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1.
Chem Biodivers ; 21(2): e202300494, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37983920

RESUMO

This study provides a comprehensive overview of the current knowledge regarding phototoxic terrestrial plants and their phototoxic and photosensitizing metabolites. Within the 435,000 land plant species, only around 250 vascular plants have been documented as phototoxic or implicated in phototoxic occurrences in humans and animals. This work compiles a comprehensive catalog of these phototoxic plant species, organized alphabetically based on their taxonomic family. The dataset encompasses meticulous details including taxonomy, geographical distribution, vernacular names, and information on the nature and structure of their phototoxic and photosensitizing molecule(s). Subsequently, this study undertook an in-depth investigation into phototoxic molecules, resulting in the compilation of a comprehensive and up-to-date list of phytochemicals exhibiting phototoxic or photosensitizing activity synthesized by terrestrial plants. For each identified molecule, an extensive review was conducted, encompassing discussions on its phototoxic activity, chemical family, occurrence in plant families or species, distribution within different plant tissues and organs, as well as the biogeographical locations of the producer species worldwide. The analysis also includes a thorough discussion on the potential use of these molecules for the development of new photosensitizers that could be used in topical or injectable formulations for antimicrobial and anticancer phototherapy as well as manufacturing of photoactive devices.


Assuntos
Dermatite Fototóxica , Fármacos Fotossensibilizantes , Humanos , Animais , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Plantas
2.
Int J Mol Sci ; 25(5)2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38473970

RESUMO

Chamaecyparis obtusa (Siebold & Zucc.) Endl., which belongs to the Cupressaceae family, occurs naturally in North America and Asia, especially in Korea, Taiwan and Japan, where it is an evergreen, coniferous, sacred, ethnic tree. It has many useful varieties that are widespread throughout the world and grown for decorative purposes. It is most commonly used as an ornamental plant in homes, gardens or parks. It is also widely used in many areas of the economy; for example, its wood is used in architecture as well as furniture production. In addition, oil extracted from Chamaecyparis obtusa is increasingly used in cosmetology for skin care. Due to its wide economic demand, mainly in Japan, it represents the largest area of plantation forest. Despite this, it is on the red list of endangered species. Its use in ethnopharmacology has led to more and more research in recent years in an attempt to elucidate the potential mechanisms of its various biological activities, such as antimicrobial, antioxidant, anticancer, antidiabetic, antiasthmatic, anti-inflammatory, antiallergic, analgesic and central nervous system effects. It has also been shown that Chamaecyparis obtusa can be used as an insect repellent and an ingredient in plant disease treatment. This thesis provides a comprehensive review of the biological studies to date, looking at different areas of the economic fields of potential use of Chamaecyparis obtusa.


Assuntos
Chamaecyparis , Chamaecyparis/fisiologia , Árvores/fisiologia , Japão , Anti-Inflamatórios , Ásia
3.
Int J Mol Sci ; 25(2)2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38256118

RESUMO

Plectranthus scutellarioides (L.) R.Br. is a medicinal plant that has long been used in traditional medicine to treat conditions such as abscesses, ulcers, and ear and eye infections. It is known to have a wide range of biological properties, such as antibacterial, antioxidant, antifungal, anti-inflammatory, anti-diabetic and anti-cancer effects. In this study, we established in vitro cultures from both the aerial parts and roots of Plectranthus scutellarioides. Subsequently, we compared the basic phytochemical profile of the obtained extracts and conducted a biological analysis to assess their potential for inducing apoptosis in breast (MCF-7) and lung (A549) cancer cells. Phytochemical analysis by HPLC-MS revealed the presence of compounds belonging to phenolic acids (ferulic, syringic, vanillic, rosmarinic, chlorogenic, caffeic, coumaric, dihydroxybenzoic acids), flavonoids (eriodyctiol and cirsimaritin), and terpenes such as 6,11,12,14,16-Pentahydroxy-3,17diacetyl-8,11,13-abietatrien-7-one, 6,11,12,14,16-Pentahydroxy-3,17-diacetyl5,8,11,13-abietatetraen-7-one, and 3,6,12-Trihydroxy-2-acetyl-8,12-abietadien7,11,14-trione. The results show that both extracts have a cytotoxic and genotoxic effect against MCF-7 and A549 cancer cells, with a different degree of sensitivity. It was also shown that both extracts can induce apoptosis by altering the expression of apoptotic genes (Bax, Bcl-2, TP53, Fas, and TNFSF10), reducing mitochondrial membrane potential, increasing ROS levels, and increasing DNA damage. In addition, it has been shown that the tested extracts can alter blood coagulation parameters. Our results indicate that extracts from in vitro cultures of Plectranthus scutellarioides aerial parts and roots have promising therapeutic application, but further research is needed to better understand the mechanisms of their action in the in vitro model.


