Fisetin treatment decreased senescent gene expressions and inflammasomes in other organs, such as the lung and the liver. Fisetin treatment represents a promising therapeutic strategy for age-related diseases.

Source from: Huard, Charles A et al. “Effects of Fisetin Treatment on Cellular Senescence of Various Tissues and Organs of Old Sheep.” Antioxidants (Basel, Switzerland) vol. 12,8 1646. 21 Aug. 2023, doi:10.3390/antiox12081646

Fisetin promotes hair growth by the same mechanism as dutasteride,and Fisetin is a strong human telomerase reverse transcriptase (hTERT) augmenting compound to promote hair growth of shaved skin.

Source from: Kubo, Chisato et al. “Fisetin Promotes Hair Growth by Augmenting TERT Expression.” Frontiers in cell and developmental biology vol. 8 566617. 15 Oct. 2020, doi:10.3389/fcell.2020.566617

The application of senolytics in the progeria-aged muscles can be an efficient strategy to remove senescent cells, including senescent Fibro-adipogenic progenitors (FAPs), which results in improved function of muscle progenitor/stem cells. The senescent FAPs can be a potential novel target for therapeutic treatment of progeria ageing related muscle diseases.

Source from: Liu, Lei et al. “Reduction of senescent fibro-adipogenic progenitors in progeria-aged muscle by senolytics rescues the function of muscle stem cells.” Journal of cachexia, sarcopenia and muscle vol. 13,6 (2022): 3137-3148. doi:10.1002/jcsm.13101

Targeting SnCs by using senolytic drugs (Fisetin) before or after pathogen exposure significantly reduced mortality, cellular senescence, and inflammatory markers and increased antiviral antibodies. Thus, reducing the SnC burden in diseased or aged individuals should enhance resilience and reduce mortality after viral infection, including that of SARS-CoV-2.

Source from: Camell, Christina D et al. “Senolytics reduce coronavirus-related mortality in old mice.” Science (New York, N.Y.) vol. 373,6552 (2021): eabe4832. doi:10.1126/science.abe4832

Fisetin may regulate the inflammatory process to produce beneficial actions in LPS-induced acute lung injury by inhibiting the expression of TLR4 and subsequently leads to the suppression of TLR4-mediated NF-κB pathway in lung tissues.

Source from: Huang, Wei et al. “Fisetin-treatment alleviates airway inflammation through inhbition of MyD88/NF-κB signaling pathway.” International journal of molecular medicine vol. 42,1 (2018): 208-218. doi:10.3892/ijmm.2018.3582

Fisetin activates ERK and induces cAMP response element-binding protein (CREB) phosphorylation in rat hippocampal slices, facilitates long-term potentiation in rat hippocampal slices, and enhances object recognition in mice.

Source from: Maher, Pamela et al. “Flavonoid fisetin promotes ERK-dependent long-term potentiation and enhances memory.” Proceedings of the National Academy of Sciences of the United States of America vol. 103,44 (2006): 16568-73. doi:10.1073/pnas.0607822103

Oral administration of fisetin to AD mice prevents the development of learning and memory deficits, this correlates with an increase in ERK phosphorylation along with a decrease in protein carbonylation, a marker of oxidative stress, and additional anti-inflammatory effects by reducing p25, alterations in global eicosanoid synthesis, and the maintenance of markers of synaptic function in the AD mice.

Source from: Currais, Antonio et al. “Modulation of p25 and inflammatory pathways by fisetin maintains cognitive function in Alzheimer's disease transgenic mice.” Aging cell vol. 13,2 (2014): 379-90. doi:10.1111/acel.12185

The cardiorotective effect of fisetin in the heart at doses of 10 and 20mg/kg via suppression of oxidative stress mediated apoptosis and inflammation and further showed the RAGE/NF-kB suppressing property of fisetin.

Source from: Garg, Shanky et al. “Fisetin attenuates isoproterenol-induced cardiac ischemic injury in vivo by suppressing RAGE/NF-κB mediated oxidative stress, apoptosis and inflammation.” Phytomedicine : international journal of phytotherapy and phytopharmacology vol. 56 (2019): 147-155. doi:10.1016/j.phymed.2018.09.187

Senescent immune cells, such as macrophages, are greatly involved in the development of muscle dystrophy by impacting the function of muscle stem cells, and the senolytic ablation of these senescent cells with fisetin can be an effective therapeutic strategy for improving function of muscle stem cells and phenotypes of dystrophic muscles.

