Orientin, a flavanoid, mitigates 1, 2 dimethylhydrazine-induced colorectal lesions in Wistar rats fed a high-fat diet

Thangaraj, Kalaiyarasu; Natesan, Karthi; Palani, Mariyappan; Vaiyapuri, Manju

doi:10.1016/j.toxrep.2018.09.004

Cited by 20 publications

(13 citation statements)

References 54 publications

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“…In the current study, the growth rate was observed to be decreased in DMH/HFD rats when compared with control rats matching with Darband et al study [35]. This may be a consequence of higher tumor incidence, loss of appetite along with an increase in cachexia and anorexia [36,37]. Tenofovir-50 treatment did show an improvement in the colon architecture and tumor incidence; however, it lacked a marked effect on the growth rate compared with DMH/HFD group which was parallel to the reduction of food consumption.…”

Section: Discussionsupporting

confidence: 82%

The HIV reverse transcriptase Inhibitor Tenofovir suppressed DMH/HFD‐induced colorectal cancer in Wistar rats

Sherif

Makled

Suddеk

2021

Fundamemntal Clinical Pharma

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Colon rectal cancer (CRC) is the second commonest malignancy in developed countries and a significant cause of mortality. Tenofovir reportedly reduces the risk of hepatocellular carcinoma and interferes with cell cycle and cell proliferation. The current study investigated the potential antitumor effect of tenofovir against experimentally induced CRC. CRC was induced by 1,2-dimethylhydrazine (DMH, 20 mg/kg, once a week) and high-fat diet (HFD) in Wistar rats. Rats received tenofovir at a dose of 25 or 50 mg/kg (i.p.) for 24 weeks. Tenofovir-25 failed to significantly decrease the total number of dysplasia, adenoma and adenocarcinoma and to improve histopathological changes; however, tenofovir-50 resulted in no tumors seen in the colon lumen and a significant decrease in the total number of dysplasia and no adenoma or adenocarcinoma observed compared to DMH/HFD group. Tenofovir-25 failed to attenuate DMH/HFD-induced cell proliferation, whereas tenofovir-50 significantly decreased cell proliferation revealed by the decreased PCNA expression. Tenofovir-25 also failed to attenuate DMH/HFD-induced oxidative stress, whereas tenofovir-50 significantly attenuated oxidative stress as indicated by the decreased MDA concentration and SOD activity along with the increased GSH concentrations. Moreover, tenofovir-50 decreased Bcl-2 and cyclin D1 expressions in colon tissues compared with DMH/HFD group.Tenofovir-50 also significantly decreased INF-ɤ concentration in colon tissues. These findings suggest that the high dose of tenofovir (50 mg/kg) has antitumor potential against DMH/HFD-induced CRC, which might be mediated through the inhibition of cell proliferation, oxidative stress, and inflammation.

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Section: Discussionsupporting

confidence: 82%

The HIV reverse transcriptase Inhibitor Tenofovir suppressed DMH/HFD‐induced colorectal cancer in Wistar rats

Sherif

Makled

Suddеk

2021

Fundamemntal Clinical Pharma

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“…In vivo, orientin administration (10 mg/kg) resulted in antiproliferative effects on 1,2-dimethyl hydrazine (DMH)-induced colorectal cancer in rats, and improved tumor marker levels while decreasing proliferative marker levels, such as proliferating cell nuclear antigen (PCNA) and Ki67 [396]. Orientin also reduced the occurrence of colonic polyps and aberrant crypt foci and increased the antioxidant defense in rats with DMH-induced colorectal cancer, demonstrating its antiproliferative and antioxidant properties in vivo [397].…”

Section: Orientinmentioning

confidence: 97%

“…Improved tumor marker levels and decreased proliferative marker levels [396]. Reduced occurrence of polyps and aberrant crypt foci [397]. Increased antioxidant defense [397].…”

Section: Orientinmentioning

confidence: 99%

Anti-Cancer Potential of Cannabinoids, Terpenes, and Flavonoids Present in Cannabis

Tomko

Whynot

Ellis

et al. 2020

Cancers

148

139

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In recent years, and even more since its legalization in several jurisdictions, cannabis and the endocannabinoid system have received an increasing amount of interest related to their potential exploitation in clinical settings. Cannabinoids have been suggested and shown to be effective in the treatment of various conditions. In cancer, the endocannabinoid system is altered in numerous types of tumours and can relate to cancer prognosis and disease outcome. Additionally, cannabinoids display anticancer effects in several models by suppressing the proliferation, migration and/or invasion of cancer cells, as well as tumour angiogenesis. However, the therapeutic use of cannabinoids is currently limited to the treatment of symptoms and pain associated with chemotherapy, while their potential use as cytotoxic drugs in chemotherapy still requires validation in patients. Along with cannabinoids, cannabis contains several other compounds that have also been shown to exert anti-tumorigenic actions. The potential anti-cancer effects of cannabinoids, terpenes and flavonoids, present in cannabis, are explored in this literature review.

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“…Previously reported SrtA inhibitors include natural products [9,[16][17][18], synthetic products [19,20], and designed peptidomimetic compounds [21,22]. Orientin, a flavonoid isolated from various medicinal plants, is widely used in medicine because of its antiinflammatory, antioxidant, and antitumor effects [23][24][25][26]. In this study, we observed that it was an effective inhibitor of SrtA.…”

Section: Introductionmentioning

confidence: 71%

Orientin mediates protection against MRSA-induced pneumonia by inhibiting Sortase A

Wang

Jing

et al. 2021

Virulence

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Drug-resistant pathogenic Staphylococcus aureus (S. aureus) has severely threatened human health and arouses widespread concern. Sortase A (SrtA) is an essential virulence factor of S. aureus, which is responsible for the covalent anchoring of a variety of virulence-related proteins to the cell wall. SrtA has always been regarded as an ideal pharmacological target against S. aureus infections. In this research, we have determined that orientin, a natural compound isolated from various medicinal plants, can effectively inhibit the activity of SrtA with an IC 50 of 50.44 ± 0.51 µM. We further demonstrated that orientin inhibited the binding of S. aureus to fibrinogen and diminished biofilm formation and the attaching of Staphylococcal protein A (SpA) to the cell wall in vitro. Using the fluorescence quenching assay, we demonstrated a direct interaction between orientin and SrtA. Further mechanistic studies revealed that the residues Glu-105, Thr-93, and Cys-184 were the key sites for the binding of SrtA to orientin. Importantly, we demonstrated that treatment with orientin attenuated S. aureus virulence of in vivo and protected mice against S. aureus-induced lethal pneumonia. These findings indicate that orientin is a potential drug to counter S. aureus infections and limit the development of drug resistance.

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Orientin, a flavanoid, mitigates 1, 2 dimethylhydrazine-induced colorectal lesions in Wistar rats fed a high-fat diet

Abstract: Graphical abstract

Cited by 20 publications

References 54 publications

The HIV reverse transcriptase Inhibitor Tenofovir suppressed DMH/HFD‐induced colorectal cancer in Wistar rats

The HIV reverse transcriptase Inhibitor Tenofovir suppressed DMH/HFD‐induced colorectal cancer in Wistar rats

Anti-Cancer Potential of Cannabinoids, Terpenes, and Flavonoids Present in Cannabis

Orientin mediates protection against MRSA-induced pneumonia by inhibiting Sortase A

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