Biochanin A mitigates ulcerative colitis and intestinal inflammation in mice by inhibiting MAPK/NF-kB (p65) axis.

Ulcerative colitis (UC) is a chronic problem of the intestine and relapsing in nature. Biochanin A is a nature-derived isoflavonoid and has numerous bioactivities. However, its role against UC and intestinal inflammation remains obscure. We aimed to comprehensively explore the pharmacological effect of biochanin A in alleviating colitis and to evaluate the potential mechanisms. Initially, we explored the anti-inflammatory action of biochanin A (15, 30, and 60 µM) by employing lipopolysaccharide (LPS)-activated RAW 264.7 cells. In RAW 264.7 cells under LPS stimulation, biochanin A inhibited the elevation of reactive oxygen species (ROS) (p < 0.0001), interleukin (IL)-1ß (p < 0.0001), IL-18 (p < 0.01), and tumor necrosis factor (TNF)-α (p < 0.01) release, nitrite production (p < 0.0001), and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins. Next, we studied the effectiveness of biochanin A (20 and 40 mg/kg) in mouse colitis induced with dextran sulfate sodium (DSS) by assessing colon length, disease activity index (DAI) scoring, and performing colonoscopy and histological analysis. The pro-inflammatory cytokines were estimated using ELISA. Western blot studies were performed to assess underlying mechanisms. In mice, biochanin A treatment alleviated DAI score (p < 0.0001), restored colon length (p < 0.05) and morphology, and re-established colon histopathology. Biochanin A affects the phosphorylation of proteins associated with NF-κB (p65) and mitogen-activated protein kinase (MAPK) axis and regulates colonic inflammation by reducing the expression of inflammatory cytokines and myeloperoxidase (MPO) activity. Altogether, our findings support the idea that the anticolitis potential of biochanin A is allied with anti-inflammatory activity by inhibiting the MAPK/NF-κB (p65) axis. Hence, biochanin A may be an alternative option to alleviate the risk of colitis.

Design, synthesis, and histone deacetylase inhibition study of novel 4-(2-aminoethyl) phenol derivatives.

Histone deacetylases (HDACs) have been identified as promising targets for anticancer treatment. The study demonstrates virtual screening, molecular docking, and synthesis of 4-(2-aminoethyl) phenol derivatives as HDAC inhibitors. The virtual screening and molecular docking analysis led to the identification of 10 representative compounds, which were evaluated based on their drug-like properties. The results demonstrated that these compounds effectively interacted with the active site pocket of HDAC 3 through π-stacking, Zn2+ coordination, hydrogen bonding, and hydrophobic interactions with catalytic residues. Furthermore, a series of 4-(2-aminoethyl) phenol derivatives were synthesized, and their HDAC inhibitory activity was evaluated. Compounds 18 and 20 showed significant HDAC inhibitory activity of 64.94 ± 1.17% and 52.45 ± 1.45%, respectively, compared to the solvent control. The promising results of this study encourage further research on 4-(2-aminoethyl) phenol derivatives and may provide significant insight into the design of novel small molecule HDAC inhibitors to fight against target-specific malignancies of chronic obstructive pulmonary disease and nonsmall cell lung cancer in the future.

Colon-targeted delivery of niclosamide from solid dispersion employing a pH-dependent polymer via hotmelt extrusion for the treatment of ulcerative colitis in mice.

Niclosamide (NCL) is repurposed to treat inflammatory bowel disease due to its anti-inflammatory properties and potential to reduce oxidative stress. This therapeutic activity remains challenging if administered directly due to its low solubility and high recrystallization tendency in gastric pH. Solid dispersions using pH-dependent polymer will be a better idea to improve the solubility, dissolution and targeted delivery at the colon. Hot melt extrusion was used to formulate a solid dispersion with 30% NCL utilising hydroxypropyl methylcellulose acetate succinate as a pH-dependent polymer. In vitro drug release studies revealed formulation (F1) containing 10%w/w Tween 80 showed minimal release (2.06%) at the end of 2 h, followed by 47.87% and 82.15% drug release at 6 h and 14 h, respectively, indicating the maximum amount of drug release in the colon. The drug release from the formulations containing no plasticiser and 5%w/w plasticiser was comparable to the pure crystalline drug (approximately 25%). Solid-state analysis confirmed particle conversion of crystalline NCL to amorphous form, and the optimised formulation was stable for 6 months without significant changes in dissolution profile. In contrast to pure NCL, the F1 formulation substantially reduced the disease activity index, colonic inflammation, histological alterations and oxidative damage in colitis mice. These findings reveal that the prepared formulation can potentially deliver the drug locally at the colon, making it an effective tool in treating ulcerative colitis.