Source from: Liu, Lei et al. “Senolytic elimination of senescent macrophages restores muscle stem cell function in severely dystrophic muscle.” Aging vol. 14,19 (2022): 7650-7661. doi:10.18632/aging.204275

Fisetin alleviates liver damage, cell apoptosis, and oxidative stress induced by liver IRI, at least through Nrf2/HO-1 signaling pathway, suggesting that fisetin could be considered as a targeted drug for liver IRI treatment.

Source from: Li, Zexin et al. “Protective Effects of Fisetin on Hepatic Ischemia-reperfusion Injury Through Alleviation of Apoptosis and Oxidative Stress.” Archives of medical research vol. 52,2 (2021): 163-173. doi:10.1016/j.arcmed.2020.10.009

Fisetin, when dosed orally and chronically in mice with type 1 diabetes, exerted analgesic effects on thermal hyperalgesia and mechanical allodynia. These pain-reducing actions can be achieved by preemptive treatment at lower doses than the doses required once sensitization was already established. Chronic fisetin treatment also displayed in diabetic mice beneficial actions on exacerbated oxidant stress, thereby reversing a pivotal pathophysiological process that leads to diabetic neuropathic pain. The analgesic actions of fisetin in diabetic mice may require antioxidant mechanisms and implicate the recruitment of downstream GABAA receptors in spinal cord.

Source from: Zhao, Xin et al. “Antinociceptive effects of fisetin against diabetic neuropathic pain in mice: Engagement of antioxidant mechanisms and spinal GABAA receptors.” Pharmacological research vol. 102 (2015): 286-97. doi:10.1016/j.phrs.2015.10.007

Fisetin decreases inflammatory responses induced by keratinocytes and CD4+ T lymphocytes, suppresses the Akt/mTOR signaling pathway, promotes autophagy and differentiation, and improves both the immune and epidermal phenotypes of IMQ-induced psoriasis-like skin lesions in mice, provide the pre-clinical evidence for further development of fisetin as a potential natural product- derived anti-psoriatic agent

Source from: Roy, Tithi et al. “Dual targeting of mTOR/IL-17A and autophagy by fisetin alleviates psoriasis-like skin inflammation.” Frontiers in immunology vol. 13 1075804. 18 Jan. 2023, doi:10.3389/fimmu.2022.1075804

Fisetin attenuated UVB-induced oxidative stress, photodamage, and inflammation by modulating the expression of MMPs, MAP kinases, AP-1, COX-2, and p-CREB Ser-133. In addition, fisetin effectively restored UV-induced IκB degradation, resulting in NF-κB inhibition.

Source from: Chiang, Hsiu-Mei et al. “Fisetin Ameliorated Photodamage by Suppressing the Mitogen-Activated Protein Kinase/Matrix Metalloproteinase Pathway and Nuclear Factor-κB Pathways.” Journal of agricultural and food chemistry vol. 63,18 (2015): 4551-60. doi:10.1021/jf502500t

Fisetin treatment reduced the number of senescent TECs and myofibroblasts, thus attenuating kidney fibrosis, decreasing SASP expression, and increasing TEC proliferation.

Source from: Ijima, Shogo et al. “Fisetin reduces the senescent tubular epithelial cell burden and also inhibits proliferative fibroblasts in murine lupus nephritis.” Frontiers in immunology vol. 13 960601. 17 Nov. 2022, doi:10.3389/fimmu.2022.960601

Provide evidence of a novel activity of the flavonoid fisetin that suppresses the expression of TH2-type cytokines (IL-4, IL-13, and IL-5) by basophils.

Source from: Higa, Shinji et al. “Fisetin, a flavonol, inhibits TH2-type cytokine production by activated human basophils.” The Journal of allergy and clinical immunology vol. 111,6 (2003): 1299-306. doi:10.1067/mai.2003.1456

Fisetin excretes cholesterol through enhancing TICE by activation of intestinal PPARδ and could be used as functional dietary supplement for eliminating cholesterol and reducing the incidence of cardiovascular diseases.

Source from: Guo, Yao et al. “Fisetin, a dietary flavonoid, promotes transintestinal cholesterol excretion through the activation of PPARδ.” Food research international (Ottawa, Ont.) vol. 175 (2024): 113783. doi:10.1016/j.foodres.2023.113783