19 research outputs found
Starting Anti-COVID-19 Drug Discovery with Natural Products
COVID-19 was characterized as a pandemic regarding its rapid international spread and severity on March 2020. The Coronaviridae family receives this name regarding the organization of the spike glycoprotein located in the envelope, which resembles a stellar corona when observed under a microscope. Coronaviruses undergo frequent mutations in their genome due to errors made by RNA-dependent RNA polymerase (RdRp). The SARS-CoV-2 was characterized by high infectivity and person to person transmission, with an incubation period of up to fourteen days. Potent antiviral activities of several natural products such as alkaloids, chalcones, triterpenoids have been reported but with unconfirmed efficacy or safety in the clinic as well as the complete underlying mechanisms. Also, CQ, HCQ and Ivermectin, remdesivir, lopinavir, ritonavir, favipiravir and pegylated interferon with ribavirin have been tested to develop both an effective therapy and a vaccine to treat COVID-19. This study presents the antiviral effects of the natural products against SARS-CoV, HCoV-NL63, HCoV-229E and HCoV-OC43 showing that Lycorine, Emodin, Promazine, Saikosaponins B2, Silvestrol, Cepharanthine, Fangchinoline, Tetrandrine, Caffeic acid, Chlorogenic acid, Gallic acid and Emetine are a good candidates on treatment of coronaviruses infections.La COVID-19 se caracterizó como una pandemia debido a su rápida propagación y severidad en marzo de 2020. La familia Coronaviridae recibe su nombre de la organización de la glucoproteína 'espigas' ubicada en el sobre, en forma de corona cuando se observa al microscopio. . Los coronavirus sufren mutaciones frecuentes en su genoma debido a errores cometidos por la ARN polimerasa dependiente de ARN (RdRp, RDR). El SARS-CoV-2, el agente causal del COVID-19, es un virus altamente infeccioso y puede transmitirse de persona a persona. Se han informado actividades antivirales potentes de varios productos naturales, como alcaloides, chalcones, triterpenoides, pero sin eficacia ni seguridad clínicamente confirmadas, así como con los mecanismos subyacentes completos. Este artículo de revisión presenta los efectos antivirales de los productos naturales contra el SARS-CoV, HCoV-NL63, HCoV-229E y HCoV-OC43, mostrando que el licorino, emodina, promazina, saikosaponinas B2, silvestrol, la cefarantina, fangchinolina, tetrandrina, el ácido cafeico, el ácido clorogénico, el ácido gálico y la emetina son buenos candidatos para el tratamiento de las infecciones por coranavirus.Le COVID-19 a été caractérisé comme une pandémie en raison de sa propagation internationale rapide et de sa gravité en mars 2020. La famille des Coronaviridae reçoit ce nom concernant l'organisation de la glycoprotéine 'pointes' située dans l'enveloppe, en forme une couronne lorsqu'elle est observée au microscope. Les coronavirus subissent de fréquentes mutations dans leur génome en raison d'erreurs commises par l'ARN polymérase ARN-dépendante (RdRp, RDR). Le SARS-CoV-2 a un pouvoir infectieux élevé et une transmission d'une personne à l'autre. De puissantes activités antivirales de plusieurs produits naturels tels que les alcaloïdes, les chalcones, les triterpénoïdes ont été signalées mais avec une efficacité ou une sécurité non confirmée en clinique ainsi que les mécanismes sous-jacents complets. Cette étude présente les e ets antiviraux des produits naturels contre le SARS-CoV, le HCoV-NL63, le HCoV-229E et le HCoV-OC43 montrant que la lycorine, l'émodine, la promazine, les saikosaponines B2, le silvestrol, la cépharanthine, la fangchinoline, la tétrandrine, l'acide caféique, l'acide chlorogénique , L'acide gallique et l'émétine sont de bons candidats pour le traitement de l'infection par le coranaviruses infections.A COVID-19 foi caracterizada como uma pandemia devido à sua rápida disseminação e severidade em março de 2020. A família Coronaviridae recebe esse nome em relação à organização da glicoproteína 'spikes' localizada no envelope, em forma de uma coroa quando vista sob um microscópio. Os coronavírus sofrem mutações frequentes em seu genoma devido a erros cometidos pela RNA polimerase dependente de RNA (RdRp, RDR). O SARS-CoV-2, agente causador da COVID-19, é um vírus altamente infeccioso e pode ser transmitido de pessoa para pessoa. Foram relatadas atividades antivirais potentes de vários produtos naturais, como alcalóides, chalconas, triterpenóides, mas com eficácia ou segurança não confirmada clinicamente, bem como com os mecanismos subjacentes completos. O presente artigo de revisão apresenta os efeitos antivirais de produtos naturais contra SARS-CoV, HCoV-NL63, HCoV-229E e HCoV-OC43, mostrando que a licorina, emodina, promazina, saikosaponinas B2, silvestrol, la cefarantina, fangchinolina, tetrandrina, ácido cafeico, ácido clorogênico, ácido gálico e emetina são bons candidatos ao tratamento de infecções por coranavírus
