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Phytomedicine : International Journal... Nov 2023Hypertension is a serious global public health issue. Blood pressure (BP) is still not effectively controlled in about 20 - 30% of hypertensive patients. Therefore, it...
BACKGROUND
Hypertension is a serious global public health issue. Blood pressure (BP) is still not effectively controlled in about 20 - 30% of hypertensive patients. Therefore, it is imperative to develop new treatments for hypertension. Veratrum alkaloids were once used for the clinical treatment of hypertension, the mechanism of which is still unclear. It was gradually phased out due to adverse reactions.
PURPOSE
This study aimed to investigate the short-term and long-term hypotensive profiles of different components of Veratrum alkaloids in spontaneously hypertensive rats (SHRs) to unveil their mechanisms of action.
RESULTS
Total Veratrum alkaloid (V), component A (A), and veratramine (M) quickly decreased BP within 30 min of treatment, reduced renal and cardiovascular damage, and improved relevant biochemical indicators (nitric oxide [NO], endothelin-1 [ET-1], angiotensin II [Ang II)], noradrenaline [NE], etc) in SHRs to delay stroke occurrence. Thereinto, A exhibited excellent protective effects in cardiovascular disease. The metabolomic profiles of SHRs treated with V, A, and M were significantly different from those of SHRs treated with vehicle. Thirteen metabolites were identified as potential pharmacodynamic biomarkers. Through Kyoto Encyclopedia of Genes and Genomes analysis, V, A, and M-induced hypotension was mainly related to alterations in nicotinate and nicotinamide metabolism, GABAergic synapses, linoleic acid metabolism, ketone body synthesis and degradation, arginine and proline metabolism, and urea cycle, of which nicotinate and nicotinamide metabolism was the key metabolic pathway to relieve hypertension.
CONCLUSION
This work shows that A is an effective and promising antihypertensive agent for hypertension treatment to reduce BP and hypertensive target organ damage, which is mainly mediated through modulating nicotinate and nicotinamide metabolism, RAS, and NO-ET homeostasis.
Topics: Humans; Animals; Rats; Antihypertensive Agents; Niacin; Veratrum Alkaloids; Hypertension; Data Analysis; Niacinamide
PubMed: 37647672
DOI: 10.1016/j.phymed.2023.155033 -
Molecules (Basel, Switzerland) Jul 2023Matrine is a quinoline alkaloid extracted and separated from the dried root, fruit, and other parts of the plant using an organic solvent. Matrine exhibits a variety of... (Review)
Review
Matrine is a quinoline alkaloid extracted and separated from the dried root, fruit, and other parts of the plant using an organic solvent. Matrine exhibits a variety of biological activities and is widely used in pharmacy, agronomy, and other fields. Due to its low bioavailability, poor chemical stability, and toxicity to the central nervous system, a large number of researchers have searched for matrine derivatives with higher biological activity and safety by modifying its structure. In this review article, the research progress of matrine derivatives obtained using two methods (extraction from and structural modifications) from 2018 to 2022 in terms of pharmacological activity, mechanism of action, and structure-activity relationship are presented. The modification of matrine over the past five years has been mainly on the D-ring. Many new matrine alkaloids have been extracted from natural products, some of which have good pharmacological activity, which broadens the strategy for matrine structural modification in the future.
