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Volume 18, Issue 2 (2026)
Iran J War Public Health 2026, 18(2): 227-234 |
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Received: 2026/06/8 | Accepted: 2026/07/23 | Published: 2026/07/28
Received: 2026/06/8 | Accepted: 2026/07/23 | Published: 2026/07/28
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Ali D, Qasim M, Jebur N. Biological and Antimicrobial Activities of Rhus coriaria (Sumac) Extracts against Bacteria and Fungi. Iran J War Public Health 2026; 18 (2) :227-234
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Biological and Antimicrobial Activities of Rhus coriaria (Sumac) Extracts against Bacteria and Fungi
1- Department of Microbiology, Al-Manara College for Medical Sciences, University of Manara, Al-Amarah, Iraq
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Introduction
Medicinal plants have long represented one of the richest reservoirs of structurally diverse phytochemicals with significant biological properties. Throughout history, herbal medicines have played a central role in the prevention and treatment of infectious and chronic diseases, particularly in regions where traditional medicine remains an integral component of health care. Unlike many synthetic drugs designed to target a single molecular pathway, plant-derived compounds frequently exhibit pleiotropic biological effects because of the presence of multiple bioactive constituents that act synergistically. Polyphenols, flavonoids, tannins, alkaloids, terpenoids, and phenolic acids have attracted considerable attention because of their documented antimicrobial, antiviral, antioxidant, anti-inflammatory, and metabolic regulatory activities. Consequently, medicinal plants continue to provide valuable leads for the discovery of novel therapeutic compounds and functional food ingredients [1].
Among these medicinal plants, Rhus coriaria L. (sumac), a deciduous shrub belonging to the family Anacardiaceae, has attracted increasing scientific interest because of its broad spectrum of pharmacological properties and long history of traditional use.
The plant is indigenous to the Mediterranean Basin and Western Asia, where its fruits have been consumed for centuries both as a culinary spice and as a traditional herbal remedy. Historical records indicate that different parts of the plant have been used in folk medicine to treat wounds, gastrointestinal disorders, inflammatory conditions, diarrhea, fever, and various microbial infections. These traditional applications have encouraged modern microbiological investigations aimed at validating its therapeutic potential through experimental and clinical studies [1, 2].
The growing interest in R. coriaria has largely been driven by advances in phytochemical analysis, which have revealed an exceptionally rich composition of secondary metabolites. Sumac fruits contain abundant hydrolyzable tannins, flavonoids, anthocyanins, phenolic acids, organic acids, essential oils, and numerous other bioactive constituents that collectively contribute to the plant’s biological activity [3-5]. Advanced analytical techniques, including high-performance liquid chromatography (HPLC) and gas chromatography–mass spectrometry (GC-MS), have enabled the identification of numerous phenolic compounds, among which gallic acid, methyl gallate, quercetin, rutin, anthocyanins, and related flavonoids are consistently reported as dominant constituents. These compounds are recognized for their strong antioxidant capacity and ability to modulate multiple cellular pathways involved in inflammation, oxidative damage, microbial survival, and lipid metabolism [3, 4].
R. coriaria extracts exhibit broad-spectrum antibacterial activity against both Gram-positive and Gram-negative microorganisms, including clinically important pathogens, such as Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Bacillus subtilis [6-8]. The antimicrobial efficacy of sumac has been largely attributed to its high concentrations of phenolic acids and hydrolyzable tannins, particularly gallic acid and methyl gallate, which are considered among the principal bioactive constituents responsible for inhibiting microbial growth [9].
In addition to its antibacterial properties, R. coriaria has demonstrated remarkable antifungal activity against several medically important fungal species. Opportunistic fungal pathogens, such as Candida albicans have become increasingly significant causes of both superficial and invasive infections, particularly among immunocompromised individuals. The emergence of resistance to commonly prescribed antifungal agents has further complicated the clinical management of these infections. Sumac extracts inhibit fungal growth by damaging cell-wall architecture, altering membrane permeability, impairing ergosterol biosynthesis, and inducing oxidative damage within fungal cells. These mechanisms collectively contribute to growth inhibition and may enhance the susceptibility of fungal pathogens to conventional antifungal drugs [6-8].
Phenolic-rich extracts of R. coriaria exhibit inhibitory activity against enveloped viruses, particularly herpes simplex virus type 1 (HSV-1) and influenza A virus [10, 11]. The proposed antiviral mechanisms include inhibition of viral adsorption to host-cell receptors, prevention of viral entry, suppression of viral genome replication, and modulation of host immune responses through the regulation of inflammatory mediators and cytokine production.
Another important biological property of R. coriaria is its potent antioxidant activity. Oxidative stress arises when the production of reactive oxygen species exceeds the capacity of endogenous antioxidant defense systems, leading to oxidative damage to lipids, proteins, and nucleic acids. Persistent oxidative stress has been implicated in the pathogenesis of numerous chronic disorders, including cardiovascular diseases, diabetes mellitus, chronic inflammatory diseases, neurodegenerative disorders, and several forms of cancer [12]. Consequently, reducing oxidative stress has become an important therapeutic objective in preventive medicine.
Polyphenol-rich medicinal plants are widely recognized as effective natural antioxidants because of their ability to donate electrons, chelate transition
metals, interrupt free-radical chain reactions, and enhance endogenous antioxidant defense mechanisms. R. coriaria possesses exceptionally high antioxidant capacity because of its abundance of phenolic acids, flavonoids, anthocyanins, and hydrolyzable tannins [13, 14]. These compounds have been shown to efficiently scavenge reactive oxygen species while simultaneously enhancing the activity of endogenous antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and reduced glutathione (GSH).
In addition to infectious diseases, metabolic disorders have become some of the leading causes of morbidity and mortality worldwide. Among these disorders, hyperlipidemia is recognized as a major modifiable risk factor for atherosclerosis, coronary artery disease, ischemic stroke, and other cardiovascular complications. Elevated concentrations of total cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-C), together with reduced levels of high-density lipoprotein cholesterol (HDL-C), contribute to endothelial dysfunction, chronic inflammation, and accelerated plaque formation within arterial walls [15].
The phenolic constituents of R coriaria may exert beneficial effects on lipid homeostasis through multiple biochemical pathways. Gallic acid, flavonoids, tannins, and other polyphenolic compounds can inhibit key enzymes involved in hepatic lipid synthesis, reduce intestinal cholesterol absorption, improve reverse cholesterol transport, and enhance cholesterol efflux from peripheral tissues [16-18].
