Cannabis sativa L. (var. indica) Exhibits Hepatoprotective Effects by Modulating Hepatic Lipid Profile and Mitigating Gluconeogenesis and Cholinergic Dysfunction in Oxidative Hepatic Injury

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.

Pharmacological Evaluation of Newly Synthesized Cannabidiol Derivates on H9c2 Cells

“…Interestingly, Usami and colleagues, in an ex vivo experiment using mouse hepatic microsomes, found that CBD and its hydroxy-quinone derivatives produced by CYP3A11 reduced the activity of SOD and catalase [ 38 ]. On the contrary, in another ex vivo model in which FeSO 4 was employed to induce oxidative stress in isolated hepatic tissue, leading to decreased activity of SOD and catalase, CBD treatment enhanced the antioxidant defense, including SOD and catalase activity [ 39 ]. The authors suggested that this contributes to the hepatoprotective effect of CDB and Cannabis sativa .…”

Lippia javanica (Burm. F.) Herbal Tea: Modulation of Hepatoprotective Effects in Chang Liver Cells via Mitigation of Redox Imbalance and Modulation of Perturbed Metabolic Activities

“…Glucose toxicity characterised by hepatic glucose accumulation promotes hepatic oxidative stress which results in severe liver oxidative injury and eventual hepatic cell death ( Chandrasekaran et al, 2012 ; Mota et al, 2016 ). Reports have shown the protective property of various plant-based antioxidants in scavenging free radical and the improvement of liver carbohydrate metabolism ( Yazdi et al, 2019 ; Erukainure et al, 2021a ; Olofinsan et al, 2022 ). This is in accordance with the ability of L. javanica herbal infusion to significantly reduce the activities of glucose-6-phosphatase, fructose-1,6-bisphosphatase and glycogen phosphorylase in oxidative hepatic injury ( Figures 6A–C ), suggesting a hepatoprotective and hepatic metabolic function-improving potential of the herbal tea infusion.…”

“…Excess cellular levels of glucose and lipids can serve as substrates for the generation of glucotoxic and lipotoxic species, respectively, which can cause damage to biomolecules, induce metabolic stress and eventual cell death ( Mota et al, 2016 ; Chen et al, 2020 ). Additionally, altered cholinergic enzyme activities have been implicated in the pathogenesis of liver diseases and studies have reported oxidative stress as facilitator of cholinergic dysfunction ( Garcia-Ayllon et al, 2012 ; Erukainure et al, 2021a ). These corroborates the use of antioxidants as therapies for targeting oxidative stress in the management of liver diseases ( Upadhyay et al, 2022 ).…”

Supporting gut health with medicinal cannabis in people with advanced cancer: potential benefits and challenges

“…However, both CBD and THC are metabolised by CYP2C9, suggesting the possibility of impaired drug clearance [ 109 ] or renal/liver toxicity. However, there are no data to suggest CBD and THC cause renal/liver toxicity, and in fact there is data to suggest hepatoprotective effects [ 110 ] and prevention of cisplatin-induced renal toxicity [ 111 ]. However safety profiles of MC in the context of cancer care remains superficially addressed, underscoring the importance of regular renal and liver function tests, appropriately titrated dosing, and studies with co-primary endpoints that address efficacy and safety [ 88 ].…”