Isabel Rivero-Cruz’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.

The roots of the cactus Peniocereus greggii, which grows in Northern Mexico and in the south of Arizona, are highly valued by the Pima to treat diabetes and other illnesses, such as breast pain and common cold. As part of our chemical and pharmacological investigation on medicinal plants used for treating diabetes, herein we report the hypoglycemic and antihyperglycemic action of a decoction prepared from the roots of the plant. The active compounds were a series of cholestane steroids, namely, peniocerol (2), desoxyviperidone (3), viperidone (4), and viperidinone (5). Also, a new chemical entity was obtained from an alkalinized chloroform extract (CE1), which was characterized as 3,6-dihydroxycholesta-5,8(9),14-trien-7-one (6) by spectroscopic means. Desoxyviperidone (3) showed an antihyperglycemic action during an oral glucose tolerance test. Compound 3 was also able to decrease blood glucose levels during an intraperitoneal insulin tolerance test in hyperglycemic mice only in combination with insulin, thus behaving as an insulin sensitizer agent. Nevertheless, mitochondrial bioenergetic experiments revealed that compounds 3 and 6 increased basal respiration and proton leak, without affecting the respiration associated with ATP production in C2C12 myotubes. Finally, an ultraefficiency liquid chromatographic method for quantifying desoxyviperidone (3) and viperidone (4) in the crude drug was developed and validated. Altogether, our results demonstrate that Peniocereus greggii decoction possesses a hypoglycemic and antihyperglycemic action in vivo, that sterols 2 and 6 promotes insulin secretion in vitro, and that desoxyviperidone (3) physiologically behaves as an insulin sensitizer agent by a mechanism that may involve mitochondrial proton leak.

Chemical investigation of Punctularia atropurpurascens strain HM1 (Punctulariaceae), a corticioid isolated from a decorticated piece of Quercus bark collected in Bosque de Tlalpan, Mexico City, led to the isolation of a new drimane, 1-α-hydroxy-isodrimenine (1) and a new tetrahydroxy kauranol, 16-hydroxy-phlebia-nor-kauranol (2), together with the known N-phenylacetamide (3). Structures of all compounds were elucidated by spectroscopic and spectrometric methods, and the absolute configuration of 1 and 2 was confirmed via single-crystal X-ray crystallography. The isolated compounds showed modest antimycobacterial activity.

From solid rice-based cultures of Malbranchea albolutea, three undescribed ardeemins and sartoryglabrins analogs were discovered and named alboluteins A-C. 1H-Indole-3-carbaldehyde, and anthranilic acid were also isolated. 1D and 2D-NMR techniques, as well as DFT-calculated chemical shifts, allowed characterizing alboluteins A-C. Testing these compounds against PTP1B indicated their inhibitory activity with IC50's ranging from 19 to 129 μM (ursolic acid IC50 = 29.8 μM, positive control). Kinetic analysis revealed that albolutein C behaved as a non-competitive inhibitor. Docking studies of alboluteins A-C into the crystal structure of PTP1B (PDB ID: 1T49) predicted that all compounds prefer to bind at the allosteric site of the enzyme, with Ki values of 2.02 × 10⁻⁴, 1.31 × 10⁻⁴, and 2.67 × 10⁻⁴ mM, respectively. Molecular dynamic studies indicated that the active compounds remained tied to the enzyme with good binding energy.

An infusion prepared from the aerial parts of Salvia amarissima Ortega inhibited the enzyme protein tyrosine phosphatase 1B (PTP-1B) (IC50~88 and 33 μg/mL, respectively). Phytochemical analysis of the infusion yielded amarisolide (1), 5,6,4′-trihydroxy-7,3′-dimethoxyflavone (2), 6-hydroxyluteolin (3), rutin (4), rosmarinic acid (5), isoquercitrin (6), pedalitin (7) and a new neo-clerodane type diterpenoid glucoside, named amarisolide G (8a,b). Compound 8a,b is a new natural product, and 2–6 are reported for the first time for the species. All compounds were tested for their inhibitory activity against PTP-1B; their IC50 values ranged from 62.0 to 514.2 μM. The activity was compared to that of ursolic acid (IC50 = 29.14 μM). The most active compound was pedalitin (7). Docking analysis predicted that compound 7 has higher affinity for the allosteric site of the enzyme. Gas chromatography coupled to mass spectrometry analyses of the essential oils prepared from dried and fresh materials revealed that germacrene D (15) and β-selinene (16), followed by β-caryophyllene (13) and spathulenol (17) were their major components. An ultra-high performance liquid chromatography coupled to mass spectrometry method was developed and validated to quantify amarisolide (1) in the ethyl acetate soluble fraction of the infusion of S. amarissima.

Chemical analysis of the ethyl acetate soluble fraction prepared from the infusion of Hydrangea seemannii L. Riley, Hydrangeaceae, an endemic medicinal plant of México, afforded thirteen polyphenols identified as chlorogenic acid (1), 3,5- and 4,5-dicaffeoylquinic acids (2 and 3), and ten flavonoids (4–13). Of these, the isolation of guajaverin (6) and juglalin (7) are reported for the first time in the Hydrangea genus. The structures were elucidated on basis of the spectroscopic and spectrometric data. Next, a selective LC-MS method was developed for the simultaneous determination of five flavonoids in the ethyl acetate soluble fraction and then validated according to the ICH guidelines (2005). Finally, the developed LC-MS method was successfully applied to quantify the flavonoids content of 4 (3.69 mg/g), 6 (3.83 mg/g), 7 (5.84 mg/g), 8 (2.30 mg/g), and 12 (1.40 mg/g). Graphical Abstract

The term copalchi has been used in the scientific literature to define a group of plants of the Rubiaceae and Euphorbiaceae families with extremely bitter stem-barks, useful for treating diabetes and malaria. In this review we summarized the most relevant chemical and pharmacological works carried out in the last century with the copalchis of the Rubiaceae family, namely Hintonia latiflora, H. standleyana and Exostema caribaeum. Their major components are 4-phenylcoumarins 5,7,3′,4′- or 5,7,4′-substituted with oxygenated functionalities, with the former having the most common pattern. These along with a few cucurbitacins are responsible for the antidiabetic properties of both Hintonia species. E. caribaeum contained mostly 4-phenylcoumarins, which apparently are the antimalarial constituents of these plants. Toxicological reports on these plants are discussed. The quality control procedures (chromatographic and molecular) developed for the three species are summarized. These will be valuable for their unequivocal identification, which in turn will avoid their partial adulteration or substitution. Future studies are required to solve the puzzle around the toxicity of the copalchis and for better understanding their pharmacological actions. Finally, establishment of their metabolomics profiles will provide a better knowledge of their secondary metabolism and help map their biosynthesis pathways.

During our ongoing research on fungal strains from unexplored sources, the reinvestigation of the CHCl 3 −MeOH extract of the marine-facultative Aspergillus sp. MEXU 27854 yielded a new N-methyl cyclic pentapeptide (1) along with known butyrolactone II and PF1233 A. In addition, from the marine-facultative Gymnoascus hyalinosporus MEXU 29901, a new alternariol glucoside, 10-O-[β-D-(4-methoxyl-glucopyranosyl)]-4-O-methylalternariol (2) and known alternariol 4-O-methyl ether, alternariol and beauvericin, were isolated. The structures of 1 and 2 were established by detailed spectroscopic data, and their absolute configuration was ascertained by Marfey's analysis and HRESIMS-MS/MS data for 1, and by chemical degradation and optical rotation analysis for 2.