Bibenzyls and bisbybenzyls of bryophytic origin as promising source of novel therapeutics: pharmacology, synthesis and structure-activity.

BACKGROUND: The amphibian, non-vascular, gametophyte-dominant, bio-indicator class, bryophytes; with their wide ranges of habitat have attained importance due to their promising medicinal attributions and therapeutic role; mostly aided by presence of aromatic bibenzyl and bisbybenzyl class of compounds. Bibenzyls are steroidal ethane derivatives, resembling the structural moiety of bioactive dihydro-stilbenoids or iso-quinoline alkaloids. These stress triggered secondary metabolites are the by-products of the flavonoid biosynthetic pathway. Different classes of bryophytes (Bryophyta, Marchantiophyta and Anthocerotophyta) possess different subtypes of bibenzyls and dimeric bisbibenzyls. Among the liverwort, hornwort and mosses, former one is mostly enriched with bibenzyl type constituents as per the extensive study conducted for phytochemical deposit. Considering macrocyclic and acyclic group of bibenzyls and bisbybenzyls, generally marchantin type compounds are reported vividly for significant biological activity that includes neuro-nephro-cardio-protection besides anti-allergic, anti-microbial, anti-apoptotic and cytotoxic activities studied on in-vitro and in-vivo models or on cell lines. RESULT: The critical analysis of reported chemical and pharmaceutical attributions of bibenzyls and bis-bibenzyls yielded detailed report on this compound class along with their application, mode of action, natural source, techniques of synthesis, extraction procedure, isolation and characterization. Further, the structure activity relationship studies and bioactivity of bibenzyls derived from non-bryophytic origin were also summarized. CONCLUSION: This review encompasses prospective biological application of botanical reservoir of this primarily ignored, primeval land plant group where recent technical advances has paved the way for qualitative and quantitative isolation and estimation of novel compounds as well as marker components to study their impact on environment, as bio-control agents and as key leads in future drug designing. Graphical abstract.

Bryophytes as a source of bioactive volatile terpenoids - A review.

Bryophytes, phylogenetically placed between the algae and pteridophytes, are divided into three classes: mosses, liverworts, and hornworts. Traditional system of medicine throughout the world has been utilizing this group of plants to treat various ailments. One of the outstanding features of these spore forming plants is their chemistry, especially that of the liverworts. Liverworts have yielded a rich array of terpenoids, especially sesqui- and diterpenoids. Many of these compounds are characterized by unprecedented structures, and some have not been found in any other plants, fungi or marine organisms. Among the bryophytes, the chemical constituents of liverworts and their biological activity have been studied in the most detail. In this review the chemistry of the terpenoids found in bryophytes have been presented, and their phytotoxic, antimicrobial, antifungal, cytotoxic, anti-inflammatory, piscicidal, insect repellent, antileishmanial and antitrypanosomal activities.

Contrasting pectin polymers in guard cell walls of Arabidopsis and the hornwort Phaeoceros reflect physiological differences.

BACKGROUND AND AIMS: In seed plants, stomata regulate CO2 acquisition and water relations via transpiration, while minimizing water loss. Walls of guard cells are strong yet flexible because they open and close the pore by changing shape over the substomatal cavity. Pectins are necessary for wall flexibility and proper stomata functioning. This study investigates the differences in pectin composition in guard cells of two taxa that represent key lineages of plants with stomata: Arabidopsis, an angiosperm with diurnal stomatal activity, and Phaeoceros, a bryophyte that lacks active stomatal movement. METHODS: Using immunolocalization techniques in transmission electron microscopy, this study describes and compares the localization of pectin molecule epitopes essential to stomata function in guard cell walls of Arabidopsis and Phaeoceros. KEY RESULTS: In Arabidopsis, unesterified homogalacturonans very strongly localize throughout guard cell walls and are interspersed with arabinan pectins, while methyl-esterified homogalacturonans are restricted to the exterior of the wall, the ledges and the junction with adjacent epidermal cells. In contrast, arabinans are absent in Phaeoceros, and both unesterified and methyl-esterified homogalacturonans localize throughout guard cell walls. CONCLUSIONS: Arabinans and unesterified homogalacturonans are required for wall flexibility, which is consistent with active regulation of pore opening in Arabidopsis stomata. In contrast, the lack of arabinans and high levels of methyl-esterified homogalacturonans in guard cell walls of Phaeoceros are congruent with the inability of hornwort stomata to open and close with environmental change. Comparisons across groups demonstrate that variations in guard cell wall composition reflect different physiological activity of stomata in land plants.

