Julio C. Escalona,
1Renato Peres-Roses,
2Jesús R. Rodriguez,
1Claudio Laurido,
3Raúl Vinet,
4Ariadna Lafourcade,
1Luisauris
Jaimes
5and José L. Martinez
6,*
Introduction
The use of medicinal plants is as old as the history of human beings. They set out to discover, use and convey knowledge that each of them had (Martinez and Marinoff 2008). The fi rst text known of medicinal plants dates back to approximately 3000 BC, along with written evidence of civilizations such as China, India, North Africa and Greece, based mainly on the treatment of diseases, their description and categorization. For instance “The use of aloe leaves for burns” is one such specifi c pharmacological effect (Newall et al. 1996).
The exploitation of medicinal and aromatic plants by man occurred in ancient times, as recorded in the historical evidence belonging to different civilizations and cultures that have been evolving on Earth (Subhaktha et al. 2006, Martinez and Marinoff 2008). Plants with medicinal properties were fi rst used empirically for the cure of diseases affl icting man; they also differentiated the ones that cured to those which killed, knowledge passed down orally from generation to generation, because of lack of writing in these early phases of human evolution. Subsequently, when writing developed and with the appearance of papyrus, men began collecting information, recording the heritage of a few in societies in which it has traversed humanity until today (Marinoff 2002). For example, the Bible describes approximately 200 medicinal plants and also its applications (CLIE 1985, Duke 2008).
1 Facultad de Farmacia, Universidad de Oriente, Santiago de Cuba, Cuba.
2 Unidad de Farmacología y Farmacognosia, Universidad de Barcelona, España.
3 Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago, Chile.
4 Facultad de Farmacia, Universidad de Valparaíso & CREAS, Valparaíso, Chile.
5 Facultad de Ciencias de la Educación, Universidad de Carabobo, Valencia, Venezuela.
6 Vicerrectoría de Investigación, Desarrollo e Innovación, Universidad de Santiago de Chile, Santiago, Chile.
* Corresponding author: joseluis.martinez@usach.cl
The Ebers Papyrus, written nearly 3,500 years ago, describes diseases and directions to solve them by using plant species. During the 12th–13th centuries, the Arabian school—reknowned for its physicians- and that of Salerno in Italy, prescribed many herbal drugs, many of which are in use today. At that time, the famous Arab physician Ibn Wafi d (born in Toledo in 1008 and passed away in 1074), author of ‘The Pillow Book’, a famous recipe book of the 11th century. His most original recipes, remedies included direct complaints or disturbances from the head to the toe nail. Numerous plants almost all of them from Spain and North Africa were used. In the 15th century, essences of bitter almonds, lavender, cinnamon, ginger, roses, sage and lavender among others, were recognized. A century later, more than 60 new scents were added to the list (Martinez and Marinoff 2008).
In 1511, in Barcelona, the fi rst regional pharmacopoeia in the world was published, the ‘Concordia Pharmacopolarum’. The famous Codex ‘De la Cruz Badiano’ written in 1552 by the Indian Xochimilca Martin de la Cruz and translated from Nahuatl into Latin by Juan Badiano in Mexico. It contains the herbal treasure of the ancient Mexicans. In the Middle Ages, the Arabs perfected the distillation of aromatic plants, hence encouraging the evolution of nascent and rudimentary pharmacy. In the 19(?) century, the fi rst chemical analysis of perfumes and other active components of the plant, with the help of analytical chemistry and microscope were performed. Leading to pharmacochemistry. In the early nineteenth century, morphine was isolated from opium (Sosa 1998). It can be said therefore that phytotherapy consists of the usage of plant products for therapeutic uses, either to forestall, mitigate or cure a diseased state.
In societies, especially those that are not highly developed economically, home remedies based on medicinal plants, usually provided by the older people (grandparents) are a common practice (Martinez and Marinoff 2008). Phytotherapy is therefore the outcome of a slow evolution, backed by practical experience.
It is believed, in general, that the discovery includes all the necessary steps so that it can be guaranteed that the compound possesses a desirable activity profi le; and comprises four principal stages: (1) Obtaining (from chemical synthesis, natural origin, or biotech variety), (2) Pharmaceutical formulation, (3) Preclinical pharmacology, and (4) Preclinical toxicology (studies in animal models). Thus, those compounds that carry through these stages are established as an accepted criterion for effi cacy and safety for testing in man.
