Snakebite envenomation (SBE) is the world's most lethal neglected tropical disease. Bothrops jararaca is the species that causes the greatest number of SBEs in the South and Southeastern of Brazil. ...The main symptoms are local (inflammation, edema, hemorrhage, and myonecrosis) and systemic (hemorrhage, hemostatic alterations with consumptive coagulopathy, and death) effects. Species of the genus Siparuna, Siparunaceae, are used in folk and traditional medicine to treat SBE. However, limited information is available concerning Brazilian Siparuna species against SBE.
To investigate the correlation between the compounds present in the extracts of five Siparuna species as potential agents against proteolytic activity, plasma coagulation, and phospholipase A2 (PLA2) activity caused by B. jararaca venom, using data obtained by UHPLC-MS/MS, biological activity, and multivariate statistics.
The ethanol extracts from leaves of S. ficoides, S. decipiens, S. glycycarpa, S. reginae, and S. cymosa were fractionated by liquid-liquid extraction using different solvents of increasing polarity (hexane, dichloromethane, ethyl acetate, and n-butanol), affording their respective extracts, totaling 25 samples that were assayed through in vitro plasma coagulation and proteolytic activity assays. Moreover, the extracts were analyzed by UHPLC-MS/MS, using electrospray ionization (ESI) and atmospheric-pressure chemical ionization (APCI) in negative and positive ionization modes. The data was processed in MZmine v. 2.53 and evaluated by multivariate statistical tests (PLS) using the software UnscramblerX v. 10.4. These data were also used to build molecular networks (GNPS), and some ions of interest could be annotated using the library of molecules on the GNPS platform.
A total of 19 extracts inhibited B. jararaca-induced plasma coagulation, with emphasis on S. cymosa and S. reginae (800 s). The inhibition of the proteolytic activity was also promising, ranging from 16% (S. glycycarpa) to 99% (S. cymosa, S. decipiens, and S. reginae). In addition, most extracts from S. cymosa and S. reginae inhibited 70–90% of PLA2 activity. Based on data from positive mode APCI analyses, it was possible to obtain a statistic model with reliable predictive capacity which exhibited an average R2 of 0.95 and a Q2 of 0.88, indicating a robust fit. This process revealed five ions, identified as the alkaloids: coclaurine (1), stepholidine (2) O-methylisopiline (3), nornantenine (4) and laurolitsine (5). This is the first study to evidence the potential antivenom of alkaloids from Siparuna species.
Altogether, our results give support to the popular use of Siparuna extracts in SBE accidents, suggesting their potential as an alternative or complementary strategy against envenoming by B. jararaca venom. The predicted ions in the chemometric analysis for the assayed activities can also be correlated with the blocking activity and encourage the continuation of this study for possible isolation and testing of individual compounds on the used models.
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•Siparuna spp. are used in folk medicine to counter snakebite envenomation in tropics.•Siparuna extracts inhibited B. jararaca snake venom proteolytic activity (30–96%).•Siparuna extracts inhibit B. jararaca venom-induced plasma coagulation (75–800s).•Siparuna extracts can inhibit up to 90% of PLA2 of B. jararaca activity.•Five alkaloids in the PLSr model are candidates with potential antivenom activity.
The objective of this study was to evaluate the effect of ChromatiNet on vegetative growth, total antioxidant capacity, phenolic and essential oils (EOs) composition of Lippia gracilis. The plants ...were cultivated under full sunlight, black, blue and red ChromatiNet. The flavonoid content and antioxidant capacity were quantified spectrophotometrically. The C‐glycosylflavone isomers (orientin and isoorientin) were isolated and identified by conventional spectroscopic techniques and measured using high‐performance liquid chromatography‐diode array detection. The EO was analysed by gas chromatography and gas chromatography‐mass spectrometry. Environment influenced growth, total antioxidant capacity and phytochemical levels. Shoot dry weight, thymol, carvacrol and (E)‐caryophyllene were favoured under red and black ChromatiNet. Root growth, EOs, caryophyllene oxide, p‐cymene, flavonoids, orientin and isoorientin were favoured in sunlight. Growth and accumulation of EOs, flavonoids and photosynthetic pigments increased under blue ChromatiNet. Therefore, Lippia gracilis plants have plasticity related to the spectral quality of light and it cultivate depends of the phytochemicals of interest.
