Natural Products Treat Atopic Dermatitis via NF-κB Signaling Pathway： A Review / 中国实验方剂学杂志

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.

Research Advances in Traditional Chinese Medicine and Natural Products for Cancer Treatment by Targeting Ferroptosis / 医药导报

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.

Antibacterial potential of marine organisms and coastal plants in combating antibacterial resistance: A review

@#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.

Strategies on biosynthesis and production of bioactive compounds in medicinal plants / 中草药·英文版

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.

Genomics-driven derivatization of the bioactive fungal sesterterpenoid variecolin: Creation of an unnatural analogue with improved anticancer properties

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.

Quimioprospecção de cianobactérias brasileiras utilizando metabolômica e ensaios biológicos / Chemoprospecting of Brazilian cyanobacteria using metabolomics and biological assays

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

Antioxidant rich medicinal plants as a potential candidate to treat gastric ulcer / Plantas medicinales ricas en antioxidantes como candidatas potenciales para tratar la úlcera gástrica

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.

Research progress on the biological activity of pyrrole 1,2-α indole alkaloids / 中国基层医药

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.

Neuroprotection of Natural Products Based on Keap1/Nrf2/ARE Signaling Pathway： A Review / 中国实验方剂学杂志

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.

Neuroprotective potential of cannabidiol: Molecular mechanisms and clinical implications / 中西医结合学报

Cannabidiol (CBD), a nonpsychotropic phytocannabinoid that was once largely disregarded, is currently the subject of significant medicinal study. CBD is found in Cannabis sativa, and has a myriad of neuropharmacological impacts on the central nervous system, including the capacity to reduce neuroinflammation, protein misfolding and oxidative stress. On the other hand, it is well established that CBD generates its biological effects without exerting a large amount of intrinsic activity upon cannabinoid receptors. Because of this, CBD does not produce undesirable psychotropic effects that are typical of marijuana derivatives. Nonetheless, CBD displays the exceptional potential to become a supplementary medicine in various neurological diseases. Currently, many clinical trials are being conducted to investigate this possibility. This review focuses on the therapeutic effects of CBD in managing neurological disorders like Alzheimer's disease, Parkinson's disease and epilepsy. Overall, this review aims to build a stronger understanding of CBD and provide guidance for future fundamental scientific and clinical investigations, opening a new therapeutic window for neuroprotection. Please cite this article as: Tambe SM, Mali S, Amin PD, Oliveira M. Neuroprotective potential of Cannabidiol: Molecular mechanisms and clinical implications. J Integr Med. 2023; 21(3): 236-244.

Heterologous production of bioactive xenoacremone analogs in Aspergillus nidulans / 中国天然药物

Tyrosine-decahydrofluorene derivatives are a class of hybrid compounds that integrate the properties of polyketides and nonribosomal peptides. These compounds feature a [6.5.6] tricarbocyclic core and a para-cyclophane ether moiety in their structures and exhibit anti-tumor and anti-microbial activities. In this study, we constructed the biosynthetic pathway of xenoacremones from Xenoacremonium sinensis ML-31 in the Aspergillus nidulans host, resulting in the identification of four novel tyrosine-decahydrofluorene analogs, xenoacremones I-L (1-4), along with two known analogs, xenoacremones A and B. Remarkably, compounds 3 and 4 contained a 12-membered para-cyclophane ring system, which is unprecedented among tyrosine-decahydrofluorene analogs in X. sinensis. The successful reconstruction of the biosynthetic pathway and the discovery of novel analogs demonstrate the utility of heterologous expression strategy for the generation of structurally diverse natural products with potential biological activities.

Lysohexaenetides A and B, linear lipopeptides from Lysobacter sp. DSM 3655 identified by heterologous expression in Streptomyces / 中国天然药物

Lysobacter harbors a plethora of cryptic biosynthetic gene clusters (BGCs), albeit only a limited number have been analyzed to date. In this study, we described the activation of a cryptic polyketide synthase (PKS)/nonribosomal peptide synthetase (NRPS) gene cluster (lsh) in Lysobacter sp. DSM 3655 through promoter engineering and heterologous expression in Streptomyces sp. S001. As a result of this methodology, we were able to isolate two novel linear lipopeptides, lysohexaenetides A (1) and B (2), from the recombinant strain S001-lsh. Furthermore, we proposed the biosynthetic pathway for lysohexaenetides and identified LshA as another example of entirely iterative bacterial PKSs. This study highlights the potential of heterologous expression systems in uncovering cryptic biosynthetic pathways in Lysobacter genomes, particularly in the absence of genetic manipulation tools.