Topics: Matrines; Biological Products; Sophora flavescens; Plant Roots; Fruit; Structure-Activity Relationship; Humans; Animals; Cell Line
PubMed: 37570750
DOI: 10.3390/molecules28155780 -
Naunyn-Schmiedeberg's Archives of... Nov 2023Cepharanthine (CEP) is a bisbenzylisoquinoline alkaloid compound found in plants of the Stephania genus, which has biological functions such as regulating autophagy,... (Review)
Review
Cepharanthine (CEP) is a bisbenzylisoquinoline alkaloid compound found in plants of the Stephania genus, which has biological functions such as regulating autophagy, inhibiting inflammation, oxidative stress, and apoptosis. It is often used for the treatment of inflammatory diseases, viral infections, cancer, and immune disorders and has great clinical translational value. However, there is no detailed research on its specific mechanism and dosage and administration methods, especially clinical research is limited. In recent years, CEP has shown significant effects in the prevention and treatment of COVID-19, suggesting its potential medicinal value waiting to be discovered. In this article, we comprehensively introduce the molecular structure of CEP and its derivatives, describe in detail the pharmacological mechanisms of CEP in various diseases, and discuss how to chemically modify and design CEP to improve its bioavailability. In summary, this work will provide a reference for further research and clinical application of CEP.
Topics: Humans; COVID-19; Benzylisoquinolines; Alkaloids; Apoptosis
PubMed: 37338575
DOI: 10.1007/s00210-023-02537-y -
Fitoterapia Jul 2023Oxymatrine (OMT), was identified as a quinolizidine alkaloid, which was one of the major matrine-type alkaloids extracted from Sophora medicinal plants. Growing studies... (Review)
Review
Oxymatrine (OMT), was identified as a quinolizidine alkaloid, which was one of the major matrine-type alkaloids extracted from Sophora medicinal plants. Growing studies revealed that OMT has a wide range of beneficial pharmacological values, consisting of anticancer, antidiabetic, antivirus, and antiinflammtion, as well as the protective activities to the brain, liver, heart, lung, vascular, gastrointestinal, bone, kidney, and skin organs. Various in vitro and in vivo models of pharmacological actions were recorded in regard to the usage of alkaloidal OMT. Mechanisms underlying anticancer activity of this compound may have been possibly involved anti-proliferation, invasion, migration, angiogenesis, epithelial-mesenchymal transition of cells, autophagy, especially apoptotic cell deaths. OMT could reduce hyperglycemia and hyperlipemia in a high-fat diet and streptozotocin-stimulated diabetic mice by improving insulin secretion and sensitivity. OMT suppressed gastric ulcer via gastric inflammatory and oxidative inhibitions, and pro-apoptotic actions. It turns out that OMT is relatively safe for cell and animal experiments. In this study, we offer a systematic review of natural occurrence, pharmacological potentials, possible mechanisms of action, pharmacokinetics, and bioavailability. Clinical research with OMT is needed to extensively elucidate its health potential benefits.
Topics: Mice; Animals; Diabetes Mellitus, Experimental; Molecular Structure; Alkaloids; Matrines; Quinolizines
PubMed: 37295753
DOI: 10.1016/j.fitote.2023.105565 -
Journal of Chemical Ecology Oct 2023Amphibians are one of the most remarkable sources of unique natural products. Biogenic amines, peptides, bufodienolides, alkaloids, and volatile organic compounds have... (Review)
Review
Amphibians are one of the most remarkable sources of unique natural products. Biogenic amines, peptides, bufodienolides, alkaloids, and volatile organic compounds have been characterized in different species. The superfamily Dendrobatoidea represents one of the most enigmatic cases of study in chemical ecology because their skin secretome is composed by a complex mixture (i.e. cocktail) of highly lethal and noxious unique alkaloid structures. While chemical defences from dendrobatoids (families Dendrobatidae and Aromobatidae) have been investigated employing ecological, behavioral, phylogenetic and evolutionary perspectives, studies about the analytical techniques needed to perform the chemical characterization have been neglected for many years. Therefore, our aim is to summarize the current methods applied for the characterization of chemical profiles in dendrobatoids and to illustrate innovative Eco-metabolomics strategies that could be translated to this study model. This approach could be extended to natural products other than alkaloids and implemented for the chemical analysis of different species of dendrobatoids employing both low- and high-resolution mass spectrometers. Here, we overview important biological features to be considered, procedures that could be applied to perform the chemical characterization, steps and tools to perform an Eco-metabolomic analysis, and a final discussion about future perspectives.