Biochemical characterization of microbial type terpene synthases in two closely related species of hornworts, Anthoceros punctatus and Anthoceros agrestis.

Microbial terpene synthase-like (MTPSL) genes are a type of terpene synthase genes only recently identified in plants. In contrast to typical plant terpene synthase genes, which are ubiquitous in land plants, MTPSL genes appear to occur only in nonseed plants. Our knowledge of catalytic functions of MTPSLs is very limited. Here we report biochemical characterization of the enzymes encoded by MTPSL genes from two closely related species of hornworts, Anthoceros punctatus and Anthoceros agrestis. Seven full-length MTPSL genes were identified in A. punctatus (ApMTPSL1-7) based on the analysis of its genome sequence. Using homology-based cloning, the apparent orthologs for six of the ApMTPSL genes, except ApMTPSL2, were cloned from A. agrestis. They were designated AaMTPSL1, 3-7. The coding sequences for each of the 13 Anthoceros MTPSL genes were cloned into a protein expression vector. Escherichia coli-expressed recombinant MTPSLs from hornworts were assayed for terpene synthase activities. Six ApMTPSLs and five AaMTPSLs, except for ApMTPSL5 and AaMTPSL5, showed catalytic activities with one or more isoprenyl diphosphate substrates. All functional MTPSLs exhibited sesquiterpene synthase activities. In contrast, only ApMTPSL7 and AaMTPSL7 showed monoterpene synthase activity and only ApMTPSL2, ApMTPSL6 and AaMTPSL6 showed diterpene synthase activity. Most MTPSLs from Anthoceros contain uncanonical aspartate-rich motif in the form of either 'DDxxxD' or 'DDxxx'. Homology-based structural modeling analysis of ApMTPSL1 and ApMTPSL7, which contain 'DDxxxD' and 'DDxxx' motif, respectively, showed that 'DDxxxD' and 'DDxxx' motifs are localized in the similar positions as the canonical 'DDxxD' motif in known terpene synthases. To further understand the role of individual aspartate residues in the motifs, ApMTPSL1 and ApMTPSL7 were selected as two representatives for site-directed mutagenesis studies. No activities were detected when any of the conserved aspartic acid was mutated into alanine. This study provides new information about the catalytic functions of MTPSLs and the functionality of their uncanonical aspartate-rich motifs, and builds a knowledge base for studying the biological importance of MTPSL genes and their terpene products in nonseed plants.

Bryophytes: liverworts, mosses, and hornworts: extraction and isolation procedures.

There are more than 20,000 species of bryophytes in the world. Among them, almost of liverworts (Marchantiophyta) possess beautiful blue, yellow colored or colorless cellular oil bodies from which over several hundred new terpenoids, acetogenins, and aromatic compounds including flavonoids with more than 40 new carbon skeletons have been isolated. Some of the isolated compounds from liverworts show antimicrobial, antifungal, antiviral, allergenic contact dermatitis, cytotoxicity, insect antifeedant and mortality, antioxidant, nitric oxide (NO) production and plant growth inhibitory, neurotrophic and piscicidal activity, tublin polymerization inhibitory, muscle relaxing, and liver X-receptor (LXR)α agonist and (LXR)ß antagonist activities, among others. The bio- and chemical diversity, chemical analysis of bryophytes including extraction, distillation, purification, TLC, GC and GC-MS, and HPLC analysis of oil bodies of liverworts are surveyed.

Phytochemical and biological studies of bryophytes.

The bryophytes contain the Marchantiophyta (liverworts), Bryophyta (mosses) and Anthocerotophyta (hornworts). Of these, the Marchantiophyta have a cellular oil body which produce a number of mono-, sesqui- and di-terpenoids, aromatic compounds like bibenzyl, bis-bibenzyls and acetogenins. Most sesqui- and di-terpenoids obtained from liverworts are enantiomers of those found in higher plants. Many of these compounds display a characteristic odor, and can have interesting biological activities. These include: allergenic contact dermatitis, antimicrobial, antifungal and antiviral, cytotoxic, insecticidal, insect antifeedant, superoxide anion radical release, 5-lipoxygenase, calmodulin, hyaluronidase, cyclooxygenase, DNA polymerase ß, and α-glucosidase and NO production inhibitory, antioxidant, piscicidal, neurotrophic and muscle relaxing activities among others. Each liverwort biosynthesizes unique components, which are valuable for their chemotaxonomic classification. Typical chemical structures and biological activity of the selected liverwort constituents as well as the hemi- and total synthesis of some biologically active compounds are summarized.