Demystifying the liverwort Radula marginata, a critical review on its taxonomy, genetics, cannabinoid phytochemistry and pharmacology

Hussain, Tajammul; Espley, Richard V.; Gertsch, Jürg; Whare, Tracey; Stehle, Felix; Kayser, Oliver

doi:10.1007/s11101-019-09638-8

Cited by 21 publications

(28 citation statements)

References 57 publications

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“…(Radulaceae), liverworts that are native to the northern island of New Zealand. These bibenzyl analogs of Δ 9 -THC, (−)-cis-perrottetinene, and (−)-cisperrottetinenic acid are noteworthy for their inverted stereoconfiguration compared to nonbryophyte cannabinoids [16][17][18][19].…”

Section: Illustration Of the Structural Characteristics Of Cannabinoimentioning

confidence: 99%

“…The ecological function of perrottetinenic acid and perrottetinene is unclear, but might resemble those of cannabinoids in C. sativa. An extensive review on liverworts with a focus on Radula marginata taxonomy, genetics, cannabinoid phytochemistry, and pharmacology was recently published by Hussain et al [19]. Mosses (Bryophyta) and hornworts (Anthocerotophyta) do not possess oil bodies [40,48].…”

Section: Trends Trends In In Plant Plant Science Sciencementioning

confidence: 99%

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Phytocannabinoids: Origins and Biosynthesis

Gülck

Møller

2020

Trends in Plant Science

258

240

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Phytocannabinoids are bioactive natural products found in some flowering plants, liverworts, and fungi that can be beneficial for the treatment of human ailments such as pain, anxiety, and cachexia. Targeted biosynthesis of cannabinoids with desirable properties requires identification of the underlying genes and their expression in a suitable heterologous host. We provide an overview of the structural classification of phytocannabinoids based on their decorated resorcinol core and the bioactivities of naturally occurring cannabinoids, and we review current knowledge of phytocannabinoid biosynthesis in Cannabis, Rhododendron, and Radula species. We also highlight the potential in planta roles of phytocannabinoids and the opportunity for synthetic biology approaches based on combinatorial biochemistry and protein engineering to produce cannabinoid derivatives with improved properties. Phytocannabinoids The term phytocannabinoid (see Glossary, also cannabinoid) defines meroterpenoids with a resorcinyl core typically decorated with a para-positioned isoprenyl, alkyl, or aralkyl side chain [1]. The alkyl side chain typically contains an odd number of carbon atoms, where orcinoids contain one carbon, varinoids three, and olivetoids five. Cannabinoids with an even number of carbon atoms in the side chain are known but rare. The term cannabinoid generally refers to molecules with a characteristic chemical structure; however, the term may also refer to pharmacological ligands of human endocannabinoid receptors [2]. In this review we use the chemical definition of cannabinoids. Phytocannabinoids occur in flowering plants, liverworts, and fungi (Figure 1, Key Figure). They were first isolated from Cannabis sativa L. (Cannabaceae), a plant with a long and controversial history of use and abuse [3]. The mammalian brain has receptors that respond to compounds found in C. sativa. Accordingly, these receptors were named cannabinoid receptors (CB x) and are the basis of the endocannabinoid system. Studies in human and animals demonstrated that the endocannabinoid system regulates a broad range of biological functions, including memory, mood, brain reward systems, and drug addiction, as well as metabolic processes such as lipolysis, glucose metabolism, and energy balance [2]. More than 113 different cannabinoids have been isolated from C. sativa and these are classified into distinct types: cannabigerols (CBGs), cannabichromenes (CBCs), cannabidiols (CBDs), (−)-Δ 9-trans-tetrahydrocannabinols (Δ 9-THCs), (−)-Δ 8-trans-tetrahydrocannabinols (Δ 8-THCs), cannabicyclols (CBLs), cannabielsoins (CBEs), cannabinols (CBNs), cannabinodiols (CBNDs), cannabitriols (CBTs), and the miscellaneous cannabinoids (Figure 2) [4]. C. sativa predominantly produces alkyl type cannabinoids that carry a monoterpene isoprenyl moiety (C10) and a pentyl side chain (C5) [1]. The most abundant constituents are trans-Δ 9-THC, CBD, CBC, and CBG, together with their respective acid forms (Δ 9-THCA, CBDA, CBCA, and CBGA) [5]. Cannabinoid biosynthetic pathways ty...

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Section: Illustration Of the Structural Characteristics Of Cannabinoimentioning

confidence: 99%

Section: Trends Trends In In Plant Plant Science Sciencementioning

confidence: 99%

Phytocannabinoids: Origins and Biosynthesis

Gülck

Møller

2020

Trends in Plant Science

258

240

View full text Add to dashboard Cite

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“…Notably, Radula preparations are also popular as "legal-high" due to high cannabinoid content [105]. The cannabinoids, (extracted from C. sativa and other angiosperms), extensively studied for psycho-active efficacy but the natural compound perrottetinene acid and its decarboxylated form perrottetinene, (harvested from bryophyte), have not been studied well and thus their pharmacological applications are not validated scientifically [103].…”

Section: Discussionmentioning

confidence: 99%

“…Δ8-tetrahydrocannabinol and Δ9-tetrahydrocannabinol (isolated from Cannabis sativa L.), both structurally quite similar to the Δ1-tetrahydrocannabinol (isolated from R. perrottetii) are already reported for psychopharmacological activities [102]. No pharmacological study on Δ1-tetrahydrocannabinol has yet been reported but R. perrottetii has been commercially exploited for cosmetics grade cannabinoids [103]. Perrottetinen is another BC reported from R. perrottetii and its structure has been established by spectral analysis [10].…”

Section: Bibenzyl Cannabinoids: Therapeutically Most Studied Derivatimentioning

confidence: 99%

“…These compounds are known to ameliorate the progression of atherosclerosis, myocardial and cerebral ischaemia [106]. Identification and validation of genes [cannabigerolic acid (CBGA), stilbene acid (SA) geranyl diphosphate (GPP)] associated with cannabinoid biosynthesis have already been achieved [103]. Moreover, transcriptome analysis based approach revealed the presence of six transcription factor (TF)family unique in R. marginata.…”

Section: Bibenzyl Cannabinoids: Therapeutically Most Studied Derivatimentioning

confidence: 99%

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

Nandy

Dey

2020

DARU J Pharm Sci

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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 byproducts 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.

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Novel biotechnological substances from bryophytes

Núñez‐Olivera

2021

Natural Bioactive Compounds

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Demystifying the liverwort Radula marginata, a critical review on its taxonomy, genetics, cannabinoid phytochemistry and pharmacology

Cited by 21 publications

References 57 publications

Phytocannabinoids: Origins and Biosynthesis

Phytocannabinoids: Origins and Biosynthesis

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

Novel biotechnological substances from bryophytes

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