Albendazole-loaded cubosomes interrupt the ERK1/2-HIF-1α-p300/CREB axis in mice intoxicated with diethylnitrosamine: A new paradigm in drug repurposing for the inhibition of hepatocellular carcinoma progression

Saber, Sameh; Nasr, Mohamed; Saad, Ahmed S.; Mourad, Ahmed A.E.; Gobba, Naglaa A.; Shata, Ahmed; Abdel-Moneim, Abdel-Moneim Hafez; Elsergany, Ramy N.; Elagamy, Heba I.; El‐Ahwany, Eman; Amin, Noha A.; Girgis, Samuel; Elewa, Yaser Hosny Ali; Mahmoud, Mohamed H.; Batiha, Gaber El‐Saber; El-Rous, Magdy Abou; Kamal, Islam; Kaddah, Mohamed M.Y.; Khodir, Ahmed E.

doi:10.1016/j.biopha.2021.112029

Cited by 32 publications

(15 citation statements)

References 45 publications

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“…Emerging evidence indicates that TLR4 participates in the stimulation of innate immune response by triggering signaling cascades along with the release of several inflammatory cytokines such as TNF-α [38,39]. Here, we found that HS ointment downregulates TNF-α to <50 pg/mL, as the normal skin TNF-α level is <50 pg/mL [40].…”

Section: Discussionmentioning

confidence: 52%

Emerging Approach for the Application of Hibiscus sabdariffa Extract Ointment in the Superficial Burn Care

et al. 2022

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Wound healing comprises organized events involving tissue repair and regeneration. The discovery of toll-like receptors (TLRs) sheds recent light on the mechanisms involved in initiating inflammatory responses throughout the healing cascades. Hibiscus sabdariffa (HS) components may exhibit a wound healing action, owing to their antioxidant and anti-inflammatory activities. This study was designed to investigate the early effects of HS loaded in an ointment base on wound healing, antioxidant, antimicrobial effects, burning intensity, and histopathological features on the rat burn model in comparison to the standard treatment, Iruxol® ointment. A burn injury model was used to evaluate the wound healing potency of the preparation. Rats were treated with ointments three times on the day of the induction of the burn. Findings revealed that the strong antioxidant properties of the HS-loaded ointment augmented the skin healing potential by stimulating biomarkers required for skin regeneration. HS repressed the burning-induced inflammation by the effective reduction in the levels of tumor necrosis factor α (TNF-α) and IL-6 through TLR4 protein inhibition. Topical HS downregulates transforming growth factor-beta (TGF-β) levels. HS extract possesses a potential bactericidal activity against highly resistant clinical isolates of Pseudomonas aeruginosa. Overall, this study proclaims that HS-loaded topical preparations could be a valuable product that serves as adjuvants to accelerate burn wound healing through inactivating the TLR4 pathway.

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Section: Discussionmentioning

confidence: 52%

Emerging Approach for the Application of Hibiscus sabdariffa Extract Ointment in the Superficial Burn Care

et al. 2022

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“…The intensity of the color is inversely proportional to the active caspase-3 concentration since active caspase-3 from samples and active caspase-3-HRP conjugate compete for the anti-active caspase-3 antibody binding site. Since the number of sites is limited, as more sites are occupied by active caspase-3 from the sample, fewer sites are left to bind active caspase-3-HRP conjugate ( Saber et al, 2021b ). The active caspase-3 was determined in duplicate.…”

Section: Methodsmentioning

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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“…The findings indicated that the cubosome formulation of the drug resulted in a two-fold increase in bioavailability and more significant tumor regression in a rat model of cancer. Their investigation revealed that albendazole might prevent liver cancer by altering the ERK1/2-HIF-1-p300/CREB pathways via the cubosome formulation [ 99 ].…”

Section: Anticancer Activity Of Cubosomementioning

confidence: 99%

Development, Therapeutic Evaluation and Theranostic Applications of Cubosomes on Cancers: An Updated Review

Almoshari

2022

Pharmaceutics

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Cancer is a group of disorders characterized by aberrant gene function and alterations in gene expression patterns. In 2020, it was anticipated that 19 million new cancer cases would be diagnosed globally, with around 10 million cancer deaths. Late diagnosis and interventions are the leading causes of cancer-related mortality. In addition, the absence of comprehensive cancer therapy adds to the burden. Many lyotropic non-lamellar liquid-crystalline-nanoparticle-mediated formulations have been developed in the last few decades, with promising results in drug delivery, therapeutics, and diagnostics. Cubosomes are nano-structured liquid-crystalline particles made of specific amphiphilic lipids in particular proportions. Their ability to encapsulate lipophilic, hydrophilic, and amphiphilic molecules within their structure makes them one of a kind. They are biocompatible, versatile drug carriers that can deliver medications through various routes of administration. Many preclinical studies on the use of cubosomes in cancer treatment and theranostic applications have been conducted. However, before cubosomes may be employed in clinical practice, significant technical advances must be accomplished. This review summarizes the development of cubosomes and their multifunctional role in cancer treatment based on the most recent reports.

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Albendazole-loaded cubosomes interrupt the ERK1/2-HIF-1α-p300/CREB axis in mice intoxicated with diethylnitrosamine: A new paradigm in drug repurposing for the inhibition of hepatocellular carcinoma progression

Cited by 32 publications

References 45 publications

Emerging Approach for the Application of Hibiscus sabdariffa Extract Ointment in the Superficial Burn Care

Emerging Approach for the Application of Hibiscus sabdariffa Extract Ointment in the Superficial Burn Care

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

Development, Therapeutic Evaluation and Theranostic Applications of Cubosomes on Cancers: An Updated Review

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