Polyphenolic Metabolites Research Articles

A Heterocyclic Compound Hispidulin: Theoretical Investigation by DFT/TD-DFT Methods and Molecular Docking Studies

Flavonoids are polyphenolic plant secondary metabolites with biological properties including Alzheimer's disease (AD) inhibition activities. Numerous studies have been conducted on naturally occurring flavonoids modified to obtain effective drugs for the management of AD. In this study, DFT/B3PW91, TD-DFT/B3LYP methods of target molecule hispidulin 4′,5,7-Trihydroxy-6-Methoxyflavone (THMF) and LANL2DZ (d,p), 6-311G (d,p) basic HOMO-LUMO energy calculations, optimized molecular geometry, molecular electrostatic potential surface (MEPS), non-linear optics (NLO), charge transfer within the molecule and mulliken atomic charges structure were determined and the results were displayed. Moreover the identification of the mechanism of action of the tested compound based on the structure-activity relationship with the molecular docking process is to provide important information to be considered for further research, and thus to design new, more efficient and selective systems.

Evaluation of Antibacterial Activity of Extracts of Curcuma Longa L. Rhizome and Estimation of Curcuminoid by HPLC

Curcuma longa L. rhizome extracts have polyphenolic secondary metabolites called curcuminoid and various volatile oils. These compounds exhibit wide spectrum of antibacterial activity. Ethanol and petroleum ether C. longa rhizome extracts were studied for their antibacterial action against two bacteria, Escherichia coli and Staphylococcus aureus. This activity had evaluated by employing Agar Well Diffusion method. Curcuminoid was interpreted by pattern of High Performance Liquid Chromatography (HPLC). The ethanol extract exhibited inhibitory effects against E. coli and S. aureus at concentration 150 mg/ml with diameter of inhibition zone (23.000 ± 0.57735 and 27.000 ± 0.57735mm) respectively. On the contrary, petroleum ether extract had inhibitory effects for E. coli and S. aureus at concentration 150 mg/ml in diameter of inhibition zone (39.000 ± 0.57735 and 41.000 ± 0.57735mm) respectively. Quantitative analysis for the curcuminoid compounds from C. longa rhizome extracts revealed highest curcumin, demethoxycurcumin and bisdemethoxycurcumin (9.12, 5.93 and 23.96 µg /ml) respectively in the extract of petroleum ether. We concluded that the C. longa extracts exhibited inhibitory effects against pathological bacterial growth. The essential oils obtained by petroleum ether extract of C. longa rhizome was more influential inhibition than ethanol extract against E. coli and S. aureus.

The Role of Dietary Polyphenols in Pregnancy and Pregnancy-Related Disorders.

Polyphenols are a group of phytochemicals with extensive biological functions and health-promoting potential. These compounds are present in most foods of plant origin and their increased widespread availability through the intake of nutritional supplements, fortified foods, and beverages, has also led to increased exposure throughout gestation. In this narrative review, we focus on the role of polyphenols in both healthy and pathological pregnancy. General information related to their classification and function is followed by an overview of their known effects in early-pregnancy events, including the current insights into molecular mechanisms involved. Further, we provide an overview of their involvement in some of the most common pregnancy-associated pathological conditions, such as preeclampsia and gestational diabetes mellitus. Additionally, we also discuss the estimated possible risk of polyphenol consumption on pregnancy outcomes. The consumption of dietary polyphenols during pregnancy needs particular attention considering the possible effects of polyphenols on the mechanisms involved in maternal adaptation and fetal development. Further studies are strongly needed to unravel the in vivo effects of polyphenol metabolites during pregnancy, as well as their role on advanced maternal age, prenatal nutrition, and metabolic risk of the offspring.

Protective effects and therapeutic applications of ellagic acid against natural and synthetic toxicants: A review article.

Traditional herbal drugs are widely used for the treatment of various diseases. Ellagic acid (EA) as an herbal polyphenol metabolite exists in many medicinal plants. EA has an important role against natural and chemical toxicities due to its antioxidant and anti-inflammatory properties. For this review, several search engines or databases such as PubMed, Scopus, the Web of Science, and Google Scholar were used, and the most relevant published papers till February 2022 were included. The protective effects of EA against natural and chemical compounds are mediated through molecular mechanisms including scavenging of free radicals, modulation of proinflammatory cytokine synthesis, and reduction of lipid peroxidation. These properties make EA a highly fascinating compound that may contribute to different aspects of health; whereas, more studies are needed, especially on the pharmacokinetic profile of EA. In this review, we selected articles that include the protective effect of EA against several synthetic and natural toxins such as aflatoxin, lipopolysaccharide, acrylamide, and rotenone.

