The Efficacy of Quercetin in Attenuating Oxidative Stress and Clinical Symptoms in Allergic Rhinitis: A Systematic Review

Allergic rhinitis (AR) affects millions worldwide as an IgE-mediated inflammatory condition triggered by environmental allergens [1]. The disease involves complex pathways where oxidative stress plays a central role, with malondialdehyde serving as a key damage marker [2,3]. Quercetin, a natural flavonoid found in common foods, demonstrates promising antioxidant and anti-inflammatory properties [4,5]. This systematic review evaluates scientific evidence regarding quercetin’s effectiveness in reducing oxidative stress markers and improving clinical symptoms in allergic rhinitis management [6].

This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement guidelines. We developed a comprehensive protocol before initiating the search to ensure transparent and reproducible methodology.

Data sources and search strategy

Four electronic databases were systematically searched: PubMed, Google Scholar, SagePub, and Semantic Scholar. Our search covered publications from January 2000 through December 2024 to capture contemporary evidence while maintaining relevance. The search strategy utilized the PICO (Population, Intervention, Comparison, Outcome) framework (Table 1). We combined relevant Medical Subject Headings terms with text keywords using Boolean operators. The search string included: (“Allergic Rhinitis” OR “Nasal Allergy” OR “Hay Fever”) AND (“Quercetin” OR “Oral Quercetin”) AND (“Malondialdehyde” OR “Clinical Improvement” OR “Symptom Severity”).

Study selection process

Two independent reviewers (N.D.A.K. and H.K.) conducted the study selection process in multiple phases. Initially, we removed duplicate records using reference management software. Subsequently, we screened titles and abstracts against predetermined inclusion criteria. Full-text articles were then retrieved and assessed for final eligibility.

Inclusion and exclusion criteria

Studies were included if they met the following criteria: experimental studies (in vivo human or animal models, relevant in vitro studies), participants with diagnosed allergic rhinitis or established experimental models, quercetin intervention as single compound or plant extract, outcome measures including malondialdehyde levels or allergic rhinitis symptoms, and peer- reviewed publications in English or Indonesian.

We excluded narrative reviews, editorials, observational studies without control groups, studies on conditions other than allergic rhinitis, interventions combining quercetin with other compounds without separate controls, and abstract-only publications.

Data extraction process

Structured data extraction forms were developed and piloted before use. Two reviewers independently extracted information, including: author details, publication year, study design, population characteristics, intervention specifics (dose, duration, route), comparison groups, outcome measures, and key findings. Discrepancies were resolved through discussion with a third reviewer (B.P.).

Quality assessment methods

Methodological quality was evaluated using appropriate tools for different study designs. Randomized controlled trials were assessed using the Cochrane Risk of Bias Tool, while observational and quasi-experimental studies were evaluated using the Newcastle-Ottawa Scale. Each reviewer independently scored studies, with disagreements resolved through consensus discussion.

Data synthesis approach

Due to significant heterogeneity in study populations (animal versus human), interventions (pure quercetin versus extracts, varying doses), and outcome measurements, quantitative meta-analysis was not feasible. We employed narrative synthesis methodology, organizing findings thematically by primary outcomes: effects on malondialdehyde levels and clinical symptom improvements.

The systematic search initially identified 5,757 records. After removing duplicates and ineligible records, 3,416 records were screened by title and abstract. Following full-text assessment of 1,920 reports, 18 studies met all eligibility criteria and were included in this systematic review (Figure 1). The included studies comprised 14 animal experimental studies and 4 human clinical trials. Study populations ranged from 18 to 100 participants in human studies, while animal studies included 24 to 70 subjects (Table 2). Quercetin doses varied from 4 mg/200g to 200 mg/kg in animal studies, and intervention durations ranged from 3 days to 8 weeks.

Quality assessment results

Methodological quality assessment revealed moderate to high quality across included studies. Animal studies were generally well-designed with clear descriptions of randomization, control groups, and outcome assessment (Table 3). However, several limitations were identified: some animal studies measured malondialdehyde in contexts other than allergic rhinitis, and human clinical trials often utilized multi-component formulations, making it challenging to isolate quercetin’s specific effects.

