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The Chinese Journal of Physiology 2022Breast cancer is one of the most common malignant tumors in women worldwide. Surgery, chemotherapy, and targeted drugs are the main methods currently used in clinical... (Review)
Review
Breast cancer is one of the most common malignant tumors in women worldwide. Surgery, chemotherapy, and targeted drugs are the main methods currently used in clinical treatment of breast cancer. Although they can improve the symptoms of patients, they are also accompanied by a large number of side effects. Because of its multiple targets, traditional Chinese medicine can improve the quality of life of breast cancer patients and reduce the side effects associated with chemotherapy, which plays an important role in the treatment of breast cancer. To a certain extent, traditional Chinese medicine has advantages that modern medicine does not have in the treatment of breast cancer. Alkaloids are active ingredients widely distributed in traditional Chinese medicine, which have a variety of pharmacological effects including anti-inflammatory, analgesic, and antitumor effects. The author reviewed the literature on the treatment of breast cancer with alkaloids extracted from traditional Chinese medicine in recent years, and discussed the unique advantages of alkaloids in the treatment of breast cancer.
Topics: Alkaloids; Breast Neoplasms; Drugs, Chinese Herbal; Female; Humans; Medicine, Chinese Traditional; Quality of Life
PubMed: 35229748
DOI: 10.4103/cjp.cjp_89_21 -
Journal of Natural Medicines Sep 2022Ophiorrhiza plants (Family Rubiaceae) are known to produce diverse monoterpenoid indole alkaloids including camptothecin with potent antitumor activity. This review... (Review)
Review
Ophiorrhiza plants (Family Rubiaceae) are known to produce diverse monoterpenoid indole alkaloids including camptothecin with potent antitumor activity. This review contains a summary of recent chemical studies reported over the past 10 years regarding alkaloids (monoterpenoid indole and tetrahydroisoquinoline alkaloids, and cyclopeptide) in Ophiorrhiza plants. In addition, the alkaloid biosynthetic pathways based on their reported structures were proposed.
Topics: Alkaloids; Biosynthetic Pathways; Camptothecin; Rubiaceae
PubMed: 35902551
DOI: 10.1007/s11418-022-01640-3 -
International Journal of Molecular... Mar 2024Trigonelline (TRG) is a natural polar hydrophilic alkaloid that is found in many plants such as green coffee beans and fenugreek seeds. TRG potentially acts on multiple... (Review)
Review
Trigonelline (TRG) is a natural polar hydrophilic alkaloid that is found in many plants such as green coffee beans and fenugreek seeds. TRG potentially acts on multiple molecular targets, including nuclear factor erythroid 2-related factor 2 (Nrf2), peroxisome proliferator-activated receptor γ, glycogen synthase kinase, tyrosinase, nerve growth factor, estrogen receptor, amyloid-β peptide, and several neurotransmitter receptors. In this review, we systematically summarize the pharmacological activities, medicinal properties, and mechanistic actions of TRG as a potential therapeutic agent. Mechanistically, TRG can facilitate the maintenance and restoration of the metabolic homeostasis of glucose and lipids. It can counteract inflammatory constituents at multiple levels by hampering pro-inflammatory factor release, alleviating inflammatory propagation, and attenuating tissue injury. It concurrently modulates oxidative stress by the blockage of the detrimental Nrf2 pathway when autophagy is impaired. Therefore, it exerts diverse therapeutic effects on a variety of pathological conditions associated with chronic metabolic diseases and age-related disorders. It shows multidimensional effects, including neuroprotection from neurodegenerative disorders and diabetic peripheral neuropathy, neuromodulation, mitigation of cardiovascular disorders, skin diseases, diabetic mellitus, liver and kidney injuries, and anti-pathogen and anti-tumor activities. Further validations are required to define its specific targeting molecules, dissect the underlying mechanistic networks, and corroborate its efficacy in clinical trials.
Topics: Humans; NF-E2-Related Factor 2; Alkaloids; Diabetes Mellitus; Oxidative Stress
PubMed: 38542359
DOI: 10.3390/ijms25063385 -
Molecules (Basel, Switzerland) Nov 2017Coniine, a polyketide-derived alkaloid, is poisonous to humans and animals. It is a nicotinic acetylcholine receptor antagonist, which leads to inhibition of the nervous... (Review)
Review
Coniine, a polyketide-derived alkaloid, is poisonous to humans and animals. It is a nicotinic acetylcholine receptor antagonist, which leads to inhibition of the nervous system, eventually causing death by suffocation in mammals. Coniine's most famous victim is Socrates who was sentenced to death by poison chalice containing poison hemlock in 399 BC. In chemistry, coniine holds two historical records: It is the first alkaloid the chemical structure of which was established (in 1881), and that was chemically synthesized (in 1886). In plants, coniine and twelve closely related alkaloids are known from poison hemlock ( L.), and several and species. Recent work confirmed its biosynthetic polyketide origin. Biosynthesis commences by carbon backbone formation from butyryl-CoA and two malonyl-CoA building blocks catalyzed by polyketide synthase. A transamination reaction incorporates nitrogen from l-alanine and non-enzymatic cyclization leads to γ-coniceine, the first hemlock alkaloid in the pathway. Ultimately, reduction of γ-coniceine to coniine is facilitated by NADPH-dependent γ-coniceine reductase. Although coniine is notorious for its toxicity, there is no consensus on its ecological roles, especially in the carnivorous pitcher plants where it occurs. Lately there has been renewed interest in coniine's medical uses particularly for pain relief without an addictive side effect.
