Monoterpenes and Sesquiterpenes of Essential Oils from Psidium Species and Their Biological Properties

Psidium (Myrtaceae) comprises approximately 266 species, distributed in tropical and subtropical regions of the world. Psidium taxa have great ecological, economic, and medicinal relevance due to their essential oils’ chemical diversity and biological potential. This review reports 18 Psidium species growing around the world and the chemical and biological properties of their essential oils. Chemically, 110 oil records are reported with significant variability of volatile constituents, according to their seasonality and collection sites. Monoterpenes and sesquiterpenes with acyclic (C10 and C15), p-menthane, pinane, bisabolane, germacrane, caryophyllane, cadinane, and aromadendrane skeleton-types, were the primary constituents. The essential oils showed various biological activities, including antioxidant, antifungal, antibacterial, phytotoxic, larvicidal, anti-inflammatory, and cytotoxic properties. This review contributes to the Psidium species rational and economic exploration as natural sources to produce new drugs.


Introduction
Psidium genus belongs to Myrtaceae, Myrtales order, Rosidae clade, Malvidae subclade, and comprises about 266 species with occurrence in the tropical and subtropical regions of the world. In the Americas, it extends from southern Mexico to Argentina. The centers of high diversity of Psidium species are western India, southern Brazil, Paraguay, and northern South America [1][2][3].
Psidium species are trees and shrubs, glabrous, glabrescent, or sparsely to densely pubescent; branches cylindrical or tetragonal. Leaves are simple and opposite, exhibiting typical brochidodromous venation; elliptic, cordate, oblong or obovate, chartaceous or coriaceous, glabrous, glabrescent or sparsely to densely pubescent, margin entire, revolute or slightly revolute, midvein slightly sulcate above and prominent below. Flowers are solitary, axillary racemes, dichasium, panicle or inflorescence growing from auxotelic axis producing vegetative shoots with adult leaves after anthesis; floral buds pyriform, entire or constricted above the ovary, round or apiculate, calyx with lobes entirely or partially fused, tearing irregularly at anthesis, 4-5 lobed, pentamerous flowers; calyx cupuliform To find the most widespread subjects of Psidium essential oils and identify their relationships, we analyzed the co-occurrence of similar terms in titles and abstracts of 158 articles in the Scopus database from 1990 to 2020. Figure 3 represents this survey and its associations. The size of the node indicates the extent of searches for the term. That is, the larger the node, the more frequently the term was searched. The search terms are grouped according to their similarity. Thus, the blue cluster includes terms related to in vivo tests, such as "rat", "animal experiment", "in humans", and others. The red cluster contains terms related to biological activities, such as "enzyme activity", "in vitro study", "antimicrobial activity", and "median inhibitory concentration (IC 50 )". The green cluster shows terms related to chemical composition, such as "essential oil composition", "chemical analysis", "hydrodistillation", "gas chromatography", "cineole", "limonene", etc. Finally, in yellow and to a lesser extent, one can observe a cluster four with terms related to this article's theme.

Volatile Profiles
The essential oils' chemical profile is influenced by environmental factors, contributing to their primary and secondary constituents' chemical variability. This fact takes along several chemical profiles, chemotypes, or different chemical races to the same species. Therefore, it is worth considering that minor constituents in essential oils can play an essential role in the chemical polymorphism of a given species [19,20].

Psidium cattleyanum Sabine
It is native to Brazil, occurring from Minas Gerais to the Rio Grande do Sul states and Uruguay northeastern, and as an isolated form in the Amazon region. It was also naturalized in tropical climates regions such as Hawaii and many Caribbean islands. Commonly, it is known as strawberry guava, bovine guava, jeju guava, cherry guava, purple guava, waiawi, guava, and araçá [28,29]. In some reports, its name has been published as Psidium cattleianum, probability by a written error [30,31]. Psidium cattleyanum fruits are similar to P. guajava (guava); however, with a slightly acid flavor. For this reason, they are widely consumed in nature or juices, jellies, and ice cream forms, with good consumer acceptance and high value for the agri-food industries [32,33]. The vitamin C content in P. cattleyanum fruits is around 3 to 4 times higher than lemon and orange [34,35]. Furthermore, this species has been used in traditional medicine for several purposes, such as antiseptic, digestive, anti-hemorrhagic, blood pressure control, and diuretic [32].

Psidium friedrichsthalianum (O. Berg) Nied
It is a fructiferous plant native from forests and savannas of higher regions from Honduras to Panama, also found in Colombia mountains and widely cultivated in Costa Rica by the trivial names 'cas' and 'goiaba costarriquenha' [45,46]. The fruits can be consumed as refreshing drinks, jellies, and jams due to its acidity and filling for pies [46,47].

Psidium guajava L.
Psidium guajava, commonly known as 'guava', is native to tropical regions from southern Mexico to northern South America. It is a species cultivated in many countries, and this fact allows its reproduction on a large scale in tropical and subtropical climates [48].
In folk medicine, this species is used as tea, infusion, decoctions, and poultice to treat inflammation, diarrhea, rheumatism, and diabetes, and as a diuretic, anti-bacterial [48]. Moreover, its fruits can be consumed in nature or sweets, ice cream, and juices forms, so this species has the highest commercial value of all Psidium species [28].

