Role of Nrf2 dysfunction in the pathogenesis of diabetic nephropathy: Therapeutic prospect of epigallocatechin-3-gallate

Mohan, Thangarajeswari; Narasimhan, Kishore Kumar S; Ravi, G.; Velusamy, Prema; Chandrasekar, Navvi; Chakrapani, Lakshmi Narasimhan; Srinivasan, A. R.; Karthikeyan, P.; Kannan, P.; Tamilarasan, Bhavani; Thanka, J; Kalaiselvan, Parkavi; Kalaiselvi, Periandavan

doi:10.1016/j.freeradbiomed.2020.07.037

Cited by 42 publications

(29 citation statements)

References 40 publications

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“…In summary, a total of twenty-nine compounds were obtained from the rhizome of L. chuanxiong, including fourteen phthalides (1 -14), four aromatics (15)(16)(17)(18), three steroids (20 -22), and eight miscellaneous compounds (19, 23-29). Among them, 2, 5, 6, 10, 11, 12, 13, 14, 17,18, 20 and 28 showed potential Nrf2 inducing effect verified by QR assay.…”

Section: Discussionmentioning

confidence: 99%

“…5. 16 Fr. 9 was isolated through CC of silica gel with PE-CH 2 Cl 2 (100 : 0!0 : 100), CH 2 Cl 2 -MeOH (1 : 1!0 : 1) to obtain 15 fractions (Fr.…”

Section: Extraction and Isolationmentioning

confidence: 99%

“…For instance, bardoxolone methyl with potent Nrf2 inducing effect have entered phase III clinical trial for the therapy of chronic kidney disease [14] . The Nrf2 activators sulforaphane (SF), ethyl ferulate, epigallocatechin‐3‐gallate, ampelopsin and icariin demonstrated anti‐DN effect in vitro and in vivo [15–18] . Therefore, Nrf2 activators are regarded to be important resource for discovering anti‐DN drugs.…”

Section: Introductionmentioning

confidence: 99%

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Chemical Constituents from the Rhizome of Ligusticum chuanxiong Hort. and Their Nrf2 Inducing Activity

Zhang

Kang

Tian

et al. 2021

Chemistry & Biodiversity

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The rhizome of Ligusticum chuanxiong Hort. has been widely used for the therapy of diabetic nephropathy (DN) in traditional Chinese medicine (TCM). The nuclear transcription factor erythroid 2‐related factor (Nrf2) is a potential target for treating DN. The purpose of this research was to study the chemical constituents from the rhizome of L. chuanxiong, evaluate their Nrf2 inducing activity, and find the molecules with potential therapeutic effect against DN. In this study, two new phthalides (1–2) along with twenty‐seven known constituents were obtained from the rhizome of L. chuanxiong. Their structures were elucidated through various spectroscopic methods. Twelve constituents, including eight phthalides (2, 5, 6,10–13, 14) and four other compounds (17, 18, 20,28), stimulated NAD(P)H: quinone reductase (QR) activity, suggesting that these bioactive constituents were potential Nrf2 activators. Among the isolated compounds, phthalide levistolide A (LA, 14) upregulated the protein levels of Nrf2, NQO1, and γ‐GCS in a dose‐dependent manner. Our results implied that the clinical application of the rhizome of L. chuanxiong as an anti‐DN drug in TCM might be attributed to the Nrf2 inducing effect of phthalides. Thus, phthalides is a group of promising leading molecules for discovering anti‐DN agents.

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Section: Discussionmentioning

confidence: 99%

“…5. 16 Fr. 9 was isolated through CC of silica gel with PE-CH 2 Cl 2 (100 : 0!0 : 100), CH 2 Cl 2 -MeOH (1 : 1!0 : 1) to obtain 15 fractions (Fr.…”

Section: Extraction and Isolationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Chemical Constituents from the Rhizome of Ligusticum chuanxiong Hort. and Their Nrf2 Inducing Activity

Zhang

Kang

Tian

et al. 2021

Chemistry & Biodiversity

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“…However, NRF2 is not translocated into the nucleus, showing a functional impairment of NRF2. Surprisingly, EGCG acts as a booster in translocating NRF2 into the nucleus and activates the NRF2/ARE pathway, which downregulates KEAP1 and its interaction with NRF2, thereby mitigating DN [ 60 ]. In another study, EGCG prevents kidney injury by activating NRF2, inhibiting NAPL3 inflammasome and increasing Treg in lupus nephritis-prone mice, suggesting the antioxidant and anti-inflammatory potential of EGCG [ 59 ].…”

