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Ashrafizadeh M, Ahmadi Z, Farkhondeh T, Samarghandian S. Autophagy regulation using luteolin: new insight into its anti-tumor activity. Cancer Cell Int. 2020;20(1):537.
Zuo T, Yue Y, Wang X, Li H, Yan S. Luteolin Relieved DSS-Induced colitis in mice via HMGB1-TLR-NF-κB signaling pathway. Inflammation. 2021;44(2):570–9. Imran M, Rauf A, Abu-Izneid T, Nadeem M, Shariati MA, Khan IA, Imran A, Orhan IE, Rizwan M, Atif M, et al. Luteolin, a flavonoid, as an anticancer agent: a review. Biomed Pharmacother. 2019;112:108612. Tan X, Yang Y, Xu J, Zhang P, Deng R, Mao Y, He J, Chen Y, Zhang Y, Ding J, et al. Luteolin exerts Neuroprotection via Modulation of the p62/Keap1/Nrf2 pathway in Intracerebral Hemorrhage. Front Pharmacol. 2019;10:1551. As a powerful bioflavonoid, Luteolin boasts antioxidant properties that support brain health, function, and cognition. Choi EJ, Bae SM, Ahn WS. Antiproliferative effects of quercetin through cell cycle arrest and apoptosis in human breast cancer MDA-MB-453 cells. Arch Pharm Res. 2008;31(10):1281–5.Although the above seven foods are wonderful sources of luteolin, they're far from the only ones out there. Researchers ranked the top sources of luteolin: They found that radicchio took the lead (by a landslide). However, trailing closely behind were other ingredients like serrano pepper, red leaf lettuce, artichoke, spinach, and broccoli. And although there aren't many luteolin-rich fruits, lemons contain a considerable amount of the flavonoid—nearly as much as celery and chicory greens. That said, there are other fruits with a smaller amount of luteolin, including watermelon, cantaloupe, navel oranges, grapefruit, kiwi, and blueberries. Institute for Biological and Medical Engineering, Schools of Engineering, Medicine and Biological Sciences, Pontificia Universidad Católica de Chile, 7820436, Santiago, Chile Be consistent: Consistency is key when taking any dietary supplement. It is generally recommended to take luteolin supplements regularly as part of a daily routine for maximum benefits. If you have any concerns or questions about the duration of use, consult your healthcare provider. This premium formula is meticulously crafted to support your well-being through a combination of these beneficial compounds. Non-GMO, soy-free, gluten-free, dairy-free, and devoid of artificial preservatives or chemicals, this product is manufactured in the USA.
Luteolin is also found to arrest cell cycle in G2/M phase in addition to the induction of apoptosis in human colon cancer cells xenografts. The flow cytometric analysis has validated the observation that luteolin promotes cell cycle arrest in G2/M phase and induces apoptosis in LoVo human colon cancer cells in time- and dose-dependent manner. Similar observation is obtained with western blot analysis which revealed that luteolin posed inhibitory effect on cell proliferation on LoVo cells by arresting cell cycle at G2/M phase transition and inactivated cyclin B1 and cell division cycle 2. These events are mediated by cytochrome c and deoxyadenosine triphosphate-mediated activation of apoptotic protease activating factor 1. Further in vivo analysis suggested a decrease in the body weight of colon tumor mice. Overall, these findings indicated chemopreventive and chemotherapeutic effect of luteolin against human colon cancer [ 24].
How the anti- or pro-oxidant effects of luteolin ensue has not been well determined. It is believed that flavonoids could behave as antioxidants or pro-oxidants, depending on the concentration and the source of the free radicals [ 32]. Also, the context and microenvironment of the cell may be important determinants of the outcome of luteolin-induced effects on cellular redox status. For example, the antioxidant activity of luteolin is dependent on Cu, V, and Cd ions in the cells. Changes in the Fe ion concentrations dramatically impact the effect of luteolin's redox-regulating activities. With low Fe ion concentrations (< 50 μM), luteolin behaves as an antioxidant while high Fe concentrations (>100 μM) induce luteolin's pro-oxidative effect [ 33]. The similar effect is achieved for 600–1200 mg/kg of orally administered luteolin. Encouraging results obtained from ferrozine assay validated that luteolin at a concentration of 30–100 µg/ml shows Fe 2+ chelating property and potent DPPH radical scavenging ability at 1–100 µg/ml concentration. These inferences indicated that administration of luteolin by oral or intrastriatal routes provides defense to the mice brain against sodium nitroprusside-induced oxidative damage due to the free radical scavenging and chelating effect of luteolin [ 17].
Onset of redox stress resulting in the cascade of several deleterious biochemical and physiological events marks the commencement of oncogenesis. It mainly arises from the generation of a diverse group of highly reactive, oxygen containing species with a short lifespan that serve as second messengers for cellular signaling. These include hydrogen peroxide (H 2O 2), hydroxyl radical (.OH), singlet oxygen ( 1O 2), superoxide radical (O 2 -), and lipid peroxyl radical (LOO). The reactive oxygen species (ROS) are known to manifest irreparable damage to DNA, proteins, and lipids. that eventually causes diseases including cancer. George BP, Chandran R, Abrahamse H. Role of Phytochemicals in Cancer Chemoprevention: insights. Antioxidants 2021;10(9):1455. Kang KA, Piao MJ, Ryu YS, Hyun YJ, Park JE, Shilnikova K, Zhen AX, Kang HK, Koh YS, Jeong YJ, et al. Luteolin induces apoptotic cell death via antioxidant activity in human colon cancer cells. Int J Oncol. 2017;51(4):1169–78.
