Traditional Uses, Phytochemistry, and Bioactivities of <i>Mesosphaerum suaveolens</i> (L.) Kuntze

Almeida-Bezerra, José Weverton; Rodrigues, Felicidade Caroline; Lima Bezerra, José Jailson; Vieira Pinheiro, Anderson Angel; Almeida de Menezes, Saulo; Tavares, Aline Belém; Costa, Adrielle Rodrigues; Augusta de Sousa Fernandes, Priscilla; Bezerra da Silva, Viviane; Martins da Costa, José Galberto; Pereira da Cruz, Rafael; Bezerra Morais-Braga, Maria Flaviana; Melo Coutinho, Henrique Douglas; Teixeira de Albergaria, Edward; Meiado, Marcos Vinicius; Siyadatpanah, Abolghasem; Kim, Bonglee; Morais de Oliveira, Antônio Fernando

doi:https://doi.org/10.1155/2022/3829180

Evidence-Based Complementary and Alternative Medicine

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Medicinal Plants and Natural Products in Health Promotion and Disease Prevention

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Review Article | Open Access

Volume 2022 | Article ID 3829180 | https://doi.org/10.1155/2022/3829180

Traditional Uses, Phytochemistry, and Bioactivities of Mesosphaerum suaveolens (L.) Kuntze

José Weverton Almeida-Bezerra,¹Felicidade Caroline Rodrigues,¹José Jailson Lima Bezerra,¹Anderson Angel Vieira Pinheiro,²Saulo Almeida de Menezes,¹Aline Belém Tavares,¹Adrielle Rodrigues Costa,¹Priscilla Augusta de Sousa Fernandes,³Viviane Bezerra da Silva,¹José Galberto Martins da Costa,³Rafael Pereira da Cruz,³and Maria Flaviana Bezerra Morais-Braga³ et al.

Academic Editor: Sekar Vijayakumar

Received01 Dec 2021

Revised28 Jan 2022

Accepted16 Feb 2022

Published10 Mar 2022

Abstract

Mesosphaerum suaveolens (L.) Kuntze is a species widely used traditionally in the treatment of ailments, such as stomach pain, hemorrhoids, cough, verminosis, ulcer, liver disease, fever, influenza, nasal congestion, and inflammation. This review aims to provide a survey of available information on seven international electronic databases (Google Scholar, Medline, ResearchGate, Web of Science, Scopus, Science Direct, and PubMed) about botanical aspects, traditional uses, phytochemistry, and biological activities of M. suaveolens. Mesosphaerum suaveolens is a tropical America native species, but it can be found in several parts of the world as a ruderal plant. The species is the most studied species of the genus Lamiaceae due its phytochemical aspect, especially regarding the chemical composition of its essential oil. Besides the essential oils, M. suaveolens is a source of numerous secondary compounds such as triterpenes, diterpenes, and phenolic compounds, which are related to its biological activities, such as allelopathic, antibacterial, antifungal, insecticidal, and larvicidal activities as described in the literature.

1. Introduction

Plant species, with medicinal properties that have always been part of human life, are being used both for the treatment of diseases as for food. For the treatment of diseases, they are accessible and culturally accepted, so their use is popular since ancient civilizations [1, 2]. The Lamiaceae family is one of the most diverse and widespread in terms of the ethnomedicinal value and variety of plants with biological and medical applications [3–8]. Regarding the genus Mesosphaerum, previous studies demonstrate the ethnomedicinal and pharmacological importance of some species that belong to it, such as Mesosphaerum sidifolium (L’Hérit.) Harley & J.F.B. Pastore, used to treat stomach disorders and headaches, as well as being used as an expectorant, carminative, and tonic. This species possesses in vivo antitumor activity against Ehrlich ascites carcinoma cells causing growth inhibition by inducing cell cycle arrest, besides not showing cytotoxicity [9]. Another species with several bioactivities is Mesosphaerum verticillatum (syn. Hyptis verticillata Jacq.) with anti-inflammatory, antimicrobial, and anticancer potentials, among other reports. Ethnomedicinal uses of this plant include cough, colds, asthma, fever, tonsillitis, uterine fibroids, bronchitis, and gastrointestinal problems [5].