The development phase consists of two steps: (1) Clinical trials phases I, II, III and IV (human experimentation) and (2) The pharmacist registration of the new drug (Escalona-Arranz et al. 2008).
The use of medicinal plants based on scientific evidence and security—A social need?
The use of drugs based on medicinal plants has become an important worldwide development in recent years.
Two different types of consumers exist: one that regards the ethnic heritage of peoples and is consumed locally according to well-defi ned populations, traditions-, and two, the one which is lawfully authorized to be made by doctors and sold by manufacturers and distributors. Both could ‘illustrate’ a society rooted in the use of natural products, but not necessarily the development of one of the two concurs with the parallel development of the other. It will be attempted to illustrate this statement with an example of each:
a country with a long tradition in the use of medicinal plants may not sustain the resources necessary for the growth and commercialization of products derived from these plants, or alternatively, lack laws to regulate and control the products obtained based on these own medicinal plants, thereby preventing the medical indication and the selling of them. On the other hand, a state or government could ‘facilitate’
the importation of foreign natural products over those of domestic output, thus undermining feedback implying acceptance by the population of the national product obtained, and may even ‘clear’ the original ethnobotanical knowledge.
If these cases can be seen as actual probable events, it can be assumed that the formation of a regulatory instrument that protects and which in turn ensures the quality of the drug product marketed, will allow the progress in parallel to both consumer lines, increasing the levels of acceptance of this practice in the worldwide population. This will precede to a literal and comprehensive development of the role of medicinal plants.
The data available to the public on the role of medicinal plants (product of the accumulation of ancestral and cultural experiences), is used by universities and research centers to demonstrate the verity of that
cognition. Grounded on this evidence, statute laws and regulations are promoted for disclosure, distribution and marketing, spreading that knowledge in society, which was the very root of the original knowledge.
This perspective of the development of natural products conforms exactly to what is technically divided into stages that defi nes the achievement of a new drug, and is taken over by the international scientifi c community; which supports two fundamental principles: the safe role of medicinal plants and established on scientifi c evidence.
From this viewpoint, the World Health Organization (WHO) in 1978 suggested incorporating traditional procedures (including the role of medicinal plants) to health systems in the context of each nation, in order to contribute to high levels of wellness. The same document states that: “Health systems can not dismiss the fact that medicinal plants and herbal medicines are a useful therapeutic resource, low cost and sustainable for all, if employed based on safety criteria, effi ciency and quality” (WHO 1978, WHO 1998).
The recognition by WHO of this need, emphasizes the importance that the organization presents to the involvement of governments, in society to establish comprehensive development policies and establish regulatory and legislative elements to sustain inquiry and evolution of products from medicinal plants.
This appeal has impacted even fi rst world nations, according to the current trend evidenced in a study conducted in 10 developed countries (Frass et al. 2012).
Other reasons why health organizations should prioritize the development of drugs from medicinal plants lie in the fact that the imbalance between the large transnational pharmaceutical development of new drug entities show by an overwhelming percentage, that the evolution of new drugs favors the elimination of health problems in industrialized nations with high income of its population. This further supports the fact that it is necessary that developing countries prioritize with endogenous resources (medicinal plants of traditional employment), studies related to pharmaceutical innovation. The existence of a scheme to ensure the protection of new products generated by the domestic industry, then emerges as essential to the survival of the same, so that innovative/production companies supported by their governments should take on IP systems (Trens 2000). This strategy will ensure a future, an increase in consumption by the population and an increase in the provision of therapeutic products associated with them.
Precisely these commercial aspects have been addressed very effectively in the study published by Alonso et al. (2008), when placed on the market of medicinal plants in the open market (depending on supply and demand) and the competitive market, where consumers can choose their treatment preferences according to their needs and their economic points. In essence, this view places all therapeutic products, food supplements and products based on medicinal plants as part of the free market (Martinez et al. 2009).
