THE CHEMICAL AND BIOLOGICAL ROLE OF PIMARANES AND LABDANES FROM MEXICAN SALVIA SPECIES

Abstract

The genus Salvia (Lamiaceae) is widely distributed in Mexico with approximately 300 species. Aerial parts, leaves, and branches of sages are prepared as infusions or decoctions in traditional Mexican medicine to treat conditions such as dysentery, diarrhea, gastritis, stomach-ache, headache, sore throat, cough, bronchitis, fever, diabetes, epilepsy, nerves, insomnia, anxiety, among other ailments. The aim of this review was to compile and resume relevant information from literature regarding the chemical constituents of the pimarane and labdane type isolated from Mexican salvias and their biological activities covering the period from 1986 to 2022. A total of 31 compounds of these types were registered with 24 pimaranes and 7 labdanes. It was noticed that scientific evidence of the participation in the medicinal effects of Salvia species has not yet been reported for most of these diterpenoids. However, those described as bioactive have shown antibacterial, anticancer, anti-inflammatory, antihypotensive, antimutagenic, and antidiabetic properties. The present review provides information on the chemical and biological properties of pimaranes and labdanes from Mexican Salvia species suggesting their potential to become an option of treatment for diabetes and cancer, among other common diseases of Mexican population and of all the world. Nevertheless, further research is encouraged to demonstrate the benefits of these chemical constituents for health. 25 26 Ortiz-Mendoza, N., et al. RESUMEN El género Salvia (Lamiaceae) está ampliamente distribuido en México con aproxima-damente 300 especies. Las partes aéreas, hojas y ramas de salvias son preparadas como infusiones o decocciones y se utilizan en la medicina tradicional mexicana para tratar padecimientos como disentería, diarrea, gastritis, dolor de estómago, dolor de cabeza, dolor de garganta, tos, bronquitis, fiebre, diabetes, epilepsia, ner-vios, insomnio, ansiedad, entre otras enfermedades. El objetivo de esta revisión fue compilar y resumir información de la literatura acerca de los constituyentes químicos de tipo pimarano y labdano aislados de salvias mexicanas cubriendo el periodo de 1986 a 2022, incluyendo aquellas con actividad biológica. Un total de 31 compuestos de este tipo fueron registrados como 24 pimaranos y 7 labdanos. La evidencia de la participación de estos diterpenoides en los efectos medicinales de las especies de Salvia aún no ha sido reportada para la mayoría de estos metabolitos. Sin embargo, los que se han descrito como bioactivos demostraron presentar pro-piedades antibacterianas, anticancerígenas, antiinflamatorias, antihipotensivas, antimutagénicas y antidiabéticas. La presente revisión proporciona información sobre la importancia química y biológica de los pimaranos y labdanos de salvias mexicanas sugiriendo a estos constituyentes como posibles alternativas para el tratamiento de la diabetes y el cáncer, entre otras enfermedades que son comunes en México y en todo el mundo. No obstante, más investigación es requerida para demostrar los beneficios de estos componentes químicos para la salud.

