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Phytomedicine : International Journal... Jun 2024Atherosclerosis (AS) is an important cause of cardiovascular disease, posing a substantial health risk. Recognized as a chronic inflammatory disorder, AS hinges on the...
BACKGROUND
Atherosclerosis (AS) is an important cause of cardiovascular disease, posing a substantial health risk. Recognized as a chronic inflammatory disorder, AS hinges on the pivotal involvement of macrophages in arterial inflammation, participating in its formation and progression. Sangzhi alkaloid (SZ-A) is a novel natural alkaloid extracted from the mulberry branches, has extensive pharmacological effects and stable pharmacokinetic characteristics. However, the effects and mechanisms of SZ-A on AS remain unclear.
PURPOSE
To explore the effect and underlying mechanisms of SZ-A on inflammation mediated by macrophages and its role in AS development.
METHODS
Atherosclerosis was induced in vivo in apolipoprotein E-deficient mice through a high-fat and high-choline diet. We utilized macrophages and vascular endothelial cells to investigate the effects of SZ-A on macrophage polarization and its anti-inflammatory properties on endothelial cells in vitro. The transcriptomic analyses were used to investigate the major molecule that mediates cell-cell interactions and the antiatherogenic mechanisms of SZ-A based on AS, subsequently validated in vivo and in vitro.
RESULTS
SZ-A demonstrated a significant inhibition in vascular inflammation and alleviation of AS severity by mitigating macrophage infiltration and modulating M1/M2 macrophage polarization in vitro and in vivo. Moreover, SZ-A effectively reduced the release of the proinflammatory mediator C-X-C motif chemokine ligand (CXCL)-10, predominantly secreted by M1 macrophages. This reduction in CXCL-10 contributed to improved endothelial cell function, reduced recruitment of additional macrophages, and inhibited the inflammatory amplification effect. This ultimately led to the suppression of atherogenesis.
CONCLUSION
SZ-A exhibited potent anti-inflammatory effects by inhibiting macrophage-mediated inflammation, providing a new therapeutic avenue against AS. This is the first study demonstrating the efficacy of SZ-A in alleviating AS severity and offers novel insights into its anti-inflammatory mechanism.
Topics: Animals; Atherosclerosis; Macrophages; Mice; Alkaloids; Morus; Male; Mice, Inbred C57BL; Anti-Inflammatory Agents; Diet, High-Fat; Humans; RAW 264.7 Cells; Mice, Knockout, ApoE; Endothelial Cells; Apolipoproteins E
PubMed: 38564921
DOI: 10.1016/j.phymed.2024.155526 -
Current Opinion in Plant Biology Aug 2023Plants synthesize tens of thousands of bioactive nitrogen-containing compounds called alkaloids, including some clinically important drugs in modern medicine. The... (Review)
Review
Plants synthesize tens of thousands of bioactive nitrogen-containing compounds called alkaloids, including some clinically important drugs in modern medicine. The discovery of new alkaloid structures and their metabolism in plants have provided ways to access these rich sources of bioactivities including new-to-nature compounds relevant to therapeutic and industrial applications. This review discusses recent advances in alkaloid biosynthesis discovery, including complete pathway elucidations. Additionally, the latest developments in the production of new and established plant alkaloids based on either biosynthesis or semisynthesis are discussed.
Topics: Biosynthetic Pathways; Drug Repositioning; Alkaloids; Plants
PubMed: 37182414
DOI: 10.1016/j.pbi.2023.102379 -
The Journal of Organic Chemistry Jul 2023Herein, we report the total synthesis of nagelamide W (), a pyrrole imidazole alkaloid of the nagelamide family isolated in 2013. The key approach in this work involves...
Herein, we report the total synthesis of nagelamide W (), a pyrrole imidazole alkaloid of the nagelamide family isolated in 2013. The key approach in this work involves the construction of the 2-aminoimidazoline core of nagelamide W from alkene 6 through a cyanamide bromide intermediate. The synthesis of nagelamide W was accomplished with an overall yield of 6.0%.
