Françoise Fons

Medicinal mushrooms in supportive cancer therapies: an approach to anti-cancer effects and putative mechanisms of action

Medicinal mushrooms have been valued as natural sources of bioactive compounds since times immemorial and have been recognized as potential immunomodulating and anti-cancer agents. Their consumption has consistently been shown to have beneficial effects on human health. Cancer is a generic term for several types of diseases that can be chronic and are responsible for a large number of deaths worldwide. Although there has been considerable progress in modern cancer therapy research, difficulties in understanding the molecular behavior of various types of cancers and the numerous side effects experienced by patients from treatments means that this whole subject area is still problematic. Thus, biological immunotherapy using natural bioactive compounds as supportive treatments in conventional cancer therapies has become in vogue. Bioactive metabolites isolated from medicinal mushrooms have shown potential successes in cancer treatment as biological immunotherapeutic agents that stimulate the immune system against cancer cells. They also act as an effective source of anti-cancer agents, capable of interfering with cellular signal transduction pathways linked to cancer development and progression. In this review we compile available data on the characteristics of medicinal mushrooms that appear to be particularly effective as biological immunotherapeutic agents. Major consideration is given to biological constituents and the putative mechanisms of action by which bioactive compounds act on the human body. Consideration is also given to the benefits that have been claimed for the use of mushrooms in treating cancer and the future prospects of using medicinal mushrooms as potent supportive candidate bioagents for treatment of cancers is discussed.

Amatoxin poisoning treatment decision-making: pharmaco-therapeutic clinical strategy assessment using multidimensional multivariate statistic analysis.

Ninety percent of fatal higher fungus poisoning is due to amatoxin-containing mushroom species. In addition to absence of antidote, no chemotherapeutic consensus was reported. The aim of the present study is to perform a retrospective multidimensional multivariate statistic analysis of 2110 amatoxin poisoning clinical cases, in order to optimize therapeutic decision-making. Our results allowed to classify drugs as a function of their influence on one major parameter: patient survival. Active principles were classified as first intention, second intention, adjuvant or controversial pharmaco-therapeutic clinical intervention. We conclude that (1) retrospective multidimensional multivariate statistic analysis of complex clinical dataset might help future therapeutic decision-making and (2) drugs such as silybin, N-acetylcystein and putatively ceftazidime are clearly associated, in amatoxin poisoning context, with higher level of patient survival.

Culture of Plantago species as bioactive components resources: a 20-year review and recent applications

Abstract Most of species from the worldwide distributed Plantago genus are greatly used as herbal medicines. Phytochemical investigations of various Plantago organs (leaves, stems) reveal their high potential to produce a wide array of bioactive secondary metabolites. So, in vitro cultures of Plantago species are managed in order to deliberately restrict the ecological factors and then to control the culture conditions. Experimental culture parameters of Plantago species, i.e. seed germination, temperature, relative humidity, light, substrates and additional nutritive solutions as well as the in vitro culture media and growth regulators are reviewed. The expensive optimizations of in vitro culture and biotransformation processes are reported. Changes in the concentration and the pattern of bioactive polyphenol compounds synthesized from in vitro cultures are discussed in the examined species of the genus Plantago in order to conclude about their potential interest as future drug candidates.

EFFECTS OF CINNAMIC ACID ON POLYPHENOL PRODUCTION IN PLANTAGO LANCEOLATA

Abstract Ribwort ( Plantago lanceolata ) contains two main caffeic acid glycoside esters, plantamoside and verbascoside. These two polyphenols were investigated in the aerial and underground parts of in vitro cultured ribworts. For the first time, it is reported that, whatever the age of this plant, plantamoside and verbascoside are concentrated in the roots with plantamoside levels double those of verbascoside. When P. lanceolata was transferred into a medium containing 10 −3 M ( E )-cinnamic acid, this chemical stress induced a slow degeneration of the initial roots. These were superseded by neoroots whose morphology was atypical during the first eight days following their appearance. In the initial roots, ( E )-cinnamic acid induced a temporary appearance of two cinnamic acid derivatives (NCD), but did not change the plantamoside and verbascoside levels. In the neoroots, high NCD levels were detected for only eight days. After the large decrease of these NCD, plantamoside and verbascoside appeared and increased. These NCDs have been identified as glucoside esters of ferulic and p -coumaric acids. These two compounds, which are absent from the traditional chemical profile of ribwort, probably arose from a ( E )-cinnamic acid detoxification pathway.

The fenugreek odor of Lactarius helvus

Lactarius helvus was investigated for vola- tile compounds by GC/MS. The volatile components proportion corresponds to 0.04% of dry weight. Thir- ty-eight components were identified. The major con- stituents were capric acid (25.6%), 3-amino-4,5-di- methyl-2(5H)-furanone (15.8%, (1)) and 2-methyl- butyric acid (12.9%). 3-Hydroxy-4,5-dimethyl-2(5H)- furanone (= sotolon, (2), 1.4%), the hydroxy furanone derivative molecule with the characteristic aroma of Trigonella foenum graecum seeds, is the key compound responsible for the fenugreek odor of L. helvus. Sotolon is widely used as an aroma compo- nent in food and tobacco industries due to its strong reminiscent odor.

