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Medicinal plants used as immunostimulants were classified into two categories: Medicinal plants with pharmacological studies of their immunostimulatory properties were subclassified into four groups as follows: Pharmacological studies have been conducted on 29 of the plants, including extracts and compounds, whereas 75 plants lack pharmacological studies regarding their immunostimulatory activity.
Medicinal plants were experimentally studied in vitro 19 plants and in vivo 8 plants. A total of 12 compounds isolated from medicinal plants used as immunostimulants have been tested using in vitro 11 compounds and in vivo 2 compounds assays. This review clearly indicates the need to perform scientific studies with medicinal flora from Mexico, Central America, and the Caribbean, to obtain new immunostimulatory agents. The immune system is a complex organization of leukocytes, antibodies, and blood factors that protect the body against pathogens [ 1 ].
Innate immunity consists of cells such as lymphocytes, macrophages, and natural killer NK cells, which are the first line of host defence [ 23 ]. The NK cells lyse pathogens and tumor cells without prior sensitization [ 4 ]. Activated macrophages defend the host by phagocytosis, releasing the enzyme lysosomal acid phosphatase, and through the synthesis and release of nitrous oxide NO and hydrogen peroxide H 2 O 2 [ 56 ].
These two components inhibit the mitochondrial respiration and the DNA replication of pathogens and cancer cells [ 7 ]. When an infection occurs, macrophages and mast cells immediately release interleukins [ 2 ].
The interleukins link the communication between cells of the immune system, facilitating innate immune reactions. Among these cytokines, IL-2 and IL-6 induce the stimulation of cytotoxic T cells and enhance the cytolytic activity of NK cells [ 89 ].
Immunodeficiency occurs when there is a loss in the number or function of the immune cells, which might lead to infections and diseases such as cancer [ 1112 ]. Therefore, the discovery of agents which enhance the immune system represents an attractive alternative to the inhibition of tumor growth and the prevention and treatment of some infections. An immunostimulatory agent is responsible for strengthening the resistance of the body against pathogens.
In preclinical and clinical studies, some immunostimulatory medicinal plants e. In ancient traditional medicine, the term immunostimulant was unknown. Some of the in vitro and in vivo tests used to evaluate the immunostimulatory effects of plant extracts and compounds include the following: In vivo studies mainly consist in the induction of an immunosuppressed state in the animals by using a chemical agents such as 5-fluorouracil, cyclophosphamide, and methotrexate or b biological agents such as tumorigenic cells.
All the above-mentioned agents have been extensively studied on inducing immunosuppression [ 1516 ]. This review provides ethnomedicinal, phytochemical, and pharmacological information about plants and their active compounds used as immunostimulants in Mexico, Central America, and the Caribbean.
This information will be useful for developing preclinical and clinical studies with the plants cited in this review. A literature search was conducted from December to July by analyzing the published scientific material on native medicinal flora from Mexico, Central America, and the Caribbean. Academic information from the last five decades that describes the ethnobotanical, pharmacological, and chemical characterization of medicinal plants used as immunostimulants was gathered.
The following keywords were used to search for the academic information: No restrictions regarding the language of publication were imposed, but the most relevant studies were published in Spanish and English. The criteria for the selection of reports in this review were as follows: The immunostimulatory activity of plant extracts or compounds in combination with a known immunostimulant agent such as lipopolysaccharide, CD3 was omitted in this review.
Medicinal plants with pharmacological studies of their immunostimulatory properties were subclassified into four groups: The information for medicinal plants without pharmacological research was obtained from both undergraduate and postgraduate theses, in addition to peer-reviewed articles, and scientific books. We documented plant species belonging to 55 families that have been used as immunostimulants.
Of these plants, 28 have pharmacological studies Table 1and 76 plants lacked pharmacological research regarding their immunostimulatory activity Table 6. All plant names and their distributions were confirmed by consulting the Missouri botanical garden http: This was confirmed, for many plant species, by consulting our previous work [ 94 ].
Therefore, we highly recommend evaluating the immunostimulatory effects of medicinal plants used for cancer treatment. Diarrhea and cough are two symptoms associated with gastrointestinal and respiratory infections, respectively. We may therefore infer that immunostimulatory plants may also be used for the treatment and prevention of infections. A total of 20 plants, belonging to 15 botanical families, have in vitro studies regarding their immunostimulatory effects Table 2.
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Furthermore, 8 plant species from 8 botanical families were assessed using in vivo assays Table 3. A total of 11 compounds, isolated from 7 plants, have been tested using in vitro assays Table 4. Only two compounds, isolated from two plants, were studied using in vivo models Table 5. Plant extracts with immunostimulatory effects tested using in vitro assays. Solvent used for the extract: Among the in vitro studies, Lophophora williamsii was one of the plant species that showed good immunostimulatory effects.
This plant tested at 0. Further studies with Lophophora williamsiias well as the isolation and purification of its active compounds, are highly recommended. The immunostimulatory effects obtained using in vitro studies were confirmed in in vivo studies for some plant species such as Mollugo verticillataPhoradendron serotinumand Petiveria alliacea and compounds such as maturin acetate Figure 1.
