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1.
Biomed Pharmacother ; 174: 116516, 2024 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-38583339

RESUMEN

The Plectranthus genus is often cited for its medicinal properties. Plectranthus ornatus Codd. is traditionally used in Africa for the treatment of gastric and liver diseases and their leaves are used for their antibiotic action. The main constituent of P. ornatus is the halimane compound, 11 R∗-acetoxyhalima-5,13E-dien-15-oic acid (Hal), described for its antimicrobial and anticancer properties. The objective of this work was to improve the activity of the halimane lead molecule. Further physiochemical characterisation was performed on Hal. To the best of our knowledge, this work constitutes the first published data of the absolute configurations by SCXRD and thermal stability of Hal. Using Hal, reactions with different amines were carried out to afford novel semi-synthetic derivatives and their structural elucidation was completed. The cytotoxicity of the derivatives was assessed against three leukaemia cancer cell lines (CCRF-CEM, K562 and HL-60). The antioxidant activity was investigated using H2O2-induced HGF-1 cells and their anti-inflammatory activity was studied using RT-PCR and ELISA. Our data showed that amide derivatives of Hal presented moderate cytotoxicity and more potent activity when compared to the parent molecule, giving insight into the SAR of Hal. The derivatives also displayed protection against oxidative damage to DNA. Finally, the derivatives possessed anti-inflammatory properties at the level of gene and protein expression for the cytokines IL-1ß, TNF-α and IL-6, induced by LPS in normal HGF-1 cells. Overall, our study provides useful insight into the enhanced biological activities of semi-synthetic Hal derivatives, as a starting point for novel drug formulations in cancer therapy.

2.
Int J Mol Sci ; 25(5)2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38473970

RESUMEN

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.


Asunto(s)
Chamaecyparis , Chamaecyparis/fisiología , Árboles/fisiología , Japón , Antiinflamatorios , Asia
3.
Int J Mol Sci ; 25(2)2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38256118

RESUMEN

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.


Asunto(s)
Ácidos Cumáricos , Plectranthus , Humanos , Células A549 , Antibacterianos , Fitoquímicos
4.
Chem Biodivers ; 21(2): e202300494, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37983920

RESUMEN

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.


Asunto(s)
Dermatitis Fototóxica , Fármacos Fotosensibilizantes , Humanos , Animales , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Plantas
5.
Cancers (Basel) ; 15(22)2023 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-38001694

RESUMEN

Prostate cancer (PC) is the second most common type of cancer and the leading cause of death among men worldwide. Preventing the progression of cancer after treatments such as radical prostatectomy, radiation therapy, and hormone therapy is a major concern faced by prostate cancer patients. Inflammation, which can be caused by various factors such as infections, the microbiome, obesity and a high-fat diet, is considered to be the main cause of PC. Inflammatory cells are believed to play a crucial role in tumor progression. Therefore, nonsteroidal anti-inflammatory drugs along with their effects on the treatment of inflammation-related diseases, can prevent cancer and its progression by suppressing various inflammatory pathways. Recent evidence shows that nonsteroidal anti-inflammatory drugs are effective in the prevention and treatment of prostate cancer. In this review, we discuss the different pathways through which these drugs exert their potential preventive and therapeutic effects on prostate cancer.

6.
Int J Mol Sci ; 24(20)2023 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-37894959

RESUMEN

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.


Asunto(s)
Investigación Biomédica , Lamiaceae , Aceites Volátiles , Humanos , Aceites Volátiles/farmacología , Aceites Volátiles/uso terapéutico , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Nanotecnología
7.
Molecules ; 28(18)2023 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-37764326

RESUMEN

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.


Asunto(s)
Antioxidantes , Leonurus , Humanos , Antioxidantes/farmacología , Araquidonato 5-Lipooxigenasa , Ciclooxigenasa 2 , Peróxido de Hidrógeno , Simulación del Acoplamiento Molecular , Xantina Oxidasa , Flavonoides/farmacología , Rutina , Antiinflamatorios/farmacología , Ácido Clorogénico , Extractos Vegetales/farmacología
8.
Molecules ; 28(13)2023 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-37446611

RESUMEN

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.