A comprehensive review of natural products with anti-hypoxic activity / 中国天然药物

Natural products exhibit substantial impacts in the field of anti-hypoxic traetment. Hypoxia can cause altitude sickness and other negative effect on the body. Headache, coma, exhaustion, vomiting and, in severe cases, death are some of the clinical signs. Currently, hypoxia is no longer just a concern in plateau regions; it is also one of the issues that can not be ignored by urban residents. This review covered polysaccharides, alkaloids, saponins, flavonoids, peptides and traditional Chinese compound prescriptions as natural products to protect against hypoxia. The active ingredients, effectiveness and mechanisms were discussed. The related anti-hypoxic mechanisms involve increasing the hemoglobin (HB) content, glycogen content and adenosine triphosphate (ATP) content, removing excessive reactive oxygen species (ROS), reducing lipid peroxidation, regulating the levels of related enzymes in cells, protecting the structural and functional integrity of the mitochondria and regulating the expression of apoptosis-related genes. These comprehensive summaries are beneficial to anti-hypoxic research and provide useful information for the development of anti-hypoxic products.

Modulation of type I interferon signaling by natural products in the treatment of immune-related diseases / 中国天然药物

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.

Anti-hepatitis B virus activities of natural products and their antiviral mechanisms / 中国天然药物

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.

Identification of Bulbocodin D and C as novel STAT3 inhibitors and their anticancer activities in lung cancer cells / 中国天然药物

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.

P450-mediated dehydrotyrosine formation during WS9326 biosynthesis proceeds via dehydrogenation of a specific acylated dipeptide substrate

WS9326A is a peptide antibiotic containing a highly unusual N-methyl-E-2-3-dehydrotyrosine (NMet-Dht) residue that is incorporated during peptide assembly on a non-ribosomal peptide synthetase (NRPS). The cytochrome P450 encoded by sas16 (P450Sas) has been shown to be essential for the formation of the alkene moiety in NMet-Dht, but the timing and mechanism of the P450Sas-mediated α,β-dehydrogenation of Dht remained unclear. Here, we show that the substrate of P450Sas is the NRPS-associated peptidyl carrier protein (PCP)-bound dipeptide intermediate (Z)-2-pent-1'-enyl-cinnamoyl-Thr-N-Me-Tyr. We demonstrate that P450Sas-mediated incorporation of the double bond follows N-methylation of the Tyr by the N-methyl transferase domain found within the NRPS, and further that P450Sas appears to be specific for substrates containing the (Z)-2-pent-1'-enyl-cinnamoyl group. A crystal structure of P450Sas reveals differences between P450Sas and other P450s involved in the modification of NRPS-associated substrates, including the substitution of the canonical active site alcohol residue with a phenylalanine (F250), which in turn is critical to P450Sas activity and WS9326A biosynthesis. Together, our results suggest that P450Sas catalyses the direct dehydrogenation of the NRPS-bound dipeptide substrate, thus expanding the repertoire of P450 enzymes that can be used to produce biologically active peptides.

Biosynthesis of natural products by non-conventional yeasts / 生物工程学报

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.

