Molecular modulators of celastrol as the keystones for its diverse pharmacological activities

Ng, Sin Wi; Chan, Yinghan; Chellappan, Dinesh Kumar; Madheswaran, Thiagarajan; Zeeshan, Farrukh; Chan, Yik Lung; Collet, Trudi; Gupta, Gaurav; Oliver, Brian G.; Wark, Peter; Hansbro, Nicole G.; Hsu, Alan; Hansbro, Philip M.; Dua, Kamal; Panneerselvam, Jithendra

doi:10.1016/j.biopha.2018.11.051

Cited by 84 publications

(64 citation statements)

References 88 publications

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“…While a few studies about DLM's poisonous quality have been reported, few investigations have been done on the protective agents utilized against such harmfulness and the mechanism of their ameliorative action. In the present examination, the renal wounds produced by DLM might be caused by the OS because of the generation of free radicals …”

Section: Discussionmentioning

confidence: 64%

“…Nrf2, which is held with Kelch‐like erythroidcellderived protein 1 (Keap1) in the cytoplasm of the cell, is discharged from the complex under states of OS (additionally alluded to as electrophilic stress) and is activated. Nrf2 then translocates to the nucleus and is tied to the antioxidant response element . This coupling causes downstream actuation of HO‐1.…”

Section: Discussionmentioning

confidence: 99%

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Curcumin synergistically potentiates the protective effect of sitagliptin against chronic deltamethrin nephrotoxicity in rats: Impact on pro‐inflammatory cytokines and Nrf2/Ho‐1 pathway

Shi

Zhang

Wang

et al. 2019

J Biochem & Molecular Tox

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Deltamethrin (DLM) is a synthesized organophosphorus acaricide and bug spray, broadly utilized for veterinary and farming purposes. Although its exposure to humans and animals causes toxicity in the kidney and other primary organs, our objective was to assess the defensive effects of sitagliptin (Sita) and additionally curcumin (Cur) in the DLM‐intoxicated rats’ kidney. DLM‐intoxicated rats revealed a huge increase of various biochemical parameters in serum identified with kidney damage: uric acid, urea, and creatinine. DLM intoxication altogether increased renal lipid peroxidation, and critically restrained antioxidative biomarkers including superoxide dismutase, glutathione, and glutathione peroxidase. Likewise, it increased the tumor necrosis factor‐α, interleukin 6 (IL‐6) and IL‐1β level in serum. Additionally, DLM intoxication diminished the outflow of the nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2)/heme oxygenase‐1 (HO‐1) pathway in rats. Both Sita and Cur act against DLM‐prompted serum along with renal tissue biochemical parameters when utilized alone or in a mix alongside DLM intoxication. Besides this, both Sita and Cur delivered synergetic nephroprotective, antioxidative, and anti‐inflammatory impacts. Consequently, it could be presumed that Sita as well as Cur administration can limit the poisonous impacts of DLM by their free radical‐scavenging, strong antioxidant, and Nrf2/HO‐1 pathway upregulation activity.

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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Curcumin synergistically potentiates the protective effect of sitagliptin against chronic deltamethrin nephrotoxicity in rats: Impact on pro‐inflammatory cytokines and Nrf2/Ho‐1 pathway

Shi

Zhang

Wang

et al. 2019

J Biochem & Molecular Tox

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“…The UK Prospective Diabetes Study (UKPDS) showed that metformin beneficially affects diverse cardiovascular hazard factors . Metformin treatment resulted in a 30% lower risk of macrovascular diseases contrasted with the other treatment modalities in the UKPDS . For MI alone, the metformin group had a 42% lesser chance than the traditional treatment group.…”

Section: Introductionmentioning

confidence: 99%

Cardioprotective role of metformin against sodium arsenite‐induced oxidative stress, inflammation, and apoptosis

et al. 2019

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Arsenic is a universal component and a notable natural poison. Its exposure to people occurs primarily through natural, therapeutic, and occupational sources. This investigation intended to discover the defensive impact of metformin (100 and 150 mg/kg body weight) against sodium arsenite (SA)‐induced cardiotoxicity in experimental animals. The study was conducted on Sprague Dawley rats (n = 50), which were separated into five different groups as follows: control, met‐150, SA, SA + met‐100, and SA + met‐150. The results demonstrated that SA caused a significant increase in the level of malondialdehyde and also reduced activities of antioxidative enzyme. SA similarly increased inflammatory reactions by increasing the level of interleukin‐6, tumor necrosis factor‐α, and interleukin‐1β. In addition, SA provoked the apoptosis by expanding the p53 and Bax levels, terminal deoxynucleotidyl transferase dUTP nick end labeling, and expression of caspase‐3. SA altered the histological integrity of cardiac tissue and 8‐hydroxy‐2′‐deoxyguanosine expression. In conclusion, metformin significantly reduced oxidative stress, inflammatory reaction, and apoptotic pathway. The present investigation showed that metformin has a cardioprotective impact because of its protective role against oxidation, inflammation, and apoptosis.