Impacts of Biotransformation on the Health Benefits of Tea Polyphenols.

Consumption of tea has been associated with many health benefits including the prevention of cardiovascular disease, cancer, and obesity. These effects are attributed to the polyphenol compounds in tea with catechins being the major components in green tea and theaflavins (TFs) and thearubigins (TRs) as the unique compounds in black tea. Tea polyphenols are extensively metabolized in vivo and have poor systematic bioavailability. It is generally believed that the metabolites of tea polyphenols retain their bioactivities and some of the microbial metabolites are more bioavailable than the parent compounds. This manuscript summarizes the recent progress on the identification of novel metabolic pathways of tea polyphenols and their contributions to the health benefits of tea.

Biodegradation of Free Gossypol by Helicoverpa armigera Carboxylesterase Expressed in Pichia pastoris.

Gossypol is a polyphenolic toxic secondary metabolite derived from cotton. Free gossypol in cotton meal is remarkably harmful to animals. Furthermore, microbial degradation of gossypol produces metabolites that reduce feed quality. We adopted an enzymatic method to degrade free gossypol safely and effectively. We cloned the gene cce001a encoding carboxylesterase (CarE) into pPICZαA and transformed it into Pichia pastoris GS115. The target protein was successfully obtained, and CarE CCE001a could effectively degrade free gossypol with a degradation rate of 89%. When esterase was added, the exposed toxic groups of gossypol reacted with different amino acids and amines to form bound gossypol, generating substances with (M + H) m/z ratios of 560.15, 600.25, and 713.46. The molecular formula was C27H28O13, C34H36N2O6, and C47H59N3O3. The observed instability of the hydroxyl groups caused the substitution and shedding of the group, forming a substance with m/z of 488.26 and molecular formula C31H36O5. These properties render the CarE CCE001a a valid candidate for the detoxification of cotton meal. Furthermore, the findings help elucidate the degradation process of gossypol in vitro.

Anthocyanin-rich extract from black beans exerts anti-diabetic effects in rats through a multi-genomic mode of action in adipose tissue.

Black beans (BB) are an important source of a range of plant bioactive compounds including polyphenols, particularly anthocyanins. Several studies support that consumption of BB is associated with health benefits, including prevention of type 2 diabetes mellitus (T2DM). However, molecular mechanisms underlying the potential health properties of BB on adipose tissue (AT) are still largely unknown. The purpose of this study was to investigate multi-genomic effects of BB intake and identify regulatory networks potentially mediating T2DM on AT. Male Wistar diabetic rats consumed an anthocyanin-rich black bean extract for 5 weeks. Global gene expression from AT, protein coding and non-coding RNA profiles were determined using RNAseq. Biological function analyses were performed using a variety of bioinformatic tools. The evaluation of global gene expression profiles exhibited significant change following BB consumption with 406 significantly differentially expressed genes, 33 miRNA and 39 lncRNA and 3 snRNA. Functional analyses indicated that these genes play an important role in regulation of PI3K signaling, NIN/NF-kB signaling, insulin secretion, and endoplasmic reticulum (ER) organization. Interestingly, transcription factors such as GATA2, or POU2AF1 demonstrated to modulate their activity by BB extract by direct interaction with polyphenol metabolites, or by interactions with cell signaling proteins, like PKB, AKT or PI3K, that could control transcription factor activity and as a result impact on adipogenesis regulation. Therefore, the constant consumption of an anthocyanin-rich black bean extract may have anti-diabetic protective effects by modulating gene expression, resulting in a promising alternative for T2DM patients.

Dietary Polyphenols as Prospective Natural-Compound Depression Treatment from the Perspective of Intestinal Microbiota Regulation

The broad beneficial effects of dietary polyphenols on human health have been confirmed. Current studies have shown that dietary polyphenols are important for maintaining the homeostasis of the intestinal microenvironment. Moreover, the corresponding metabolites of dietary polyphenols can effectively regulate intestinal micro-ecology and promote human health. Although the pathogenesis of depression has not been fully studied, it has been demonstrated that dysfunction of the microbiota-gut-brain axis may be its main pathological basis. This review discusses the interaction between dietary polyphenols and intestinal microbiota to allow us to better assess the potential preventive effects of dietary polyphenols on depression by modulating the host gut microbiota.