Topics: Alkaloids; Animals; Biosynthetic Pathways; Humans; Piperidines; Plants; Structure-Activity Relationship
PubMed: 29135964
DOI: 10.3390/molecules22111962 -
Redirecting tropane alkaloid metabolism reveals pyrrolidine alkaloid diversity in Atropa belladonna.The New Phytologist Mar 2023Plant-specialized metabolism is complex, with frequent examples of highly branched biosynthetic pathways, and shared chemical intermediates. As such, many...
Plant-specialized metabolism is complex, with frequent examples of highly branched biosynthetic pathways, and shared chemical intermediates. As such, many plant-specialized metabolic networks are poorly characterized. The N-methyl Δ -pyrrolinium cation is a simple pyrrolidine alkaloid and precursor of pharmacologically important tropane alkaloids. Silencing of pyrrolidine ketide synthase (AbPyKS) in the roots of Atropa belladonna (Deadly Nightshade) reduces tropane alkaloid abundance and causes high N-methyl Δ -pyrrolinium cation accumulation. The consequences of this metabolic shift on alkaloid metabolism are unknown. In this study, we utilized discovery metabolomics coupled with AbPyKS silencing to reveal major changes in the root alkaloid metabolome of A. belladonna. We discovered and annotated almost 40 pyrrolidine alkaloids that increase when AbPyKS activity is reduced. Suppression of phenyllactate biosynthesis, combined with metabolic engineering in planta, and chemical synthesis indicates several of these pyrrolidines share a core structure formed through the nonenzymatic Mannich-like decarboxylative condensation of the N-methyl Δ -pyrrolinium cation with 2-O-malonylphenyllactate. Decoration of this core scaffold through hydroxylation and glycosylation leads to mono- and dipyrrolidine alkaloid diversity. This study reveals the previously unknown complexity of the A. belladonna root metabolome and creates a foundation for future investigation into the biosynthesis, function, and potential utility of these novel alkaloids.
Topics: Atropa belladonna; Alkaloids; Tropanes; Pyrrolidines
PubMed: 36451537
DOI: 10.1111/nph.18651 -
Acta Pharmacologica Sinica Dec 2002Autoimmune diseases characterized by activation of immune effector cells and damage of target organs are currently treated with a combination of several... (Review)
Review
Autoimmune diseases characterized by activation of immune effector cells and damage of target organs are currently treated with a combination of several disease-modifying antirheumatic drugs (DMARDs) that preserve different immunomodulatory mechanisms. Such a combination treatment strategy not only provides synergistic effects but also reduces side effects from individual drug. Tetrandrine (Tet), purified from a creeper Stephania tetrandra S Moore, is a bis-benzylisoquinoline alkaloid and has been used to treat patients with silicosis, autoimmune disorders, and hypertension in Mainland China for decades. The accumulated studies both in vitro and in vivo reveal that Tet preserves a wide variety of immunosuppressive effects. Importantly, the Tet-mediated immunosuppressive mechanisms are evidently different from some known DMARDs. The synergistic effects have also been demonstrated between Tet and other DMARDs like FK506 and cyclosporin. These results highlight Tet a very potential candidate to be considered as one of DMARDs in the treatment of autoimmune diseases, especially rheumatoid arthritis. This review summarizes evidence-based in vivo and in vitro studies on this potential Chinese immunosuppressive herb.
Topics: Alkaloids; Animals; Apoptosis; Arthritis, Rheumatoid; Autoimmune Diseases; Benzylisoquinolines; Humans; Immunosuppressive Agents; Lymphocyte Activation; T-Lymphocytes
PubMed: 12466046
DOI: No ID Found -
Organic & Biomolecular Chemistry Jul 2016This review highlights noteworthy synthetic and biological aspects of the clavine subfamily of ergot alkaloids. Recent biosynthetic insights have laid the groundwork for... (Review)
Review
This review highlights noteworthy synthetic and biological aspects of the clavine subfamily of ergot alkaloids. Recent biosynthetic insights have laid the groundwork for a better understanding of the diverse biological pathways leading to these indole derivatives. Ergot alkaloids were among the first fungal-derived natural products identified, inspiring pharmaceutical applications in CNS disorders, migraine, infective diseases, and cancer. Pergolide, for example, is a semi-synthetic clavine alkaloid that has been used to treat Parkinson's disease. Synthetic activities have been particularly valuable to facilitate access to rare members of the Clavine family and empower medicinal chemistry research. Improved molecular target identification tools and a better understanding of signaling pathways can now be deployed to further extend the biological and medical utility of Clavine alkaloids.
