Context: Brosimum alicastrum, Cnidoscolus chayamansa, Tradescantia spathacea, Turnera diffusa, Manilkara zapota, and Jatropha gaumeri are medicinal plants recognized in Mexican Mayan Culture. Aim: ...Methanol leaves extracts of these plants were use as raw material to develop a phytochemical, spectroscopy, and pharmacological analysis. Subjects and Methods: Methanol maceration was carried out and were compared in terms of yield extraction, chlorophyll, simple phenolic and flavonoids content, antioxidant activity (DPPH and β-Carotene bleaching models), as well as isolated aorta rings (E+), precontracted with noradrenaline. Results: Best content of simple phenolic and flavonoids compounds was recorder in B. alicastrum, J. gaumeri and T. diffusa. J. gaumeri extract exert an antioxidant (β-carotene bleaching: EC50: 0.8 ± 0.1 μg/mL, Emax: 85.7% ± 0.4%; DPPH: EC50: 60.3 ± 1.8 μg/mL, Emax: 60.4% ± 1.8%; P < 0.05) and vasorelaxant (EC50: 161.61 ± 7.45 μg/mL; Emax: 79.71% ± 3.88%; P < 0.05) activity in a concentration dependent-manner. Fourier transform infrared spectroscopy analysis allowed estimating a 1.26 and 2.28% of quercetin (Q) and gallic acid (GA) in J. gaumeri. GA exerts antioxidant activity in DPPH model (EC50: 1.6 ± 0.2 μg/mL; Emax: 92.9% ± 3.3%) and Q/GA (1:2) mixture improves inhibition of β-carotene bleaching (EC50: 0.005 ± 0.005 μg/mL; Emax: 69.2% ± 0.7%; P < 0.05). Conclusion: J. gaumeri is a medicinal plant employed in Mayan traditional medicine and GA and Q could be related to traditional uses, as well as responsible for the pharmacological effects. GA and Q interactions improve inhibition β-Carotene bleaching activity, which suggests greater solubility in lipophilic systems and potential interactions at the plasma membrane level.
Hit, Lead & Candidate Discovery Protein tyrosine phosphatase 1B (PTP-1B) has attracted interest as a novel target for the treatment of type 2 diabetes, this because its role in the insulin-signaling ...pathway as a negative regulator. Thus, the aim of current work was to obtain seven ursolic acid derivatives as potential antidiabetic agents with PTP-1B inhibition as main mechanism of action. Furthermore, derivatives 1-7 were submitted in vitro to enzymatic PTP-1B inhibition being 3, 5, and 7 the most active compounds (IC
= 5.6, 4.7, and 4.6 μM, respectively). In addition, results were corroborated with in silico docking studies with PTP-1B orthosteric site A and extended binding site B, showed that 3 had polar and Van der Waals interactions in both sites with Lys120, Tyr46, Ser216, Ala217, Ile219, Asp181, Phe182, Gln262, Val49, Met258, and Gly259, showing a docking score value of -7.48 Kcal/mol, being more specific for site A. Moreover, compound 7 showed polar interaction with Gln262 and Van der Waals interactions with Ala217, Phe182, Ile219, Arg45, Tyr46, Arg47, Asp48, and Val49 with a predictive docking score of -6.43 kcal/mol, suggesting that the potential binding site could be localized in the site B adjacent to the catalytic site A. Finally, derivatives 2 and 7 (50 mg/kg) were selected to establish their in vivo antidiabetic effect using a noninsulin-dependent diabetes mice model, showing significant blood glucose lowering compared with control group (p < .05).
Objectives
To explore the antihyperglycaemic and antidiabetic effects and to determine the acute toxicity of ...5‐(4‐chlorophenyl)‐1‐(2,4‐dichloro‐phenyl)‐4‐methyl‐N‐(piperidin‐1‐yl)‐1H‐pyrazole‐3‐carboxamide (ENP‐9).
Methods
The antihyperglycaemic effect of ENP‐9 (50 mg/kg) was determined by oral glucose tolerance test (OGTT). Also, the acute (16, 50 and 160 mg/kg) and subacute (50 mg/kg/day for 10 days) antidiabetic effects of ENP‐9 were determined. After subacute treatment, blood samples were analysed to determine glucose and lipid profiles. Also, an acute toxicity determination of ENP‐9 was conducted followed the OECD recommendation. Molecular docking was performed using AutoDock 4.2.6 at human cannabinoid receptor 1 (PDB code 5TGZ).