Folic acid-conjugated long circulating co-encapsulated atorvastatin and quercetin solid lipid nanoparticles: pharmacokinetics and biodistribution in rats.

Background: Solid lipid nanoparticles (SLNs) have emerged as effective carriers for the simultaneous delivery of two drugs. Moreover, the surface modification of SLNs enhances their targetability and minimizes side effects, rendering them a promising and dynamic strategy for addressing various life-threatening diseases. The assessment of pharmacokinetic parameters is a critical aspect of this approach. In the present study, we report the development and validation of an LC-MS/MS-based bioanalytical method for the quantification of Atorvastatin (ATR) and Quercetin (QUER) encapsulated in folic acid-modified SLNs as a drug delivery system to estimate their pharmacokinetics and tissue distribution. Method: FA-SLNs were synthesized by amide linkage formation (carbodiimide reaction) and tested for their haemocompatibility. Further, an LC-MS/MS method was developed on a C18 (3 × 100 mm, 2.7 µm) column using 0.1% v/v formic acid in water and acetonitrile as the mobile phase with a 0.3 mL min-1 flow rate. For detection, analytes were ionized using an electron spray ionization (ESI) source in multiple reaction monitoring (MRM) mode. MRM for the ATR (559.0 → 440.2) m/z and IS (482.1 → 257.8) m/z in positive polarity, and QUER (301.9 → 151.0) m/z in negative polarity were optimized. Results: Pharmacokinetics studies demonstrated an increase in the half-lives of ATR and QUER of about 6.4-fold and 5.7-fold, respectively, from FA-SLN compared to pure drugs. Further, the active targeting facilitated by FA conjugation showed increased mean residence time (MRT) and decreased clearance time, resulting in long circulation time without the enhanced retention of drugs in the tissues of rats. These findings underscore the potential of FA-modified ATR and QUER-loaded SLNs as an advanced drug delivery strategy in improving the therapeutic outcomes.

Nuciferine inhibits TLR4/NF-κB/MAPK signaling axis and alleviates adjuvant-induced arthritis in rats.

Rheumatoid arthritis is an inflammatory condition primarily affecting the joints. Nuciferine (NCF), a key bioactive aporphine alkaloid biosynthesized in lotus leaves, exhibits promising anti-inflammatory and antioxidant properties. In this study, we investigated whether NCF could alleviate inflammatory arthritis conditions in a complete Freund's adjuvant (CFA)-mediated arthritis model in rats. The arthritis model was established through intradermal injection of CFA (100 µL) in the sub-plantar region of the right hind paw. The arthritic animals were treated orally with NCF at 5 and 10 mg/kg and indomethacin (Indo) at 5 mg/kg body weight as reference control. NCF treatment remarkably alleviated inflammatory joint swelling and arthritic index. The radiological and histological analysis revealed evidence of the beneficial effects of NCF. NCF treatment decreased the content of pro-inflammatory cytokines (TNF-α and IL-1ß) and myeloperoxidase (MPO) activity and restored the anti-inflammatory cytokine (IL-10) in the paw joints. The serum levels of pro-inflammatory cytokines were also markedly reduced in the NCF (10 mg/kg) treatment group. Moreover, the arthritis-induced inflammatory mediators, including cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) and the toll-like receptor (TLR)-4, mitogen-activated protein kinase (MAPK), and nuclear factor-κB (NF-κB) signaling proteins were substantially decreased in the NCF treatment groups. NCF treatment also restored the antioxidant defense enzymes and abrogated lipid peroxidation in the paw tissue. Our findings strongly suggest that NCF is a promising therapeutic molecule for rheumatoid arthritis, inspiring further research, and development in this area.

Nuciferine alleviates intestinal inflammation by inhibiting MAPK/NF-κB and NLRP3/Caspase 1 pathways in vivo and in vitro.