Therefore, this study aimed to investigate the biological potential of R. coriaria fruit extracts through an integrated phytochemical and microbiological approach. Specifically, qualitative and quantitative phytochemical analyses were performed using conventional phytochemical screening, GC-MS, and HPLC techniques to characterize the principal bioactive constituents. The biological activities of the extracts were subsequently evaluated by assessing their antibacterial, antifungal, antiviral, antioxidant, and hypolipidemic effects using both in vitro bioassays and an in vivo experimental model. By combining phytochemical profiling with multiple biological evaluations, this study aimed to provide a comprehensive understanding of the therapeutic potential of R. coriaria and to support its future application as a promising natural source of multifunctional bioactive compounds.
Materials and Methods
Collection and identification of plant materials
Fresh fruits of R. coriaria L. were collected from the Mediterranean region of northern Lebanon during the fruiting season in May 2025. The voucher specimens were identified by Assistant Professor Dr. Sadeq Sabeeh Kareem of the Department of Biology, College of Science, Misan University, Iraq. A voucher specimen (voucher No. CDRC-2025-134) was deposited in the biology laboratory of the Microbiology Department at the University of Al-Manara, College of Dentistry, Iraq. The scientific name was verified according to Plants of the World Online (POWO), Royal Botanic Gardens, Kew, where the accepted name corresponds to the IPNI Life Science Identifier (LSID): urn:lsid:ipni.org:names:702257-1.
Preparation of the extract
Soxhlet extraction was performed using 80% methanol (BDH-England) solutions. For the solvent, 200g of dried and powdered fruit was extracted for 8h. The resulting extract was filtered, dried under reduced pressure at 40°C, and stored at -20°C before further investigation [19].
Phytochemical analysis
Screening for flavonoids, phenols, tannins, alkaloids, and saponins was performed using the qualitative methods described by Harborne [19]. The Folin-Ciocalteu assay and the aluminum chloride colorimetric method were used to determine the total phenolic content (TPC) and total flavonoid content (TFC), respectively [20].
GC-MS and HPLC profiling
The methanolic extract was analyzed by GC-MS (Agilent Technologies, USA) using a 7890A system equipped with a 5975C MSD detector and helium as the carrier gas at a flow rate of 1mL/min. The compounds were identified by comparing their mass spectra with those in the NIST and Wiley spectral libraries [21, 22]. The contents of gallic acid, quercetin, and rutin were measured using HPLC (Shimadzu, Japan) on a C18 column with a UV detector set at 280nm [23].
Antimicrobial and antifungal activity
Reference bacterial strains, including E. coli (ATCC), S. aureus (ATCC), B. subtilis (ATCC), and P. aeruginosa (ATCC), Reference bacterial strains, including E. coli (ATCC), S. aureus (ATCC), B. subtilis (ATCC), and P. aeruginosa (ATCC), were obtained from the culture collection of the Department of Medical Microbiology, College of Dentistry, University of Al-Manara, Iraq. These strains were originally derived from the American Type Culture Collection (ATCC, Manassas, VA, USA). All strains were tested for antibacterial activity. The well-diffusion method [24] was also used to evaluate antifungal activity against C. albicans and Aspergillus niger (ATCC, Manassas, VA, USA). The minimum inhibitory concentrations (MICs) were determined by broth microdilution according to CLSI guidelines [25].
Antiviral activity assay
Vero cells (ATCC CCL-81; American Type Culture Collection, Manassas, VA, USA) were cultured in Dulbecco’s Modified Eagle Medium (DMEM; Gibco, Thermo Fisher Scientific, Waltham, MA, USA) supplemented with 10% fetal bovine serum (FBS; Gibco, Thermo Fisher Scientific, USA). Plaque reduction assays were used to evaluate antiviral activity against HSV-1 and influenza A virus (H1N1; ATCC VR-733, American Type Culture Collection, Manassas, VA, USA). Cytotoxicity was determined using an MTT assay (Sigma-Aldrich, St. Louis, MO, USA), and the selectivity index (SI) was calculated [26, 27].
Antioxidant assays
The antioxidant activity of the extract was measured using the DPPH radical-scavenging test, ferric-reducing antioxidant power (FRAP) assay, and ABTS radical-decolorization assay [28]. The results were expressed as IC50 values and compared with those of ascorbic acid controls.
In vivo hypolipidemic and antioxidant assessment
Male Wistar rats weighing 180-200g were divided into four groups, with six rats in each group: the normal control group (NC), hyperlipidemic control group (HC), hyperlipidemic group treated with the standard drug atorvastatin (Julphar, Ras Al Khaimah, United Arab Emirates) (HSD), and hyperlipidemic group treated with R. coriaria extract (HRC). Hyperlipidemia was induced by administering a high-fat diet. Serum lipid parameters, including total cholesterol, triglycerides, and high-density lipoprotein, as well as antioxidant enzyme activities, including SOD, CAT, and GPx, were measured [29].
Statistical analysis
The statistical analysis was performed using GraphPad Prism 9. Statistical significance was assessed using one-way ANOVA followed by Tukey’s post hoc test.
Findings
Preliminary profiling of the R. coriaria extract revealed high levels of phenolic constituents, flavonoids, tannins, and saponins, as well as trace amounts of alkaloids. The TPC and TFC of the methanolic extract were 215.6±4.3mg gallic acid equivalents/gram and 98.4±3.7mg quercetin equivalents/gram, respectively.
More than 25 phytochemical compounds, including gallic acid as the most prominent peak, were detected by GC-MS. These compounds included gallic acid, methyl gallate, malic acid, oleic acid, beta-sitosterol, and several quercetin derivatives. The presence of gallic acid (16.3mg/g), rutin (5.8mg/g), and quercetin (4.7mg/g) was further confirmed using HPLC.
The methanolic extract demonstrated strong antibacterial activity, with inhibition zones of 20.3±1.1mm for S. aureus, 18.6±0.9mm for E. coli, 19.1±1.0mm for P. aeruginosa, and 22.3±2.0mm for B. subtilis. The inhibition zones were 22.4±1.2mm for C. albicans and 18.7±1.5mm for A. niger. The minimum inhibitory concentrations (MICs) ranged from 125-250µg/mL, with the strongest effect recorded against S. aureus. Notably, strong antifungal activity was observed against C. albicans (MIC=100µg/mL) and A. niger (MIC=150µg/mL).
The R. coriaria extract exhibited dose-dependent anti-HSV-1 and anti-H1N1 effects. Viral plaque formation was inhibited by 75.7% and 71.4% for HSV-1 and influenza A, respectively, without causing cytotoxicity in Vero cells at 100µg/mL. The calculated selectivity indices were 8.1 and 6.9, respectively, indicating good antiviral potential.
The extract demonstrated significant antioxidant activity, with an IC50 of 44.6µg/mL in the DPPH assay and 61.8µg/mL in the FRAP assay, comparable to that of ascorbic acid (40.2µg/mL). The ABTS assay showed more than 80% scavenging activity at 100µg/mL, indicating a strong ability to neutralize free radicals.