Journey of Rosmarinic Acid as Biomedicine to Nano-Biomedicine for Treating Cancer: Current Strategies and Future Perspectives.

Rosmarinic acid (RA) is a polyphenolic metabolite found in various culinary, dietary sources, and medicinal plants like Coleus scutellarioides (Linn) Benth., Lavandula angustifolia Linn., Mellisa officinalis Linn., Origanum vulgare Linn., Rosmarinus officinalis Linn., Zataria multiflora Boiss. and Zhumeria majdae Rech. F. Apart from its dietary and therapeutic values, RA is an important anticancer phytochemical owing to its multi-targeting anticancer mechanism. These properties provide a scope for RA's therapeutic uses beyond its traditional use as a dietary source. However, its oral bioavailability is limited due to its poor solubility and permeability. This impedes its efficacy in treating cancer. Indeed, in recent years, tremendous efforts have been put towards the development of nanoformulations of RA for treating cancer. However, this research is in its initial stage as bringing a nanoparticle into the market itself is associated with many issues such as stability, toxicity, and scale-up issues. Considering these pitfalls during formulation development and overcoming them would surely provide a new face to RA as a nanomedicine to treat cancer. A literature search was conducted to systematically review the various biological sources, extraction techniques, and anticancer mechanisms through which RA showed multiple therapeutic effects. Various nanocarriers of RA pertaining to its anticancer activity are also discussed in this review.

UPLC-QToF-MS based fingerprinting of polyphenolic metabolites in the bark extract of Boehmeria rugulosa Wedd.

Boehmeria rugulosa Wedd. is an evergreen tree of Urticaceae family. Its bark has been extensively used in ethno-medicinal system for various ailments such as bone fracture, sprain, snakebite, and wound healing. Phyto-metabolites, which are considered as the principle components for biological activities, have been least explored for this plant. The present work investigated metabolite profiling of the stem bark of B. rugulosa in water extract using Ultra Performance Liquid Chromatography Quadrupole Time of Flight Mass Spectrometry (UPLC-QToF-MS) technique coupled with the UNIFI platform. We identified, for the first time, 20 polyphenolic metabolites belonging to seven groups: caffeoylquinic acids, coumaroylquinic acids, flavan-3-ols, oligomeric flavonoids, caffeic acid derivatives, coumaric acid derivative, and flavone glycoside in the B. rugulosa extract. UNIFI informatics-coupled UPLC-QToF-MS platform aids in the quick identification and fragmentation pattern of metabolites, with higher degree of reproducibility. The present study provides a chemical and therapeutic basis for further exploration of B. rugulosa as a valuable source of phytochemicals that could be instrumental in deciphering its ethno-medicinal utility for various human diseases.

E EFEKTIVITAS ANALGETIK EKSTRAK BATANG PEPAYA (Carica papaya L.)PADA MENCIT JANTAN YANG DIINDUKSI LEMPENG PANAS

Papaya stems (Carica papaya L.) are experimentally utilized by the community as new vegetables. Dried papaya stems contain auxiliary metabolites of flavonoids, tannins, glycosides, polyphenols, steroids and triterpenoids. This compound acts as an antioxidant. The flavonoid compounds found in papaya stems act as analgesics. The point of this ponder was to look at the pain relieving impact of papaya stems on male rats initiated by warm plate. Making wounds on creatures by implies of warming plates made with a estimate of 1cm x 1cm. The hair on the mice's backs was shaved, a warming cushion was connected to the mice's backs for around 2 seconds until they come to the dermis and fundamental tissue, causing the skin to rankle and peel in a few places. Pain relieving perceptions in test creatures were given after acceptance by regulating CMC-Na, paracetamol, papaya stem ethanol extricate at measurements of 100 mg/kgBW, 300 mg/kgBW and 600 mg/kgBW. Papaya stem extricate contains auxiliary metabolites of flavonoids, tannins and saponins that act as analgesics. At a measurements of 600 mg/kg body weight, the extricate had an pain relieving impact comparable to that of paracetamol.