Topics: Molecular Structure; Pyrroles; Alkaloids
PubMed: 37314002
DOI: 10.1021/acs.joc.3c00867 -
Neurochemical Research Nov 2023Boldine is an alkaloid obtained from the medicinal herb Peumus boldus (Mol.) (Chilean boldo tree; boldo) and belongs to the family Monimiaceae. It exhibits a wide range... (Review)
Review
Boldine is an alkaloid obtained from the medicinal herb Peumus boldus (Mol.) (Chilean boldo tree; boldo) and belongs to the family Monimiaceae. It exhibits a wide range of pharmacological effects such as antioxidant, anticancer, hepatoprotective, neuroprotective, and anti-diabetic properties. There is a dearth of information regarding its pharmacokinetics and toxicity in addition to its potential pharmacological activity. Boldine belongs to the aporphine alkaloid class and possesses lipophilic properties which enable its efficient absorption and distribution throughout the body, including the central nervous system. It exhibits potent free radical scavenging activity, thereby reducing oxidative stress and preventing neuronal damage. Through a variety of neuroprotective mechanisms, including suppression of AChE and BuChE activity, blocking of connexin-43 hemichannels, pannexin 1 channel, reduction of NF-κβ mediated interleukin release, and glutamate excitotoxicity which successfully reduces neuronal damage. These results point to its probable application in reducing neuroinflammation and oxidative stress in epilepsy, Alzheimer's disease (AD), and Parkinson's disease (PD). Moreover, its effects on serotonergic, dopaminergic, opioid, and cholinergic receptors were further investigated in order to determine its applicability for neurobehavioral dysfunctions. The article investigates the pharmacokinetics of boldine and reveals that it has a low oral bioavailability and a short half-life, requiring regular dosage to maintain therapeutic levels. The review studies boldine's potential therapeutic uses and mode of action while summarizing its neuroprotective benefits. Given the favorable results for boldine as a potential neurotherapeutic drug in laboratory animals, more research is required. However, in order to optimise its therapeutic potential, it must be more bioavailable with fewer detrimental side effects.
Topics: Animals; Kinetics; Antioxidants; Aporphines; Nervous System Diseases; Peumus
PubMed: 37462836
DOI: 10.1007/s11064-023-03992-y -
Journal of Ethnopharmacology Jun 2024Members of the plant family Amaryllidaceae are widely recorded in traditional systems of medicine. Their usage for inflammatory conditions is most prominent, with... (Review)
Review
ETHNOPHARMACOLOGICAL RELEVANCE
Members of the plant family Amaryllidaceae are widely recorded in traditional systems of medicine. Their usage for inflammatory conditions is most prominent, with substantive evidence emerging from several locations around the world.
AIM OF THE STUDY
This survey was undertaken to identify such plant taxa, highlight the countries from which they originate and afford details of the ailments against which they are utilized. The undertaking also sought to establish the in vitro and in vivo activities of Amaryllidaceae plant extracts in inflammation-based assays. Furthermore, it set out to unravel the molecular mechanisms used to explain these effects.
MATERIALS AND METHODS
Over six-hundred articles were identified in searches carried out on SciFinder, Scopus, ScienceDirect, PubMed and Google Scholar. These were condensed to around 170 that formulated the basis of the text. The keyword engaged was 'Amaryllidaceae' in conjunction with 'inflammation' or 'anti-inflammatory', as well as the names of individual genera combined with the latter two.
RESULTS
Fifty-one species from thirty-five countries were identified for their uses against inflammation. Twenty-four of such conditions were discernible, of which their applicability in wound healing and pain management was most conspicuous. The utilization of all plant parts was apparent, preparations of which were used primarily via topical application. Extracts of seventy-three species (from twenty-three genera) were examined in nearly thirty inflammation-based assays where their activities in vitro and in vivo were shown to be significant. They were effective in vivo against pain and swelling as well as wound healing, without detriment towards test subjects. The in vitro studies were carried out mainly in mononuclear cells such as macrophages, leukocytes, lymphocytes and neutrophils against which their cytotoxic effects were seen to be minimal. The modes of operation were shown to involve modulation of both pro-inflammatory (such as NF-κB, TNF-α, IL-6, IFN-γ, COX and NO) and anti-inflammatory (such as IL-10) factors.