Volatile components of Plantago lanceolata (Plantaginaceae)

Summary Fruits, leaves arid scapes of wild Plantago lanceolata (ribwort) were investigated for volatile compounds by GC/MS. Leaves of young ribworts (35-day-old) cultured in vitro were also analysed. The volatile compound proportion corresponds to 0.05%, 0.03% and 0.001% of fresh weight for fruits, leaves and scapes, respectively. Thirty-five and twenty-six components were identified from fruits and leaves, respectively, while scapes contained only seven volatile components. The major constituents of fruits were oct-1-en-3-ol (24.9%), hexahydrofarnesylacetone (15.7%), vanillic acid (9.8%) and neophytadienes (>10%); leaves contained mainly oct-1-en-3-ol (41.1%), (E),4(3-oxo-2,6,6-trimethylcyclo-hex-2-en-1-yl)-3-buten-2-ol (15.6%), 6-(3-hydroxy-1-butenyl)-1,5,5-trimethyl-7- oxabicyclo[4,1,0]heptan-3-ol (6.9%) and benzoic acid (6.3%). Neophytadienes were mainly found in both scapes of wild ribworts and leaves of seedling cultures.

Redécouverte et Typification des Champignons de la Région de Montpellier Illustrés par Michel-Félix Dunal et Alire Raffeneau-Delile

Abstract As successors of A.-P. de Candolle in Montpellier (France), M.-F. Dunal (1789– 1856) and A. Raffeneau-Delile (1778–1850) let a consequent unpublished iconography of fungi growing in this area. Investigations at the “Pôle Patrimoine scientifique” of the University Montpellier 2, based at the Institute of Botany, allowed the rediscovery and inventory of these forgotten collections. Ten species were published as new by É. Boudier, J. F. Lagarde and J. de Seynes based on these documents. Each of them is listed and lectotypified : Agaricus concolor Delile ex De Seynes, Ag. convivarum Dunal ex De Seynes, A. sulcatus Dunal ex De Seynes, Marasmius delilei De Seynes, Panaeolus regis De Seynes, Morchella dunalii Boud., Peziza atroviolacea Delile ex De Seynes, P. cynocopra Dunal ex De Seynes, P. viridifusca Delile ex De Seynes, and Plicaria planchonis Dunal ex Boud. Two varieties published by de Seynes are invalid : Agaricus sericeus var. infundibuliformis De Seynes et A. translucens var. squamulosus De Seynes. An epitype is designed for Ag. concolor. The following combinations are introduced : Tricholoma concolor (Delile ex De Seynes) P.-A. Moreau, J.-M. Bellanger et Courtec., T. concolor f. bisporum (Bon) P.-A. Moreau et Courtec., and Marasmiellus delilei (De Seynes) P.-A. Moreau et Courtec. (synonym of M. trabutii (Maire) Singer).

How to characterize three caryophyllaceous species by thé mean of thé ratio of two glucuronide prosaponins

Abstract Three main Caryophyllaceae species, Gypsophila paniculata L., Saponaria officinalis L. and Silene vulgaris (Moench) Garcke, were compared. A biological test carried on the root saponin extracts showed that S. officinalis extract was the least haemolytic and that G. paniculata extract was the most haemolytic of the three species. After a mild acid hydrolysis of the root saponins, quillaic acid 3-O-glucuronide (1) and gypsogenin 3-O-glucuronide (2), two representative prosaponins of the Caryophyllaceae, were quantified by HPLC. The content of 1 was the highest in the roots of S. vulgaris (16.2 ± 0.5 mg/g dry weight) and that of 2 was the highest in the roots of G. paniculata (30.2 ± 1.5 mg/g dry weight). S. vulgaris contained the most balanced amounts of the two prosaponins: 56% of 1 and 44% of 2. G. paniculata contained 22% of 1 and 78% of 2 whereas the relative proportions of the two prosaponins were reversed in S. officinalis: 94% of 1 and 6% of 2.

Purification and characterization of the haemolytic saponins of Silene vulgaris (Moench) Garcke native to Morocco

Abstract The saponins of Moroccan Silene vulgaris were extracted from the roots with 10% ethanol and purified using low-pressure liquid chromatography on a reversed phase column. Saponins fractions were characterized by thin layer chromatography and by their high haemolytic activity. Quantitative determination of the saponins by high performance liquid chromatography showed a higher accumulation of these glycosides in the 10–15 mm diameter wide roots (9.4% ± 0.5 saponins per dry wt) than in the 2–5 mm diameter wide roots (8.6% ± 0.5 saponins per dry wt). The high content of saponins in the roots of S. vulgaris from Morocco could justify the use of this plant as a raw material for the extraction of haemolytic saponins.

Decision-Making for the Detection of Amatoxin Poisoning: A Comparative Study of Standard Analytical Methods

Abstract Amatoxin-containing mushroom poisonings are recorded worldwide and the frequency increases due to confusion with other macrofungi. Affected regions are characterized by important disparities in relation to available technological equipment for analytical identification of amatoxins. In this context the present study was designed to define advantages and disadvantages of the most accessible standard analytical methods for amatoxin detection. Several methods were compared: (1) a commercialized immunoassay kit, (2) standard high-performance liquid chromatography (HPLC) and (3) high-performance thin layer chromatography (HP-TLC). For each method, linearity, limit of detection (LOD), limit of quantification (LOQ) and recovery were determined. Six macrofungi were analysed using these compared methods, three known to contain amatoxins: Amanita phalloides, Amanita virosa, Lepiota josserandii, and three free-amatoxin containing macrofungi: Amanita muscaria, Macrolepiota procera and Omphalotus olearius. Our results will allow for a choice of method with full knowledge of advantages and disadvantages of each technique as a function of local technological possibilities when facing suspected poisoning due to amatoxin-containing mushrooms. The final aim is to be able to reach faster and effective diagnosis in order to save a patients life.