ABSTRACT
The new flavonoid (-)-4'-O-methylepicatechin 5-O-ß-D-glucopyranoside (1), along with four known triterpenes (2-5), a steroid (6), and a flavonoid (7) were isolated from the ethyl acetate extract of Maytenus quadrangulata leaves. The chemical structures of the isolated compounds were determined through analysis of 1D NMR (1H and 13C) spectroscopic data, in addition to 2D NMR and spectrometric (MS) data for compound 1. This is the first report of the isolation of daucosterol (6) and (-)-4'-O-methylepigallocatechin (7) from this species. Compounds 1 and 7 were evaluated against the bacteria Staphylococcus aureus and Klebsiella pneumoniae, but neither exhibited activity even at the highest concentration tested.
Subject(s)
Acetates , Anti-Bacterial Agents , Flavonoids , Klebsiella pneumoniae , Microbial Sensitivity Tests , Plant Extracts , Plant Leaves , Staphylococcus aureus , Triterpenes , Plant Leaves/chemistry , Triterpenes/chemistry , Triterpenes/isolation & purification , Triterpenes/pharmacology , Flavonoids/isolation & purification , Flavonoids/chemistry , Flavonoids/pharmacology , Staphylococcus aureus/drug effects , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Klebsiella pneumoniae/drug effects , Acetates/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/chemistry , Maytenus/chemistry , Molecular StructureABSTRACT
Two new triterpenes mayteneri A (1), mayteneri B (2), and seven known compounds (3-9) were isolated from stems of Maytenus hookeri Loes. The chemical structures of compounds 1 and 2 were established by 1D, 2D NMR, HRESIMS analysis, and calculating electronic circular dichroism (ECD). The structures of known compounds 3-9 were determined by comparison of their spectral with those reported. Compounds 4-7 showed significant inhibitory activity for NLRP3 inflammasome, with the IC50 values of 2.36-3.44 µM.
Subject(s)
Maytenus , Oleanolic Acid , Molecular Structure , Oleanolic Acid/chemistry , Oleanolic Acid/analogs & derivatives , Oleanolic Acid/isolation & purification , Oleanolic Acid/pharmacology , Maytenus/chemistry , Triterpenes/chemistry , Triterpenes/pharmacology , Triterpenes/isolation & purification , Plant Stems/chemistry , Animals , Mice , Inflammasomes/drug effects , NLR Family, Pyrin Domain-Containing 3 Protein/antagonists & inhibitorsABSTRACT
BACKGROUND: The emergence of resistance to artemisinin-based combination therapy necessitates the search for new, more potent antiplasmodial compounds, including herbal remedies. The whole extract of Maytenus senegalensis has been scientifically investigated for potential biological activities both in vitro and in vivo, demonstrating strong antimalarial activity. However, there is a lack of data on the electrocardiographic effects of M. senegalensis in humans, which is a crucial aspect in the investigation of malaria treatment. Assessing the electrocardiographic effects of M. senegalensis is essential, as many anti-malarial drugs can inadvertently prolong the QT interval on electrocardiograms. Therefore, the study's objective was to evaluate the electrocardiographic effects of M. senegalensis in healthy adult volunteers. METHODS: This study is a secondary analysis of an open-label single-arm dose escalation. Twelve healthy eligible Tanzanian males, aged 18 to 45, were enrolled in four study dose groups. A single 12-lead electrocardiogram (ECG) was performed at baseline and on days 3, 7, 14, 28, and 56. RESULTS: No QTcF adverse events occurred with any drug dose. Only one volunteer who received the highest dose (800 mg) of M. senegalensis experienced a moderate transient change (â³QTcF > 30 ms; specifically, the value was 37 ms) from baseline on day 28. There was no difference in maximum QTcF and maximum â³QTcF between volunteers in all four study dose groups. CONCLUSIONS: A four-day regimen of 800 mg every 8 h of M. senegalensis did not impact the electrocardiographic parameters in healthy volunteers. This study suggests that M. senegalensis could be a valuable addition to malaria treatment, providing a safer alternative and potentially aiding in the battle against artemisinin-resistant malaria. The results of this study support both the traditional use and the modern therapeutic potential of M. senegalensis. They also set the stage for future research involving larger and more diverse populations to explore the safety profile of M. senegalensis in different demographic groups. This is especially important considering the potential use of M. senegalensis as a therapeutic agent and its widespread utilization as traditional medicine. Trial registration ClinicalTrials.gov, NCT04944966. Registered 30 June 2021-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04944966?term=kamaka&draw=2&rank=1.
