Class Of Metabolites Research Articles

Caenorhabditis elegans as an Outstanding Model to Explore Flavonoids Under Stress Conditions

Abstract: Plants produce promising chemicals called secondary metabolites in response to stress, which protect against oxidative damage in both plants and humans. Reactive oxygen species (ROS) levels combined with an imbalance in the antioxidant responses can trigger oxidative stress that is related to many conditions such as Alzheimer's disease, diabetes, and cancer. One way to counteract or avoid the stress excess is by flavonoid administration, a class of plant metabolites with a consistent antioxidant action and the ability to inactivate the free radical excess. The mechanisms, as well as the benefits and toxicity of antioxidant products, can be tested in alternative animal models. The mechanisms, as well as the benefits and toxicity of antioxidant products, can be tested in alternative animal models. In this review, we explored how Caenorhabditis elegans, a nematode with high genetic similarity to human genes and the antioxidant response pathway conserved, can be considered an attractive model organism for testing flavonoid compounds. Here, we emphasize the crucial results regarding C. elegans and the flavonoid quercetin, focusing on oxidative stress and aging investigations. Also, this review highlights the quercetin benefits in C. elegans lifespan, healthspan, neurodegeneration, and impacts on insulin/IGF-1 signaling (IIS).

Novel metabolomic predictors of incident colorectal cancer in men and women.

Metabolomic profiles may influence colorectal cancer (CRC) development. Few studies have performed pre-diagnostic metabolome-wide analyses with CRC risk. We conducted a nested case-control study among women (Nurses' Health Study (NHS)) and men (Health Professionals Follow-up Study (HPFS)) who provided blood between 1989 and 1995. Over 22.9 years, 684 (409 NHS, 275 HPFS) incident CRC cases occurred and were matched 1:1 to controls. Liquid chromatography-mass spectrometry (LC-MS) identified 255 plasma metabolites after quality control. Cohort-specific and combined metabolite association analyses were performed using conditional logistic regression. Metabolite set enrichment analysis (MSEA) was used to identify differential abundance in metabolite classes. Weighted Correlation Network Analysis (WGCNA) provided modules of covarying metabolites, which were tested for CRC association. MSEA identified specific acylcarnitines associated with higher CRC risk and triacylglycerols with lower CRC risk among women and men. Further, phosphatidylcholines were associated with a higher risk of CRC among men. In an analysis restricted to CRC cases diagnosed two years after blood draw, myristoleic acid (OR = 1.37; 95%CI = 1.15-1.62; FDR = 0.072) and C60:12 triacylglycerol (OR = 0.75; 95%CI = 0.64-0.88; FDR = 0.072 were associated with CRC risk in women. WGCNA identified amino acids associated with CRC in men, fatty acid esters (carnitines) with distal CRC in men, and triradylcglycerols inversely associated with CRC in women. We identified pre-diagnostic CRC-associated metabolites with distinct sex-specific profiles. These results provide insight into CRC etiopathogenesis and have implications for risk prediction strategies.

Bioactive metabolites: a clue to the link between MASLD and CKD?

Metabolites produced as intermediaries or end-products of microbial metabolism provide crucial signals for health and diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD). These metabolites include products of the bacterial metabolism of dietary substrates, modification of host molecules [such as bile acids (BAs), trimethylamine-N-oxide, and short-chain fatty acids], or products directly derived from bacteria. Recent studies have provided new insights into the association between MASLD and the risk of developing chronic kidney disease (CKD). Furthermore, alterations in microbiota composition and metabolite profiles, notably altered BAs, have been described in studies investigating the association between MASLD and the risk of CKD. This narrative review discusses alterations of specific classes of metabolites, BAs, fructose, vitamin D, and microbiota composition that may be implicated in the link between MASLD and CKD.

