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Phytocannabinoids and Their Potential Use As a Phytochemotherapy International Journal of Pharmacognosy & Chinese Medicine ISSN: 2576-4772 MEDWIN PUBLISHERS Committed to Create Value for Researchers Narrative Review: Phytocannabinoids and their Potential Use as a Phytochemotherapy Suttithumsatid W1 and Panichayupakaranant P1,2* Review Article 1Department of Pharmacognosy and Pharmaceutical Botany, Prince of Songkla University, Volume 4 Issue 3 Thailand Received Date: November 15, 2020 2Phytomedicine and Pharmaceutical Biotechnology Excellence Center, Faculty of Published Date: November 30, 2020 Pharmaceutical Sciences, Prince of Songkla University, Thailand DOI: 10.23880/ipcm-16000209 *Corresponding author: Pharkphoom Panichayupakaranant, Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat-Yai 90112, Thailand, Tel: +66- 74-288980; Email: [email protected] Abstract Cannabis sativa L. has been used as an herbal medicine for centuries. This plant is a natural source of cannabinoids, including research topic on their therapeutic properties. The human endocannabinoid system generally consists of receptors, endogenous ligands,Δ-9-tetrahydrocannabinol and metabolizing (THC)enzymes, and and cannabidiol plays an (CBD), important the two role major in various phytocannabinoids physiological thatand havepathological been a recently effects. interested Based on cancer therapy, phytocannabinoids have mainly been used for palliative care treatment, i.e. relieving nausea and vomiting caused by chemotherapy and stimulating appetite. Additionally, in many preclinical experiments, including in vitro and in vivo studies, cannabinoids have exhibited anticancer effects against numerous cancer cell lines through various mechanisms. For example, THC induced apoptosis of cancer cells via cannabinoid receptors by a stimulation of ceramide synthesis led to an activation of the endoplasmic reticulum stress-related signaling pathway, and the induction of autophagy through a calmodulin-activated kinase kinase β. In contrast, the anticancer activity of CBD is related to other types of receptors, i.e. orphan G-protein coupled receptor 55 (GPR55), transient receptor potential vanilloid receptor 1 (TRPV1), transient receptor to induced cancer cell death. Although, there are many reports on anticancer properties of phytocannabinoids, in vitro and potential melastatin 8 (TRPM8), which mainly relied on the stimulation of reactive oxygen species (ROS) production, leading in vivo phytochemotherapy. , high quality clinical trials concerning their efficacy and safety are still essential to approve their potential use as a Keywords: Cannabis sativa; Cannabinoid; Cancer; Tetrahydrocannabinol; Cannabidiol ; HPLC Introduction todeaths) 23.6 million and breast by 2030 cancer [1]. Currently, (627,000 conventional deaths), respectively. medicine of abnormal cells that affect the human body. Cancer is a playsThe number an important of new role cancer in cancer cases pertreatment. year is expectedThere are to many rise seriousCancer global is publica generic health term problem for the and uncontrolled the second leadinggrowth routes of cancer treatment depending on types of cancer, cause of death that estimated 9.6 million deaths in 2018. the levels of invasion and the performance status of patients The most common causes of cancer death were lung cancer or[2]. radiation However, therapy. most patients In addition, commonly immunotherapy, need a combination targeted (1.76 million deaths); colorectal cancer (862,000 deaths); of treatments, such as surgery with chemotherapy and/ liver cancer (828,945 deaths); stomach cancer (783,000 Narrative Review: Phytocannabinoids and their Potential Use as a Phytochemotherapy Int J Pharmacogn Chinese Med 2 International Journal of Pharmacognosy & Chinese Medicine cancer therapy, cannabinoids have recently been used for palliative care, i.e. relieving nausea and vomiting caused by especiallytherapy, and from hormone systemic therapy chemotherapy, also have benefitsare often in severe,cancer suchtreatment as [2,3].cardiotoxicity, Moreover, bladderside effects toxicity, of cancer neurotoxicity, treatment, preclinical experiments including in vitro and in vivo studies renal toxicity, gastrointestinal toxicity, hepatotoxicity, and havechemotherapy revealed and that stimulating cannabinoids appetite possessed [17]. However, anti-tumor many effects against numerous cancer cell lines through various mechanisms [18,19]. Nevertheless, anticancer effects of hematopoietic system injury. Subsequently, these adverse cannabinoids appear to be dependent on the type of cancer effectsCurrently, may be apotential major cause strategies of therapy to manage discontinuation adverse effect[4,5]. from cancer treatment focus on alternative