Natural Products and Bioprospecting最新文献

Bufadienolides, naturally occurring steroids primarily found in toads, have garnered attention for their pharmacological properties and ecological significance. In this study, we isolated and identified 21 bufadienolides from the gallbladders of Bufo gargarizans, comprising four new compounds and 17 known ones. Notably, the predominance of 15 bufadienolides with a 3α-OH configuration in toad bile differs significantly from the 3β-OH bufadienolides found in venom secreted by toad glands. Moreover, our investigation into the biotransformation of 3β-OH and 3α-OH bufadienolides in the liver and kidney tissues of toads revealed an irreversible conversion from 3β-OH to 3α-OH bufadienolides, suggesting a crucial role in toad self-detoxification. These findings provide valuable insights into the structural diversity of bufadienolides and advance our understanding of their medical and ecological significance.

Graphical Abstract

Scutellarin is widely distributed in Scutellaria baicalensis, family Labiatae, and Calendula officinalis, family Asteraceae, and belongs to flavonoids. Scutellarin has a wide range of pharmacological activities, it is widely used in the treatment of cerebral infarction, angina pectoris, cerebral thrombosis, coronary heart disease, and other diseases. It is a natural product with great research and development prospects. In recent years, with in-depth research, researchers have found that wild scutellarin also has good therapeutic effects in anti-tumor, anti-inflammatory, anti-oxidation, anti-virus, treatment of metabolic diseases, and protection of kidney. The cancer treatment involves glioma, breast cancer, lung cancer, renal cancer, colon cancer, and so on. In this paper, the sources, pharmacological effects, in vivo and in vitro models of scutellarin were summarized in recent years, and the current research status and future direction of scutellarin were analyzed.

Graphical Abstract

The aberrant activation of the Wnt/β-catenin signaling pathway is closely associated with the development of various carcinomas, especially colorectal cancers (CRCs), where adenomatous colorectal polyposis (APC) mutations are the most frequently observed, which limits the anti-tumor efficiency of inhibitors targeting the upstream of Wnt/β-catenin pathway. The anti-tumor activity of the naturally occurring alkaloid cepharanthine (CEP) extracted from the plant Stephania cepharantha Hayata has been reported in various types of tumors. We previously observed that its derivatives inhibited the Wnt/β-catenin signaling in liver cancer; however, the specific mechanism remains unknown. In this study, we confirmed CEP can effectively inhibit APC-mutant CRC cell lines (SW480, SW620, LoVo) through disturbing of the Wnt/β-catenin signaling and elucidated the underlying mechanisms. Here, we demonstrate that CEP attenuates the Wnt/β-catenin signaling by decreasing the β-catenin, subsequently impeding the proliferation of APC-mutant CRCs. Moreover, CEP induced β-catenin transcription inhibition rather than the instability of β-catenin protein and mRNA contributes to reduction of β-catenin. Taken together, our findings identify CEP as the first β-catenin transcriptional inhibitor in the modulation of Wnt/β-catenin signaling and indicate CEP as a potential therapeutic option for the treatment of APC-mutated CRCs.

Graphical Abstract

Neurodegenerative diseases (NDs) are common chronic diseases arising from progressive damage to the nervous system. Here, in-house natural product database screening revealed that libertellenone C (LC) obtained from the fermentation products of Arthrinium arundinis separated from the gut of a centipede collected in our Tongji campus, showed a remarkable neuroprotective effect. Further investigation was conducted to clarify the specific mechanism. LC dose-dependently reversed glutamate-induced decreased viability, accumulated reactive oxygen species, mitochondrial membrane potential loss, and apoptosis in SH-SY5Y cells. Network pharmacology analysis predicted that the targets of LC were most likely directly related to oxidative stress and the regulation of inflammatory factor-associated signaling pathways. Further study demonstrated that LC attenuated nitrite, TNF-α, and IL-1β production and decreased inducible nitric oxide synthase and cyclooxygenase expression in lipopolysaccharide-induced BV-2 cells. LC could directly inhibit NLRP3 inflammasome activation by decreasing the expression levels of NLRP3, ASC, cleaved Caspase-1, and NF-κB p65. Our results provide a new understanding of how LC inhibits the NLRP3 inflammasome in microglia, providing neuroprotection. These findings might guide the development of effective LC-based therapeutic strategies for NDs.