INTERRELATION BETWEEN MITOCHONDRIAL ENZYME ACTIVITY AND ANTIOXIDANT ACTIVITY OF SECONDARY POLYPHENOL NATURE METABOLITES IN HEMIPARASITE VISCUM ALBUM L. LEAVES

Antioxidants are widely used in practical medicine. Not only the search for new plant antioxidants, but also the study of the factors affecting their accumulation in plants, are relevant.The aim is to study the interrelation between the activity of mitochondrial enzymes and the antioxidant activity of the secondary polyphenolic nature metabolites in hemiparasite Viscum Album L. leaves.Materials and methods. The sampling material was Viscum album L. leaves, collected in winter from a host tree, Malus domestica Borkh. The extraction of biologically active substances was carried out with ethyl alcohol of various concentrations (90%, 70% and 50%), or purified water. The amount of total antioxidants was estimated by the amperometric method. The amount of total phenols was evaluated in the reaction with the Folin-Ciocalteu reagent. The concentration of total flavonoids was estimated by the change in the optical density of the rutin with aluminum (III) chloride complex. The antioxidant properties of the analyzed extracts were determined in vitro in the induced lipid peroxidation test. The activity of aconitase was assessed by a conjugated aconitase-isocitrate dehydrogenase reaction, citrate synthase – by changing the color intensity of the Ellman reagent solution, succinate dehydrogenase were determined in the reaction of succinate-dependent oxidation of 2,6-dichlorophenolindophenol.Results. The carried out study showed that the maximum amount of total phenols (2.39±0.05%) is observed in a 50% ethanol extract from Viscum album L. leaves, with the content of total flavonoids equal to 1.83±0.04%, and the antioxidants equal to 0.503±0.007 mg/g (a quercetin equivalent) and 0.322±0.006 mg/g (a gallic acid equivalent). A 50% ethanol extract suppressed lipid peroxidation in the model mixture with IC50=106.3±1.09 µg/ml. In Viscum album L. leaves, a high activity of aconitase which strongly correlated (r=0.88416) with changes in the concentration of flavonoids, has been notified.Conclusion. The optimal extractant for obtaining extracts with a high antioxidant activity is 50% ethyl alcohol. The analysis of the mitochondrial enzymes activity showed that in Viscum album L. leaves collected in winter, a high activity of aconitase strongly correlated with changes in the concentration of flavonoids (r=0.88416).

A New Strategy Based on LC-Q TRAP-MS for Determining the Distribution of Polyphenols in Different Apple Varieties.

Apples are a rich source of polyphenols in the human diet. However, the distribution of polyphenols in different apple varieties and tissues is still largely unclear. In this study, a new liquid chromatography-tandem mass spectrometry (LC-MS/MS) strategy was developed to reveal the spatial distribution of polyphenols in different apple tissues and varieties. A method based on multiple reaction monitoring (MRM)-enhanced product ion (EPI) was established in the information-dependent acquisition (IDA) mode for pseudo-target screening of major apple polyphenols. A total of 39 apple polyphenolic metabolites were finally identified. Qualitative and quantitative results showed that the variety and content of polyphenols in apple peels were higher than those of other tissues. In apple roots, stems, and leaves, the highest polyphenol variety and content were found in wild species, followed by cultivars and elite varieties. Dihydrochalcone substances, one kind of major apple polyphenols, were more abundant in apple roots, stems, and leaves. This strategy can be applied as a model for other agricultural products, in addition to revealing the distribution of polyphenols in different tissues of apples, which provides a theoretical basis for the utilization of polyphenol resources and variety selection.

Flavonoids as Antidiabetic and Anti-Inflammatory Agents: A Review on Structural Activity Relationship-Based Studies and Meta-Analysis.

Flavonoids are a group of naturally occurring polyphenolic secondary metabolites which have been reported to demonstrate a wide range of pharmacological properties, most importantly, antidiabetic and anti-inflammatory effects. The relationship between hyperglycaemia and inflammation and vascular complications in diabetes is now well established. Flavonoids possessing antidiabetic properties may alleviate inflammation by reducing hyperglycaemia through different mechanisms of action. It has been suggested that the flavonoids’ biochemical properties are structure-dependent; however, they are yet to be thoroughly grasped. Hence, the main aim of this review is to understand the antidiabetic and anti-inflammatory properties of various structurally diverse flavonoids and to identify key positions responsible for the effects, their correlation, and the effect of different substitutions on both antidiabetic and anti-inflammatory properties. The general requirement of flavonoids for exerting both anti-inflammatory and antidiabetic effects is found to be the presence of a C2–C3 double bond (C-ring) and hydroxyl groups at the C3’, C4’, C5, and C7 positions of both rings A and B of a flavonoid skeleton. Furthermore, it has been demonstrated that substitution at the C3 position of a C-ring decreases the anti-inflammatory action of flavonoids while enhancing their antidiabetic activity. Correlation is discussed at length to support flavonoids possessing essential pharmacophores to demonstrate equipotent effects. The consideration of these structural features may play an important role in synthesizing better flavonoid-based drugs possessing dual antidiabetic and anti-inflammatory effects. A meta-analysis further established the role of flavonoids as antidiabetic and anti-inflammatory agents.