Full text

THE CHEMICAL AND BIOLOGICAL ROLE OF PIMARANES
AND LABDANES FROM MEXICAN SALVIA SPECIES
Nancy Ortiz-Mendozaa,b, María Eva González-Trujanoc*, Martha J. Martínez-Gordillod,
Itzi Fragoso-Martíneze, Francisco A. Basurto-Peñaf, Iván J. Bazany-Rodríguezg,
Alejandro Dorazco-Gonzálezg, Eva Aguirre-Hernándezb*
ABSTRACT
The genus Salvia (Lamiaceae) is widely distributed in Mexico with approximately
300 species. Aerial parts, leaves, and branches of sages are prepared as infusions
or decoctions in traditional Mexican medicine to treat conditions such as dysentery,
diarrhea, gastritis, stomach-ache, headache, sore throat, cough, bronchitis, fever,
diabetes, epilepsy, nerves, insomnia, anxiety, among other ailments. The aim of this
review was to compile and resume relevant information from literature regarding
the chemical constituents of the pimarane and labdane type isolated from Mexi-
can salvias and their biological activities covering the period from 1986 to 2022.
A total of 31 compounds of these types were registered with 24 pimaranes and 7
labdanes. It was noticed that scientic evidence of the participation in the medicinal
effects of Salvia species has not yet been reported for most of these diterpenoids.
However, those described as bioactive have shown antibacterial, anticancer, anti-
inammatory, antihypotensive, antimutagenic, and antidiabetic properties. The
present review provides information on the chemical and biological properties of
pimaranes and labdanes from Mexican Salvia species suggesting their potential
to become an option of treatment for diabetes and cancer, among other common
diseases of Mexican population and of all the world. Nevertheless, further research
is encouraged to demonstrate the benets of these chemical constituents for health.
Key words: Bioactive compound, Labdanes, Pimaranes, Diterpenes, Lamiaceae,
Salvia
aPosgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México, Ciudad de México, México.
bLaboratorio de Productos Naturales, Departamento de Ecología y Recursos Naturales, Facultad de Ciencias,
Universidad Nacional Autónoma de México, Ciudad de México, México.
cLaboratorio de Neurofarmacología de Productos Naturales, Dirección de Investigaciones en Neurociencias
del Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Ciudad de México, México.
dHerbario de la Facultad de Ciencias, Departamento de Biología Comparada, Facultad de Ciencias, Univer-
sidad Nacional Autónoma de México, Ciudad de México, México.
eFlora de Veracruz, Secretaría Académica, Instituto de Ecología, A.C., Xalapa, México.
fJardín Botánico, Instituto de Biología, Universidad Nacional Autónoma de México, Ciudad Universitaria,
Ciudad de México, México.
gInstituto de Química, Universidad Nacional Autónoma de México, Ciudad de México, México.
*Corresponding authors: b +52 55 10167382. eva_aguirre@ciencias.unam.mx, c+52 55 41605084. evagon-
tru@yahoo.com.mx
25

26 Ortiz-Mendoza, N., et al.
RESUMEN
El género Salvia (Lamiaceae) está ampliamente distribuido en México con aproxima-
damente 300 especies. Las partes aéreas, hojas y ramas de salvias son preparadas
como infusiones o decocciones y se utilizan en la medicina tradicional mexicana
para tratar padecimientos como disentería, diarrea, gastritis, dolor de estómago,
dolor de cabeza, dolor de garganta, tos, bronquitis, ebre, diabetes, epilepsia, ner-
vios, insomnio, ansiedad, entre otras enfermedades. El objetivo de esta revisión
fue compilar y resumir información de la literatura acerca de los constituyentes
químicos de tipo pimarano y labdano aislados de salvias mexicanas cubriendo el
periodo de 1986 a 2022, incluyendo aquellas con actividad biológica. Un total de
31 compuestos de este tipo fueron registrados como 24 pimaranos y 7 labdanos. La
evidencia de la participación de estos diterpenoides en los efectos medicinales de las
especies de Salvia aún no ha sido reportada para la mayoría de estos metabolitos.
Sin embargo, los que se han descrito como bioactivos demostraron presentar pro-
piedades antibacterianas, anticancerígenas, antiinamatorias, antihipotensivas,
antimutagénicas y antidiabéticas. La presente revisión proporciona información
sobre la importancia química y biológica de los pimaranos y labdanos de salvias
mexicanas sugiriendo a estos constituyentes como posibles alternativas para el
tratamiento de la diabetes y el cáncer, entre otras enfermedades que son comunes
en México y en todo el mundo. No obstante, más investigación es requerida para
demostrar los benecios de estos componentes químicos para la salud.
Palabras clave: Compuestos bioactivos, Labdanos, Pimaranos, Diterpenos, La-
miaceae, Salvia.
the country (Martínez-Gordillo et al., 2013;
2017). These species mainly belong to the
subgenus Calosphace (288 spp.), followed
by subgenus Audibertia (13 spp.) and clade
Heterosphace (5 spp.). Regarding the diver-
sity of salvias in Mexico, the most species-
rich states are Oaxaca (98 species), Jalisco
(91), Guerrero (82), Puebla (79), Michoacán
(68) (Martínez-Gordillo et al., 2017). The
species of this genus are herbs and shrubs
that thrive mainly in temperate forests (e.g.,
conifer and oak forests and cloud forests),
but they can also be found in deciduous
and sub-deciduous forests and in arid zo-
nes (Espejo & Ramamoorthy, 1993).
Ethnobotanical studies in Mexico have
reported that in the traditional medicine,
the aerial parts of the sages are prepared
as an infusion or decoction to treat ail-
ments of the gastrointestinal system such
as dysentery, diarrhea, bile, gastritis, and
stomach pain (Domínguez-Vázquez & Cas-
Introduction
Mexico is a vast source of ethnobotanical
knowledge, since it encompasses a great
diversity of medicinal plant species (ca.
4,000 spp.; Ramamoorthy & Elliot, 1993).
This diversity has motivated various in-
vestigations of herbal medicine with the
purpose of endorsing its traditional use.
However, nding effective and safe molecu-
les with pharmacological activity that can
tackle health problems faced by the world
population remains a challenge.
The genus Salvia, from the mint family
(Lamiaceae), has around 1,000 species
worldwide (Etminan et al., 2018). These
species are divided into ten clades, nine
of them currently considered formally as
subgenera (Drew et al., 2017). Mexico is
one of the most important centres of di-
versication of the genus, harbouring ca.
306 species of sages, 75.6% endemic to