Asunto(s)
Quitosano , Nanopartículas , Extractos Vegetales/farmacología , Ginkgo biloba
9.
Nutrients ; 15(13)2023 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-37447342

RESUMEN

Anthocyanins are flavonoid compounds that are abundantly present in fruits and vegetables. These compounds contribute to the color of these foods and offer various health benefits to consumers due to their biological properties. There are more than 1000 types of anthocyanins in nature, all derived from 27 anthocyanidin aglycones that have different glycosylations and acylations. Malvidin is one of the most well-known anthocyanidins. Several studies, including those conducted on cell lines, animals, and humans, have suggested that malvidin and its glycosides possess anti-carcinogenic, diabetes-control, cardiovascular-disease-prevention, and brain-function-improvement properties. These health benefits are primarily attributed to their antioxidant and anti-inflammatory effects, which are influenced by the molecular mechanisms related to the expression and modulation of critical genes. In this article, we review the available information on the biological activity of malvidin and its glycosides concerning their health-promoting effects.


Asunto(s)
Antocianinas , Glicósidos , Animales , Humanos , Antocianinas/farmacología , Antocianinas/metabolismo , Glicósidos/farmacología , Antioxidantes/farmacología , Antioxidantes/metabolismo , Antiinflamatorios/farmacología
10.
Genes (Basel) ; 14(6)2023 06 20.
Artículo en Inglés | MEDLINE | ID: mdl-37372475

RESUMEN

The inhibition of histone deacetylases (HDACs) holds promise as a potential anti-cancer therapy as histone and non-histone protein acetylation is frequently disrupted in cancer, leading to cancer initiation and progression. Additionally, the use of a histone deacetylase inhibitor (HDACi) such as the class I HDAC inhibitor-valproic acid (VPA) has been shown to enhance the effectiveness of DNA-damaging factors, such as cisplatin or radiation. In this study, we found that the use of VPA in combination with talazoparib (BMN-673-PARP1 inhibitor-PARPi) and/or Dacarbazine (DTIC-alkylating agent) resulted in an increased rate of DNA double strand breaks (DSBs) and reduced survival (while not affecting primary melanocytes) and the proliferation of melanoma cells. Furthermore, the pharmacological inhibition of class I HDACs sensitizes melanoma cells to apoptosis following exposure to DTIC and BMN-673. In addition, the inhibition of HDACs causes the sensitization of melanoma cells to DTIV and BMN-673 in melanoma xenografts in vivo. At the mRNA and protein level, the histone deacetylase inhibitor downregulated RAD51 and FANCD2. This study aims to demonstrate that combining an HDACi, alkylating agent and PARPi could potentially enhance the treatment of melanoma, which is commonly recognized as being among the most aggressive malignant tumors. The findings presented here point to a scenario in which HDACs, via enhancing the HR-dependent repair of DSBs created during the processing of DNA lesions, are essential nodes in the resistance of malignant melanoma cells to methylating agent-based therapies.


Asunto(s)
Antineoplásicos , Melanoma , Humanos , Inhibidores de Histona Desacetilasas/farmacología , Inhibidores de Histona Desacetilasas/uso terapéutico , Ácido Valproico/farmacología , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Dacarbazina/uso terapéutico , Histona Desacetilasas/genética , Histona Desacetilasas/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Melanoma/tratamiento farmacológico , Melanoma/genética , Melanoma/patología , ADN , Alquilantes/uso terapéutico
11.
Int J Mol Sci ; 24(6)2023 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-36982980

RESUMEN

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.


Asunto(s)
Interleucina-8 , Senna (Planta) , Humanos , Interleucina-8/metabolismo , Senna (Planta)/genética , Cicatrización de Heridas , Extractos Vegetales/uso terapéutico , Antiinflamatorios/farmacología , Antiinflamatorios/metabolismo , Interleucina-1/metabolismo , Raíces de Plantas/genética
12.
Artículo en Inglés | MEDLINE | ID: mdl-36981614

RESUMEN

Inflammation is closely related to asthma and its defining feature: airway remodeling. The aim of this study was to determine the effects of extracts of normal (NR) and transformed (TR) Leonotis nepetifolia roots on respiratory cells and against the gingival epithelium. Extracts from NR and TR roots were added to lung fibroblast, bronchial epithelial and gingival fibroblast cell lines, in the presence of HRV-16 infection, to determine their impact on inflammation. The expression of inflammatory cytokines (IL-6, IL-1ß, GM-CSF and MCAF) as well as total thiol contents were assessed. The TR extract inhibited rhinovirus-induced IL-6 and IL-1ß expression in all tested airway cells (p < 0.05). Additionally, the extract decreased GM-CSF expression in bronchial epithelial cells. The tested extracts had positive effects on total thiol content in all tested cell lines. The TR root extract demonstrated wound healing potential. While both tested extracts exhibited anti-inflammatory and antioxidative effects, they were stronger for the TR extract, possibly due to higher concentrations of beneficial metabolites such as phenols and flavonoids. Additionally, wound healing activity was demonstrated for the TR root extract. These results suggest that TR root extract may become a promising therapeutic agent in the future.


