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Phytochemistry Sep 2023The roots of the plant Euphorbia ebracteolata Hayata (Yue Xian Da Ji) are commonly used in traditional Chinese medicine to treat multiple diseases such as chronic liver... (Review)
Review
The roots of the plant Euphorbia ebracteolata Hayata (Yue Xian Da Ji) are commonly used in traditional Chinese medicine to treat multiple diseases such as chronic liver diseases, oedema, pulmonary diseases and cancer. It is the main ingredient of the TCM called Langdu which can be prepared also from roots of E. fischeriana Steud. and occasionally from Stellera chamaejasme species. Numerous bioactive natural products have been isolated from E. ebracteolata including a large diversity of diterpenoids with anti-inflammatory and anticancer properties. One little series of compounds has been named yuexiandajisu (A, B, C, D, D, E, F) which comprises two casbane-, one isopimarane-, two abietane-, and two rosane-type diterpenes including a dimeric molecule. The origin, structural diversity and properties of these little-known natural products is discussed here. Several of these compounds have been identified in the roots of other Euphorbia species, notably the potent phytotoxic agent yuexiandajisu C. The abietane diterpenes yuexiandajisu D-E exhibit marked anticancer properties but their mechanism of action remains unresolved. The dimeric compound, renamed yuexiandajisu D, also exhibit anti-proliferative properties against cancer cell lines, unlike the rosane diterpene yuexiandajisu F. The structural or functional analogy with other diterpenoids is discussed.
Topics: Euphorbia; Diterpenes; Plant Roots; Cell Line; Neoplasms; Molecular Structure
PubMed: 37419377
DOI: 10.1016/j.phytochem.2023.113784 -
Applied Microbiology and Biotechnology May 2021Steviol glycosides (SvGls) are plant secondary metabolites belonging to a class of chemical compounds known as diterpenes. SvGls have been discovered only in a few plant... (Review)
Review
Steviol glycosides (SvGls) are plant secondary metabolites belonging to a class of chemical compounds known as diterpenes. SvGls have been discovered only in a few plant species, including in the leaves of Stevia rebaudiana Bertoni. Over the last few decades, SvGls have been extensively researched for their extraordinary sweetness. As a result, the nutritional and pharmacological benefits of these secondary metabolites have grown increasingly apparent. In the near future, SvGls may become a basic, low-calorie, and potent sweetener in the growing natural foods market, and a natural anti-diabetic remedy, a highly competitive alternative to commercially available synthetic drugs. Commercial cultivation of stevia plants and the technologies of SvGls extraction and purification from plant material have already been introduced in many countries. However, new conventional and biotechnological solutions are still being sought to increase the level of SvGls in plants. Since many aspects related to the biochemistry and metabolism of SvGls in vivo, as well as their relationship to the overall physiology of S. rebaudiana are not yet understood, there is also a great need for in-depth scientific research on this topic. Such research may have positive impact on optimization of the profile and SvGls concentration in plants and thus lead to obtaining desired yield. This research summarizes the latest approaches and developments in SvGls production. KEY POINTS: • Steviol glycosides (SvGls) are found in nature in S. rebaudiana plants. • They exhibit nutraceutical properties. • This review provides an insight on different approaches to produce SvGls. • The areas of research that still need to be explored have been identified.
Topics: Diterpenes, Kaurane; Glucosides; Glycosides; Plant Leaves; Stevia; Sweetening Agents
PubMed: 33914136
DOI: 10.1007/s00253-021-11306-x -
Natural Product Reports Apr 2021Covering: 2000 to 2020 Triptolide is a bioactive diterpene triepoxide isolated from Tripterygium wilfordii Hook F, a traditional Chinese medicinal plant whose extracts... (Review)
Review
Covering: 2000 to 2020 Triptolide is a bioactive diterpene triepoxide isolated from Tripterygium wilfordii Hook F, a traditional Chinese medicinal plant whose extracts have been used as anti-inflammatory and immunosuppressive remedies for centuries. Although triptolide and its analogs exhibit potent bioactivities against various cancers, and inflammatory and autoimmune diseases, none of them has been approved to be used in the clinic. This review highlights advances in material sourcing, molecular mechanisms, clinical progress and new drug design strategies for triptolide over the past two decades, along with some prospects for the future course of development of triptolide.
