The Source and Biological Activity of Fisetin

Description

Fisetin, chemically 3,7,3′,4′-tetrahydroxyflavone or 7,3′,4′-flavon-3-ol is a polyhydroxy flavonoid with various pharmacological potentials like antioxidant, anti-inflammatory, anti-cancer, neuroprotective and is used in vascular dementia[1].

Source

Fisetin is a dietary flavonoid found in various fruits (strawberries, apples, persimmons, mangoes, kiwis, and grapes), vegetables (tomatoes, onions, and cucumbers), nuts, and wine. The concentration of Fisetin in these sources ranged from 2 to 160 μg/g of the material. The most Fisetin is present in strawberries, apples, and persimmon. Fisetin's average daily intake has been estimated to be 0.4 mg[2]. It is also abundantly present in various acacias trees and shrubs belonging to the Fabaceae family, such as Acacia greggii, Acacia berlandieri, Gleditschia triacanthow, Anacardiaceae family members such as the parrot tree (Butea fronds), the honey locust (Gleditsia triacanthos). In addition, Fisetin can be found in the Quebracho colorado and Rhus cotinus, lac tree (Rhus vemiciflua Stokes) extract, smoke tree (Cotinus coggygria), Pinopyta species like Callitropsis nootkatensis (yellow cypress) and other trees and shrubs.

Biological activity

Because of its various bioactive properties, Fisetin is considered a health-promoting factor agent, and some dietary supplements containing Fisetin have been marketed. Fisetin is a flavonol with a diphenyl propane structure containing two aromatic rings linked via an oxygenated heterocyclic ring. It is supplemented with four OH group substitutions and one oxo group. The bioactivity of Fisetin mainly depends on the OH groups at 3, 7, 3′, and 4′ positions, the carbonyl group at four positions and with the double bond between C2 and C3; this double bond (C2 = C3), and the OH group at C-7, as well as an OH group at C3' in the ring B and at C3 are associated with the antioxidant activity of Fisetin.

Fisetin activates the intrinsic apoptosis pathway, in part through an increase of expression of pro-apoptotic proteins BAD, BAX, BID, BIM, and reduced expression of anti-apoptotic BCL-2, BCL-w, and CLAP-2, HSP70, and IAP-family members LIVIN, SURVIVIN, and XIAP, and associated with a reduction in mitochondrial membrane potential[3].

Toxicity

Generally, due to their extensive distribution in dietary plants, flavonoids are supposed to be safe and associated with little or no toxicity. Oral administration of Fisetin in animal studies has been around 5–25 mg/kg, while its intraperitoneal doses range from 0.3 to 3 mg/kg dissolved by dimethyl sulfoxide[1]. In some clinical trials, the oral dose of 20 mg/kg/day for two consecutive days and/or two consecutive months is mainly used. In the acute toxicity study of Fisetin, there were no toxicity signs/symptoms like decreased body weight, diarrhea, respiratory distress, restlessness, contractions, and coma. Furthermore, an acute toxicity study did not show signs of toxicity at doses up to 2 g/kg with no toxicity in the histopathological analysis of the heart, lungs, kidneys, liver, stomach, intestines, spleen, and reproductive organs.

References

[1] Syed Shams Ul Hassan. “The neuroprotective effects of fisetin, a natural flavonoid in neurodegenerative diseases: Focus on the role of oxidative stress.” Frontiers in Pharmacology 13 (2022): 1015835.

[2] H. Pal, F. Afaq, Ross L. Pearlman. “Fisetin and Its Role in Chronic Diseases.” Advances in experimental medicine and biology 928 (2016): 213–244.

[3] Nehlin, Jan O. “Senolytic and senomorphic interventions to defy senescence-associated mitochondrial dysfunction.” Advances in protein chemistry and structural biology 136 (2023): 217–247.