Abstract
Hydroxyphenylalkanes and diarylheptanoids possess potential therapeutic value in different pathophysiological conditions, such as malignancy. In the current study, naturally isolated hydroxyphenylalkane and diarylheptanoid compounds were investigated for potential chemo-modulatory effects in addition to potential vascular protective roles with doxorubicin. Diarylheptanoids showed stronger antioxidant effects, in comparison to hydroxyphenylalkanes, as demonstrated by DPPH assay and amelioration of CCl4-induced disturbed intracellular GSH/GSSG balance. Shogaol and 4′-methoxygingerol showed considerable cytotoxic effects against HCT116, HeLa, HepG2 and MCF7 cells, with IC50 values ranging from 3.1 to 19.4 µM. Gingerol significantly enhanced the cytotoxic profile of doxorubicin against HepG2 and Huh7, cells decreasing its IC50s by 10- and 4-fold, respectively. Cell cycle distribution was studied using DNA cytometry. Doxorubicin alone induced cell accumulation at S-phase and G2/M-phase, while in combination with gingerol it significantly induced cell cycle arrest at the G2/M-phase. Additionally, the vascular protective effect of gingerol against doxorubicin (10 µM) was examined on isolated aortic rings. Co-incubation with 6-gingerol (30 µM) completely blocked the exaggerated vasoconstriction and impaired vascular relaxation induced by doxorubicin. In conclusion, despite its relatively weak antioxidant properties, gingerol protected from DOX-induced vascular damage, apparently not through a ROS scavenging mechanism. Besides, gingerol synergized the cytotoxic effects of DOX against liver cancer cells without influencing the cellular pharmacokinetics.
Highlights
IntroductionZingiberaceae) is the only spice native to Africa and considered as an African panacea [1]
6-Gingerol is a major hydroxyphenylalkane isolated from A. melegueta and present in several plants belonging to the family Zingiberaceae, such as ginger and cardamom
Diarylheptanoids could be considered more potent than hydroxyphenylalkanes in free radical scavenging capacity, as well as in and diarylheptanoid compounds and assessed their potential cytotoxic and chemomodulatory effects, in addition to confirming their documented antioxidant activity
Summary
Zingiberaceae) is the only spice native to Africa and considered as an African panacea [1]. Seeds of A. melegueta were used, as a folk remedy, for the treatment of diarrhoea, and painful inflammatory conditions and in the control of postpartum haemorrhages [2]. Anti-ulcer, cytoprotective, antimicrobial, anti-nociceptive and aphrodisiac effects of the aqueous seed extract are reported [3,4]. Phytochemical investigations of the plant seeds revealed the presence of paradol- and gingerol-like compounds, in addition to diarylheptanoids with hepatoprotective and estrogenic effects [5,6]. 6-Gingerol is a major hydroxyphenylalkane isolated from A. melegueta and present in several plants belonging to the family Zingiberaceae, such as ginger and cardamom. The formerly mentioned plants are widely used in the Middle Eastern and Asian cuisine as a spice and everyday beverage
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