The chemical and biological role of pimaranes and labdanes from mexican Salvia species Rev. Latinoamer. Quím. 50/1-3(2023) 27
tro-Ramírez, 2002; Jenks & Seung-Chul,
2013; De La Cruz-Jiménez et al., 2014;
Ortiz-Mendoza et al., 2022). Additionally,
the infusions are also used to relieve ear,
head, and throat pain. Regarding the cen-
tral nervous system, the decoctions have
been reported to be useful against epilepsy,
“nervios’’ or anxiety and insomnia (Jenks &
Seung-Chul, 2013; Casselman et al., 2014),
fever and other conditions such as cough
and bronchitis (Ortiz-Mendoza et al., 2022).
Phytochemical and pharmacological
studies to identify, characterise, and isolate
the compounds responsible for the biologi-
cal activity of various species of Salvia have
allowed to recognize several molecules that
belong to document chemical groups such
as monoterpenes, sesquiterpenes, diterpe-
nes, triterpenes and phenolic compounds
(Ortiz-Mendoza et al., 2022). Although in
this genus the diterpenes with abietane
and clerodane-type skeleton structures
have been highlighted for being the most
abundant and diverse of the identified
compounds (Rodríguez-Hahn, et al., 1995,
Jenks & Seung-Chul, 2013; Esquivel, 2008;
Esquivel et al, 2017; Fragoso-Serrano et
al., 2019), other constituents that are less
abundant (e.g., pimaranes and labdanes)
are also important, because their presence
allows characterization of these species as
well. Pimaranes are tricycle diterpenes with
different stereochemistry features and are
biosynthetically related to labdane terpe-
noids (Isca et al., 2020). The phytochemical
and biological evaluation, and the impact
on health benets of these constituents
are not yet described. This review focuses
on compiling and integrating scientific
information of the studies focused on the
phytochemical and biological activity of the
groups of pimaranes and labdanes in spe-
cies of Salvia, which will allow to recognize
their existing contributions and to promote
their research, identication, isolation and
biological characterization.
The Mexican species of subgenera Au-
dibertia and Calosphace considered for
this review were veried following the chec-
klists of Martínez-Gordillo et al., (2017)
and González-Gallegos et al., (2020). The
ethnopharmacology and phytochemistry
studies were searched in scientic data-
bases of several platforms and editorials
such as Google, Google Scholar, PubMed,
Elsevier, Science Direct, Springer, Willey,
Taylor & Francis, ACS, and RSC, using
keywords like Salvia and more specic
terms such as epithets (e.g., Salvia ade-
nophora, S. semiatrata, S. urica, etc.). This
review includes literature from 1986 to
2022. All the literature found in databases
was classied, systematised, organised,
and nally summarised in Table 1. To
avoid duplication of information regarding
the use of names other than chemical
compounds, the digital databases of the
National Institute of Standards and Tech-
nology (NIST), of the National Center for
Biotechnology Information (NCBI) were
used, which allowed us to verify synonyms
in chemical nomenclature or the trivial
names of molecules.
Chemical compounds isolated as pimarane or
labdane from Salvia species
Terpenes are ubiquitous natural pro-
ducts generated by two well-established
biosynthetic pathways: the mevalonate
pathway and the more recently discovered
1-deoxyxylulose-5-phosphate pathway
(Reveglia et al., 2018). Of the variety of
compounds that have been isolated and
characterised in species of the genus Sal-
via, most of the diterpenes that have been
described belong to species of subgenus
Calosphace (Ortiz-Mendoza et al., 2022).
Among the nature of the different chemi-
cal groups identied in Mexican species
of Calosphace, ca. 450 compounds have
been characterised. According to their
structures, these compounds are classi-
ed into four main subgroups (i.e., mono-,
di-, sesqui- and triterpenoids). However,
the pimaranes and labdanes are the least
abundant of all the diterpenoids (Fig. 1).

