Therapeutic Potential and Pharmaceutical Development of a Multitargeted Flavonoid Phloretin

Abstract

Phloretin is a flavonoid of the dihydrogen chalcone class, present abundantly in apples and strawberries. The beneficial effects of phloretin are mainly associated with its potent antioxidant properties. Phloretin modulates several signaling pathways and molecular mechanisms to exhibit therapeutic benefits against various diseases including cancers, diabetes, liver injury, kidney injury, encephalomyelitis, ulcerative colitis, asthma, arthritis, and cognitive impairment. It ameliorates the complications associated with diabetes such as cardiomyopathy, hypertension, depression, memory impairment, delayed wound healing, and peripheral neuropathy. It is effective against various microbial infections including Salmonella typhimurium, Listeria monocytogenes, Mycobacterium tuberculosis, Escherichia coli, Candida albicans and methicillin-resistant Staphylococcus aureus. Considering the therapeutic benefits, it generated interest for the pharmaceutical development. However, poor oral bioavailability is the major drawback. Therefore, efforts have been undertaken to enhance its bioavailability by modifying physicochemical properties and molecular structure, and developing nanoformulations. In the present review, we discussed the pharmacological actions, underlying mechanisms and molecular targets of phloretin. Moreover, the review provides insights into physicochemical and pharmacokinetic characteristics, and approaches to promote the pharmaceutical development of phloretin for its therapeutic applications in the future. Although convincing experimental data are reported, human studies are not available. In order to ascertain its safety, further preclinical studies are needed to encourage its pharmaceutical and clinical development.

Concomitant inhibition of TLR-4 and SGLT2 by phloretin and empagliflozin prevents diabetes-associated ischemic acute kidney injury

“…24 Conventional treatment options do not fulfill all therapeutic needs; hence, most diabetic patients are taking complementary alternative medicines for more benefits. 25,26 Phloretin is one such nutritional supplement that can be taken along with other conventional medicines to fulfill that gap against AKI under diabetic conditions. Considering its multidimensional therapeutic effects (anti-diabetic, anti-inflammatory, anti-cancer, and hepatoprotective), phloretin was also recently studied as a TLR4 inhibitor.…”

Protective Effect of Phloretin against Hydrogen Peroxide-Induced Oxidative Damage by Enhancing Autophagic Flux in DF-1 Cells

“…At last, although PHL has a variety of biological activities, its application as a drug and additive has been restricted due to its low aqueous solubility, poor absorption and bioavailability, and PHL is quickly excreted from the body after absorption [54]. At present, the problem of poor absorption and bioavailability of PHL has been solved by changing its dosage form such as self-nano emulsion [55], liposome [56], and microemulsion formulation [57].…”

A Comprehensive Review of Various Therapeutic Strategies for the Management of Skin Cancer

“…Phloretin is a naturally occurring dihydrochalcone obtained from various vegetables and fruits, mostly found in Manchurian apricots and apple tree leaves . It possesses various therapeutic activities including immunosuppressant, hepatoprotective, antioxidant, cardioprotective, and antidiabetic properties . The study showed that phloretin reduces sunburn which occurs due to UV radiation by suppressing the expression of matrix metalloproteinase-9 and inhibiting thymidine dimer formation.…”