Effects on malondialdehyde levels

Animal studies consistently demonstrated quercetin’s ability to reduce malondialdehyde concentrations across various tissues. Bidian, et al. [11] showed that oral quercetin administration (50 mg/kg/day) for four days significantly decreased serum and lung malondialdehyde levels (p < 0.001) in allergic rhinitis rat models compared to untreated controls. Additional investigations confirmed these antioxidant effects across different contexts. Helianti, et al. [12] demonstrated that quercetin-rich onion peel infusions significantly lowered serum malondialdehyde in cigarette smoke-exposed rats. Similar protective effects were observed in liver and muscle tissues of hyperthyroid rats [13], kidney tissues following pesticide exposure [14], and cardiac tissues after aluminum intoxication [15]. The consistency of malondialdehyde reduction across diverse tissues and oxidative. Stress conditions indicate quercetin’s fundamental cytoprotective mechanisms against lipid peroxidation. This systemic antioxidant capacity appears to be a core biochemical property applicable to allergic rhinitis pathophysiology (Table 4).

Clinical symptom improvements

Human clinical trials demonstrated significant therapeutic benefits when quercetin supplementation was added to standard treatments. Marogna and Ciprandi [16] investigated adults with grass pollen-induced allergic rhinitis, finding that multicomponent nutraceuticals containing quercetin, perilla, and vitamin D3 added to standard therapy produced 39% greater symptom improvement compared to conventional treatment alone. Gori, et al. [17] conducted randomized controlled trials in children with allergic rhinitis, reporting that quercetin-based nutraceutical (Quertal®) combined with antihistamines resulted in significantly superior symptom resolution versus antihistamine monotherapy. These clinical improvements were sustained throughout three-month treatment periods. Animal studies provided additional mechanistic support. Ravikumar and Kavitha [18] demonstrated that oral quercetin significantly reduced nasal hyperresponsiveness in mouse allergic rhinitis models. Sutanegara and Fredlina [19] found that flavonoid-rich Eugenia uniflora leaf extracts were equally effective as corticosteroids in reducing nasal symptom scores in rat models (Tables 5,6).

Mechanistic insights

Evidence indicates quercetin exerts therapeutic effects through multiple complementary mechanisms. Primary actions include direct antioxidant activity via free radical scavenging and transition metal chelation [20]. Additionally, quercetin activates nuclear factor erythroid 2 2-related factor 2 (Nrf2) signaling pathways, enhancing endogenous antioxidant enzyme production, including superoxide dismutase, catalase, and glutathione peroxidase [21].

Anti-allergic properties involve mast cell membrane stabilization, reducing histamine and inflammatory mediator release [22]. Quercetin also modulates immune responses by suppressing Th2 cytokine production and inhibiting immunoglobulin E synthesis, targeting allergic cascades at fundamental levels [23].

This systematic review presents robust evidence demonstrating quercetin’s therapeutic potential in allergic rhinitis management through two primary mechanisms: oxidative stress attenuation and direct anti-inflammatory effects. The consistency of malondialdehyde reduction across 14 animal studies, combined with clinically meaningful symptom improvements in human trials, establishes a compelling case for quercetin as an adjunctive therapeutic agent in allergic rhinitis management. The clinical significance becomes particularly apparent when examining the magnitude of therapeutic benefits observed.

Marogna and Ciprandi’s study [16] demonstrated a 39% greater improvement in allergic rhinitis symptoms when quercetin-based nutraceuticals were added to standard therapy compared to conventional treatment alone. This substantial improvement suggests that quercetin addresses pathophysiological mechanisms not adequately targeted by current first-line therapies, specifically the oxidative stress component of allergic inflammation.

Mechanistic insights and pathophysiological relevance

The therapeutic efficacy of quercetin in allergic rhinitis can be understood through its multi-targeted approach to disease pathogenesis. Allergic rhinitis involves a complex interplay between IgE-mediated immune responses, inflammatory cell activation, and subsequent oxidative stress generation [1,2]. Our analysis reveals that quercetin effectively interrupts this pathological cascade at multiple critical points.