The fi nal decades of the 20th century has seen a profound transformation of the pharmaceutical sector. The adoption of the TRIPS agreement (Trade Related Aspects of Intellectual Property Rights) with the recognition of intellectual property rights and widespread international patent system for medicinal products, as defi ned in the agreements and the GATT (General Agreement on Tariffs and Trade), and explicitly adopted in 1994 by most ministers of the 123 participating states, has clearly favored the growth of the sector, but also the imbalance in terms of meeting social needs. Given this reality, it becomes more important as postulated by WHO and, which can be summarized as: the accumulated knowledge of the people about the utility of medicinal plants should be exploited by the most economically disadvantaged countries for the sake of satisfying the social need it intends to cover, basing it on scientifi c evidence and security of the developed formulations.
Legislative and regulatory landscape in Latin America
Wellness, as a concept, is the state of perfect physical, mental and social wellbeing and not just the absence of disease or debility. The benefi t of the highest attainable standard of health is one of the fundamental rights of every human being without distinction of race, religious belief, political opinion, economic or societal status.
Human rights refer mainly to the relationship between the nation and the individual; this generates state obligations and the individual’s access to such rights. Thus, governments have the main obligation for public health, hence resulting from formulating national health policies and/or the acceptance of legal instruments that regulate it.
Undoubtedly, the progressive Latin American integration (started in the late 20s and strengthened at the outset of this century), has been one of the main tasks of governments and parties of every nation in the area. Mercosur and the Community of Latin American and Caribbean States are, to mention just two, some major pacts that dominate the economic and political landscape of the region. The fraternity among the peoples of America has also seen a major boost in the past two decades. The political will for integration and cooperation among the American masses is now more than a statement or an intention, a reality.
Although this emerging exchange until today covers the main exportable area as energy (principally of petroleum and its derivatives), the agro industry and other industrial profi les, other fi elds of collaboration are more focused on social issues concerning each country, which undoubtedly pass by health problems.
The legislative and regulatory aspects of each Latin American country that will favor the pharmaceutical industry and natural products derived from, it can be part of these great economic operations with derivative social impact in small towns.
The confl icts between the laws of countries with large economic exchange for merchandise based on medicinal plants, has already generated more than one battle. Exemplars of this problem can be found in the common European market, especially prior to the European Directive 2004/24/EC which recognized that “these differences may hinder trade in traditional medicines in the residential area and lead to discrimination and distortions of competition between manufacturers of these wares. They can also impact on the protection of public health, as there always are currently offered the necessary guarantees of quality, safety and effi cacy”. This actually happened in Europe and can serve as an example in Latin America, to ensure that trade in medicinal plants and products thereof can enjoy a sound market based primarily on the quality and safety of the product sold (European Commission 2014).
The fi rst real intention of harmonization among Latin American nations emerged during the First International Coordination Meeting of the Latin American Network of Phyto-pharmaceuticals (RIPROFITO), X. Sub Pharmaceutical Fine Chemicals Iberoamerican Program of Science and Technology for Development (CYTED) made in 1996, where it established one of its aims, the advancement of Latin American plant protection products legislation.
In 2004 (García et al. 2004), a work that assesses the status of laws, rules and/or ordinances referred to natural products and herbal medicines of the 16 countries in Latin America so far issued, were implemented (Argentina, Bolivia, Brazil, Colombia, Costa Rica, Cuba, Ecuador, Spain, Guatemala, Mexico, Nicaragua, Panama, Peru, Dominican Republic and Venezuela) (Cañigueral et al. 2003). The picture revealed is quite complex. There are multiple problems that undermine the foundation of a single law, and among them were:
• The existence of different terms in the aim of legislation.
• Only 12 of the 16 countries had a list of offi cially recognized medicinal plants.
• Only eight of the 16 countries had a list of toxic plants or restricted use.
• Only fi ve nations had chosen to set up categories for enrollment and/or registration of the drug.
• Of the 16 countries, only 13 asked for product registration trial phytochemical identifi cation of the active constituent or characteristic constituents.
• Only four of the 16 countries requested the test or experiment preclinical toxicity and only two do so with respect to clinical toxicity.
• Only eight of the 16 countries applied for clinical trial or effi cacy.
• The genotoxic study is only requested by Cuba.
• The product stability tests are not demanded in two of the 16 countries (Costa Rica and Nicaragua).