Assuntos
Ácidos Cumáricos , Plectranthus , Humanos , Células A549 , Antibacterianos , Compostos Fitoquímicos
4.
Int J Mol Sci ; 25(8)2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38674113

RESUMO

The diterpene 7α-acetoxy-6ß-hydroxyroyleanone isolated from Plectranthus grandidentatus demonstrates promising antibacterial, anti-inflammatory and anticancer properties. However, its bioactivity may be enhanced via strategic structural modifications of such natural products through semisynthesis. The anticancer potential of 7α-acetoxy-6ß-hydroxyroyleanone and five derivatives was analyzed in silico via the prediction of chemicals absorption, distribution, metabolism, excretion, and toxicity (ADMET), quantum mechanical calculations, molecular docking and molecular dynamic simulation. The protein targets included regulators of apoptosis and cell proliferation. Additionally, network pharmacology was used to identify potential targets and signaling pathways. Derivatives 7α-acetoxy-6ß-hydroxy-12-O-(2-fluoryl)royleanone and 7α-acetoxy-6ß-(4-fluoro)benzoxy-12-O-(4-fluoro)benzoylroyleanone achieved high predicted binding affinities towards their respective protein panels, with stable molecular dynamics trajectories. Both compounds demonstrated favorable ADMET parameters and toxicity profiles. Their stability and reactivity were confirmed via geometry optimization. Network analysis revealed their involvement in cancer-related pathways. Our findings justify the inclusion of 7α-acetoxy-6ß-hydroxy-12-O-(2-fluoryl)royleanone and 7α-acetoxy-6ß-(4-fluoro)benzoxy-12-O-(4-fluoro)benzoylroyleanone in in vitro analyses as prospective anticancer agents. Our binding mode analysis and stability simulations indicate their potential as selective inhibitors. The data will guide studies into their structure optimization, enhancing efficacy and drug-likeness.


Assuntos
Diterpenos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Plectranthus , Humanos , Plectranthus/química , Diterpenos/química , Diterpenos/farmacologia , Diterpenos/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Simulação por Computador , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Proliferação de Células/efeitos dos fármacos
5.
Molecules ; 29(8)2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38675627

RESUMO

The abietane diterpenoid 7α-acetoxy-6ß-hydroxyroyleanone (Roy) isolated from Plectranthus grandidentatus demonstrates cytotoxicity across numerous cancer cell lines. To potentiate anticancer attributes, a series of semi-synthetic Roy derivatives were generated and examined computationally. ADMET predictions were used to evaluate drug-likeness and toxicity risks. The antineoplastic potential was quantified by PASS. The DFT models were used to assess their reactivity and stability. Molecular docking determined cancer-related protein binding. MS simulations examined ligand-protein stability. Additionally, network pharmacology was used to identify potential targets and signaling pathways. Favorable ADME attributes and acceptable toxicity profiles were determined for all compounds. Strong anticancer potential was shown across derivatives (Pa 0.819-0.879). Strategic modifications altered HOMO-LUMO gaps (3.39-3.79 eV) and global reactivity indices. Favorable binding was revealed against cyclin-dependent kinases, BCL-2, caspases, receptor tyrosine kinases, and p53. The ligand exhibited a stable binding pose in MD simulations. Network analysis revealed involvement in cancer-related pathways. In silico evaluations predicted Roy and derivatives as effective molecules with anticancer properties. Experimental progress is warranted to realize their chemotherapeutic potential.