Nuciferine (NCF) is an aporphine alkaloid and a principal bioactive constituent in the lotus plant. Herewith, we investigated the potential anti-inflammatory effect and underlying mechanisms of NCF employing dextran sulfate sodium (DSS)-induced ulcerative colitis in mice, a predominant intestinal inflammatory disease, and mouse RAW 264.7 cells in vitro. Lipopolysaccharide (LPS) was used to generate an inflammatory response in the RAW 264.7 cells. The disease activity index (DAI), colon morphology, colonoscopy, and colon histopathology were performed to assess experimental colitis. The biochemical assays, enzyme-linked immunosorbent assay (ELISA), and immunoblot analysis were performed to understand the underlying mechanisms. In RAW 264.7 cells, NCF pretreatment significantly decreased the expression of inducible nitric oxide synthase (iNOS), the expression and release of pro-inflammatory cytokines including interleukin (IL)-1ß, IL-18, and tumor necrosis factor-α (TNF-α) and interfered with the activation of mitogen-activated protein kinase (MAPK), nuclear factor-κB (NF-κB), and NOD-like family pyrin domain containing 3 (NLRP3) signaling pathways. The oral treatment of NCF substantially alleviated the DSS-induced DAI, increased colon length, and restored colon morphology and histology. Compared to the DSS-induced mice, the proteins involved in the activation of MAPK/NF-κB/NLRP3 pathways and the cytokines were markedly decreased in the NCF-treated mice. Moreover, the tight junction architecture of the colon was well-maintained in NCF treatment groups by regulating the expression of claudin-1 and zonula occludens-1 (ZO-1) proteins. All these findings suggest that NCF can be a promising molecule to modulate ulcerative colitis.

Fisetin attenuates arsenic and fluoride subacute co-exposure induced neurotoxicity via regulating TNF-α mediated activation of NLRP3 inflammasome.

Groundwater is considered safe, however, the occurrence of contaminants like arsenic and fluoride has raised a major healthcare concern. Clinical studies suggested that arsenic and fluoride co-exposure induced neurotoxicity, however efforts to explore safe and effective management of such neurotoxicity are limited. Therefore, we investigated the ameliorative effect of Fisetin against arsenic and fluoride subacute co-exposure-induced neurotoxicity, and associated biochemical and molecular changes. Male BALB/c mice were exposed to Arsenic (NaAsO2: 50 mg/L) and fluoride (NaF: 50 mg/L) through drinking water and fisetin (5, 10, and 20 mg/kg/day) was administered orally for 28 days. The neurobehavioral changes were recorded in the open field, rotarod, grip strength, tail suspension, forced swim, and novel object recognition test. The co-exposure resulted in anxiety-like behaviour, loss of motor coordination, depression-like behaviour, and loss of novelty-based memory, along with enhanced prooxidant, inflammatory markers and loss of cortical and hippocampal neurons. The treatment with fisetin reversed the co-exposure-induced neurobehavioral deficit along with restoration of redox & inflammatory milieu, and cortical and hippocampal neuronal density. Apart from antioxidants, inhibition of TNF-α/ NLRP3 expression has been suggested as one of the plausible neuroprotective mechanisms of Fisetin in this study.

Anti-inflammatory activity of carvacrol protects the heart from lipopolysaccharide-induced cardiac dysfunction by inhibiting pyroptosis via NLRP3/Caspase1/Gasdermin D signaling axis.