Topics: Humans; Animals; Phylogeny; Anura; Alkaloids; Biological Products
PubMed: 37594619
DOI: 10.1007/s10886-023-01443-0 -
Journal of Ethnopharmacology Mar 2024Piper longum L., a medicinal and food homologous herb, has a traditional history of use in treating gastrointestinal and neurological disorders. Piperine (PIP) the main...
ETHNOPHARMACOLOGICAL RELEVANCE
Piper longum L., a medicinal and food homologous herb, has a traditional history of use in treating gastrointestinal and neurological disorders. Piperine (PIP) the main alkaloid of P. longum, exists neuroprotective effects on various animal models of Parkinson's disease (PD). Nevertheless, the underlying mechanism, particularly the role of PIP in promoting gut-brain autophagy for α-Synuclein (α-Syn) degradation in PD, remains incompletely understood.
AIM OF THE STUDY
To explore the role of PIP in regulating the gut-brain autophagy signaling pathway to reduce α-Syn levels in both the colon and substantia nigra (SN) of PD model rats.
MATERIALS AND METHODS
Behavioral experiments were conducted to assess the impact of PIP on 6-hydroxydopamine (6-OHDA)-induced PD rats. The intestinal microbiome composition and intestinal metabolites were analyzed by metagenomics and GC-MS/MS. The auto-phagosomes were visualized by transmission electron microscopy. Immunohistochemistry, immunofluorescence, and western blotting were performed to assess the levels of tyrosine hydroxylase (TH), α-Syn, LC3II/LC3I, p62, and the PI3K/AKT/mTOR pathway in both the SN and colon of the rats. The pathway-related inhibitor and agonist were used to verify the autophagy mechanism in the SH-SY5Y cells overexpressing A53T mutant α-Syn (A53T-α-Syn).
RESULTS
PIP improved autonomic movement and gastrointestinal dysfunctions, reduced α-Syn aggregation and attenuated the loss of dopaminergic neurons in 6-OHDA-induced PD rats. After oral administration of PIP, the radio of LC3II/LC3I increased and the expression of p62 was degraded, as well as the phosphorylation levels of PI3K, AKT and mTOR decreased in the SN and colon of rats. The effect of PIP on reducing A53T-α-Syn through the activation of the PI3K/AKT/mTOR-mediated autophagy pathway was further confirmed in A53T-α-Syn transgenic SH-SY5Y cells. This effect could be inhibited by the autophagy inhibitor bafilomycin A1 and the PI3K agonist 740 Y-P.
CONCLUSIONS
Our findings suggested that PIP could protect neurons by activating autophagy to degrade α-Syn in the SN and colon, which were related to the suppression of PIP on the activation of PI3K/AKT/mTOR signaling pathway.
Topics: Rats; Humans; Animals; Parkinson Disease; alpha-Synuclein; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinases; Oxidopamine; Tandem Mass Spectrometry; Neuroblastoma; Alkaloids; TOR Serine-Threonine Kinases; Brain; Autophagy; Piperidines; Benzodioxoles; Polyunsaturated Alkamides
PubMed: 38158101
DOI: 10.1016/j.jep.2023.117628 -
Chemical Reviews Aug 2023The tetrahydroisoquinoline (THIQ) natural products constitute one of the largest families of alkaloids and exhibit a wide range of structural diversity and biological... (Review)
Review
The tetrahydroisoquinoline (THIQ) natural products constitute one of the largest families of alkaloids and exhibit a wide range of structural diversity and biological activity. Ranging from simple THIQ natural products to complex trisTHIQ alkaloids such as the ecteinascidins, the chemical syntheses of these alkaloids and their analogs have been thoroughly investigated due to their intricate structural features and functionalities, as well as their high therapeutic potential. This review describes the general structure and biosynthesis of each family of THIQ alkaloids as well as recent advancements of the total synthesis of these natural products from 2002 to 2020. Recent chemical syntheses that have emerged harnessing novel, creative synthetic design, and modern chemical methodology will be highlighted. This review will hopefully serve as a guide for the unique strategies and tools used in the total synthesis of THIQ alkaloids, as well as address the longstanding challenges in their chemical and biosynthesis.
