Empagliflozin adjunct with metformin for the inhibition of hepatocellular carcinoma progression: Emerging approach for new application

Abdelhamid, A. M.; Saber, Sameh; Youssef, Mahmoud E.; Gaafar, Ahmed Gaafar Ahmed; Eissa, Hanan; Abdel-Dayem, Marwa A.; Alqarni, Mohammed; Batiha, Gaber El‐Saber; Obaidullah, Ahmad J.; Shahien, Mohamed Awad; El‐Ahwany, Eman; Amin, Noha A.; Etman, Mohamed Ali; Kaddah, Mohamed M.Y.; El-Fattah, Eslam E. Abd

doi:10.1016/j.biopha.2021.112455

Cited by 33 publications

(16 citation statements)

References 80 publications

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“…The NFκB signaling pathway has been reported to be activated by AA-administration ( Viennois et al, 2012 ; Rezayat et al, 2018 ; Rashidian et al, 2019 ). Growth factors, oxidative stress-related enzymes, and cytokines are overexpressed when NFκB is activated ( Khalil et al, 2020 ; Abd El-Fattah et al, 2022a ; Abdelhamid et al, 2022 ; Abd El-Fattah et al, 2022b ). Furthermore, this activation influences physiologic or pathologic events including immunological and inflammatory responses.…”

Section: Discussionmentioning

confidence: 99%

Carbocisteine as a Modulator of Nrf2/HO-1 and NFκB Interplay in Rats: New Inspiration for the Revival of an Old Drug for Treating Ulcerative Colitis

et al. 2022

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Ulcerative colitis (UC), an inflammatory bowel disease, is a chronic condition of a multifaceted pathophysiology. The incidence of UC is increasing internationally. The current therapies for UC lack relative effectiveness and are associated with adverse effects. Therefore, novel therapeutic options should be developed. It has been well documented that modulating the Nrf2/NFκB is a promising therapeutic target in inflammation. Carbocisteine is a mucoregulatory medication and its efficacy in COPD was found to be more closely related to its antioxidant and anti-inflammatory properties. Carbocisteine has not yet been examined for the management of UC. Hence, our approach was to investigate the potential coloprotective role of carbocisteine in acetic acid-induced colitis in rats. Our results revealed that carbocisteine improved colon histology and macroscopic features and subdued the disease activity as well. Additionally, carbocisteine attenuated colon shortening and augmented colon antioxidant defense mechanisms via upregulating catalase and HO-1 enzymes. The myeloperoxidase activity was suppressed indicating inhibition of the neutrophil infiltration and activation. Consistent with these findings, carbocisteine boosted Nrf2 expression along with NFκB inactivation. Consequently, carbocisteine downregulated the proinflammatory cytokines IL-6 and TNF-α and upregulated the anti-inflammatory cytokine IL-10. Concomitant to these protective roles, carbocisteine displayed anti-apoptotic properties as revealed by the reduction in the Bax: BCL-2 ratio. In conclusion, carbocisteine inhibited oxidative stress, inflammatory response, and apoptosis in acetic acid-induced UC by modulating the Nrf2/HO-1 and NFκB interplay in rats. Therefore, the current study provides a potential basis for repurposing a safe and a commonly used mucoregulator for the treatment of UC.

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Section: Discussionmentioning

confidence: 99%

Carbocisteine as a Modulator of Nrf2/HO-1 and NFκB Interplay in Rats: New Inspiration for the Revival of an Old Drug for Treating Ulcerative Colitis

et al. 2022

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“…The tissue samples underwent fixation in formalin, followed by embedding in paraffin blocks and sectioning into 4 μm-thick slices. These sections were then subjected to standard procedures for H&E staining [ 44 , 55 ]. Following staining, the liver sections were examined using a microscope.…”

Section: Methodsmentioning

confidence: 99%

STA9090 as a Potential Therapeutic Agent for Liver Fibrosis by Modulating the HSP90/TβRII/Proteasome Interplay: Novel Insights from In Vitro and In Vivo Investigations