They are also important differences corresponding to the implementation and impact of herbal productions among the countries studied. In Argentina, for instance, nearly half of the production of drugs comes from laboratories of national origin. Despite this panorama so encouraging, and being Argentina one traditionally agricultural country, pharmaceutical agribusiness is almost nonexistent. In Bolivia, although the practice of traditional is medicine is legally protected, there is no a national integration program for the practice to the general health and, therefore, the use of medicinal plants is not part of the therapeutic arsenal of resources of offi cial medicine. Despite this situation, it is evident the importance of medicinal plants in the national culture, easily quantifi able when noticing the leading role present in shops and popular markets (Cañigueral et al. 2003).
The opposite side of this phenomenon was proposed by Brazil and Cuba, countries where there are legal mechanisms (for more than two decades ago) that give herbs a special position in the context of the conventional health system. In both areas, their own state structures encouraged research and the presentation of these solutions to daily therapy. This made it possible to use various preparations from medicinal plants, enshrined in the popular tradition and confi rmed by scientifi c means for the main causes of action in the primary health network. It has also allowed them to offer an effi cient treatment option to people at affordable prices.
Irrespective of the differences in legislation and regulatory orders of the Latin American regions, in regards to the organization of health concern, there is consensus on the need to see alternatives and treatment choices that take advantage of local technical and production infrastructure. The clear objective is to reduce system costs and realize effi ciency and bargaining power. Rescue Practice of Phytotherapy, with its integration to therapeutic application systems, is a strategy that presents ample opportunities for consolidation, considering the great success that shows this practice for the general population.
A circle of natural processes to reach this end, especially those planned to surmount the troubles linked to technological dependence are defi nitely required. It is therefore an essential investment in the processes of research and development by state agencies, training of human resources and the junction with the productive sector. The possibility of use of phytotherapy in therapeutic practices, skill-based, multisectorial actions involving demands of primary production of medicinal plants to build quality control procedures of new textiles and medicines. These actions should be centered primarily on native plants present in the various ecosystems in the area, involving professionals from a broad scope of fi elds of knowledge, focusing on pharmaceutical and medical sciences, but also from chemistry, biology, agronomy, technology, among others.
The Cuban experience
Before addressing the development of herbal medicine in Cuban medicinal plants, it is necessary to defi ne the characteristics of the Cuban health system, which is based on the principle that health is a right of the people and a state responsibility. Cuba has chosen to produce a drug policy based on the needs and demand, not supply and market mechanisms, while preserving its unique health system, free and worldwide coverage;
but the fact remains that the economic needs of the rural area in the last years have been supported by the effi ciency of this system of wellness maintenance.
In its strategy on drugs, WHO identifi ed four central objectives: policy, access, quality and rational usage. It likewise said that an appropriate National Drug Policy is one that would ensure equitable availability and access to essential drugs for quality, safety and proven effi cacy; and assure the rational exercise of them by promoting their proper therapeutic use. Without losing this perspective, the growth of natural medicine in Cuba found political support that has contributed to progress levels shown today.
Backdrop to the usage of medicinal plants in Cuba
Unlike other parts of Latin America, the natives who inhabited the Cuban archipelago left no written or pictorial evidence on the role of medicinal plants to treat their ailments. It’s fast and violent extermination is another reason why it is considered that in Cuba, the introduction of herbal medicine began in the 15th century with the Spanish conquest. Apparently, it has been enriched over time with the arrival of migration from several regions of the globe, primarily from Africa and China, but also from other European nations such as France. In this operation of commingling of cultures accounted by the Cuban scholar Fernando Ortiz as Cuban acculturation, a civilization based on the use of herbal remedies has been well documented to this day. Without doubt, the greatest work collecting lore properties of medicinal plants used in Cuba is ‘Medicinal Plants, Aromatic and Poisonous of Cuba’, the fi rst version in 1945 and written by Dr. Juan Tomás Roig and Mesa, investigating the mountains and fi elds all over the island over 15 years. It names a total of 595 species that were employed by the Cuban population for different therapeutic uses and clearly calls for the national scientifi c community to examine these plants in order to verify their safety and effi cacy, with the resultant need to produce the domestic pharmaceutical industry (Roig 1945). While