AIMS: Lipopolysaccharide (LPS) is a well-known agent to induce septic conditions. Sepsis-induced cardiomyopathy has an overwhelming death rate. Carvacrol (CVL), a monoterpene phenol, has anti-inflammatory and antioxidant properties. This research aimed to investigate the effect of CVL on LPS-induced dysfunction in the heart. In this study, we evaluated the effect of CVL in LPS-stimulated H9c2 cardiomyoblast cells and Balb/C mice. MAIN METHODS: LPS was used to induce septic conditions in H9c2 cardiomyoblast cells in vitro and in Balb/C mice. A survival study was conducted to assess the survival rate of mice after LPS and/or CVL treatment. KEY FINDINGS: In vitro studies indicated that CVL inhibits reactive oxygen species (ROS) generation and abates pyroptosis mediated by NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome in H9c2 cells. In mice, CVL intervention improved the survival rate in septic conditions. The CVL administration markedly improved the echocardiographic parameters and alleviated the LPS-induced reduction in the ejection fraction (%) and fraction shortening (%). The CVL intervention restored the myocardial antioxidants and histopathological alterations and decreased the pro-inflammatory cytokine contents in the heart. Further findings disclosed that CVL reduced the protein levels of NLRP3, apoptosis-associated speck-like protein (ASC), caspase 1, interleukin (IL)-18, IL-1ß, and the pyroptosis-indicative protein, gasdermin-D (GSDMD) in the heart. The autophagy-indicative proteins, beclin 1 and p62 in the heart were also restored in the CVL-treated group. SIGNIFICANCE: Altogether, our findings demonstrated that CVL has a beneficial effect and can be a potential molecule against sepsis-induced myocardial dysfunction.

Alternanthera brasiliana L. extract alleviates carbon tetrachloride-induced liver injury and fibrotic changes in mice: Role of matrix metalloproteinases and TGF-ß/Smad axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Alternanthera brasiliana L. is a flowering plant belonging to the family Amaranthaceae and is popularly known as "penicillin". It is used in folk medicine to treat infections, coughs, wound healing, and inflammatory diseases. AIM OF THE STUDY: We investigated the effect of Alternanthera brasiliana L. leaves hydroalcoholic extract (AB) against oxidative stress, inflammation, and fibrotic changes in an experimental model of carbon tetrachloride (CCl4)-induced liver injury and fibrosis in mice. MATERIALS AND METHODS: Thirty-six male Balb/C mice were randomized into five groups: normal control, AB control, CCl4 control, CCl4 + AB-200 mg/kg, and CCl4 + AB-400 mg/kg. In mice, liver injury was induced by intraperitoneal injection of CCl4 (20% in corn oil, 5 ml/kg body weight) thrice a week for six consecutive weeks. AB extract at two doses (200 mg/kg and 400 mg/kg body weight) was administered orally for six consecutive weeks. Liver injury-related serum markers (ALT, AST, ALP), antioxidants (GSH, GST, SOD, and vitamin C), pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, and IL-18, ultrasonographic and histological alterations, proteins of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinase-1 (TIMP-1), nuclear factor-κB (p65) (NF-κB), nod-like receptor protein 3 (NLRP3), and TGF-ß/Smad signaling were accessed. LC-Q-TOF-MS/MS analysis of AB was performed. RESULTS: AB treatment significantly decreased the CCl4-induced rise in serum ALT, AST, and ALP activities and improved the histological alterations. Compared with the CCl4-treated group, treatment with AB significantly restored the hepatic antioxidants and reduced the pro-inflammatory cytokines in the liver. The antioxidant activity of AB may be attributed to its terpenoid constituents, which was confirmed by LC-Q-TOF-MS/MS analysis. The CCl4-induced rise in expression of MMP-2 and MMP-9 and decrease in TIMP-1 were markedly restored in the AB-treated groups. Further findings revealed a significant reduction in the protein levels of phospho-NF-κB (p65), NLRP3, TGF-ß, pSmad2/3, collagen I, and α-smooth muscle actin (α-SMA) in the AB treatment groups. CONCLUSIONS: The hepatoprotective effect of AB may be attributed to the high content of terpenoid compounds and alleviates liver injury and associated fibrotic changes through modulating MMPs, NF-κB (p65), and the TGF-ß/Smad axis.

Biochanin A alleviates unilateral ureteral obstruction-induced renal interstitial fibrosis and inflammation by inhibiting the TGF-ß1/Smad2/3 and NF-kB/NLRP3 signaling axis in mice.