In Northeast Brazil, the use of plant species as therapeutic resources is widespread, and one species present in this region is Mesosphaerum suaveolens (L.) Kuntze, known as “bamburral,” “erva-canudo,” or “alfazema-brava” [10]. Its leaves are mainly used to treat respiratory diseases (asthma, bronchitis, colds, and flu) and diseases related to the gastrointestinal tract [1]. Such medicinal uses are related to the chemical heterogeneity arising from the secondary metabolism of the species, a recurrent characteristic in species of the Lamiaceae family [6].

Several works in the literature indicate that M. suaveolens presents a high biotechnological potential, mainly regarding its essential oil [10]. In addition, a large number of studies have emphasized the biological activities of the essential oil and extracts of this species against pathogenic microorganisms to humans [6]. Taking into account that M. suaveolens is a medicinal species widely studied by the scientific community, the main objective of this work was to make a general review of the botanical aspects, traditional uses, phytochemistry, toxicity and biological, and pharmacological activities.

2. Materials and Methods

Methodologically, it was used the keywords “Mesosphaerum suaveolens” and its synonym “Hyptis suaveolens” associated to the terms “biological activity,” “bioactive,” “ethnomedicinal use,” “traditional use,” “ethnobotany,” “ethnopharmacology,” “toxicity,” “natural products,” “phytochemistry,” and “allelopathy” to collect information available on Google Scholar, Medline, ResearchGate, Web of Science, Scopus, ScienceDirect, and PubMed databases. The consideration insertion criteria of the articles were as follows: full article only, articles written in English and/or Portuguese languages, and all available and opened access articles, with no time limit determined.

It was obtained 190 articles dated between 1971 and 2021 which were grouped into some categories. (1) Botanical aspects, with information on description, classification, and geographical distribution; (2) phytochemistry; (3) ethnobotany; (4) biological activities; and (5) pharmacological activities. The trial process (collecting of the articles, reading of the abstracts, and checking the insertion criteria) took three months, and all the selected articles had been read completely and summarized in a table with the isolated chemical constituents and their respective biological activities.

3. Review

3.1. Botanical Aspects: Description, Classification, and Distribution

Mesosphaerum suaveolens (L.) Kuntze is an herbaceous plant belonging to the Lamiaceae family. The word “mesosphairon” comes from the Greek and Latin “mesosphaerum,” meaning “a type of tuberose with medium-sized leaves,” while its specific epithet suaveolens, means “with a sweet fragrance” due to the aroma of essential oils exhaled by the trichomes present on its leaves [11, 12].

Its vernacular name varies widely according to the region of occurrence. In the northeastern region of Brazil, the species is known as “bamburral” and “alfazema-brava” and in the southern region of the country, the herbaceous plant is called “erva-canudo” and “betônica-brava” [10]. In other parts of the world, such as in India, it is known as “pignut,” “beejabandha,” “sima tulasi,” “sakavong,” “pichi tulas,” and “bushmint” [13], while in Nigeria, it is known as “false buttonweed” and in Bangladesh as “tukma” [14]. In French-speaking countries, the species is called “horehound,” “pignut,” “wild spikenard,” “gros baume,” and “Hyptis à odeur.” In other languages, the plant is called “chao,” “hierba de las muelas,” “menta de campo” (Spanish), “wilaiti tulsi” (Hindi), “bhustrena,” “darp tulas,” “jungli tulas” (Marathi), “sirna tulasi” (Telugu), “bilati tulas” (Bengali), “ganga tulasi” (Ora), and “bhustrena” (Sanskrit) [13].

Taxonomically, M. suaveolens presents as botanical synonyms Ballota suaveolens L., Hyptis suaveolens (L.) Poit., Bystropogon suaveolens (L.) L’Hér., Bystropogon graveolens Blume, Hyptis congesta Leonard, Hyptis ebracteata R.Br., Hyptis plumierii Poit., and Marrubium indicum Blanco, with H. suaveolens as the most widespread synonym in scientific circles. However, the current circumscription of the genus Mesosphaerum P. Browne was recognized in 2012 after phylogenetic studies [15].

