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1.
Article | IMSEAR | ID: sea-237483

ABSTRACT

The group screened and identified the content of Hibiscus schizopetalus by protein–protein interaction, molecular docking, and dynamics as a potential therapy for obesity through pancreatic lipase (PNLIP) as a protein target. First, the group collected all active ingredients of H. schizopetalus from an online database (http://www.knapsackfamily. com/ and http://ijah.apps.cs.ipb.ac.id/) to identify and isolate active compounds. The 3-D structures and canonical of the active compound were taken from the PubChem database, and then all compounds were analyzed by pkCSM and Tox-Protox II to get pharmacokinetics and physical-chemistry properties. The protein target of obesity was identified using the Open Target Platform. After the protein targets of plant extract and obesity were collected, the group analyzed them using Cytoscape. Protein–protein interaction was analyzed using String, Gene ontology, and KEGG pathway. Virtual screening was done by Pyrx software, and visualization was done by Discovery Studio Biovia, proceed by molecular docking using AutoDockTools-1.5.7, and finally, molecular dynamics (MDs) was done using YASARA software. The group collected 70 compounds from a research journal and found 196 protein targets. The target of obesity was 165 protein targets. The 196 protein targets of H. schizopetalus and 165 protein targets were analyzed and merged using Cytoscape and 11 proteins targeting H. schizopetalus and obesity. After that, the group analyzed which compound of H. schizopetalus affected 11 protein targets by Pyrx with the highest binding affinity. PNLIP has the highest binding affinity compared to other proteins, so the group analyzed this PNLIP protein with its relationship to obesity. The group found that three proteins that work on PNLIP are betasitosterol, kaempferol, and gallocatechin gallate. After docking these three proteins, the group found only one active compound has the highest binding affinity compared to the commercial drug Orlistat. Then, the process ended by performing MDs of the active compound as a candidate drug for anti-obesity. In this study, the group found that gallocatechin gallate, as an active compound of H. schizopetalus, can inhibit PNLIP enzymes for obesity therapy by bio-informatics study.

2.
J Ayurveda Integr Med ; 2024 Jan; 15(1): 1-9
Article | IMSEAR | ID: sea-236979

ABSTRACT

Introduction: Rasayanas are Ayurvedic natural products that have adaptogenic effects. The extensive research on rasayanas in oncology is not currently well summarized. The aim of this review is to investigate the range and nature of the current body of research, identify gaps in knowledge, and to summarize the existing literature as it relates to Ayurvedic rasayanas and oncology. Materials and methods: A comprehensive literature search of fifteen Ayurvedic adaptogen rasayanas was con- ducted using three main concepts: Ayurvedic herbal terms, neoplasm terms, and oncological pathways. After screening was performed, key variables were extracted (tagged) including type of adaptogen, cancer type, type of study design, constituent type, and mechanisms of action (MOA). The results were synthesized and summarized using descriptive statistics and narrative summaries. Results: Five hundred and eighty-four articles were reviewed and tagged. The two most tagged adaptogens were Glycyrrhiza glabra (Yashthimadhu/licorice) (n = 166 (28.4 %)) and Withania somnifera (Ashwagandha) (n = 151 (25.9 %)). The most frequently tagged cancer diagnostic categories were gastrointestinal (n = 175 (30 %)), and breast (n = 126 (21 %)). Most of the articles focused on in vitro studies (n = 470 (80.3 %)). Of the 12 MOA tags, the most frequently tagged was apoptosis (n = 298 (29.2 %)). Conclusion: A large body of pre-clinical literature exists on adaptogen rasayanas in oncology, indicating this field of research is still in its early phase. Comparatively few studies focused on the effects on the immune system. Given the growing interest in immuno-oncology therapeutics and the potential impact of adaptogen rasayanas on the immune system, future research may focus more in this area, along with work that is more directly linked to future clinical studies.