28 Ortiz-Mendoza, N., et al.
Only nine species of Mexican sages have
been reported to synthesise labdanes (LB)
and pimaranes (PM). Eight of these species
belong to subgenus Calosphace and one to
subgenus Audibertia, and they are integra-
ted in this review as 24 PM (7%) and 7 LB
(2%) as follows: S. cinnabarina (4 LB & 3
PM), S. elegans (1 LB & 3 PM), S. dugesii (1
LB & 2 PM), S. parryi (7 PM), S. microphylla
(5 PM), S. greggii (4 PM), S. leucantha (1 LB
& 1 PM), S. mellifera (2 PM), S. fulgens (1
PM) (Table 1, Figure 2). It is important to
mention that four pimaranes are found in
more than one Salvia species.
It is worth noting that eight of these spe-
cies, all belonging to subgenus Calospha-
ce, are widely distributed (S. cinnabarina,
S. elegans, S. leucantha, S. tiliifolia, S.
mexicana, S. hispanica, S. coccinea and S.
microphylla) and therefore inhabit different
microenvironments. Additionally, three of
them share both types of diterpenes, su-
ggesting that greater diversity of metaboli-
tes can contribute to their ability to adapt to
different ecological conditions and increase
their dispersal ability.
Figure 1. Secondary metabolites in Mexican species of Salvia specifying the number of
constituents that have been characterised per group.
Figure 2. Chemical structure describing the pimaranes and labdane-type skeletons and
derivatives found in Mexican species of Salvia.

The chemical and biological role of pimaranes and labdanes from mexican Salvia species Rev. Latinoamer. Quím. 50/1-3(2023) 29
Figure 2. Chemical structure describing the pimaranes and labdane-type skeletons and
derivatives found in Mexican species of Salvia (Continuation).