Morphologically, M. suaveolens is an erect herb or subshrub that measures up to 2 m in height. Its photosynthetic quadrangular stem is hairy with closely spaced branches and nodes. It has oval leaves, serrate or cordate margin, pilose limb, acute apex, and obtuse base with opposite crossed phyllotaxis. The petioles are short, canaliculate, as are its stems. Its inflorescences consist of up to 20 flowers located around the nodes and near the leaf axils. The flowers are pedunculate, with a persistent, tubular calyx, and 5 pointed sepals. The corolla is also tubular with five lilac petals, and the lobes are evident. Its fruits are dry, indehiscent, and uniseminated, originating from a bicarpellate gynoecium. Such fruits originate dimorphic seeds, two per fruit. Morphologically, such diaspores are elongated with dorsoventral flattening, longitudinal median ridge, starting near the hilum and extending to the apex of the seed with retusa boundary with black coloration (Figure 1) [16–18].

As for the geographical distribution, M. suaveolens is native to tropical America; however, as it is ruderal, it ended up invading natural ecosystems in tropical and subtropical regions of the globe, so that, due to this widespread occurrence, the species is considered a pantropical ruderal species [19–22]. In Brazil, M. suaveolens is present in almost the entire territory [23].

3.2. Phytochemistry

Mesosphaerum suaveolens is an important source of essential oils, alkaloids, flavonoids, phenols, saponins, triterpenes, and sterols [13, 24]. The essential oil of this species, obtained exclusively from its leaves, has already been chemically characterized in several studies. However, since this species exhibits a high level of genetic polymorphism and allows adaptation to changes in environmental characteristics, high variability in the composition and content of the major constituents (>20%) has been found [25]. In M. suaveolens extracts, terpenoids had a great predominance (mono, di, tri, and sesquiterpenes) (Table 1) (Table 1). Among the diterpenes, suaveolic acid stood out with recognized antimicrobial and allelopathic action [26]. Furthermore, phenolic acids, phenylpropanoids, flavonoids [10, 27], and fatty acids [28, 29] were also identified in different parts of M. suaveolens (Table 1).

3.3. Ethnobotany

Traditionally, M. suaveolens is taken to treat ailments in Brazil, Benin, India, Nigeria, Thailand, and Togo. In Brazil, the leaves in the form of infusions, decoctions, teas, and syrups are used to treat ulcers, inflammation, respiratory diseases (asthma, bronchitis, colds, flu, and sinusitis), diseases related to the gastrointestinal tract, pain, dizziness, nausea, nervousness, and constipation [1, 56–64]. The leaves are also used to treat headaches [65], malaria [14, 66], fever [67, 68], and used to reduce labor time and labor pain [69]. The flowers of M. suaveolens are employed as therapeutic resources against dysmenorrhea, respiratory diseases, and as a febrifuge [70, 71].

In the Asian continent, more specifically in India, the leaves, stems, inflorescence, and roots are used to treat urinary calculi [72], stomach pain [73], healing, itching [74], boil, eczema, diabetes [75], pneumonia [76], and fever [77]. Besides that, the seeds of M. suaveolens are used to treat gynecological disorders such as menorrhagia, leucorrhea, and rheumatism [78, 79]. The fresh poultice of the leaves is applied to snake bites, wounds, and mycoses [80], while the paste of the fresh leaves is also indicated for skin diseases [81].

In South Asia, in Bangladesh, traditional communities use the seeds in juice preparations to treat constipation and weakness [82, 83]; in addition, the seeds are consumed along with roots of Bombax ceiba to treat gonorrhea [84, 85], and the paste of the leaves is used to treat skin infections [86]. In Togo, the leaves of the species are spent in decoction form for the treatment of gynecological disorders [87], while in Thailand, the decoction of the roots is indicated in cases of food poisoning [88]. On the African continent, more specifically in Benin and Nigeria, the whole plant of M. suaveolens is used for the treatment of candidiasis and as a blood tonic [89, 90].

From a veterinary point of view, M. suaveolens has also been used for the treatment of diseases in animals. Such use is reported in India for the treatment of inflammation in cattle, with the juice of the leaves being applied to the animal’s eyes [91]. In Brazil, the species is employed against diarrhea [92]. In the African continent, more specifically in Kenya, the aerial parts of the plant are utilized as a repellent for the mosquito Anopheles gambiae Giles, 1926 (Diptera: Culicidae) [93, 94].

