Galphimia Glauca Cav Research Articles

Isolation, Characterization and Assessment for Muscle Relaxant Activity of Novel Phytomolecule from Galphimia glauca Cav. Stems

Objectives: Galphimia glauca Cav (Gg) is an evergreen medicinal herb found growing in Indian subcontinent and more in the Deccan plateau regions of south India. The objective of the current work is to isolate, characterize and explore the muscle relaxant activity of the novel isolated phytomolecule (BS-4) from G. glauca stems using in vivo models. Methods: The obtained bio-active fraction (methanol fraction) of the G. glauca stem methanol extract (GgSME) was subjected to column chromatography and Preparative thin layer chromatography (TLC) to isolate the bioactive phytomolecule. The novel isolated bioactive phytomolecule was coded as “BS-4”, it is then characterized by Rf value, melting point, IR spectra, HPLC, Mass spectra, 1H-NMR spectrum and 13C NMR spectrum and evaluated for muscle relaxant activity by administering BS-4 in Swiss albino mice in one day to animal models like Rota rod test and Grip strengthening test. Results: The LD50 of BS-4 was > 2000 mg/kg. The mice were treated with BS-4 at 12.5, 25 and 50mg/kg doses. The BS-4 showed dose dependent significant (P ≤ 0.001) effects on muscle relaxant activity in Rota rod test and Grip strengthening test in mice (P ≤ 0.001). Conclusion: The current study results conclude that the isolated novel phytomolecule BS-4 has significant muscle relaxant effects. Keywords: Galphimia glauca Clav, Column chromatography, Rota rod test, Grip strengthening test, Phytomolecule.

DNA barcoding and TLC as tools to properly identify natural populations of the Mexican medicinal species Galphimia glauca Cav.

Galphimia glauca is a plant that is endemic to Mexico and has been commonly used since pre-Hispanic times to treat various illnesses, including central nervous system disorders and inflammation. The first studies investigating a natural population of G. glauca in Mexico showed that the plant has anxiolytic and sedative activities in mice and humans. The plant’s bioactive compounds were isolated and identified, and they belong to a family of nor-secofriedelanes called galphimines. The integration of DNA barcoding and thin-layer chromatography analysis was performed to clarify whether the botanical classification of the populations in the study, which were collected in different regions of Mexico, as G. glauca was correct or if the populations consist of more than one species of the genus Galphimia. We employed six DNA barcodes (matK, rbcL, rpoC1, psbA-trnH, ITS1 and ITS2) that were analyzed individually and in combination and then compared each other, to indicate differences among the studied populations. In the phylogenetic analysis, ITS1 and ITS2 markers as well as the combination of all DNA regions were the most efficient for discriminating the population studied. The thin-layer chromatography analysis exhibited four principal chemical profiles, one of which corresponded to the populations that produced galphimines. DNA barcoding was consistent and enabled us to differentiate the populations that produce galphimines from those that do not. The results of this investigation suggest that the studied populations belong to at least four different species of the genus Galphimia. The phylogenetic analysis and the thin-layer chromatography chemical profiles were convenient tools for establishing a strong relationship between the genotype and phenotype of the studied populations and could be used for quality control purposes to prepare herbal medicines from plants of the genus Galphimia.

Isolation, Characterization and Assessment for Central Nervous System Effects of Novel Phytomolecule from Galphimia glauca Cav. Stems

The investigation had explored the in vivo central nervous system (CNS) effects of novel isolated phytoconstituent from Galphimia glauca stems. The isolated molecule coded as “BS-2” was subjected to toxicological, central analgesic and central nervous system depressant studies on Swiss albino mice and Wistar rats. The LD-50 of BS-2 was found to be > 2000 mg/kg. The mice treated with BS-2 at 12.5, 25 and 50 mg/kg doses exhibited significant effect in the hot plate test (P < 0.5) and tail clip test (83 % inhibition). Mice treated with BS-2 prolonged the time of sleep induced by sodium pentobarbital (40 mg/kg, i.p.). Throughout the hole-board experiment and open field test the BS-2 at 50 mg/kg exhibited a significant (P ≤ 0.001) dose-dependent activity. The BS-2 was characterized by Rf value, melting point, IR spectra, mass spectra and 1H NMR spectrum. The BS-2 showed potential in vivo central pain relieving and central nervous system depressant effects.