Assuntos
Abietanos , Diterpenos , Simulação de Acoplamento Molecular , Plectranthus , Humanos , Abietanos/química , Abietanos/farmacologia , Plectranthus/química , Simulação por Computador , Antineoplásicos/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Simulação de Dinâmica Molecular , Estrutura Molecular
6.
Int J Mol Sci ; 24(6)2023 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-36982980

RESUMO

Asthma is an inflammatory disease whose etiology remains unclear. Its characteristics encompass a wide range of clinical symptoms, inflammatory processes, and reactions to standard therapies. Plants produce a range of constitutive products and secondary metabolites that may have therapeutic abilities. The aim of this study was to determine the effects of Senna obtusifolia transgenic hairy root extracts on virus-induced airway remodeling conditions. Three cell lines were incubated with extracts from transformed (SOA4) and transgenic (SOPSS2, with overexpression of the gene encoding squalene synthase 1) hairy roots of Senna obtusifolia in cell lines undergoing human rhinovirus-16 (HRV-16) infection. The effects of the extracts on the inflammatory process were determined based on the expression of inflammatory cytokines (IL-8, TNF-α, IL-1α and IFN-γ) and total thiol content. The transgenic Senna obtusifolia root extract reduced virus-induced expression of TNF, IL-8 and IL-1 in WI-38 and NHBE cells. The SOPSS2 extract reduced IL-1 expression only in lung epithelial cells. Both tested extracts significantly increased the concentration of thiol groups in epithelial lung cells. In addition, the SOPPS2 hairy root extract yielded a positive result in the scratch test. SOA4 and SOPPS2 Senna obtusifolia hairy root extracts demonstrated anti-inflammatory effects or wound healing activity. The SOPSS2 extract had stronger biological properties, which may result from a higher content of bioactive secondary metabolites.


Assuntos
Interleucina-8 , Senna , Humanos , Interleucina-8/metabolismo , Senna/genética , Cicatrização , Extratos Vegetais/uso terapêutico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/metabolismo , Interleucina-1/metabolismo , Raízes de Plantas/genética
7.
Int J Mol Sci ; 24(20)2023 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-37894959

RESUMO

The Lamiaceae is one of the most important families in the production of essential oils known to have a wide spectrum of biological activity. Recent research has highlighted the dermatological capabilities of various Lamiaceae essential oils, which appear to offer potential in free radical scavenging and anti-inflammatory activity. Some have also been extensively studied for their tissue remodeling and wound-healing, anti-aging, anti-melanogenic, and anti-cancer properties. Certain Lamiaceae essential oils are promising as novel therapeutic alternatives for skin disorders. This potential has seen substantial efforts dedicated to the development of modern formulations based on nanotechnology, enabling the topical application of various Lamiaceae essential oils. This review provides a comprehensive summary of the utilization of various essential oils from the Lamiaceae family over the past decade. It offers an overview of the current state of knowledge concerning the use of these oils as antioxidants, anti-inflammatory agents, wound-healers, anti-aging agents, anti-melanogenic agents, and anticancer agents, both alone and in combination with nanoparticles. Additionally, the review explores their potential applicability in patents regarding skin diseases.


Assuntos
Pesquisa Biomédica , Lamiaceae , Óleos Voláteis , Humanos , Óleos Voláteis/farmacologia , Óleos Voláteis/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Nanotecnologia
8.
Molecules ; 28(13)2023 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-37446611

RESUMO

Nanoparticles (NPs), due to their size, have a key position in nanotechnology as a spectrum of solutions in medicine. NPs improve the ability of active substances to penetrate various routes: transdermal, but also digestive (active endocytosis), respiratory and injection. Chitosan, an N-deacetylated derivative of chitin, is a natural biodegradable cationic polymer with antioxidant, anti-inflammatory and antimicrobial properties. Cross-linked chitosan is an excellent matrix for the production of nanoparticles containing active substances, e.g., the Ginkgo biloba extract (GBE). Chitosan nanoparticles with the Ginkgo biloba extract (GBE) were obtained by ion gelation using TPP as a cross-linking agent. The obtained product was characterized in terms of morphology and size based on SEM and Zeta Sizer analyses as well as an effective encapsulation of GBE in nanoparticles-FTIR-ATR and UV-Vis analyses. The kinetics of release of the active substance in water and physiological saline were checked. Biological studies were carried out on normal and cancer cell lines to check the cytotoxic effect of GBE, chitosan nanoparticles and a combination of the chitosan nanoparticles with GBE. The obtained nanoparticles contained and released GBE encapsulated in research media. Pure NPs, GBE and a combination of NPs and the extract showed cytotoxicity against tumor cells, with no cytotoxicity against the physiological cell line.


