Wolfgang Schühly

Jacaranda—An ethnopharmacological and phytochemical review

The genus Jacaranda, an important representative of the tribe Tecomeae in the family Bignoniaceae, is interesting from both biological and chemical perspectives. In this review, a contemporary summary of biological and pharmacological research on Jacaranda species will be presented and critically evaluated. Significant findings in the treatment of protozoa-caused diseases as well as of skin illnesses have been presented in ethnobotanical reports and recent studies were performed on crude extracts for certain Jacaranda species. Jacaranone, the most important constituent isolated is known to possess anti-cancer activity. Recently, high cutaneous toxicity together with moderate activity against leishmaniasis was described. Very few additional data are available on the biological activities and cytotoxicity of pure compounds from Jacaranda. Thirteen of the forty-nine distinguished species of Jacaranda have been reported in scientific literature as ethnobotanically used or phytochemically investigated. However, information about a chemical profile is available only for six species. The following article gives a critical assessment of the literature to date and aims to show that the pharmaceutical potential of this genus has been underestimated and deserves closer attention.

In vitro metabolism and disposition of honokiol in rat and human livers

The biotransformation of honokiol, a major constituent of the bark of Magnolia officinalis, was investigated in rat and human livers. When isolated, rat livers were perfused with 10 µM honokiol and two metabolites, namely hydroxylated honokiol conjugated with glucuronic and sulfuric acid (M1) and honokiol monoglucuronide (M2), were quantified in bile and perfusate by high-performance liquid chromatography. The hepatic extraction ratio and clearance of honokiol was very high in rat liver (E: 0.99 ± 0.01 and 35.8 ± 0.04 mL/min, respectively) leading to very low bioavailability (F = 0.007 ± 0.001). M2 formation was also highly efficient in human liver microsomes [V(max) /K(m) = 78.1 ± 6.73 µL/(min mg)], which appeared to be catalyzed mainly by UDP-glucuronosyltransferases 1A1, A3, 1A8, and 1A10, indicating hepatic and extrahepatic glucuronidation. Monosulfation of honokiol to the minor metabolite honokiol monosulfate [V(max) /K(m) = 27.9 ± 4.33 µL/(min mg)] by human liver cytosol was less pronounced and is mediated by sulfotransferases 1A1* 1, 1A1* 2, 1A2, 1A3, 1B1, and 1E1. P450-mediated oxidation of honokiol by liver microsomes, however, was below detection limit. In summary, this study established that glucuronidation and sulfation are the main metabolic pathways for honokiol in rat and human liver, suggesting their major contribution to clearance in vivo.

Pregnane Glycosides from Caralluma adscendens var. fimbriata

Eleven novel pregnane glycosides, 2–7 and 9–13, of which four, i.e., 10–13, comprised a new pregnane‐type genin exhibiting a hydroxymethylene instead of a Me group at C(19), and the known pregnane glycoside stalagmoside V (8) were isolated from whole plants of Caralluma adscendens var. fimbriata, a native Indian succulent plant. Their structures were elucidated by extensive 2D‐NMR spectroscopic studies.

Absolute configuration of eremophilane sesquiterpenes from Petasites hybridus: Comparison of experimental and calculated circular dichroism spectra

In-depth conformational analyses of 10 known eremophilane (= (1S,4aR,7R,8aR)-decahydro-1,8a-dimethyl-7-(1-methylethyl)napththalene) sesquiterpenes, 1-10, from Petasites hybridus were performed with molecular mechanics as well as density functional theory methods. Electronic transition energies and rotational strengths of these eight eremophilane lactones and two petasins were calculated by time-dependent density functional theory (B3PW91/TZVP). The absolute configurations of the constituents could be assigned by comparison of their simulated and experimental circular dichroism (CD) spectra in methanol as (4S,5R,8S,10R) (1, 2), (2R,4S,5R,8S,10R) (3, 4, 5), (2R,4S,5R,8R,9R,10R) (6), (2R,4S,5R,8R,10R) (7, 8), and (3R,4R,5R) (9, 10). Single-crystal X-ray diffraction data of 8beta-hydroxyeremophilanolide ((8S)-8-hydroxyeremophil-7(11)-en-12,8-olide) (1) served as starting point for the theoretical conformational calculations of the 8beta-epimers of the eremophilane lactones. Experimental CD spectra as well as (1)H NMR spectra of compound 1 in methanol were considerably dependent on sample concentration.

Cycloartane triterpenes from dikamali, the gum resin of Gardenia gummifera and Gardenia lucida.

We report on the chemical investigation of dikamali gum, which is the resin of Gardenia gummifera and G. lucida (Rubiaceae). Six new cycloartane triterpenes, dikamaliartanes A–F (1–6, resp.), together with a known flavonoid (7), were isolated and identified by NMR spectroscopy. All six cycloartanes are characterized by an open A‐ring with a free COOH group at C(3). In four of them, the C‐atoms C(23)–C(27) form a 4‐methylfuran‐2‐yl moiety. Bacterial assays using Staphylococcus aureus, Candida albicans, and Mycobacteria have been carried out but did not reveal significant activity.