CONCLUSIONS
The Amaryllidaceae is showcased as a platform highly conducive towards studies in the inflammation arena. Potent activities in instances were observed via in vitro and in vivo models of study, bolstered by the significant amounts of information emerging from traditional forms of medicine. It is conceivable that the family may yield future anti-inflammatory chemotherapeutics, particularly those related to its alkaloid principles.
Topics: Humans; Amaryllidaceae; Plant Extracts; Alkaloids; Anti-Inflammatory Agents; Inflammation
PubMed: 38387683
DOI: 10.1016/j.jep.2024.117943 -
Future Microbiology Nov 2023To review , , and studies examining the antibacterial and immunomodulatory properties of piperine (PPN). This systematic review followed PRISMA guidelines, and five... (Review)
Review
To review , , and studies examining the antibacterial and immunomodulatory properties of piperine (PPN). This systematic review followed PRISMA guidelines, and five databases were searched. A total of 40 articles were included in this study. Six aspects of PPN activity were identified, including antibacterial spectrum, association with antibiotics, efflux pump inhibition, biofilm effects, protein target binding, and modulation of immune functions/virulence factors. Most studies focused on spp. and . Cell lineages and models were employed to study PPN antibacterial effects. We highlight PPN as a potential adjuvant in the treatment of bacterial infections. PPN possesses several antibacterial properties that need further exploration to determine the mechanisms behind its pharmacological activity.
Topics: Anti-Bacterial Agents; Alkaloids; Benzodioxoles; Piperidines; Microbial Sensitivity Tests
PubMed: 37882762
DOI: 10.2217/fmb-2023-0101 -
Frontiers in Endocrinology 2023Colorectal cancer (CRC) is one of the most deaths causing diseases worldwide. Several risk factors including hormones like insulin and insulin like growth factors (e.g.,... (Review)
Review
Colorectal cancer (CRC) is one of the most deaths causing diseases worldwide. Several risk factors including hormones like insulin and insulin like growth factors (e.g., IGF-1) have been considered responsible for growth and progression of colon cancer. Though there is a huge advancement in the available screening as well as treatment techniques for CRC. There is no significant decrease in the mortality of cancer patients. Moreover, the current treatment approaches for CRC are associated with serious challenges like drug resistance and cancer re-growth. Given the severity of the disease, there is an urgent need for novel therapeutic agents with ideal characteristics. Several pieces of evidence suggested that natural products, specifically medicinal plants, and derived phytochemicals may serve as potential sources for novel drug discovery for various diseases including cancer. On the other hand, cancer cells like colon cancer require a high basal level of reactive oxygen species (ROS) to maintain its own cellular functions. However, excess production of intracellular ROS leads to cancer cell death disturbing cellular redox homeostasis. Therefore, medicinal plants and derived phytocompounds that can enhance the intracellular ROS and induce apoptotic cell death in cancer cells modulating various molecular targets including IGF-1 could be potential therapeutic agents. Alkaloids form a major class of such phytoconstituents that can play a key role in cancer prevention. Moreover, several preclinical and clinical studies have also evidenced that these compounds show potent anti-colon cancer effects and exhibit negligible toxicity towards the normal cells. Hence, the present evidence-based study aimed to provide an update on various alkaloids that have been reported to induce ROS-mediated apoptosis in colon cancer cells targeting various cellular components including hormones and growth factors, which play a role in metastasis, angiogenesis, proliferation, and invasion. This study also provides an individual account on each such alkaloid that underwent clinical trials either alone or in combination with other clinical drugs. In addition, various classes of phytochemicals that induce ROS-mediated cell death in different kinds of cancers including colon cancer are discussed.