Subject(s)
Antimalarials , Artemisinins , Malaria , Maytenus , Adult , Humans , Male , Antimalarials/pharmacology , Electrocardiography , Healthy Volunteers , Malaria/drug therapy , Tanzania , Volunteers , Young Adult , Middle AgedABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Monteverdia ilicifolia (Maytenus ilicifolia, Celastraceae), known as "espinheira-santa", has been widely used in Brazil to manage mainly gastrointestinal diseases. This species has been listed in the Brazilian Pharmacopeia and in the National List of Essential Medicines (RENAME). Considering that clinical studies about M. ilicifolia are rare, our group has been performing a broader project designed to evaluate the efficacy of M. ilicifolia capsules in a clinical trial, for this reason, approaches to provide safety to those patients are relevant. AIM OF THE STUDY: We aimed to investigate the potential pharmacokinetic interaction and hepatotoxicity and intestinal toxicity of an aqueous extract of M. ilicifolia and its main phytocompounds, catequin, epicatequin, and quercetin. METHODS AND MATERIALS: Slices of liver and intestine of Wistar rats were incubated with different concentrations of M. ilicifolia extract or isolated compounds (catechin, epicatechin and quercetin). Commercial kits were used to evaluate enzyme activities of CYP2D6 and CYP3A4 isoforms, as well as cell viability (MTT) assay and intracellular enzymes leakage, specifically lactate dehydrogenase (LDH), alkaline phosphatase (AP), aspartate aminotransferase (AST), alanine aminotransferase (ALT) were studied. RESULTS: Incubation with M. ilicifolia extract, catechin, epicatechin and quercetin did not affect significantly any evaluated parameter in intestines. The intracellular enzymes leakages, CYP2D6, LDH and AST, were increased with M. ilicifolia extract and quercetin in liver slices. CONCLUSIONS: Our in vitro findings highlighted, for the first time, the potential hepatotoxicity induced by an aqueous extract of M. ilicifolia, consequently this species and its products should be avoided in liver diseases, supporting that studies of safety must be performed including in the context of traditional medicinal plants.
Subject(s)
Catechin , Celastraceae , Chemical and Drug Induced Liver Injury , Maytenus , Plants, Medicinal , Humans , Rats , Animals , Brazil , Plant Extracts/toxicity , Quercetin , Cytochrome P-450 CYP2D6 , Rats, WistarABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Maytenus ilicifolia Mart. ex Reissek, a medicinal plant used for treating gastritis, ulcers, and gastric disorders, possesses therapeutic properties attributed to diverse leaf compounds-terpenoids, alkaloids, flavonoids, phenols, and tannins, reflecting the ethnopharmacological knowledge of traditional users. AIMS OF THE STUDY: We aimed to assess the antioxidant and antiglycant capacities of Maytenus ilicifolia's ethanolic extract and organic fractions, identify bioactive compounds through HPLC-MS/MS analysis, and conduct phytochemical assessments. We also assessed their potential to inhibit digestive and cholinesterase enzymes, mitigate oxidation of human LDL and rat hepatic tissue, and examine their antimicrobial and cytotoxic properties. MATERIALS AND METHODS: Organic fractions (hexane - HF-Mi, dichloromethane - DMF-Mi, ethyl acetate - EAF-Mi, n-butanol - BF-Mi, and hydromethanolic - HMF-Mi) were obtained via liquid-liquid partitioning. Antioxidant (DPPH, FRAP, ORAC) and antiglycant (BSA/FRU, BSA/MGO, ARG/MGO/LDL/MGO models) capacities were tested. Phytochemical analysis employed HPLC-MS/MS. We also studied the inhibitory effects on α-amylase, acetylcholinesterase, butyrylcholinesterase, human LDL and rat hepatic tissue oxidation, antimicrobial activity, and cytotoxicity against RAW 264.7 macrophages. RESULTS: HPLC-ESI-MS/MS identified antioxidant compounds such as catechin, quercetin, and kaempferol derivatives. Ethanolic extract (EE-Mi) and organic fractions demonstrated robust antioxidant and antiglycant activity. EAF-Mi and BF-Mi inhibited α-amylase (2.42 µg/mL and 7.95 µg/mL) compared to acarbose (0.144 µg/mL). Most organic fractions exhibited â¼50% inhibition of acetylcholinesterase and butyrylcholinesterase, rivaling galantamine and rivastigmine. EAF-Mi, BF-Mi, and EE-Mi excelled in inhibiting lipid peroxidation. All fractions, except HMF-Mi, effectively countered LDL oxidation, evidenced by the area under the curve. These fractions protected LDL against lipid peroxidation. CONCLUSION: This study unveils Maytenus ilicifolia's ethanolic extract and organic fractions properties. Through rigorous analysis, we identify bioactive compounds and highlight their antioxidant, antiglycant, enzyme inhibition, and protective properties against oxidative damage. These findings underline its significance in modern pharmacology and its potential applications in healthcare.