Asunto(s)
Citocinas , Lamiaceae , Humanos , Citocinas/metabolismo , Factor Estimulante de Colonias de Granulocitos y Macrófagos , Interleucina-6 , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Lamiaceae/metabolismo , Inflamación/tratamiento farmacológico
13.
J Clin Med ; 12(5)2023 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-36902820

RESUMEN

Inflammation is an etiological factor of various chronic diseases contributing to more than 50% of worldwide deaths. In this study, we focus on the immunosuppressive role of the programmed death-1 (PD-1) receptor and its ligand (PD-L1) in inflammatory-related diseases, including chronic rhinosinusitis and head and neck cancers. The study included 304 participants. Of this number, 162 patients had chronic rhinosinusitis with nasal polyps (CRSwNP), 40 patients had head and neck cancer (HNC) and there were 102 healthy subjects. The expression level of the PD-1 and PD-L1 genes in the tissues of the study groups was measured by qPCR and Western blot methods. The associations between the age of the patients and the extent of disease and genes' expression were evaluated. The study showed a significantly higher mRNA expression of PD-1 and PD-L1 in the tissues of both the CRSwNP and HNC patient groups compared to the healthy group. The severity of CRSwNP significantly correlated with the mRNA expression of PD-1 and PD-L1. Similarly, the age of the NHC patients influenced PD-L1 expression. In addition, a significantly higher level of PD-L1 protein was noticed also for both the CRSwNP and HNC patient groups. The increased expression of PD-1 and PD-L1 may be a potential biomarker of inflammatory-related diseases, including chronic rhinosinusitis and head and neck cancers.

14.
Cancers (Basel) ; 16(1)2023 Dec 25.
Artículo en Inglés | MEDLINE | ID: mdl-38201542

RESUMEN

The number of cancer cases will reach 24 million in 2040, according to the International Agency for Research on Cancer. Current treatments for cancer are not effective and selective for most patients; for this reason, new anticancer drugs need to be developed and researched enough. There are potentially useful drugs for cancer isolated from plants that are being used in the clinic. Available information about phytochemistry, traditional uses, in vitro and in vivo experiments with plants, and pure compounds isolated from the Euphorbiaceae family indicates that this family of plants has the potential to develop anticancer drugs. This review examines selected species from the Euphorbiaceae family and their bioactive compounds that could have potential against different types of cancer cells. It reviews the activity of crude extracts, isolated compounds, and nanoparticles and the potential underlying mechanisms of action.

15.
Int J Mol Sci ; 23(23)2022 Nov 26.
Artículo en Inglés | MEDLINE | ID: mdl-36499134

RESUMEN

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.


Asunto(s)
Hiperpigmentación , Hipopigmentación , Humanos , Rayos Ultravioleta , Melaninas , Pigmentación de la Piel , Hiperpigmentación/tratamiento farmacológico , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Monofenol Monooxigenasa , Melanocitos
16.
Cells ; 11(20)2022 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-36291112