Direct Antioxidant Mechanisms: Quercetin’s molecular structure, featuring multiple hydroxyl groups in strategic positions, enables efficient free radical scavenging capabilities. The consistent reduction in malondialdehyde levels observed across studies by Bidian, et al. [11], Helianti, et al. [12], and others demonstrates quercetin’s ability to prevent lipid peroxidation, a key mechanism of cellular damage in allergic inflammation. This direct antioxidant activity is particularly relevant in allergic rhinitis, where activated eosinophils and neutrophils generate substantial reactive oxygen species burdens that overwhelm endogenous antioxidant defenses [4,5].

Nrf2 Pathway Activation: Perhaps more significantly for long-term therapeutic benefits, quercetin activates the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway [21]. This transcription factor functions as the cellular master regulator of antioxidant responses, controlling the expression of over 200 genes involved in cellular protection.

Quercetin-induced Nrf2 activation leads to increased synthesis of endogenous antioxidant enzymes, including superoxide dismutase, catalase, and glutathione peroxidase. This mechanism explains the sustained protective effects observed in longer-duration studies and suggests that quercetin treatment may provide cumulative benefits over time.

Anti-allergic properties: Beyond its antioxidant effects, quercetin demonstrates direct anti-allergic properties crucial for allergic rhinitis management. The compound stabilizes mast cell and basophil membranes, preventing degranulation and subsequent histamine release [22]. This mechanism directly addresses the immediate hypersensitivity reactions characteristic of allergic rhinitis, explaining the rapid symptom improvements observed in clinical trials.

Additionally, quercetin modulates T-helper cell differentiation, suppressing Th2 responses while promoting Th1 immunity, thereby addressing the fundamental immune dysregulation underlying allergic diseases [23].

Comparative analysis with current therapeutic options

Current allergic rhinitis management relies primarily on antihistamines, intranasal corticosteroids, and leukotriene receptor antagonists [1]. While these treatments effectively control symptoms, they primarily target downstream inflammatory mediators rather than addressing the underlying oxidative stress component of disease pathogenesis. The clinical trials included in our review suggest that quercetin supplementation provides additive benefits when combined with conventional therapies, indicating complementary rather than competitive mechanisms of action. The study by Gori, et al. [17] in pediatric populations is particularly noteworthy, as it demonstrates superior symptom control when quercetin-based formulations are added to antihistamine therapy compared to antihistamine monotherapy. This finding suggests that quercetin addresses therapeutic gaps in current treatment.

Paradigms, particularly the oxidative stress component that conventional therapies do not adequately target.

Dose-response relationships and bioavailability considerations

Analysis of included studies reveals significant variability in quercetin dosing, ranging from 10 - 200 mg/kg in animal studies and varying formulations in human trials. This variability reflects the ongoing challenge of establishing optimal dosing protocols and highlights the critical importance of bioavailability optimization. Natural quercetin exhibits poor oral bioavailability due to limited water solubility, extensive first-pass metabolism, and rapid elimination [27]. The development of enhanced bioavailability formulations, such as the phytosome technology described by Riva, et al. [28], represents a crucial advancement for clinical applications. These formulations achieve up to 20-fold increases in plasma quercetin concentrations compared to standard preparations, suggesting that many previous studies may have been physiologically under-dosing despite high oral doses administered.

Safety profile and clinical implementation

Quercetin demonstrates an excellent safety profile across all reviewed studies, with no significant adverse effects reported in either animal or human investigations. This safety profile, combined with quercetin’s natural occurrence in common dietary sources, supports its potential for long-term use in chronic conditions like allergic rhinitis. The compound’s GRAS (Generally Recognized as Safe) status by regulatory authorities further supports its clinical application potential. From a practical implementation perspective, quercetin supplementation offers several advantages: oral administration convenience, absence of significant drug interactions, and compatibility with existing therapeutic regimens. These characteristics make quercetin particularly suitable for patients seeking integrative approaches to allergic rhinitis management or those experiencing inadequate symptom control with conventional therapies alone.

This review acknowledges several limitations. The predominance of animal studies limits direct clinical translation. Multi-component formulations in human trials prevent quercetin-Specific effect determination. Additionally, heterogeneous study designs, populations, and outcome measures precluded quantitative meta-analysis performance.

