Search

Etnopharmacological Relevance: The Convolvulaceae or morning glory family, with about 2000 species in the world's Tropics and subtropics, stands out among the plants used in traditional medicine. Medicinal plant complexes with important purgative properties have been developed in Mexico and Brazil from members of the genera Ipomoea and Operculina with storage roots. Popularly known as the jalap roots, their resin glycosides cause purgative and laxative activities that facilitate bowel movements., Aim of the Study: This article reviews the importance of the Convolvulaceae family in herbal medicine with a holistic approach that includes a historical perspective, as well as descriptions of crude drugs, phytopharmaceuticals, and chemical constituents. It further considers the family's distribution and biological properties, such as documented purging and cytotoxic activities of the Mexican and Brazilian jalap roots. The main aim of this review is to afford insights into the use and management of medicinal jalap roots for their potential development as herbal medicines., Materials and Methods: A search for available information on the genera and species that constitute the jalap roots was conducted using scientific databases, including PubMed, Google Scholar, ScienceDirect, and the International Plant Names Index. Also, numerous historical European herbals, botanical books, and pharmacopeias were reviewed using the Biodiversity Heritage Library and Internet Archive., Results: The review establishes that from the initial introduction of the medicinal jalap roots to Europe in the 16th century, various types of Neotropical purging roots were confused. The misunderstanding resulted from similar traditional uses of several species with common morphological features, organoleptic characteristics, and vernacular names. Subordinate species were also frequently used as substitutes for the signature or officinal crude drug. A compendium of contemporary uses of Mexican and Brazilian jalaps in herbal medicine is also presented., Conclusions: Mexican and Brazilian jalap roots, still in use in traditional medicine, offer great potential as sources of biologically active principles. Research should prioritize the investigation on their chemical markers, toxicity, mechanisms of action, ecological requirements, and ecological networks. An integrated ethnopharmacological approach, which has not been adequately explored, would promote their proper management as novel phytopharmaceuticals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

The jalap roots, Operculina hamiltonii D.F. Austin & Staples (Convolvulaceae), are extensively commercialized as a depurative and laxative remedy in traditional medicine of the north and northeast regions of Brazil. The purification by recycling HPLC and structure elucidation of three new acyl sugars or resin glycosides are described here from a commercial product made of powdered roots. Three macrocyclic structures of a tetrasaccharide of (11S)-hydroxyhexadecanoic acid, operculinic acid C (1), the undescribed hamiltonins II and III (3 and 4), in addition to the known batatinoside III (5), presented a diastereoisomeric relationship as one residue of n-dodecanoic acid esterified the oligosaccharide core on a different position in each compound. Furthermore, hamiltonin IV (6) was characterized as an ester-type homodimer of acylated operculinic acid C with the same substitution pattern identified in hamiltonins II (3) and III (4) for each of the dimer subunits. All the isolated resin glycosides did not display any intrinsic cytotoxicity (IC 50  > 25 μM). However, a combination of the individual isolated compounds 3-6 (1-50 μM) demonstrated an enhancement of cytotoxic effects with sublethal doses of vinblastine and podophyllotoxin (0.003 μM) in multidrug-resistant breast carcinoma epithelial cells (MCF-7/Vin)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Operculina hamiltonii is a vine native to the north and northeast region of Brazil, where its roots are traded as a depurative and laxative remedy with the name of Brazilian jalap in traditional medicine. Procedures for the isolation, purification by recycling HPLC, and structure elucidation of three undescribed resin glycosides are presented herein. Hamiltonin I ( 1 ) represents a macrocyclic structure of a tetrasaccharide of (11 S )-hydroxyhexadecanoic acid. Additionally, two acyclic pentasaccharides, named hamiltoniosides I ( 2 ) and II ( 3 ), were also isolated, which are related structurally to the known compounds 4 and 5 , macrocyclic lactone-type batatinosides. The tetrasaccharide core of 1 was diacylated by n -decanoic acid and the unusual n -hexadecanoic acid moiety, while the pentasaccharides 2 - 5 were esterified by one unit of n -decanoic or n -dodecanoic acid. All the isolated compounds were found to be inactive as cytotoxic agents. However, when they were evaluated (1-25 μM) in combination with a sublethal concentration of the anticancer agent vinblastine (0.003 μM), a significant enhancement of the resultant cytotoxicity was produced, especially for multidrug-resistant breast carcinoma epithelial cells. Such combined synergistic potency may be beneficial for chemotherapy, making resin glycosides potential candidates for drug repurposing of conventional chemotherapeutic drugs to reduce their side effects.

