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Molecules (Basel, Switzerland) Nov 2023Alkaloids represent a large family of natural products with diverse structures and bioactivities. These compounds and their derivatives have been widely used in clinics... (Review)
Review
Alkaloids represent a large family of natural products with diverse structures and bioactivities. These compounds and their derivatives have been widely used in clinics to treat various diseases. The endophytic is a filamentous fungus renowned for its extraordinary ability to produce active natural products of high therapeutic value and economic importance. This review is the first to focus on -derived alkaloids. Through an extensive literature review and data analysis, 263 alkaloids are categorized according to their structural features into those containing cytochalasans, diketopiperazine alkaloids, quinazoline alkaloids, quinoline alkaloids, indole alkaloids, pyrrolidine alkaloids, and others. These metabolites exhibited diverse biological activities, such as antibacterial activity, cytotoxicity, anti-inflammatory activity, and α-glucosidase, ACE, and DPPH inhibitory activities. The bioactivity, structural diversity, and occurrence of these alkaloids are reviewed in detail.
Topics: Alkaloids; Aspergillus; Fungi; Indole Alkaloids; Plants; Biological Products
PubMed: 38067519
DOI: 10.3390/molecules28237789 -
Biomedicine & Pharmacotherapy =... Feb 2024Cytisine is a naturally occurring bioactive compound, an alkaloid mainly isolated from legume plants. In recent years, various biological activities of cytisine have... (Review)
Review
Cytisine is a naturally occurring bioactive compound, an alkaloid mainly isolated from legume plants. In recent years, various biological activities of cytisine have been explored, showing certain effects in smoking cessation, reducing drinking behavior, anti-tumor, cardiovascular protection, blood sugar regulation, neuroprotection, osteoporosis prevention and treatment, etc. At the same time, cytisine has the advantages of high efficiency, safety, and low cost, has broad development prospects, and is a drug of great application value. However, a summary of cytisine's biological activities is currently lacking. Therefore, this paper summarizes the pharmacological action, mechanism, and pharmacokinetics of cytisine by referring to numerous databases, and analyzes the new and core targets of cytisine with the help of computer simulation technology, to provide reference for doctors.
Topics: Computer Simulation; Alkaloids; Smoking Cessation; Azocines; Quinolizines; Quinolizidine Alkaloids
PubMed: 38271893
DOI: 10.1016/j.biopha.2024.116210 -
Chemico-biological Interactions Sep 2023Gastric cancer (GC) is a highly aggressive and deadly disease worldwide. Given the limitations of current treatments, it is crucial to discover more effective antitumor...
Gastric cancer (GC) is a highly aggressive and deadly disease worldwide. Given the limitations of current treatments, it is crucial to discover more effective antitumor drugs. Here, we demonstrated that arthpyrone M (Art-M), a novel 4-hydroxy-2-pyridone alkaloid derived from the marine fungus Arthrinium arundinis, inhibited the proliferation, invasion and migration of GC both in vivo and in vitro. The underlying mechanism of Art-M in GC cells was explored by RNA-sequencing analysis, qRT-PCR and immunoblotting, which demonstrated that Art-M significantly suppressed the mTORC1 pathway by decreasing phosphorylated mTOR and p70S6K. Moreover, Art-M feedback increased the activities of AKT and ERK. Co-immunoprecipitation and immunoblotting analysis revealed that Art-M induced dissociation of Raptor from mTOR and promoted Raptor degradation, leading to the inhibition of mTORC1 activity. Art-M was identified as a novel and potent mTORC1 antagonist. Furthermore, Art-M enhanced GC cell sensitivity to apatinib, and the combination of Art-M and apatinib showed better efficacy in the treatment of GC. Taken together, these results demonstrate that Art-M is a promising candidate drug for the treatment of GC by suppressing the mTORC1 pathway.
Topics: Humans; Mechanistic Target of Rapamycin Complex 1; Stomach Neoplasms; Cell Line, Tumor; Signal Transduction; TOR Serine-Threonine Kinases; Antineoplastic Agents; Cell Proliferation; Alkaloids; Fungi; Proto-Oncogene Proteins c-akt
PubMed: 37394161
DOI: 10.1016/j.cbi.2023.110618 -
Phytochemistry Jul 2023Eight unprecedented monoterpenoid indole alkaloid (MIA) adducts and dimers, melofusinines A-H (1-8), and three undescribed melodinus-type MIA monomers, melofusinines I-K...