30 Ortiz-Mendoza, N., et al.
BIOLOGICAL ACTIVITIES
Pimaranes and labdane-type diterpenes
found in Mexican sages have been scarcely
explored for biological activity. However,
these kinds of metabolites have been iden-
tied and explored for their biological acti-
vities in other plant species (see Table 1).
The pimarane, isopimarane, and ent-
pimarane-type diterpenes are associated
to a wide range of biological activities in-
cluding antimicrobial, antifungal, antiviral,
cytotoxicity, antispasmodic and relaxant
effects (Reveglia et al., 2018). Similarly, the
labdane-type diterpenes possess biological
activities such as antibacterial, antifun-
gal, antiprotozoal, enzyme inducing, anti-
inammatory activities and modulation
of immune cell functions, in cancer and
in cardiovascular disorders (Singh et al.,
1999).
Pimaranes are tricycle diterpenes with
different stereochemistry features and are
biosynthetically related to labdane terpe-
noids (Isca et al., 2020). The presence of
both types has been identied in Mexican
species of Salvia, being the pimaranes
more representative than labdanes, since
24 molecules were found in contrast to 7
cases, respectively.
The diversity of terpenoid compounds
produced by plants plays an important
role in mediating various plant-herbivore,
plant-pollinator, and plant-pathogen
interactions, where a single amino acid
mutation can switch levopimaradiene/
abietadiene synthase to produce isopima-
radiene or sandaracopimaradiene (Keeling
et al., 2008). Derivatives found in the spe-
cies of Salvia so far lack scientic evidence
on their biological activity are included in
Table 1.
Diterpenoids, especially of the isopima-
rane type have been reported in specic
taxa such as those from the genus Kaem-
pferia (Zingiberaceae), which are plants wi-
dely used in traditional medicine worldwide
(Elshamy et al., 2019).
Salvia cinnabarina (subgenus Calospha-
ce) is one of the most studied species, and
pimaranes and labdane-type constituents
have been isolated from it. This species is
recognized as a medicinal plant in Chiapas
and Oaxaca, where it is used for pain relief
in rheumatism as an antispasmodic (Ortiz-
Mendoza et al., 2022). From this species,
the leaf exudate of populations collected in
Puebla was investigated, leading to the iso-
lation of a 3,4-seco-isopimarane diterpenoid
whose structure and relative stereochemis-
try was established as 3,4-seco-isopimara-
4(18),7,15-trien-3-oic acid as possible res-
ponsible of the antispasmodic in in vitro as-
says (Romussi et al., 2001). This compound
has also been identied in S. elegans, which
is closely related to S. cinnabarina (Martínez-
Gordillo et al., 2013; Fragoso-Martínez et
al., 2018). In addition, two new labdane-
type diterpenoids—malonylcommunol and
6β-hydroxy-trans-communic acid—were
evaluated in yeast α-glucosidases to de-
monstrate a concentration-dependent
inhibition together to two already known
labdane diterpenoids, trans-communic acid
and trans-communol (Bustos-Brito et al.,
2020). Antimutagenic activity was repor-
ted for a pimarane diterpene isolated from
this species and named 3,4-secoisopimar-
4(18),7,15-trien-3-oic acid. It is suggested
that the antimutagenic mechanism of action
of this compound is through the alteration of
cell permeability, which blocks the mutagen
adsorption across the bacterial membrane,
or by chemical or enzymatic inhibition of
the mutagens (Di Sotto et al., 2009). Dose-
response hypotensive action was reported
for the natural diterpene 3,4-seicosopimar-
4(18),7,15-triene-3-oic acid isolated from S.
cinnabarina by an independent nitric oxide
mechanism of action (Aleri et al., 2007).
Whereas NO production was observed
when this constituent inhibited rat bladder
contractility (Capasso et al., 2004), as well
as spasmolytic activity by several neuro-
transmission systems mechanisms of action
(Romussi et al., 2001).