3.
Herald of Medicine ; (12): 408-413, 2024.
Article in Chinese | WPRIM | ID: wpr-1023728

ABSTRACT

Ferroptosis is a unique iron-dependent cell death pattern,a novel death phenotype distinct from apoptosis,va-rious forms of necrosis,and autophagy.Numerous active ingredients extracted from traditional Chinese medicine have been found to exert anti-cancer effects by inducing ferroptosis in various cancers.An increasing number of studies have found that the regulation of ferroptosis can influence the sensitivity of tumor cells to drugs and even reverse drug resistance.When combined with chemo-therapy drugs such as cisplatin,5-FU and gemcitabine,some natural products enhance cancer cells'sensitivity to chemothera-peutic drugs by inducing ferroptosis.This paper mainly summarizes traditional Chinese medicine and its natural products that can exert anti-cancer effects by inducing ferroptosis,providing new insights for cancer treatment and drug resistance reversal.Addition-ally,it contributes to exploring the potential advantages of traditional Chinese medicine,thereby expanding its scope of applica-tion.

4.
Chinese Herbal Medicines ; (4): 13-26, 2024.
Article in English | WPRIM | ID: wpr-1010744

ABSTRACT

Medicinal plants are a valuable source of essential medicines and herbal products for healthcare and disease therapy. Compared with chemical synthesis and extraction, the biosynthesis of natural products is a very promising alternative for the successful conservation of medicinal plants, and its rapid development will greatly facilitate the conservation and sustainable utilization of medicinal plants. Here, we summarize the advances in strategies and methods concerning the biosynthesis and production of natural products of medicinal plants. The strategies and methods mainly include genetic engineering, plant cell culture engineering, metabolic engineering, and synthetic biology based on multiple "OMICS" technologies, with paradigms for the biosynthesis of terpenoids and alkaloids. We also highlight the biosynthetic approaches and discuss progress in the production of some valuable natural products, exemplifying compounds such as vindoline (alkaloid), artemisinin and paclitaxel (terpenoids), to illustrate the power of biotechnology in medicinal plants.

5.
Acta Pharmaceutica Sinica B ; (6): 421-432, 2024.
Article in English | WPRIM | ID: wpr-1011246

ABSTRACT

A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin ( 1) and variecolactone ( 2) was identified in Aspergillus aculeatus ATCC 16872. Heterologous production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 VrcB. Intriguingly, the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues ( 5- 7). Analysis of the compounds' anticancer activity in vitro and in vivo revealed that although 5 and 1 had comparable activities, 5 was associated with significantly reduced toxic side effects in cancer-bearing mice, indicating its potentially broader therapeutic window. Our study describes the first tests of variecolin and its analogues in animals and demonstrates the utility of synthetic biology for creating molecules with improved biological activities.

6.
Article in Chinese | WPRIM | ID: wpr-1005277

ABSTRACT

Atopic dermatitis (AD) is a chronic, recurrent, inflammatory, and pruritus skin disease caused by multiple internal and external factors, ranking first in the global burden of skin diseases. Due to the adverse reactions and high costs of conventional treatments and biologics, the development of natural products has attracted much attention. The nuclear factor-κB (NF-κB) signaling pathway is a key pathway for inhibiting inflammation and modulating immunity. This paper summarizes the pharmacological effects and molecular mechanisms of natural products such as flavonoids, alkaloids, phenols, terpenoids, coumarins, glycosides, and anthraquinones via NF-κB signaling pathway, aiming to provide guidance for the development of natural products. Basic studies have shown that natural products have high safety and efficacy. Oral or topical administration of natural products can regulate the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), mitogen-activated protein kinase (MAPK), nuclear factor erythroid 2-related factor 2 (Nrf2), high mobility group box 1 protein (HMGB1)/receptor for advanced glycation endproducts (RAGE), and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) signaling pathways to exert anti-inflammatory, anti-allergy, antioxidant activities, thus reversing the pathological changes of AD. However, it is worth noting that the clinical application of natural products is still insufficient, and more rigorous clinical trials are still needed to verify their effects. The basic experiments and clinical evidence prove that natural products may play a role in alleviating AD, which provide a basis for evaluating the functioning mechanism of natural active substances and enrich the candidates for the development of potential drugs.