Cutting-Edge Search for Safer Opioid Pain Relief: Retrospective Review of Salvinorin A and Its Analogs
Over the years, pain has contributed to low life quality, poor health, and economic loss. Opioids are very effective analgesic drugs for treating mild, moderate, or severe pain. Therapeutic application of opioids has been limited by short and long-term side effects. These side effects and opioid-overuse crisis has intensified interest in the search for new molecular targets and drugs. The present review focuses on salvinorin A and its analogs with the aim of exploring their structural and pharmacological profiles as clues for the development of safer analgesics. Ethnopharmacological reports and growing preclinical data have demonstrated the antinociceptive effect of salvinorin A and some of its analogs. The pharmacology of analogs modified at C-2 dominates the literature when compared to the ones from other positions. The distinctive binding affinity of these analogs seems to correlate with their chemical structure and in vivo antinociceptive effects. The high susceptibility of salvinorin A to chemical modification makes it an important pharmacological tool for cellular probing and developing analogs with promising analgesic effects. Additional research is still needed to draw reliable conclusions on the therapeutic potential of salvinorin A and its analogs
The Newly Synthesized Pyrazole Derivative 5-(1-(3 Fluorophenyl)-1H-Pyrazol-4-yl)-2H-Tetrazole Reduces Blood Pressure of Spontaneously Hypertensive Rats via NO/cGMO Pathway
The search for new antihypertensive drugs has grown in recent years because of high rate of morbidity among hypertensive patients and several side effects that are associated with the first-line medications. The current study sought to investigate the antihypertensive effect of a newly synthesized pyrazole derivative known as 5-(1-(3 fluorophenyl)-1H-pyrazol-4-yl)-2H-tetrazole (LQFM-21). Spontaneously hypertensive rats (SHR) were used to evaluate the effect of LQFM-21 on mean arterial pressure (MAP), heart rate (HR), renal vascular conductance (RVC), arterial vascular conductance (AVC), baroreflex sensitivity (BRS) index, and vascular reactivity. Acute intravenous (iv) administration of LQFM-21 (0.05, 0.1, 0.2, and 0.4 mg kg-1) reduced MAP and HR, and increased RVC and AVC. Chronic oral administration of LQFM-21 (15 mg kg-1) for 15 days reduced MAP without altering BRS. The blockade of muscarinic receptors and nitric oxide synthase by intravenous infusion of atropine and L-NAME, respectively, attenuated cardiovascular effects of LQFM-21. In addition, ex vivo experiments showed that LQFM-21 induced an endothelium-dependent relaxation in isolated aortic rings from SHR. This effect was blocked by guanylyl cyclase inhibitor (ODQ) and L-NAME. These findings suggest the involvement of muscarinic receptor and NO/cGMP pathway in the antihypertensive and vasodilator effects of LQFM-21
Neuropharmacological evaluation of anxiolytic and/or antidepressant like activities of dichloromethane fraction, oleanolic acid and (E)-metilisoeugenol of the leaves of pimenta pseudocaryophyllus (Gomes) L. R. Landrum (Myrtaceae) Chemotype (E)- metilisoeugenol
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Tese - James Oluwagbamigbe Fajemiroye - 2015.pdf: 1734029 bytes, checksum: c1790bce6e7eace236dd1d68cec686a8 (MD5)
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Previous issue date: 2015-10-16Depression and anxiety are widely acclaimed as psychiatric disorders of global concern.
These disorders are among the leading causes of disability worldwide. Unsatisfactory
responses of patients to the available pharmacotherapy make the search for new drugs a
necessity. Medicinal plants remain important source of new drugs and new chemical
entities. The ethnopharmacological knowledge and previous data have revealed calming
and anxiolytic like effects of the organic leaf extract of Pimenta pseudocaryophyllus
(Gomes) L.R. Landrum. The present study sought to investigate antidepressive like effect
of dichloromethane fraction (DF) of the ethanolic leaf extract of Pimenta
pseudocaryophyllus as well as anxiolytic and antidepressive like effects of oleanolic acid
(OA), (E) methyl isoeugenol (MIE) and possible mechanisms of action that are involved.
