Biotechnological herbal product from Uncaria tomentosa

• Grant number: 23/05517-3
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2025
• End date: April 30, 2027
• Field of knowledge: Interdisciplinary Subjects
• Principal Investigator: Juliana da Silva Coppede
• Grantee: Juliana da Silva Coppede
• Host Institution: Universidade de Ribeirão Preto (UNAERP). Campus Ribeirão Preto. Ribeirão Preto , SP, Brazil
• Associated researchers: Adriana Aparecida Lopes ; Ana Maria Soares Pereira ; Bianca Waleria Bertoni ; Fabio Carmona

Abstract

In 2022, the Food and Drug Administration's (FDA) Center for Drug Evaluation and Research (CDER) approved 37 new drugs. This number of approved molecules remains above the historical average since 1993, of approximately 34 drugs per year (Mullard, 2022). Among the main global pharmaceutical industries, the company AbbVie stands out, which in 2017 was highlighted worldwide for its sales of Humira (Adalimumab®), a medicine used to treat rheumatoid arthritis. In 2020, this medicine generated sales of 19.8 billion dollars, and in 2021 it exceeded US$ 20.7 billion. The main factors driving this market are the growing incidence of rheumatoid arthritis coupled with the increase in the geriatric population. Although there are several therapies and medications developed in recent years to treat the symptoms of rheumatoid arthritis, the management of these medications is generally associated with a high cost. In August 2022, the Institute of Immunobiological Technology (Bio-Manguinhos/Fiocruz) began supplying the drug Adalimumab to the Unified Health System (SUS). Currently, more than 60 thousand patients are using this medicine in the SUS. An alternative to the treatment of rheumatoid arthritis, as well as other inflammatory diseases, is the medicinal species Uncaria tomentosa (Willd. ex. Schult.) DC., a plant native to the Amazon region. In Brazil, the species occurs in the states of Acre, Amapá, Amazonas and Pará, has potent anti-inflammatory action and produces oxindolic alkaloids, which appear to be related to this activity (Setty; Sigal, 2005; Rojas-Duran et al., 2012 ; Azizian et al., 2021). Currently, dozens of phytomedicines are being sold nationally in various pharmaceutical forms. The raw material of U. tomentosa, in the form of an input, is sold by several industries, in particular by Givaudan, based in Switzerland, and by Centroflora, a Brazilian company that was recently incorporated into Givaudan. Although this plant is widely used in several countries as a herbal medicine, and in Brazil it is included in the list of RENAME (National List of Essential Medicines) of the SUS (Unified Health System), there is, to date, no cultivation and management of U. tomentosa, and all raw materials used in the production of herbal medicines are obtained extractively. Another factor to be considered is that the European Medicines Agency (EMA), in its official document dated November 24, 2015, concludes that the sample size of human clinical studies, as well as the use of different extracts, carried out up to the time of preparation of the document, did not provide conclusive evidence on the clinical efficacy of preparations based on the Uncaria tomentosa plant. Therefore, the objective of this project is to characterize the genetic and chemical variability of individuals maintained in the U. tomentosa in vitro germplasm bank with the purpose of finding elite genotypes for establishing cultivation and obtaining a standardized phytomedicine. The characterization of genetic variability will be carried out using the molecular marker SCoT, while the chemical analysis of oxindolic alkaloids will be carried out using HPLC-UV and metabolomics, carried out using data obtained through UPLC-MS, analyzed in databases. The execution of this project will allow us to understand the genetic and chemical diversity of the individuals that make up the germplasm bank, with the most promising accessions being evaluated for the production of oxindole alkaloids. Once identified, these individuals will be multiplied and made available for planting in Life Pharmacy aiming at the production of herbal medicines from plants cultivated or obtained from biotechnological processes. (AU)