Chemical Profile, Antibacterial and Toxicological Study of Asparagus setaceus (KUNTH)

Objective: The objective of this work was to obtain the chemical profile and verify the biological activities of ethanolic extract from the leaves of Asparagus setaceus. Method: The extract was obtained with cold ethanol and the classes of secondary metabolites were identified with specific reagents. The antibacterial assays were performed using the microdilution method against the standard bacteria, Gram +: Sthaphylococcus aureus, Streptococcus mutans and Enterococcus faecalis and Gram -: Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoneae and two multidrug-resistant strains: Escherichia coli 27 and Staphylococcus aureus 358 and the resistance modulation assay was performed using aminoglycoside and beta- lactam antibiotics. Toxicity was tested against the microcrustacean Artemia salina (Leach) ranging in concentrations from 10 to 500 μg/mL Results and Discussion: The ethanolic extract of Asparagus setaceus (EEAS) indicated the presence of phenols, condensed tannins, anthocyanins, anthocyanidins, flavones, flavonols, xanthones, chalcones, aurones, flavononols, catechins, leukoanthocyanidins, flavones and saponins. The EEAS presented CL50 of 90.22 μg/ mL. The microbial assay showed inhibition for standard strains of Gram + and Gram bacteria - but in the multidrug-resistant strains it showed clinically non-signific results. For the modulation of antibiotic action against bacterial strains, EEAS presented both synergistic and antagonistic action, with the synergistic action being more expressive on benzylpenicillin, amikacin and gentamicin in front of Escherichia coli 27. The aminoglycoside antibiotics showed synergistic activity on all bacteria tested. Research Implications: Given the results, it was found that the ethanolic extract of the leaves of Asparagus setaceus (Kunth) disp of chemical and biological properties that can contribute to the elaboration of therapeutic resources against inflammatory and bacterial infectious processes. Keywords: Antibacterial Assay, Secondary Metabolites, Modulation, Asparagus setaceus.

Catechol acetylglucose: a newly identified benzoxazinoid-regulated defensive metabolite in maize.

An enormous diversity of specialized metabolites is produced in the plant kingdom, with each individual plant synthesizing thousands of these compounds. Previous research showed that benzoxazinoids, the most abundant class of specialized metabolites in maize, also function as signaling molecules by regulating the production callose as a defense response. We searched for additional benzoxazinoid-regulated specialized metabolites, characterized them, examined whether they too function in herbivore protection, and determined how Spodoptera frugiperda (fall armyworm), a prominent maize pest, copes with these metabolites. We identified catechol acetylglucose (CAG) as a benzoxazinoid-regulated metabolite that is produced from salicylic acid via catechol and catechol glucoside. Genome-wide association studies of CAG abundance identified a gene encoding a predicted acetyltransferase. Knockout of this gene resulted in maize plants that lack CAG and over-accumulate catechol glucoside. Upon tissue disruption, maize plants accumulate catechol, which inhibits S. frugiperda growth. Analysis of caterpillar frass showed that S. frugiperda detoxifies catechol by glycosylation, and the efficiency of catechol glycosylation was correlated with S. frugiperda growth on a catechol-containing diet. Thus, the success of S. frugiperda as an agricultural pest may depend partly on its ability to detoxify catechol, which is produced as a defensive metabolite by maize.

The Influence of Different Factors on the Metabolism of Capsaicinoids in Pepper (Capsicum annuum L.)

Pepper is a globally cultivated vegetable known for its distinct pungent flavor, which is derived from the presence of capsaicinoids, a class of unique secondary metabolites that accumulate specifically in pepper fruits. Since the accumulation of capsaicinoids is influenced by various factors, it is imperative to comprehend the metabolic regulatory mechanisms governing capsaicinoids production. This review offers a thorough examination of the factors that govern the metabolism of capsaicinoids in pepper fruit, with a specific focus on three primary facets: (1) the impact of genotype and developmental stage on capsaicinoids metabolism, (2) the influence of environmental factors on capsaicinoids metabolism, and (3) exogenous substances like methyl jasmonate, chlorophenoxyacetic acid, gibberellic acid, and salicylic acid regulate capsaicinoid metabolism. The findings of this study are expected to enhance comprehension of capsaicinoids metabolism and aid in the improvement of breeding and cultivation practices for high-quality pepper in the future.

