Cannabidiol (CBD) is one of the main pharmacologically active phytocannabinoids of Cannabis sativa L. CBD is non-psychoactive but exerts a number of beneficial pharmacological effects, including anti-inflammatory and antioxidant properties. The chemistry and pharmacology of CBD, as well as various molecular targets, including cannabinoid receptors and other components of the endocannabinoid system with which it interacts, have been extensively studied. In addition, preclinical and clinical studies have contributed to our understanding of the therapeutic potential of CBD for many diseases, including diseases associated with oxidative stress. Here, we review the main biological effects of CBD, and its synthetic derivatives, focusing on the cellular, antioxidant, and anti-inflammatory properties of CBD.

Ascorbic acid, as a one of the basic exogenous vitamins, occurs in the body in the form of ascorbate, known for its strong antioxidant and anti-inflammatory properties. The presented review shows not only the importance of ascorbate as a free radical scavenger but also summarizes its antioxidant action based on other mechanisms, including the activation of intracellular antioxidant systems and its effect on the NFκB/TNFα pathway and apoptosis. Ascorbate interacts with small-molecule antioxidants, including tocopherol, glutathione, and thioredoxin; it can also stimulate biosynthesis and the activation of antioxidant enzymes, such as superoxide dismutase, catalase, or glutathione peroxidase. Moreover, ascorbate promotes the activity of transcription factors (Nrf2, Ref-1, AP-1), which enables the expression of genes encoding antioxidant proteins. Additionally, it supports the action of other exogenous antioxidants, mainly polyphenols. In this regard, both DNA, proteins, and lipids are protected against oxidation, leading to an inflammatory reaction and even cell death. Although ascorbate has strong antioxidant properties, it can also have pro-oxidant effects in the presence of free transition metals. However, its role in the prevention of DNA mutation, inflammation, and cell apoptosis, especially in relation to cancer cells, is controversial.

The current understanding of the complex role of ROS in the organism and pathological sequelae of oxidative stress points to the necessity of comprehensive studies of antioxidant reactivities and interactions with cellular constituents. Studies of antioxidants performed within the COST B-35 action has concerned the search for new natural antioxidants, synthesis of new antioxidant compounds and evaluation and elucidation of mechanisms of action of both natural and synthetic antioxidants. Representative studies presented in the review concern antioxidant properties of various kinds of tea, the search for new antioxidants of herbal origin, modification of tocopherols and their use in combination with selenium and properties of two promising groups of synthetic antioxidants: derivatives of stobadine and derivatives of 1,4-dihydropyridine.

Reactive oxygen species (ROS) can induce carcinogenesis via DNA injury. Both enzymatic and non-enzymatic parameters participate in cell protection against harmful influence of oxidative stress. The aim of the present study was to assess the levels of final lipid peroxidation products like malondialdehyde (MDA) and 4-hydroxy-2-nonenal (4-HNE) in primary colorectal cancer. Moreover, we analysed the activity of main antioxidative enzymes, superoxide dismutase (Cu, Zn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione reductase (GSSRG-R) and the level of non-enzymatic antioxidants (glutathione, vitamins C and E). Investigations were conducted in 81 primary colorectal cancers. As a control, the same amount of sample was collected from macroscopically unchanged colon regions of the most distant location to the cancer. Homogenisation of specimens provided 10% homogenates for our evaluations. Activity of antioxidant enzymes and level of glutathione were determined by spectrophotometry. HPLC revealed levels of vitamins C and E and served as a method to detect terminal products of lipid peroxidation in colorectal cancer. Our studies demonstrated a statistically significant increase in the level of lipid peroxidation products (MDA-Adc.muc.-2.65+/-0.48 nmol/g, Adc.G3-2.15+/-0.44 nmol/g, clinical IV stage 4.04+/-0.47 nmol/g, P<0.001 and 4-HNE-Adc.muc. -0.44+/-0.07 nmol/g, Adc.G3-0.44+/-0.10 nmol/g, clinical IV stage 0.52+/-0.11 nmol/g, P<0.001) as well as increase of Cu,Zn-SOD (Adc.muc.-363+/-72 U/g, Adc.G3-318+/-48 U/g, clinical IV stage 421+/-58 U/g, P<0.001), GSH-Px (Adc.muc. -2143+/-623 U/g, Adc.G3-2005+/-591 U/g, clinical IV stage 2467+/-368 U/g, P<0.001) and GSSG-R (Adc.muc.-880+/-194 U/g, Adc.G3-795+/-228 U/g, clinical IV stage 951+/-243 U/g, P<0.001) in primary tumour comparison with normal colon (MDA-1.39+/-0.15 nmol/g, HNE-0.29+/-0.03 nmol/g, Cu, Zn-SOD-117+/-25 U/g, GSH-Px-1723+/-189 U/g, GSSG-R-625+/-112 U/g) especially in mucinous and G3-grade adenocarcinomas as well as clinical IV stage of colorectal cancer. We also observed a decrease of CAT activity (Adc.muc. -40+/-14 U/g, clinical IV stage 33+/-18 U/g vs 84+/-17 U/g, P<0.001) as well as a decreased level of reduced glutathione (clinical IV stage 150+/-48 nmol/g vs 167+/-15 nmol/g, P<0.05) and vitamins C and E (vit. C-clinical IV stage 325+/-92 nmol/g vs 513+/-64 nmol/g, P<0.001; vit. E-clinical IV stage 13.3+/-10.3 nmol/g vs 37.5+/-5.2 nmol/g). Colorectal carcinogenesis is associated with serious oxidative stress and confirms that gradual advancement of oxidative-antioxidative disorders is followed by progression of colorectal cancer.