Key findings
Acute Administration of ENP‐9 showed significant antidiabetic effect and decreased the maximum OGTT peak, compared to the control group (P < 0.05). Moreover, the 10 days treatment induced a decrease in plasma glucose levels, being significant at the end of the experiments (P < 0.05); however, triacylglycerols and cholesterol were not modified. Finally, LD50 of ENP‐9 was estimated to be greater than 2000 mg/kg. Molecular docking suggests that ENP‐9 may act as rimonabant does.
Conclusions
ENP‐9 showed significant antihyperglycaemic and antidiabetic properties and also was demonstrated to be safety in the studied doses, which might allow future studies for its potential development as antidiabetic agent.
Ursolic (UA), oleanolic (OA) and rosmarinic (RA) acids are bioactive metabolites found in
that have generated interest for their health benefits, which include antimicrobial, antioxidant, ...antimutagenic, gastroprotective, antidiabetic, antihypertensive and anti-inflammatory properties, among others. To date, very few attempts have been made to evaluate the potential for simultaneous production of these bioactive compounds, using a biotechnological approach. Hairy root cultures offer a biotechnology approach that can be used to study the factors affecting the biosynthesis and the production of UA, OA and RA. In the current study, we established hairy root cultures of
and evaluated the effect of sucrose on biomass accumulation, and the effect of different concentrations and times of exposure of methyl jasmonate (MeJA), on the accumulation of UA, OA and RA.
Leaves from plants of
were inoculated with
strain ATCC 15834
PCR of
gene confirmed the transgenic nature of hairy roots. Hairy roots were subcultured in semisolid MSB5 medium, supplemented with 15, 30, 45 or 60 g/L sucrose and after 4 weeks, dry weight was determined. The accumulation of UA, OA and RA of wild plants and hairy roots were determined by HPLC. Finally, the hairy roots were treated with 0, 100, 200 and 300
M of MeJA and the content of bioactive compounds was analyzed, after 24, 48 and 72 h.
High frequency transformation (75%) was achieved, using leaf explants from axenic seedlings, infected with
. The hairy roots showed an enhanced linear biomass accumulation, in response to the increase in sucrose concentration. The hairy root cultures in MSB5 medium, supplemented with 45 g/L sucrose, were capable to synthesizing UA (0.29 ± 0.00 mg/g DW), OA (0.57 ± 0.00 mg/g DW) and RA (41.66 ± 0.31 mg/g DW), about two, seven and three times more, respectively, than in roots from wild plants. Elicitation time and concentration of MeJA resulted in significant enhancement in the production of UA, OA and RA, with treatments elicited for 24 h, with a concentration of 300
M of MeJA, exhibiting greatest accumulation.
This is the first report on development of hairy root cultures of
. Future studies should aim towards further improving triterpenes and polyphenolic compound production in hairy roots of
for use in the pharmaceutical and biotechnological industry.
Senna septemtrionalis
(Viv.) H.S. Irwin & Barneby, Fabaceae, is a shrub used for treating asthma, diarrhea, and sore throat. This work evaluated for the first time the vasorelaxant, tracheo-relaxant ...effect, spasmolytic, and antidiarrheal activity of a dichloromethane extract of the aerial parts of
Senna septemtrionalis.
The chemical characterization of the plant extract using GC–MS showed that octacosanol was the main component. The antidiarrheal actions of octacosanol (from a supplier) were assessed with the castor oil–induced diarrhea and enteropooling, and the motility test using charcoal. The possible mechanism of action of the antidiarrheal activity exerted by octacosanol was assessed using naloxone, pilocarpine, and yohimbine.
Senna septemtrionalis
showed antidiarrheal activity (ED
50
50 mg/kg,
p.o
.) but lacked vasorelaxant, tracheo-relaxant, and spasmolytic effects. Octacosanol showed antidiarrheal activity (ED
50
0.3 mg/kg) with similar activity to 2.5 mg/kg loperamide. Octacosanol delayed the onset of diarrhea, decreased fluid accumulation, and intestinal transit. Yohimbine (1 mg/kg) reversed the inhibition of intestinal transit shown by octacosanol at 50 mg/kg. A docking study revealed that the mode of action for octacosanol is very similar to the partial agonist of α2-adrenoreceptors. Octacosanol, a main component of
S. septemtrionalis
, exerts antidiarrheal actions in mice by decreasing intestinal transit with the possible participation of α2-adrenergic receptors.