Subject(s)
Anti-Infective Agents , Celastraceae , Maytenus , Humans , Animals , Rats , Lipid Peroxidation , Acetylcholinesterase , Butyrylcholinesterase , Antioxidants/pharmacology , Maillard Reaction , Magnesium Oxide , Tandem Mass Spectrometry , Phytochemicals , alpha-Amylases , Plant Extracts/pharmacologyABSTRACT
Eleven densely functionalized new dihydro-ß-agarofuran sesquiterpenoid derivatives, named maytenoids A-K (1-11), as well as one known analog, were isolated and characterized from Maytenus austroyunnanensis. Their structures were assigned based on analysis of spectroscopic data and X-ray crystallography. Compounds 1-9 are macrocyclic sesquiterpene pyridine alkaloids generated by the respective acylation of the hydroxy groups at C-3 and C-13 of dihydro-ß-agarofuran sesquiterpenoids via diverse pyridine dicarboxylic acids. Compounds 1, 2, 5-10, and 12 exhibited significant inhibitory effects on NO production at 10 µM in lipopolysaccharide (LPS)-stimulated BV2 cells.
Subject(s)
Alkaloids , Maytenus , Sesquiterpenes , Maytenus/chemistry , Molecular Structure , Alkaloids/pharmacology , Alkaloids/chemistry , Sesquiterpenes/pharmacology , Sesquiterpenes/chemistry , Pyridines/chemistryABSTRACT
Maytenus dhofarensis Sebsebe (Celestraceae) is a naturally growing shrub in Oman. It is not a reputed medicinal plant in Oman, but it is regionally endemic and causes shivering attacks on goats that graze on it. The chemical investigation of the hexane and chloroform extracts of the fruits and stems of M. dhofarensis afforded dihydro-ß-agarofuran-type sesquiterpene pyridine alkaloid (1), lupanyl myristoate (2) and lignanolactone (3). Compounds (1-3) are new isolates from M. dhofarensis. The structures of these compounds were assigned through comprehensive IR, NMR, and ESI-MS analyses, and the relative configurations of compounds 1 and 3 were deduced from density function theory (DFT) calculations and NMR experiments. Compound 1 was assayed against the kinase enzyme and showed no inhibition activity for p38 alpha and delta at a 10 µM test concentration. Compound 3 inhibited the 2,2'-diphenyl-1-picrylhydrazyl radical (DPPH) by 69.5%, compared to 70.9% and 78.0% for gallic acid and butylated hydroxyanisole, respectively, which were used as positive controls.
Subject(s)
Maytenus , Animals , Biological Assay , Butylated Hydroxyanisole , Chloroform , Fruit , GoatsABSTRACT
The leaves of Monteverdia ilicifolia (syn. Maytenus ilicifolia), commonly called espinheira-santa, are widely used in South American traditional medicines to treat gastritis and ulcers. Several products labeled as espinheira-santa are sold as dietary supplements in retail stores and via e-commerce. Many different species with similar leaf morphology are often mistaken for Monteverdia ilicifolia and used as espinheira-santa, including Monteverdia aquifolia (Celastraceae), Citronella gongonha (Cardiopteridaceae), Jodina rhombifolia (Santalaceae), Sorocea bonplandii (Moraceae), and Zollernia ilicifolia (Fabaceae). This study aimed to characterize M. ilicifolia and distinguish it from adulterants using morphological and microscopic techniques. In addition, foreign matter and powder characteristics of botanical materials sold as "espinheira-santa" were analyzed. The morphoanatomical studies of the leaves and stems of M. ilicifolia and its five adulterant species have revealed noteworthy features that can help species identification and quality control of commercial espinheira-santa. This study showed that many commercial espinheira-santa materials were adulterated and of inferior quality.