Section: Phytochemicals and Regulation Of Nrf2 Signaling In Various Diseasesmentioning

confidence: 99%

Bioactive Compounds in Oxidative Stress-Mediated Diseases: Targeting the NRF2/ARE Signaling Pathway and Epigenetic Regulation

Venkidasamy²,

et al. 2021

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Oxidative stress is a pathological condition occurring due to an imbalance between the oxidants and antioxidant defense systems in the body. Nuclear factor E2-related factor 2 (NRF2), encoded by the gene NFE2L2, is the master regulator of phase II antioxidant enzymes that protect against oxidative stress and inflammation. NRF2/ARE signaling has been considered as a promising target against oxidative stress-mediated diseases like diabetes, fibrosis, neurotoxicity, and cancer. The consumption of dietary phytochemicals acts as an effective modulator of NRF2/ARE in various acute and chronic diseases. In the present review, we discussed the role of NRF2 in diabetes, Alzheimer’s disease (AD), Parkinson’s disease (PD), cancer, and atherosclerosis. Additionally, we discussed the phytochemicals like curcumin, quercetin, resveratrol, epigallocatechin gallate, apigenin, sulforaphane, and ursolic acid that have effectively modified NRF2 signaling and prevented various diseases in both in vitro and in vivo models. Based on the literature, it is clear that dietary phytochemicals can prevent diseases by (1) blocking oxidative stress-inhibiting inflammatory mediators through inhibiting Keap1 or activating Nrf2 expression and its downstream targets in the nucleus, including HO-1, SOD, and CAT; (2) regulating NRF2 signaling by various kinases like GSK3beta, PI3/AKT, and MAPK; and (3) modifying epigenetic modulation, such as methylation, at the NRF2 promoter region; however, further investigation into other upstream signaling molecules like NRF2 and the effect of phytochemicals on them still need to be investigated in the near future.

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“…The TG/GSSG ratio was estimated in the cerebral tissue of mice by colorimetric assay kit (Elabscience) [35]. The estimation was based on oxidation-reduction reaction using DTNB.…”

Section: Tissue Total Glutathione/oxidized Glutathione Ratio (Tg/gssg)mentioning

confidence: 99%

Oleanolic Acid, a Prospective Protective Agent Against Brain Energy Metabolism and Oxidative Dysfunctions Following Hexavalent Chromium Exposure in Mice

Pal

2021

Asian J Pharm Clin Res

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Objective: Effect of oleanolic acid against hexavalent chromium-induced altered brain energy metabolism associated with oxidative stress was evaluated in the present study. Methods: Swiss albino mice were divided into three groups, Control (n=6), chromium-treated (n=6), and oleanolic acid (OA) supplemented (n=6). The chromium treated group was orally administered with K2Cr2O7 for 30 days at a dose of 10 mg/kg b.w/day. OA supplementation was given at a dose of 5 mg/kg bw/day for the past 14 days of chromium treatment. Control group received the vehicle only. After the treatment, whole brain was removed for examining the parameters such as pyruvic acid, free amino nitrogen, tissue protein, TCA cycle enzyme activities, NADH dehydrogenase function, and oxidative stress markers. Results: Significant decrease in cerebral pyruvic acid content associated with suppressed malate dehydrogenase and succinate dehydrogenase activities were observed. The NADH dehydrogenase activity was inhibited owing to enhanced accumulation of chromium in cerebral tissue. Depletion of proteins and increased free amino acid nitrogen were accompanied with inhibited cathepsin, pronase and trypsin activities, and increased transaminase function. In addition, GSH content was decreased along with increased lipid peroxidation, oxidized GSSG content, TG/GSSG ratio, carbonylated protein content, and tissue free hydroxyl radical formation. Superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase were also inhibited by hexavalent chromium. Oleanolic acid supplementation was found to have significant protective effect against brain metabolic and oxidative dysfunctions. Conclusion: The present study elucidated therapeutic efficacy of oleanolic acid against hexavalent chromium toxicity in brain tissue of mice.

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Role of Nrf2 dysfunction in the pathogenesis of diabetic nephropathy: Therapeutic prospect of epigallocatechin-3-gallate

Cited by 42 publications

References 40 publications

Chemical Constituents from the Rhizome of Ligusticum chuanxiong Hort. and Their Nrf2 Inducing Activity

Chemical Constituents from the Rhizome of Ligusticum chuanxiong Hort. and Their Nrf2 Inducing Activity

Bioactive Compounds in Oxidative Stress-Mediated Diseases: Targeting the NRF2/ARE Signaling Pathway and Epigenetic Regulation

Oleanolic Acid, a Prospective Protective Agent Against Brain Energy Metabolism and Oxidative Dysfunctions Following Hexavalent Chromium Exposure in Mice

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