7.
Article in English | WPRIM | ID: wpr-1030551

ABSTRACT

@#The increasing number of drug-resistant pathogens is a global issue and becoming worse because it has reduced the effectiveness of current antibiotics in the management of infectious diseases. Therefore, this situation highlights the urgency of an action plan to identify and develop novel and potent antimicrobials derived from natural resources. Therapeutic compounds from natural resources can offer novel, straightforward approaches against pathogenic bacteria with the least toxic manifestations and a low risk of acquiring resistance. Marine organisms and coastal plants receive much interest among researchers nowadays for developing new pharmaceuticals because they are rich in secondary metabolites that have various pharmacological effects, such as antibacterial, anti-cancer, antiviral, anti-inflammatory and others. This review's goal is to highlight the phytochemical components of marine organisms and coastal plants that might be accountable for their antibacterial properties that have been scientifically confirmed and can be potential aids in treating infectious diseases caused by multidrug resistant (MDR) bacteria in humans.

8.
Biosci. j. (Online) ; 40: e40016, 2024.
Article in English | LILACS-Express | LILACS | ID: biblio-1571915

ABSTRACT

Chagas disease is a public health problem affecting approximately seven million people worldwide. Thus, there is a need to discover drugs for the adequate treatment of this disease because currently available drugs have serious side effects. Therefore, this study aimed to evaluate the in vitro trypanocidal activity of (-)-6,6'-dinitrohinokinin, obtained from the partial synthesis of (-)-hinokinin, on the trypomastigotes and amastigotes forms. For the trypomastigote assay, blood was collected from mice infected with Trypanosoma cruzi through cardiac puncture at the parasitemic peak. The results show that (-)-6,6'-dinitrohinokinin was effective against the trypomastigote forms, presenting an IC50 of 19.83 µM and lysis percentage values ​​of 78.4% and 69.4% at concentrations of 200 and 100 µM, respectively. Molecular docking calculations indicate that (-)-6,6'-dinitrohinokinin favorably interacts with the amino acids present in the active site of the protein trypanothione reductase, a typical target for anti-trypanosomal drug development. According to the results, the (-)-6,6'-dinitrohinokinin showed more significant trypanocidal activity with IC50 of 1.83 µM than benzonidazole positive control with IC50 of 53.2 µM, showing to be a prototype molecule promising for the development of a new antiparasitic drug.

9.
São Paulo; s.n; s.n; 2024. 122 p tab, graf.
Thesis in Portuguese | LILACS | ID: biblio-1565949

ABSTRACT

Os produtos naturais são uma importante fonte de moléculas com aplicações terapêuticas e biotecnológicas. No entanto, a complexidade inerente às matrizes biológicas e as crescentes taxas de redescoberta de moléculas impõem desafios para a busca por novos compostos bioativos. A exploração de novos espécimes da biodiversidade e a aplicação de ferramentas computacionais são imperativos para a identificação de novas entidades químicas promissoras. Foi proposto catalisar o processo de prospecção química para demonstrar o potencial das cianobactérias brasileiras como fonte de novas moléculas bioativas. Nove linhagens de cianobactérias de água doce/terrestres foram cultivadas, extraídas e fracionadas. Extratos e frações foram testados quanto ao potencial citotóxico contra o microcrustáceo Artemia salina, antiproliferativo contra linhagens celulares de melanoma humano e contra promastigotas de Leishmania (L.) amazonensis. As amostras foram analisadas em paralelo via UPLC-HRMS/MS. Foi criada uma rede molecular através da plataforma GNPS. A desreplicação contou também com o suporte da plataforma DAFdiscovery, ferramenta que, através da fusão de informações dos dados de LC-MS/MS com os metadados contendo informações obtidas dos bioensaios, elenca quais as features se correlacionam com a atividade biológica. A anotação seguida de busca em base de dados foi realizada com auxílio do software SIRIUS. Quatro linhagens de cianobactérias foram selecionadas seguindo essa abordagem devido ao seu potencial ineditismo químico e bioatividade, sendo elas Brasilonema octagenarum, Anagnostidinema amphibium, Nostoc sp. e Komarekiella atlântica