In vitro effects of lapachol and β-lapachone against Leishmania amazonensis

Leishmaniasis is a neglected disease that affects millions of people worldwide, and special attention should be given to treatment because the available drugs have limitations, which can lead to low therapeutic adherence and parasitic resistance. This study evaluated the activity of the bioactive naphthoquinones, lapachol and β-lapachone, against Leishmania amazonensis. The cell alterations were evaluated in vitro on promastigote and amastigote forms. The lethal dose (LD50) at 24, 48, and 72 h on the promastigote's forms using lapachol was 75.60, 72.82, and 58.85 μg/mL and for β-lapachone was 0.65, 1.24, and 0.71 μg/mL, respectively. The naphthoquinones significantly inhibited the survival rate of L. amazonensis amastigotes at 83.11, 57.59, and 34.95% for lapachol (82.28, 41.14, and 20.57 µg/mL), and 78.49, 83.25, and 80.22% for β-lapachone (3.26, 1.63, and 0.815 µg/mL). The compounds on the promastigote's forms led to the loss of mitochondrial membrane potential, induced changes in the integrity of the membrane, caused damage to cells suggestive of the apoptotic process, and showed inhibition of tumor necrosis factor (TNF)-α and interleukin (IL)-6 production. The results showed that these naphthoquinones are promising candidates for research on new drugs with anti-Leishmania activity derived from natural products.

Amoebicidal and trichomonicidal capacity of polymeric nanoparticles loaded with extracts of the plants Curcuma longa (Zingiberaceae) and Berberis vulgaris (Berberidaceae) / Capacidad amebicida y tricomonicida de nanopartículas poliméricas cargadas con extractos de las plantas Curcuma longa (Zingiberaceae) y Berberis vulgaris (Berberidaceae)

Abstract Introduction: Pathogenic protozoans, like Entamoeba histolytica and Trichomonas vaginalis, represent a major health problem in tropical countries; and polymeric nanoparticles could be used to apply plant extracts against those parasites. Objective: To test Curcuma longa ethanolic extract and Berberis vulgaris methanolic extracts, and their main constituents, against two species of protozoans. Methods: We tested the extracts, as well as their main constituents, curcumin (Cur) and berberine (Ber), both non-encapsulated and encapsulated in polymeric nanoparticles (NPs), in vitro. We also determined nanoparticle characteristics by photon correlation spectroscopy and scanning electron microscopy, and hemolytic capacity by hemolysis in healthy erythrocytes. Results: C. longa consisted mainly of tannins, phenols, and flavonoids; and B. vulgaris in alkaloids. Encapsulated particles were more effective (P < 0.001); however, curcumin and berberine nanoparticles were the most effective treatments. CurNPs had IC50 values (µg/mL) of 9.48 and 4.25, against E. histolytica and T. vaginalis, respectively, and BerNPs 0.24 and 0.71. The particle size and encapsulation percentage for CurNPs and BerNPs were 66.5 and 73.4 nm, and 83.59 and 76.48 %, respectively. The NPs were spherical and significantly reduced hemolysis when compared to non-encapsulated extracts. Conclusions: NPs represent a useful and novel bioactive compound delivery system for therapy in diseases caused by protozoans.

Resumen Introducción: Los protozoos patógenos, como Entamoeba histolytica y Trichomonas vaginalis, representan un importante problema de salud en los países tropicales; y se podrían usar nanopartículas poliméricas para aplicar extractos de plantas contra esos parásitos. Objetivo: Probar los extractos etanólicos de Curcuma longa y Berberis vulgaris, y sus principales constituyentes, contra dos especies de protozoos. Métodos: Probamos los extractos, así como sus principales constituyentes, curcumina (Cur) y berberina (Ber), tanto no encapsulados como encapsulados en nanopartículas poliméricas (NPs), in vitro. También determinamos las características de las nanopartículas por espectroscopía de correlación de fotones y microscopía electrónica de barrido, y la capacidad hemolítica por hemólisis en eritrocitos sanos. Resultados: C. longa tenía principalmente: taninos, fenoles y flavonoides; y B. vulgaris, alcaloides. Las partículas encapsuladas fueron más efectivas (P < 0.001); sin embargo, las nanopartículas de curcumina y berberina fueron los tratamientos más efectivos. CurNPs tenía valores IC50 (µg/mL) de 9.48 y 4.25, contra E. histolytica y T. vaginalis, respectivamente, y BerNPs 0.24 y 0.71. El tamaño de partícula y el porcentaje de encapsulación para CurNPs y BerNPs fueron: 66.5 y 73.4 nm, y 83.59 y 76.48 %, respectivamente. Los NP son esféricos y redujeron significativamente la hemólisis en comparación con los extractos no encapsulados. Conclusiones: Las NP representan un sistema de administración de compuestos bioactivos útil y novedoso para la terapia enfermedades causadas por protozoos.