Ethnobotanical, Phytochemical, and Pharmacological Properties of the Subfamily Nepetoideae (Lamiaceae) in Inflammatory Diseases.

Nepetoideae is the most diverse subfamily of Lamiaceae, and some species are well known for their culinary and medicinal uses. In recent years, there has been growing interest in the therapeutic properties of the species of this group regarding inflammatory illnesses. This study aims to collect information on traditional uses through ethnobotanical, pharmacological, and phytochemical information of the subfamily Nepetoideae related to inflammatory diseases. UNAM electronic resources were used to obtain the information. The analysis of the most relevant literature was compiled and organised in tables. From this, about 106 species of the subfamily are traditionally recognised to alleviate chronic pain associated with inflammation. Pharmacological studies have been carried out in vitro and in vivo on approximately 308 species belonging to the genera Salvia, Ocimum, Thymus, Mentha, Origanum, Lavandula, and Melissa. Phytochemical and pharmacological evaluations have been performed and mostly prepared as essential oil or high polarity extracts, whose secondary metabolites are mainly of a phenolic nature. Other interesting and explored metabolites are diterpenes from the abietane, clerodane, and kaurane type; however, they have only been described in some species of the genera Salvia and Isodon. This review reveals that the Nepetoideae subfamily is an important source for therapeutics of the inflammatory process.

Variation in Terpenoid and Flavonoid Content in Different Samples of Salvia semiatrata Collected from Oaxaca, Mexico, and Its Effects on Antinociceptive Activity.

Salvia semiatrata Zucc. (Lamiaceae) is endemic to Oaxaca, Mexico, and is known for its analgesic properties. Terpenoids and phenolic compounds with antinociceptive potential have been characterised from this species. The aim of this research was to determine the variation in terpenoids and flavonoids in ethyl acetate extracts of S. semiatrata collected from ten different localities, as well as to evaluate the antinociceptive effect between plants with higher and lower contents of these secondary metabolites. Quantification of S. semiatrata compounds was performed via HPLC-DAD, whereas in vivo evaluation of the antinociceptive effect was performed via formalin test. The results showed that the most abundant groups of metabolites are oleanolic acid (89.60-59.20 µg/mg), quercetin (34.81-16.28 µg/mg), catechin (11.30-9.30 µg/mg), and 7-keto-neoclerodan-3,13-dien-18,19:15,16-diolide (7-keto) (8.01-4.76 µg/mg). Principal component and canonical correspondence analysis showed that the most contrasting localities in terms of compound content and climatic variables are Miahuatlán and Santiago Huauclilla. The differences in metabolite content between the two locations did not affect the antinociceptive effects evaluated at a dose of 300 mg/kg, p.o. In conclusion, the results indicate that S. semiatrata is effective in relieving pain, regardless of the site of collection, reinforcing its traditional use as analgesic.

A Review on the Ethnopharmacology and Phytochemistry of the Neotropical Sages (Salvia Subgenus Calosphace; Lamiaceae) Emphasizing Mexican Species.

Salvia is the most diverse genus within the mint family (Lamiaceae), many of its species are well-known due to their medicinal and culinary uses. Most of the ethnopharmacological and phytochemical studies on Salvia are centred on species from the European and Asian clades. However, studies about the most diverse clade, the Neotropical sages (Salvia subgenus Calosphace; 587 spp.), are relatively scarce. This review aims to compile the information on the traditional medicinal uses, pharmacological and phytochemistry properties of the Neotropical sages. To do so, we carried out a comprehensive review of the articles available in different online databases published from the past to 2022 (i.e., PubMed, Scopus, and Web of Science, among others) and summarized the information in tables. To uncover phylogenetic patterns in the distribution of four different groups of metabolites (mono-, sesqui-, di-, and triterpenes), we generated presence-absence matrices and plotted the tip states over a dated phylogeny of Salvia. We found several studies involving Mexican species of Salvia, but only a few about taxa from other diversity centres. The main traditional uses of the Mexican species of Calosphace are medicinal and ceremonial. In traditional medicine 56 species are used to treat diseases from 17 categories according to the WHO, plus cultural-bound syndromes. Pharmacological studies reveal a wide range of biological properties (e.g., antinociceptive, anti-inflammatory, anxiolytic, cytotoxic, and antidiabetic, etc.) found in extracts and isolated compounds of 38 Neotropical sages. From extracts of these species, at least 109 compounds have been isolated, identified and evaluated pharmacologically; 73 of these compounds are clerodanes, 21 abietanes, six flavonoids, five sesquiterpenoids, and four triterpenoids. The most characteristic metabolites found in the Neotropical sages are the diterpenes, particularly clerodanes (e.g., Amarisolide A, Tilifodiolide), that are found almost exclusively in this group. The Neotropical sages are a promising resource in the production of herbal medication, but studies that corroborate the properties that have been attributed to them in traditional medicine are scarce. Research of these metabolites guided by the phylogenies is recommended, since closely related species tend to share the presence of similar compounds and thus similar medicinal properties.

Lamiaceae in Mexican Species, a Great but Scarcely Explored Source of Secondary Metabolites with Potential Pharmacological Effects in Pain Relief.