RESUMEN

Plectranthus ornatus Codd, the genus Plectranthus of the Lamiaceae family, has been used as traditional medicine in Africa, India and Australia. Pharmacological studies show the use of this plant to treat digestive problems. In turn, leaves were used for their antibiotic properties in some regions of Brazil to treat skin infections. The present study examines the anti-inflammatory, antioxidant and cytotoxic effects of the halimane and labdane diterpenes (11R*,13E)-11-acetoxyhalima-5,13-dien-15-oic acid (HAL) and 1α,6ß-diacetoxy-8α,13R*-epoxy-14-labden-11-one (PLEC) and the forskolin-like 1:1 mixture of 1,6-di-O-acetylforskolin and 1,6-di-O-acetyl-9-deoxyforskolin (MRC) isolated from P. ornatus on lung (A549) and leukemia (CCRF-CEM) cancer cell lines, and on normal human retinal pigment epithelial (ARPE-19) cell line in vitro. Additionally, molecular docking and computational approaches were used. ADMET properties were analysed through SwissADME and proTox-II-Prediction. The results indicate that all tested compounds significantly reduced the viability of the cancer cells and demonstrated no cytotoxic effects against the non-neoplastic cell line. The apoptosis indicators showed increased ROS levels for both the tested A549 and CCRF-CEM cancer cell lines after treatment. Furthermore, computational studies found HAL to exhibit moderate antioxidant activity. In addition, selected compounds changed mitochondrial membrane potential (MMP), and increased DNA damage and mitochondrial copy number for the CCRF-CEM cancer cell line; they also demonstrated anti-inflammatory effects on the ARPE-19 normal cell line upon lipopolysaccharide (LPS) treatment, which was associated with the modulation of IL-6, IL-8, TNF-α and GM-CSF genes expression. Docking studies gave indication about the lowest binding energy for 1,6-di-O-acetylforskolin docked into IL-6, TNF-α and GM-CSF, and 1,6-di-O-acetyl-9-deoxyforskolin docked into IL-8. The ADMET studies showed drug-likeness properties for the studied compounds. Thus, halimane and labdane diterpenes isolated from P. ornatus appear to offer biological potential; however, further research is necessary to understand their interactions and beneficial properties.


Asunto(s)
Diterpenos , Plectranthus , Humanos , Antibacterianos/farmacología , Antiinflamatorios/farmacología , Antiinflamatorios/metabolismo , Antioxidantes/metabolismo , Colforsina , Diterpenos/química , Diterpenos/aislamiento & purificación , Diterpenos/farmacología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Lipopolisacáridos/metabolismo , Simulación del Acoplamiento Molecular , Plectranthus/química , Plectranthus/metabolismo , Protoporfirinógeno-Oxidasa/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Pigmentos Retinianos/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
17.
Int J Mol Sci ; 23(19)2022 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-36232954

RESUMEN

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.


Asunto(s)
Antineoplásicos , Diterpenos , Plectranthus , Antineoplásicos/farmacología , Apoptosis , Caspasa 3/genética , Caspasa 3/metabolismo , Línea Celular Tumoral , Colforsina/farmacología , ADN Mitocondrial/metabolismo , Diterpenos/farmacología , Colorantes Fluorescentes/farmacología , Yoduros , Potencial de la Membrana Mitocondrial , Proteína 1 de la Secuencia de Leucemia de Células Mieloides/metabolismo , Fitoquímicos/metabolismo , Fitoquímicos/farmacología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Superóxidos , Proteína X Asociada a bcl-2/metabolismo
18.
Mar Drugs ; 20(8)2022 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-36005527

RESUMEN

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.


Asunto(s)
Archaea , Carotenoides , Archaea/metabolismo , Biotecnología , Carotenoides/metabolismo , Pigmentación
19.
Molecules ; 27(14)2022 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-35889231

RESUMEN

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.


Asunto(s)
Melaninas , Melanoma Experimental , Animales , Línea Celular Tumoral , Melanocitos/metabolismo , Melanoma Experimental/tratamiento farmacológico , Melanoma Experimental/metabolismo , Monofenol Monooxigenasa/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Extractos Vegetales/metabolismo , Extractos Vegetales/farmacología
20.
Cancers (Basel) ; 14(6)2022 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-35326606

RESUMEN

Many of the anticancer agents that are currently in use demonstrate severe side effects and encounter increasing resistance from the target cancer cells. Thus, despite significant advances in cancer therapy in recent decades, there is still a need to discover and develop new, alternative anticancer agents. The plant kingdom contains a range of phytochemicals that play important roles in the prevention and treatment of many diseases. The Solanaceae family is widely used in the treatment of various diseases, including cancer, due to its bioactive ingredient content. The purpose of this literature review is to highlight the antitumour activity of Solanaceae extracts-single isolated compounds and nanoparticles with extracts-and their synergistic effect with chemotherapeutic agents in various in vitro and in vivo cancer models. In addition, the biological properties of many plants of the Solanaceae family have not yet been investigated, which represents a challenge and an opportunity for future anticancer therapy.

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