Abstract
Cannabis sativa L. is a crop utilized globally for recreational, therapeutic, and religious purposes. Although considered as an illicit drug in most countries, C. sativa until recently started gaining attention for its medicinal application. This study sought to investigate the hepatoprotective effect of C. sativa on iron-mediated oxidative hepatic injury. Hepatic injury was induced ex vivo by incubating hepatic tissues with Fe2+, which led to depleted levels of reduced glutathione, superoxide dismutase, catalase and ENTPDase activities, triglyceride, and high-density lipoprotein–cholesterol (HDL-C). Induction of hepatic injury also caused significant elevation of malondialdehyde, nitric oxide, cholesterol, and low-density lipoprotein–cholesterol (LDL-C) levels while concomitantly elevating the activities of ATPase, glycogen phosphorylase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, amylase, and lipase. Treatment with the hexane, dichloromethane (DCM), and ethanol extracts of C. sativa leaves significantly (p < 0.05) reversed these levels and activities to almost near normal. However, there was no significant effect on the HDL-C level. The extracts also improved the utilization of glucose in Chang liver cells. High-performance liquid chromatography (HPLC) analysis showed the presence of phenolics in all extracts, with the ethanol extract having the highest constituents. Cannabidiol (CBD) was identified in all the extracts, while Δ-9-tetrahydrocannabinol (Δ-9-THC) was identified in the hexane and DCM extracts only. Molecular docking studies revealed strong interactions between CBD and Δ-9-THC with the β2 adrenergic receptor of the adrenergic system. The results demonstrate the potential of C. sativa to protect against oxidative-mediated hepatic injury by stalling oxidative stress, gluconeogenesis, and hepatic lipid accumulation while modulating cholinergic and purinergic activities. These activities may be associated with the synergistic effect of the compounds identified and possible interactions with the adrenergic system.
Highlights
The roles of the liver in the metabolic functions of the body are well documented (Abdel-Salam et al, 2014; Seif, 2016)
The induction of oxidative injury in isolated rat hepatic tissues was established by incubating with iron II sulfate (FeSO4) in the presence of C. sativa extracts and CBD
The molecular interactions between the phytocannabinoids and the receptor may indicate the potentials of CBD and Δ-9-THC to inactivate the β2 adrenergic receptor, modulating the adrenergic system. This may explain the ability of C. sativa extracts to inhibit hepatic lipase activity (Figure 6B) and suppress hepatic TG level (Figure 7) in oxidative hepatic injury. These results indicate that the induction of oxidative hepatic injury led to oxidative stress (Figure 1), which has been implicated in proinflammation when O2.− arising from suppressed superoxide dismutase (SOD) activity (Figure 1B) reacts with high nitric oxide (NO) level (Figure 2) to form peroxynitrite radicals
Summary
The roles of the liver in the metabolic functions of the body are well documented (Abdel-Salam et al, 2014; Seif, 2016). Iron is regarded as one of the essential elements owing to its roles in the body leading to optimal health It is involved in several metabolic reactions and is a cofactor for enzymes involved in most physiological functions due to its ability to assume two different ionic states [ferrous (Fe2+) and ferric (Fe3+)] (Rishi and Subramaniam, 2017). Dysregulation of iron homeostasis leading to excessive increase in hepatic (liver) iron storage has been implicated in exacerbated production of free radicals (Anderson and Shah, 2013) This increased production causes an imbalance in the redox state owing to suppression of the tissues’ intrinsic antioxidant defense system, which leads to oxidative hepatic injury. Oxidative injury has been implicated as an important mechanism in the pathogenesis and progression of several hepatic diseases such as cirrhosis, hepatitis, hepatocellular carcinoma, and fibrosis (Anderson and Shah, 2013; Milic et al, 2016)
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.