Traditional medicine shows several treatment protocols for COVID-19 based on natural products, revealing its potential as a possible source of anti-SARS-CoV-2 agents.
is popularly used in the ...Brazilian Amazon as a fortifier and tonic, and recently, it has been reported to relieve COVID-19 symptoms. This work aimed to investigate the antiviral potential of
, focusing on the inhibition of spike and ACE2 receptor interaction, a key step in successful infection. Although saponins are the major compounds of this plant and often reported as its active principles, a polyphenol-rich extract was the best inhibitor of the spike and ACE2 interaction. Chemical characterization of
bark extracts by LC-DAD-APCI-MS/MS before and after clean-up steps for polyphenol removal showed that the latter play an essential role in maintaining this activity. The effects of the extracts on viral replication were also assessed, and all samples (aqueous and ethanol extracts) demonstrated in vitro activity, inhibiting viral titers in the supernatant of Calu-3 cells after 24 hpi. By acting both in the SARS-CoV-2 cell entry process and its replication,
bark extracts stand out as a multitarget agent, highlighting the species as a promising candidate in the development of anti-SARS-CoV-2 drugs.
Alkaloids are nitrogen-containing compounds of the secondary metabolism of plants and microorganisms, which can also be found in animals, insects, and marine organisms. Because of the presence of one ...or more nitrogen atoms in the molecule, these compounds can form salts in the presence of acids, which are soluble in water and not in organic solvents. This characteristic is useful for their extraction from the matrix source and is explored in liquid–liquid partitioning techniques like countercurrent chromatography. Solvent systems used in classic purifications of alkaloids by this separation technique consist of an organic solvent such as chloroform or dichloromethane and a water buffer where the pH varies along the purification. The addition of other organic solvents like methanol and other alcohols to the solvent system is discussed, as well as the use of less polar systems. Recently developed techniques in countercurrent separations, such as pH-zone-refining countercurrent chromatography, are also presented. This comprehensive review covers the early work on separation of alkaloids with the Craig and Post apparatus and the evolution in the use of modern equipment for the isolation and purification of this class of bioactive natural products.
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The phenolic compound content, the antioxidant and α-amylase inhibition potentials of different extracts of the Plectranthus amboinicus, P. barbatus and P. ornatus were evaluated. We also evaluated ...the influence of plant growth and harvest time on the chemical composition of the essential oil (EO) of P. amboinicus, its antioxidant and anti-Candida activities and the α-amylase and lipoxygenase inhibitions. The turbo-extract of P. barbatus showed the greatest phenolic compound content and antioxidant activity. No α-amylase inhibition activity was observed in the analyzed extracts, but the turbo-extraction and refluxing extracts possessed high antioxidant activities. Protected cultivation and morning harvest conditions gave the best antioxidant activities, which was associated to the highest carvacrol content. P. amboinicus EO antioxidant activity could contribute to the reduction of oxidative stress in diabetes. Causal Candida strains of diabetic foot ulcers showed sensitivity to P. amboinicus EO. C. albicans and C. dubliniensis were the most sensitive of the selected Candida strains. Turbo-extracts or refluxing of the three species extracts and the EO of P. amboinicus should be considered as a potential candidate for the management the complications of type 2 diabetes.
The LABEXTRACT plant extract bank, featuring diverse members of the Myrtaceae family from Brazilian hot spot regions, provides a promising avenue for bioprospection. Given the pivotal roles of the ...Spike protein and 3CL
and PL
proteases in SARS-CoV-2 infection, this study delves into the correlations between the Myrtaceae species from the Atlantic Forest and these targets, as well as an antiviral activity through both
and
analyses. The results uncovered notable inhibitory effects, with
and
standing out, while
proved to be multitarget, presenting inhibition values above 72% in the three targets analyzed. All extracts inhibited viral replication in Calu-3 cells (EC
was lower than 8.3 µg·mL
). Chemometric analyses, through LC-MS/MS, encompassing prediction models and molecular networking, identified potential active compounds, such as myrtucommulones, described in the literature for their antiviral activity. Docking analyses showed that one undescribed myrtucommulone (m/z 841 M - H
) had a higher fitness score when interacting with the targets of this study, including ACE2, Spike, PL
and 3CL
of SARS-CoV-2. Also, the study concludes that Myrtaceae extracts, particularly from
and
, exhibit promising inhibitory effects against crucial stages in SARS-CoV-2 infection. Compounds like myrtucommulones emerge as potential anti-SARS-CoV-2 agents, warranting further exploration.