Optimization of microwave parameters to enhance phytochemicals, antioxidants and metabolite profile of de-oiled rice bran

The current study explores the effects of microwave treatment at varying wattage and durations on the phytoconstituents, antioxidant status, anti-nutritional factors (ANFs), and metabolite profiles of de-oiled rice bran. The total phenolics and flavonoids showed both increases and decreases depending on specific microwave parameters, while flavonol content consistently increased across all treated groups compared to the control. The DPPH and ABTS free radical scavenging activity, total antioxidant capacity, FRAP, CUPRAC, metal chelating activity, and ascorbic acid content were enhanced in most of the microwaved samples; however, longer microwave exposure at higher wattage led to their reduction. A treatment-specific decrease in ANFs, including condensed tannins, oxalates, and phytates, was observed. HRMS-based untargeted metabolomics identified a diverse range of primary and secondary metabolites, which clustered in a group-specific manner, indicating notable group-wise metabolite variations. Analysis of discriminating metabolites revealed no significant differences in the overall levels of phenolics, flavonoids, vitamins and cofactors, sugars, amino acids, terpenoids, fatty acids, and their derivatives among the treated groups compared to the control; however, several individual metabolites within these metabolite classes differed significantly. These findings suggest that optimized microwaving of de-oiled rice bran can enhance phytochemicals and antioxidants while improving the metabolite profile.

Nutrient content and ultra-performance liquid chromatography tandem mass spectrometry metabolomic comparative analysis of Lithocarpus corneus and Lithocarpus pachylepis.

China possesses abundant species resources in genus Lithocarpus Blume, commonly known as "acorns." These nuts are traditional foods in China, holding significant potential for local specialty food and rural economic development. To explore their edible value, we compared the nutritional components and metabolites between the fruits of Lithocarpus corneus (YD) and Lithocarpus pachylepis (HL), which are cultivated widely in south of China. Non-targeted metabolomics analysis of YD and HL was performed using ultra-performance liquid chromatography tandem mass spectrometry technology. A total of eight classes of differential metabolites (DAMs) were detected: alkaloids, amino acids and peptides, carbohydrates, fatty acids, polyketides, shikimates and phenylpropanoids, terpenoids, and other metabolites. In the positive ion mode, 225 DAMs were identified, whereas in the negative ion mode, 116 DAMs were identified. KEGG pathway enrichment analysis showed that the differentially abundant metabolites were generally enriched in three pathways: aminoacyl-tRNA biosynthesis, alanine, aspartate, and glutamate metabolism, and ABC transporters. The nutritional content of YD has higher moisture, fructose, and total flavonoid levels, but lower starch, protein, fat, glucose, sucrose, and total sugar content than HL. Additionally, YD contains more Ca, K, P, and Fe, but less Mg and Zn compared to HL. Analyses indicate that YD is nutrient-rich and beneficial, making it suitable for further development. Two species of Lithocarpus contain nandrolone, suggesting a new direction for specialty food development. The unique chemical composition and rich nutritional content of Lithocarpus fruits provide a theoretical basis for their development and application as food resources. PRACTICAL APPLICATION: L. corneus and L. pachylepis are traditional Chinese nuts, rich in starch, minerals, and flavonoids, making them suitable for consumption or use as food constituents. Their fruits contain various unique natural chemical compounds, indicating high application value and development potential.

De novo production of protoberberine and benzophenanthridine alkaloids through metabolic engineering of yeast

Protoberberine alkaloids and benzophenanthridine alkaloids (BZDAs) are subgroups of benzylisoquinoline alkaloids (BIAs), which represent a diverse class of plant-specialized natural metabolites with many pharmacological properties. Microbial biosynthesis has been allowed for accessibility and scalable production of high-value BIAs. Here, we engineer Saccharomyces cerevisiae to de novo produce a series of protoberberines and BZDAs, including palmatine, berberine, chelerythrine, sanguinarine and chelirubine. An ER compartmentalization strategy is developed to improve vacuole protein berberine bridge enzyme (BBE) activity, resulting in >200% increase on the production of the key intermediate (S)-scoulerine. Another promiscuous vacuole protein dihydrobenzophenanthridine oxidase (DBOX) has been identified to catalyze two-electron oxidation on various tetrahydroprotoberberines at N7-C8 position and dihydrobenzophenanthridine alkaloids. Furthermore, cytosolically expressed DBOX can alleviate the limitation on BBE. This study highlights the potential of microbial cell factories for the biosynthesis of a diverse group of BIAs through engineering of heterologous plant enzymes.

