molecules Review A Systematic Approach to Agastache mexicana Research: Biology, Agronomy, Phytochemistry, and Bioactivity Mariana Palma-Tenango 1 , Rosa E. Sánchez-Fernández 2 and Marcos Soto-Hernández 3,* 1 Facultad de Ciencias, Universidad Nacional Autónoma de México, Ciudad Universitaria, Coyoacán, 04510 Ciudad de México, Mexico; [email protected] 2 Laboratorio Nacional de Investigación y Servicios Agroalimentarios y Forestales (LANISAF), Edificio Efraím Hernández Xolocotzi Nivel 1 y 2, Universidad Autónoma Chapingo, 56230 Texcoco, Mexico; [email protected] 3 Posgrado en Botánica, Colegio de Postgraduados-Campus Montecillo, km 36.5, Carretera México-Texcoco, 56230 Texcoco, Mexico * Correspondence: [email protected]; Tel.: +52-595952-0200 (ext. 1361) Abstract: Mexico is the center of origin of the species popularly known as toronjil or lemon balm (Agastache mexicana Linton & Epling). Two subspecies have been identified and are commonly called purple or red (Agastache mexicana Linton & Epling subspecies. mexicana) and white (Agastache mexicana subspecies xolocotziana Bye, E.L. Linares & Ramamoorthy). Plants from these subspecies differ in the size and form of inflorescence and leaves. They also possess differences in their chemical compositions, including volatile compounds. Traditional Mexican medicine employs both subspecies. A. mexicana exhibits a broad range of pharmacological properties, such as anti-inflammatory, anxi- Citation: Palma-Tenango, M.; olytic, and antioxidant. A systematic vision of these plant’s properties is discussed in this review, Sánchez-Fernández, R.E.; exposing its significant potential as a source of valuable bioactive compounds. Furthermore, this Soto-Hernández, M. A Systematic review provides an understanding of the elements that make up the species’ holistic system to benefit Approach to Agastache mexicana from lemon balm sustainably. Research: Biology, Agronomy, Phytochemistry, and Bioactivity. Keywords: toronjil; Mexican agastache; aromatic plants Molecules 2021, 26, 3751. https:// doi.org/10.3390/molecules26123751 Academic Editors: Young Hae Choi, Young Pyo Jang, Yuntao Dai and Luis 1. Introduction Francisco Salomé-Abarca Lamiaceae is the eighth most diverse plant family in Mexico and 5.5% of the species worldwide are found in this country. Thus, Mexico may be one of the most important Received: 25 April 2021 diversification centers [1]. This family contains a wide range of aromatic plants possessing Accepted: 7 June 2021 agronomical, pharmacological, and commercial potential. Mexican Agastache belongs to Published: 20 June 2021 this family and its use and commercialization for traditional Mexican medicine make it the most important member of the Agastache genus in Mexico [2,3]. The species Agastache Publisher’s Note: MDPI stays neutral mexicana divides into two subspecies, based on anatomical characteristics [2] and chemical with regard to jurisdictional claims in composition [4]: red lemon balm, Agastache mexicana Linton & Epling subspecies mexi- published maps and institutional affil- cana, and white toronjil, Agastache mexicana subspecies xolocotziana Bye, E.L. Linares & iations. Ramamoorthy [5]. The species is distributed in the states of Guanajuato, Mexico, Michoacán, Puebla, Querétaro, Hidalgo, Veracruz, Chihuahua, Morelos, and Tlaxcala, as well as in Mexico City (Figure1). The species concentrates in the volcanic axis of Central Mexico [2,6]. Copyright: © 2021 by the authors. This article presents a review of the research on Agastache mexicana from the perspective Licensee MDPI, Basel, Switzerland. of a holistic system to understand its components and interactions. A literature search This article is an open access article was sourced from meta-analyses of available Agastache data. Data were sourced from distributed under the terms and bibliographic engines like Web of Science®, Scopus®, ScienceDirect®, and Google Scholar® conditions of the Creative Commons using “Agastache mexicana” as a keyword. Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). Molecules 2021, 26, 3751. https://doi.org/10.3390/molecules26123751 https://www.mdpi.com/journal/molecules MoleculesMolecules 20212021, ,2626, ,x 3751 FOR PEER REVIEW 2 of 16 2 of 18 FigureFigure 1. 1.Distribution Distribution of Agastacheof Agastache mexicana mexicanain Mexico in Mexico [7]. [7]. 