Topics: Alkaloids; Tetrahydroisoquinolines; Biological Products
PubMed: 37429001
DOI: 10.1021/acs.chemrev.3c00054 -
Chemistry & Biodiversity Jun 2024Two new C-diterpenoid alkaloids of the lycoctonine-type (liangshanine A and liangshanine B) and nineteen known compounds (3-21) were isolated from the whole plant of...
Two new C-diterpenoid alkaloids of the lycoctonine-type (liangshanine A and liangshanine B) and nineteen known compounds (3-21) were isolated from the whole plant of Delphinium liangshanense W. T. Wang, and all the compounds were identified by different spectroscopic analyses, such as IR, HR-ESI-MS and NMR. All the compounds were isolated from this plant for the first time and tested for the anti-proliferation effects on MH7 A and SF9 cells to figure their anti-rheumatoid arthritis and anti-insect activity, but none of them showed remarkable activity.
Topics: Delphinium; Diterpenes; Alkaloids; Animals; Cell Proliferation; Cell Line; Spodoptera; Molecular Structure; Humans; Molecular Conformation
PubMed: 38191840
DOI: 10.1002/cbdv.202301923 -
Journal of Ethnopharmacology Dec 2023The dried and mature seeds of Strychnons pierriana A.W.Hill. have been called Strychnine Semen(S. Semen). It have been used in traditional Chinese medicine for nearly... (Review)
Review
ETHNOPHARMACOLOGICAL RELEVANCE
The dried and mature seeds of Strychnons pierriana A.W.Hill. have been called Strychnine Semen(S. Semen). It have been used in traditional Chinese medicine for nearly 400 years. In recent decades, scholars at home and abroad have widely used S. Semen in the treatment of tumor diseases, showing good anti-tumor effects. In this paper, the modern research achievements of S. Semen are reviewed, including traditional uses, phytochemistry, pharmacology, and toxicology.
AIM OF THE STUDY
In recent years, the research on S. Semen has increased gradually, especially the research on its anti-tumor. This paper not only reviewed the traditional uses, chemical constituents and pharmacological activities of S. Semen, but also comprehensively listed the mechanisms of Strychnos in the treatment of different tumors, providing a review for further research and development of Strychnos resources.
MATERIALS AND METHODS
A systematic review of the literature on Fuzi was performed using several resources, namely classic books on Chinese herbal medicine and various scientific databases, such as PubMed, the Web of Science, and the China Knowledge Resource Integrated databases.
RESULTS
The main constituents of S. Semen include alkaloids, terpenoids, steroids, and their glycosides. Modern studies have proved that S. Semen has a wide range of pharmacological effects, including anti-inflammatory and analgesic, anti-thrombotic, myocardial cell protection, immune regulation, nerve excitation, and anti-tumor effects. Among them, the anti-tumor effect has been the focus of research in recent years. S. Semen have a certain therapeutic effect on many kinds of tumors, such as liver cancer, colon cancer, and stomach cancer in the digestive system, breast, cervical, and ovarian cancer in the reproductive system, myeloma and leukemia in the blood system, and those in the nervous system and the immune system.
CONCLUSION
Strychnine has an inhibitory effect on a variety of tumors. However, modern studies of strychnine are incomplete, and more in-depth studies are needed on its stronger bioactive constituents and potential pharmacological effects. The antitumor effect of Strychnine is worth further exploration.
Topics: Strychnine; Seeds; Drugs, Chinese Herbal; Alkaloids; Medicine, Chinese Traditional; Analgesics; Phytochemicals; Ethnopharmacology; Plant Extracts
PubMed: 37348797
DOI: 10.1016/j.jep.2023.116748 -
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