Hyptis monticola Mart. ex Benth. (Lamiaceae) is an endemic species of altitude regions of Brazil. From the leaves of this plant, two 5,6-dihydro-α-pyrones, named monticolides A and B, have been reported as cytotoxic agents against different tumor cell lines. The isolation by high-speed countercurrent chromatography in combination with recycling preparative high-performance liquid chromatography of the undescribed monticolides C-F is presented. These compounds corresponded to a series of related monticolide derivatives differing from each other by the number of acyl substituents. Their characterization by mass spectrometry and nuclear magnetic resonance is also presented, in conjunction with an evidence by a simple chemical correlation for their absolute stereochemistry. The distribution of these chemical markers in extracts of flowers, leaves and branches collected in different seasons by electrospray ionization ion trap mass spectrometry in positive mode was analyzed. Multivariate data analyses indicated that seasonality affects monticolide concentrations in different organs of the aerial parts. Monticolides A-F seem to be present as the original markers of the analyzed plant. However, mono-, di- and triacetylated monticolides can undergo acid-catalyzed transesterifications and their natural yields estimated were affected during the isolation procedures., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Dihydro-furanones are bioactive compounds isolated from various plants, marine fungi, and sponges. The present investigation describes the isolation by recycling HPLC and structural characterization by NMR of four previously undescribed 2(5H)-furanones, monticofuranolide A and pectinolides N-P, one phenylpropanoid, rosmarinic acid, and five known flavonoids, in addition to the undescribed natural flavonoid, 2R,3R-dihydrogossipetin or 5,7,8,3',4'-pentahydroxy flavanonol, from collections of H. monticola Mart. ex Benth and Hyptis pectinata (L.) Poit. Chemical correlations, resembling the biogenetic relationship of the isolated 2(5H)-furanones with their 5,6-dihydro-2H-pyran-2-one precursors, were accomplished to confirm their absolute configuration. Density functional theory-NMR/ECD calculations have been used to solve the absolute configuration for this type of compounds., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Hyptis verticillata Jacq. (Lamiaceae) is a Mexican medicinal plant for the treatment of skin infections and illness affecting the respiratory and gastrointestinal systems., Objective: To associate the efficient resolution provided by ultra-high-performance liquid chromatography combined to the accuracy of a hybrid Fourier-transform (FT) mass spectrometer in order to dereplicate podophyllotoxin-type lignans in a plant extract., Methods: An ultra-high-performance liquid chromatography-photodiode array-high resolution electrospray ionisation tandem mass spectrometry (UHPLC-PDA-HRESI-MS/MS) method was applied in an Orbitrap hybrid FT spectrometer for dereplication of podophyllotoxin and related cytotoxic lignans in wild bushmint. This procedure included high-resolution mass values for positively charged ions [M + H] + and [M + NH 4 ] + , MS/MS data, and comparison of UV maxima and retention times with pure compounds., Results: Podophyllotoxin in addition to seven aryltetralins, four arylnaphthalenes, and one dibenzylbutyrolactone were dereplicated from the methanol extract in a short-time analysis (5 min). 4'-O-Demethyl-dehydro-deoxypodophyllotoxin was identified as a new natural product., Conclusion: The applied UHPLC-MS/MS dereplication method is suitable for a rapid analysis of podophyllotoxin-type lignans and the resulting chemical fingerprinting could be valuable in quality control of herbal drugs and their phytopharmaceuticals., (© 2019 John Wiley & Sons, Ltd.)