Assuntos
Quitosana , Nanopartículas , Extratos Vegetais/farmacologia , Ginkgo biloba
9.
Molecules ; 28(18)2023 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-37764326

RESUMO

Leonurus sibiricus L. has great ethnobotanical and ethnomedicinal significance. This study aimed to assess the antioxidant and anti-inflammatory properties of Leonurus sibiricus L. transgenic roots extracts transformed by Rhizobium rhizogenes, with and without the AtPAP1 transcriptional factor. The study determined the total phenolic and flavonoid contents, as well as in vitro antioxidant assays, including hydrogen peroxide and nitric oxide scavenging activity. In addition, in silico computational studies and molecular docking were conducted to evaluate the antioxidant and anti-inflammatory potential of the identified compounds. The ligands were docked to NADPH oxidase, cyclooxygenase 2,5-lipoxygenase, inducible nitric synthase and xanthine oxidase: enzymes involved in the inflammatory process. The total phenolic and flavonoid contents ranged from 85.3 ± 0.35 to 57.4 ± 0.15 mg/g GAE/g and 25.6 ± 0.42 to 18.2 ± 0.44 mg/g QUE/g in hairy root extracts with and without AtPAP1, respectively. H2O2 scavenging activity (IC50) was found to be 29.3 µg/mL (with AtPAP1) and 37.5 µg/mL (without AtPAP1 transcriptional factor), and NO scavenging activity (IC50) was 48.0 µg/mL (with AtPAP1) and 68.8 µg/mL (without AtPAP1 transcriptional factor). Leonurus sibiricus L. transformed root extracts, both with and without AtPAP1, are a source of phytochemicals belonging to different classes of molecules, such as flavonoids (catechin and rutin), phenolic compounds (caffeic acid, coumaric acid, chlorogenic acid, ferulic acid) and phenylpropanoid (verbascoside). Among the radicals formed after H removal from the different -OH positions, the lowest bond dissociation enthalpy was observed for rutin (4'-OH). Rutin was found to bind with cyclooxygenase 2, inducible nitric synthases and xanthine oxidase, whereas chlorogenic acid demonstrated optimal binding with 5-lipoxygenase. Therefore, it appears that the Leonurus sibiricus L. transformed root extract, both with and without the AtPAP1 transcriptional factor, may serve as a potential source of active components with antioxidant and anti-inflammatory potential; however, the extract containing AtPAP1 demonstrates superior activities. These properties could be beneficial for human health.


Assuntos
Antioxidantes , Leonurus , Humanos , Antioxidantes/farmacologia , Araquidonato 5-Lipoxigenase , Ciclo-Oxigenase 2 , Peróxido de Hidrogênio , Simulação de Acoplamento Molecular , Xantina Oxidase , Flavonoides/farmacologia , Rutina , Anti-Inflamatórios/farmacologia , Ácido Clorogênico , Extratos Vegetais/farmacologia
10.
J Cell Mol Med ; 26(3): 736-749, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34939316

RESUMO

Bronchial epithelial cells and fibroblasts play an essential role in airway remodelling, due to their protective and secretory functions. There are many studies proving that infection caused by human rhinovirus may contribute to the process of airway remodelling. The beneficial properties of curcumin, the basic ingredient of turmeric, have been proved in many studies. Therefore, the aim of this study was the evaluation of curcumin immunomodulatory properties in development of airway remodelling. Fibroblasts (WI-38 and HFL1) and epithelial cells (NHBE) were incubated with curcumin. Additionally, remodelling conditions were induced with rhinovirus (HRV). Airway remodelling genes were determined by qPCR and immunoblotting. Moreover, NF-κB, c-Myc and STAT3 were silenced to analyse the pathways involved in airway remodelling. Curcumin reduced the expression of the genes analysed, especially MMP-9, TGF-ß and collagen I. Moreover, curcumin inhibited the HRV-induced expression of MMP-9, TGF-ß, collagen I and LTC4S (p < 0.05). NF-κB, c-Myc and STAT3 changed their course of expression. Concluding, our study shows that curcumin significantly downregulated gene expression related to the remodelling process, which is dependent on NF-κB and, partially, on c-Myc and STAT3. The results suggest that the remodelling process may be limited and possibly prevented, however this issue requires further research.