Multiple screening of medicinal plants from Oaxaca, Mexico: ethnobotany and bioassays as a basis for phytochemical investigation

Based on ethnobotanical data collected among Zapotec Indians in Mexico, nine species traditionally applied to treat skin diseases and two species used to treat gastrointestinal disorders were subjected to several bioassays as further selection criteria for phytochemical investigation. Ten were active against at least one of the pathogenic and/or non-pathogenic bacteria and one against a non-pathogenic fungus in bioautographic TLC and agar diffusion tests. Cytotoxic/antitumor potential was found for one plant species with cell lines (KB, Caco-2) and for six with the brine shrimp assay. In the NF-κB- and the HET-CAM-test used to test for anti-inflammatory potential, two respectively one plant extract showed noteworthy activity. Furthermore, a potentially immunomodulating activity was investigated by evaluating the influence of extracts in various in vitro assays using murine and human lymphoid cells. In addition to the reported biological activities of the eleven plant species, comparisons of the ethnobotanical data and strategies for the selection for further phytochemical investigations are discussed.

Jacaranone-derived glucosidic esters from Jacaranda glabra and their activity against Plasmodium falciparum

In a survey of plants from Ecuador with antiprotozoal activity, Jacaranda glabra was found to show promising activity against the Plasmodium falciparum K1 strain. Subsequently, activity-guided isolation of the dichloromethane extract from the leaves of J. glabra afforded four new phenylethanoid glucosides containing jacaranone-type moieties (1-4), named jacaglabrosides A-D. Their chemical structures were identified using NMR spectroscopy and MS techniques. The compounds were found to be active in vitro against the P. falciparum K1 strain (IC(50) 1, 1.02; 2, 0.56; 3, 0.56; and 4, 0.55 microg/mL) and generally possessed a low cytotoxicity toward L-6 cells, with the exception of compound 1 (IC(50) 1, 8.3; 2, >90; 3, 87; and 4, 85 microg/mL).

Activities of Psilostachyin A and Cynaropicrin against Trypanosoma cruzi In Vitro and In Vivo

ABSTRACT In vitro and in vivo activities against Trypanosoma cruzi were evaluated for two sesquiterpene lactones: psilostachyin A and cynaropicrin. Cynaropicrin had previously been shown to potently inhibit African trypanosomes in vivo, and psilostachyin A had been reported to show in vivo effects against T. cruzi, albeit in another test design. In vitro data showed that cynaropicrin was more effective than psilostachyin A. Ultrastructural alterations induced by cynaropicrin included shedding events, detachment of large portions of the plasma membrane, and vesicular bodies and large vacuoles containing membranous structures, suggestive of parasite autophagy. Acute toxicity studies showed that one of two mice died at a cynaropicrin dose of 400 mg/kg of body weight given intraperitoneally (i.p.). Although no major plasma biochemical alterations could be detected, histopathology demonstrated that the liver was the most affected organ in cynaropicrin-treated animals. Although cynaropicrin was as effective as benznidazole against trypomastigotes in vitro, the treatment (once or twice a day) of T. cruzi-infected mice (up to 50 mg/kg/day cynaropicrin) did not suppress parasitemia or protect against mortality induced by the Y and Colombiana strains. Psilostachyin A (0.5 to 50 mg/kg/day given once a day) was not effective in the acute model of T. cruzi infection (Y strain), reaching 100% animal mortality. Our data demonstrate that although it is very promising against African trypanosomes, cynaropicrin does not show efficacy compared to benznidazole in acute mouse models of T. cruzi infection.

Hypericum species in the Páramos of Central and South America: a special focus upon H. irazuense Kuntze ex N. Robson

Knowledge about members of the flowering plant family Clusiaceae occurring in the tropical mountain regions of the world is limited, in part due to endemism and restricted distributions. High altitude vegetation habitats (Páramos) in Central and South America are home to numerous native Hypericum species. Information related to the phytochemistry of páramo Hypericum, as well as ecological factors with the potential to influence chemical defenses in these plants, is briefly reviewed. Results of the phytochemical analysis of Hypericum irazuense, a species collected in the páramo of the Cordillera de Talamanca in Costa Rica, are presented. Lastly, guidelines for the viable and sustainable collections of plant material, to facilitate future investigations of these interesting plants, are given.

Processing of a Sesquiterpene Lactone by Papilio glaucus Caterpillars

Papilio glaucus caterpillars encounter a diverse array of sesquiterpene lactones, including parthenolide, in the leaves of host plants Liriodendron tulipifera and Magnolia virginiana. These compounds are toxic to unadapted herbivores, and the development of P. glaucus caterpillars likely depends on their ability to excrete or detoxify them efficiently. A new metabolite of parthenolide, 2-α-hydroxydihydroparthenolide, identified by crystal structure determination and nuclear magnetic resonance, was present in the waste of the caterpillars. The parent compound was modified by the reduction of an α-methylene group, rendering the compound less reactive, and the addition of a hydroxyl group, which increases the polarity and prepares it for the conjugation reactions of phase II metabolism. Unmetabolized parthenolide was also present in large amounts in waste. P. glaucus larvae are apparently capable of excreting intact sesquiterpene lactones and sesquiterpene lactone metabolites during consumption of foliage rich in these compounds.