Mushroom alkaloids as nutraceuticals, bioactive and medicinal properties: a preliminary review

Mushroom alkaloids are quite interesting due to their distinct secondary metabolites. Alkaloids are a class of secondary metabolites that are found in different types of organisms. The primary focus of this study is the alkaloids that were taken out of the mushrooms. Mainly the mushrooms alkaloids are classified as 2 groups like indoles and isoxazoles. In the present paper 68 distinct alkaloids produced from mushrooms were attempted to be listed under 24 distinct groups; i.e. 24 alkaloids were kept under Indole group, 5 different alkaloids were kept under ? - carboline group and pyrroloquinoline group, 4 different alkaloids were kept under pyrrole group, and 3 different alkaloids were mentioned under quinoline groups. Mushrooms were used as food in many parts of the world. The alkaloids obtained from mushrooms showing different bioactivities like antimicrobial, anticancer, anti-diabetic, hepatoprotective, anti-inflammatory, antioxidant, immunomodulatory, anti-obesity, anti - ageing, nematicidal, helmintic, against cardiovascular disease and as antiasthmatic agent. Mushrooms were widely used in the traditional medicine of many countries like china, India, Taiwan, Japan etc. these mushrooms became great resources for many groups of alkaloids with bioactivities which should be useful in present day modern clinical and pharmacological research. The present review aims at listing the applications of mushroom alkaloids in different fields like medicine, health science, pharmacy etc.

Efficient Production of 4’-Hydroxydihydrochalcones Using Non-Conventional Yeast Strains

The quest for novel therapeutic agents has rekindled interest in natural products, particularly those derived from biotransformation processes. Dihydrochalcones, a class of plant secondary metabolites, exhibit a range of pharmacological properties. Chalcone and dihydrochalcone compounds with the characteristic 4’-hydroxy substitution are present in ‘dragon’s blood’ resin, known for its traditional medicinal uses and complex composition, making the isolation of these compounds challenging. This study investigates the efficient production of 4′-hydroxydihydrochalcones using non-conventional yeast strains. We evaluated the biotransformation efficiency of various 4′-hydroxychalcone substrates utilizing yeast strains such as Yarrowia lipolytica KCh 71, Saccharomyces cerevisiae KCh 464, Rhodotorula rubra KCh 4 and KCh 82, and Rhodotorula glutinis KCh 242. Our findings revealed that Yarrowia lipolytica KCh 71, Rhodotorula rubra KCh 4 and KCh 82, and Rhodotorula glutinis KCh 242 exhibited the highest conversion efficiencies, exceeding 98% within one hour for most substrates. The position of methoxy substituents in the chalcone ring significantly influenced hydrogenation efficiency. Moreover, we observed isomerization of trans-4′-hydroxy-2-methoxychalcone to its cis isomer, catalyzed by light exposure. This study underscores the potential of using yeast strains for the sustainable and efficient production of dihydrochalcones, providing a foundation for developing new therapeutic agents and nutraceuticals.

Advances in Chiral Metabolomic Profiling and Biomarker Discovery.