Analysis of the methanol-soluble resin glycosides from the roots of Operculina macrocarpa was assessed by generating NMR profiles of five glycosidic acids obtained through saponification, acetylation, and recycling HPLC purification. Operculinic acid H (1), two novel hexasaccharides, operculinic acids I (2) and J (3), the known purgic acid A (4), and a quinovopyranoside of (-)-(7 R)-hydroxydecanoic acid, operculinic acid K (5), were isolated. Three intact resin glycosides related to 1, the novel macrocarposidic acids A (6) and B (7), in addition to the previously known macrocarposidic acid C (8), were also purified with isovaleroyl, tigloyl, and exogonoyl [(3 S,9 R)-3,6:6,9-diepoxydecanoyl] groups as esterifying residues. A selective intramolecular lactonization was produced to generate a macrocyclic artifact (17) during acetylation of 1, resembling the distinctive structure of the Convolvulaceous resin glycosides.

Cytotoxic 6-heptyl-5,6-dihydro-2 H-pyran-2-ones are chemical markers of Hyptis (Lamiaceae) and are responsible for some of the therapeutic properties of species with relevance to traditional medicine. The present investigation describes the isolation of known pectinolides A-C (1-3), in addition to the new pectinolides I-M (4-8), from two Mexican collections of H. pectinata by HPLC. The novel biosynthetically related monticolides A (9) and B (10) were also isolated by high-speed countercurrent chromatography from H. monticola, an endemic species of the Brazilian southeastern high-altitude regions. A combination of chemical correlations, chiroptical measurements, and Mosher ester NMR analysis was used to confirm their absolute configuration. The utility of DFT-NMR chemical shifts and J H-H calculations was assessed for epimer differentiation. Molecular docking studies indicated that 6-heptyl-5,6-dihydro-2 H-pyran-2-ones have a high affinity for the pironetin-binding site of α-tubulin, which may be a possible mechanism contributing to the cytotoxic potential of these small and flexible molecules.

Nine terpenoids were isolated from the leaves and flowers of Salvia amarissima, including a new acylated diterpenoid glucoside, amarisolide F (1), a new neo-clerodane diterpenoid, amarissinin D (2), which was isolated as an acetyl derivative (2a), and four known diterpenoids. The structure of amarisolide F (1) was elucidated by NMR and MS data analyses, as well as its methanolysis products 7 and 8, which also constituted new diterpenoids, named amarissinin E and 8- epi-amarissinin E, respectively. The absolute configuration of compound 7 was established by single-crystal X-ray diffraction. The cytotoxicity and anti-MDR effect of 1 in three phenotypes of the MCF-7 cell lines were assayed. Compound 1 was 2-3.6-fold more active than amarissinins A (3) and B (4), but several orders of magnitude less active than teotihuacanin (6) and reserpine.

Context: Echinacea (Asteraceae) is used because of its pharmacological properties. However, there are few studies that integrate phytochemical analyses with pharmacological effects., Objective: Evaluate the chemical profile and biological activity of hydroalcoholic Echinacea extracts., Materials and Methods: Density, dry matter, phenols (Folin-Ciocalteu method), flavonoids (AlCl 3 method), alkylamides (GC-MS analysis), antioxidant capacity (DPPH and ABTS methods), antiproliferative effect (SRB assay), anti-inflammatory effect (paw oedema assay, 11 days/Wistar rats; 0.4 mL/kg) and hypoglycaemic effect (33 days/Wistar rats; 0.4 mL/kg) were determined in three Echinacea extracts which were labelled as A, B and C (A, roots of Echinacea purpurea L. Moench; B, roots, leaves, flowers and seeds of Echinacea purpurea; C, aerial parts and roots of Echinacea purpurea and roots of Echinacea angustifolia DC)., Results: Extract C showed higher density (0.97 g/mL), dry matter (0.23 g/mL), phenols (137.5 ± 2.3 mEAG/mL), flavonoids (0.62 ± 0.02 mEQ/mL), and caffeic acid (0.048 mg/L) compared to A and B. A, B presented 11 alkylamides, whereas C presented those 11 and three more. B decreased the oedema (40%) on day 2 similar to indomethacin. A and C showed hypoglycaemic activity similar to glibenclamide. Antiproliferative effect was only detected for C (IC 50 270 μg/mL; 8171 μg/mL; 9338 μg/mL in HeLa, MCF-7, HCT-15, respectively)., Discussion and Conclusion: The difference in the chemical and pharmacological properties among extracts highlights the need to consider strategies and policies for standardization of commercial herbal extracts in order to guarantee the safety and identity of this type of products.