AIMS: Tubulointerstitial fibrosis, a frequent complication of chronic kidney disease (CKD) is a major public health issue. Biochanin A (BCA), an isoflavone, has numerous pharmacological activities. However, its effect on renal fibrosis and underlying molecular mechanism has not yet been clarified. This study explored the effect of BCA on renal tubulointerstitial fibrosis and inflammation in mice. MAIN METHODS: The mouse model of unilateral ureteral obstruction (UUO) in vivo and transforming growth factor (TGF)-ß1 activated renal fibroblast (NRK 49F) cells in vitro model were used to assess the antifibrotic effect of BCA. Biochemical analysis, histopathology, western blotting, and immunofluorescent staining methods were performed to elucidate the mechanism of BCA. KEY FINDINGS: In vitro, BCA suppressed the expression of fibrogenic proteins in TGF-ß1-activated renal fibroblasts. The treatment with BCA displayed less tubular injury, prevented the aberrant accumulation of extracellular matrix (ECM) components, and inhibited the TGF-ß1/Smad2/3 signaling axis in the kidneys. Furthermore, BCA impeded the phosphorylation of NF-kB(p65) and blunted the expression of inflammatory genes in the obstructed kidneys. The UUO induced expressions of nod-like receptor protein 3 (NLRP3), active caspase 1, interleukin(IL)-18, and IL-1ß proteins were decreased in the BCA treated groups. We also found the increased expression of redox-sensitive nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) proteins in BCA treated groups compared to the UUO control. SIGNIFICANCE: These findings indicate that BCA has a therapeutic benefit against renal fibrosis, and the ameliorative effect is mediated via inhibiting the TGF-ß1/Smad2/3 and NF-kB/NLRP3 signaling axis.

Up-regulation of Nrf2/HO-1 and inhibition of TGF-ß1/Smad2/3 signaling axis by daphnetin alleviates transverse aortic constriction-induced cardiac remodeling in mice.

Oxidative damage and accumulation of extracellular matrix (ECM) components play a crucial role in the adverse outcome of cardiac hypertrophy. Evidence suggests that nuclear factor erythroid-derived factor 2 related factor 2 (Nrf2) can modulate oxidative damage and adverse myocardial remodeling. Daphnetin (Daph) is a coumarin obtained from the plant genus Daphne species that exerts anti-oxidative and anti-inflammatory properties. Herein, we investigated the roles of Daph in transverse aortic constriction (TAC)-induced cardiac hypertrophy and fibrosis in mice. TAC-induced alterations in cardiac hypertrophy markers, histopathological changes, and cardiac function were markedly ameliorated by oral administration of Daph in mice. We found that Daph significantly reduced the reactive oxygen species (ROS) generation, increased the nuclear translocation of Nrf2, and consequently, reinstated the protein levels of NAD(P)H quinone dehydrogenase1 (NQO1), heme oxygenase-1 (HO-1), and other antioxidants in the heart. Besides, Daph significantly inhibited the TAC-induced accumulation of ECM components, including α-smooth muscle actin (α-SMA), collagen I, collagen III, and fibronectin, and interfered with the TGF-ß1/Smad2/3 signaling axis. Further studies revealed that TAC-induced terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive nuclei and the protein levels of Bax/Bcl2 ratio and cleaved caspase 3 were substantially decreased by Daph treatment. We further characterized the effect of Daph on angiotensin II (Ang-II)-stimulated H9c2 cardiomyoblast cells and observed that Daph markedly decreased the Ang-II induced increase in cell size, production of ROS, and proteins associated with apoptosis and fibrosis. Mechanistically, Daph alone treatment enhanced the protein levels of Nrf2, NQO1, and HO-1 in H9c2 cells. The inhibition of this axis by Si-Nrf2 transfection abolished the protective effect of Daph in H9c2 cells. Taken together, Daph effectively counteracted the TAC-induced cardiac hypertrophy and fibrosis by improving the Nrf2/HO-1 axis and inhibiting the TGF-ß1/Smad2/3 signaling axis.

Aloin alleviates pathological cardiac hypertrophy via modulation of the oxidative and fibrotic response.