Innovative research on isolation, characterization, and identification of bioactivity in the isolated constituent from methanol extract of Galphimia glauca cav. stems

Background: Galphimia glauca Cav (GG) is naturalized in tropical and subtropical regions of the world including India. Objective: The present study has been opted to shed light on GG stems to isolate, characterize, and explore the analgesic and anti-inflammatory potential of the isolated phytomolecule using in vivo models. Materials and Methods: The bioactive fraction of the active stem methanol extract was subjected to column chromatography followed by preparative thin layer chromatography to separate the phytoconstituent. The isolated phytoconstituent was characterized and evaluated for toxicological studies, analgesic, and anti-inflammatory activity. Results: The isolated phytoconstituent “BS-1” was characterized by melting point, Rf value, IR spectra, mass spectra, 1H-NMR spectrum, and 13C NMR spectrum. The LD50of BS-1 was found to be >2000 mg/kg. The results were significant (P Abbreviations Used: GG: Galphimia glauca, GGSME: Galphimia glauca stem methanol extract, GGH: G. glauca n-hexane fraction, GGC: G. glauca chloroform fraction, GGEA: G. glauca ethyl acetate fraction, GGM: G. glauca methanol fraction, IAEC: Institutional Animal Ethics Committee, CPCSEA: Committee for the Purpose of Control and Supervision of Experimental Animals, OECD: The Organization for Economic Co-operation and Development, WHO: World Health Organization, b.w: Body weight, i.p: Intraperitoneal, p.o: per oral, NSAIDS: Nonsteroidal anti-inflammatory drugs, IPE (%): Indicates percentage inhibition of paw edema, 1H-NMR: Proton nuclear magnetic resonance, 13C NMR: Carbon-13 nuclear magnetic resonance, LCP: Lalitha College of Pharmacy, AGI: Anurag Group of Institutions, BS-1: Novel isolated molecule.

Therapeutic Effectiveness of Galphimia glauca vs. Lorazepam in Generalized Anxiety Disorder. A Controlled 15-Week Clinical Trial

Galphimia glauca Cav. has demonstrated anxiolytic activity attributable to nor-seco-triterpenes denominated galphimines, the most active of which is galphimine-B. Galphimine-B inhibits ventral tegmental area dopaminergic neurons and interacts with the serotoninergic system of the dorsal hippocampus. A previous clinical study that administered a G. glauca herbal medicinal product for 4 weeks evidenced high percentages of therapeutic effectiveness and safety in patients with generalized anxiety disorder. Based on the previous findings, the goal of the present study was to evaluate the effectiveness, safety, and tolerability of G. glauca herbal medicinal product administered during 15 weeks in patients with generalized anxiety disorder. double-blind, randomized, lorazepam-controlled clinical trial. adult males and females, ambulatory, diagnosed with generalized anxiety disorder, with 20 or more points on the Hamilton anxiety scale, without data of depression, and without anxiolytic treatment in the previous month. Interventions were as follows. Experimental treatment: G. glauca herbal medicinal product in capsules containing the dry extract of G. glauca standardized in 0.175 mg of galphimine-B, one or two capsules twice a day, during 12 weeks plus 3 withdrawal weeks, and control treatment: lorazepam 0.5 mg with the same presentation and posology. anxiolytic effectiveness (≥ 50 % reduction of initial Hamilton anxiety scale score). tolerability and safety. One hundred ninety-one patients initiated the study with 94 in the experimental group. One hundred four patients concluded the study, 51 of these in the experimental group. Anxiolytic effectiveness, measured as 0 in a negative case and as 1 in a positive case, was assessed 593 times in the experimental group and 631 in the control; the mean effectiveness observed was 0.686 ± 0.019 vs. 0.588 ± 0.019 (repeated-measures ANOVA; p = 0.0003). In the same way, G. glauca-herbal medicinal product diminished the score in the Hamilton anxiety scale to 11.51 ± 8.27 points and lorazepam to 12.40 ± 8.07 points (repeated-measures ANOVA; p = 0.05). The tolerability analysis, which comprised patients who concluded the treatment plus 11 patients who withdrew due to adverse reactions did not show differences between treatments (p = 0.35), nor did therapeutic safety demonstrate differences between groups (p = 0.21). There were no cases of tolerance, intoxication, dependence, or suppression syndrome. We concluded that G. glauca herbal medicinal product, standardized in 0.175 mg of galphimine-B and administered for 15 weeks to patients with generalized anxiety disorder, showed greater anxiolytic effectiveness than that obtained with lorazepam, with high percentages of therapeutic tolerability and safety.