The multidrug resistance (MDR) phenotype is considered as a major cause of the failure in cancer chemotherapy. The acquisition of MDR is usually mediated by the overexpression of drug efflux pumps of a P-glycoprotein. The development of compounds that mitigate the MDR phenotype by modulating the activity of these transport proteins is an important yet elusive target. Here, we screened the saponification and enzymatic degradation products from Salvia hispanica seed's mucilage to discover modulating compounds of the acquired resistance to chemotherapeutic in breast cancer cells. Preparative-scale recycling HPLC was used to purify the hydrolysis degradation products. All compounds were tested in eight different cancer cell lines and Vero cells. All compounds were noncytotoxic at the concentration tested against the drug-sensitive and multidrug-resistant cells (IC 50  > 29.2 μM). For the all products, a moderate vinblastine-enhancing activity from 4.55-fold to 6.82-fold was observed. That could be significant from a therapeutic perspective. Copyright © 2017 John Wiley & Sons, Ltd., (Copyright © 2017 John Wiley & Sons, Ltd.)

Brevipolides K-O (1-5), five new cytotoxic 6-(6'-cinnamoyloxy-2',5'-epoxy-1'-hydroxyheptyl)-5,6-dihydro-2H-pyran-2-ones (IC 50 values against six cancer cell lines, 1.7-10 μM), were purified by recycling HPLC from Hyptis brevipes. The structures, containing a distinctive tetrahydrofuran ring, were established by comprehensive quantum mechanical calculations and experimental spectroscopic analysis of their NMR and ECD data. Detailed analysis of the experimental NMR 1 H- 1 H vicinal coupling constants in comparison with the corresponding DFT-calculated values at the B3LYP/DGDZVP level confirmed the absolute configuration of 3 and revealed its conformational preferences, which were further strengthened by NOESY correlations. NMR anisotropy experiments by the application of Mosher's ester methodology and chemical correlations were also used to conclude that this novel brevipolide series (1-5) share the same absolute configuration corresponding to C-6(R), C-1'(S), C-2'(R), C-5'(S), and C-6'(S).

Multidrug resistance is the expression of one or more efflux pumps, such as P-glycoprotein, and is a major obstacle in cancer therapy. The use of new potent and noncytotoxic efflux pump modulators, coadministered with antineoplastic agents, is an alternative approach for increasing the success rate of therapy regimes with different drug combinations. This report describes the isolation and structure elucidation of six new resin glycosides from moon vine seeds (Ipomoea alba) as potential mammalian multidrug-resistance-modifying agents. Albinosides IV-IX (1-6), along with the known albinosides I-III (7-9), were purified from the CHCl 3 -soluble extract. Degradative chemical reactions in combination with NMR spectroscopy and mass spectrometry were used for their structural elucidation. Four new glycosidic acids, albinosinic acids D-G (10-13), were released by saponification of natural products 3-6. They were characterized as tetrasaccharides of either convolvulinolic (11S-hydroxytetradecanoic) or jalapinolic (11S-hydroxyhexadecanoic) acids. The potentiation of vinblastine susceptibility in multidrug-resistant human breast carcinoma cells of albinosides 1-6 was evaluated by modulation assays. The noncytotoxic albinosides VII (4) and VIII (5), at a concentration of 25 μg/mL, exerted the strongest potentiation of vinblastine susceptibility, with a reversal factor (RF MCF-7/Vin + ) of 201- and >2517-fold, respectively.