2. A Holistic Approach to Agastache mexicana Usage SystemsThis article biology presents analysis a review allows theof the understanding research on of Agastache different biologicalmexicana from elements the perspec- andtive their of a interactionsholistic system with to non-biological understand its elements, components such as and the interactions. environment A or literature human search impactswas sourced (for example, from meta-analyses the analysis of variousof available traditional Agastache medicine data. systems Data were like traditional sourced from bib- Chineseliographic medicine) engines [8]. like Systems Web biology,of Science in tandem®, Scopus with®, ScienceDirect reverse pharmacology,®, and Google may allow Scholar® us- discoveringing “Agastache new activemexicana biological” as a keyword. compounds [9]. Life science studies relying on systems biology and holistic approaches shy away from2. A reductionistHolistic Approach views and to incorporate Agastache biologicalmexicana effects Usage and their interaction with the environment [8,9]. A biological system contains numerous components interacting in a vast varietySystems of combinations. biology analysis Once theallows components the understanding and interactions of ofdifferent a system biological are known, elements aand system’s their behaviorinteractions may bewith understood non-biological [10]. elements, such as the environment or human impactsWe used (for systemsexample, biology the analysis principles of various for a holistic traditional analysis medicine of different systems components like traditional withinChinese the medicine) lemon balm [8]. plant Systems system biology, and its environment in tandem with (Figure reverse2). This pharmacology, system’s insights may allow arediscovering derived from new a generalactive biol visionogical that includescompounds the system [9]. components’ relationships and interactions.Life science This approach studies may relying provide on newsystems collaborative biology information, and holistic fresh approaches insights, and shy away researchfrom reductionist prospects for views the species. and incorporate biological effects and their interaction with the 2.1.environment Biology [8,9]. A biological system contains numerous components interacting in a vastA. variety mexicana ofis combinations. a native vascular Once plant the of Mexico components [11]. It isand a perennial interactions herb. Plantsof a system of are bothknown, subspecies a system’s have behavior a typical Lamiaceae may be understood morphology: [10]. opposite, petiolate leaves, a four- angledWe stem, used and systems numerous biology trichomes principles [12]. In the for two a subspecies,holistic analysis the stem of is different quadrangular components inwithin cross section;the lemon in A.balm mexicana plant ssp.system mexicana, and its theenvironment basal and middle (Figure part 2). This of the system’s stem is insights purple.are derived The cuticle from a is general smooth, vision but in that the includ angles,es it the is observed system components’ to be crenulated, relationships with and ainteractions. thickness of 4–8Thisµ m.approach The three may types provide of epidermal new collaborative appendages described information, for the fresh leaf insights, areand observed, research but prospects uniseriate for non-glandular the species. trichomes are abundant in A. mexicana ssp. xolocotziana, while they are more scattered and not visible to the naked eye in A. mexicana ssp. mexicana [2]. The plant height reaches between 50 and 150 cm [2] and the base chromosome number is 9. The plants have slender and spreading rhizomes [5]. Various plants from the Agastache genus are used for bee forage and honey produc- tion [13,14]. Toronjil is a honey plant; its flowers produce nectar for bee collection [15]. Molecules 2021, 26, 3751 3 of 16 Molecules 2021, 26, x FOR PEER REVIEW 3 of 18 FigureFigure 2. Systems 2. Systems biology biology approaches approaches of the ofstudy the studyof Agastache of Agastache mexicana. mexicana . 2.1. Biology2.1.1. A. mexicana ssp. mexicana A. mexicanaThe stem is a of nativeA. mexicana vascularssp. plant mexicana of Mexico is erect, [11].branched, It is a perennial and four-angled. herb. Plants The of basal both andsubspecies middle have part ofa typical the stem Lamiaceae is purple. mo Therphology: form of theopposite, leaves ispetiolate ovate-lanceolate, leaves, a four- measuring angled4.4 stem, to 6.3 and cm numerous long and 2.1 trichomes to 2.5 cm [12]. wide In [the2]. two The subspecies, petiole is 1 cmthe longstem [is2], quadrangu- and the corolla is lar inpurplish cross section; red to in red A. [mexicana2,5]. The ssp. seeds mexicana, measure the approximately basal and middle 4 to 5 part mm of (Figure the stem3). is purple. The cuticle is smooth, but in the angles, it is observed to be crenulated, with a thickness2.1.2. ofA. 4–8 mexicana μm. Thessp. three xolocotziana types of epidermal appendages described for the leaf are observed, Thebut stemuniseriate of A. non-glandular mexicana ssp. xolocotzianatrichomes are is abundant erect, branched, in A. mexicana and four-angled. ssp. xo- The locotziana,form