Topics: Animals; Autoimmune Diseases; Diterpenes; Drug Design; Drug Discovery; Epoxy Compounds; Forecasting; Humans; Inflammation; Neoplasms; Phenanthrenes; Tripterygium
PubMed: 33146205
DOI: 10.1039/d0np00054j -
Molecules (Basel, Switzerland) Dec 2020Andrographolide is a labdane diterpene and the main active ingredient isolated from the herb . Andrographolide possesses diverse biological effects including... (Review)
Review
Andrographolide is a labdane diterpene and the main active ingredient isolated from the herb . Andrographolide possesses diverse biological effects including anti-inflammatory, antioxidant, and antineoplastic properties. Clinical studies have demonstrated that andrographolide could be useful in therapy for a wide range of diseases such as osteoarthritis, upper respiratory diseases, and multiple sclerosis. Several targets are described for andrographolide, including the interference of transcription factors NF-κB, AP-1, and HIF-1 and signaling pathways such as PI3K/Akt, MAPK, and JAK/STAT. In addition, an increase in the Nrf2 (nuclear factor erythroid 2-related factor 2) signaling pathway also supports its antioxidant and anti-inflammatory properties. However, this scenario could be more complex since recent evidence suggests that andrographolide targets can modulate glucose metabolism. The metabolic effect of andrographolide might be the key to explaining the diverse therapeutic effects described in preclinical and clinical studies. This review discusses some of the most recent evidence about the anti-inflammatory and metabolic effects of andrographolide.
Topics: Animals; Anti-Inflammatory Agents; Biomarkers; Diterpenes; Humans; Metabolic Networks and Pathways; Plant Extracts; Signal Transduction; Tissue Distribution
PubMed: 33374961
DOI: 10.3390/molecules26010005 -
Journal of Ethnopharmacology Dec 2021Kirenol (Kr) is an ent-pimarane type diterpenoid that has been reported from Siegesbeckiaorientalis, S. pubescens, and S. glabrescens (family Asteraceae). These plants... (Review)
Review
ETHNOPHARMACOLOGICAL RELEVANCE
Kirenol (Kr) is an ent-pimarane type diterpenoid that has been reported from Siegesbeckiaorientalis, S. pubescens, and S. glabrescens (family Asteraceae). These plants have been used traditionally for treating various ailments such as hypertension, neurasthenia, rheumatoid arthritis, asthma, snakebites, allergic disorders, paralysis, soreness, cutaneous disorders, rubella, menstrual disorders, numbness of limbs, dizziness, headache, and malaria. Importantly, in recent years, Kr has received great attention due to its diversified pharmacological activities.
AIM OF THE STUDY
The current work aims to give an overview on the reported pharmacological activities of Kr. Furthermore, the findings regarding its methods for extraction, quantitative analysis, purification, pharmacokinetics, pharmaceutical and food preparations, biosynthesis, identification, semisynthetic analogues, and toxicity are highlighted to provide a reference and perspective for its further investigation.
METHODS
Electronic databases including ScienceDirect, Web of Knowledge, SCOPUS, Wiley Online Library, Taylor & Francis, PubMed, Springer, JACS, and Google Scholar were searched up to the beginning of 2021 to identify the reported studies.
RESULTS
A total of 93 articles have been reviewed. The reported data suggested that Kr possessed various bioactivities including cytotoxic, apoptotic, anticancer, anti-inflammatory, cardio-protective, anti-photo-aging, anti-adipogenic, antimicrobial, muscle function improvement, fracture and wound healing, and anti-arthritic. In addition, studies revealed that the antioxidative and anti-inflammatory activities of Kr may mediate many of its therapeutic potentials as confirmed by several in-vitro and in-vivo studies.
CONCLUSION
This review provides an updated summary of the recent studies on Kr, including methods for extraction, quantitative analysis, purification, pharmacokinetics, pharmaceutical and food preparations, biosynthesis, and identification, as well as semisynthetic analogues, pharmacological activities, and toxicity. Thus, this work can provide useful considerations for planning and design future research on Kr.