AIMS: Pathological cardiac hypertrophy is a characteristic feature in many cardiovascular diseases (CVDs). Aloin is an anthraquinone glycoside from Aloe species, and the effect of aloin on cardiac hypertrophy and associated fibrotic changes have not been elucidated. This study investigated the effect of aloin against the isoproterenol (ISO)-induced cardiac hypertrophy in rats. MAIN METHODS: Cardiac hypertrophy experimental model was induced in rats by subcutaneous injection of ISO for 14 days. Meanwhile, the animals were administered orally with aloin at doses of 25 and 50 mg/kg/day. On the 15th day, cardiac echocardiography was performed, the heart was collected and subjected for histopathological, gene expression, and immunoblot studies. Additionally, the effect of aloin on ISO-induced hypertrophic changes in H9c2 cells was investigated. KEY FINDINGS: Aloin markedly alleviated ISO-induced heart injury, reduced cardiac hypertrophy, improved cardiac function, and histological alterations in the heart. Mechanistically, aloin attenuated ISO-induced fibrosis via inhibition of the levels of collagen I, α-smooth muscle actin (α-SMA), fibronectin, transforming growth factor-ß (TGF-ß) and pSmad2/3 proteins in the heart. Aloin alleviated ISO-induced myocardial oxidative damage and up-regulated the levels of antioxidant transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins. Moreover, aloin treatment attenuated ISO-induced hypertrophic changes and the generation of reactive oxygen species (ROS) in H9c2 cells in vitro. SIGNIFICANCE: Our findings demonstrated that aloin alleviated ISO-induced cardiac hypertrophy and fibrosis via inhibiting TGF-ß/pSmad2/3 signaling and restoring myocardial antioxidants, and therefore has promising therapeutic potential against cardiac hypertrophy and fibrosis.

Biological Activities, Pharmacokinetics and Toxicity of Nootkatone: A Review.

Plant-based drugs have a significant impact on modern therapeutics due to their vast array of pharmacological activities. The integration of herbal plants in the current healthcare system has emerged as a new field of research. It can be used for the identification of novel lead compound candidates for future drug development. Nootkatone is a sesquiterpene derivative and an isolate of grapefruit. Shreds of evidence illustrate that nootkatone targets few molecular mechanisms to exhibit its pharmacological activity and yet needs more exploration. The current review is related to nootkatone, drafted through a literature search using research articles and books from different sources, including Science Direct, Google Scholar, Elsevier, PubMed, and Scopus. It has been reported to possess a wide range of pharmacological activities such as anti-inflammatory, anticancer, antibacterial, hepatoprotective, neuroprotective, and cardioprotective. Although preclinical studies in experimental animal models suggest that nootkatone has therapeutic potential, it is further warranted to evaluate its toxicity and pharmacokinetic parameters before being applied to humans. Hence, in the present review, we have summarized the scientific knowledge on nootkatone with a particular emphasis on its pharmacological properties to encourage researchers for further exploration in preclinical and clinical settings.

Nootkatone confers antifibrotic effect by regulating the TGF-ß/Smad signaling pathway in mouse model of unilateral ureteral obstruction.

Chronic kidney disease (CKD) with underlying interstitial fibrosis is often associated with end-stage renal disease (ESRD). In the present study, we investigated the renoprotective and antifibrotic potential of nootkatone (NTK), a bioactive sesquiterpene, in an experimental model of renal fibrosis. Unilateral ureteral obstruction (UUO) model was performed to induce renal fibrosis in Balb/C mice. The animals were randomly assigned into 5 groups: sham, NTK control, UUO control, UUO and NTK 5 mg/kg, and UUO and NTK 10 mg/kg. Animals received NTK at a dose of 5 mg/kg and 10 mg/kg orally for the next 14 consecutive days. UUO induced histological alterations, accumulation of extracellular matrix (ECM) components including collagens, fibronectin, and alpha-smooth muscle actin (α-SMA), activation of the transforming growth factor-ß (TGF-ß)/Smad signaling and oxidative damage in the obstructed kidneys. Our study revealed that NTK (10 mg/kg) inhibits UUO mediated kidney fibrosis in vivo. Administration of NTK (10 mg/kg) prevented the activation of the TGF-ß/Smad signaling, expression of ECM components, markedly attenuated the renal tubular injury and fibrosis area (% area: 6.66 ± 1.45% vs UUO: 26.33 ± 2.90%). Administration of NTK at 10 mg/kg significantly restored the endogenous antioxidants and prevented the reactive oxygen species generation (25.31 ± 1.65% vs UUO: 45.01 ± 4.85%) and reduced the level of tumor necrosis factor (TNF)-α (95.22 ± 12.39 vs UUO: 215.57 ± 60.45 pg/mg protein) in the kidneys. Altogether, our findings suggest that NTK might be a budding therapeutic candidate for renal fibrosis.