Evaluation of Total Phenolic Content, HPLC Analysis, and Antioxidant Potential of Three Local Varieties of Mushroom: A Comparative Study.

Functional foods such as mushrooms are rich in polyphenolic compounds and secondary metabolites with health-promoting properties such as antioxidant, antimicrobial, antidiabetic and immunostimulatory effects. The present study is aimed to investigate the ethanolic extracts of three varieties of mushrooms, namely, G. lucidum, G. tropicum, and C. indica grown in Bangladesh for phenolic and flavonoid content and their antioxidant properties. Moreover, the phenolic composition of the extracts was analyzed by using the HPLC-DAD system. G. lucidum extract exhibited the highest antioxidant potential as evidenced by its lowest IC50 value in all the tested assay models (40.44 ± 2.09 μg/mL, 151.32 ± 0.35 μg/mL, 137.89 ± 1.85 μg/mL in DPPH, H2O2, and NO scavenging assay, respectively) along with the highest phenolic content (81.34 ± 0.68 GAE g−1 extract). G. tropicum and C. indica extracts also showed significant antioxidant properties and a good amount of phenolic content, 52.16 ± 0.25 GAE g−1 extract, and 47.1 ± 0.26 GAE g−1 extract, respectively. The scavenging activity increased with the increasing concentration of extracts in all cases. The total phenolic content of the ethanolic extracts of mushroom species was highly correlated with antioxidant effects with Pearson's correlation coefficient (r) values ranging from 0.8883–0.9851. The α-amylase inhibitory and antibacterial activity of G. lucidum was evaluated by using 3,5-dinitrosalicylic acid and disc diffusion method, respectively. The maximum inhibitory activity recorded against α-amylase was 70.98 ± 0.042% at a concentration of 500 μg/mL. G. lucidum extract exhibited the highest antibacterial activity against Pseudomonas aeruginosa with 23.00 ± 1.00 mm clear zone of inhibition and an MIC value of 3.5 mg/mL. The results indicate that the mushroom species tested in this study could serve as a potential source of natural antioxidants in the development of nutraceuticals and herbal drugs for the management of oxidative stress-associated diseases as well as infectious diseases.

Comparative Studies of Experimental and Simulated IR Spectra of Some Selected Flavonoid Compounds

Flavonoid compounds are a class of poly-phenolic secondary metabolites usually found in various plants. These compounds were of interest in the study of various workers in the past because of their utility as medicinal compounds. These compounds can be extracted from plants and workers have tried to synthesize them also. A lot of references related to the studies of these compounds are available in the literature to explore their structural and other related properties. This communication reports the studies on experimental and simulated IR spectra of some selected Flavonoid compounds based on quantum-chemical semi-empirical methods using different AM1 and PM3 approaches. Other related geometrical parameters obtained after optimizations are also reported. It has also been tried to study and include parameters related to the FMO approach theoretically for these compounds.

Modulation of gut microbiota and their metabolites by functional mulberry juice non-thermally pasteurized using microfiltration

Background: Mulberry fruit is a source of phenolic compounds and has biological properties. This study aimed to assess the effects of isomaltooligosaccharide (IMO) added to mulberry juice on prebiotic activity and gut fermentation properties.Objectives: The study aimed to produce mulberry juice supplemented with IMO, which might generate short chain fatty acids (SCFA), and to examine the effects of a prebiotic activity after fecal fermentation.Materials and methods: Functional mulberry juices were prepared with three different levels of isomaltooligosaccharide (IMO), namely 0% (MBI0), 2% (MBI2), and 8% (MBI8). The study tested mulberry juices supplemented with IMO, which generated short-chain fatty acids (SCFA), phenolic metabolites, and favored beneficial gut bacteria, and examined the prebiotic activity after fecal fermentation by the colonic microbiota. A crossflow hollow fiber microfiltration system with a 0.22 μm pore size was employed to deliver permeates considered non-thermally pasteurized juices.Results: The results show that short chain fatty acids (SCFA) included large propionic acid and butyric acid concentrations at 48h. The percent of bifidobacteria significantly increased to 5.03% and 17.53% in 24 hours fermentation of MBI2 and MBI8, respectively. After fecal batch culture fermentation, some anthocyanin metabolites such as 3-(2-hydroxyphenyl) propionic acid, 3,4-dihydroxybenzaldehyde, L-phenylalanine, and aminocaproic acid, were detected. Therefore, IMO can serve as a potential prebiotic ingredient added in mulberry juice for promoting the growth of beneficial gut microbiota.Conclusion: The results show that IMO favored beneficial microorganisms in the gut and contributed to biologically active compounds such as metabolites of polyphenols and anthocyanins in the gut.Keywords: Mulberry, isomaltooligosaccharide, prebiotic, gut microbiota, metabolites