Subject(s)
Celastraceae , Maytenus , Brazil , Microscopy , Quality Control , Plant ExtractsABSTRACT
The relationship between oxidative stress and inflammation is well known, and exogenous antioxidants, primarily phytochemical natural products, may assist the body's endogenous defense systems in preventing diseases due to excessive inflammation. In this study, we evaluated the antioxidant properties of ethnomedicines from Peru that exhibit anti-inflammatory activity by measuring the superoxide scavenging activity of ethanol extracts of Maytenus octogona aerial parts using hydrodynamic voltammetry at a rotating ring-disk electrode (RRDE). The chemical compositions of these extracts are known and the interactions of three methide-quinone compounds found in Maytenus octogona with caspase-1 were analyzed using computational docking studies. Caspase-1 is a critical enzyme triggered during the activation of the inflammasome and its actions are associated with excessive release of cytokines. The most important amino acid involved in active site caspase-1 inhibition is Arg341 and, through docking calculations, we see that this amino acid is stabilized by interactions with the three potential methide-quinone Maytenus octogona inhibitors, hydroxytingenone, tingenone, and pristimerin. These findings were also confirmed after more rigorous molecular dynamics calculations. It is worth noting that, in these three compounds, the methide-quinone carbonyl oxygen is the preferred hydrogen bond acceptor site, although tingenone's other carbonyl group also shows a similar binding energy preference. The results of these calculations and cyclovoltammetry studies support the effectiveness and use of anti-inflammatory ethnopharmacological ethanol extract of Maytenus octogona (L'Héritier) DC.
Subject(s)
Maytenus , Superoxides , Maytenus/chemistry , Caspase 1 , Plant Extracts/pharmacology , Plant Extracts/chemistry , Antioxidants/pharmacology , Quinones , Anti-Inflammatory Agents/pharmacology , Inflammation , EthanolABSTRACT
The objective of this work was to identify and classify the plants species designated as medicinal by the population of Taboco in different categories of use and investigate the specie with higher value of use with medicinal potential in experimental models. The field research took place between June and November 2018, with periodic visits to the Taboco Village, Brazil. The community makes use of a diversity of native, cultivated and domesticated species, corresponding to 89 plant species, belonging to 44 families, for cure or prevention over 60 types of health problems. The species Maytenus ilicifolia, with the highest use value was evaluated in experimental models. In this treatment a higher keratin production, reconstitution of the epithelium and the structured dermis was observed, with thick collagen fibers rich in fibroblasts, which favored the healing of exposed wounds.
El objetivo de este trabajo fue identificar y clasificar las especies de plantas designadas como medicinales por la población de Taboco en diferentes categorías de uso e investigar la especie con mayor valor de uso con potencial medicinal en modelos experimentales. La investigación de campo se llevó a cabo entre junio y noviembre de 2018, con visitas periódicas a Villa de Taboco, Brasil. La comunidad hace uso de una diversidad de especies nativas, cultivadas y domesticadas, correspondientes a 89 especies vegetales, pertenecientes a 44 familias, para la curación o prevención de más de 60 tipos de problemas de salud. La especie Maytenus ilicifolia, con mayor valor de uso, fue evaluada en modelos experimentales. En este tratamiento se observó una mayor producción de queratina, reconstitución del epitelio y de la dermis estructurada, con espesas fibras de colágenoricas en fibroblastos, lo que favoreció la cicatrización de las heridas expuestas.