After 28 days of treatment, the R. coriaria group had significantly lower serum total cholesterol (171±7mg/dL), triglyceride levels and significantly higher HDL cholesterol levels (61±4 mg/dL) than the hyperlipidemic control group, which had cholesterol, TG, and HDL levels of 220±10mg/dL, 200±8mg/dL, and 45±6mg/dL, respectively. In the hyperlipidemic plus standard drug group (HSD), the cholesterol level was 180±8mg/dL, the TG level was 150±2mg/dL, and the HDL level was 45±4mg/dL. These changes were statistically significant (p<0.01).
Discussion
This study aimed to evaluate the composition and the antimicrobial, antioxidant, and hypolipidemic activities of R. coriaria (sumac) fruit extract using both in vitro and in vivo approaches. The phytochemical characterization of R. coriaria fruit extract revealed a complex profile of phenolic acids, flavonoids, tannins, and other bioactive metabolites. These findings support the traditional medicinal value of this plant and provide a biochemical basis for the diverse biological activities observed in the present study. Qualitative phytochemical screening confirmed the presence of several major classes of secondary metabolites, while chromatographic analyses using GC-MS and HPLC demonstrated that phenolic compounds were the predominant constituents of the extract. These findings are consistent with the well-established concept that the pharmacological properties of R. coriaria largely depend on its abundance of polyphenolic compounds, which possess potent antioxidant, antimicrobial, antiviral, and anti-inflammatory activities. The high concentration of these metabolites is considered one of the principal factors contributing to the broad therapeutic potential of this species.
The present phytochemical profile is in close agreement with findings of Batiha et al., who described R. coriaria as one of the richest dietary sources of naturally occurring polyphenols, including gallic acid derivatives, hydrolyzable tannins, flavonoids, anthocyanins, and organic acids. They emphasize that the remarkable biological versatility of sumac results from synergistic interactions among these phytochemicals rather than from the activity of a single compound alone. This interpretation supports the our findings, where multiple classes of phytochemicals were detected simultaneously, suggesting that the biological responses observed in the antimicrobial, antioxidant, antiviral, and hypolipidemic assays are likely attributable to the combined effects of structurally diverse secondary metabolites rather than to a single isolated constituent [1, 30, 31].
Similarly, Calabrò et al. report that R. coriaria possesses exceptional nutraceutical value because of its chemically diverse phenolic composition and its ability to influence numerous biological pathways associated with oxidative stress, chronic inflammation, microbial infections, and metabolic disorders. They declare that compounds, such as gallic acid, methyl gallate, quercetin derivatives, anthocyanins, and hydrolyzable tannins act cooperatively to regulate cellular redox homeostasis and inflammatory signaling pathways. These observations provide a mechanistic explanation for the present results and further support the hypothesis that the therapeutic efficacy of R. coriaria depends on the cumulative biological activities of multiple phytochemical constituents rather than on individual molecules [2, 32].
The chromatographic analyses performed in this study also demonstrated substantial qualitative agreement with other investigations, which employed advanced chromatographic platforms to characterize the chemical composition of R. coriaria [3, 33-36].
Abu-Reidah et al. [3] identified numerous phenolic acids and flavonoids, whereas Arena et al. [36] combined headspace solid-phase microextraction gas chromatography with comprehensive two-dimensional liquid chromatography to reveal an even broader spectrum of volatile and nonvolatile metabolites. The similarity between these reports and the present findings confirms that the phytochemical profile of R. coriaria is highly reproducible despite differences in analytical platforms. Minor variations in the abundance of individual compounds are expected and can reasonably be attributed to differences in geographical origin, climatic conditions, harvesting season, soil characteristics, postharvest handling, extraction solvent, and extraction methodology, all of which are recognized determinants of phytochemical composition in medicinal plants.
Our antibacterial findings are consistent with those reported by Koşar et al. [35], demonstrating that ethanolic extracts of R. coriaria possess significant inhibitory activity against both Gram-positive and Gram-negative bacteria. They attribute this effect primarily to the high concentrations of gallic acid, hydrolyzable tannins, and flavonoids, which can damage bacterial cell membranes and disrupt intracellular metabolic pathways. Similarly, Perrone et al. [14] conclude that the antimicrobial efficacy of sumac is closely associated with its phenolic profile, particularly gallic acid derivatives and condensed tannins, which increase membrane permeability, induce the leakage of intracellular constituents, and inhibit several bacterial enzymes required for survival. The agreement between these reports and our findings reinforces the hypothesis that phenolic compounds constitute the principal antimicrobial components of R. coriaria.
Comparable observations are also reported by Batiha et al. [1], who reviewed numerous experimental studies demonstrating that R. coriaria extracts inhibit a wide variety of clinically important bacterial pathogens, including both Gram-positive and Gram-negative species. The antimicrobial activity results from synergistic interactions among multiple phytochemicals rather than from the effects of a single constituent. Alsamri et al. [4] reached similar conclusions and emphasized that the biological activity of sumac cannot be explained solely by its total phenolic content but also depends on the diversity and relative abundance of individual compounds acting cooperatively. This synergistic phenomenon provides a plausible explanation for the strong antimicrobial activity observed in the present study despite the complexity of the crude extract.
The predominance of identified phenolic compounds is particularly important because these metabolites are known to possess multiple complementary biological functions. Hydrolyzable tannins and gallic acid derivatives interact with microbial cell envelopes, increase membrane permeability, inhibit extracellular enzymes, and interfere with nucleic acid synthesis. Flavonoids can modulate intracellular signaling pathways involved in oxidative stress and inflammation while also exhibiting antiviral activity through the inhibition of viral attachment, replication, and protein synthesis. In addition, several polyphenols can chelate transition metals, scavenge reactive oxygen species, and interrupt lipid peroxidation chain reactions, thereby contributing to antimicrobial, antioxidant, and cytoprotective activities. The coexistence of these chemically diverse constituents therefore provides a plausible biochemical explanation for the multiple biological effects observed throughout the present study. These mechanistic interpretations are consistent with the conclusions reported by Alsamri et al. [4], Perrone et al. [14], and Calabrò et al. [2], all of whom emphasize that the pharmacological potential of R. coriaria results from the synergistic action of numerous phenolic metabolites rather than from isolated phytochemicals.
Overall, the phytochemical characterization confirmed that R. coriaria is a rich source of biologically active phenolic compounds with considerable pharmacological relevance. The close agreement between our findings and those of previous chromatographic investigations further strengthens the reliability of the analytical approach used in this work and supports the subsequent interpretation of the antimicrobial, antiviral, antioxidant, and hypolipidemic activities demonstrated by the extracts [1-4, 14, 36].