Eight unprecedented monoterpenoid indole alkaloid (MIA) adducts and dimers, melofusinines A-H (1-8), and three undescribed melodinus-type MIA monomers, melofusinines I-K (9-11), together with six putative biogenetic precursors were isolated from the twigs and leaves of Melodinus fusiformis Champ. ex Benth. Compounds 1 and 2 are unusual hybrid indole alkaloids incorporating an aspidospermatan-type MIA with a monoterpenoid alkaloid unit via C-C coupling. Compounds 3-8 feature the first MIA dimers constructed through an aspidospermatan-type monomer and a rearranged melodinus-type monomer with two different types of couplings. Their structures were elucidated by spectroscopic data, single crystal X-ray diffraction, and calculated electric circular dichroism spectra analysis. In addition, dimers 5 and 8 showed significant neuroprotection effects on MPP -injured primary cortical neurons.
Topics: Monoterpenes; Indole Alkaloids; Antineoplastic Agents; Plant Leaves; Apocynaceae; Secologanin Tryptamine Alkaloids; Molecular Structure
PubMed: 37059289
DOI: 10.1016/j.phytochem.2023.113678 -
International Journal of Molecular... Nov 2023Heterocyclic organic compounds named pyrrolizidine alkaloids (PAs) belong to a group of alkaloids and are synthesized by either plants or microorganisms. Therefore, they... (Review)
Review
Heterocyclic organic compounds named pyrrolizidine alkaloids (PAs) belong to a group of alkaloids and are synthesized by either plants or microorganisms. Therefore, they are naturally occurring secondary metabolites. They are found in species applied in the pharmaceutical and food industries, thus a thorough knowledge of their pharmacological properties and toxicology to humans is of great importance for their further safe employment. This review is original because it synthesizes knowledge of plant and microbial PAs, which is unusual in the scientific literature. We have focused on the family, which is unique due to the exceptional richness and diversity of its PAs in plant species. We have also presented the microbial sources of PAs, both from fungi and bacteria. The structure and metabolism of PAs have been discussed. Our main aim was to summarize the effects of PAs on humans, including both negative, toxic ones, mainly concerning hepatotoxicity and carcinogenicity, as well as potentially positive ones for pharmacological and medical applications. We have collected the results of studies on the anticancer activity of PAs from plant and microbial sources (mainly strains) and on the antimicrobial activity of PAs on different strains of microorganisms (bacteria and fungi). Finally, we have suggested potential applications and future perspectives.
Topics: Humans; Pharmaceutical Preparations; Plants; Pyrrolizidine Alkaloids
PubMed: 38069294
DOI: 10.3390/ijms242316972 -
Current Medicinal Chemistry 2024Berberine is the main active compound of different herbs and is defined as an isoquinoline quaternary botanical alkaloid found in barks and roots of numerous plants. It... (Review)
Review
BACKGROUND
Berberine is the main active compound of different herbs and is defined as an isoquinoline quaternary botanical alkaloid found in barks and roots of numerous plants. It exhibits a wide range of pharmacological effects, such as anti-obesity and antidiabetic effects. Berberine has antibacterial activity against a variety of microbiota, including many bacterial species, protozoa, plasmodia, fungi, and trypanosomes.
OBJECTIVE
This review describes the role of berberine and its metabolic effects. It also discusses how it plays a role in glucose metabolism, fat metabolism, weight loss, how it modulates the gut microbiota, and what are its antimicrobial properties along with its potential side effects with maximal tolerable dosage.
METHODS
Representative studies were considered and analyzed from different scientific databases, including PubMed and Web of Science, for the years 1982-2022.
RESULTS
Literature analysis shows that berberine affects many biochemical and pharmacological pathways that theoretically yield a positive effect on health and disease. Berberine exhibits neuroprotective properties in various neurodegenerative and neuropsychological ailments. Despite its low bioavailability after oral administration, berberine is a promising tool for several disorders. A possible hypothesis would be the modulation of the gut microbiome. While the evidence concerning the aging process in humans is more limited, preliminary studies have shown positive effects in several models.