Natural products are an important source of molecules with therapeutic and biotechnological applications. However, the inherent complexity of biological matrices and the increasing rediscovery rates challenge the search for new bioactive compounds. Exploring new specimens of biodiversity and applying computational tools are imperative for identifying promising new chemical entities. In this study, we proposed to catalyze the chemical prospecting process to demonstrate the potential of Brazilian cyanobacteria as a source of new bioactive molecules. Nine strains of freshwater cyanobacteria were cultivated, extracted, and fractionated. Extracts and fractions were tested for cytotoxic potential against the microcrustacean Artemia salina, antiproliferative against human melanoma cell lines, and Leishmania (L.) amazonensis promastigotes. Samples were analyzed in parallel via UPLCHRMS/MS. A molecular network was created using the GNPS platform. Dereplication was guided by DAFdiscovery, a computational tool that, through the fusion of information from LC-MS/MS data with metadata containing information obtained from bioassays, indexed which features correlate with biological activity. Annotation followed by a database search was performed using the SIRIUS software. Brasilonema octagenarum, Anagnostidinema amphibium, Nostoc sp., and Komarekiella atlântica were selected following this approach due to their potential chemical novelty and bioactivity


Subject(s)
Biological Products/analysis , Cyanobacteria/classification , Liquid Chromatography-Mass Spectrometry/methods , Leishmania/classification , Melanoma/classification
10.
Article | IMSEAR | ID: sea-236450

ABSTRACT

SARS-Cov-2 is the culprit behind the acute respiratory syndrome COVID-19. Immunopathological mechanisms that cause excessive inflammation and neutrophil activation cause this syndrome. Neutrophils are crucial for the removal of viruses and other infectious agents. This study aims to comprehensively examine the relationship between elastase enzymes and COVID-19, as well as natural resources as elastase inhibitors. The literature was searched using electronic databases such as Directory Open-Access Journal, Google Scholar, National Health Institute, PubMed, ScienceDirect, and Web of Science between October 2021 and August 2022. This narrative review article highlights some aspects of the relationship between elastase and COVID-19, including the general pathophysiology of COVID-19, protease enzymes and protease inhibitors, neutrophil extracellular traps (NET), NET cell death, elastin and desmosine, elastase and antielastase, elastase and thrombin, elastase and angiotensin-converting enzyme 2 (ACE2), elastase and cathepsin C, correlation of elastase and COVID-19, COVID-19 therapy, and natural products resource as elastase inhibitors.

11.
Article | IMSEAR | ID: sea-236448

ABSTRACT

The majority of natural products currently used in the medical field are derived from microbial or plant sources. The bioactive compounds derived from natural sources exhibit tremendous structural and chemical diversity. According to previous research, only a small percentage of the world’s plant and microbial diversity has been examined for bioactivities. The compounds originating from secondary metabolites of microorganisms are more useful for the development of novel drugs due to their biological friendliness and drug-likeness than any other compounds. Thus, recent research suggests that microorganisms obtained from diverse habitats and natural resources offer various bioactive secondary metabolites with incredibly wider chemical entities, hopefully, an alternative remedy for many diseases. Soil bacteria are capable of producing a variety of natural bioactive compounds for the treatment of various diseases. The three genera Bacillus spp., Streptomyces spp., and Pseudomonas spp. have been the prime focus to produce different types of antibiotics. However, to date, there are no reviews that evaluated the antimicrobial and anticancer properties of soil bacterial metabolites. Hence, the current review aimed to assess the antimicrobial and anticancer potential of soil bacterial metabolites.