R. coriaria fruit extract exhibited marked antibacterial and antifungal activities against the tested microorganisms, indicating that the plant possesses broad-spectrum antimicrobial properties. The observed inhibitory effects are most likely attributable to the high concentrations of phenolic acids, hydrolyzable tannins, flavonoids, and other bioactive phytochemicals identified during phytochemical characterization. These secondary metabolites are known to target multiple microbial structures simultaneously, thereby reducing the likelihood of resistance development and enhancing antimicrobial efficacy. Unlike conventional antibiotics, which generally interfere with a single cellular target, plant-derived polyphenols frequently exert their antimicrobial effects through multiple complementary mechanisms, including disruption of membrane integrity, inhibition of essential metabolic enzymes, interference with nucleic acid synthesis, and impairment of quorum sensing. Such multitarget activity may explain the considerable inhibitory activity observed in the present investigation [1, 4, 36].
The antifungal activity is likewise supported by previous studies evaluating R. coriaria against pathogenic yeasts and filamentous fungi. Perrone et al. report that the phenolic constituents of sumac interfere with fungal membrane integrity by interacting with ergosterol-rich membranes, ultimately increasing membrane permeability and promoting the leakage of essential intracellular metabolites. Additionally, tannins can form stable complexes with fungal cell wall proteins and extracellular enzymes, thereby inhibiting fungal growth and colonization. These mechanisms are likely responsible for the antifungal activity observed in the present study and may explain the susceptibility of the fungal isolates to the tested extracts [14].
Another important explanation for the antimicrobial activity observed in this work involves the strong antioxidant properties of the identified polyphenols. Oxidative homeostasis is essential for microbial survival, and several phenolic compounds have been shown to disrupt intracellular redox balance by generating oxidative stress within microbial cells while simultaneously inhibiting antioxidant defense enzymes. Calabrò et al. [2] highlight that the pharmacological activity of R. coriaria depends on the integrated actions of antioxidant and antimicrobial phytochemicals, which modulate microbial physiology through interconnected biochemical pathways. Likewise, Arena et al. [36] and Hariri et al. demonstrate that extracts containing higher concentrations of phenolic constituents generally exhibit stronger antioxidant and antimicrobial activities, suggesting a positive correlation between phytochemical composition and biological efficacy. Our findings agree well with these observations and further support the role of phenolic-rich extracts as multifunctional antimicrobial agents [2, 37].
Differences in antimicrobial potency reported among various studies should also be interpreted in light of methodological variations. Factors, such as the geographical origin of the plant material, harvesting season, climatic conditions, extraction solvent, extraction technique, phytochemical composition, microbial strain diversity, inoculum density, incubation conditions, and susceptibility-testing protocols may substantially influence the measured antimicrobial activity. Balouiri et al. emphasize that methodological standardization is essential for reliable comparisons among antimicrobial investigations because differences in experimental procedures frequently account for discrepancies among published studies. Therefore, minor variations between the present findings and previous reports should be considered expected rather than contradictory [24].
Collectively, the obtained antibacterial and antifungal results provide additional evidence supporting the therapeutic potential of R. coriaria as a natural antimicrobial agent. The close agreement between the current observations and those reported by Calabrò et al., Alsamri et al., Shidfar et al., Mohammadi et al., and Al-Shwuaili et al. strengthens the reliability of the present findings and suggests that the antimicrobial activity of sumac is primarily driven by the synergistic actions of phenolic acids, tannins, flavonoids, and other secondary metabolites that act through multiple complementary mechanisms [2, 4, 38-40 ].
This study has several strengths. First, it adopted an integrated experimental approach by combining phytochemical profiling with evaluations of antimicrobial, antiviral, antioxidant, and hypolipidemic activities within a single study, thereby allowing a comprehensive assessment of the biological potential of R. coriaria. Second, the use of complementary analytical techniques enhanced the reliability of the phytochemical characterization and facilitated the interpretation of the observed biological activities. Third, the integration of both in vitro assays and an in vivo experimental model provided broader evidence supporting the pharmacological potential of the investigated extracts. Collectively, these methodological strengths enhance the scientific robustness of the study and increase its translational relevance to future pharmaceutical and nutraceutical research.
This study has several limitations that should be considered when interpreting the findings. First, the biological activities were evaluated using the extract prepared from R. coriaria fruits collected from a single geographical location during one harvesting season, which may not fully represent the natural phytochemical variability associated with different environmental conditions or cultivation practices. Second, although GC-MS and HPLC analyses identified the principal phytochemical constituents, the biological activities were assessed using the crude extract rather than purified individual compounds; therefore, the specific contribution of each constituent and the potential synergistic interactions among them were not investigated. Third, the antimicrobial and antiviral evaluations were limited to selected reference microorganisms and viral strains, and broader testing against clinically relevant multidrug-resistant isolates and additional viral pathogens would provide a more comprehensive assessment of the therapeutic potential. Furthermore, the hypolipidemic activity was evaluated in an experimental animal model with a relatively short treatment period, and the results cannot be directly extrapolated to human clinical settings. Finally, the molecular mechanisms underlying the observed pharmacological activities were not explored through gene expression analysis, molecular docking, or protein-level investigations. Therefore, future studies should include mechanistic experiments, toxicity and pharmacokinetic evaluations, and well-designed clinical trials to further validate the efficacy, safety, and translational potential of R. coriaria extract.
Importantly, this study integrated phytochemical characterization with multiple biological evaluations, providing a more comprehensive understanding of the relationship between chemical composition and biological activity than has been reported in many previous investigations. These findings contribute to the growing body of evidence supporting the therapeutic value of R. coriaria and reinforce its potential as a natural source of bioactive compounds for the development of novel complementary therapeutic agents.
Nevertheless, additional studies are warranted to isolate and characterize the individual active constituents, elucidate their molecular mechanisms of action, evaluate their pharmacokinetic and toxicological profiles, and validate their efficacy in well-designed clinical trials. Such investigations will be essential for translating the promising experimental findings into safe and effective therapeutic applications.
Conclusion
R. coriaria shows promising antimicrobial, antiviral, antioxidant, and hypolipidemic potential for pharmaceutical and nutraceutical applications.
Acknowledgments: The authors are very grateful to all faculty members and technicians for their assistance in completing this study.
Ethical Permissions: This study was conducted in accordance with the ethical standards of the Declaration of Helsinki and was approved by the Ethical Approval Committee (Institutional Review Board) of Al-Manara University/College of Dentistry under Decision No. 63, issued on 12-11-2024 (NO.63 -IN 12-11-2024).
Conflicts of Interests: The authors declared no conflicts of interest.
