Page 50 - IMO-2-1

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

sepsis models by specifically inhibiting cyclooxygenase-2 by lead exposure, preventing nephrotoxicity. Similarly,
65
(COX-2) and ameliorating liver damage in animal studies. quercetin’s anti-apoptotic and antioxidant properties
Moreover, kaempferol decreased the excessive production protect against kidney damage caused by titanium dioxide
of TNF-α, IL-1β, IL-6, ICAM-1, and VCAM-1 in LPS- nanoparticles. In addition, quercetin treatment improved
treated groups. Kaempferol reduces COX-2 expression kidney function by increasing serum SOD and lactate
while simultaneously inhibiting the production of MCP-1, dehydrogenase levels, and total antioxidant activity,
ICAM-1, and VCAM-1. Oxidative stress is triggered by demonstrating nephroprotective properties. This activity is
61
major signaling pathways, such as the MAPK signaling believed to be caused by quercetin’s ability to decrease the
cascades. Activation of these proteins alters stress response production of malondialdehyde and its capacity to remove
pathways unique to particular cell types and conditions, ROS. Nrf2 and HO-1 are primarily activated by free
causing apoptosis through phosphorylation of JNK and radicals and ROS. The Nrf2/HO-1 pathway may be crucial
P38. As a biological mediator between oxidative stress for boosting the antioxidant moieties of glutathione (GSH),
and the pathogenic processes, ASK1 could be a potential SOD, and GPx in relation to nephrotoxicity. In animals
therapeutic target to stop oxidative stress-related kidney with copper sulfate-induced and gentamicin-induced
66
damage. By blocking the ROS-mediated MAPK signaling kidney damage, quercetin significantly increased the
pathway, kaempferol lessens drug-induced renal tubular mRNA expression of HO-1 and Nrf2 when administered at
damage. The cytoplasm contains the inhibitory protein a dose of 50 mg/kg. 67-69 The Food and Drug Administration
62
IκBα, while cisplatin-mediated ROS trigger signaling has classified quercetin as “Generally Recognized as Safe”
cascades involving p53, MAPK, and NF-κB. It has been for use as a dietary supplement due to its well-established
demonstrated that phosphorylation of IκBα contributes to safety and tolerability profile in humans. Another study
the activation of NF-κB, which translocates to the nucleus reported that myricetin is a bioactive phytocompound that
and activates inflammation-related genes, causing damage has historically been used to treat a variety of ailments,
to renal cells. Kaempferol modulates NF-κB levels by including malaria, dysentery, diarrhea, and hypertension.
preventing IκB kinase (IKK) phosphorylation and IκBα Different parts of the plant, such as its fruits, bark, and
degradation, thereby reducing the risk of cisplatin-induced leaves, have been utilized in these treatments. Other
kidney damage. According to Yuan et al., calcium oxalate reported uses include antihypertensive and vasodilatory
63
(CaOx) crystal deposition and crystal-induced renal properties, analgesic and anti-inflammatory properties,
TEC injury are the main factors to the development of antimalarial activity, and antidiabetic properties.
51
CaOx nephrolithiasis. Excess ROS generated during Flavonoids are potential substances to explore further
oxidative stress is regulated by NOX. Renal oxidative for the development of innovative CKD therapy agents.
stress and inflammation have been associated with However, the dearth of clinical studies implies that further
elevated NOX2 expression. The activation of the NOX research is required before flavonoids can be applied in
isoenzyme suppresses the oxidative and inflammatory medical treatments. Finding the metabolites produced
damage produced by the crystals, as well as the generation after dosage and increasing bioavailability is also essential,
of adhesion molecules, by downregulating the NOX2 as they could increase the advantages of flavonoids. A
70
signaling pathway. Kaempferol may have a significant role flavone called luteolin, which is naturally present in various
in reducing the quantity of CaOx crystals that deposit plants, has several pharmaceutical properties, like anti-
in the renal cell. Nevertheless, kaempferol treatment inflammatory effects. It also lessens kidney damage caused
64
decreased production of proinflammatory cytokines such by mercuric chloride. Luteolin decreases total TNF-α
as TNF and MPO, which lessens leukocyte infiltration and expression and several other indicators of inflammation
kidney damage. In addition, kaempferol regulated NF-kB by blocking NF-kB and activating the Nrf2 pathway. In
71
levels, inhibited the activation of the IKK, and reduced the Middle East, it has been used as traditional medicine
drug-induced renal inflammation. since ancient times. The primary aglycones found are
rhamnocitrin, kaempferol, quercetin, and rhamnetin.
3.7.4. Other bioactive compounds Renal colic and its associated symptoms were treated by the
Quercetin, a flavonol has been shown to protect DNA ancient Egyptians with a fruit decoction that also relieved
by lowering oxidative stress. In kidney damage caused prostatic pain, urolithiasis, and kidney inflammation.
by ionizing radiation, quercetin inhibits neutrophil Raising urine pH and citrate concentration, reducing urine
infiltration and subsequent release of proinflammatory oxalates, and protecting renal epithelial cells from calcium
biomarkers, reducing oxidative stress-related DNA oxalate monohydrate crystals have been shown to limit
damage and apoptosis. Moreover, quercetin reduced the oxalate formation associated with the formation of
oxidative stress, ROS, and thiobarbituric acid induced kidney stones. 72,73 Among the Lespedeza species, Lespedeza

Volume 2 Issue 1 (2025) 44 doi: 10.36922/imo.4969