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Synthetic Compounds vs. Phytochemicals for the Treatment of Human Cutaneous Malignant Melanoma
Published in Namrita Lall, Medicinal Plants for Cosmetics, Health and Diseases, 2022
Jacqueline Maphutha, Namrita Lall
Fisetin, a phytochemical present in strawberries, onions, grapes and persimmons, inhibited the proliferation of A375 cells at concentrations ranging from 20–80 µM. The IC50 values were 38.1 µM (24 h) and 20.3 µM (48 h), respectively. Furthermore, fisetin at concentrations of 40 µM and 80 µM were used to treat melanoma reconstructs. After 16 days, the fisetin-treated melanoma constructs had undetectable lesions compared to the control, where several tumor nests were evident. The inhibition of tumor growth in both the melanoma monolayer (A375) and 3-D melanoma constructs was through the downregulation of mTOR, Akt and PI3K. These were determined through immunohistochemical analysis of fisetin-treated melanoma constructs, Western blotting using whole-cell lysates from fisetin (20–40 µM) treated A375 and 451 Lu melanoma cells (Syed et al., 2014). Fisetin at concentrations ranging from 5–20 µM, significantly decreased the phosphorylation of MEK 1/2 and ERK 1/2 in A375 and RPMI-7951 cells when exposed for a 24-hour period (Pal et al., 2014).
Involvement of Dopamine with Various Cancers
Published in Nira Ben-Jonathan, Dopamine, 2020
All five DAR subtypes were expressed in HepG2 cells, an immortalized human liver carcinoma cell line [58]. Cell treatment with the D1R agonists SKF82958 or SKF38393 increased D1R expression and stimulated SULT2A1 sulfotransferase activity. These effects were partially blocked by co-treatment with the specific D1R antagonist SCH23390. These data suggest that D1R is involved in metabolism of drugs and xenobiotics through up-regulation of SULT2A1. 3,3′,4′,7-Tetrahydroxyflavone (fisetin) is an abundant flavonoid that is produced in some vegetables and fruits. It has a similar structure to DA and appears to mimic DA action [59]. Both fisetin and bromocriptine, albeit at high micromolar doses, suppressed the proliferation, migration, and invasion of liver cancer cells. Growth of orthotopically implanted liver cancer xenografts was inhibited by fisetin administration, which was accompanied by higher levels of serum and tumor DA and increased survival rate of the mice [59]. The authors concluded that DA represents a novel therapeutic strategy for suppressing liver cancer progression.
Plant-Based Natural Products Against Huntington’s Disease: Preclinical and Clinical Studies
Published in Megh R. Goyal, Hafiz Ansar Rasul Suleria, Ademola Olabode Ayeleso, T. Jesse Joel, Sujogya Kumar Panda, The Therapeutic Properties of Medicinal Plants, 2019
Banadipa Nanda, Samapika Nandy, Anuradha Mukherjee, Abhijit Dey
Fisetin, a dietary bioflavonoid that naturally occurs in vegetables and fruits, has a neuroprotective function as an anti-inflammatory agent against aluminum chloride (AlCl3)-induced neurotoxicity [94]. In PC12 cells and mutant Httex1 Drosophila model and R6/2 HD mouse, fisetin prevented mHtt-mediated damage via up-regulation of extracellular signal-regulated kinases (ERK) [72].
PM2.5 from diesel exhaust attenuated fisetin mediated cytoprotection in H9c2 cardiomyocytes subjected to ischemia reoxygenation by inducing mitotoxicity
Published in Drug and Chemical Toxicology, 2023
Bhavana Sivakumar, Gino A. Kurian
Air pollution related toxicity can be significantly reduced by flavonoids like quercetin (Izawa et al. 2008, Mi et al. 2010). Fisetin (5-deoxyquercetin), a form of quercetin is expected to be a promising agent against IR injury. Moreover, the ability of fisetin to attenuate ischemia reperfusion injury in rat model is already reported (Shanmugam et al. 2018). In agreement with the early report, fisetin significantly reduced IR in H9c2 cells, but it failed to render protection when the cells were administered with DPM. Evidence from literature showed the ability of fisetin to provide cardio protection by reducing oxidative stress, improving mitochondrial function and activating pro survival signaling pathways (Shanmugam et al. 2021). In this line of thought, we evaluated the antioxidant status, mitochondrial ETC activity and protein expression of PI3K/Akt (pathways activated by fisetin) in DPM exposed H9c2 cells subjected to IR. Interestingly, we noted that fisetin failed to reverse these parameters in DPM treated cells whereas they could successfully alter the detrimental changes to beneficial state in the absence of DPM.
Bazi Bushen capsule attenuates cognitive deficits by inhibiting microglia activation and cellular senescence
Published in Pharmaceutical Biology, 2022
Chuanyuan Ji, Cong Wei, Mengnan Li, Shuang Shen, Shixiong Zhang, Yunlong Hou, Yiling Wu
Notably, several small molecules originating from herbal medicines have been proven to be effective in delaying ageing and exert protective effects on neurodegenerative diseases (Tewari et al. 2018; Kim and Kim 2019; Cui et al. 2020; Ahmad et al. 2021). Intermittent treatment of APP/PS1 mice with the FDA-approved combination of dasatinib and quercetin was found to selectively clear senescent oligodendrocyte progenitor cells and to ameliorate both cognitive impairments and Aβ plaque-associated inflammation (Zhang et al. 2019). Quercetin is designated as a senolytic due to its ability to prolong healthy lifespan and reduce the likelihood of developing age-related diseases by selectively killing senescent cells (Zhu et al. 2015). More recently, fisetin has been identified as a new senolytic that is capable for protecting neurons and improving cognitive function via anti-inflammatory processes, promotion of synaptic plasticity, and elimination of cellular senescence (Singh et al. 2018; Yousefzadeh et al. 2018).
Fisetin, a potential caloric restriction mimetic, modulates ionic homeostasis in senescence induced and naturally aged rats
Published in Archives of Physiology and Biochemistry, 2022
Sandeep Singh, Geetika Garg, Abhishek Kumar Singh, Shambhoo Sharan Tripathi, Syed Ibrahim Rizvi
Fisetin (3,7,3′,4′-tetrahydroxyflavone) is one of the major polyphenolic flavonoid found in fruits and vegetables such as apples, grapes, persimmons, strawberries, cucumbers etc. (Khan et al.2013). Based on studies involving different model systems, fisetin has been reported to exert numerous beneficial biological activities including antioxidant, anti-inflammatory, anti-angiogenic, hypolipidemic, neuroprotective, and antitumor (Naeimi and Alizadeh 2017). Multiple mechanisms of actions have been proposed to explain diverse health-promoting effects of fisetin such as antioxidant and activation of sirtuins (Currais et al.2017, Yen et al.2017). Interest in the biological activity of fisetin has recently been in focus due to its role as a potential caloric restriction mimetic (CRM) (Singh et al.2018). In a recent report we have shown that fisetin effectively alleviates ROS generation, lipid peroxidation, protein oxidation and eryptosis in erythrocytes as well as improve the activities of non-enzymatic antioxidants such as glutathione and total thiol (Singh et al.2019). However, the molecular targets of fisetin that mediate its diverse biological effects remain speculative.