Paving Luteolin Therapeutic Potentialities and Agro‐Food‐Pharma Applications: Emphasis on In Vivo Pharmacological Effects and Bioavailability Traits

Abstract

Luteolin is a naturally occurring secondary metabolite belonging to the class of flavones. As many other natural flavonoids, it is often found in combination with glycosides in many fruits, vegetables, and plants, contributing to their biological and pharmacological value. Many preclinical studies report that luteolin present excellent antioxidant, anticancer, antimicrobial, neuroprotective, cardioprotective, antiviral, and anti-inflammatory effects, and as a consequence, various clinical trials have been designed to investigate the therapeutic potential of luteolin in humans. However, luteolin has a very limited bioavailability, which consequently affects its biological properties and efficacy. Several drug delivery strategies have been developed to raise its bioavailability, with nanoformulations and lipid carriers, such as liposomes, being the most intensively explored. Pharmacological potential of luteolin in various disorders has also been underlined, but to some of them, the exact mechanism is still poorly understood. Given the great potential of this natural antioxidant in health, this review is aimed at providing an extensive overview on the in vivo pharmacological action of luteolin and at stressing the main features related to its bioavailability, absorption, and metabolism, while essential steps determine its absolute health benefits and safety profiles. In addition, despite the scarcity of studies on luteolin bioavailability, the different drug delivery formulations developed to increase its bioavailability are also listed here.

Anti-Inflammatory and Analgesic Activity of Methanolic Root Extract of Verbascum sinaiticum Benth

“…As illustrated in the phytochemical screening and quantification result, V. sinaiticum extract is rich in numerous phytochemicals which are known to elicit several pharmacological activities including analgesia and anti-inflammatory effect. According to studies conducted on the biological activities of the various phytochemicals, the flavolignans 41 and flavones, 42 , 43 glycosides, 44 saponins 45 and tannins 46 have been shown to induce analgesia and anti-inflammatory effects due to their ability to inhibit key enzymes involved in the inflammation process such as COX-1 (cyclooxygenase 1), COX-2 (cyclooxygenase 2), sPLA2 (secretory phospholipase A2) and 15-LOX-2 (15-lipoxygenase).…”

Luteolin-Induced Activation of Mitochondrial BKCa Channels: Undisclosed Mechanism of Cytoprotection

“…From the analysis of the literature, it emerges that LUT has a poor bioavailability—in animals as well as in humans—for the extensive first-pass metabolism by phase II enzymes. Indeed, the plasmatic peak was reached 30–40 min after oral administration, and 3 h later the main metabolites were the glucuro- and sulpho-conjugates; finally, elimination half-life (t1/2) was quantified as 2–3 h [ 82 ]. Although the low bioavailability is one of the major limitations to the therapeutic use of LUT, as well as of flavonoids, different delivery strategies, including lipid carriers and nanoformulations, have been developed and investigated in order to improve it and enable the clinical use of dietary supplements containing LUT.…”

Cancer treatment: from traditional Chinese herbal medicine to the liposome delivery system

“…In recent years, many experiments and clinical studies have proved that heat-clearing TCH medicines have good antiinflammatory effects [105]. LUT has a variety of pharmacologic activities, such as anti-inflammation, anti-allergic, anti-tumor, anti-bacterial, and anti-virus activity [106]. LUT also blocks cancer development in vitro and in vivo by inhibiting the proliferation of tumor cells, protecting against carcinogenic stimuli, activating cell cycle arrest, and inducing apoptosis via different signal pathways [107]; however, the bioavailability of LUT is very low after oral administration, and it is difficult to administer intravenously or intraperitoneally due to its poor water solubility, so many drug delivery strategies have been used to improve the bioavailability of LUT in the human system, especially liposomes [106].…”

“…LUT also blocks cancer development in vitro and in vivo by inhibiting the proliferation of tumor cells, protecting against carcinogenic stimuli, activating cell cycle arrest, and inducing apoptosis via different signal pathways [107]; however, the bioavailability of LUT is very low after oral administration, and it is difficult to administer intravenously or intraperitoneally due to its poor water solubility, so many drug delivery strategies have been used to improve the bioavailability of LUT in the human system, especially liposomes [106]. Moreover, the exact pharmacologic mechanism and dosage of LUT have not been established [106], and there is no LUT liposome for clinical use.…”