scholarly journals Carotenoid-Enriched Fractions From Spondias mombin Demonstrate HER2 ATP Kinase Domain Inhibition: Computational and In Vivo Animal Model of Breast Carcinoma Studies

2021 ◽  
Vol 11 ◽  
Author(s):  
Damilohun Samuel Metibemu ◽  
Oluseyi Adeboye Akinloye ◽  
Idowu Olaposi Omotuyi ◽  
Jude Ogechukwu Okoye ◽  
Mustapha Ayodele Popoola ◽  
...  

Human epidermal growth factor 2 (HER2) is overexpressed in about 20% of breast cancer and is associated with a poor prognosis. We report in this study that carotenoid-enriched fractions from Spondias mombin demonstrate HER2 ATP kinase domain inhibition. HER2 breast carcinoma was modeled in female Wistar rats and authenticated via immunohistochemical studies. Inhibition of HER2 ATP kinase domain by the carotenoid-enriched fractions was investigated by molecular docking, atomistic simulation, and the expression of HER2 mRNA in HER2-positive breast carcinoma model in female Wistar rats. The therapeutic efficacy of the treatments (carotenoid-rich fractions) was determined by biochemical, tumor volume, and histopathological analysis. Immunohistochemical analysis revealed 7,12-dimethylbenz[a]anthracene (DMBA)-induced HER2-positive breast carcinoma. Phytoconstituents of the carotenoid-enriched fractions astaxanthin, 7,7′,8,8′-tetrahydro-β,β-carotene, beta-carotene-15,15′-epoxide, and lapatinib (standard drug) demonstrate inhibition of HER2 with docking scores of −3.0, −8.5, −11.5, and −10.6 kcal/mol, respectively; and during atomistic simulation, the compounds ruptured the canonical active-state K753/E770 salt-bridge interaction. The treatment similarly downregulated HER2 mRNA expression significantly at p < 0.05. It also upregulated the expression of p53 and p27 mRNAs significantly at p < 0.05 and reduced creatinine and urea concentrations in the serum at p < 0.05. The tumor volume was also significantly reduced when compared with that of the untreated group. Carotenoid-enriched fractions from S. mombin demonstrate anti-HER2 positive breast carcinoma potentials via HER2 ATP kinase domain inhibition.

2021 ◽  
Vol 8 ◽  
pp. 489-498
Author(s):  
Damilohun Samuel Metibemu ◽  
Oluseyi Adeboye Akinloye ◽  
Adio Jamiu Akamo ◽  
Jude Ogechukwu Okoye ◽  
David Ajiboye Ojo ◽  
...  

1974 ◽  
Vol 75 (3) ◽  
pp. 569-578 ◽  
Author(s):  
G. Buffler ◽  
S. Roser

ABSTRACT The mechanisms involved in the prolongation of the oestrous cycle following LH administration were studied in 4-day cyclic female Wistar rats. In females injected with LH on the morning of dioestrus I there was an increase in ovarian venous blood progesterone as compared with non-injected animals. In both LH-treated females, and those injected with progesterone on the morning of dioestrus I, a slowing up in follicular growth was observed from the afternoon of dioestrus I. The size of follicles greater than 400 urn present in LH or progesterone injected animals on the third day of cycle was similar to the size reached by the same range of follicles in non-injected animals on the second day of the cycle. Hence, the increase in endogenous ovarian progesterone elicited by LH was considered as the cause of the slowing up of follicular growth and therefore of the lengthening of the oestrous cycle duration in female rats injected with LH at the beginning of 4-day cycle.


2010 ◽  
Vol 58 (3) ◽  
pp. 171-176 ◽  
Author(s):  
Roland Pálffy ◽  
Michal Behuliak ◽  
Roman Gardlík ◽  
Peter Jáni ◽  
L'udevít Kádaši ◽  
...  

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Izuchukwu Azuka Okafor ◽  
Uchenna Somtochukwu Nnamah ◽  
Jude Nnaka

Abstract Background Purslane is a widely distributed shrub used for the treatment of different ailments. The increasing reproductive complications associated with herbal treatments have led to the need to critically evaluate the safety and/or reproductive potentials of commonly used plant extracts. This study investigated the reproductive effect of methanolic extracts of Portulaca oleracea (MEPO) in adult female Wistar rats. Results Group C showed a significant decrease both in relative ovarian weight (p = 0.000), and relative uterine weight (p = 0.037), when compared with the control. There were no significant (p ˃ 0.05) changes in the levels of follicle-stimulating hormone, luteinizing hormone, progesterone, and estradiol. When compared to the control, groups B and C showed abnormal estrous cycle and cycle arrest especially at the metestrus phase with mild congestion of a few blood vessels in the ovary and uterus. Conclusions MEPO may possess some anti-fertility effect, as it disrupts the estrous cycle of adult female Wistar rats; although it has no major effect on the reproductive hormones, uterus, and ovarian histology of adult female Wistar rats. However, high dose consumption should be taken with precaution.


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