Therapeutic Potential of Citrus Species Against Metabolic Syndrome: Insights from Preclinical and Clinical Studies

Metabolic syndrome (MetSyn) is a multifactorial disorder affecting 12.5-31.4% of adults characterized by a cluster of conditions including obesity, type 2 diabetes, hypertension, cardiovascular diseases, and dyslipidemia. Lifestyle and dietary interventions are essential components of its management. With growing interest in natural sources, citrus species are one source that has been traditionally used to treat the symptoms of MetSyn. This review paper aims to provide a comprehensive summary of preclinical and clinical studies to assess the effects of citrus species and their derived phytoconstituents, such as flavonoids, limonoids, and carotenoids, on key metabolic parameters. To evaluate the therapeutic potential of citrus species in the prevention and management of metabolic syndrome based on preclinical studies using essential oils and extracts, clinical studies, and the activity of their bioactive phytoconstituents.

Citrus species such as Citrus limon, Citrus medica, Citrus bergamia, Citrus aurantifolia, Citrus aurantium, Citrus grandis, Citrus maxima, Citrus sinensis, Citrus assamensis, Citrus sphaerocarpa, Citrus reticulata, Citrus japonica, and Citrus unshiu have been reported to treat metabolic syndrome. Preclinical studies demonstrate that citrus essential oils and extracts improve insulin sensitivity, reduce body weight and lipid levels, and aid in blood pressure regulation. Prominent bioactive phytoconstituents from citrus species include d-limonene, β-pinene, neral, citronellal, thymol, β-sitosterol, oleic acid, limonene, linalool, citral, α-pinene, coumarin, hexadecenoic acid, hesperidin, neohesperidin, eugenol, geraniol, and p-cymene, have also been reported to demonstrate anti-obesity, antidiabetics, antihypertensive, antidyslipidemic, and cardiovascular protective properties. Clinical trials support these findings, showing significant improvements in metabolic markers in human subjects following citrus-based interventions. Citrus species, due to their rich phytochemical composition, show considerable promise as natural therapeutic agents for mitigating the risks associated with metabolic syndrome. Further well-designed clinical trials are warranted to establish standardized dosages, to concentrate on their mechanisms of action, routes of administration, safe dosage, and potential side effects to ensure their efficacy and safety in treating MetSyn.