Topics: Asteraceae; Diterpenes; Humans; Molecular Structure
PubMed: 34438028
DOI: 10.1016/j.jep.2021.114552 -
Applied Microbiology and Biotechnology Oct 2021Andrographis paniculata (AP) is a medicinal plant that is traditionally used in Indian, Chinese, Malay, Thai, and Oriental system of medicines to treat various... (Review)
Review
Andrographis paniculata (AP) is a medicinal plant that is traditionally used in Indian, Chinese, Malay, Thai, and Oriental system of medicines to treat various disorders. AP consists of andrographolide (AD), 14-deoxy-11,12-didehydroandrographolide (DDAD), and neoandrographolide (NAD) as major diterpene lactones which has extremely bitter properties; therefore, AP is commonly called "King of bitters." AD, DDAD, and NAD are reported to possess therapeutic values such as antioxidant, immunostimulatory, hepatoprotective, anti-cancer, anti-inflammatory, anti-rheumatoidal, anti-malarial, anti-leishmanial, anti-fertility, anti-obesity, antipyretic, and antimicrobial attributes. According to the Indian Pharmacopoeia, the leaves and tender shoots of AP yield up to 1%, 0.16%, and 0.11% of AD, DDAD, and NAD, respectively, on a dry-weight basis. However, variability in the accumulation of AD, DDAD, and NAD in plants has been reported with respect to species, genotype, season, phenological stage, plant part used, and geography of a region of cultivation. Therefore, cell and tissue culture systems especially cell, shoot, and adventitious root cultures are explored as alternatives for constant and higher production of AD, DDAD, and NAD. This review explores the prospects of exploiting the plant cell and tissue culture systems for the controlled production of AD, DDAD, and NAD. Various strategies such as elicitation by using biological and chemical elicitors are explored for the enhancement of accumulation of AD, DDAD, and NAD in cell and organ cultures. KEY POINTS: • This review explores the possibilities of diterpene lactone production from cell and organ cultures. • Various strategies are explored for the enhanced accumulation of AD, DDAD, and NAD in cell and organ cultures. • Prospects of diterpene lactone production are highlighted.
Topics: Andrographis; Diterpenes; Lactones; Organ Culture Techniques; Plant Extracts; Plant Leaves
PubMed: 34568965
DOI: 10.1007/s00253-021-11599-y -
Phytochemistry Apr 2020Among the myriad specialized metabolites that plants employ to mediate interactions with their environment, diterpenoids form a chemically diverse group with vital... (Review)
Review
Among the myriad specialized metabolites that plants employ to mediate interactions with their environment, diterpenoids form a chemically diverse group with vital biological functions. A few broadly abundant diterpenoids serve as core pathway intermediates in plant general metabolism. The majority of plant diterpenoids, however, function in specialized metabolism as often species-specific chemical defenses against herbivores and microbial diseases, in below-ground allelopathic interactions, as well as abiotic stress responses. Dynamic networks of anti-microbial diterpenoids were first demonstrated in rice (Oryza sativa) over four decades ago, and more recently, unique diterpenoid blends with demonstrated antibiotic bioactivities were also discovered in maize (Zea mays). Enabled by advances in -omics and biochemical approaches, species-specific diterpenoid-diversifying enzymes have been identified in these and other Poaceous species, including wheat (Triticum aestivum) and switchgrass (Panicum virgatum), and are discussed in this article with an emphasis on the critical diterpene synthase and cytochrome P450 monooxygenase families and their products. The continued investigation of the biosynthesis, diversity, and function of terpenoid-mediated crop defenses provides foundational knowledge to enable the development of strategies for improving crop resistance traits in the face of impeding pest, pathogen, and climate pressures impacting global agricultural production.
Topics: Crops, Agricultural; Diterpenes; Oryza; Triticum; Zea mays
PubMed: 32036187
DOI: 10.1016/j.phytochem.2020.112289 -
Natural Product Research Oct 2020A new isopimarane-type diterpenoid, crolaevinoid A, along with four known analogues was isolated from the twigs and leaves of . The structures of the isolated compounds...