Subject(s)
Plants, Medicinal , Ethnobotany , Wound Healing , Brazil , Maytenus/chemistry , Medicine, TraditionalABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Mayaro virus (MAYV) is an arbovirus endemic to the Amazon region, which comprises the states of the North and Midwest region of Brazil and encompasses the largest tropical forest in the world, the Amazon Forest. The confirmation of its potential transmission by Aedes aegypti and recent cases in Brazil, mainly in large centers in the northern region, led to the classification of Mayaro fever as an emerging disease. Traditional medicine is commonly used to treat various diseases, mainly by local riverside populations. Some species of the genus Maytenus, which have similar morphologies, are popularly used to treat infections and inflammations. In this context, our research group has studied and confirmed the antiviral activity of several plant-derived compounds. However, several species of this same genus have not been studied and therefore deserve attention. AIM OF THE STUDY: This study aimed to demonstrate the effects of ethyl acetate extracts of leaves (LAE) and branches (TAE) of Maytenus quadrangulata against MAYV. MATERIALS AND METHODS: Mammalian cells (Vero cells) were used to evaluate the cytotoxicity of the extracts. After cell infection by MAYV and the treatment with the extracts, we evaluated the selectivity index (SI), the virucidal effect, viral adsorption and internalization, and the effect on viral gene expression. The antiviral action was confirmed by quantifying the viral genome using RT-qPCR and by analyzing the effect on virus yield in infected cells. The treatment was performed based on the effective concentration protective for 50% of the infected cells (EC50). RESULTS: The leaves (LAE; EC50 12.0 µg/mL) and branches (TAE; EC50 101.0 µg/mL) extracts showed significative selectivity against the virus, with SI values of 79.21 and 9.91, respectively, which were considered safe. Phytochemical analysis revealed that the antiviral action was associated with the presence of catechins, mainly in LAE. This extract was chosen for the subsequent studies since it reduced the viral cytopathic effect and virus production, even at high viral loads [MOI (multiplicity of infection) 1 and 5]. The effects of LAE resulted in a marked reduction in viral gene expression. The viral title was drastically reduced when LAE was added to the virus before infection or during replication stages, reducing virus production up to 5-log units compared to infected and untreated cells. CONCLUSION: Through kinetic replication, MAYV was not detected in Vero cells treated with LAE throughout the viral cycle. The virucidal effect of LAE inactivates the viral particle and can intercept the virus at the end of the cycle when it gains the extracellular environment. Therefore, LAE is a promising source of antiviral agents.
Subject(s)
Alphavirus , Catechin , Maytenus , Animals , Chlorocebus aethiops , Antiviral Agents/pharmacology , Antiviral Agents/chemistry , Catechin/pharmacology , Vero Cells , Alphavirus/genetics , MammalsABSTRACT
Two new triterpenes, 3ß, 7ß-dihydroxyolean-12-en-11-one (1) and 3ß-O-acetyl-7ß-hydroxyolean-12-en-11-one (2), along with four known triterpenes 3ß-hydroxyolean-12-en-11-one (3), ß-amyrin (4), lup-20(29)-ene-1ß, 3ß-diol (5) and 1ß, 3ß-dihydroxy-urs-9(11)-12-diene (6), were isolated from the stems and leaves of Maytenus guangxiensis C. Y. Cheng et W. L. Sha. Their structures were elucidated using 1D and 2D NMR spectroscopy as well as MS and IR experiments. Compounds (3-6) were isolated from M. guangxiensis for the first time. Compounds 1-6 were evaluated for their antiproliferative activities against Eca-109, PANC-1, EJ and HeLa cell lines. The results showed that compounds 1-6 displayed a certain degree of inhibitory effects against the proliferation of various human cancer cell lines.
Subject(s)
Maytenus , Triterpenes , Humans , Triterpenes/chemistry , Maytenus/chemistry , HeLa Cells , Plant Leaves/chemistry , Magnetic Resonance Spectroscopy , Molecular StructureABSTRACT
Due to the widespread use of Maytenus ilicifolia leaves in the treatment of gastric ulcers, herbal medicines derived from such species are distributed by the national health system in Brazil. A related species, Maytenus aquifolium, is also used for the same disorders, and both are popularly known as Espinheira-santa. Due to their popular use, the quality and efficiency of the herbal medicines derived from these species is an important public health issue. The purpose of this study was to develop and test an analytical method that could quantify the content of catechin and epicatechin in dry Maytenus spp. leaves and simultaneously obtain their chemical profile to determine authenticity of the leaf samples. Ultra-high performance liquid chromatography coupled to mass spectrometry (UHPLC-MS) was used to quantify these isomers, in the selected ion monitoring (SIM) mode, while simultaneously analyzing the extract in full-scan mode. This approach was successfully applied to the analysis of commercial and authentic samples of Maytenus spp. Fewer than half the samples presented the minimum epicatechin content of 2.8 mg per g of dry leaf mass, as specified in the 6th Brazilian Pharmacopoeia (2019) for M. ilicifolia. Furthermore, by using untargeted metabolomics, it was observed that the chemical profile of most the samples was not compatible with M. ilicifolia leaves, indicating the need for stricter quality control of this material. The method described herein could be used for this control; moreover, its concept could be adapted and used for an ample variety of medicinal plant products.