How luteolin benefits your health
Treatment of HeLa cells with luteolin has been shown to exhibit cytotoxicity in a dose- and time-dependent manner. Luteolin also exhibited anti-proliferative activity as indicated by the accumulation of luteolin-incubated cells in sub-G1 phase of cell cycle. Treatment with luteolin causes depolarization of mitochondrial membrane potential that manifests cytotoxicity towards cancer cells. Furthermore, the expression of proapoptotic genes such as FAS, FADD, BAX, BAD, BOK, BID, TRADD upregulates, while the anti-apoptotic genes NAIP, BCL-2, and MCL-1 experience downregulation. The expression of cell cycle regulatory genes CDK2, CDKN2B, CCNE2, CDKN1A, and CDK4 decreased on incubation with luteolin. Wu HT, Lin J, Liu YE, Chen HF, Hsu KW, Lin SH, Peng KY, Lin KJ, Hsieh CC, Chen DR. Luteolin suppresses androgen receptor-positive triple-negative breast cancer cell proliferation and metastasis by epigenetic regulation of MMP9 expression via the AKT/mTOR signaling pathway. Phytomedicine. 2021;81:153437. In a 20-methycholanyrene-induced fibrosarcoma model using Swiss albino mice, luteolin administered in diet significantly suppressed tumor incidences, which are associated with reduction in lipid peroxides and cytochrome P450, increased activity of GST, and suppressed DNA synthesis [ 150]. In a murine two-stage skin carcinogenesis model, topical application of luteolin prior to 12-tetradecanoylphorbol 13-acetate (TPA) treatment in DMBA-initiated mouse skin resulted in a significant reduction in tumor incidence and multiplicity, which is associated with inhibiting the inflammatory response and scavenging reactive oxygen radicals [ 151, 152]. In a colon carcinogenesis model induced by 1, 2-dimethyl hydrazine (DMH), luteolin (0.1, 0.2, or 0.3 mg/kg body weight/daily p.o.) significantly reduced colon cancer incidence when it was administered at either the initiation or post-initiation stages [ 153]. The results demonstrate that luteolin exerts chemopreventive and anticarcinogenic effects, in association with its antiperoxidative and antioxidant effects, against colon cancer [ 153]. People, especially in Asian countries, have been using various herbs and other plant parts to cure diseases for ages. However, the craze for utilizing plants, fruits, or even their extracts is the recent hype for curing inflammations, sleeping problems, and cancer. Autophagy has been identified as a potential approach for limiting the proliferation and viability of cancer cells. Autophagy is a catabolic process that provides energy during starvation. This energy is derived from the degradation of aged cells and organelles, in addition to the toxic cellular components. Autophagy begins with the disruption of mitochondria and various organelles in cytoplasm. The main role of autophagy is to maintain homeostasis of eukaryotic cells during abiotic and biotic stress. The cellular mechanism of autophagy includes the transferring of damaged cells and organelles and deleterious proteins into lysosomes for the onset of their degradation. The simple end products of degradation, such as amino acids are eventually recycled in the cells.
The flavonoid luteolin may also be able to reduce non-allergic inflammation, including in brain inflammation in multiple sclerosis (MS). Further evidence published in the journal Nutrition and Lifestyle in Neurological Autoimmune Diseases suggests that luteolin could reduce inflammation related to MS. Related research has demonstrated that luteolin could play a role in reducing inflammation in the gut. Gastrointestinal inflammation is linked to many serious diseases, including Crohn’s disease and cancers of the GI tract. Cancer After reading the names of the sources, it might seem that these are present in our daily diet. But here’s the thing, even though Luteolin’s source is quite common, we tend to get as less as 1mg per day, even with a typical diet. Introduction Besides, several metals and metal ions are known to trigger a series of events that cater to the production of ROS and generate oxidative stress in cells. Free radical scavenging by metal chelation serves as an attractive approach for exerting the antioxidant effect. Especially, the low molecular weight metal chelators have received a considerable attention as therapeutics that function by mitigating the oxidative stress generated by metal ions by scavenging the free radicals generated thereof. Luteolin serves as a good metal-chelating agent owing to the presence of dihydroxyl substituents on the aromatic ring framework. These groups can chelate a variety of divalent, trivalent and tetravalent metal ions including Zn(II), V(II), Cu(II), Fe(II), Sn(II), Fe(III), Cr(III), Vn(IV), and Mo(IV) [ 11]. Recently, the complexation of Mn(II) with luteolin has been reported through the carbonyl group and the adjacent hydroxyl group of latter [ 12]. This complex has been reported to show enhanced antioxidant activity as compared to the parent molecule itself. Luteolin-Mn(II) complex reversibly inhibited the xanthine oxidase in competitive manner, which is a main enzyme involved in the production of reactive oxygen species [ 13]. Hong Z, Cao X, Li N, Zhang Y, Lan L, Zhou Y, Pan X, Shen L, Yin Z, Luo L. Luteolin is effective in the non-small cell lung cancer model with L858R/T790M EGF receptor mutation and erlotinib resistance. Br J Pharmacol. 2014;171(11):2842–53.Studies performed on animal models indicate that luteolin may help reduce anxiety. Along with decreased levels of anxiety, luteolin could promote better social interaction. However, these studies were conducted on mice and do not necessarily translate to human populations. Side Effects of Luteolin Han K, Meng W, Zhang JJ, Zhou Y, Wang YL, Su Y, Lin SC, Gan ZH, Sun YN, Min DL. Luteolin inhibited proliferation and induced apoptosis of prostate cancer cells through miR-301. Onco Targets Ther. 2016;9:3085–94. Derived from the Sophora flower, the Luteolin in this complex is sourced at a purity level exceeding 98%, ensuring a potent and effective solution.
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