Topics: Humans; Reactive Oxygen Species; Insulin-Like Growth Factor I; Colonic Neoplasms; Alkaloids; Hormones
PubMed: 37560308
DOI: 10.3389/fendo.2023.1201198 -
Molecules (Basel, Switzerland) Sep 2023Benzophenanthridine alkaloids are a class of isoquinoline compounds, which are widely found in the plants of , , and . Biological activities and clinical studies have... (Review)
Review
Benzophenanthridine alkaloids are a class of isoquinoline compounds, which are widely found in the plants of , , and . Biological activities and clinical studies have shown that benzophenanthridine alkaloids have inhibitory effects on many cancers. Considering that the anticancer activities and mechanisms of many natural benzophenanthridine alkaloids have been discovered in succession, the purpose of this paper is to review the anticancer effects of benzophenanthridine alkaloids and explore the application potential of these natural products in the development of antitumor drugs. A literature survey was carried out using Scopus, Pubmed, Reaxys, and Google Scholar databases. This review summarizes and analyzes the current status of research on the antitumor activity and antitumor mechanism of natural products of benzophenanthridine from different sources. The research progress of the antitumor activity of natural products of benzophenanthridine from 1983 to 2023 was reviewed. The antitumor activities of 90 natural products of benzophenanthridine and their related analogues were summarized, and the results directly or indirectly showed that natural products of benzophenanthridine had the effects of antidrug-resistant tumor cell lines, antitumor stem cells, and inducing ferroptosis. In conclusion, benzophenanthridine alkaloids have inhibitory effects on a variety of cancers and have the potential to counteract tumor resistance, and they have great application potential in the development of antitumor drugs.
Topics: Benzophenanthridines; Alkaloids; Biological Products; Cell Line, Tumor; Corydalis
PubMed: 37764364
DOI: 10.3390/molecules28186588 -
Naunyn-Schmiedeberg's Archives of... May 2024Piperlongumine (PL), an alkaloid found primarily in the fruits and roots of the plant Piper longum L. (Piperaceae), is a natural compound that exhibits potent activity... (Review)
Review
Piperlongumine (PL), an alkaloid found primarily in the fruits and roots of the plant Piper longum L. (Piperaceae), is a natural compound that exhibits potent activity against various cancer cell proliferation. The most frequently caused malignancy in women globally, breast cancer (BC), has been demonstrated to be significantly inhibited by PL. Apoptosis, cell cycle arrest, increased ROS generation, and changes in the signalling protein's expression are all caused by the numerous signalling pathways that PL impacts. Since BC cells resist conventional chemotherapeutic drugs (doxorubicin, docetaxel etc.), researchers have shown that the drugs in combination with PL can exhibit a synergistic effect, greater than the effects of the drug or PL alone. Recently, techniques for drug packaging based on nanotechnology have been employed to improve PL release. The review has presented an outline of the chemistry of PL, its molecular basis in BC, its bioavailability, toxicity, and nanotechnological applications. An attempt to understand the future prospects and direction of research about the compound has also been discussed.
Topics: Dioxolanes; Humans; Breast Neoplasms; Piper; Female; Antineoplastic Agents, Phytogenic; Animals; Alkaloids; Apoptosis; Piperidones
PubMed: 37955690
DOI: 10.1007/s00210-023-02673-5 -
Journal of Asian Natural Products... Dec 2023Three new hetisine type C-diterpenoid alkaloids, named as trichophorines A-C (), were isolated from , together with nine known alkaloids (). Their structures were...
Three new hetisine type C-diterpenoid alkaloids, named as trichophorines A-C (), were isolated from , together with nine known alkaloids (). Their structures were elucidated on the basis of spectroscopic data (1D, 2D NMR, single-crystal X-ray, and HR-ESI-MS). All compounds were evaluated for the inhibitory activities against LPS induced NO production in RAW 264.7 macrophage cells, and none of them showed considerable inhibitory activity.
Topics: Delphinium; Magnetic Resonance Spectroscopy; Alkaloids; Diterpenes; Molecular Structure
PubMed: 37218665
DOI: 10.1080/10286020.2023.2209564