3.4. Biological Activities

3.4.1. Allelopathic Activity

According to Sharma et al. [95], after the establishment of M. suaveolens in an area, it becomes evident that the species imposes a profound impact on the local vegetation, as the number of species, richness, diversity, and uniformity is severely reduced. Although M. suaveolens is native to the Brazilian territory, it is distributed in different ecosystems, such as Caatinga, a seasonally dry tropical forest [20].

Mesosphaerum suaveolens produces numerous seeds of rapid germination and subsequent growth and thus manages to occupy and dominate environments because of its allelopathic action [96]. Islam et al. [26], for example, isolated suaveolic acid from M. suaveolens and demonstrated in bioassays that this diterpene exhibits allelopathic action, interfering with the growth of the caulicle and radicle of Lepidium sativum L. (Brassicaceae), Lactuca sativa L. (Asteraceae), Lolium multiflorum Lam. (Poaceae), and Echinochloa crus-galli (L.). P. Beauv. (Poaceae). Their extracts present allelopathic action against Echinochloa crus-galli (L.) P. Beauv. [97], Sorghum vulgare Pers., Raphanus sativus L., and Lactuca sativa L. [98].

Allelochemicals present in the species have been reported to act by causing oxidative stress, reduction in chlorophyll content, and inducing the formation of chromosomal aberrations [99, 100]. Such damage may occur in response to the synergistic action of the constituents.

In addition to heterotoxicity, M. suaveolens has been found to exhibit autotoxicity; however, its constituents affect other species more than itself [101]. Thus, the low amounts of allelochemicals released by M. suaveolens affect the ecological succession of other species, but do not affect the species itself as much.

Despite reports of the allelopathic action of M. suaveolens, it is worth noting that most of these studies were conducted under laboratory conditions and with extracts of the plant, so these actions do not match the allelopathic actions found in the environment. Thus, it is necessary to conduct studies that simulate as much as possible the natural conditions, to affirm whether one species can affect another. Only Kapoor [99] evaluated the allelopathic action of M. suaveolens in conditions similar to those found in the environment, demonstrating in fact that the species has allelopathic action on Parthenium hysterophorus L. (Asteraceae).

M. suaveolens has allelochemicals from its secondary metabolism, which compromise the structure and plant diversity [102].

3.4.2. Antimicrobial Activity

Teas of M. suaveolens are used to treat diseases related to the gastrointestinal and respiratory tracts [1], so numerous researchers have hypothesized that the species exhibits biological activity against strains of pathogenic microorganisms.

Cyrille et al. [103] evaluated the antibacterial action of the hydroethanolic extract (70%) of the leaves and found that the species presented low antibacterial activity since an MIC of 3.12 mg/ml was observed against Staphylococcus aureus (Rosenbach, 1884) (Staphylococaceae) ATCC 25923 and Pseudomonas aeruginosa (Schroeter, 1872) (Pseudomonadaceae) ATCC 27853 strains. It is worth noting that MIC values obtained above 1 mg/ml (1000 μg/ml) do not reflect clinically notable activity (Van Vuuren, 2008) (Table 2).

The works evaluating the antimicrobial action of the species highlight the use of the volatile terpenes (essential oils) of the leaves (Table 2). Xu et al. [104] demonstrated that the oil of M. suaveolens showed antimicrobial action through the microdilution technique with MIC values of great clinical relevance, notably against Bacillus subtilis (Cohn, 1872) (Bacillaceae) CMCC 63501, Escherichia coli (T. Escherich, 1885) (Enterobacteriaceae) CMCC 44102, and Botrytis cinerea (De Bary) Whetzel, 1945 (Sclerotiniaceae). The oil was also very active against S. aureus CMCC 26001, P. aeruginosa CMCC 10104, Fusarium graminearum Schwabe, 1839 (Nectriaceae), Exerohilum turcicum (Pass.) K.J. Leonard & Suggs, 1974 (Pleosporaceae), and Lecanosticta acicola (Thüm.) Syd., 1924 (Mycosphaerellaceae).

