DTI Drug Target Insights 2023; 17: 1-4ISSN 1177-3928 | DOI: 10.33393/dti.2023.2548EDITORIAL Drug Target Insights - ISSN 1177-3928 - www.aboutscience.eu/dti © 2023 The Authors. This article is published by AboutScience and licensed under Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). Commercial use is not permitted and is subject to Publisher’s permissions. Full information is available at www.aboutscience.eu Natural Products & Phytotherapeutics Natural Products & Phytotherapeutics: why a new section? Marcello Iriti Department of Biomedical, Surgical and Dental Sciences, Università degli Studi di Milano, Milan - Italy Received: December 12, 2022 Accepted: December 15, 2022 Published online: January 16, 2023 Corresponding author: Marcello Iriti Department of Biomedical, Surgical and Dental Sciences Università degli Studi di Milano Milan - Italy Marcello.iriti@polimi.it According to one of the most authoritative reports focus- ing on natural products as sources of new drugs, the use of natural products and their synthetic derivatives is still piv- otal in the discovery of new drugs (1). Indeed, among the new drugs approved (N = 1881) in the last four decades, about 25% are natural products (Fig. 1A). This scenario is particularly relevant for antibacterial and anticancer agents (Fig. 1B, C). This should not be surprising. Since ancient times, human- ity has made use of medicinal plants to heal itself, and even today, traditional medicine represents the dominant health care system in many parts of the world and for billions of people (2). This is the case of herbal medicines, the corner- stone of phytotherapy, which include, according to the World Health Organization (WHO), ‘herbs, herbal materials, herbal preparations and finished herbal products that contain, as active ingredients, parts of plants, other plant materials or combinations thereof’ (3). Several famous examples could be cited, from aspirin to many anticancer drugs (Tab. I). However, natural product research still suffers from some important limitations. First, the validation of traditional uses. Despite hundreds (or even thousands) of preclinical (in vitro/ in vivo) studies, evidence in humans is still scanty, due to the paucity of clinical trials evaluating the real efficacy of natu- ral products. Second, the poor oral bioavailability of natu- ral products. Phytochemicals are xenobiotics metabolized, detoxified and eliminated by phase I and II metabolizing enzymes and phase III transporters involved in efflux mech- anisms. This drawback can be bypassed by proper (nano) formulation. Third, natural does not always mean safe. The safety of natural products is rarely investigated and the avail- able information is scanty, as are the phytochemical-drug interactions with possible changes in therapeutic efficacy for some drugs with a narrow therapeutic index (4). These issues call for an evidence-based approach to be followed even for phytotherapeutics, where randomized controlled trials are at the top of the evidence-based pyramid (5). Fig. 1 - A) All new approved drugs by source from 1981 to 2019 (N = 1881). B) All antibacterial drugs by source from 1981 to 2019 (N = 162). C) All anticancer drugs by source from 1981 to 2019 (N = 247). Categories of sources: B = biological; N = natural product; NB = natural product – botanical; ND = natural product derivative; S = synthetic; S* = synthetic (with pharmacophore from a natural product); V = vaccine. Subcategory: NM = natural product mimic. Adapted from Newman and Cragg (1). A B C https://doi.org/10.33393/dti.2023.2548 https://creativecommons.org/licenses/by-nc/4.0/legalcode Natural Products & Phytotherapeutics: why a new section?2 © 2023 The Authors. Drug Target Insights - ISSN 1177-3928 - www.aboutscience.eu/dti TABLE I - Selected examples of drugs developed from medicinal plants Medicinal plant Drugs Indications Chemical structure Salix spp. Acetylsalicylic acid Anti-inflammatory, antiaggregant Catharanthus roseus Vinca alkaloids (vincristine, vinblastine, vinorelbine) Anticancer Camptotheca acuminata Camptothecin derivatives (topotecan, irinotecan) Anticancer Taxus brevifolia Taxane derivatives (paclitaxel, docetaxel, cabazitaxel) Anticancer Podophyllum peltatum Podophyllotoxin derivatives (etoposide, teniposide) Anticancer Cannabis sativa Cannabinoids (tetrahydrocannabinol, cannabidiol) Psychotropic Cinchona spp. Quinine Antimalarial Artemisia annua Artemisinin Antimalarial Iriti Drug Target Insights 2023; 17: 3 © 2023 The Authors. Published by AboutScience - www.aboutscience.eu Medicinal plant Drugs Indications Chemical structure Papaver somniferum Morphine, codeine Analgesic Digitalis spp. Glicosidi digitalici (digoxin, digitoxin) Cardiotonic Atropa belladonna Atropine Anticholinergic Hyoscyamus niger Hyoscyamine Anticholinergic Datura stramonium Scopolamine Anticholinergic Pilocarpus jaborandi Pilocarpine Cholinergic Colchicum autumnale Colchicine Antigout Galanthus spp. Galantamine Cholinesterase inhibitor Syzygium aromaticum Eugenol Antiseptic, anesthetic Rauwolfia serpentina Reserpine Antihypertensive Natural Products & Phytotherapeutics: why a new section?4 © 2023 The Authors. Drug Target Insights - ISSN 1177-3928 - www.aboutscience.eu/dti Not least, the combination of natural products with con- ventional drugs offers another area of application that should be pursued extensively. This has previously been investigated with natural products used in combination with anticancer drugs and antimicrobials. This therapeutic approach was able to (chemo)sensitize chemoresistant cancer cells, fungi and bacterial strains by inhibiting the cellular active efflux system, a conserved drug resistance mechanism that pumps xenobiotics out of the cell. The rationale for the use of natu- ral products is based on their multitarget action mechanism of particular interest in the treatment of disorders with mul- tistage pathogenesis. In this complex scenario, natural prod- ucts still offer the best options for finding new active agents/ templates and provide the unlimited potential for discover- ing new structures that can lead to effective drugs in a variety of communicable and non-communicable diseases. References 1. Newman DJ, Cragg GM. Natural products as sources of new drugs over the nearly four decades from 01/1981 to 09/2019. J Nat Prod. 2020;83(3):770-803. CrossRef PubMed 2. Iriti M. Journal of Phytomoleculs & Pharmacology: ‘Why a new journal?’ J Phytomol Pharmacol. 2022;1(1):1-2. Online 3. WHO Global Report on Traditional and Complementary Medicine 2019. World Health Organization; 2019. Online Accessed December 2022. 4. Peluso I. Phytomolecules-drug interactions: clinical and nutri- tional implications. J Phytomol Pharmacol. 2022;1(2):56-57. CrossRef 5. Varoni EM, Lodi G, Iriti M. Efficacy behind activity – phytother- apeutics are not different from pharmaceuticals. Pharm Biol. 2015;53(3):404-406. CrossRef PubMed https://doi.org/10.1021/acs.jnatprod.9b01285 https://www.ncbi.nlm.nih.gov/pubmed/32162523 https://leafletpub.com/article-detail/12 https://apps.who.int/iris/handle/10665/312342 https://doi.org/10.56717/jpp.2022.v01i02.008 https://doi.org/10.3109/13880209.2014.923000 https://www.ncbi.nlm.nih.gov/pubmed/25472494