Assuntos
Remodelação das Vias Aéreas , Curcumina , Curcumina/farmacologia , Células Epiteliais/metabolismo , Fibroblastos/metabolismo , Humanos , NF-kappa B/genética , NF-kappa B/metabolismo
11.
Mar Drugs ; 20(8)2022 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-36005527

RESUMO

For more than 40 years, marine microorganisms have raised great interest because of their major ecological function and their numerous applications for biotechnology and pharmacology. Particularly, Archaea represent a resource of great potential for the identification of new metabolites because of their adaptation to extreme environmental conditions and their original metabolic pathways, allowing the synthesis of unique biomolecules. Studies on archaeal carotenoids are still relatively scarce and only a few works have focused on their industrial scale production and their biotechnological and pharmacological properties, while the societal demand for these bioactive pigments is growing. This article aims to provide a comprehensive review of the current knowledge on carotenoid metabolism in Archaea and the potential applications of these pigments in biotechnology and medicine. After reviewing the ecology and classification of these microorganisms, as well as their unique cellular and biochemical characteristics, this paper highlights the most recent data concerning carotenoid metabolism in Archaea, the biological properties of these pigments, and biotechnological considerations for their production at industrial scale.


Assuntos
Archaea , Carotenoides , Archaea/metabolismo , Biotecnologia , Carotenoides/metabolismo , Pigmentação
12.
Int J Mol Sci ; 23(23)2022 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-36499134

RESUMO

The kingdom of plants as a "green biofabric" of valuable bioactive molecules has long been used in many ailments. Currently, extracts and pure compounds of plant origin are used to aid in pigmentation skin problems by influencing the process of melanogenesis. Melanin is a very important pigment that protects human skin against ultraviolet radiation and oxidative stress. It is produced by a complex process called melanogenesis. However, disturbances in the melanogenesis mechanism may increase or decrease the level of melanin and generate essential skin problems, such as hyperpigmentation and hypopigmentation. Accordingly, inhibitors or activators of pigment formation are desirable for medical and cosmetic industry. Such properties may be exhibited by molecules of plant origin. Therefore, that literature review presents reports on plant extracts, pure compounds and compositions that may modulate melanin production in living organisms. The potential of plants in the therapy of pigmentation disorders has been highlighted.


Assuntos
Hiperpigmentação , Hipopigmentação , Humanos , Raios Ultravioleta , Melaninas , Pigmentação da Pele , Hiperpigmentação/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Monofenol Mono-Oxigenase , Melanócitos
13.
Int J Mol Sci ; 23(19)2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36232954