Chiral metabolomics entails the enantioselective measurement of the metabolome present in a biological system. Over recent years, it has garnered significant interest for its potential in discovering disease biomarkers and aiding clinical diagnostics. D-Amino acids and D-hydroxy acids, traditionally overlooked as unnatural, are now emerging as novel signaling molecules and potential biomarkers for a range of metabolic disorders, brain diseases, kidney disease, diabetes, and cancer. Despite their significance, simultaneous measurements of multiple classes of chiral metabolites in a biological system remain challenging. Hence, limited information is available regarding the metabolic pathways responsible for synthesizing D-amino/hydroxy acid and their associated pathophysiological mechanisms in various diseases. Capitalizing on recent advancements in sensitive analytical techniques, researchers have developed various targeted chiral metabolomic methods for the analysis of chiral biomarkers. Here, we highlight the pivotal role of chiral metabolic profiling studies in disease diagnosis, prognosis, and therapeutic interventions. Furthermore, we describe cutting-edge chromatographic and mass spectrometry methods that enable enantioselective analysis of chiral metabolites. These advanced techniques are instrumental in unraveling the complexities of disease biomarkers, contributing to the ongoing efforts in disease biomarker discovery.

Effects of thermal and UV stress on the polar and non-polar metabolome of photosymbiotic jellyfish and sea anemones

Recently, the impacts of climate change, notably ocean warming and solar ultraviolet radiation, have led to significant stress and mortality in cnidarians. The objective of this study is to decode the metabolic responses of sea anemones Entacmaea quadricolor and upside-down jellyfish Cassiopea andromeda upon exposure to thermal and ultraviolet stress. Gas chromatography-mass spectrometry and ultraperformance liquid chromatography coupled with high-resolution mass spectrometry targeting polar and non-polar metabolites were applied. In total, 72 polar and 242 lipophilic metabolites were detected in jellyfish and sea anemones, respectively. Amino acids are the major metabolite class in jellyfish, and triacylglycerides are the predominant lipids in jellyfish and anemones. Exposure to stressors led to metabolic alterations, marked by elevated amino acids in jellyfish and increased amino acids and sugar alcohols in sea anemones at 34 °C and after four days of ultraviolet radiation. Non-polar metabolome analysis indicated distinct responses to ultraviolet radiation and thermal stress in both species.

Metabolit Sekunder dan Uji Bioaktivitas Sitotoksik Ekstrak Buah Sumpit (Brucea javanica (L.) Merr) terhadap Artemia salina Leach

Research carried out with the title of Secondary Metabolite Identification and bioactivity Fruit Extract Sumpit (Brucea javanica (L) Merr) to the shrimp larvae Artemia salina Leach. This study aims to identifying classes of secondary metabolites as well as test the bioactivity of secondary metabolites sumpit. Identifikasi fruit extracts performed to test the Chopsticks fruit extracts and fractions against reagent, while the bioactivity test was conducted using Brine Shrimp Lethality Test (BSLT). Data were analyzed using the method of Reed and Muench to get Lethality Concrentation value 50% (LC50). The results showed that the fruit extract Sumpit contain the alkaloid class of secondary metabolites, karatenoid, saponins, tannins, phenolic compounds, steroids, and terpenoids. Sumpit fruit bioactivity test results had LC50 values of the methanol extract of 3.10 ppm, n-hexane fraction of 2.09 ppm, 0.79 ppm ethyl acetate fraction and n-butanol fractions of 0.74 ppm.

The Influence of Rhizobial Nod Factors on the Synthesis of Flavonoids in Common Buckwheat (Fagopyrum esculentum Moench)

Flavonoids constitute a class of polyphenolic secondary metabolites synthesised mainly by plants and possessing anticancer, antioxidant, anti-inflammatory, and antiviral properties. Common buckwheat (F. esculentum Moench) is a dicotyledonous plant rich in different classes of flavonoids (e.g., rutin) and other phenolic compounds. Lipochitooligosaccharides (LCOs), i.e., rhizobial Nod factors and important signalling molecules for the initiation of symbiosis with legumes, are very effective mitogens that stimulate cell division in plant meristems and the production of secondary metabolites. They can also act in this way in non-legume plants. It has been shown that rhizobial Nod factors noticeably improve plant growth. Rhizobial Nod factors influence the production of flavonoids in common buckwheat grown in greenhouse conditions. The amount of rutin and isoorientin in leaves and flowers has been shown to increase in a statistically significant way after application of Nod factors to buckwheat seeds. The presence of rhizobial Nod factors has no influence on the flavonoid content in stems and roots.