Topics: Animals; Chemistry Techniques, Synthetic; Ergot Alkaloids; Humans; Stereoisomerism
PubMed: 27215547
DOI: 10.1039/c6ob00878j -
International Journal of Molecular... Nov 2023Palmatine, a natural alkaloid found in various plants, has been reported to have diverse pharmacological and biological effects, including anti-inflammatory,...
Palmatine, a natural alkaloid found in various plants, has been reported to have diverse pharmacological and biological effects, including anti-inflammatory, antioxidant, and cardiovascular effects. However, the role of palmatine in mitophagy, a fundamental process crucial for maintaining mitochondrial function, remains elusive. In this study, we found that palmatine efficiently induces mitophagy in various human cell lines. Palmatine specifically induces mitophagy and subsequently stimulates mitochondrial biogenesis. Palmatine did not interfere with mitochondrial function, similar to CCCP, suggesting that palmatine is not toxic to mitochondria. Importantly, palmatine treatment alleviated mitochondrial dysfunction in PINK1-knockout MEFs. Moreover, the administration of palmatine resulted in significant improvements in cognitive function and restored mitochondrial function in an Alzheimer's disease mouse model. This study identifies palmatine as a novel inducer of selective mitophagy. Our results suggest that palmatine-mediated mitophagy induction could be a potential strategy for Alzheimer's disease treatment and that natural alkaloids are potential sources of mitophagy inducers.
Topics: Mice; Animals; Humans; Mitophagy; Alzheimer Disease; Mitochondria; Alkaloids; Ubiquitin-Protein Ligases
PubMed: 38003731
DOI: 10.3390/ijms242216542 -
Chemical & Pharmaceutical Bulletin May 2018Uncaria rhynchophylla is woody climber plant distributed mainly in China and Japan, the stems and hooks of which can be collected as "Gou-Teng" for the treatment of...
Uncaria rhynchophylla is woody climber plant distributed mainly in China and Japan, the stems and hooks of which can be collected as "Gou-Teng" for the treatment of hyperpyrexia, epilepsy and preeclampsia. Fudan University first manufactured KHR98, the extract of Uncaria rhynchophylla. In order to study the active components and structural information of KHR98, we established a HPLC coupled with quadrupole time-of-flight (Q-TOF)-MS method for rapid analysis of alkaloids. In qualitative analysis, a total of eight compounds, including four known alkaloids and four unknown components, were detected and identified. The fragmentation behaviors, such as the fragment ion information and the fragmentation pathways of the eight components were summarized simultaneously, and the concentration of the above components was determined by HPLC-MS method. The quantitative method was proved to be reproducible, precise and accurate. This study shed light on the standardization and quality control of the KHR98 and provided a foundation for the further research on pharmacology, follow-up clinical research and New Drug Applications.
Topics: Alkaloids; Chromatography, High Pressure Liquid; Molecular Conformation; Tandem Mass Spectrometry; Uncaria
PubMed: 29503397
DOI: 10.1248/cpb.c17-00710 -
Nature Dec 2023Plants synthesize numerous alkaloids that mimic animal neurotransmitters. The diversity of alkaloid structures is achieved through the generation and tailoring of unique...
Plants synthesize numerous alkaloids that mimic animal neurotransmitters. The diversity of alkaloid structures is achieved through the generation and tailoring of unique carbon scaffolds, yet many neuroactive alkaloids belong to a scaffold class for which no biosynthetic route or enzyme catalyst is known. By studying highly coordinated, tissue-specific gene expression in plants that produce neuroactive Lycopodium alkaloids, we identified an unexpected enzyme class for alkaloid biosynthesis: neofunctionalized α-carbonic anhydrases (CAHs). We show that three CAH-like (CAL) proteins are required in the biosynthetic route to a key precursor of the Lycopodium alkaloids by catalysing a stereospecific Mannich-like condensation and subsequent bicyclic scaffold generation. Also, we describe a series of scaffold tailoring steps that generate the optimized acetylcholinesterase inhibition activity of huperzine A. Our findings suggest a broader involvement of CAH-like enzymes in specialized metabolism and demonstrate how successive scaffold tailoring can drive potency against a neurological protein target.
Topics: Animals; Acetylcholinesterase; Alkaloids; Carbonic Anhydrases; Cholinesterase Inhibitors; Gene Expression Regulation, Plant; Models, Neurological; Neurotransmitter Agents; Plants; Sesquiterpenes; Lycopodium
PubMed: 37938780
DOI: 10.1038/s41586-023-06716-y