The chemical and biological role of pimaranes and labdanes from mexican Salvia species Rev. Latinoamer. Quím. 50/1-3(2023) 31
Compound identied Salvia species Biological activity Reference
Pimaranes
1 Isopimaradiene S. mellifera n.d. Luis et al., 1993
2 Isopimara-6,8(14),15-
triene
S. parryi n.d.Guajardo et al.,
1997
3 Isopimara-8(14),15-dien-
7-one
S. parryi n.d. Guajardo et al.,
1997
4 Isopimara-8,15-dien-
7-one
S. parryi n.d. Guajardo et al.,
1997
57α-hydroxyisopimara-
8(14),15-diene
S. parryi n.d. Guajardo et al.,
1997
6 8(14),15-isopimaradien-
7α-ol
S. mellifera n.d. Luis et al., 1993
7 Isopimaric acid S. gregii Activity against Sta-
phylococcus aureus
multidrug-resistant
(MIC 32-64 µg/mL).
Inhibitory effects
Epstein-Barr virus
(IC50 =352 mol ratio/
TPA)
Smith et al., 2005,
Tanaka et al.,
2008
8 Isopimara-7,15-dien-
3-one
S. cinnabarina n.d. Bustos-Brito et al.,
2020
9Isopimara-7,15-dien-3β-ol S. cinnabarina n.d. Busto-Brito et al.,
2020
10 3β-hydroxy-isopimaric
acid
S. gregii n.d. Bruno et al., 1986
11 14α-hydroxyisopimaric acid S. microphylla/S.
gregii
n.d. Bruno et al., 1986;
Luis et al., 1993
12 14α, 18-dihydroxy-7,15-
isopimaradiene
S. gregii/S.
microphylla
n.d. Bruno et al., 1986;
Luis et al., 1993
13 14α-hydroxyisopimara-
7,15-diene
S. parryi n.d. Guajardo et al.,
1997
14 Pimaradiene S. leucantha n.d. Upadhyaya et al.,
2013
15 Pimara-7,15-dien-3-one S. elegans n.d. Mathew & Thoppil,
2011
16 Pimara-7,15-dien-3-ol S. elegans n.d. Mathew & Thoppil,
2011
17 Pimaradiene-7α,18-diol S. microphylla n.d. Luis et al., 1993
18 Sandaracopimaradiene S. dugesii/S.
parryi
Nitric oxide inhibitory
activity (IC50 =18.6 μM)
Calderón-Oropeza
et al., 2021; Gua-
jardo et al., 1997;
Tungcharoen et
al., 2020
Table 1. Pimaranes and labdane-type diterpenes found in Mexican species of Salvia and their biological
activities

32 Ortiz-Mendoza, N., et al.
Compound identied Salvia species Biological activity Reference
19 Sandaracopimaric acid S. fulgens Relaxation of pulmo-
nary artery via P13K/
Akt-eNOS
Gao et al., 2014
20 7α-hydroxy-
sandaracopimaric acid
S. microphylla n.d. Luis et al., 1993
21 7α-acetoxy-
sandaracopimaric acid
S. microphylla n.d. Luis et al., 1993
22 3,4-secoisopimar-
4(18),7,15-trien-3-oic acid
S.
cinnabarina/S.
elegans
Hypotensive effect (30
mg/kg, i.v.), in male
Wistar rats. Spas-
molytic activity on
acetylcholine-induced
contractions in the iso-
lated guinea-pig ileum
(IC50= 1.5 µg/mL).
Antimutagenic acti-
vity, Ames ‘test on S.
typhimurium TA98 and
TA100 and on E. coli
(92.2% against 2-ami-
noanthracene).
Romussi et al.,
2000; Aleri et al.,
2007; Di Sotto et
al., 2009
23Rimuene S. dugesii n.d. Calderón-Oropeza
et al., 2021
24Parryin S. parryi n.d. Guajardo et al., 1997
Labdanes
25 Malonylcommunol S. cinnabarina α-glucosidase inhibitor
in yeast (IC50 =20.96
µM)
Bustos-Brito et al.,
2020
26 6β-hydroxy-trans-communic
acid
S. cinnabarina Anti-inammatory in
edema induced by TPA
(21.72% inhibition at
1.0 µmol/ear). The
α-glucosidase inhibitor in
yeast (IC50 =43.74 µM)
Bustos-Brito et al.,
2020
27 Trans-communic acid S. cinnabarina Anti-inammatory
in edema induced by
TPA (9.09% inhibition
at 1.0 µmol/ear). The
α-glucosidase inhibitor in
yeast (IC50 =45.15 µM)
Bustos-Brito et al.,
2020
28 Trans-communol S. cinnabarina n.d. Bustos-Brito et al.,
2020
29 Sclareol oxide S. dugesii n.d. Calderón-Oropeza et
al., 2021
30 Sclareol S. elegans Anti-cancer, anti-inam-
matory, anti-hyperten-
sive, and anti-diabetic
effects.
Zhou et al., 2020
31 Sclarene S. leucantha n.d. Villalta et al., 2021
n.d. no data
Table 1. Continuation

