The flavone luteolin, 3′,4′,5,7-tetrahydroxyflavone, is a polyphenol commonly found in fruits, vegetables, and medicinal herbs (Curr. Cancer Drug Targets 2008;8:634–46). Luteolin is most often present in leaves, but is also found in rinds and other parts of plants.
The flavone and its glycosides have been identified in Bryophyta, Magnoliophyta, Pinophyta, Pteridophyta, and Salvia (Mini Rev. Med. Chem. 2009;9:31–59).
Luteolin is believed to have the potential to play a significant role in health, as it is considered to exhibit broad-ranging anti-inflammatory benefits (Proc. Natl. Acad. Sci. U.S.A. 2008;105:7534–9), as well as anticarcinogenic, antimicrobial, antioxidant, and immunomodulatory effects. Cancer, hypertension, inflammation, and other conditions have been treated with luteolin-rich plants in traditional Chinese medicine (Curr. Cancer Drug Targets 2008;8:634–46).
Notably, this antioxidant is present in the typical human diet in relatively low amounts (less than 1 mg/day) (Molecules 2008;13:2628–51). Dietary sources of luteolin include carrots, chamomile tea, celery, olive oil, oregano, peppermint, peppers, perilla, rosemary, and thyme (Mini Rev. Med. Chem. 2009;9:31–59; FEBS Lett. 1998;438:220–4).
This column will focus on recent research conducted on this antioxidant, particularly studies that imply potential dermatologic applications.
Antitumor Actions
In 2002, Ueda et al. studied the effects of orally administered perilla leaf extract on mice, and found that it inhibited production of tumor necrosis factor-alpha. The in vitro phase of the study led to their identifying luteolin, caffeic acid, and rosmarinic acid as active constituents of perilla. The investigators noted that only luteolin exhibited in vivo activity, however. Luteolin was responsible not only for suppressing the production of serum tumor necrosis factor-alpha, but also for suppressing arachidonic acid-induced ear edema, 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear edema, and oxazolone-induced allergic edema (Biol. Pharm. Bull. 2002;25:1197–202).
A year later, the same team reported on its examination of the effects of topically applied perilla leaf extract and luteolin on murine skin papillomas induced by TPA and 7,12-dimethyl- benz[a]anthracene. Significant decreases in tumor incidence and multiplicity were observed in mice topically treated with perilla leaf extract before TPA treatment, especially in mice treated with luteolin prior to TPA (Biol. Pharm. Bull. 2003;26:560–3).
Anticancer Actions
Recent reviews on the diverse benefits of luteolin suggest that the flavone exhibits anti-inflammatory and anticarcinogenic properties, not all of which can be attributed to its antioxidant activity. By protecting against carcinogenic stimuli, luteolin is believed to have the capacity, in vitro and in vivo, to delay or inhibit cancer cell development, suppress tumor proliferation, induce cell cycle arrest, and spur apoptosis through intrinsic and extrinsic signaling pathways. Interestingly, some epidemiologic evidence points to an inverse relationship between luteolin consumption and the risk of developing some types of cancer (Molecules 2008;13:2628–51).
In a recent review of the distribution and biologic activities of luteolin, López-Lázaro summarized preclinical studies of the flavone, which have demonstrated that it has wide-ranging pharmacologic activities, particularly anticancer, anti-inflammatory, antimicrobial, and antioxidant properties.
Significant cancer chemopreventive and chemotherapeutic potential is suggested by the capacity of luteolin to block angiogenesis, induce apoptosis, prevent carcinogenesis in animal models, decrease tumor growth in vivo, and sensitize tumor cells to the cytotoxic impact of some anticancer drugs. López-Lázaro also noted a wide range of potential mechanisms of action for the various biologic activities of luteolin (Mini Rev. Med. Chem. 2009;9:31–59). In fact, luteolin has been found to sensitize cancer cells to induced cytotoxicity by inhibiting cell survival pathways (e.g., phosphatidylinositol 3′-kinase, nuclear factor kappa B, and X-linked inhibitor of apoptosis protein), and by promoting apoptosis pathways, leading to, for example, the induction of tumor suppressor p53 (Curr. Cancer Drug Targets 2008;8:634–46).
Seelinger et al. compared the anticarcinogenic effects of luteolin to those of other flavonoids, and found that luteolin was typically the most effective, inhibiting tumor cell proliferation with half-maximal inhibitory concentrations (IC50) between 3 and 50 mmol in vitro and in vivo by intragastric application or as a food additive. They concluded that because luteolin has also been demonstrated to penetrate human skin, this polyphenolic compound is potentially a suitable agent for preventing and treating skin cancer and photoaging (Molecules 2008;13:2628–51).
Antioxidant Actions
In a 2004 study of the components of Zostera marina leaves, Kim et al. found that the constituents apigenin, chrysoeriol, and luteolin scavenged radicals and reactive oxygen species, specifically the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and the superoxide radical in the xanthine/xanthine oxidase system.
Luteolin also inhibited matrix metalloproteinase-1 (MMP-1) expression by up to 44%, and suppressed the synthesis of interleukin-6, a cytokine known to spur MMP-1 expression.
The investigators concluded that the antioxidant capacity of luteolin and the other Zostera marina constituents tested, as well as their ability to suppress MMP-1 expression, suggests the potential use of these compounds as agents to prevent cutaneous photoaging (Arch. Pharm. Res. 2004;27:177–83).