Three new diterpenes (amarissinins A-C, 1-3) containing several oxygenated functionalities were isolated from the leaves and flowers of Salvia amarissima. The structures of these compounds were established through the analysis of their NMR spectroscopy and mass spectrometry data. The structures of compounds 1 and 2 were confirmed by single crystal X-ray diffraction. Compound 2 was identified as a C-10 epimer of dugesin F (5). The cytotoxic activity of these compounds against five human cancer cell lines was determined. Additionally, the capability to modulate the multidrug resistance (MDR) in the MCF-7 cancer cell line resistant to vinblastine was tested., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Carbohydrates can be used as substrates to synthesize new complex molecules; these molecules contain several chiral centers that can be used in organic synthesis. D-Fucose diphenyl thioacetal reacts differentially with acetone, and this paper describes a study of the mechanism of this reaction using theoretical chemistry methods. The conformer distribution was studied using a Monte Carlo method for the reaction products, and the obtained conformers were validated by calculating the hydrogen spin-spin coupling constants with the DFT/B3LYP/DGDZVP method. Results agreed with the experimental coupling constants with an adequate root mean squared deviation. The free energies and enthalpies of formation of the resulting global minimum conformers were calculated with the same method and with the thermochemical compound method CBS-4 M. This technique, combined with the conformational analysis, allowed comparison of the formation enthalpies of the compounds involved in this reaction, and, with this information, we can postulate the correct reaction pathway. Graphical abstract Reaction pathway.

Recycling liquid chromatography was used for the isolation and purification of resin glycosides from the CHCl3-soluble extracts prepared using flowers of Ipomoea wolcottiana Rose var. wolcottiana. Bioassay-guided fractionation, using modulation of both antibiotic activity against multidrug-resistant strains of Gram-negative bacteria and vinblastine susceptibility in breast carcinoma cells, was used to isolate the active glycolipids as modulators of the multidrug resistance phenotype. An ester-type dimer, wolcottine I, one tetra- and three pentasaccharides, wolcottinosides I-IV, in addition to the known intrapilosin VII, were characterized by NMR spectroscopy and mass spectrometry. In vitro assays established that none of these metabolites displayed antibacterial activity (MIC>512 μg/mL) against multidrug-resistant strains of Escherichia coli, and two nosocomial pathogens: Salmonella enterica serovar Typhi and Shigella flexneri; however, when tested (25 μg/mL) in combination with tetracycline, kanamycin or chloramphenicol, they exerted a potentiation effect of the antibiotic susceptibility up to eightfold (64 μg/mL from 512 μg/mL). It was also determined that these non-cytotoxic (CI50>8.68 μM) agents modulated vinblastine susceptibility at 25 μg/mL in MFC-7/Vin(+) cells with a reversal factor (RFMCF-7/Vin(+)) of 2-130 fold., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Teotihuacanin (1), an unusual rearranged clerodane diterpene with a new carbon skeleton containing a spiro-10/6 bicyclic system, was isolated from the leaves and flowers of Salvia amarissima. Its structure was determined through spectroscopic analyses. Its absolute configuration was established by single-crystal X-ray diffraction. Compound 1 showed potent modulatory activity of multidrug resistance in vinblastine-resistant MCF-7 cancer cell line (reversal fold, RFMCF-7/Vin+ > 10703) at 25 μg/mL.

Density functional theory (DFT) (1) H-(1) H NMR coupling constant calculations, including solvation parameters with the polarizable continuum model B3LYP/DGDZVP basis set together with the experimental values measured by spectral simulation, were used to predict the configuration of hydroxylated 6-heptenyl-5,6-dihydro-2H-pyran-2-ones 1, 2, 4, and 7, allowing epimer differentiation. Modeling of these flexible compounds requires the inclusion of solvation models that account for stabilizing interactions derived from intramolecular and intermolecular hydrogen bonds, in contrast with peracetylated derivatives (3, 5, and 6) in which the solvation consideration can be omitted. Using this DFT NMR integrated approach as well as spectral simulation, the configurational reassignment of synargentolide A (8) was accomplished by calculations in the gas phase among four possible diastereoisomers (8-11). Calculated (3) JH,H values established its configuration as 6R-[4'S,5'S,6'S-(triacetyloxy)-2E-heptenyl]-5,6-dihydro-2H-pyran-2-one (8), in contrast with the incorrect 6R,4'R,5'R,6'R-diastereoisomer previously proposed by synthesis (12). Application of this approach increases the probability for successful enantiospecific total syntheses of flexible compounds with multiple chiral centers., (Copyright © 2014 John Wiley & Sons, Ltd.)