treatments, especially the use of natural products including crude herbal and concentration of cannabinoids [20]. This review aims to botanicalsummarize sources, the scientific physicochemical studies on anticancerproperties, potentials biogenesis, of anticancer agents are being clinically used to treat or prevent quantitativeTHC and CBD. HPLC Moreover, analysis, important and toxicity information, assessment including are developmentextracts and pureof cancer. phytochemicals These plants-derived [4]. Many plant-derived anticancer described. agents can be divided into 4 groups, namely Vinca alkaloids Catharanthus roseus Taxus Taxus Retrieval Strategies and Methods brevifolia Podophyllum Podophyllum peltatum and(from P. hexandrum ), Camptotheca diterpenes (from Cannabis Camptotheca), acuminate lignansVinca (from alkaloids, i.e. vinblastine sativa, cannabinoid, endocannabinoid, phytocannabinoid, and vincristine, are ),common and allopathic medicine alkaloids used (from for anticancer,Based on thisantitumor, narrative review,tetrahydrocannabinol, the keywords of and treatment of Hodgkin’s) [6].disease and acute lymphoblastic leukemia in children by inhibiting the dynamics of (https://pubmed.ncbi.nlm.nih.gov/ advancedcannabidiol) were searched in the online search engines, ® Taxus including PubMed themicrotubules microtubule by disruptorsbinding to forβ-tubulin treatment in the of ovarian,mitotic spindlebreast, , Science Direct. (https://www.sciencedirect.com/ lung,[7,8]. Paclitaxelhead, and (Taxol neck cancers) is a [9,10]. diterpene Podophyllotoxin widely used is asa search) and Google (https://www.google.com) to obtain 100 podophyllum lignan that has been used for treatment of selected scientific articles Most of them have been published numerous cancers including testicular, breast, pancreatic, betweenCannabinoids 2006-2020. lung, stomach, and ovarian cancers. A mechanism of action Endocannabinoids: Basically, cannabinoids can be preventing cell division [11]. Camptothecin, a Camptotheca divided into 3 groups, namely endocannabinoids, alkaloidof podophyllotoxin that has been is basedused as on a broad-spectrumbinding with tubulin, anticancer thus phytocannabinoids and synthetic cannabinoids [20]. agent for different types of cancer patient, such as small- Endocannabinoids are the endogenous ligands that are cell and non-small cell lung, breast and liver cancers [12]. produced in the human body and bind to the cannabinoid Camptothecin binds to the topoisomerase I and DNA complex, thus causing DNA damage and resulting in cell N apoptosis [13,14]. receptors. Two major endocannabinoids, anandamide ( -arachidonoylethanolamine; AEA) and 2-arachidonoyl Cannabis sativa has been used as an herbal medicine inglycerol response (2-AG) to haveincrease been intracellular identified asCa arachidonic2+ concentration acid for centuries. It is a natural source of natural cannabinoids, and/orderivatives to (Figureactivate 1), Gq/11-coupledwhich are produced receptor on demand[21,22]. Endocannabinoids are produced from postsynaptic pharmacologicalincluding Δ-9-tetrahydrocannabinol properties [15]. Therefore, medical(THC) use ofand C. retrograde signaling systems in the brain [23]. AEA acts as sativacannabidiol (CBD), which have been investigated for their terminals following neuronal activation and mediated investigation and publication. The endocannabinoid systemhas consisting recently beenof receptors, increasing endogenous with the rise ligands, of scientific and a partial agonist of cannabinoid receptors type 1 (CB1) with metabolizing enzymes, makes important contributions higher affinity and is almost inactive against cannabinoid in physiological and pathological processes of the human receptors type 2 (CB2). AEA also activates transient receptor body [16]. Currently, there are many preclinical and clinical potential vanilloid receptor 1 (TRPV1) and the peroxisome studies indicating that cannabinoids have therapeutic phospholipaseproliferator-activated D and degraded receptor (PPAR).by fatty AEAacid isamide catalyzed hydrolase from potential in many diseases, such as nausea and vomiting N-acyl-phosphatidylethanolamine (NAPE) by NAPE-specific into arachidonic acid and ethanolamine whereas 2-AG acts andassociated they witheven cancerdisplay chemotherapy, some anticancer intractable properties. childhood In eitheras a full DAG agonist lipase-alpha on both or CB1-beta, and and CB2 mostly with hydrolyzed moderate byto epilepsy, muscle spasms in patients with multiple sclerosis, low affinity. 2-AG is produced from diacylglycerol (DAG) by Suttithumsatid W and Panichayupakaranant P. Narrative Review: Phytocannabinoids and their Copyright© Suttithumsatid W and Panichayupakaranant P. Potential Use as a Phytochemotherapy. Int J
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