Graphical Abstract
Background: The production of triterpenes from plants for pharmacological purposes varies in concentration, due to genetic and environmental factors. In vitro culture enables the control and increase ...of these bioactive molecules. Objective: To evaluate the effect of plant growth regulators and elicitors in the induction of calli and the production of ursolic acid (UA) and oleanolic acid (OA) in Lepechinia caulescens. Materials and Methods: Leaf explants were exposed for the induction of calli at different concentrations and combinations of 2,4-dichlorophenoxyacetic acid (2,4-D) and 6-benzylaminopurine (BAP). Methyl jasmonate (MJ) and salicylic acid were used as elicitors. High-performance liquid chromatography method was used to quantify UA and OA content in each treatment. Results: Treatment with 3.0 mg/L of 2,4-D and 0.1 mg/L of BAP produced the best results for calli induction and production of UA (1.57 mg/g dry weight DW) and OA (1.13 mg/g DW). Both elicitors facilitated the accumulation of triterpenes. Conclusion: The combination of auxins and cytokinins showed favorable results for the induction of calli. Variation concerning the accumulation of UA and OA was observed between treatments. MJ increased the production of triterpenes five times after 8 h of exposure, compared to control treatment. There is a greater accumulation of UA (16.58 mg/g DW) and OA (1.94 mg/g DW) in leaves of wild plants.
Abbreviations used: 2,4-D: 2,4-dichlorophenoxyacetic acid, BAP: 6-benzylaminopurine, DW: Dry weight, MJ: Methyl jasmonate, OA: Oleanolic acid, PGRs: Plant growth regulators, UA: Ursolic acid, SA: Salicylic acid.
Smooth muscle is a central structure involved in the regulation of airway tone. In addition, it plays an important role in the development of some pathologies generated by alterations in contraction, ...such as hypercontractility and the airway hyperresponsiveness observed in asthma. The molecular processes associated with smooth muscle contraction are centered around myosin light chain (MLC) phosphorylation, which is controlled by a balance in the activity of myosin light-chain kinase (MLCK) and myosin light-chain phosphatase (MLCP). MLCK activation depends on increasing concentrations of intracellular Ca
2+
, while MLCP activation is independent of Ca
2+
. MLCP contains a phosphatase subunit (PP1c) that is regulated through myosin phosphatase target subunit 1 (MYPT1) and other subunits, such as glycogen-associated regulatory subunit and myosin-binding subunit 85 kDa. Interestingly, MLCP inhibition may contribute to exacerbation of smooth muscle contraction by increasing MLC phosphorylation to induce hypercontractility. Many pathways inhibiting MLCP activity in airway smooth muscle have been proposed and are focused on inhibition of PP1c, inhibitory phosphorylation of MYPT1 and dissociation of the PP1c-MYPT1 complex.
Asthma is a chronic inflammatory disorder that causes contraction in the smooth muscle of the airway and blocking of airflow. Reversal the contractile process is a strategy for the search of new ...drugs that could be used for the treatment of asthma. This work reports the semisynthesis, ex vivo relaxing evaluation and SAR studies of a series of 18 coumarins. The results pointed that the ether derivatives 1–3, 7–9 and 13–15 showed the best activity (Emax = 100%), where compound 2 (42 μM) was the most potent, being 4-times more active than theophylline (positive control). The ether homologation (methyl, ethyl and propyl) in position 7 or positions 6 and 7 of coumarins lead to relaxing effect, meanwhile formation of esters generated less active compounds than ethers. The SAR analysis showed that it is necessary the presence of two small ether groups and the methyl group at position 4 (site 3) encourage biological activity through soft hydrophobic changes in the molecule, without drastically affecting the cLogP.
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•Eighteen coumarin derivatives were semisynthesized with potential antiasthmatic properties.•Results indicate that ether derivatives 1–3, 7–9 and 13–15 showed the best relaxant activity.•Compound 2 (42 μM) was the most potent of the entire series, being 4-times more active than theophylline (positive control).
Extensive knowledge of diabetes and its complications is helpful to find new drugs for proper treatment to stop degenerative changes derived from this disease. In this context, chrysin ...(5,7-dihydroxyflavone) is a natural product that occurs in a variety of flowers and fruits with anti-inflammatory and antidiabetic effects, among others. Thus, a diabetic model in athymic nude mice was developed and used to establish the ability of chrysin to decrease the secretion of pro-inflammatory cytokines. Also, it was determined the acute (50 mg/kg) and sub-acute (50 mg/kg/day/10 days) antidiabetic and antihyperlipidemic activities after the period of time treatment. Results indicate that chrysin has significant acute antihyperglycemic and antidiabetic effects in nude diabetic mice (
< 0.05). Moreover, triglyceride blood levels were reduced and IL-1β and TNF-α were diminished after 10 days' treatment compared with control group (
< 0.05). In conclusion, it was found that chrysin could produce similar effects as metformin, a drug used for the treatment of diabetes, since both test samples decreased glucose and triglycerides levels, they impaired the generation of pro-inflammatory cytokines involved in the development of diabetes and its consequences, such as atherosclerosis and other cardiovascular diseases.
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