Authors' Contribution: Ali D (First Author), Introduction Writer/Methodologist/Main Researcher/Discussion Writer/Statistical Analyst (40%); Qasim MJ (Second Author), Introduction Writer/Methodologist/Assistant Researcher/Discussion Writer/Statistical Analyst (35%); Jebur NH (Third Author), Assistant Researcher/Discussion Writer/Statistical Analyst (25%)
Funding/Support: No funding was received for this research.
Medicinal plants have long represented one of the richest reservoirs of structurally diverse phytochemicals with significant biological properties. Throughout history, herbal medicines have played a central role in the prevention and treatment of infectious and chronic diseases, particularly in regions where traditional medicine remains an integral component of health care. Unlike many synthetic drugs designed to target a single molecular pathway, plant-derived compounds frequently exhibit pleiotropic biological effects because of the presence of multiple bioactive constituents that act synergistically. Polyphenols, flavonoids, tannins, alkaloids, terpenoids, and phenolic acids have attracted considerable attention because of their documented antimicrobial, antiviral, antioxidant, anti-inflammatory, and metabolic regulatory activities. Consequently, medicinal plants continue to provide valuable leads for the discovery of novel therapeutic compounds and functional food ingredients [1].
Among these medicinal plants, Rhus coriaria L. (sumac), a deciduous shrub belonging to the family Anacardiaceae, has attracted increasing scientific interest because of its broad spectrum of pharmacological properties and long history of traditional use.
The plant is indigenous to the Mediterranean Basin and Western Asia, where its fruits have been consumed for centuries both as a culinary spice and as a traditional herbal remedy. Historical records indicate that different parts of the plant have been used in folk medicine to treat wounds, gastrointestinal disorders, inflammatory conditions, diarrhea, fever, and various microbial infections. These traditional applications have encouraged modern microbiological investigations aimed at validating its therapeutic potential through experimental and clinical studies [1, 2].
The growing interest in R. coriaria has largely been driven by advances in phytochemical analysis, which have revealed an exceptionally rich composition of secondary metabolites. Sumac fruits contain abundant hydrolyzable tannins, flavonoids, anthocyanins, phenolic acids, organic acids, essential oils, and numerous other bioactive constituents that collectively contribute to the plant’s biological activity [3-5]. Advanced analytical techniques, including high-performance liquid chromatography (HPLC) and gas chromatography–mass spectrometry (GC-MS), have enabled the identification of numerous phenolic compounds, among which gallic acid, methyl gallate, quercetin, rutin, anthocyanins, and related flavonoids are consistently reported as dominant constituents. These compounds are recognized for their strong antioxidant capacity and ability to modulate multiple cellular pathways involved in inflammation, oxidative damage, microbial survival, and lipid metabolism [3, 4].
R. coriaria extracts exhibit broad-spectrum antibacterial activity against both Gram-positive and Gram-negative microorganisms, including clinically important pathogens, such as Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Bacillus subtilis [6-8]. The antimicrobial efficacy of sumac has been largely attributed to its high concentrations of phenolic acids and hydrolyzable tannins, particularly gallic acid and methyl gallate, which are considered among the principal bioactive constituents responsible for inhibiting microbial growth [9].
In addition to its antibacterial properties, R. coriaria has demonstrated remarkable antifungal activity against several medically important fungal species. Opportunistic fungal pathogens, such as Candida albicans have become increasingly significant causes of both superficial and invasive infections, particularly among immunocompromised individuals. The emergence of resistance to commonly prescribed antifungal agents has further complicated the clinical management of these infections. Sumac extracts inhibit fungal growth by damaging cell-wall architecture, altering membrane permeability, impairing ergosterol biosynthesis, and inducing oxidative damage within fungal cells. These mechanisms collectively contribute to growth inhibition and may enhance the susceptibility of fungal pathogens to conventional antifungal drugs [6-8].
Phenolic-rich extracts of R. coriaria exhibit inhibitory activity against enveloped viruses, particularly herpes simplex virus type 1 (HSV-1) and influenza A virus [10, 11]. The proposed antiviral mechanisms include inhibition of viral adsorption to host-cell receptors, prevention of viral entry, suppression of viral genome replication, and modulation of host immune responses through the regulation of inflammatory mediators and cytokine production.
Another important biological property of R. coriaria is its potent antioxidant activity. Oxidative stress arises when the production of reactive oxygen species exceeds the capacity of endogenous antioxidant defense systems, leading to oxidative damage to lipids, proteins, and nucleic acids. Persistent oxidative stress has been implicated in the pathogenesis of numerous chronic disorders, including cardiovascular diseases, diabetes mellitus, chronic inflammatory diseases, neurodegenerative disorders, and several forms of cancer [12]. Consequently, reducing oxidative stress has become an important therapeutic objective in preventive medicine.
Polyphenol-rich medicinal plants are widely recognized as effective natural antioxidants because of their ability to donate electrons, chelate transition
metals, interrupt free-radical chain reactions, and enhance endogenous antioxidant defense mechanisms. R. coriaria possesses exceptionally high antioxidant capacity because of its abundance of phenolic acids, flavonoids, anthocyanins, and hydrolyzable tannins [13, 14]. These compounds have been shown to efficiently scavenge reactive oxygen species while simultaneously enhancing the activity of endogenous antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and reduced glutathione (GSH).
In addition to infectious diseases, metabolic disorders have become some of the leading causes of morbidity and mortality worldwide. Among these disorders, hyperlipidemia is recognized as a major modifiable risk factor for atherosclerosis, coronary artery disease, ischemic stroke, and other cardiovascular complications. Elevated concentrations of total cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-C), together with reduced levels of high-density lipoprotein cholesterol (HDL-C), contribute to endothelial dysfunction, chronic inflammation, and accelerated plaque formation within arterial walls [15].
The phenolic constituents of R coriaria may exert beneficial effects on lipid homeostasis through multiple biochemical pathways. Gallic acid, flavonoids, tannins, and other polyphenolic compounds can inhibit key enzymes involved in hepatic lipid synthesis, reduce intestinal cholesterol absorption, improve reverse cholesterol transport, and enhance cholesterol efflux from peripheral tissues [16-18].
Therefore, this study aimed to investigate the biological potential of R. coriaria fruit extracts through an integrated phytochemical and microbiological approach. Specifically, qualitative and quantitative phytochemical analyses were performed using conventional phytochemical screening, GC-MS, and HPLC techniques to characterize the principal bioactive constituents. The biological activities of the extracts were subsequently evaluated by assessing their antibacterial, antifungal, antiviral, antioxidant, and hypolipidemic effects using both in vitro bioassays and an in vivo experimental model. By combining phytochemical profiling with multiple biological evaluations, this study aimed to provide a comprehensive understanding of the therapeutic potential of R. coriaria and to support its future application as a promising natural source of multifunctional bioactive compounds.