This indicates that these plants and the compound can be metabolized, and their immunostimulatory effects are also shown in animals. Chemical structures of some compounds with immunostimulatory effects isolated from medicinal plants. On the other hand, in many works cited in this review, only one concentration or dose was tested.
In many studies, a single immunostimulant test is used e. Authors are encouraged to perform more than one immunostimulatory test in further studies to provide more information on the immunostimulant effects of plant extracts or compounds. In some cases, the initial screening of the in vivo immunostimulatory effects is carried out using immunocompetent mice.
Further studies are necessary to be performed on plant extracts and compounds using models of immunosuppressed mice, induced with chemical or biological agents. We documented 75 medicinal plants used as immunostimulants that lack pharmacological studies Table 6.
Plants from the Smilax genus S. Taking this into consideration, further studies with plants from the Smilax and Juglans genera should be carried out. Furthermore, mistletoe species such as Phoradendron brachystachyum and Psittacanthus calyculathus could be a good option for discovering immunostimulatory agents since the related species Phoradendron serotinum showed good immunostimulatory activity [ 41 ].
However, the toxicity of the mistletoe species should be assessed. More ethnobotanical studies are necessary to provide information on medicinal plants used as immunostimulants in Mexico, Central America, and the Caribbean. The ethnomedicinal information of plant species will be updated with these studies.
The toxicity of plant species cited in this review should also be assessed. For instance, Xanthium strumarium is considered a toxic plant. Recently, it was described that this plant induces hepatotoxicity [ 97 ]. On the contrary, Hymenaea courbaril was shown to lack genotoxic and mutagenic effects [ 98 ]. Toxicological studies are necessary to provide safety in the use of plant extracts and their compounds in clinical trials.
To our knowledge, there are no pharmacokinetic studies carried out with plant compounds cited in this review. This might be due to a the lack of established methodologies for their quantitation, b the quantity of the obtained compound being not enough to carry out a pharmacokinetic study, and c many plants extracts not being chemically characterized, and there is no main metabolite for its quantification using HPLC.
Further pharmacokinetic studies will provide additional pharmacological information prior to carrying out clinical trials. The isolation and elucidation of the structure of bioactive principles should also be encouraged. Eight percent of medicinal plants listed in this review are classified as endangered. In the order of most endangered, Juglans jamaicensisCedrela odorataand Lophophora williamsii are cataloged as vulnerable, whereas Taxodium mucronatumRhizophora mangleEysenhardtia polystachyaCordia alliodoraand Hymenaea courbaril are cataloged as of least concern [ 99 ].
For instance, Lophophora williamsii peyote is a species that has been overexploited because of its high content of hallucinogenic alkaloids.
Medicinal Plants from Mexico, Central America, and the Caribbean Used as Immunostimulants
The conservation of these species, as well as their habitats, should be encouraged by national and international programs to preserve biodiversity. There is null oadaquea limited information regarding the trade of medicinal plants used as immunostimulants.
Two of the markets are located in Xochimilco. In order of importance, the most recommended plant species used as immunostimulants are Justicia spicigeraPolygonum aviculareCarlowrightia cordifolia, Amphipterygium adstringens, Uncaria tomentosa, and others.
Its way of preparation consists of the following: The recommended administration is 3 times daily. Trade of slaud plants used as immunostimulants in Mexico City.
The demand for medicinal plants used as immunostimulants clearly indicates that these plant species are a current topic of interest.
This indicates that ethnobotanical knowledge is a valuable tool, which supports the selection of plants to carry out pharmacological studies. Some of the medicinal plants cited in our survey have been pharmacologically investigated. Carlowrightia cordifolia showed poor immunostimulatory effects [ 17 ].
Amphipterygium adstringens showed in vivo immunostimulatory effects [ 51 ], whereas masticadienonic acid Figure 1its active compound at 0. Justicia spicigera and kaempferitrin Figure 1its active compound, showed in vitro immunostimulatory effects [ 1454 ]. Nevertheless, the in vivo immunostimulatory effects remain to be performed with Justicia spicigerakaempferitrin, and masticadienonic acid.
The molecular mechanism by which this plant and the compounds exert their immunostimulatory effects should also be assessed. Finally, this review highlights the need to perform pharmacological, phytochemical, toxicological, and ethnobotanical studies with medicinal flora, from Mexico, Central America, and the Caribbean, to obtain new immunostimulatory agents. The authors wish to thank the Directorate for Research Support and Postgraduate Programs at the University of Guanajuato for their support in the editing of the English-language version of this paper.
National Center for Biotechnology InformationU. Evid Based Complement Alternat Med. Published online Mar 3.
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Introduction The immune system is a complex organization of leukocytes, antibodies, and blood factors that protect the body against pathogens [ 1 ]. Methodology A literature search was conducted from December to July by analyzing the published scientific material on native medicinal flora from Mexico, Central America, and the Caribbean.