CONCLUSION
Berberine could serve as a potential candidate for the treatment of several diseases. Previous literature has provided a basis for scientists to establish clinical trials in humans. However, for obesity, the evidence appears to be sufficient for hands-on use.
Topics: Humans; Berberine; Alkaloids; Aging; Antineoplastic Agents; Hypoglycemic Agents
PubMed: 36748808
DOI: 10.2174/0929867330666230207112539 -
Applied Microbiology and Biotechnology Jul 2023In the quest for novel medications, researchers have kept on studying nature to unearth beneficial plant species with medicinal qualities that may cure various diseases... (Review)
Review
In the quest for novel medications, researchers have kept on studying nature to unearth beneficial plant species with medicinal qualities that may cure various diseases and disorders. These medicinal plants produce different bioactive secondary metabolites with immense therapeutic importance. One such valuable secondary metabolite, reserpine (CHNO), has been used for centuries to cure various ailments like hypertension, cardiovascular diseases, neurological diseases, breast cancer, and human promyelocytic leukaemia. Rauvolfia spp. (family Apocynaceae) is an essential reservoir of this reserpine. The current review thoroughly covers different non-conventional or in vitro-mediated biotechnological methods adopted for pilot-scale as well as large-scale production of reserpine from Rauvolfia spp., including techniques like multiple shoot culture, callus culture, cell suspension culture, precursor feeding, elicitation, synthetic seed production, scale-up via bioreactor, and hairy root culture. This review further analyses the unexplored and cutting-edge biotechnological tools and techniques to alleviate reserpine production. KEY POINTS: • Reserpine, a vital indole alkaloid from Rauvolfia spp., has been used for centuries to cure several ailments. • Overview of biosynthetic pathways and biotechnological applications for enhanced production of reserpine. • Probes the research gaps and proposes novel alternative techniques to meet the pharmaceutical industry's need for reserpine while reducing the over-exploitation of natural resources.
Topics: Humans; Reserpine; Biotechnology; Rauwolfia; Bioreactors; Plants, Medicinal; Alkaloids; Plant Roots
PubMed: 37212883
DOI: 10.1007/s00253-023-12570-9 -
BMC Plant Biology Jun 2024Murraya tetramera Huang is a traditional Chinese woody medicine. Its leaves contain flavonoids, alkaloids, and other active compounds, which have anti-inflammatory and...
Integrated metabolomic and transcriptomic analysis reveals the regulatory mechanisms of flavonoid and alkaloid biosynthesis in the new and old leaves of Murraya tetramera Huang.
BACKGROUND
Murraya tetramera Huang is a traditional Chinese woody medicine. Its leaves contain flavonoids, alkaloids, and other active compounds, which have anti-inflammatory and analgesic effects, as well as hypoglycemic and lipid-lowering effects, and anti-tumor effects. There are significant differences in the content of flavonoids and alkaloids in leaves during different growth cycles, but the synthesis mechanism is still unclear.
RESULTS
In April 2021, new leaves (one month old) and old leaves (one and a half years old) of M. tetramera were used as experimental materials to systematically analyze the changes in differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) with transcriptomics and metabolomics technology. This was done to identify the signaling pathways of flavonoid and alkaloid synthesis. The results showed that the contents of total alkaloids and flavonoids in old leaves were significantly higher than those in new leaves. Thirteen flavonoid compounds, three isoflavone compounds, and nineteen alkaloid compounds were identified, and 125 and 48 DEGs related to flavonoid and alkaloid synthesis were found, respectively. By constructing the KEGG (Kyoto Encyclopedia of Genes and Genomes) network of DEGs and DAMs, it was shown that the molecular mechanism of flavonoid biosynthesis in M. tetramera mainly focuses on the "flavonoid biosynthetic pathway" and the "flavonoid and flavonol biosynthetic pathway". Among them, p-Coumaryl alcohol, Sinapyl alcohol, Phloretin, and Isoquercitrin were significantly accumulated in old leaves, the up-regulated expression of CCR (cinnamoyl-CoA reductase) might promote the accumulation of p-Coumaryl alcohol, upregulation of F5H (ferulate-5-hydroxylase) might promote Sinapyl alcohol accumulation. Alkaloids, including indole alkaloids, pyridine alkaloids, imidazole alkaloids, and quinoline alkaloids, were significantly accumulated in old leaves, and a total of 29 genes were associated with these substances.