Comparison between Traditional and Novel NMR Methods for the Analysis of Sicilian Monovarietal Extra Virgin Olive Oils: Metabolic Profile Is Influenced by Micro-Pedoclimatic Zones.

Nuclear magnetic resonance (NMR) metabolomic analysis was applied to investigate the differences within nineteen Sicilian Nocellara del Belice monovarietal extra virgin olive oils (EVOOs), grown in two zones that are different in altitude and soil composition. Several classes of endogenous olive oil metabolites were quantified through a nuclear magnetic resonance (NMR) three-experiment protocol coupled with a yet-developed data-processing called MARA-NMR (Multiple Assignment Recovered Analysis by Nuclear Magnetic Resonance). This method, taking around one-hour of experimental time per sample, faces the possible quantification of different class of compounds at different concentration ranges, which would require at least three alternative traditional methods. NMR results were compared with the data of traditional analytical methods to quantify free fatty acidity (FFA), fatty acid methyl esters (FAMEs), and total phenol content. The presented NMR methodology is compared with traditional analytical practices, and its consistency is also tested through slightly different data treatment. Despite the rich literature about the NMR of EVOOs, the paper points out that there are still several advances potentially improving this general analysis and overcoming the other cumbersome and multi-device analytical strategies. Monovarietal EVOO's composition is mainly affected by pedoclimatic conditions, in turn relying upon the nutritional properties, quality, and authenticity. Data collection, analysis, and statistical processing are discussed, touching on the important issues related to the climate changes in Sicily and to the specific influence of pedoclimatic conditions.

Exploring the Potential of Terpenoids as a Possible Treatment for Cancer: Structure-Activity Relationship and Mechanistic Studies.

Cancer stands as a significant global health challenge due to its mortality rates and the complexities involved in its treatment. Addressing issues, such as metastasis, recurrence, chemoresistance, and treatment-related toxicity, remains pivotal in cancer therapy advancement. Therefore, exploration of novel therapeutic agents has emerged as a priority. As the risk of cancer continues to rise, effective measures must be taken to combat it. One promising approach is to explore natural remedies, such as terpenoids, which have demonstrated anticancer activity. Utilizing terpenoids could aid in the development of potent compounds to fight cancer. By studying the structural makeup of various terpenoid derivatives from previous research, we can identify which structural groups are essential for their anticancer activity. This understanding of the structure-activity relationship is crucial for developing new, effective anticancer agents based on terpenoids. Terpenoids, a diverse class of plant-derived secondary metabolites composed of multiple isoprene units, have garnered attention for their potential anticancer and pharmacological qualities. Some terpenoids exhibit notable anticancer effects by concentrating on several stages of cancer development. They show promise in blocking the initiation of early carcinogenesis by the induction of cell cycle arrest, the inhibition of cancer cell differentiation, and the induction of apoptosis. This study delves into the investigation of specific terpenoids showcasing promising anticancer activity against prevalent malignancies, including breast, colon, ovarian, and lung cancers. The study also explores the relationship between the structure and activity of these compounds, which sheds light on how effective they are against a variety of cancer cell types. The comprehensive discussion centres on elucidating terpenoids with substantial potential for combating diverse cancer types, offering insights into their structural features and promising anticancer mechanisms.

Non-Targeted Metabolomics of Serum Reveals Biomarkers Associated with Body Weight in Wumeng Black-Bone Chickens.