12.
Bol. latinoam. Caribe plantas med. aromát ; 22(5): 657-675, sep. 2023. tab, ilus
Article in Spanish | LILACS | ID: biblio-1561292

ABSTRACT

Phytochemical bio-guided studies are used to find compounds with biological activity. Flavonoids from seeds of Leucaena species have antimicrobial activity in strains of medical interest, therefore, fresh seeds were collected from the town of Tlayacapan, Morelos, Mexico. The methanolic extracts were obtained by the maceration technique, targeted fractionation was performed using adsorption and molecular exclusion chromatographic techniques; to observe the antimicrobial activity, agar diffusion techniques were used; spectrometric and spectroscopic techniques were used for the characterization of D-pinitol, resulting from the fractionation of L. leucocephala. Antimicrobial activity was found on strains of Escherichia coli CUSI and Staphylococcus aureus ATCC 29213 of the most polar fractions, identifying the responsible compounds by HPLC: caffeic acid, gallic acid, p-coumaric acid, quercetin, catechin and apigenin, these compounds can inhibit the activation enzymatic, synthesis of nucleic acids and proteins, chelating with different ions, etc.


Los estudios biodirigidos fitoquímicos son empleados para encontrar compuestos con actividad biológica. Los flavonoides de semillas de especies de Leucaena son reportados por tener actividad antimicrobiana sobre cepas de interés médico, por tanto, se colectaron semillas frescas de la localidad de Tlayacapan, Morelos, México. Se obtuvieron los extractos metanólicos mediante la técnica de maceración, el fraccionamiento dirigido se realizó empleando técnicas cromatográficas de adsorción y exclusión molecular; la actividad antimicrobiana se determinó mediante técnicas de difusión en agar; se utilizaron técnicas espectrométricas y espectroscópicas para la caracterización del D-pinitol, resultado del fraccionamiento de L. leucocephala. Se encontró actividad antimicrobiana sobre cepas de Escherichia coli CUSI y Staphylococcus aureus ATCC 29213 de las fracciones más polares, identificando los compuestos responsables vía HPLC: ácido caféico, ácido gálico, ácido p-cumárico quercetina, catequina y apigenina, dichos compuestos pueden inhibir activación enzimática, síntesis de ácidos nucleicos y proteínas, quelarse con diferentes iones, etc.


Subject(s)
Plant Extracts/chemistry , Inositol/analogs & derivatives , Fabaceae/chemistry , Anti-Infective Agents/chemistry , Seeds/chemistry , Flavonoids/isolation & purification , Plant Extracts/pharmacology , Microbial Sensitivity Tests , Chromatography, High Pressure Liquid , Escherichia coli/drug effects , Inositol/isolation & purification , Mexico
13.
Bol. latinoam. Caribe plantas med. aromát ; 22(5): 560-580, sep. 2023. ilus, tab
Article in English | LILACS | ID: biblio-1560799

ABSTRACT

Oxidative stress is a key cause of gastrointestinal disorders, primarily stomach ulcers. Multiple intrinsic and extrinsic mechanisms caused the body to produce reactive oxygen species (ROS). The body's antioxidant defense system protects against these reactive species. When the degree of ROS production exceeds the normal range, the body's natural defense system fails to neutralize these dangerous free radicals, necessitating need for an exogenous source of natural antioxidants. Natural herbal remedies have been widely employed as antioxidants to relieve oxidative stress in gastric ulcers. Polyphenols, tannins, essential oils, flavonoids, notably quercetin, carotenoids, vitamin C, vitamin A, and minerals are among the molecules of immense interest in bioassays due to their significant antioxidant effects. In the present review, several natural anti-ulcer medicinal plants along with their antioxidative mechanism have been reported. Electronic databases including PubMed, Google Scholar and Scopus were explored to identify the antioxidant and gastroprotective potential of all the plants.


