Traditionally Used Sideritis cypria Post.: Phytochemistry, Nutritional Content, Bioactive Compounds of Cultivated Populations

V.1: Agricultural chemicals; Contaminants; Drugs. V.2: Food composition; Additives; Natural contaminants.

Abstract Natural bicyclic sesquiterpenes, β‐caryophyllene (BCP) and β‐caryophyllene oxide (BCPO), are present in a large number of plants worldwide. Both BCP and BCPO (BCP(O)) possess significant anticancer activities, affecting growth and proliferation of numerous cancer cells. Nevertheless, their antineoplastic effects have hardly been investigated in vivo. In addition, both compounds potentiate the classical drug efficacy by augmenting their concentrations inside the cells. The mechanisms underlying the anticancer activities of these sesquiterpenes are poorly described. BCP is a phytocannabinoid with strong affinity to cannabinoid receptor type 2 (CB 2), but not cannabinoid receptor type 1 (CB 1). In opposite, BCP oxidation derivative, BCPO, does not exhibit CB 1/2 binding, thus the mechanism of its action is not related to endocannabinoid system (ECS) machinery. It is known that BCPO alters several key pathways for cancer development, such as mitogen‐activated protein kinase (MAPK), PI3K/AKT/mTOR/S6K1 and STAT3 pathways. In addition, treatment with this compound reduces the expression of procancer genes/proteins, while increases the levels of those with proapoptotic properties. The selective activation of CB 2 may be considered a novel strategy in pain treatment, devoid of psychoactive side effects associated with CB 1 stimulation. Thus, BCP as selective CB 2 activator may be taken into account as potential natural analgesic drug. Moreover, due to the fact that chronic pain is often an element of cancer disease, the double activity of BCP, anticancer and analgesic, as well as its beneficial influence on the efficacy of classical chemotherapeutics, is particularly valuable in oncology. This review is focused on anticancer and analgesic activities of BCP and BCPO, the mechanisms of their actions, and potential therapeutic utility.

The best described pharmacological property of flavonoids is their capacity to act as potent antioxidant that has been reported to play an important role in the alleviation of diabetes mellitus. Flavonoids biochemical properties are structure dependent; however, they are yet to be thoroughly understood. Hence, the main aim of this work was to investigate the antioxidant and antidiabetic properties of some structurally related flavonoids to identify key positions responsible, their correlation, and the effect of methylation and acetylation on the same properties. Antioxidant potential was evaluated through dot blot, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, ABTS+ radical scavenging, ferric reducing antioxidant power (FRAP), and xanthine oxidase inhibitory (XOI) assays. Antidiabetic effect was investigated through α-glucosidase and dipeptidyl peptidase-4 (DPP-4) assays. Results showed that the total number and the configuration of hydroxyl groups played an important role in regulating antioxidant and antidiabetic properties in scavenging DPPH radical, ABTS+ radical, and FRAP assays and improved both α-glucosidase and DPP-4 activities. Presence of C-2-C-3 double bond and C-4 ketonic group are two essential structural features in the bioactivity of flavonoids especially for antidiabetic property. Methylation and acetylation of hydroxyl groups were found to diminish the in vitro antioxidant and antidiabetic properties of the flavonoids.