Besides the essential oil, the fixed oil from M. suaveolens seeds showed activities of clinical relevance against E. coli MTCC 443 (MIC 0.5 mg/ml), Salmonella typhi Typhi (Enterobacteriaceae) MTCC 531 (MIC 0.125 mg/ml), Shigella flexneri Castellani & Chalmers, 1919 (Enterobacteriaceae) MTCC 1457 (MIC 0.5 mg/ml), Vibrio vulnificus (Reichelt et al.) Farmer, 1980 (Vibrionaceae) MTCC 1145 (MIC 0.5 mg/ml), P. aeruginosa MTCC 424 (MIC 0.125 mg/ml), Lactobacillus plantarum (Orla-Jensen) Bergey et al., 1923 (Lactobacillaceae) MTCC 2621 (MIC 0.125 mg/ml), Lactobacillus leishmanii (Henneberg) Bergey et al. 1923 (Lactobacillaceae) MTCC 911 (MIC 0.25 mg/mL), S. aureus MTCC 737 (MIC 0.25 mg/ml), Candida tropicalis Berkhout, 1923 (Saccharomycetaceae) MTCC 227 (MIC 0.125 mg/ml), and Candida albicans Berkhout, 1923 (Saccharomycetaceae) MTCC 227 (MIC 0.25 mg/ml) (Table 2).

3.4.3. Insecticidal Activity

Popularly, in Kenya, the aerial parts of M. suaveolens are burned to repel mosquitoes of the species Anopheles gambiae [84, 94]. Subsequently, other researchers have highlighted that the oil has biological action against various insects, such as A. gambiae itself (Table 3).

Works evaluating the insecticidal action showed that the essential oil of M. suaveolens by fumigation showed the effect against Callosobruchus maculatus (Fabricius 1775; Coleoptera: Chrysomelidae) (CL₅₀ 4.7 μg/ml), Rhyzopertha dominica (Fabricius 1972; Coleoptera: Bostrichidae) (CL₅₀ 12 μg/ml), Sitophilus oryzae (Linnaeus 1763; Coleoptera: Curculionidae) (CL₅₀ 10.6 μg/ml), Tribolium castaneum (Herbst 1932; Coleoptera: Tenebrionidae) (CL₅₀ 23.2 μg/ml) (Tripathi; Upadhyay 2009), and Sitophilus granarius (Linnaeus, 1758) (CL₅₀ 0.251 μl/insect) [138].

Mesosphaerum suaveolens oil showed toxicity through contact and ingestion against Mediterranean flies (Ceratitis capitata (Wiedemann, 1824) (Diptera: Tephritidae)) with CL₅₀ 13.041 μl/l through ingestion and CL₅₀ 0.066 μl/l through contact [30]. Canale et al. [139], when evaluating the toxicity of the oil against Bactrocera oleae (Rossi, 1790) (Diptera: Tephritidae), demonstrated that, by ingestion, the product showed a CL₅₀ of 4.9 mg/ml. Bezerra et al. [10] evaluated by fumigation the action of the oil and highlighted that it presents great insecticidal action with CL₅₀ of 15.5 μg/ml against adults of Drosophila melanogaster (Meigen, 1830) (Diptera: Drosophilidae). Also, via the fumigation test, Wangrawa et al. [35] found a CL₅₀ of 1.86 μg/ml (oil/air) against A. gambiae. Recently, Adjou et al. (2019) found the insecticidal action of M. suaveolens oil against Tenebroides mauritanicus (Linnaeus, 1758) (Coleoptera: Trogossitidae) with a CL₅₀ 0.35 μl/g.

3.4.4. Repellent Activity

Besides causing mortality in insects, the products of M. suaveolens, especially the essential oil of the leaves, can repel insects and arachnids of public health and economic interests (Table 4). As for Diptera, the essential oil by fumigation and the fresh leaves by contact were able to repel mosquitoes of the species Anopheles gambiae, malaria vector, with the former showing an effective rate of 98% repellency at a low concentration (6%) [152], while the leaves when rubbed on the body had a rate of 66.5% [153]. Besides this Diptera, Aedes aegypti vector of arboviruses, such as dengue, yellow fever, chikungunya, and zika, was also repelled when in contact with the ethyl acetate extract of the leaves.

As for insects of economic interest, the leaves of M. suaveolens showed that the phytochemicals released by the leaves can repel two species of coleoptera, being Sitophilus granarius and Callosobruchus maculatus. As for arachnid repellency, the essential oil was able to repel Amblyomma cajennense and Ixodes ricinus.