Growth performance is an important economic trait of broilers but the related serum metabolomics remains unclear. In this study, we utilized non-targeted metabolomics using ultra-high-performance liquid phase tandem mass spectrometry (UHPLC-MS/MS) to establish metabolite profiling in the serum of Chinese Wumeng black-bone chickens. The biomarker metabolites in serum associated with growth performance of chickens were identified by comparing the serum metabolome differences between chickens that significantly differed in their weights at 160 days of age when fed identical diets. A total of 766 metabolites were identified including 13 differential metabolite classes such as lipids and lipid-like molecules, organic acids and their derivatives, and organoheterocyclic compounds. The results of difference analysis using a partial least squares discriminant analysis (PLS-DA) model indicated that the low-body-weight group could be differentiated based on inflammatory markers including prostaglandin a2, kynurenic acid and fatty acid esters of hydroxy fatty acids (FAHFA), and inflammation-related metabolic pathways including tryptophan and arachidonic acid metabolism. In contrast, the sera of high-body-weight chickens were enriched for riboflavin and 2-isopropylmalic acid and for metabolic pathways including riboflavin metabolism, acetyl group transfer into mitochondria, and the tricarboxylic acid (TCA) cycle. These results provide new insights into the practical application of improving the growth performance of local chickens.

Sulfated Bile Acids in Serum as Potential Biomarkers of Disease Severity and Mortality in COVID-19.

The fight against coronavirus disease 2019 (COVID-19) continues. Since the pandemic's onset, several biomarkers have been proposed to assess the diagnosis and prognosis of this disease. This research aimed to identify potential disease severity biomarkers in serum samples of patients with COVID-19 during the disease course. Data were collected using untargeted and targeted mass spectrometry methods. The results were interpreted by performing univariate and multivariate analyses. Important metabolite classes were identified by qualitative untargeted metabolomics in 15 serum samples from survivors of COVID-19. Quantitative targeted metabolomics on a larger patient cohort including 15 non-survivors confirmed serum 3-sulfate bile acids (i.e. GLCA-3S) were significantly increased in non-survivors compared to survivors during the early disease stage (p-value < 0.0001). Notably, it was associated with a higher risk of mortality (odds ratio of 26). A principal component analysis showed the ability to discriminate between survivors and non-survivors using the BA concentrations. Furthermore, increased BA-S is highly correlated with known parameters altered in severe clinical conditions.

Unveiling Lobophytum sp. the neuroprotective potential of Parkinson's disease through multifaceted mechanisms, supported by metabolomic analysis and network pharmacology

A main feature of neurodegenerative diseases is the loss of neurons. One of the most prevalent neurodegenerative illnesses is Parkinson disease (PD). Although several medications are already approved to treat neurodegenerative disorders, most of them only address associated symptoms. The main aim of the current study was to examine the neuroprotective efficacy and underlying mechanism of Lobophytum sp. crude extract in a rotenone-induced rat model of neurodegeneration mimicking PD in humans. The influence of the treatment on antioxidant, inflammatory, and apoptotic markers was assessed in addition to the investigation of TH (tyrosine hydroxylase) immunochemistry, histopathological changes, and α-synuclein. Metabolomic profiling of Lobophytum sp. crude extract was done by using High-Resolution Liquid Chromatography coupled with Mass Spectrometry (HR-LC–ESI–MS), which revealed the presence of 20 compounds (1–20) belonging to several classes of secondary metabolites including diterpenoids, sesquiterpenoids, steroids, and steroid glycosides. From our experimental results, we report that Lobophytum sp. extract conferred neuroprotection against rotenone-induced PD by inhibiting ROS formation, apoptosis, and inflammatory mediators including IL-6, IL-1β, and TNF-α, NF-кB, and subsequent neurodegeneration as evidenced by decreased α-synuclein deposition and enhanced tyrosine hydroxylase immunoreactivity. Moreover, a computational network pharmacology study was performed for the dereplicated compounds from Lobophytum sp. using PubChem, SwissTarget Prediction, STRING, DisGeNET, and ShinyGO databases. Among the studied genes, CYP19A1 was the top gene related to Parkinson’s disease. Dendrinolide compounds annotated a high number of parkinsonism genes. The vascular endothelial growth factor (VEGF) pathway was the top signaling pathway related to the studied genes. Therefore, we speculate that Lobophytum sp. extract, owing to its pleiotropic mechanisms, could be further developed as a possible therapeutic drug for treating Parkinson's disease.