CONCLUSIONS
These data are helpful to better understand the biosynthesis of flavonoids and alkaloids in M. tetramera and provide a scientific basis for the development of medicinal components in M. tetramera.
Topics: Flavonoids; Plant Leaves; Alkaloids; Gene Expression Profiling; Murraya; Metabolomics; Transcriptome; Gene Expression Regulation, Plant
PubMed: 38840069
DOI: 10.1186/s12870-024-05066-9 -
Chemistry & Biodiversity Apr 2024One new fawcettimine-type Lycopodium alkaloid, hupertimine F (1), together with five known (2-6) Lycopodium alkaloids were isolated from Huperzia goebelii. The structure...
One new fawcettimine-type Lycopodium alkaloid, hupertimine F (1), together with five known (2-6) Lycopodium alkaloids were isolated from Huperzia goebelii. The structure of 1 was elucidated by 1D and 2D NMR spectra, HRESIMS, and X-ray diffraction. Structurally, 1 represents the fourth example of Lycopodium alkaloids characterized by a 5/5/5/5/6 pentacyclic ring system with a 1-aza-7-oxabicyclo[2.2.1]heptane moiety. These known compounds 2, 3, 5, and 6 were isolated from H. goebelii for the first time. Compounds 1-6 were evaluated for acetylcholinesterase, butyrylcholinesterase and monoamine oxidase B inhibitory activities in vitro.
Topics: Huperzia; Lycopodium; Butyrylcholinesterase; Acetylcholinesterase; Molecular Structure; Cholinesterase Inhibitors; Alkaloids
PubMed: 38419385
DOI: 10.1002/cbdv.202400209 -
Genes & Genomics Mar 2024Secondary metabolites such as benzylisoquinoline alkaloids (BIA) have attracted considerable attention because of their pharmacological properties and potential...
BACKGROUND
Secondary metabolites such as benzylisoquinoline alkaloids (BIA) have attracted considerable attention because of their pharmacological properties and potential therapeutic applications. Methyltransferases (MTs) can add methyl groups to alkaloid molecules, altering their physicochemical properties and bioactivity, stability, solubility, and recognition by other cellular components. Five types of O-methyltransferases and two types of N-methyltransferases are involved in BIA biosynthesis.
OBJECTIVE
Since MTs may be the source for the discovery and development of novel biomedical, agricultural, and industrial compounds, we performed extensive molecular and phylogenetic analyses of O- and N-methyltransferases in BIA-producing plants.
METHODS
MTs involved in BIA biosynthesis were isolated from transcriptomes of Berberis koreana and Caulophyllum robustum. We also mined the methyltransferases of Coptis japonica, Papaver somniferum, and Nelumbo nucifera from the National Center for Biotechnology Information protein database. Then, we analyzed the functional motifs and phylogenetic analysis.
RESULT
We mined 42 O-methyltransferases and 8 N-methyltransferases from the five BIA-producing plants. Functional motifs for S-adenosyl-L-methionine-dependent methyltransferases were retained in most methyltransferases, except for the three O-methyltransferases from N. nucifera. Phylogenetic analysis revealed that the methyltransferases were grouped into four clades, I, II, III and IV. The clustering patterns in the phylogenetic analysis suggested a monophyletic origin of methyltransferases and gene duplication within species. The coexistence of different O-methyltransferases in the deep branch subclade might support some cases of substrate promiscuity.
CONCLUSIONS
Methyltransferases may be a source for the discovery and development of novel biomedical, agricultural, and industrial compounds. Our results contribute to further understanding of their structure and reaction mechanisms, which will require future functional studies.
Topics: Benzylisoquinolines; Methyltransferases; Phylogeny; Alkaloids; Plants
PubMed: 38095842
DOI: 10.1007/s13258-023-01477-4