Extraction of The Chemical Components of Dengen Leaves (Dillenia serrata Thunb) by MAE Method and Activity Test as Antioxidant and Toxicity

Research on the extraction of chemical components of Dengen (Dillenia serrata Thumb) leaves using the MAE (microwave-assisted extraction) method and activity as an antioxidant and toxicity test has been carried out. This study aimed to extract the chemical components of Dengen leaves using the MAE method and to test the antioxidant activity and toxicity of the ethanol extract of Dengen leaves. The chemical components of Dengen leaves were extracted by the MAE method and obtained ethanol extract with a yield of 47%. Dengen leaves ethanol extract was partitioned with n-hexane and ethanol as solvents and obtained yields of 5% (n-hexane) and 65% (ethanol). The chemical components of Dengen leave ethanol extract were identified by phytochemical screening. The results of phytochemical screening showed the presence of secondary metabolites of alkaloids, flavonoids, saponins, polyphenols, terpenoids, and steroids. The antioxidant activity test of the ethanol extract of Dengen leaves was carried out using the DPPH (2,2-diphenyl-1-picrihydrazil) method and obtained the value of IC50 = 100,363 ppm (strong antioxidant). A toxicity test of the ethanol extract of Dengen leaves was carried out using the BSLT (Brine Shrimp Lethality Test) method and obtained the value of LC50 = 18.3443 ppm (very toxic).

Role of the Gut Microbiome in Skeletal Muscle Physiology and Pathophysiology.

This review aims to summarize the recent findings about the contribution of the gut microbiome to muscle pathophysiology and discuss molecular pathways that may be involved in such process. Related findings in the context of cancer cachexia are outlined. Many bacterial metabolites have been reported to exert a beneficial or detrimental impact on muscle physiology. Most of the evidence concentrates on short-chain fatty acids (SCFAs), with an emerging role for bile acids, bacterial amino acid metabolites (bAAms), and bacterial polyphenol metabolites. Other molecular players worth considering include cytokines, hormones, lipopolysaccharides, and quorum sensing molecules. The current literature clearly establishes the ability for the gut microbiome to modulate muscle function and mass. The understanding of the mechanisms underlying this gut-muscle axis may lead to the delivery of novel therapeutic tools to tackle muscle wasting in cancer cachexia, chronic kidney disease, liver fibrosis, and age-related sarcopenia.

Chemodiversity is closely linked to genetic and environmental diversity: Insights into the endangered populations of the local endemic plant Sideritis euboea Heldr. of Evia Island (Greece)

Sideritis euboea is a perennial medicinal, local endemic species to mountainous areas of Central and Southern Evia Island (Greece) with isolated populations threatened with extinction. In this context, a genetic and phytochemical survey has been performed to evaluate the present status of S. euboea inter- and intra-population diversity in three mountainous areas (Dirfis, Xerovouni, Ochi) of Evia, while its occurrence data have been used to define the species-specific climate requirements and to simulate the habitat suitability. Our analysis revealed differences between the populations concerning their polymorphism and genetic homogenity, resulting in a clear clustering of the main three populations based on PCA analysis. An admixture of individuals was identified between distant populations, indicating a possible gene flow between them. The phytochemical analysis revealed significant differences concerning their content in species-specific polyphenolic metabolites, especially isoscutellarein and hypolaetin derivatives; based on the PCA analysis of the cumulative polyphenolic groups’ pattern, two populations were the more distinctive, while different functional groups of metabolites could result to more clear clustering. The ecological profile analysis revealed that the more diverse S. euboea populations in terms of genetics and cumulative polyphenolics are found under comparatively wetter conditions with lower annual temperature and higher annual precipitation. The findings herein support the distinct climate in the habitats of the main populations of S. euboea from the three mountains, suggesting that all three populations should be considered as distinct units for conservation management with Mt. Ochi’s population firstly prioritized.