Animal models like barbiturate-induced sleep, light dark box test (LDB), elevated plusmaze
(EPM), open field (OF), wire hanging test, pentylenetetrazol-induced convulsion test,
forced swimming test (FST), tail suspension test (TST) were conducted to evaluate
behavioural alterations that were elicited by the administrations of vehicle, DF, OA, MIE or
reference drugs. Bioassays (ex vivo and in vitro) of monoamine oxidase (MAO) and
quantification of hippocampal level of brain derived neurotrophic factor (BDNF) were
conducted in an attempt to elucidate possible mechanisms of action. Oral administration of
DF 125, 250 or 500 mg/kg (potentiated the hypnotic effect of sodium pentobarbital). In the
TST and FST, DF 125 or 250 mg/kg induced antidepressant-like response. The data
obtained in the OF suggest sedative effect of DF at 500 mg/kg. Pretreatment (i.p) with pchlorophenylalanine
methyl ester (PCPA) 100 mg/kg (serotonin depletor) or -methyl-ptyrosine
(AMPT) 100 mg/kg (catecholamine depletor) blocked anti-immobility effect of DF
viii
in the FST. The enzymatic activity of MAO remained unaltered by DF. Oral administration
of OA (5-20 mg/kg) increased the duration of barbiturate - induced sleep and
demonstrated anxiolytic like effect in both LDB and EPM. In the FST and TST, OA 5-20
mg/kg elicited antidepressant like effect without altering locomotion activity of the animals.
The antidepressant like effect of OA was attenuated by NAN-190 (non-selective antagonist
of 5-HT1A), AMPT, PCPA, WAY and PRAZ. Chronic administration of OA increased
hippocampal level of BDNF. Oral administration of MIE 250 or 500 mg/kg potentiated
hypnotic effect of sodium pentobarbital without protecting mice against PTZ - induced
convulsion. The parameters evaluated in the LDB, EPM and OF demonstrated anxiolytic
like property of MIE. This effect was blocked by WAY (selective antagonist of 5-HT1A)
pretreatment. MIE 125 or 250 mg/kg showed antidepressant like effect in the FST.
Locomotion activity of the animal in the OF remained unaltered by MIE administration at
125 or 250 mg/kg. Pretreatment of mice with PCPA attenuated antidepressant like
property of MIE. In conclusion, our findings demonstrated anxiolytic and/or antidepressant
like effects of dichloromethane fraction, oleanolic acid and (E) methyl isoeugenol, thereby
suggesting the involvement of monoaminergic pathway.Ansiedade e depressão são transtornos psiquiátricos de interesse global. Estes
transtornos estão entre as principais causas da incapacidade laboral das pessoas.
Apesar de uma gama de farmacoterapias disponíveis, os resultados clínicos mostram
que os fármacos não produziram efeitos terapêuticos desejados e se faz necessário a
busca de novos fármacos. As plantas medicinais continuam sendo uma das fontes
mais importantes para a descoberta de novos fármacos e entidades químicas. Estudos
anteriores mostraram efeito calmante e ansiolítico da fração orgânica do extrato das
folhas de Pimenta pseudocaryophyllus (Gomes) L. R. Landrum (Myrtaceae). O
presente estudo buscou investigar a atividade tipo antidepressiva da fração
diclorometano (FD) do extrato etanólico das folhas desta espécie, bem como
antidepressiva e ansiolítica do ácido oleanólico (AO), (E)-metilisoeugenol (MIE) e os
possíveis mecanismos de ações envolvidos. Modelos experimentais como o sono
induzido por barbitúricos, caixa claro escuro (CCE), labirinto em cruz elevado (LCE),
campo aberto (CA), teste de arame, teste de convulsão induzida por pentilenotetrazol,
teste de natação forçada (TNF) e teste de suspensão pela cauda (TSC) foram
realizados para avaliar alterações comportamentais induzidas pela administração do
veículo, FD, AO, MIE ou fármacos de referência. Na tentativa de elucidar os possíveis
mecanismos de ação, foram realizados bioensaios (ex vivo e in vitro) da monoamina
oxidase (MAO) e do fator neurotrófico derivado do cérebro (BDNF do hipocampo). A
administração oral da FD 125, 250 ou 500 mg/kg potencializou o efeito hipnótico de
pentobarbital sódico. No TNF e TSC, a FD 125 ou 250 mg/kg induziu efeito tipo
antidepressivo. Os dados obtidos no campo aberto sugerem efeito sedativo da fração
vi
diclorometano na dose de 500 mg/kg. O pré-tratamento (i.p) com p - clorofenilalanina
metil éster (PCPA) 100 mg/kg (depletor de serotonina) ou α - metil - p - tirosina (AMPT)
