Title : Luteolin as a bioactive compound for the neurodegenerative chemoprevention of cancer treatment
Abstract:
Luteolin (3′,4′,5,7-tetrahydroxyflavone), is a bioactive compound which is obtained from celery broccoli, green pepper, dandelion and chrysanthemum flowers and so on and can also be extracted from as peanut husk, carrot leaves, broccoli waste etc. is an extensively researched flavonoid in different fields like nutrition, pharmacology, medicine etc. It is seen as heat stable in nature; Thus, interestingly, the molecule cannot be lost during cooking processes. In traditional medicine of Chinese and Ayurvedhi, it is also used to treat hypertension, cancer and inflammatory disorders. Luteolin has shown multiple useful effects such as anti-inflammatory, anti-tumor, anti-cardiovascular, and anti-neurodegenerative diseases among which the interest of this review was the neurodegenerative chemo-preventive effect of luteolin in the cancer treatment. Luteolin has been tested for the level of toxicity as well in rat and mice trails which was reported higher than 2500 and 5000 mg/kg, respectively, which was shown to be equal to approximately 219.8-793.7 mg/kg in humans. One of the deadliest diseases currently affecting the humankind is cancer with a global death ratio of one out of six people die. The chemo treatment of cancer propagates the prevalence of neurodegenerative disorders in cancer patients including Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, and multiple sclerosis affecting millions of people around the world. Recently many studies have focused on natural bioactive compounds that can be used in adjuvant therapy in the inhibition of these neurodegenerative disorders.
The bioactive compounds mainly include flavonoids among which the focus of the review was luteolin, it possesses various chemo-preventive activities such as anti-oxidant, anti-cancer, anti-microbial, anti-diabetic, anti-inflammatory and the neuroprotective effect, which was the focus of the review. Increasing evidence from previous researches suggests that luteolin was able to protect against neurodegenerative effects of chemotherapy. It showed a protective effect to neuro system by inhibiting the NFĸB, MAPK/AP-1, and JAK-STAT pathways suppressing neuro-inflammation and apoptotic signaling and by activating Nrf2/ARE signaling by luteolin enhances cellular antioxidant defenses, thereby mitigating neuronal damage. Emerging evidences also suggested that luteolin effectively reduced neurotoxic effects by regulating inflammatory cytokine production, stabilizing mitochondrial function, and maintaining redox homeostasis. Preclinical studies have provided robust evidence supporting the bioactive compound luteolin ability in mitigating neurodegeneration suggesting it can be used in future as a neurodegenerative chemo-prevention agent. Despite these preclinical trials, the therapeutic effect of luteolin is hindered by its poor aqueous solubility and rapid metabolism which limits it bioavailability (approx. 17.5% for free luteolin). This hinderance has encouraged the innovation of advanced delivery system such as ionic gelation microencapsulation to improve the stability and enhance the bioavailability of the luteolin. Researches have reported different nanoparticulate of luteolin, which includes chitosan coated luteolin and luteolin loaded nano-capsules, with entrapment efficiency of 65.55% and 95.37% and 54 % and 100 %, respectively, they have shown increased bioavailability and increased stability of the compound. In the future, researches should focus on optimizing these luteolin delivery platforms to translate luteolin’s chemo preventive potential into viable human neurotherapeutics.