Subject(s)
Catechin , Maytenus , Plants, Medicinal , Chromatography, High Pressure Liquid/methods , Mass Spectrometry , Maytenus/chemistry , Plant Extracts/chemistryABSTRACT
Free (epi) catechin, quercetin, (epi) gallocatechin, flavonol glycosides and condensed tannins were identified according to their molecular mass, characteristic product ions and retention times in extracts obtained from leaves and branches of Maytenus ilicifolia (Congorosa) by mass spectrometry. The in vitro anthelmintic activity against cattle gastrointestinal nematodes of Congorosa extract was determined using the Egg Hatch Inhibition Assay. Additionally, commercial quercetin, gallocatechin and epicatechin were evaluated. Although total phenolics, total tannins and condensed tannins contents were lower in branches extract than in leaves extract, the EC50 were 0.065 mg/mL and 0.890 mg/mL for branches and leaves extract, respectively. Moreover, the use of polyvinylpyrrolidone as a blocking agent of tannins, did not change significantly the EC50 for branches extract, but significantly changed for leaves extract. Quercetin and gallocatechin EC50 values were in the range 0.03-0.05 mg/mL and epicatechin showed 100% inhibition of the egg hatching process at 0.004 mg/mL.
Subject(s)
Anthelmintics , Catechin , Maytenus , Proanthocyanidins , Animals , Anthelmintics/pharmacology , Catechin/analysis , Cattle , Maytenus/chemistry , Phenols/analysis , Phenols/pharmacology , Plant Extracts/chemistry , Plant Leaves/chemistry , Proanthocyanidins/analysis , Quercetin/analysis , Quercetin/pharmacology , Tannins/analysisABSTRACT
Friedelin, a pentacyclic triterpene found in the leaves of the Celastraceae species, demonstrates numerous biological activities and is a precursor of quinonemethide triterpenes, which are promising antitumoral agents. Friedelin is biosynthesized from the cyclization of 2,3-oxidosqualene, involving a series of rearrangements to form a ketone by deprotonation of the hydroxylated intermediate, without the aid of an oxidoreductase enzyme. Mutagenesis studies among oxidosqualene cyclases (OSCs) have demonstrated the influence of amino acid residues on rearrangements during substrate cyclization: loss of catalytic activity, stabilization, rearrangement control or specificity changing. In the present study, friedelin synthase from Maytenus ilicifolia (Celastraceae) was expressed heterologously in Saccharomyces cerevisiae. Site-directed mutagenesis studies were performed by replacing phenylalanine with tryptophan at position 473 (Phe473Trp), methionine with serine at position 549 (Met549Ser) and leucine with phenylalanine at position 552 (Leu552Phe). Mutation Phe473Trp led to a total loss of function; mutants Met549Ser and Leu552Phe interfered with the enzyme specificity leading to enhanced friedelin production, in addition to α-amyrin and ß-amyrin. Hence, these data showed that methionine 549 and leucine 552 are important residues for the function of this synthase.
Subject(s)
Alkyl and Aryl Transferases/metabolism , Maytenus/enzymology , Plant Proteins/metabolism , Triterpenes/metabolism , Alkyl and Aryl Transferases/chemistry , Alkyl and Aryl Transferases/genetics , Amino Acid Substitution , Biosynthetic Pathways , Cyclization , Genes, Plant , Leucine/chemistry , Maytenus/genetics , Methionine/chemistry , Models, Molecular , Mutagenesis, Site-Directed , Oleanolic Acid/analogs & derivatives , Oleanolic Acid/biosynthesis , Pentacyclic Triterpenes/metabolism , Plant Proteins/chemistry , Plant Proteins/genetics , Protein Structure, Secondary , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Substrate SpecificityABSTRACT
The genus Maytenus is a member of the Celastraceae family, of which several species have long been used in traditional medicine. Between 1976 and 2021, nearly 270 new compounds have been isolated and elucidated from the genus Maytenus. Among these, maytansine and its homologues are extremely rare in nature. Owing to its unique skeleton and remarkable bioactivities, maytansine has attracted many synthetic endeavors in order to construct its core structure. In this paper, the current status of the past 45 years of research on Maytenus, with respect to its chemical and biological activities are discussed. The chemical research includes its structural classification into triterpenoids, sesquiterpenes and alkaloids, along with several chemical synthesis methods of maytansine or maytansine fragments. The biological activity research includes activities, such as anti-tumor, anti-bacterial and anti-inflammatory activities, as well as HIV inhibition, which can provide a theoretical basis for the better development and utilization of the Maytenus.
