Withaferin-A attenuates multiple low doses of Streptozotocin (MLD-STZ) induced type 1 diabetes

Tekula, Sravani; Khurana, Amit; Anchi, Pratibha; Godugu, Chandraiah

doi:10.1016/j.biopha.2018.07.090

Cited by 71 publications

(53 citation statements)

References 55 publications

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“…The treatment with WfA was started after 2 days to allow induction and establishment of inflammatory and fibrotic signaling. The dose of WfA was selected based on previous studies carried out by us and others . On the 14th day, all the animals were sacrificed and blood was collected after cardiac puncture.…”

Section: Methodsmentioning

confidence: 99%

“…The dose of WfA was selected based on previous studies carried out by us and others. 2,13,14 On the 14th day, all the animals were sacrificed and blood was collected after cardiac puncture. The kidneys were harvested from animals, washed with phosphate-buffered saline (PBS), cleaned with blotting paper, weighed and stored at −80 C. A small piece of kidney was kept in formalin solution for histopathological evaluation.…”

Section: Experimental Designmentioning

confidence: 99%

“…W. somnifera preparations are commonly used in traditional medicine due to its broad‐spectrum activities in different disorders. WfA was shown to possess strong antidiabetic properties by sensitization of leptin and reduction of apoptosis . Although anticancer properties of this molecule are well studied and widely reported in the literature, there are no reports on the renoprotective properties of WfA .…”

Section: Introductionmentioning

confidence: 99%

“…WfA was shown to possess strong antidiabetic properties by sensitization of leptin and reduction of apoptosis. 1,2 Although anticancer properties of this molecule are well studied and widely reported in the literature, there are no reports on the renoprotective properties of WfA. [3][4][5] Furthermore, WfA is shown to be a potent antioxidant, anti-inflammatory, 6,7 anti-angiogenic, 8 anti-EMT, 9 immunomodulatory, 10 and vimentin inhibitor.…”

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confidence: 99%

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Withaferin A ameliorates renal injury due to its potent effect on inflammatory signaling

et al. 2019

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Chronic kidney disease (CKD) is one of the major global health concerns and is responsible for end‐stage renal disease (ESRD) complications. Inflammation plays a pivotal role in the progression of CKD. In the present study, we evaluated the renoprotective effects of a potent immunomodulator steroidal lactone, Withaferin A (WfA), in an animal model of renal injury (unilateral ureteral obstruction, UUO) and further investigated if the inhibition of inflammatory signaling can be a useful approach to reduce renal injury. Animals were randomly divided into five groups: Sham control, UUO control, WfA control, WfA low dose (1 mg/kg), and WfA high dose (3 mg/kg). Oxidative stress was measured by the estimation of reduced glutathione and lipid peroxidation levels. H&E and Picrosirius Red staining were performed to assess the extent of histological damage and collagen deposition. Furthermore, the molecular mechanism of the WfA effects was explored by immunohistochemistry, enzyme‐linked immunosorbent assay, multiplex analysis of transforming growth factor β (TGF‐β) pathway, and an array of inflammatory cytokines/chemokines. Interestingly, our pharmacological intervention significantly attenuated tissue collagen, inflammatory signaling, and macrophage signaling. WfA intervention abrogated the inflammatory signaling as evident from the modulated levels of chemokines and cytokines. The levels of TGF‐β along with downstream signaling molecules were also attenuated by WfA treatment as revealed by inhibition in the expression of TGF‐β1, TGF‐β2, p‐Smad2, p‐Smad3, total Smad4, p‐Akt, and p‐ERK. We, to the best of our knowledge, prove for the first time that WfA has potential renoprotective activity against UUO‐induced nephropathy due to its outstanding anti‐inflammatory properties.