Psidium guineense Sw.
It is a native species of South America, from northern Argentina throughout the Brazilian territory and in isolation form in southern Mexico. Commonly known as 'araçá', 'araçá-comum', 'araçá-azedo', and 'araçá-do-campo' [28,76]. Psidium guineense (syn. Psidium araca Raddi or P. guianense Pers., due to a written error that gave it an African name despite its American origin) presents a significant economic and medicinal potential exploitation [77,78]. Psidium guineense fruits have a high content of minerals and functional elements, such as vitamins and phenolic compounds, consumed freshly or used to prepare sweets, juices, ice cream, and jellies [79][80][81]. In folk medicine, all parts of "araçá" are widely used in South America to treat gastrointestinal and genitourinary infections [82].

Psidium laruotteanum Cambess
The species occurs in Central Brazil, and it is commonly known as 'araçá-cascudo' Its fruits are similar to the gooseberry, showing a more acidic flavor than 'araçá'. It is consumed in nature by wild animals and as jams and juice forms by people. This plant has low fruit productivity [30,86,87].

Psidium myrsinites DC
Native from Brazil, it is also known as 'araçá', and the fruits are used in folk medicine for cauterization and to treat diarrhea due to its astringent properties [28,88].
Three P. myrsinites records showed quantitative and qualitative differences in the chemical composition of their leaves' essential oils, with the predominance of caryophyllanetype skeletons.

Psidium sartorianum (O.Berg) Nied
It is native to Mexico, known as 'arrayan'. Also, it occurs in Southeast Brazil, but there are reports of isolated occurrences in other regions [30].

Seasonal Variation in the Essential Oils Composition
Reports of Psidium myrtoides and P. salutare have focused on the effects of seasonality in the essential oils' chemical composition. Both species were registered to the Chapada do Araripe, Ceará state, Brazil, with their leaves sampled in February, May, August, and November, which encompasses the dry and rainy seasons of that region [25,93]. The variation in the leaf essential oils is illustrated in Figure 5.

Antioxidant Activity
Antioxidants compounds can prevent disorders and diseases caused by free radicals, stabilizing them. In recent years, the interest in replacing synthetic antioxidants with aromatic and medicinal plants has been growing. The following methods have evaluated the antioxidant activity of Psidium essential oils, DPPH, ABTS, linoleic acid oxidation, XO, OH, NO, ORAC, FRAP, deoxyribose degradation, and MDA [105].

Antifungal Activity
The growing resistance to azole antimycotics, the most used antifungals class, has been a recurrent problem in the treatment of fungal pathologies. Today new efforts are dedicated to discovering new antimycotics agents with different mechanisms of action [106]. Therefore, the use of natural products stands out as a viable alternative for the treatment of several mycoses due to its broad spectrum of bioactive compounds [107]. In this context, essential oils gain prominence as fungicides, with many studies addressing this aspect [108].
The fungicidal activity of these Psidium species can be attributed to the mono-and sesquiterpenes present in their essential oils, as these compound classes showed fungicidal potential previously reported [109,110].

Antibacterial Activity
In the last years, the antimicrobial resistance to antibiotics has increased due to the adaptive evolution of bacteria and fungi. Thus, the treatment of pathologies caused by these agents has been hampered. For this reason, research focused on the potential of new antimicrobials based on natural products has been explored, especially essential oils, generating an excellent source of bioactive compounds for the pharmaceutical industry, among others [111][112][113].

Phytotoxic Activity
The phytotoxic potential of plants and their chemical constituents against invasive plants is increasingly investigated as a possible alternative to synthetic herbicides in crops weed control [114]. Some Psidium essential oils inhibited parasitic herbs' growth, showing the potential to be used against the crops' invasive plants [22].

Anti-Inflammatory
Natural products with anti-inflammatory activity have long been used in folk medicine for inflammatory diseases and their symptoms, such as fever, pain, migraine, and arthritis [116]. Scientists are focused on herbal medicine research and active compounds to develop new drugs as useful therapeutic agents [117]. Thus, essential oils gain importance in the field of human health, acting as anti-inflammatories [118].
Psidium guineense leaf oil from Mato Grosso do Sul, Brazil, dominated by spathulenol (80.1%) showed the inhibition of 59.46% in a carrageenan-induced mouse paw model, at 300 mg/kg, reduction of 45.33% (at 30 mg/kg) and 77.70% (at 100 mg/kg) in the increase of total leukocytes in pleurisy model, and reduction in the rise of protein levels of 49.72% (at 30 mg/kg) and 78.40% (at 100 mg/kg) [84].

Conclusions
The Psidium genus essential oils present a significant chemical variability. They are composed of mono-and sesquiterpenes with acyclic (C 10 and C 15 ), p-menthane, pinane, bisabolane, germacrane, caryophyllane, cadinane, and aromadendrene skeleton-types. Geographical occurrence and seasonality can influence the chemical composition of Psidium essential oils. Also, it has exhibited a wide range of biological activities, directly influenced by its chemical variability. Although Psidium species display a broad spectrum of ethnomedicinal uses, studies on their biological activities are mostly restricted to P. guajava and P. cattleyanum species. Furthermore, a reduced number of species with known chemical composition, 18 species of 266 contained in the genus, from 110 studied samples. Thus, it is necessary to further explore the volatile content of Psidium species and their therapeutic properties. Variations in the chemical profile of the species indicate the importance of optimizing protocols for the collection, processing, and extraction of plant material.