400 mg/kg body weight) of BERM before high-dose ethanol via intraperitoneal injection was performed in mice. On day 7, liver sections were dissected for histopathological examination. The ethanol intoxication caused liver injury and large areas of necrosis. The pre-BERM administration decreased the ethanol-induced liver damage marker tumor necrosis factor-alpha (TNF-α) expression, reduced hepatotoxicity revealed by nuclear deoxyribonucleic acid (DNA) fragmentation and decreased oxidative stress indicated by malondialdehyde and glutathione contents. Our in silico studies have identified BERM-derived metabolites exhibiting the highest predicted antioxidant and free radical scavenger activities. Molecular docking studies showed that most of the metabolites were predicted to be enzyme inhibitors such as carbonic anhydrase inhibitors, which were reported to stimulate the antioxidant defense system. The metabolites predominantly presented acceptable pharmacokinetics and safety profiles, suggesting them as promising new antioxidant agents. Altogether, the BERM extract exerts antioxidative activities and shows promising hepatoprotective effects against ethanol intoxication. Identification of related bioactive compounds will be of interest for future use at physiological concentrations in ethanol-intoxicated individuals.