Materials and Methods
Collection and identification of plant materials
Fresh fruits of R. coriaria L. were collected from the Mediterranean region of northern Lebanon during the fruiting season in May 2025. The voucher specimens were identified by Assistant Professor Dr. Sadeq Sabeeh Kareem of the Department of Biology, College of Science, Misan University, Iraq. A voucher specimen (voucher No. CDRC-2025-134) was deposited in the biology laboratory of the Microbiology Department at the University of Al-Manara, College of Dentistry, Iraq. The scientific name was verified according to Plants of the World Online (POWO), Royal Botanic Gardens, Kew, where the accepted name corresponds to the IPNI Life Science Identifier (LSID): urn:lsid:ipni.org:names:702257-1.
Preparation of the extract
Soxhlet extraction was performed using 80% methanol (BDH-England) solutions. For the solvent, 200g of dried and powdered fruit was extracted for 8h. The resulting extract was filtered, dried under reduced pressure at 40°C, and stored at -20°C before further investigation [19].
Phytochemical analysis
Screening for flavonoids, phenols, tannins, alkaloids, and saponins was performed using the qualitative methods described by Harborne [19]. The Folin-Ciocalteu assay and the aluminum chloride colorimetric method were used to determine the total phenolic content (TPC) and total flavonoid content (TFC), respectively [20].
GC-MS and HPLC profiling
The methanolic extract was analyzed by GC-MS (Agilent Technologies, USA) using a 7890A system equipped with a 5975C MSD detector and helium as the carrier gas at a flow rate of 1mL/min. The compounds were identified by comparing their mass spectra with those in the NIST and Wiley spectral libraries [21, 22]. The contents of gallic acid, quercetin, and rutin were measured using HPLC (Shimadzu, Japan) on a C18 column with a UV detector set at 280nm [23].
Antimicrobial and antifungal activity
Reference bacterial strains, including E. coli (ATCC), S. aureus (ATCC), B. subtilis (ATCC), and P. aeruginosa (ATCC), Reference bacterial strains, including E. coli (ATCC), S. aureus (ATCC), B. subtilis (ATCC), and P. aeruginosa (ATCC), were obtained from the culture collection of the Department of Medical Microbiology, College of Dentistry, University of Al-Manara, Iraq. These strains were originally derived from the American Type Culture Collection (ATCC, Manassas, VA, USA). All strains were tested for antibacterial activity. The well-diffusion method [24] was also used to evaluate antifungal activity against C. albicans and Aspergillus niger (ATCC, Manassas, VA, USA). The minimum inhibitory concentrations (MICs) were determined by broth microdilution according to CLSI guidelines [25].
Antiviral activity assay
Vero cells (ATCC CCL-81; American Type Culture Collection, Manassas, VA, USA) were cultured in Dulbecco’s Modified Eagle Medium (DMEM; Gibco, Thermo Fisher Scientific, Waltham, MA, USA) supplemented with 10% fetal bovine serum (FBS; Gibco, Thermo Fisher Scientific, USA). Plaque reduction assays were used to evaluate antiviral activity against HSV-1 and influenza A virus (H1N1; ATCC VR-733, American Type Culture Collection, Manassas, VA, USA). Cytotoxicity was determined using an MTT assay (Sigma-Aldrich, St. Louis, MO, USA), and the selectivity index (SI) was calculated [26, 27].
Antioxidant assays
The antioxidant activity of the extract was measured using the DPPH radical-scavenging test, ferric-reducing antioxidant power (FRAP) assay, and ABTS radical-decolorization assay [28]. The results were expressed as IC50 values and compared with those of ascorbic acid controls.
In vivo hypolipidemic and antioxidant assessment
Male Wistar rats weighing 180-200g were divided into four groups, with six rats in each group: the normal control group (NC), hyperlipidemic control group (HC), hyperlipidemic group treated with the standard drug atorvastatin (Julphar, Ras Al Khaimah, United Arab Emirates) (HSD), and hyperlipidemic group treated with R. coriaria extract (HRC). Hyperlipidemia was induced by administering a high-fat diet. Serum lipid parameters, including total cholesterol, triglycerides, and high-density lipoprotein, as well as antioxidant enzyme activities, including SOD, CAT, and GPx, were measured [29].
Statistical analysis
The statistical analysis was performed using GraphPad Prism 9. Statistical significance was assessed using one-way ANOVA followed by Tukey’s post hoc test.
Findings
Preliminary profiling of the R. coriaria extract revealed high levels of phenolic constituents, flavonoids, tannins, and saponins, as well as trace amounts of alkaloids. The TPC and TFC of the methanolic extract were 215.6±4.3mg gallic acid equivalents/gram and 98.4±3.7mg quercetin equivalents/gram, respectively.
More than 25 phytochemical compounds, including gallic acid as the most prominent peak, were detected by GC-MS. These compounds included gallic acid, methyl gallate, malic acid, oleic acid, beta-sitosterol, and several quercetin derivatives. The presence of gallic acid (16.3mg/g), rutin (5.8mg/g), and quercetin (4.7mg/g) was further confirmed using HPLC.
The methanolic extract demonstrated strong antibacterial activity, with inhibition zones of 20.3±1.1mm for S. aureus, 18.6±0.9mm for E. coli, 19.1±1.0mm for P. aeruginosa, and 22.3±2.0mm for B. subtilis. The inhibition zones were 22.4±1.2mm for C. albicans and 18.7±1.5mm for A. niger. The minimum inhibitory concentrations (MICs) ranged from 125-250µg/mL, with the strongest effect recorded against S. aureus. Notably, strong antifungal activity was observed against C. albicans (MIC=100µg/mL) and A. niger (MIC=150µg/mL).
The R. coriaria extract exhibited dose-dependent anti-HSV-1 and anti-H1N1 effects. Viral plaque formation was inhibited by 75.7% and 71.4% for HSV-1 and influenza A, respectively, without causing cytotoxicity in Vero cells at 100µg/mL. The calculated selectivity indices were 8.1 and 6.9, respectively, indicating good antiviral potential.
The extract demonstrated significant antioxidant activity, with an IC50 of 44.6µg/mL in the DPPH assay and 61.8µg/mL in the FRAP assay, comparable to that of ascorbic acid (40.2µg/mL). The ABTS assay showed more than 80% scavenging activity at 100µg/mL, indicating a strong ability to neutralize free radicals.