El estrés oxidativo es una causa clave de trastornos gastrointestinales, principalmente úlceras estomacales. Múltiples mecanismos intrínsecos y extrínsecos hacen que el cuerpo produzca especies reactivas de oxígeno (ROS). El sistema de defensa antioxidante del cuerpo protege contra estas especies reactivas. Cuando el grado de producción de ROS excede el rango normal, el sistema de defensa natural del cuerpo no logra neutralizar estos peligrosos radicales libres, lo que requiere de una fuente exógena de antioxidantes naturales. Los remedios herbales naturales se han empleado ampliamente como antioxidantes para aliviar el estrés oxidativo en las úlceras gástricas. Los polifenoles, los taninos, los aceites esenciales, los flavonoides, en particular la quercetina, los carotenoides, la vitamina C, la vitamina A y los minerales se encuentran entre las moléculas de mayor interés en los bioensayos debido a sus importantes efectos antioxidantes. En la presente revisión se han reportado varias plantas medicinales naturales antiulcerosas junto con su mecanismo antioxidante. Se exploraron bases de datos electrónicas como PubMed, Google Scholar y Scopus para identificar el potencial antioxidante y gastroprotector de todas las plantas.


Subject(s)
Stomach Ulcer/prevention & control , Plant Extracts/administration & dosage , Antioxidants/administration & dosage , Plants, Medicinal , Plant Extracts/chemistry , Reactive Oxygen Species , Gastrointestinal Diseases/prevention & control , Medicine, Traditional , Anti-Ulcer Agents , Antioxidants/chemistry
14.
Acta biol. colomb ; 28(1): 143-153, ene.-abr. 2023. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1573606

ABSTRACT

ABSTRACT Wild edible plant species can be a good source of biologically active compounds. Therefore, the aims of this research were to evaluate the antioxidant activity and quantify the phenolic compounds present in ethanolic (70% v/v) and aqueous extracts of Tinantia erecta, and to evaluate their antifungal activity against phytopathogenic fungi. The total phenol and flavonoid content and the in vitro antioxidant activity of extracts were assessed, and the phenolic compounds were quantified by HPLC. The extracts (250 µg mL-1) from T. erecta were tested for antifungal activity against Fusarium oxysporum, Phytophthora capsici, Colletotrichumgloeosporioides, Sclerotium rolfsii, and Rhizoctonia solani. The plant organ with the highest concentration of antioxidant compounds was the leaf, and the most efficient solvent for the extraction of these compounds was 70% ethanol. The phenolic compounds found in high concentrations were phloridzin (97.5 mg g-1), naringenin (19.3 mg g-1), and rutin (14.8 mg g-1). The extract obtained from leaves with 70% ethanol inhibited mycelial growth by 84 to 100%, with F. oxysporum being the least sensitive and R. solani being the most sensitive to the effect of the extract. The maximum percentage inhibition of the aqueous extracts was 15.6% against P. capsici. Extracts from the endemic species T. erecta exhibited good antioxidant activity, primarily due to the presence of phenolic compounds, and showed a great potential to inhibit phytopathogenic microorganisms.


RESUMEN Las plantas comestibles de origen silvestre pueden ser una fuente importante de compuestos biológicamente activos. Por tanto, el objetivo de la presente investigación fue evaluar la actividad antioxidante y cuantificar los compuestos fenólicos presentes en extractos etanólicos (70% v/v) y acuosos de Tinantia erecta y evaluar su actividad antifúngica frente a hongos fitopatógenos. Se evaluó el contenido de fenoles totales, flavonoides y la actividad antioxidante in vitro de los extractos, así mismo se cuantificaron los compuestos fenólicos por HPLC. También se evaluó la actividad antifúngica de los extractos (250 µg mL-1) de T. erecta frente a Fusarium oxysporum, Phytophthora capsici, Colletotrichum gloeosporioides, Sclerotium rolfsii y Rhizoctonia solani. El órgano de la planta con mayor concentración de compuestos antioxidantes fue la hoja, y el solvente más eficiente para la extracción de estos compuestos fue el etanol al 70%. Los compuestos fenólicos encontrados en más altas concentraciones fueron floridzina (97.5 mg g-1), naringenina (19.3 mg g-1) y rutina (14.8 mg g-1). El extracto obtenido de hojas con etanol al 70% inhibió el crecimiento micelial en un 84 a 100%, siendo F. oxysporum el menos sensible y R. solani el más sensible al efecto del extracto. El máximo porcentaje de inhibición de los extractos acuosos fue de tan sólo 15.6% frente a P. capsici. Los extractos de la especie endémica T. erecta exhibieron una buena actividad antioxidante, debido a la presencia de los compuestos fenólicos, así mismo mostraron un gran potencial para inhibir microorganismos fitopatógenos.