Mohammed,

Abdel-Reheim,

Alamri

et al. 2023

Pharmaceuticals

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Liver fibrosis is a progressive condition characterized by the build-up of fibrous tissue resulting from long-term liver injury. Although there have been advancements in research and treatment, there is still a need for effective antifibrotic medication. HSP90 plays a crucial role in the development of fibrosis. It acts as a molecular chaperone that assists in the proper folding and stability of TβRII, potentially regulating the signaling of TGF-β1. It has been established that TβRII can be degraded through the proteasome degradation system, either via ubiquitination-dependent or -independent pathways. In the present study, STA9090 demonstrated promising effects in both in vitro and in vivo models. It reduced LDH leakage, prolonged the survival rate of hepatocytes in rats with liver fibrosis, and improved liver function. Importantly, STA9090 exerted pleiotropic effects by targeting proteins involved in limiting collagen production, which resulted in improved microscopic features of the rat livers. Our findings suggest that STA9090-induced inhibition of HSP90 leads to the degradation of TβRII, a fibrogenic client protein of HSP90, through the activation of the 20S proteasomal degradation system. We also revealed that this degradation mechanism is not dependent on the autophagy–lysosomal pathway. Additionally, STA9090 was found to destabilize HIF-1α and facilitate its degradation, leading to the reduced transcription of VEGF. Moreover, STA9090’s ability to deactivate the NFκB signaling pathway highlights its potential as an anti-inflammatory and antifibrotic agent. However, further research is necessary to fully elucidate the underlying mechanisms and fully capitalize on the therapeutic benefits of targeting HSP90 and associated pathways.

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“…The main function of AMPK is to maintain energy balance by reducing ATP-consuming processes, including the transcription of genes involved in the synthesis of fat and ribosomal proteins, and the production of cholesterol and fatty acids [ 63 ]. Meanwhile, AMPK increases metabolic pathways such as glucose and fatty acid transport, fatty acid oxidation, autophagy, mitochondrial synthesis, and oxidative metabolism to preserve ATP during times of energy deficiency [ 64 , 65 , 66 , 67 , 68 , 69 ].…”

Section: Cardiovascular Effects Of Sglt2 Inhibitorsmentioning

confidence: 99%

Unlocking the Full Potential of SGLT2 Inhibitors: Expanding Applications beyond Glycemic Control

Youssef

Yahya

Popoviciu

et al. 2023

IJMS

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The number of diabetic patients has risen dramatically in recent decades, owing mostly to the rising incidence of type 2 diabetes mellitus (T2DM). Several oral antidiabetic medications are used for the treatment of T2DM including, α-glucosidases inhibitors, biguanides, sulfonylureas, meglitinides, GLP-1 receptor agonists, PPAR-γ agonists, DDP4 inhibitors, and SGLT2 inhibitors. In this review we focus on the possible effects of SGLT2 inhibitors on different body systems. Beyond the diabetic state, SGLT2 inhibitors have revealed a demonstrable ability to ameliorate cardiac remodeling, enhance myocardial function, and lower heart failure mortality. Additionally, SGLT2 inhibitors can modify adipocytes and their production of cytokines, such as adipokines and adiponectin, which enhances insulin sensitivity and delays diabetes onset. On the other hand, SGLT2 inhibitors have been linked to decreased total hip bone mineral deposition and increased hip bone resorption in T2DM patients. More data are needed to evaluate the role of SGLT2 inhibitors on cancer. Finally, the effects of SGLT2 inhibitors on neuroprotection appear to be both direct and indirect, according to scientific investigations utilizing various experimental models. SGLT2 inhibitors improve vascular tone, elasticity, and contractility by reducing oxidative stress, inflammation, insulin signaling pathways, and endothelial cell proliferation. They also improve brain function, synaptic plasticity, acetylcholinesterase activity, and reduce amyloid plaque formation, as well as regulation of the mTOR pathway in the brain, which reduces brain damage and cognitive decline.

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Empagliflozin adjunct with metformin for the inhibition of hepatocellular carcinoma progression: Emerging approach for new application

Cited by 33 publications

References 80 publications

Carbocisteine as a Modulator of Nrf2/HO-1 and NFκB Interplay in Rats: New Inspiration for the Revival of an Old Drug for Treating Ulcerative Colitis

Carbocisteine as a Modulator of Nrf2/HO-1 and NFκB Interplay in Rats: New Inspiration for the Revival of an Old Drug for Treating Ulcerative Colitis

STA9090 as a Potential Therapeutic Agent for Liver Fibrosis by Modulating the HSP90/TβRII/Proteasome Interplay: Novel Insights from In Vitro and In Vivo Investigations

Unlocking the Full Potential of SGLT2 Inhibitors: Expanding Applications beyond Glycemic Control

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