After 28 days of treatment, the R. coriaria group had significantly lower serum total cholesterol (171±7mg/dL), triglyceride levels and significantly higher HDL cholesterol levels (61±4 mg/dL) than the hyperlipidemic control group, which had cholesterol, TG, and HDL levels of 220±10mg/dL, 200±8mg/dL, and 45±6mg/dL, respectively. In the hyperlipidemic plus standard drug group (HSD), the cholesterol level was 180±8mg/dL, the TG level was 150±2mg/dL, and the HDL level was 45±4mg/dL. These changes were statistically significant (p<0.01).
Discussion
This study aimed to evaluate the composition and the antimicrobial, antioxidant, and hypolipidemic activities of R. coriaria (sumac) fruit extract using both in vitro and in vivo approaches. The phytochemical characterization of R. coriaria fruit extract revealed a complex profile of phenolic acids, flavonoids, tannins, and other bioactive metabolites. These findings support the traditional medicinal value of this plant and provide a biochemical basis for the diverse biological activities observed in the present study. Qualitative phytochemical screening confirmed the presence of several major classes of secondary metabolites, while chromatographic analyses using GC-MS and HPLC demonstrated that phenolic compounds were the predominant constituents of the extract. These findings are consistent with the well-established concept that the pharmacological properties of R. coriaria largely depend on its abundance of polyphenolic compounds, which possess potent antioxidant, antimicrobial, antiviral, and anti-inflammatory activities. The high concentration of these metabolites is considered one of the principal factors contributing to the broad therapeutic potential of this species.
The present phytochemical profile is in close agreement with findings of Batiha et al., who described R. coriaria as one of the richest dietary sources of naturally occurring polyphenols, including gallic acid derivatives, hydrolyzable tannins, flavonoids, anthocyanins, and organic acids. They emphasize that the remarkable biological versatility of sumac results from synergistic interactions among these phytochemicals rather than from the activity of a single compound alone. This interpretation supports the our findings, where multiple classes of phytochemicals were detected simultaneously, suggesting that the biological responses observed in the antimicrobial, antioxidant, antiviral, and hypolipidemic assays are likely attributable to the combined effects of structurally diverse secondary metabolites rather than to a single isolated constituent [1, 30, 31].
Similarly, Calabrò et al. report that R. coriaria possesses exceptional nutraceutical value because of its chemically diverse phenolic composition and its ability to influence numerous biological pathways associated with oxidative stress, chronic inflammation, microbial infections, and metabolic disorders. They declare that compounds, such as gallic acid, methyl gallate, quercetin derivatives, anthocyanins, and hydrolyzable tannins act cooperatively to regulate cellular redox homeostasis and inflammatory signaling pathways. These observations provide a mechanistic explanation for the present results and further support the hypothesis that the therapeutic efficacy of R. coriaria depends on the cumulative biological activities of multiple phytochemical constituents rather than on individual molecules [2, 32].
The chromatographic analyses performed in this study also demonstrated substantial qualitative agreement with other investigations, which employed advanced chromatographic platforms to characterize the chemical composition of R. coriaria [3, 33-36].
Abu-Reidah et al. [3] identified numerous phenolic acids and flavonoids, whereas Arena et al. [36] combined headspace solid-phase microextraction gas chromatography with comprehensive two-dimensional liquid chromatography to reveal an even broader spectrum of volatile and nonvolatile metabolites. The similarity between these reports and the present findings confirms that the phytochemical profile of R. coriaria is highly reproducible despite differences in analytical platforms. Minor variations in the abundance of individual compounds are expected and can reasonably be attributed to differences in geographical origin, climatic conditions, harvesting season, soil characteristics, postharvest handling, extraction solvent, and extraction methodology, all of which are recognized determinants of phytochemical composition in medicinal plants.
Our antibacterial findings are consistent with those reported by Koşar et al. [35], demonstrating that ethanolic extracts of R. coriaria possess significant inhibitory activity against both Gram-positive and Gram-negative bacteria. They attribute this effect primarily to the high concentrations of gallic acid, hydrolyzable tannins, and flavonoids, which can damage bacterial cell membranes and disrupt intracellular metabolic pathways. Similarly, Perrone et al. [14] conclude that the antimicrobial efficacy of sumac is closely associated with its phenolic profile, particularly gallic acid derivatives and condensed tannins, which increase membrane permeability, induce the leakage of intracellular constituents, and inhibit several bacterial enzymes required for survival. The agreement between these reports and our findings reinforces the hypothesis that phenolic compounds constitute the principal antimicrobial components of R. coriaria.
Comparable observations are also reported by Batiha et al. [1], who reviewed numerous experimental studies demonstrating that R. coriaria extracts inhibit a wide variety of clinically important bacterial pathogens, including both Gram-positive and Gram-negative species. The antimicrobial activity results from synergistic interactions among multiple phytochemicals rather than from the effects of a single constituent. Alsamri et al. [4] reached similar conclusions and emphasized that the biological activity of sumac cannot be explained solely by its total phenolic content but also depends on the diversity and relative abundance of individual compounds acting cooperatively. This synergistic phenomenon provides a plausible explanation for the strong antimicrobial activity observed in the present study despite the complexity of the crude extract.
The predominance of identified phenolic compounds is particularly important because these metabolites are known to possess multiple complementary biological functions. Hydrolyzable tannins and gallic acid derivatives interact with microbial cell envelopes, increase membrane permeability, inhibit extracellular enzymes, and interfere with nucleic acid synthesis. Flavonoids can modulate intracellular signaling pathways involved in oxidative stress and inflammation while also exhibiting antiviral activity through the inhibition of viral attachment, replication, and protein synthesis. In addition, several polyphenols can chelate transition metals, scavenge reactive oxygen species, and interrupt lipid peroxidation chain reactions, thereby contributing to antimicrobial, antioxidant, and cytoprotective activities. The coexistence of these chemically diverse constituents therefore provides a plausible biochemical explanation for the multiple biological effects observed throughout the present study. These mechanistic interpretations are consistent with the conclusions reported by Alsamri et al. [4], Perrone et al. [14], and Calabrò et al. [2], all of whom emphasize that the pharmacological potential of R. coriaria results from the synergistic action of numerous phenolic metabolites rather than from isolated phytochemicals.
Overall, the phytochemical characterization confirmed that R. coriaria is a rich source of biologically active phenolic compounds with considerable pharmacological relevance. The close agreement between our findings and those of previous chromatographic investigations further strengthens the reliability of the analytical approach used in this work and supports the subsequent interpretation of the antimicrobial, antiviral, antioxidant, and hypolipidemic activities demonstrated by the extracts [1-4, 14, 36].