Zika virus (ZIKV) is involved in the etiology of serious nervous system pathologies. Currently, there are no specific and effective vaccines or antiviral drugs to prevent the diseases caused by ZIKV. ...This study aimed to assess the activity of flavonoids present in crude hydroethanolic extract (CHE) and fractions obtained from B. holophylla leaves against ZIKV. O-glycosylated flavonoids were characterized by high-performance liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS/MS). The cytotoxic concentration and the effective concentration for 50% of the cells (CC50 and EC50, respectively) were determined, and the selectivity index (SI) was calculated. Molecular networks were constructed based on the chemical composition of the samples and global antiviral activity data using the Global Natural Products Social Molecular Networking (GNPS) platform. Protein–ligand docking was performed in the NS2B-NS3 protease, NS3 helicase, and NS5 methyltransferase of the ZIKV. CHE showed greater antiviral activity at a multiplicity of infection (MOI) of 1.0, with an EC50 of 11.93 µg/mL, SI = 13.38, and reduced cytopathic effects. Molecular networks indicated that O-glycosylated flavonoids are responsible for the activity against ZIKV, being quercetin-O-deoxyhexoside more selective and effective. Molecular docking confirmed the inhibitory activity of quercetin-O-deoxyhexoside, which showed an affinity for the tested targets, especially for NS2B-NS3 protease. The results showed that B. holophylla has flavonoids with potential for future therapeutic applications against ZIKV.
Ziziphus joazeiro
Mart., Rhamnaceae, is a plant native to northeast Brazil where it is known as “juazeiro.” Its bark, rich in saponins, is widely utilized in folk medicine and as a supply to produce ...cosmetics. Aiming at the preservation of the species and the search for an alternative vegetal raw material, the phytochemical profiles of bark and leaves were compared by chemical techniques. The foaming index and gravimetric studies indicated that, in general, bark values were approximately twice than those of the leaves. The same occurred with the hemolysis indexes. Extracts were dereplicated by liquid chromatography with diode array detection coupled to mass spectrometry analyses using an atmospheric pressure chemical ionization source, which indicated that at least 5 saponins were common to all bark and leaf samples. The direct infusion high-resolution mass spectrometry analyses revealed at least 44 different saponins distributed between the bark and leaves of the analyzed plant, of which 40 were described for the first time. The data showed that there were similarities between the studied plant organs as demonstrated by mass spectrometry, foaming index, and hemolysis indexes. Therefore, with the application of a suitable standardization procedure the leaves could be a promising source for obtaining “juazeiro-type” saponins.
Graphical abstract
Traditional medicine shows several treatment protocols for COVID-19 based on natural products, revealing its potential as a possible source of anti-SARS-CoV-2 agents. Ampelozizyphus amazonicus is ...popularly used in the Brazilian Amazon as a fortifier and tonic, and recently, it has been reported to relieve COVID-19 symptoms. This work aimed to investigate the antiviral potential of A. amazonicus, focusing on the inhibition of spike and ACE2 receptor interaction, a key step in successful infection. Although saponins are the major compounds of this plant and often reported as its active principles, a polyphenol-rich extract was the best inhibitor of the spike and ACE2 interaction. Chemical characterization of A. amazonicus bark extracts by LC-DAD-APCI-MS/MS before and after clean-up steps for polyphenol removal showed that the latter play an essential role in maintaining this activity. The effects of the extracts on viral replication were also assessed, and all samples (aqueous and ethanol extracts) demonstrated in vitro activity, inhibiting viral titers in the supernatant of Calu-3 cells after 24 hpi. By acting both in the SARS-CoV-2 cell entry process and its replication, A. amazonicus bark extracts stand out as a multitarget agent, highlighting the species as a promising candidate in the development of anti-SARS-CoV-2 drugs.
Ampelozizyphus amazonicus Ducke, known as "saracura‐mirá" in the Amazon rainforest, is valued for its traditional use in malaria prevention and treatment. The plant's roots and bark are employed for ...these purposes, while the wood is often overlooked. Given the global importance of leishmaniasis, research focused on A. amazonicus anti‐Leishmania amazonensis potential. The ethyl acetate extract from the bark (EAEB) exhibited the most effective inhibition of intracellular amastigote growth with IC50 7.0 µg.mL‐1 but showed high toxicity (CC50 9.0 µg.mL‐1). The wood ethanol (EW) and ethyl acetate (EAEW) extracts demonstrated promising results against L. amazonensis with IC50 15.8 µg.mL‐1 and 10.0 µg.mL‐1, CC50 50.5 µg.mL‐1 and 22.7 µg.mL‐1, respectively. High‐speed countercurrent chromatography combined with mass spectrometry off‐line detection was employed for the bioassay‐guided fractionation of EAEB and EAEW using HEMWat as solvent system. These extracts showed to be rich in saponins and triterpenes, besides minor glycosylated flavonoids. HSCCC was effective in obtaining high purity fractions, leading to the identification of a di‐glycosylated triterpene saponin from EAEB, and melaleucic acid from EAEW. These findings highlight A. amazonicus as a potential source for developing new therapeutic alternatives for leishmaniasis and HSCCC as a technique enabling better separation efficiency of complex saponin matrices.