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Section: Methodsmentioning

confidence: 99%

Section: Experimental Designmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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confidence: 99%

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Withaferin A ameliorates renal injury due to its potent effect on inflammatory signaling

et al. 2019

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“…Immunohistochemistry was performed on 5 μm thick sections after deparaffinisation, as per our previously optimized protocol (Godugu, Doddapaneni, & Singh, ; Khurana, Tekula, & Godugu, ; Tekula et al, ). Sections were subjected to dehydration in graded alcohol followed by washing with Tris buffered saline (TBS) and incubation of the sections with proteinase‐K at 37°C for 20 min.…”

Section: Methodsmentioning

confidence: 99%

Modulation of cerulein‐induced pancreatic inflammation by hydroalcoholic extract of curry leaf (Murraya koenigii)

Khurana

Sikha

Ramesh

et al. 2019

Phytotherapy Research

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This study was performed to study the in vitro and in vivo efficacy of hydroalcoholic extract of curry leaf (CLE) rich in carbazole alkaloids, against LPS‐induced inflammation in Raw 264.7 macrophages and cerulein‐induced acute pancreatitis, respectively. CLE was characterized by Fourier‐transform infrared (FTIR) and liquid chromatography–mass spectrometry. Raw 264.7 cells were stimulated with LPS (2 μg/ml) and treated with CLE. The animals were treated with two doses of CLE (100 and 300 mg/kg). Plasma biochemistry, tissue lipid peroxidation, cytokines, and histological examination were evaluated. CLE was found to decently scavenge the activity of DPPH radical. It dose dependently suppressed nitrite production and oxidative stress in macrophages. CLE alleviated LPS‐induced inflammation in macrophages as evident from the results of various inflammatory cytokines (IL‐1β, IL‐6, and TNF‐α). In vivo, CLE reduced cerulein‐induced pancreatic edema. CLE significantly abrogated the cerulein‐induced lipid peroxidation, nitrite, MPO, and GSH levels. The inflammatory cytokines and p65‐NFκB activity were significantly reduced by CLE. Mechanistically, CLE reduced the expression of NT, MPO, IL‐1β, ICAM‐1, and COX‐2, and increased the expression of Nrf2. It reduced distant organ damage markers as well. We report for the first time that CLE holds substantial potential for the prevention of acute pancreatitis.

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Withaferin A reverses bile duct ligation‐induced liver fibrosis by modulating extracellular matrix deposition: Role of LOXL2/Snail1, vimentin, and NFκB signaling

et al. 2019

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Herein, we studied the effect of Withaferin A (WFA) in reversing bile duct ligation (BDL)‐induced liver fibrosis. BDL was performed on C57BL/6J mice and 2 days later, WFA (1 and 3 mg/kg) was administered for 12 days. Estimation of liver enzymes and assays for lipid peroxidation, reduced glutathione, and nitrite levels were performed. Picrosirius red, Masson's trichrome, and H&E staining were performed to study histological changes. WFA proved to be a holistic intervention for the attenuation and reversal of liver fibrosis. Reduction in inflammatory stimulus and oxidative stress restored the levels of stress‐related chaperone Hsp70 (p < .001 vs. BDL) in WFA treated groups. We found 3.59‐fold (p < .001) and 1.37‐fold (p < .01) reduction in the expression of lysyl oxidase like2 (LOXL2) and Snail1, respectively, in WFA‐treated animals as compared with BDL animals. These reductions led to 1.9‐fold (p < .001) elevation in levels of E‐cadherin signifying the reversal of epithelial to mesenchymal transition by WFA. Further, the reduction in LOXL2 levels enhanced the susceptibility of fibrotic scar toward degradation. The picrosirius red and Masson's trichrome staining done on liver tissue sections supported the above results. We, for the first time, report the role of WFA in modulating the expression of LOXL2 and Snail1 in addition to vimentin inhibition and regulation of NFκB signaling for the treatment of liver fibrosis.

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Withaferin-A attenuates multiple low doses of Streptozotocin (MLD-STZ) induced type 1 diabetes

Cited by 71 publications

References 55 publications

Withaferin A ameliorates renal injury due to its potent effect on inflammatory signaling

Withaferin A ameliorates renal injury due to its potent effect on inflammatory signaling

Modulation of cerulein‐induced pancreatic inflammation by hydroalcoholic extract of curry leaf (Murraya koenigii)

Withaferin A reverses bile duct ligation‐induced liver fibrosis by modulating extracellular matrix deposition: Role of LOXL2/Snail1, vimentin, and NFκB signaling

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