15.
Article in Chinese | WPRIM | ID: wpr-991797

ABSTRACT

Pyrrole [1,2-α] indole is a novel fused heterocyclic skeleton, which is also the basic structural unit and synthetic intermediate of many natural active products and drugs. Pyrrole [1,2-α] indole heterocyclic derivatives have attracted much attention in organic synthesis and medicinal chemistry because of their extensive and marked biological activities. Plant extracts have always been an important source of active compounds. At present, the alkaloids based on the pyrrole [1,2-α] indole heterocyclic structure discovered and isolated from plant extracts include isatisine, isoborreverine, flinderoles, polyavolensin and yuremamine. This paper reviews the research progress on the biological activity of pyrrole [1,2-α] indole heterocyclic derivatives and has found that pyrrole [1,2-α] indole heterocyclic derivatives have a good development prospect in screening active compounds and developing candidate drugs.

16.
Article in Chinese | WPRIM | ID: wpr-962650

ABSTRACT

The pathological manifestations of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis, are abnormal protein aggregation and accumulation, microglia activation, and mitochondrial dysfunction, which eventually lead to the gradual loss of neuronal structure or function and deteriorate over time. These pathological processes are related to the production of reactive oxygen species (ROS), which can cause oxidative stress and damage proteins, lipids, and DNA, leading to cell and tissue injuries. The Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway is the main mechanism to maintain the redox balance of the body and defend against oxidative stress injury. Nrf2 activates the expression of a series of antioxidant genes related to ARE through the dissociation of Keap1 and nuclear transfer in the cytoplasm to protect the body from oxidative damage. Therefore, the discovery and study of the Keap1/Nrf2/ARE signaling pathway activator is of great significance for the prevention and treatment of neurodegenerative diseases. Because of the remarkable biological activity and slight side effects, natural products are a treasure trove for new drug research and development. Studies have shown that a variety of natural products can activate the Keap1/Nrf2/ARE signaling pathway and play a neuroprotective role. According to the structural characteristics, natural products can be divided into flavonoids, terpenoids, volatile oils, polyphenols, and phenylpropanoids. This study summarized the underlying mechanism of the Keap1/Nrf2/ARE signaling pathway in regulating diseases and reviewed the research progress on natural products based on this signaling pathway in neuroprotection to provide references for the development of clinical drugs for the prevention and treatment of neurodegenerative diseases.

17.
Article in English | WPRIM | ID: wpr-971661

ABSTRACT

Type I interferon (IFN) is considered as a bridge between innate and adaptive immunity. Proper activation or inhibition of type I IFN signaling is essential for host defense against pathogen invasion, tumor cell proliferation, and overactive immune responses. Due to intricate and diverse chemical structures, natural products and their derivatives have become an invaluable source inspiring innovative drug discovery. In addition, some natural products have been applied in clinical practice for infection, cancer, and autoimmunity over thousands of years and their promising curative effects and safety have been well-accepted. However, whether these natural products are primarily targeting type I IFN signaling and specific molecular targets involved are not fully elucidated. In the current review, we thoroughly summarize recent advances in the pharmacology researches of natural products for their type I IFN activity, including both agonism/activation and antagonism/inhibition, and their potential application as therapies. Furthermore, the source and chemical nature of natural products with type I IFN activity are highlighted and their specific molecular targets in the type I IFN pathway and mode of action are classified. In conclusion, natural products possessing type I IFN activity represent promising therapeutic strategies and have a bright prospect in the treatment of infection, cancer, and autoimmune diseases.