According to The World Alzheimer Report 2023 by Alzheimer’s Disease International (ADI) estimates that 33 to 38.5 million people worldwide suffer from Alzheimer’s Disease (AD). A crucial hallmark associated with this disease is associated with the deficiency of the brain neurotransmitter acetylcholine, due to an affected acetylcholinesterase (AChE) activity. Marine organisms synthesize several classes of compounds, some of which exhibit significant AChE inhibition, such as petrosamine, a coloured pyridoacridine alkaloid. The aim of this work was to characterize the activity of petrosamine isolated for the first time from a Brazilian marine sponge, using two neurotoxicity models with aluminium chloride, as exposure to aluminium is associated with the development of neurodegenerative diseases. The in vitro model was based in a neuroblastoma cell line and the in vivo model exploited the potential of zebrafish (Danio rerio) embryos in mimicking hallmarks of AD. To our knowledge, this is the first report on petrosamine’s activity over these parameters, either in vitro or in vivo, in order to characterize its full potential for tackling neurotoxicity.

Graphical Abstract

A type of high molecular weight bioactive polymers called exopolysaccharides (EPS) are produced by thermophiles, the extremophilic microbes that thrive in acidic environmental conditions of hot springs with excessively warm temperatures. Over time, EPS became important as natural biotechnological additives because of their noncytotoxic, emulsifying, antioxidant, or immunostimulant activities. In this article, we unravelled a new EPS produced by Staphylococcus sp. BSP3 from an acidic (pH 6.03) San Pedro hot spring (38.1 °C) located in the central Andean mountains in Chile. Several physicochemical techniques were performed to characterize the EPS structure including Scanning electron microscopy–energy dispersive X-ray spectroscopy (SEM–EDS), Atomic Force Microscopy (AFM), High-Performance Liquid Chromatography (HPLC), Gel permeation chromatography (GPC), Fourier Transform Infrared Spectroscopy (FTIR), 1D Nuclear Magnetic Resonance (NMR), and Thermogravimetric analysis (TGA). It was confirmed that the amorphous surface of the BSP3 EPS, composed of rough pillar-like nanostructures, is evenly distributed. The main EPS monosaccharide constituents were mannose (72%), glucose (24%) and galactose (4%). Also, it is a medium molecular weight (43.7 kDa) heteropolysaccharide. NMR spectroscopy demonstrated the presence of a [→ 6)-⍺-d-Manp-(1 → 6)-⍺-d-Manp-(1 →] backbone 2-O substituted with 1-⍺-d-Manp. A high thermal stability of EPS (287 °C) was confirmed by TGA analysis. Emulsification, antioxidant, flocculation, water-holding (WHC), and oil-holding (OHC) capacities are   also studied for biotechnological industry applications. The results demonstrated that BSP3 EPS could be used as a biodegradable material for different purposes, like flocculation and natural additives in product formulation.

Graphical Abstract

Marine-derived fungi of the genus Trichoderma have been surveyed for pharmaceuticals and agrochemicals since 1993, with various new secondary metabolites being characterized from the strains of marine animal, plant, sediment, and water origin. Chemical structures and biological activities of these metabolites are comprehensively reviewed herein up to the end of 2022 (covering 30 years). More than 70 strains that belong to at least 18 known Trichoderma species have been chemically investigated during this period. As a result, 445 new metabolites, including terpenes, steroids, polyketides, peptides, alkaloids, and others, have been identified, with over a half possessing antimicroalgal, zooplankton-toxic, antibacterial, antifungal, cytotoxic, anti-inflammatory, and other activities. The research is highlighted by the molecular diversity and antimicroalgal potency of terpenes and steroids. In addition, metabolic relevance along with co-culture induction in the production of new compounds is also concluded. Trichoderma strains of marine origin can transform and degrade heterogeneous molecules, but these functions need further exploration.