Subject(s)
Alkaloids/chemistry , Maytansine/analogs & derivatives , Maytenus/chemistry , Phytochemicals/chemistry , Sesquiterpenes/chemistry , Triterpenes/chemistry , Alkaloids/classification , Alkaloids/isolation & purification , Alkaloids/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/pharmacology , Anti-HIV Agents/chemistry , Anti-HIV Agents/isolation & purification , Anti-HIV Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Anti-Inflammatory Agents/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Humans , Maytansine/isolation & purification , Maytansine/pharmacology , Maytenus/metabolism , Molecular Structure , Phytochemicals/classification , Phytochemicals/isolation & purification , Phytochemicals/pharmacology , Plants, Medicinal , Sesquiterpenes/classification , Sesquiterpenes/isolation & purification , Sesquiterpenes/pharmacology , Structure-Activity Relationship , Triterpenes/classification , Triterpenes/isolation & purification , Triterpenes/pharmacologyABSTRACT
Leaves of Monteverdia ilicifolia ("espinheira-santa") are considered a medicinal tea by the Brazilian Sanitary Surveillance Agency (Anvisa), by their anti-dyspeptic, anti-acid and protective of the gastric mucosa properties. Their spiny margins are similar to those of other botanical species, which may lead to misidentifications. The aim of this work was to evaluate the authenticity of 32 samples of herbal drugs commercialized as "espinheira-santa" in the formal trade in Brazil, by macro and microscopic morphological studies of the leaves. The evaluation of the botanical authenticity was based on leaf venation patterns, shape and anatomy of the petiole and midrib region in cross section, vascular system arrangement and epidermal characters. Analysis of these characters compared to literature data suggests that 34% of the samples are M. ilicifolia and the remaining 66% are Sorocea bonplandii, a species with no clinical studies assuring its effective and safe use, representing thus a potential risk to public health.
Las hojas de Monteverdia ilicifolia ("espinheira-santa") son consideradas tés medicinales por la Agencia Nacional de Vigilancia Sanitaria (Anvisa), Brasil, por las indicaciones terapéuticas como antidispépticos, antiácidos y protectores de la mucosa gástrica. Sus márgenes foliares espinescentes se parecen a los de otras especies, conduciendo a identificaciones erróneas. El objetivo de este trabajo fue evaluar la autenticidad de 32 muestras de drogas vegetales vendidas como "espinheira-santa" en el comercio legal de Brasil, realizando un estudio morfológico de las hojas. Esta evaluación se ha basado en observar de la hoja, sus patrones de nerviación, su forma y anatomía (pecíolo y nervadura central en corte transversal), disposición del sistema vascular y caracteres epidérmicos. El análisis de la morfología, comparado con los datos de literatura, sugiere que el 34% de las muestras son M. ilicifoliay el 66% son Sorocea bonplandii, una especie que no cuenta con los estudios clínicos que garantizan su uso efectivo y seguro, representando un riesgo para la salud pública.
Subject(s)
Plants, Medicinal , Maytenus/anatomy & histology , Fraud , Quality Control , Brazil , Drug Contamination , Plant Leaves/anatomy & histology , Celastraceae/anatomy & histologyABSTRACT
Maytenus roylanus (MEM) is a plant with anti-proliferative effects against prostate cancer. We aimed to explore the mechanism of action of MEM in prostate cancer (PCa) by employing an in vitro global proteome approach to get useful information of various signaling pathways and effected genes to define the mechanism of MEM action in prostate cancer. We conducted a global proteome analysis of CWR22Rv1after treatment with methanolic extract of MEM. The result of the proteomic profiling of in vitro PCa cells demonstrated the reduction in tumor protein D52 (TPD52) expression after treatment with methanolic extract of MEM. Down-regulation of TPD52 expression at mRNA level was observed by MEM treatment in CWR22Rν1 and C4-2 cells in a dose-dependent fashion probably by cleavage of Caspase 3 and PARP, or by modulation of cyclin-dependent kinases in CWR22Rν1 and C4-2 cells. The progressive character of the TRAMP model demonstrates a chance to evaluate the potential of chemo-preventive agents for both initial and late stages of prostate cancer development, and induction in TPD52 protein expression with development as well as the progression of prostate cancer was observed in the TRAMP model. Analyses of the tissue microarray collection of 25 specimens confirmed the clinical significance of our findings identifying TPD52 as a potential marker for PCa progression. We determined that knockdown of TPD52 (CWR22Rν1 cells), a considerable downregulation was seen at the protein level. Downregulation of TPD52 inhibited the migration and invasive behavior of prostate cancer cells as observed. Moreover, we observed that the siRNA-TPD52 transfection of CWR22Rν1 cells resulted in tumor growth inhibition with a marked reduction in the secretion of prostate-specific antigen (PSA) in the serum. Intraperitoneal injection of MEM considerably slowed tumor growth in athymic mice, inhibited TPD52 expression, and caused a marked reduction in PSA levels of serum as demonstrated by immunoblot screening and immune-histochemical staining. This report illustrates a molecular overview of pathological processes in PCa, indicating possible new disease biomarkers and therapeutic targets.