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“…The present investigation concentrated on CCl 4 administration for a week that caused hepatic damage because of increased ALT, AST, and ALP levels. Treatment with CCl 4 prompted critical development of MDA levels in the hepatic tissues, trailed by concealment in the major enzymatic antioxidants levels . The subsequent pattern was strong of the theory that after CCl 4 treatment, the main consideration prompting organ injury was OS.…”

Section: Discussionmentioning

confidence: 97%

“…Treatment with CCl 4 prompted critical development of MDA levels in the hepatic tissues, trailed by concealment in the major enzymatic antioxidants levels. [33][34][35] The subsequent pattern was strong of the theory that after CCl 4 treatment, the main consideration prompting organ injury was OS. For alteration of the hepatotoxicity impact of CCl 4 , Met and Lut portions were administered into the mixture and, furthermore independently, when the latter demonstrated better defensive outcomes.…”

Section: Discussionmentioning

confidence: 99%

Combination of metformin and luteolin synergistically protects carbon tetrachloride‐induced hepatotoxicity: Mechanism involves antioxidant, anti‐inflammatory, antiapoptotic, and Nrf2/HO‐1 signaling pathway

Yang¹,

Yang²,

Jiangmei³

2019

BioFactors

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Liver diseases are one of the fatal disorders due to the vital role of the liver. Carbon tetrachloride (CCl4) is the most perceived chemical substance utilized in developing models of hepatic damage. Metformin (Met) is a potent antidiabetic and redox modulatory agent that has shown anticancer and protective effects on various organs. Therefore, addition of therapy with natural antioxidative agents or herbal extracts shows defensive impacts against different injuries inside the body. Luteolin (Lut) can be found in several customary Chinese remedies. It has been reported for various pharmacological actions such as antitumor, antioxidative, and anti‐inflammatory impacts. Here, the liver injury rat model was established using CCl4 (1.00 mL/kg body weight) in vivo. The protective roles of Met and Lut separately or in combination were observed in hepatotoxicity induced by CCl4. The result was shown that both Met and Lut, while individually used, were normally active in diminishing CCl4‐caused hepatotoxicity. The combination of two drugs performed synergistically to improve liver damage caused by CCl4, as shown by the considerably improved liver dysfunction. Met and Lut showed highly antioxidative effects on CCl4‐treated rats moderately by increasing the activities and expression of the antioxidant enzymes. Along with this, a combination of Met and Lut significantly suppressed inflammatory responses, which is evidenced by the reduced level of inflammatory cytokines together with interleukin 1 beta (IL‐1β), tumor necrosis factor alpha (TNF‐α), and interleukin 6 (IL‐6). Additionally, CCl4‐agitated apoptosis was intensely reduced by Met and Lut through reducing cleaved caspase‐3 and Bax (pro‐apoptotic factor) while increasing Bcl‐2 (antiapoptotic factor) signaling pathways. Cotreatments of Met and Lut upregulated nuclear factor erythroid 2‐related factor 2 (NRF2) and heme oxygenase‐1 (HO‐1) expression in the CCl4‐intoxicated rat's liver. The above result recommended that combination of Met and Lut may have a substantial potential and synergizing impact against CCl4‐induced hepatotoxicity.

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Molecular modulators of celastrol as the keystones for its diverse pharmacological activities

Cited by 84 publications

References 88 publications

Curcumin synergistically potentiates the protective effect of sitagliptin against chronic deltamethrin nephrotoxicity in rats: Impact on pro‐inflammatory cytokines and Nrf2/Ho‐1 pathway

Curcumin synergistically potentiates the protective effect of sitagliptin against chronic deltamethrin nephrotoxicity in rats: Impact on pro‐inflammatory cytokines and Nrf2/Ho‐1 pathway

Cardioprotective role of metformin against sodium arsenite‐induced oxidative stress, inflammation, and apoptosis

Combination of metformin and luteolin synergistically protects carbon tetrachloride‐induced hepatotoxicity: Mechanism involves antioxidant, anti‐inflammatory, antiapoptotic, and Nrf2/HO‐1 signaling pathway

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