RESUMO

Since cancer treatment by radio- and chemotherapy has been linked to safety concerns, there is a need for new and alternative anticancer drugs; as such, compounds isolated from plants represent promising candidates. The current study investigates the anticancer features of halimane (11R*,13E)-11-acetoxyhalima-5,13-dien-15-oic acid (HAL) and the labdane diterpenes 1α,6ß-diacetoxy-8α,13R*-epoxy-14-labden-11-one (PLEC) and forskolin-like 1:1 mixture of 1,6-di-O-acetylforskolin and 1,6-di-O-acetyl-9-deoxyforskolin (MRC) isolated from Plectranthus ornatus in MCF7 and FaDu cancer cell lines. Cytotoxicity was assessed by MTT assay, ROS production by Di-chloro-dihydro-fluorescein diacetate assay (DCFH) or Red Mitochondrial Superoxide Indicator (MitoSOX) and Mitochondrial Membrane Potential (MMP) by fluorescent probe JC-1 (5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide). In addition, the relative amounts of mitochondrial DNA (mtDNA) were determined using quantitative Real-Time-PCR (qRT-PCR) and damage to mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) by semi-long run quantitative Real-Time-PCR (SLR-qRT-PCR). Gene expression was determined using Reverse-Transcription-qPCR. Caspase-3/7 activity by fluorescence was assessed. Assessment of General In Vivo Toxicity has been determined by Brine Shrimp Lethality Bioassay. The studied HAL and PLEC were found to have a cytotoxic effect in MCF7 with IC50 = 13.61 µg/mL and IC50 = 17.49 µg/mL and in FaDu with IC50 = 15.12 µg/mL and IC50 = 32.66 µg/mL cancer cell lines. In the two tested cancer cell lines, the phytochemicals increased ROS production and mitochondrial damage in the ND1 and ND5 gene regions and reduced MMP (ΔΨm) and mitochondrial copy numbers. They also changed the expression of pro- and anti-apoptotic genes (Bax, Bcl-2, TP53, Cas-3, Cas-8, Cas-9, Apaf-1 and MCL-1). Studies demonstrated increase in caspase 3/7 activity in tested cancer cell lines. In addition, we showed no toxic effect in in vivo test for the compounds tested. The potential mechanism of action may have been associated with the induction of apoptosis in MCF7 and FaDu cancer cells via the mitochondrial pathway; however, further in vivo research is needed to understand the mechanisms of action and potential of these compounds.


Assuntos
Antineoplásicos , Diterpenos , Plectranthus , Antineoplásicos/farmacologia , Apoptose , Caspase 3/genética , Caspase 3/metabolismo , Linhagem Celular Tumoral , Colforsina/farmacologia , DNA Mitocondrial/metabolismo , Diterpenos/farmacologia , Corantes Fluorescentes/farmacologia , Iodetos , Potencial da Membrana Mitocondrial , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Compostos Fitoquímicos/metabolismo , Compostos Fitoquímicos/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Superóxidos , Proteína X Associada a bcl-2/metabolismo
14.
Molecules ; 27(14)2022 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-35889231

RESUMO

Plants are a rich source of secondary metabolites that exhibit numerous desired properties. The compounds may influence the biology of melanocytes, pigment cells that produce melanin, by modulating numerous signaling pathways, including cAMP/PKA, MAPKs and PI3K/AKT. Its downstream target is microphthalmia-associated transcription factor, responsible for the expression of the tyrosinase enzyme, which plays a major role in melanogenesis. Therefore, this literature review aims to provide insights related to melanogenesis modulation mechanisms of plant extracts and isolated plant compounds in B16 cells. Database searches were conducted using online-based library search instruments from 2012 to 2022, such as NCBI-PubMed and Google Scholar. Upregulation or downregulation of signaling pathways by phytochemicals can influence skin hypo- and hyperpigmentation by changing the level of melanin production, which may pose a significant cosmetic issue. Therefore, plant extracts or isolated plant compounds may be used in the therapy of pigmentation disorders.


Assuntos
Melaninas , Melanoma Experimental , Animais , Linhagem Celular Tumoral , Melanócitos/metabolismo , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/metabolismo , Monofenol Mono-Oxigenase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Extratos Vegetais/metabolismo , Extratos Vegetais/farmacologia
15.
Molecules ; 27(3)2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-35164060

RESUMO

In recent years, there has been a considerable increase in interest in the use of transgenic plants as sources of valuable secondary metabolites or recombinant proteins. This has been facilitated by the advent of genetic engineering technology with the possibility for direct modification of the expression of genes related to the biosynthesis of biologically active compounds. A wide range of research projects have yielded a number of efficient plant systems that produce specific secondary metabolites or recombinant proteins. Furthermore, the use of bioreactors allows production to be increased to industrial scales, which can quickly and cheaply deliver large amounts of material in a short time. The resulting plant production systems can function as small factories, and many of them that are targeted at a specific operation have been patented. This review paper summarizes the key research in the last ten years regarding the use of transgenic plants as small, green biofactories for the bioreactor-based production of secondary metabolites and recombinant proteins; it simultaneously examines the production of metabolites and recombinant proteins on an industrial scale and presents the current state of available patents in the field.