Subject(s)
Maytenus/chemistry , Neoplasm Proteins/metabolism , Plant Extracts/pharmacology , Prostatic Neoplasms/metabolism , Proteomics/methods , Tissue Array Analysis/methods , Animals , Cell Line, Tumor , Cell Movement/drug effects , Cell Movement/genetics , Gene Expression Regulation, Neoplastic/drug effects , Humans , Male , Mice, Nude , Neoplasm Proteins/genetics , PC-3 Cells , Plant Extracts/administration & dosage , Plant Leaves/chemistry , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/genetics , RNA Interference , Xenograft Model Antitumor Assays/methodsABSTRACT
Maytenus ilicifolia or "Espinheira-Santa" is a renowned Brazilian medicinal plant usually used against intestinal and stomach ulcers. Other species with similar thorny leaves have raised great confusion in order to discern the authentic M. ilicifolia. Misidentifications can lead to product adulteration of authentic M. ilicifolia with other species, which can be found on the Brazilian market. The intake of misclassified herbal products potentially could be fatal, demanding faster reliable fingerprinting-based classification methods. In this study, the use of 1H HR-MAS NMR metabolomics fingerprinting and principal component analysis (PCA) allowed an evaluation of the authenticity for both collected and commercial M. ilicifolia samples, from the content of the flavanol, (-)-epicatechin (2), by observing variations in metabolic patterns. Plant specimen types from cultivated and natural habitats were analyzed by considering seasonal and topological differences. The interand intraplant topological metabolic profiles were found to be affected by seasonal and/or ecological trends such as sunlight, shade, rain, and the presence of pathogens. Moreover, several commercial samples, labeled as M. ilicifolia, were evaluated, but most of these products were of an inadequate quality.
Subject(s)
Maytenus/chemistry , Metabolome , Brazil , Catechin/analysis , Environment , Plant Leaves/chemistry , Plants, Medicinal/chemistry , SeasonsABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Maytenus ilicifolia Mart. ex Reissek, Celastraceae, is popularly known as "espinheira-santa" and used to treat pathologies related to the stomach. However, in popular culture, this species has also been used to treat other disorders such as diabetes, but without scientific evidence, requiring more phytochemical and pharmacological studies on the plant. AIM OF THE STUDY: This work aims to investigate the anti-hyperglycemic potential of ethanolic extracts obtained from leaves from two different accessions of Maytenus ilicifolia (MIA and MIB) in normal hyperglycemic rats. MATERIALS AND METHODS: The animals were divided into different experimental groups: normal hyperglycemic (negative control); MIA (treatment of Maytenus ilicifolia extract from access 116); MIB (treatment with Maytenus ilicifolia extract from access 122; and glipizide (positive control). At 30 min after treatment, all animals received glucose overload orally. Blood collection occurred at different periods for the assessment of blood glucose (0, 60, 90 and 210 min after treatment) and at the end of the experiment blood was collected through cardiac puncture and the liver, muscle, pancreas and intestine were dissected for further analysis. RESULTS: Chromatographic analysis identified oleic and palmitic acid as the most common constituents, and both extracts of Maytenus ilicifolia caused a reduction in blood glucose levels within 60 min after administration of glucose overload when compared to the normal hyperglycemic group. No significant changes were observed in hepatic and muscular glycogen levels, plasma insulin concentration and disaccharidases activity with none of the extracts in the model employed. However, hyperglycemic rats treated with the extracts showed a marked increase in triglyceride and HDL cholesterol levels. CONCLUSIONS: Our data suggest that Maytenus ilicifolia extracts from different locations showed differences in chemical composition which did not reflect significant differences in the results of biological tests. In addition, it was possible to conclude that the treatment with Maytenus ilicifolia had a discreet anti-hyperglycemic effect; however, it was not possible to identify the responsible mechanism, being necessary, therefore, new studies using different technologies in order to determine the possible mechanisms of action of the extract.