Subject(s)
Biological Products/therapeutic use , Immunity, Innate , Signal Transduction , Interferon Type I/metabolism
18.
Chinese Journal of Biotechnology ; (12): 2284-2312, 2023.
Article in Chinese | WPRIM | ID: wpr-981203

ABSTRACT

Non-conventional yeasts such as Yarrowia lipolytica, Pichia pastoris, Kluyveromyces marxianus, Rhodosporidium toruloides and Hansenula polymorpha have proven to be efficient cell factories in producing a variety of natural products due to their wide substrate utilization spectrum, strong tolerance to environmental stresses and other merits. With the development of synthetic biology and gene editing technology, metabolic engineering tools and strategies for non-conventional yeasts are expanding. This review introduces the physiological characteristics, tool development and current application of several representative non-conventional yeasts, and summarizes the metabolic engineering strategies commonly used in the improvement of natural products biosynthesis. We also discuss the strengths and weaknesses of non-conventional yeasts as natural products cell factories at current stage, and prospects future research and development trends.


Subject(s)
Yeasts/genetics , Yarrowia/metabolism , Gene Editing , Metabolic Engineering
19.
Article in English | WPRIM | ID: wpr-1010992

ABSTRACT

Chronic hepatitis B (CHB) infections caused by the hepatitis B virus (HBV) continue to pose a significant global public health challenge. Currently, the approved treatments for CHB are limited to interferon and nucleos(t)ide analogs, both of which have their limitations, and achieving a complete cure remains an elusive goal. Therefore, the identification of new therapeutic targets and the development of novel antiviral strategies are of utmost importance. Natural products (NPs) constitute a class of substances known for their diverse chemical structures, wide-ranging biological activities, and low toxicity profiles. They have shown promise as potential candidates for combating various diseases, with a substantial number demonstrating anti-HBV properties. This comprehensive review focuses on the current applications of NPs in the fight against HBV and provides a summary of their antiviral mechanisms, considering their impact on the viral life cycle and host hepatocytes. By offering insights into the world of anti-HBV NPs, this review aims to furnish valuable information to support the future development of antiviral drugs.


Subject(s)
Humans , Hepatitis B virus , Hepatitis B, Chronic/drug therapy , Antiviral Agents/therapeutic use , Biological Products/therapeutic use , Hepatocytes
20.
Article in English | WPRIM | ID: wpr-1010995

ABSTRACT

Cancer stands as one of the predominant causes of mortality globally, necessitating ongoing efforts to develop innovative therapeutics. Historically, natural products have been foundational in the quest for anticancer agents. Bulbocodin D (BD) and Bulbocodin C (BC), two bibenzyls derived from Pleione bulbocodioides (Franch.) Rolfe, have demonstrated notable in vitro anticancer activity. In human lung cancer A549 cells, the IC50s for BD and BC were 11.63 and 11.71 μmol·L-1, respectively. BD triggered apoptosis, as evidenced by an upsurge in Annexin V-positive cells and elevated protein expression of cleaved-PARP in cancer cells. Furthermore, BD and BC markedly inhibited the migratory and invasive potentials of A549 cells. The altered genes identified through RNA-sequencing analysis were integrated into the CMap dataset, suggesting BD's role as a potential signal transducer and activator of transcription 3 (STAT3) inhibitor. SwissDock and MOE analyses further revealed that both BD and BC exhibited a commendable binding affinity with STAT3. Additionally, a surface plasmon resonance assay confirmed the direct binding affinity between these compounds and STAT3. Notably, treatment with either BD or BC led to a significant reduction in p-STAT3 (Tyr 705) protein levels, regardless of interleukin-6 stimulation in A549 cells. In addition, the extracellular signal-regulated kinase (ERK) was activated after BD or BC treatment. An enhancement in cancer cell mortality was observed upon combined treatment of BD and U0126, the MEK1/2 inhibitor. In conclusion, BD and BC emerge as promising novel STAT3 inhibitors with potential implications in cancer therapy.


Subject(s)
Humans , Lung Neoplasms/metabolism , STAT3 Transcription Factor/metabolism , Antineoplastic Agents/chemistry , A549 Cells , Apoptosis , Cell Line, Tumor , Cell Proliferation
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