Assuntos
Reatores Biológicos , Biotecnologia , Indústrias , Plantas Geneticamente Modificadas/metabolismo , Técnicas de Cultura de Células/métodos , Proteínas Recombinantes/metabolismo
16.
Chem Biodivers ; 18(8): e2100455, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34185351

RESUMO

Betulinic acid, which is found in transgenic roots of Senna obtusifolia (L.) H.S.Irwin & Barneby, is a pentacyclic triterpene with distinctive pharmacological activities. In this study, we report the differences in the content of betulinic acid and selected anthraquinones in transgenic S. obtusifolia hairy roots with overexpression of the PgSS1 gene (SOPSS2 line) and in transformed hairy roots without this genetic construct (SOA41 line). Both hairy root lines grew in 10 L sprinkle bioreactor. Additionally, the extracts obtained from this plant material were used for biological tests. Our results demonstrated that the SOPSS2 hairy root cultures from the bioreactor showed an increase in the content of betulinic acid (38.125 mg/g DW), compared to the SOA41 hairy root line (4.213 mg/g DW). Biological studies have shown a cytotoxic and antiproliferative effect on U-87MG glioblastoma cells, and altering the level of apoptotic proteins (Bax, p53, Puma and Noxa). Antimicrobial properties were demonstrated for both tested extracts, with a stronger effect of SOPSS2 extract. Moreover, both extracts showed moderate antiviral properties on norovirus surrogates.


Assuntos
Modelos Biológicos , Triterpenos Pentacíclicos/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Senna/metabolismo , Antraquinonas/química , Antraquinonas/metabolismo , Antraquinonas/farmacologia , Apoptose/efeitos dos fármacos , Reatores Biológicos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Glucosiltransferases/genética , Glucosiltransferases/metabolismo , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Triterpenos Pentacíclicos/química , Triterpenos Pentacíclicos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raízes de Plantas/química , Raízes de Plantas/metabolismo , Plantas Geneticamente Modificadas/química , Senna/química , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo , Ácido Betulínico
17.
Int J Mol Sci ; 22(22)2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34830374

RESUMO

The plant kingdom is a rich source of secondary metabolites with numerous properties, including the potential to modify keratinocyte biology. Keratinocytes are important epithelial cells that play a protective role against various chemical, physical and biological stimuli, and participate in reactive oxygen scavenging and inflammation and wound healing processes. The epidermal cell response may be modulated by phytochemicals via changes in signal transduction pathways. Plant extracts and single secondary compounds can possess a high antioxidant capacity and may suppress reactive oxygen species release, inhibit pro-apoptotic proteins and apoptosis and activate antioxidant enzymes in keratinocytes. Moreover, selected plant extracts and single compounds also exhibit anti-inflammatory properties and exposure may result in limited production of adhesion molecules, pro-inflammatory cytokines and chemokines in keratinocytes. In addition, plant extracts and single compounds may promote keratinocyte motility and proliferation via the regulation of growth factor production and enhance wound healing. While such plant compounds may modulate keratinocyte functions, further in vitro and in vivo studies are needed on their mechanisms of action, and more specific toxicity and clinical studies are needed to ensure their effectiveness and safety for use on human skin.


Assuntos
Queratinócitos/efeitos dos fármacos , Compostos Fitoquímicos/uso terapêutico , Plantas/química , Cicatrização/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Compostos Fitoquímicos/química , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Metabolismo Secundário/efeitos dos fármacos
18.
Molecules ; 26(20)2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34684788

RESUMO

It is known that Senna obtusifolia has been used in medicine since ancient times due to the content of many valuable compounds with a pro-health effect. One of them is betulinic acid, which is a pentacyclic triterpene with antimalarial, antiviral, anti-inflammatory and anticancer properties. In this work, a continuation of our previous research, an attempt was made to increase the level of betulinic acid accumulation by the cultivation of transgenic hairy roots that overexpress the squalene synthase gene in a 10 L sprinkle bioreactor with methyl jasmonate elicitation. We present that the applied strategy allowed us to increase the content of betulinic acid in hairy root cultures to the level of 48 mg/g dry weight. The obtained plant extracts showed a stronger cytotoxic effect on the U87MG glioblastoma cell line than the roots grown without elicitors. Additionally, the induction of apoptosis, reduction of mitochondrial membrane potential, chromosomal DNA fragmentation and activation of caspase cascades are demonstrated. Moreover, the tested extract showed inhibition of topoisomerase I activity.