Graphical Abstract

Glycosylation is a prevalent post-modification found in natural products and has a significant impact on the structural diversity and activity variation of natural products. Glucosylation is the most common type of glycosylation, whereas xylosylation is relatively rare. Despite their unique chemical structures and beneficial activities, xylosylated natural products from microorganisms have received little attention. This review provides, for the first time, a comprehensive summary of 126 microbial-derived xylosylated natural products, including xylosyl-cyathane diterpenes, xylosylated triterpenes, xylosyl aromatic compounds, and others. Among these compounds, xylosyl-cyathane diterpenes represent the highest number of derivatives, followed by xylosylated triterpenes. Xylosyl compounds from bacterial sources have less defined structural profiles compared to those from fungi. The characterization of xylosyltransferase EriJ from Basidiomycota extended the structural diversity of xylosyl cyathane diterpenes. This work provides a valuable reference for the research and use of xylosyltransferase for drug discovery and synthetic chemistry. Further work is needed to explore the potential applications of microbial derived xylosyl compounds and to develop novel xylosyl transferases. With the deepening of genomic sequencing of medicinal fungi, more biosynthesis of bioactive xylosyl compounds is expected to be elucidated in the future.

Graphical Abstract

Marine natural products (MNPs) and marine organisms include sea urchin, sea squirts or ascidians, sea cucumbers, sea snake, sponge, soft coral, marine algae, and microalgae. As vital biomedical resources for the discovery of marine drugs, bioactive molecules, and agents, these MNPs have bioactive potentials of antioxidant, anti-infection, anti-inflammatory, anticoagulant, anti-diabetic effects, cancer treatment, and improvement of human immunity. This article reviews the role of MNPs on anti-infection of coronavirus, SARS-CoV-2 and its major variants (such as Delta and Omicron) as well as tuberculosis, H. Pylori, and HIV infection, and as promising biomedical resources for infection related cardiovascular disease (irCVD), diabetes, and cancer. The anti-inflammatory mechanisms of current MNPs against SARS-CoV-2 infection are also discussed. Since the use of other chemical agents for COVID-19 treatment are associated with some adverse effects in cardiovascular system, MNPs have more therapeutic advantages. Herein, it’s time to protect this ecosystem for better sustainable development in the new era of ocean economy. As huge, novel and promising biomedical resources for anti-infection of SARS-CoV-2 and irCVD, the novel potential mechanisms of MNPs may be through multiple targets and pathways regulating human immunity and inhibiting inflammation. In conclusion, MNPs are worthy of translational research for further clinical application.

Graphical Abstract

Reacting to the challenges presented by the evolving nexus of environmental change, defossilization, and diversified natural product bioprospecting is vitally important for advancing global healthcare and placing patient benefit as the most important consideration. This overview emphasizes the importance of natural and synthetic medicines security and proposes areas for global research action to enhance the quality, safety, and effectiveness of sustainable natural medicines. Following a discussion of some contemporary factors influencing natural products, a rethinking of the paradigms in natural products research is presented in the interwoven contexts of the Fourth and Fifth Industrial Revolutions and based on the optimization of the valuable assets of Earth. Following COP28, bioprospecting is necessary to seek new classes of bioactive metabolites and enzymes for chemoenzymatic synthesis. Focus is placed on those performance and practice modifications which, in a sustainable manner, establish the patient, and the maintenance of their prophylactic and treatment needs, as the priority. Forty initiatives for natural products in healthcare are offered for the patient and the practitioner promoting global action to address issues of sustainability, environmental change, defossilization, quality control, product consistency, and neglected diseases to assure that quality natural medicinal agents will be accessible for future generations.

Graphical Abstract