The search for molecules that contribute to the relief of pain is a field of research in constant development. Lamiaceae is one of the most recognized families world-wide for its use in traditional medicine to treat diseases that include pain and inflammation. Mexico can be considered one of the most important centers of diversification, and due to the high endemism of this family, it is crucial for the in situ conservation of this family. Information about the most common genera and species found in this country and their uses in folk medicine are scarcely reported in the literature. After an extensive inspection in bibliographic databases, mainly Sciencedirect, Pubmed and Springer, almost 1200 articles describing aspects of Lamiaceae were found; however, 217 articles were selected because they recognize the Mexican genera and species with antinociceptive and/or anti-inflammatory potential to relieve pain, such as Salvia and Agastache. The bioactive constituents of these genera were mainly terpenes (volatile and non-volatile) and phenolic compounds such as flavonoids (glycosides and aglycone). The aim of this review is to analyze important aspects of Mexican genera of Lamiaceae, scarcely explored as a potential source of secondary metabolites responsible for the analgesic and anti-inflammatory properties of these species. In addition, we point out the possible mechanisms of action involved and the modulatory pathways investigated in different experimental models. As a result of this review, it is important to mention that scarce information has been reported regarding species of this family from Mexican genera. In fact, despite Calosphace being one of the largest subgenera of Salvia in the world, found mainly in Mexico, it has been barely investigated regarding its potential biological activities and recognized bioactive constituents. The scientific evidence regarding the different bioactive constituents found in species of Lamiaceae demonstrates that several species require further investigation in preclinical studies, and of course also in controlled clinical trials evaluating the efficacy and safety of these natural products to support their therapeutic potential in pain relief and/or inflammation, among other health conditions. Since Mexico is one of the most important centers of diversification, and due to the high endemism of species of this family, it is crucial their rescue, in situ conservation, and investigation of their health benefits.

Antinociceptive and anxiolytic-like effects of a neo-clerodane diterpene from Salvia semiatrata aerial parts.

CONTEXT: Salvia semiatrata Zucc. (Lamiaceae) is a species used as a tranquilizer and to relieve pain in folk medicine in Santiago Huauclilla, Oaxaca, Mexico. OBJECTIVE: To evaluate the antinociceptive and anxiolytic-like effects of S. semiatrata extracts and identify a bioactive metabolite. MATERIALS AND METHODS: The extracts were obtained by maceration of S. semiatrata aerial parts using solvents in increasing polarity (hexane, ethyl acetate and methanol). A neo-clerodane diterpene was extracted from the ethyl acetate fraction using open column chromatography. Identification of this metabolite was performed by crystallography, 1H NMR, 13C NMR, ATR-IR, ECD, MS and elemental analysis. The antinociceptive activity was explored using the writhing and formalin tests. Whereas, the anxiolytic-like responses were analysed in the open-field, hole-board and plus-maze tests. All the treatments were administered using oral gavage in male CD1 mice and explored 30 min after administration of the individual extracts (300 mg/kg) or the compound 1 (0.1, 1 or 10 mg/kg). RESULTS: All the extracts produced significant reduction in the nociceptive and anxiety-like behaviour compared to mice treated with the vehicle (0.5% tween 80 in saline solution). The spectroscopic analysis corroborated the presence of the neo-clerodane diterpene 7-keto-neoclerodan-3,13-dien-18,19:15,16-diolide (1), as partial responsible of the antinociceptive and anxiolytic-like effects, which produced a dose-dependent response in the writhing test with an ED50=4.15 mg/kg. Discussion and conclusions: These results reinforce the medicinal properties of S. semiatrata in folk medicine, where participation of a neo-clerodane diterpene was evidenced in the inhibitory central nervous system activity of this species.

A pilot study applying the plant Anchored Hybrid Enrichment method to New World sages (Salvia subgenus Calosphace; Lamiaceae).

We conducted a pilot study using Anchored Hybrid Enrichment to resolve relationships among a mostly Neotropical sage lineage that may have undergone a recent evolutionary radiation. Conventional markers (ITS, trnL-trnF and trnH-psbA) have not been able to resolve the relationships among species nor within portions of the backbone of the lineage. We sampled 12 representative species of subgenus Calosphace and included one species of Salvia's s.l. closest relative, Lepechinia, as outgroup. Hybrid enrichment and sequencing were successful, yielding 448 alignments of individual loci with an average length of 704bp. The performance of the phylogenomic data in phylogenetic reconstruction was superior to that of conventional markers, increasing both support and resolution. Because the captured loci vary in the amount of net phylogenetic informativeness at different phylogenetic depths, these data are promising in phylogenetic reconstruction of this group and likely other lineages within Lamiales. However, special attention should be placed on the amount of phylogenetic noise that the data could potentially contain. A prior exploration step using phylogenetic informativeness profiles to detect loci with sites with disproportionately high substitution rates (showing "phantom" spikes) and, if required, the ensuing filtering of the problematic data is recommended. In our dataset, filtering resulted in increased support and resolution for the shallow nodes in maximum likelihood phylogenetic trees resulting from concatenated analyses of all the loci. Additionally, it is expected that an increase in sampling (loci and taxa) will aid in resolving weakly supported, short deep internal branches.