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Innovative Medicines & Omics Current approach in the management of kidney disease

inflammation, anti-oxidative, anti-diabetic, anticancer, decreased levels of miR-192, a crucial miRNA involved in
and nephroprotective action. Phytocompounds, including the development and exacerbation of nephropathy, and
flavonoids, have the ability to both directly and indirectly the increase of SIP1. Further research is required to assess
reduce renal damage. Significant biological benefits of troxerutin’s effects on collagen levels and ECM proteins, to
flavonoids in CKD include reducing oxidative stress, evaluate its potential as a natural preventive component
immunological modulation, antioxidant actions, anti- that can help avoid renal problems Similarly, research
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inflammation, anti-apoptosis, gut microbiota regulation, has found that troxerutin may reduce cisplatin-induced
anti-diabetic, and antihypertensive; they also help to relieve kidney cell death in rats by increasing microtubule-
renal fibrosis. In addition, they serve as intermediaries for associated protein 4 (MAP4) expression and activating the
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the activation of the Nrf2 antioxidant action, which lowers PI3K/AKT signaling pathway, one of the most effective
oxidative stress. 50 intracellular pathways for enhancing cell survival. In
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addition, troxerutin has been demonstrated to prevent
3.7.1. Troxerutin renal damage caused by drug-induced cytotoxicity in rat
Troxerutin, a derivative of the naturally occurring models by increasing the antioxidant defense system and
bioflavonoid and found in tea and coffee. The ability of reducing lipid peroxidation.
troxerutin to reduce drug-induced nephrotoxicity has
been investigated in earlier research. Troxerutin reduces 3.7.2. Fisetin
the oxidative stress induced by cisplatin and methotrexate Fisetin, a flavonoid is isolated from a variety of fruits,
by inhibiting lipid peroxidase and nicotinamide adenine vegetables, seaweeds, and persimmons, as well as
dinucleotide phosphate oxidase 1 (NOX-1), restoring strawberries, apples, and onions. After being given
superoxide dismutase (SOD), GSH, and glutathione orally to mice, it can penetrate the blood-brain barrier
peroxidase (GPx) levels, and activating the Nrf2/HO-1 and accumulate in the brain. Fisetin is rapidly bio-
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signaling pathway. Long-term administration of transformed through conjugative metabolism, mostly
2,2,4,4-tetrabromodiphenyl ether (PBDE-47) increased by glucuronidation, sulfation, and methylation in
Kelch-like ECH associated protein 1 (KEAP1) levels, the liver, and is eliminated through urine and feces.
leading to Nrf2 ubiquitination and degradation, which Cytochrome P450 enzymes are among the Phase I
in turn decreased Nrf2 activity and its downstream genes and II metabolic enzymes involved in the metabolic
in the kidneys of mice, including catalase, GPx, SOD, process. In vitro research demonstrated that fisetin,
and heme oxygenase 1 (HO-1). Nevertheless, troxerutin like other flavonoids, inhibits a number of cytochrome
enhanced Nrf2 activity, prevented the negative effects P450 enzymes, potentially leading to drug interactions
of PBDE-47 and partially mimicking the action of when combined with other medications. Fisetin inhibits
carbobenzoxy-l-leucyl-l-leucinal (MG132). In the liver of myeloperoxidase (MPO) activity, inflammatory cytokines,
mice, PBDE-47 was found to increase caspase-3 action and renal production of iNOS, thereby protecting the
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and the levels of B-cell lymphoma 2 (Bcl-2)-associated kidney from drug-induced renal impairment. In the
X (Bax) and Bcl-2. Activated TGF-β has been linked to context of ureteric obstruction, TGF-β is essential for
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the pathogenesis of diabetic KD. TGF-β triggers receptor cell development, proliferation, differentiation, apoptosis,
activation through autocrine and paracrine pathways, immunological response, and renal fibrosis. TGF-β1
initiating a signaling cycle that ultimately regulates the binds to its receptor, TβRII, causing phosphorylation of
production of ECM, leading to the impaired mesangial cell TβRI and activation of TGF-β1 downstream effectors,
function. As nephropathy progresses, TGF-β builds up in including suppressor of mothers against decapentaplegic
mesenchymal cells and influences the synthesis of ECM (SMAD). Canonical pathway involves receptor-regulated
proteins, such as collagen I and collagen II. TGF-β inhibits SMADs (R-SMADs), such as SMAD2/3, which are both
E-box repressors like δEF1 and SMAD interacting protein overexpressed in human fibrotic kidneys, and responsible
1 (SIP1), which regulate collagen gene expression. The role for TGF-β1 signaling transduction. Non-canonical SMAD-
and target of certain kidney-dwelling microRNAs, such as independent pathways, including Rho-like GTPase,
miR-192, miR-194, miR-204, and miR-215, in the setting PI3K/AKT, Jun N-terminal kinases (JNKs), and MAPK,
of nephropathy have received significant attention. Since also regulate gene transcription, promoting apoptosis
miR-192 has been shown to target SIP1, the low levels of and the epithelial-to-mesenchymal transition (EMT).
SIP1 observed in diabetics may validate the interaction In experimental models, fisetin injections (25 mg/kg)
between elevated TGF-β and miR-192, leading to low administered intraperitoneally one hour prior to surgery
levels of SIP1 in renal tissue. Troxerutin’s effects on the and every other day for seven days. In addition, fisetin
kidney in a diabetic rat model appear to be mediated by pretreatment (40 µM) dramatically decreased TGF-β1-

Volume 2 Issue 1 (2025) 42 doi: 10.36922/imo.4969