100 mg/kg (depletor de catecolamina) bloqueou o efeito tipo antidepressivo da FD no
TNF. O bioensaio da atividade enzimática mostrou que a FD não alterou a atividade da
MAO. A administração oral do AO (5-20 mg/kg) aumentou a duração do sono induzido
por pentobarbital sódico e demonstrou efeito tipo ansiolítico no CCE e LCE. O AO 5-20
mg/kg demonstrou efeito tipo antidepressivo no TNF e TSC sem alterar a atividade
locomotora dos animais. O efeito tipo antidepressivo do AO foi atenuado por prétratamento
com NAN-190 (antagonista não-seletivo do receptor 5-HT1A), AMPT, PCPA
e PRAZ-prazosin (antagonista do receptor α1 adrenérgico). A administração crônica do
AO aumentou o nível de BDNF no hipocampo. A administração oral do MIE 250 ou 500
mg/kg potencializou o efeito hipnótico de pentobarbital sódico sem proteger os animais
contra a convulsão induzida por PTZ. Os parâmetros avaliados na CCE e LCE sugerem
que MIE têm efeito tipo ansiolítico. Este efeito foi bloqueado pelo pré-tratamento com
WAY100635 (antagonista seletivo do receptor 5-HT1A). MIE 125 ou 250 mg/kg
apresentou efeito tipo antidepressivo no TNF. Não houve alteração na atividade
locomotora dos animais no CA após a administração do MIE 125 ou 250 mg/kg. O prétratamento
com PCPA atenuou o efeito tipo antidepressivo do MIE no TNF. Os
resultados demonstraram efeito tipo ansiolítico e/ou antidepressivo da fração
diclorometano, ácido oleanólico e (E)-metilisoeugenol, sugerindo o envolvimento de
vias monoaminérgicas nestes efeitos
The gastroprotective effect of Memora nodosa roots against experimental gastric ulcer in mice
ABSTRACT Memora nodosa is popularly known as "caroba" and widely found in the Cerrado regions of Brazil. In traditional medicine, the leaves and stems are used for the healing of external ulcer and the roots for abdominal pain. This study investigated the effect of ethanolic roots extract of Memora nodosa (EMN) on the gastric mucosa of mice. In the indomethacin induced gastric ulcer model, the treatments of the animals with EMN at doses of 100, 300 and 1000 mg/kg, p.o., markedly reduced the index of lesions. In the gastric ulcer models induced by ethanol and cold restraint-stress the previous treatment with EMN at dose of 300 mg/kg showed 69% and 43% of protection, respectively. Seven days after food-restriction, the animals treated with EMN (300 mg/kg p.o.) showed reduction in the index of lesion by 65% as compared to control group. The intraduodenal administration of EMN (300 mg/kg) did not alter the gastric acid secretion parameters. The treatment with EMN (300 mg/kg p.o.) did not alter glutathione levels (GSH), but showed an increase of adhered gastric mucus as compared to the control group with lesion. These results showed that EMN has gastroprotective activity probably due with an increase of adhered gastric mucus
Antidepressive-like property of dichloromethane fraction of pimenta pseudocaryophyllus and relevance of monoamine metabolic enzymes
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Previous issue date: 2013Pimenta pseudocaryophyllus popularly referred to as craveiro is considered as a calming agent in different local preparations. e
present study attempted to examine antidepressant-like effect of dichloromethane fraction (DF) and role of monoamine oxidase
(MAO), tryptophan, and tyrosine hydroxylase. Based on the research focus, tail suspension (TS), forced swimming (FS), and
open �eld (OF) tests were conducted a�er oral administration of DF (125, 250, or 500 mg/Kg). Ex vivo assay of MAO was also
conducted to evaluate inhibitory effect of DF (250 mg/Kg). Administration of DF elicits antidepressant-like response in the TS and
FS. However, DF 500 mg/Kg did not alter mice performance in these models. e data obtained in the OF showed a reduction
in total crossing and rearing activity; these effects suggest motor interference in TS and FS performance. Mice pretreatment with
p-chlorophenylalanine methyl ester (PCPA) (100 mg/kg, i.p.—serotonin biosynthesis inhibitor) for 4 consecutive days or acute
administration of αα-methyl-p-tyrosine (AMPT) (100 mg/kg, i.p.—catecholamine synthesis inhibitor) blocked anti-immobility
effect of DF in the FS. In ex vivo assay of MAO, DF did not inhibit catabolic activity of MAO. Our �ndings support antidepressant