The chemical and biological role of pimaranes and labdanes from mexican Salvia species Rev. Latinoamer. Quím. 50/1-3(2023) 33
Salvia elegans, S. greggii, and S. ofci-
nalis L. prepared as decoction were repor-
ted to possess benets against metabolic
diseases because of their α-glucosidase,
α-amylase, and pancreatic lipase activities,
as well as antioxidant properties. However,
these effects were only associated with
possible involvement of phenolic acids (Pe-
reira et al., 2018). It should be interesting
to investigate the role of possible labdanes
and pimaranes found in this species but
not yet explored for their biological activity.
Sandaracopimaradiene and rimuene,
two pimaranes already reported in Kaem-
pferia galanga (Zingiberaceae) describing
anti-inammatory activity (Tungcharoen
et al., 2020) and as a useful treatment
against polycystic ovary syndrome in Thuja
occidentalis were identied in S. dugessi
(Cupressaceae; Küpeli-Akkol et al., 2015).
No specic activities have been descri-
bed for pimarane-type diterpenes isolated
of S. parryi. However, some of their consti-
tuents in other species have been conside-
red to possess antimicrobial activity (Porto
et al., 2009) and vascular relaxation (Hi-
pólito et al., 2009). The sclarene identied
in S. leucantha has been described among
the constituents in the immunostimulant
effects of frankincense oil (Mikhaeil et al.,
2003), as well as antibacterial activity iso-
lated from Nicotiana glutinosa (Solanaceae;
Popova et al., 2019). Whereas, the sclareol
characterised in S. elegans has been re-
ported to possess antimicrobial but also
proapoptotic activity (Wang et al., 2015).
The resistance that microorganisms
have developed against various drugs has
led to the search for new sources of anti-
microbials and anti-inammatories, which
also have fewer side effects. Among the
compounds explored are diterpenes of the
pimarane and labdane type, for example,
isopimarane isolated from Aeollanthus
rydingianus van Jaarsv & A.E.van Wyk
(Lamiaceae) has been tested. This com-
pound has proven to be effective on strains
of S. aureus and E. faecalis, E. faecium, E.
avescens, and E. hirae (Isca et al., 2020).
Labdanes of Vitex negundo L. (Lamiaceae)
are effective on E. coli and S. aureus strains
(Sichaem et al., 2021).
In conclusion, few studies have been
done by analysing the biological properties
of pimarane- and labdane-type diterpenes
in salvias. Although they were found to be
less abundant metabolites of this genus,
they are also scarcely examined to inves-
tigate their value for biological activities.
Nevertheless, scientic evidence found in
literature suggests their involvement in
diseases of major importance around the
world. Since according to reports of WHO
in 2022, cardiovascular diseases, diabetes,
and cancer as non-communicable diseases
now outnumber infectious diseases as the
“top killers globally”. Therefore, it is of great
relevance to look for health alternatives,
where Salvia species might be a source of
new drugs for effective and safety therapy.
ACKNOWLEDGMENTS
This work was supported by the program
UNAM-PAPIIT [No. IN221221]. Ortiz-Men-
doza thanks Postgraduate in Biological
Sciences at the National Autonomous Uni-
versity of Mexico for having received Ph.D.
academic training and CONACYT fellowship
number 793655.
AUTHOR CONTRIBUTIONS
Aguirre-Hernández, Martínez-Gordillo, and
González-Trujano participated in the con-
ceptualization, investigation, supervision,
and writhing original draft preparation.
Ortiz-Mendoza participated in the compi-
lation, systematization, and elaboration
of the tables to resume information of the
labdanes and pimaranes in Mexican Salvia
species. Fragoso-Martínez and Basurto-
Peña participated in the investigation of
literature information. Ortiz-Mendoza,
Dorazco-González, and Bazany-Rodríguez
contributed with the chemical information

34 Ortiz-Mendoza, N., et al.
of labdanes and pimaranes. All authors
have read and agreed to the nal version
of the manuscript. This paper was taken in
part from the Ph.D. of the Student Nancy
Ortiz-Mendoza.
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