José Alberto Gutiérrez-González’s research while affiliated with National Autonomous University of Mexico and other places

Background Ageratina is an American genus of the tribe Eupatorieae (Asteraceae) comprising about 320 species. In Mexico, some species of this genus are highly valued for their medicinal properties, particularly A. pichinchensis, A. petiolaris and A. grandifolia. Furthermore, herbal preparations of A. pichinchensis are available for treating several mycoses. Aim and Objective The present review is aimed to summarize the chemical and pharmacological properties of 36 species of Ageratina genus up to April 2022. Methods Data were recorded using online scientific databases including Scopus, PubMed, Google Scholar, Taylor and Francis Imprints, National Center for Biotechnology Information, Science Direct, JSTOR, and SciFinder. The information was assembled from research articles, relevant books on herbal medicinal plants and the history of medicinal plants from Mexico, theses, reports, and web pages. Results The specialized metabolites present in Ageratina genus belong to different chemical classes including flavonoids, benzyl benzoates, benzofurans, chromenes, and terpenoids. The chromenes, benzofurans, and benzyl benzoates are the metabolites most widespread in the genus. So far, the species more thoroughly investigated is A. adenophora. Ageratina has received little attention from the pharmacological point of view. The studies are limited to 10 species. The biological studies have been conducted with extracts and/or compounds isolated from plants collected mainly in China and Mexico. The results revealed that the extracts and metabolites possess several biological activities, which include antiviral, antioxidant, antimicrobial, anti-inflammatory, antinociceptive, antifeedant, larvicidal, acaricidal, antidiabetic, antiprotozoal, and wound-healing properties. In the case of A. pichinchensis, A. petiolaris, and A. grandifolia, the pharmacological studies provided evidence for their use for treating gastrointestinal complaints and diabetes. Furthermore, herbal preparations of A. pichinchensis are now widely used for alleviating onicomycoses. A. adenophora, endemic to Mexico, is the most investigated species, chemically and biologically, however some hepatotoxicity effect has been recorded. Conclusion This review recapitulates information on the Ageratina genus highlighting on the phytochemistry and biological activities of the species investigated so far. It is important to point out that, the pharmacological potential of this large genus remains largely unexplored.

An infusion from the aerial parts of Justicia spicigera Schltdl., an herb commonly used to treat diabetes, inhibited the activity of protein tyrosine phosphatase 1B (PTP1B). Two undescribed compounds, 2-N-(p-coumaroyl)-3H-phenoxazin-3-one, and 3″-O-acetyl-kaempferitrin, along with kaempferitrin, kaempferol 7-O-α-L-rhamnopyranoside, perisbivalvine B and 2,5-dimethoxy-p-benzoquinone were isolated from the active extract. Their structures were elucidated by a combination of spectroscopic and spectrometric methods. The isolates were evaluated for their inhibitory activity against PTP1B; the most active compounds were 2-N-(p-coumaroyl)-3H-phenoxazin-3-one, and perisbivalvine B with IC50 values of 159.1 ± 0.02 μM and 106.6 ± 0.01 μM, respectively. However, perisbivalvine B was unstable. Kinetic analysis of 2-N-(p-coumaroyl)-3H-phenoxazin-3-one and 2,5-dimethoxy-p-benzoquinone (obtained in good amounts) indicated that both compounds behaved as parabolic competitive inhibitors and bind to the enzyme forming complexes with 1:1 and 1:2 stoichiometry. Docking of 2-N-(p-coumaroyl)-3H-phenoxazin-3-one and 2,5-dimethoxy-p-benzoquinone to PTP1B1-400 predicted a good affinity of these compounds for PTP1B catalytic site and demonstrated that the binding of a second ligand is sterically possible. The 1:2 complex was also supported by the second docking analysis, which predicted an important contribution of π-stacking interactions to the stability of these 1:2 complexes. Finally, an UHPLC-MS method was developed and validated to quantify the content of kaempferitrin in the infusion of the plant.

Calea ternifolia Kunth (Asteraceae), the “dream herb”, is an important medicinal plant that grows from Mexico to Costa Rica. The plant is highly valued for rituals and for treating several illnesses including anorexia, upset stomach, diabetes, periodic fevers, diarrhea, bile problems, and skin diseases. This comprehensive literature survey on C. ternifolia was performed up to January 2021. Our review focuses on traditional uses, botanical aspects, chemical constituents, quality control tests, as well as pharmacological and toxicological studies. Data were recorded using online scientific databases including Scopus, PubMed, Google Scholar, Taylor and Francis Imprints, National Center for Biotechnology Information, Science Direct, JSTOR, and SciFinder. The information was assembled from research articles, relevant books on herbal medicinal plants and the history of medicinal plants from Mexico, theses, reports, and web pages. The more significant botanical and ethnomedical aspects were recorded including the discovery of the oneirogenic use (enhancer of dreams) of C. ternifolia by the Chontal Indigenous communities in Oaxaca, Mexico. The plant contains sesquiterpenes and flavonoids as the major constituents. Some properties associated with the plant’s traditional uses have been demonstrated including spasmolytic, antidiabetic, antidepressant, anti-inflammatory, and antinociceptive effects. The plant’s toxicity will be discussed in this paper. Solid pharmacological research provided evidence supporting the use of the dream herb for oneiromancy.

Fractionation of an aqueous extract from the aerial parts of Ageratina grandifolia yielded a new natural product, namely, 4-hydroxy-3-((S)-1'-angeloyloxy-(R)-2',3'-epoxy-3'-methyl)butylacetophenone (1), along with eight known compounds, including three flavonoids (2-4) and five chromenes (5-9). NMR data interpretation and DFT-calculated chemical shifts combined with DP4+ statistical and J-DP4 probability analyses allowed for the complete characterization of compound 1. The presence of compound 1 in a plant that biosynthesizes 2,2-dimethylchromenes is noteworthy, because an epoxy derivative has long been postulated as the reaction intermediate from the prenylated p-hydroxyacetophenones to cyclic dimethylchromenes. So far, this key intermediate has not been isolated, due to its purported chemical instability. Thus, this is the first report of a potential epoxide intermediate, leading to any of the chromene constituents of this plant. Compounds 1-9 inhibited yeast α-glucosidase with IC50 values ranging from 0.79 to 460 μM (acarbose, IC50 = 278.7 μM). The most active compounds were quercetagetin-7-O-(6-O-caffeoyl-β-d-glucopyranoside (3) and 6-hydroxykaempferol-7-O-(6-O-caffeoyl-β-d-glucopyranoside (4). Kinetic analysis of 3 revealed its mixed-type inhibitor nature. Docking studies into the crystallographic structure of yeast α-glucosidase (pdb 3A4A) predicted that 3 and 4 bind at the catalytic site of the enzyme.