R. coriaria fruit extract exhibited marked antibacterial and antifungal activities against the tested microorganisms, indicating that the plant possesses broad-spectrum antimicrobial properties. The observed inhibitory effects are most likely attributable to the high concentrations of phenolic acids, hydrolyzable tannins, flavonoids, and other bioactive phytochemicals identified during phytochemical characterization. These secondary metabolites are known to target multiple microbial structures simultaneously, thereby reducing the likelihood of resistance development and enhancing antimicrobial efficacy. Unlike conventional antibiotics, which generally interfere with a single cellular target, plant-derived polyphenols frequently exert their antimicrobial effects through multiple complementary mechanisms, including disruption of membrane integrity, inhibition of essential metabolic enzymes, interference with nucleic acid synthesis, and impairment of quorum sensing. Such multitarget activity may explain the considerable inhibitory activity observed in the present investigation [1, 4, 36].
The antifungal activity is likewise supported by previous studies evaluating R. coriaria against pathogenic yeasts and filamentous fungi. Perrone et al. report that the phenolic constituents of sumac interfere with fungal membrane integrity by interacting with ergosterol-rich membranes, ultimately increasing membrane permeability and promoting the leakage of essential intracellular metabolites. Additionally, tannins can form stable complexes with fungal cell wall proteins and extracellular enzymes, thereby inhibiting fungal growth and colonization. These mechanisms are likely responsible for the antifungal activity observed in the present study and may explain the susceptibility of the fungal isolates to the tested extracts [14].
Another important explanation for the antimicrobial activity observed in this work involves the strong antioxidant properties of the identified polyphenols. Oxidative homeostasis is essential for microbial survival, and several phenolic compounds have been shown to disrupt intracellular redox balance by generating oxidative stress within microbial cells while simultaneously inhibiting antioxidant defense enzymes. Calabrò et al. [2] highlight that the pharmacological activity of R. coriaria depends on the integrated actions of antioxidant and antimicrobial phytochemicals, which modulate microbial physiology through interconnected biochemical pathways. Likewise, Arena et al. [36] and Hariri et al. demonstrate that extracts containing higher concentrations of phenolic constituents generally exhibit stronger antioxidant and antimicrobial activities, suggesting a positive correlation between phytochemical composition and biological efficacy. Our findings agree well with these observations and further support the role of phenolic-rich extracts as multifunctional antimicrobial agents [2, 37].
Differences in antimicrobial potency reported among various studies should also be interpreted in light of methodological variations. Factors, such as the geographical origin of the plant material, harvesting season, climatic conditions, extraction solvent, extraction technique, phytochemical composition, microbial strain diversity, inoculum density, incubation conditions, and susceptibility-testing protocols may substantially influence the measured antimicrobial activity. Balouiri et al. emphasize that methodological standardization is essential for reliable comparisons among antimicrobial investigations because differences in experimental procedures frequently account for discrepancies among published studies. Therefore, minor variations between the present findings and previous reports should be considered expected rather than contradictory [24].
Collectively, the obtained antibacterial and antifungal results provide additional evidence supporting the therapeutic potential of R. coriaria as a natural antimicrobial agent. The close agreement between the current observations and those reported by Calabrò et al., Alsamri et al., Shidfar et al., Mohammadi et al., and Al-Shwuaili et al. strengthens the reliability of the present findings and suggests that the antimicrobial activity of sumac is primarily driven by the synergistic actions of phenolic acids, tannins, flavonoids, and other secondary metabolites that act through multiple complementary mechanisms [2, 4, 38-40 ].
This study has several strengths. First, it adopted an integrated experimental approach by combining phytochemical profiling with evaluations of antimicrobial, antiviral, antioxidant, and hypolipidemic activities within a single study, thereby allowing a comprehensive assessment of the biological potential of R. coriaria. Second, the use of complementary analytical techniques enhanced the reliability of the phytochemical characterization and facilitated the interpretation of the observed biological activities. Third, the integration of both in vitro assays and an in vivo experimental model provided broader evidence supporting the pharmacological potential of the investigated extracts. Collectively, these methodological strengths enhance the scientific robustness of the study and increase its translational relevance to future pharmaceutical and nutraceutical research.
This study has several limitations that should be considered when interpreting the findings. First, the biological activities were evaluated using the extract prepared from R. coriaria fruits collected from a single geographical location during one harvesting season, which may not fully represent the natural phytochemical variability associated with different environmental conditions or cultivation practices. Second, although GC-MS and HPLC analyses identified the principal phytochemical constituents, the biological activities were assessed using the crude extract rather than purified individual compounds; therefore, the specific contribution of each constituent and the potential synergistic interactions among them were not investigated. Third, the antimicrobial and antiviral evaluations were limited to selected reference microorganisms and viral strains, and broader testing against clinically relevant multidrug-resistant isolates and additional viral pathogens would provide a more comprehensive assessment of the therapeutic potential. Furthermore, the hypolipidemic activity was evaluated in an experimental animal model with a relatively short treatment period, and the results cannot be directly extrapolated to human clinical settings. Finally, the molecular mechanisms underlying the observed pharmacological activities were not explored through gene expression analysis, molecular docking, or protein-level investigations. Therefore, future studies should include mechanistic experiments, toxicity and pharmacokinetic evaluations, and well-designed clinical trials to further validate the efficacy, safety, and translational potential of R. coriaria extract.
Importantly, this study integrated phytochemical characterization with multiple biological evaluations, providing a more comprehensive understanding of the relationship between chemical composition and biological activity than has been reported in many previous investigations. These findings contribute to the growing body of evidence supporting the therapeutic value of R. coriaria and reinforce its potential as a natural source of bioactive compounds for the development of novel complementary therapeutic agents.
Nevertheless, additional studies are warranted to isolate and characterize the individual active constituents, elucidate their molecular mechanisms of action, evaluate their pharmacokinetic and toxicological profiles, and validate their efficacy in well-designed clinical trials. Such investigations will be essential for translating the promising experimental findings into safe and effective therapeutic applications.
Conclusion
R. coriaria shows promising antimicrobial, antiviral, antioxidant, and hypolipidemic potential for pharmaceutical and nutraceutical applications.
Acknowledgments: The authors are very grateful to all faculty members and technicians for their assistance in completing this study.
Ethical Permissions: This study was conducted in accordance with the ethical standards of the Declaration of Helsinki and was approved by the Ethical Approval Committee (Institutional Review Board) of Al-Manara University/College of Dentistry under Decision No. 63, issued on 12-11-2024 (NO.63 -IN 12-11-2024).
Conflicts of Interests: The authors declared no conflicts of interest.
Authors' Contribution: Ali D (First Author), Introduction Writer/Methodologist/Main Researcher/Discussion Writer/Statistical Analyst (40%); Qasim MJ (Second Author), Introduction Writer/Methodologist/Assistant Researcher/Discussion Writer/Statistical Analyst (35%); Jebur NH (Third Author), Assistant Researcher/Discussion Writer/Statistical Analyst (25%)
Funding/Support: No funding was received for this research.
Keywords:
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