Assuntos
Acetatos/farmacologia , Antineoplásicos Fitogênicos/metabolismo , Ciclopentanos/farmacologia , Oxilipinas/farmacologia , Triterpenos Pentacíclicos/metabolismo , Senna/efeitos dos fármacos , Senna/metabolismo , Células A549 , Antineoplásicos Fitogênicos/biossíntese , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Reatores Biológicos , Biotecnologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA , Fragmentação do DNA/efeitos dos fármacos , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Triterpenos Pentacíclicos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Reguladores de Crescimento de Plantas/farmacologia , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Plantas Geneticamente Modificadas , Plantas Medicinais/efeitos dos fármacos , Plantas Medicinais/crescimento & desenvolvimento , Plantas Medicinais/metabolismo , Senna/crescimento & desenvolvimento , Ácido Betulínico
19.
Int J Mol Sci ; 21(24)2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33339446

RESUMO

The plant kingdom is a source of important therapeutic agents. Therefore, in this review, we focus on natural compounds that exhibit efficient anti-inflammatory activity via modulation signaling transduction pathways in macrophage cells. Both extracts and pure chemicals from different species and parts of plants such as leaves, roots, flowers, barks, rhizomes, and seeds rich in secondary metabolites from various groups such as terpenes or polyphenols were included. Selected extracts and phytochemicals control macrophages biology via modulation signaling molecules including NF-κB, MAPKs, AP-1, STAT1, STAT6, IRF-4, IRF-5, PPARγ, KLF4 and especially PI3K/AKT. Macrophages are important immune effector cells that take part in antigen presentation, phagocytosis, and immunomodulation. The M1 and M2 phenotypes are related to the production of pro- and anti-inflammatory agents, respectively. The successful resolution of inflammation mediated by M2, or failed resolution mediated by M1, may lead to tissue repair or chronic inflammation. Chronic inflammation is strictly related to several disorders. Thus, compounds of plant origin targeting inflammatory response may constitute promising therapeutic strategies.


Assuntos
Anti-Inflamatórios/farmacologia , Macrófagos/efeitos dos fármacos , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Transdução de Sinais , Macrófagos/imunologia , Fosfatidilinositol 3-Quinases/metabolismo , Plantas Medicinais , Proteínas Proto-Oncogênicas c-akt/metabolismo
20.
Int J Mol Sci ; 21(14)2020 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-32707732

RESUMO

The skin is an important organ that acts as a physical barrier to the outer environment. It is rich in immune cells such as keratinocytes, Langerhans cells, mast cells, and T cells, which provide the first line of defense mechanisms against numerous pathogens by activating both the innate and adaptive response. Cutaneous immunological processes may be stimulated or suppressed by numerous plant extracts via their immunomodulatory properties. Several plants are rich in bioactive molecules; many of these exert antimicrobial, antiviral, and antifungal effects. The present study describes the impact of plant extracts on the modulation of skin immunity, and their antimicrobial effects against selected skin invaders. Plant products remain valuable counterparts to modern pharmaceuticals and may be used to alleviate numerous skin disorders, including infected wounds, herpes, and tineas.


Assuntos
Anti-Infecciosos/administração & dosagem , Extratos Vegetais/administração & dosagem , Dermatopatias Infecciosas/tratamento farmacológico , Dermatopatias Infecciosas/microbiologia , Dermatomicoses/tratamento farmacológico , Dermatomicoses/imunologia , Dermatomicoses/microbiologia , Sinergismo Farmacológico , Humanos , Fatores Imunológicos/administração & dosagem , Plantas Medicinais/química , Pele/efeitos dos fármacos , Pele/imunologia , Pele/microbiologia , Dermatopatias Bacterianas/tratamento farmacológico , Dermatopatias Bacterianas/imunologia , Dermatopatias Bacterianas/microbiologia , Dermatopatias Infecciosas/imunologia , Viroses/tratamento farmacológico , Viroses/imunologia , Viroses/virologia
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