3.4.5. Larvicidal Activity

Besides microbiological and insecticidal activities, apolar and polar extracts of M. suaveolens showed larvicidal action in some studies (Table 5). Its oil, for example, showed activity against Aedes albopictus (Skuse, 1894) (Diptera: Culicidae) (CL₅₀ 240.3 μg/ml) [159], Aedes aegypti (Linnaeus, 1762) (Diptera: Culicidae) (CL₅₀ 0.4 μL/ml) [160], Artemia salina (Linnaeus, 1758) (Anostraca: Artemiidae) (CL₅₀ 49.72 μg/ml) [10], and Chrysodeixis chalcites (Esper, 1789) (Lepidoptera: Noctuidae) (CL₅₀ 2.42 μg/ml) [32].

3.4.6. Cytotoxic Activity

Besides microbiological and insecticidal activities, it was evidenced that M. suaveolens products present biologically active compounds against cancer cells (Table 6). The activities evaluated using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay demonstrated that the leaves are the source of the anticancer compounds against some cell types. Among these, Lautié et al. [175] evaluated the bioactivities of chlorophore and butanolic extracts against MCF-7 cell lines and showed that such products have low IC₅₀ (12 and 2.8 μg/ml, respectively). Besides these cell lines, activities were demonstrated against EAC (Ehrlich ascites carcinoma), human breast epithelial adenocarcinoma (MDA-MB-231), and T-lymphocyte leukemia cells.

Among the studies against cancer cell lines, only the aqueous extract of the leaves showed low cytotoxicity (IC₅₀ 1,356.17 μg/ml) when evaluated against T-lymphocyte leukemia-causing cells [176]. Concomitantly in the same study, the ethanolic extract of the same organs had moderate cytotoxicity (IC₅₀ 553.52 μg/ml); such fact is explained by the variation of solvent used for the extraction of the compounds.

3.4.7. Other Biological Activities (Antiarachnidic, Antiparasitic, and Molluscicides)

In addition to the aforementioned activities, the herbaceous species present bioactive compounds against other biological organisms. Among these were highlighted parasitic organisms of humans, as reported by Shittu et al. [180], in which evaluating the trypanocidal action (Trypanosoma brucei brucei) in vivo of gold nanoparticles from M. suaveolens demonstrated that the species can cause a complete clearance of the parasite after seven days of infection. As well as in insecticidal action against malaria vectors (Anopheles spp.), M. suaveolens exhibits antiplasmodial activity (Plasmodium falciparum 3D7) [45, 46, 181]. Noronha et al. [181] evaluated the antiparasitic action of the methanolic extract of M. suaveolens leaves and observed that the natural product has an IC₅₀ of 3.906 μg/ml against chloroquine-sensitive Plasmodium falciparum strains. In the study by Ziegler et al. [45], the researchers isolated a diterpene (dehydroabietinol) from the leaves and observed that the compound was able to inhibit 50% of parasite growth at a low concentration of 7.3 μg/ml. Similarly, Chukwujekwu et al. [46] demonstrated that another diterpene (13α-epi-dioxiabiet-8(14)-en-18-ol) isolated from the same organ showed an IC₅₀ of 0.11 μg/ml, against P. falciparum D10, being of great clinical interest.

Research involving the extracts and essential oil of M. suaveolens focus on insecticidal activities, so only one work aimed to evaluate the bioactive potential against Arachnida species [182]. In this study, the authors demonstrated that the essential oil of the leaves at the concentration of 31.3 mg/ml can cause 50% mortality of Rhipicephalus (Boophilus) microplus for engorged females, while for juvenile forms of the tick, CL₅₀ is 51.6 mg/mL, demonstrating that females are more susceptible to the oil.

Salawu and Odaibo [182] evaluated the molluscicide action of the ethanolic extract of M. suaveolens against Bulinus globosus, found that the product presents both lethality in adult individuals (LC₅₀ 77 μg/ml), and also presents an ovicidal potential (LC₅₀ 614 μg/ml).

3.5. Pharmacological Activities

3.5.1. Antioxidant Activity

Narayanaswamy and Balakrishnan [84] evaluated the extracts of thirteen plants of ethnomedicinal importance and identified that M. suaveolens species among all had the highest activity in both aqueous and ethanolic extracts evaluated. Thus, it demonstrates that the species is a source of compounds of pharmacological interest for the development of natural antioxidant products.