A new isopimarane-type diterpenoid, crolaevinoid A, along with four known analogues was isolated from the twigs and leaves of . The structures of the isolated compounds were established on the basis of NMR and MS spectroscopic analyses. The isolated compounds were examined the antibacterial activities. Unfortunately, the compounds showed no antibacterial activity against , Methicillin-resistant , , , , and
Topics: Abietanes; Anti-Bacterial Agents; Croton; Diterpenes; Drug Evaluation, Preclinical; Magnetic Resonance Spectroscopy; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Molecular Structure; Plant Leaves; Spectrometry, Mass, Electrospray Ionization
PubMed: 30990080
DOI: 10.1080/14786419.2019.1596096 -
Phytochemistry Jul 2024Cembranoids and labdanes are two important types of diterpenes in tobacco (Nicotiana genus) that are predominantly found in the leaf and flower glandular trichome... (Review)
Review
Cembranoids and labdanes are two important types of diterpenes in tobacco (Nicotiana genus) that are predominantly found in the leaf and flower glandular trichome secretions. This is the first systematic review of the biosynthesis, chemical structures, bioactivities, and utilisation values of cembranoid and labdane diterpenes in tobacco. A total of 131 natural cembranoid diterpenes have been reported in tobacco since 1962; these were summarised and classified according to their chemical structure characteristics as isopropyl cembranoids (1-88), seco-cembranoids (89-103), chain cembranoids (104-123), and polycyclic cembranoids (124-131). Forty natural labdane diterpenes reported since 1961 were also summarised and divided into epoxy side chain labdanes (132-150) and epoxy-free side chain labdanes (151-171). Tobacco cembranoid and labdane diterpenes are both formed via the methylerythritol 4-phosphate pathway and are synthesised from geranylgeranyl diphosphate. Their biosynthetic pathways and the four key enzymes (cembratrienol synthase, cytochrome P450 hydroxylase, copalyl diphosphate synthase, and Z-abienol cyclase) that affect their biosynthesis have been described in detail. A systematic summary of the bioactivity and utilisation values of the cembranoid and labdane diterpenes is also provided. The agricultural bioactivities associated with cembranoid and labdane diterpenes include antimicrobial and insecticidal activities as well as induced resistance, while the medical bioactivities include cytotoxic and neuroprotective activities. Further research into the cembranoid and labdane diterpenes will help to promote their development and utilisation as plant-derived pesticides and medicines.
Topics: Diterpenes; Trichomes; Nicotiana; Molecular Structure; Humans
PubMed: 38697243
DOI: 10.1016/j.phytochem.2024.114117 -
The Journal of Biological Chemistry Sep 2021Glycosyltransferases constitute a large family of enzymes across all domains of life, but knowledge of their biochemical function remains largely incomplete,...
Glycosyltransferases constitute a large family of enzymes across all domains of life, but knowledge of their biochemical function remains largely incomplete, particularly in the context of plant specialized metabolism. The labdane diterpenes represent a large class of phytochemicals with many pharmacological benefits, such as anti-inflammatory, hepatoprotective, and anticarcinogenic. The medicinal plant kalmegh (Andrographis paniculata) produces bioactive labdane diterpenes; notably, the C19-hydroxyl diterpene (andrograpanin) is predominantly found as C19-O-glucoside (neoandrographolide), whereas diterpenes having additional hydroxylation(s) at C3 (14-deoxy-11,12-didehydroandrographolide) or C3 and C14 (andrographolide) are primarily detected as aglycones, signifying scaffold-selective C19-O-glucosylation of diterpenes in planta. Here, we analyzed UDP-glycosyltransferase (UGT) activity and diterpene levels across various developmental stages and tissues and found an apparent correlation of UGT activity with the spatiotemporal accumulation of neoandrographolide, the major diterpene C19-O-glucoside. The biochemical analysis of recombinant UGTs preferentially expressed in neoandrographolide-accumulating tissues identified a previously uncharacterized UGT86 member (ApUGT12/UGT86C11) that catalyzes C19-O-glucosylation of diterpenes with strict scaffold selectivity. ApUGT12 localized to the cytoplasm and catalyzed diterpene C19-O-glucosylation in planta. The substrate selectivity demonstrated by the recombinant ApUGT12 expressed in plant and bacterium hosts was comparable to native UGT activity. Recombinant ApUGT12 showed significantly higher catalytic efficiency using andrograpanin compared with 14-deoxy-11,12-didehydroandrographolide and trivial activity using andrographolide. Moreover, ApUGT12 silencing in plants led to a drastic reduction in neoandrographolide content and increased levels of andrograpanin. These data suggest the involvement of ApUGT12 in scaffold-selective C19-O-glucosylation of labdane diterpenes in plants. This knowledge of UGT86 function might help in developing plant chemotypes and synthesis of pharmacologically relevant diterpenes.
Topics: Andrographis; Biosynthetic Pathways; Diterpenes; Glycosyltransferases; Phylogeny; Plant Proteins; Plants; Protein Transport
PubMed: 34363833
DOI: 10.1016/j.jbc.2021.101045