Future investigations should prioritize large-scale, double-blind, randomized controlled trials in diverse human populations utilizing standardized, high-bioavailability quercetin formulations. Head-to-head comparisons against first-line allergic rhinitis therapies would help establish quercetin’s therapeutic positioning. Dose-response relationship studies and optimal treatment duration determination are also essential for clinical guideline development.

Based on systematic evaluation of 18 preclinical and clinical studies, quercetin demonstrates significant therapeutic potential in allergic rhinitis management. The evidence consistently shows quercetin effectively reduces oxidative stress markers, particularly malondialdehyde, and ameliorates clinical symptoms when added to standard therapy. These benefits derive from multifaceted mechanisms, including direct antioxidant actions, enhancement of endogenous defense systems via Nrf2 pathway activation, and direct anti-allergic effects.

Despite promising results, current evidence is limited by the predominance of animal studies and the use of multi-component formulations in human trials. Clinicians may consider recommending high-quality quercetin supplements as safe adjuvant therapy, particularly for patients with inadequate responses to conventional treatments. However, large-scale, rigorously designed human clinical trials utilizing standardized, high-bioavailability formulations are critically needed to establish definitive evidence-based clinical guidelines.

The future of quercetin research may depend more on optimizing delivery systems than proving basic efficacy. Enhanced formulations hold potential to bridge the gap between strong preclinical effects and modest human trial results, paving the way for evidence-based dosing recommendations and standardized clinical protocols.

We sincerely thank the faculty members of the Doctoral Program of Medical Sciences at Universitas Sebelas Maret and UNS Hospital for their invaluable guidance throughout this systematic review. We also express our gratitude to the librarians at Universitas Sebelas Maret and Universitas Padjajaran for their assistance in accessing full-text articles and database searches. Special appreciation goes to all researchers whose rigorous work contributed to the evidence base examined in this review.

Conflicts of interest

The authors declare no conflicts of interest related to this systematic review. All contributions were made independently to advance evidence-based therapeutic approaches for allergic rhinitis management. No financial or material support was received from pharmaceutical companies, nutraceutical manufacturers, or any commercial entities with interests in quercetin research. The research was conducted with complete academic freedom, ensuring analyses and conclusions were based solely on available scientific evidence.

Funding sources

This systematic review was supported by the Doctoral Program of Medical Sciences at Sebelas Maret University, Surakarta, Indonesia, through institutional academic resources. No external funding was received from government agencies, private foundations, or commercial organizations. All costs associated with database access, literature retrieval, and manuscript preparation were covered through the authors’ institutional affiliations. The absence of external funding ensured complete independence in study design and data interpretation.

Data availability

Data supporting the findings of this systematic review, including search strategies, data extraction forms, and quality assessment scores, are available upon reasonable request from the corresponding author. Access will be provided in accordance with PRISMA guidelines and institutional research policies. Interested researchers seeking data access for validation or further analysis are encouraged to contact the corresponding author with specific requests and intended use descriptions.

Source(s) of support: This systematic review was supported by the Doctoral Program of Medical Sciences at Sebelas Maret University, Surakarta, Indonesia, through institutional academic resources. No external funding was received from government agencies, private foundations, or commercial organizations. All costs associated with database access, literature retrieval, and manuscript preparation were covered through the authors’ institutional affiliations. The absence of external funding ensured complete independence in study design and data interpretation.

Author contributions

Niken Dyah Aryani K: Has extensive clinical experience in otorhinolaryngology with a specific focus on allergic rhinitis management. Currently pursuing doctoral research on oxidative stress mechanisms in allergic diseases and has published multiple peer-reviewed articles on rhinology and allergy immunotherapy.

Harijono Kariosentono: Expert in dermatology and immunology with significant research experience in allergic diseases and inflammatory conditions. Has supervised numerous systematic reviews and meta-analyses in the field of allergy and immunology.

Bambang Purwanto: Internal medicine specialist with expertise in clinical research methodology and systematic review conduct. Has extensive experience in evidence-based medicine and has mentored multiple doctoral students in clinical research.

Other contributors: All contributing authors have relevant clinical and research experience in their respective fields, contributing to the multidisciplinary expertise required for a comprehensive systematic review of quercetin’s therapeutic applications in allergic rhinitis.

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