Agarwal [183] showed that the methanolic extract of M. suaveolens leaves has potent antioxidant activity evaluated by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method with IC₅₀ value = 40.91 μg/ml, and there is about 69% free radical inhibition capacity at the highest concentration (100 μg/ml). It was also found that the percentage of inhibition is concentration dependent, the higher the concentration the greater the inhibition of free radicals, and that the main phytochemicals involved in this activity may be phenols and flavonoids. The methanolic extract also demonstrated antioxidant activity with assays other than DPPH, such as ferric reducing antioxidant power (FRAP) and 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) [184].

Other studies have also evaluated the free radical scavenging potential by the DPPH method. Gavani and Paarakh [185] evaluated the methanolic extract of M. suaveolens leaves and obtained an IC₅₀ of 14.04 μg/ml. The aqueous and ethanolic extracts of the fresh leaves of M. suaveolens demonstrated high antioxidant activity. The former product had an IC₅₀ = 20.32 μg/ml, while the ethanolic extract had a statistically equal result to the positive control, ascorbic acid, with IC₅₀ of 7.06 ± 0.82 and 6.69 ± 0.85 μg/mL, respectively [186]. Such results are attributed to the phenolic compounds present in such extracts.

Iqbal et al. [187] reported that the methanolic extract of the seeds of M. suaveolens showed better antioxidant activity by the DPPH method (IC₅₀ = 72 ± 0.45 μg/ml) when compared to the methanolic extracts of the stem (IC₅₀ = 250 ± 5.46 μg/ml) and root (IC₅₀ = 143 ± 2.15 μg/ml).

In the work of Priyadharshini and Sujatha [188], four types of leaf extracts were evaluated; in the DPPH assay, three of the extracts had significant results, the best of them being the ethyl acetate extract with a percentage of inhibition (IC₅₀ = 137 μg) very close to that of the standard used, ascorbic acid (IC₅₀ = 127 μg). In this same study, the acetate extract also stood out with other tests; in the superoxide anion radical scavenging assay, the IC₅₀ value = 22.94 μg, and the standard had a value of 21.47 μg.

In addition to leaves, antioxidant potentials of other organs such as flowers were investigated in the study by Banerjee and De [189]. However, the results were not promising, as the extract of the reproductive parts exhibited an IC₅₀ of 1690.21 μg/ml against DPPH. Antioxidant studies involving M. suaveolens are not restricted to extracts only. Nantitanon et al. [126] evaluated the effect of the essential oil from the leaves; however, it showed low potential to reduce free radicals (IC₅₀ of 3.7200 mg/ml). Hsu et al. [190] demonstrated that the seeds also exhibit antioxidant action, as they showed moderate inhibitory activity against xanthine oxidase. In a study conducted by Lima et al. [191], it was observed that the essential oil from M. suaveolens leaves showed moderate Fe²⁺ chelating activity at the concentration of 480 μg/ml.

3.5.2. Healing Potential

The healing potential of M. suaveolens leaves was evaluated by three types of extracts (petroleum ether, ethanolic, and aqueous) in different wound models (excision, incision, and healing) using albino Wistar rats [192]. In this study, it was revealed that the extract using petroleum ether had the greatest significant effect on wound healing in murine wounds. Shirwaikar et al. [193] evaluated the ethanolic extract on these same three types of wounds, also obtaining significant results which were justified by the free radical scavenging action of this species.

3.5.3. Neuroprotective Activity

Ghaffari et al. [184] determined the neuroprotective potential of the methanolic extract of the aerial parts of M. suaveolens on mouse N2A neuroblastoma cells, in which they observed that the natural product inhibits hydrogen peroxide (H₂O₂)-induced neuronal death. The authors justified this effect by the fact that the extract can regulate the activation of antioxidant and protective genes of the nerve cells. These results are promising, and the methanolic extract can be employed to treat stress-induced neurodegeneration.

3.5.4. Anti-Inflammatory Activity

Shenoy and Shirwaikar [194] evaluated the anti-inflammatory potential of ethanolic extract of the leaves against inflammation induced by carrageenan in albino rats; the extract showed significant results when compared to standard ibuprofen; this result is justified by the good antioxidant activity of this extract. In the study by Grassi et al. [42], two diterpenes (C₂₀) isolated from M. suaveolens, suaveolol and methyl suaveolate, showed anti-inflammatory potential when evaluated regarding the reduction of ear edema in rats. In such research, it was observed that the compounds reduced inflammation with ID₅₀ = 0.71 μmol/cm² (dose giving 50% edema inhibition) for suaveolol and ID₅₀ = 0.60 μmol/cm²; however, despite the pharmacological effect, the results were only two to three times less active than the standard drug used in the study indomethacin (ID₅₀ = 0.26 μmol/cm²).

3.5.5. Antiulcer Activity

Mesosphaerum suaveolens leaves are popularly used for the treatment of gastric ulcers; however, no active ingredient had been identified. The first study evaluating such an effect was by Vera-Arvaze et al. [43], in which such authors isolated the diterpene suaveolol from the leaves and evaluated it against an induced experimental model; the results presented indicated that this compound had a gastroprotective effect of more than 70%.

One year after the publication of the mentioned study, Jesus et al. [195] using the ethnopharmacological approach of M. suaveolens evaluated its antiulcer potential through the ethanolic extract and its fractions. The results for all products had high significance, , with the hexanic fraction of the extract being the most effective with 74% inhibition of induced gastric ulcer at a dose of 500 mg/kg.

3.5.6. Antidiarrheal Activity

Although M. suaveolens is popularly used to treat gastrointestinal disorders such as diarrhea, only the work of Shaikat et al. [196] evaluated its antidiarrheal potential. The researchers prepared ethanolic extracts of the leaves and based on the popular use, evaluated against an experimental model of diarrhea induced in mice; the results obtained show that this species presents compounds with the antidiarrheal effect () that may be acting in an isolated or synergistic way.

3.5.7. Antihyperglycemic Activity

The ethanolic extract of M. suaveolens leaves was evaluated in the in vivo experimental model of streptozotocin-induced diabetes. The extract at doses of 250 and 500 mg/kg bodyweight was administered orally over 21 days; at the end of the treatment, a decrease in the levels of triglycerides, total cholesterol, and low-density lipoprotein can be seen; these results indicate that this species has significant antidiabetic activity [197].

3.5.8. Hepatoprotective Effect

Ghaffari et al. [198] induced damage to livers of Wistar rats using carbon tetrachloride (CCl4) and subsequently administered doses of 50 and 100 ml/kg of methanolic extract of the aerial parts of M. suaveolens. The results were promising, demonstrating that the extract has a hepatoprotective effect, which can be explained by the antioxidant potential of the product, also demonstrated in the study.

3.5.9. Toxicity

A topical cream based on M. suaveolens essential oil was prepared based on its popular use in Thailand, where they pointed out further investigations related to its toxicity in humans. This study was conducted on Wistar rats for 28 days under 3, 10, and 30% concentration of essential oil. The results showed us that concentrations of 3 and 10% did not cause a statistically significant dermal toxicity unlike the 30% concentration in which some female rats presented signs of erythema on its shaved dorsal skin between 11 and 14 days after the cream application [199].

4. Conclusions

It is evident that M. suaveolens is the most studied species of the genus, traditionally used in the new and old world to combat several diseases. Chemically, the species is much investigated, mainly about the composition of its essential oils that can vary according to the locality of occurrence. Mesosphaerum suaveolens also behaves as ruderal, and its success may be due to the release of allelochemicals. The species also presents a biotechnological potential corroborated by the remarkable activity against pathogenic microorganisms, insects, and other arthropods that transmit diseases. Finally, the pharmacological applications of the species are highlighted, especially the antioxidant action found in several organs of the species.

Data Availability

The data used to support the findings of this study are available from the corresponding author upon request.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

Authors’ Contributions

J.W.A.B. conceptualized the study. J.J.L.B. and F.C.R. developed methodology. A.A.V.P. developed software. M.F.B.M.B. and J.G.M.d.C. validated the study. F.C.R., P.A.d.S.F., and V.B.d.S. performed formal analysis. S.A.d.M. investigated the study. A.R.C. curated data. A.S. and J.W.A.B. wrote original draft. B.K. and A.B.T. reviewed and edited the article. A.F.M.d.O. and M.V.M. supervised the study. H.D.M.C administered the project. All authors have read and agreed to the published version of the manuscript.

Acknowledgments

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2020R1I1A2066868), the National Research Foundation of Korea (NRF) grant funded by the Korea Government (MSIT) (2020R1A5A2019413), a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (HF20C0116), and a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (HF20C0038).

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