New anxiolytic phytopharmaceutical elaborated with the standardized extract of Galphimia glauca

A new phytopharmaceutical with anxiolytic effectiveness has been developed. This product was elaborated with the standardized extract obtained from the plant species Galphimia glauca Cav. (Malpighiaceae). Galphimia glauca has for many years been used in Mexican traditional medicine as a “tranquilizer”. Different in vivo and in vitro pharmacological studies have demonstrated the anxiolytic activity of crude extract obtained from G. glauca. The pharmacological effect produced by the G. glauca extract has been attributed to the nor-seco,triterpene galphimine-B (G-B). This compound has exhibited an innovative action mechanism, selective of dopaminergic neurons on ventral tegmental area.The therapeutic effectiveness, safety, and tolerability of the new phytopharmaceutical was compared with lorazepam on patients with Generalized Anxiety Disorder (GAD). By means of a controlled, randomized, double-blind clinical trial, outpatients of either sex who matched the DSM-IV's diagnostic criteria with a score of ≥19 points on the Hamilton Anxiety Scale (HAM-A) were included. The experimental group was treated orally with the phytopharmaceutical in capsules twice a day for 4 weeks. The control group received lorazepam (1mg) under the same conditions and presentation. A total of 152 patients were included in the trial (72 in the experimental group). From the first week of treatment, the phytopharmaceutical showed important anxiolytic effectiveness, very similar to that produced with lorazepam. Both treatments showed therapeutic safety, nevertheless, concerning side effects the phytopharmaceutical evidenced considerably higher tolerability than lorazepam.

Interaction of the natural anxiolytic Galphimine-B with serotonergic drugs on dorsal hippocampus in rats

Galphimine-B (G-B) is a nor-seco triterpene with an anxiolytic-like effect obtained from the plant species Galphimia glauca Cav. By means of a double blind clinical trial, it has been demonstrated that the extract from this plant, standardized in G-B content, possesses therapeutic effectiveness in patients with generalized anxiety. The mechanism of action of this compound remains unknown to date, but it has already demonstrated a non interaction with the γ-aminobutyric acid (GABA)ergic system. For this reason, the objective of this work was to evaluate the pharmacological interaction between G-B with the 5-hydroxytryptamine 1A (5HT(1A)) and 5-hydroxytryptamine 2A (5HT(2A)) serotonergic receptors on CA1 neurons of hippocampus. Electrophysiological records were performed as the frequency of discharge of in vivo CA1 cells from dorsal hippocampus in rats. G-B was able to increase the frequency of discharge of neurons of the CA1 cells with some characteristics that support an interaction with the serotonergic system in this zone. It was demonstrated that this triterpene modulates the induced response of 5HT(1A) receptors, in an allosteric manner. This effect demonstrated an interaction between G-B and the serotonergic system in dorsal hippocampus and evidenced that the mechanism of action of this compound could involve a complex series of actions on different neurotransmitter systems related with the anxiety disorder.

Efficacy and Tolerability of a Standardized Herbal Product from Galphimia glauca on Generalized Anxiety Disorder. A Randomized, Double-Blind Clinical Trial Controlled with Lorazepam

Galphimia glauca Cav. is a plant used in Mexican traditional medicine as a "nerve tranquilizer". Previous studies have demonstrated that the methanolic extract from this plant species possess an anxiolytic effect. Galphimine B (GB, a nor-seco-triterpene), is the active principle, with an innovative action mechanism. Against this background, a standardized herbal medicinal product was developed from the aqueous extract of G. glauca (GgHP). The present work compared the therapeutic effectiveness, safety, and tolerability of the new GgHP with lorazepam on patients with generalized anxiety disorder (GAD). By means of a controlled, randomized, double-blind clinical trial, outpatients of either sex who matched the DSM-IV diagnostic criteria with a score of > or = 19 points on the Hamilton Anxiety Scale (HAM-A) were included. The experimental group was treated orally with GgHP in capsules twice a day for 4 weeks. The control group received lorazepam (1 mg) under the same conditions and presentation. A total of 152 patients were included in the trial (72 in the experimental group). From the first week of treatment, GgHP showed important anxiolytic effectiveness, very similar to that produced with lorazepam. Both treatments showed therapeutic safety (no alterations on biochemical analysis of hepatic and renal function). Nevertheless, concerning side effects, GgHP evidenced a considerably higher tolerability than lorazepam.

Qualitative and quantitative analysis of multiple galloyl derivatives of quinic acid from the medicinal plant Galphimia glauca Cav. using HPLC-ESI-MS

Qualitative and quantitative analysis of multiple galloyl derivatives of quinic acid from the medicinal plant Galphimia glauca Cav. using HPLC-ESI-MS

Toxicological and cytotoxic evaluation of standardized extracts of Galphimia glauca

Galphimia glauca Cav (Malpighiaceae) has been widely used in Mexican traditional medicine as a remedy for the treatment of mental disorders, principally as a sedative and tranquilizer. The sedative activity of extracts obtained from this plant has been demonstrated with different neuropharmacological models. Different triterpenes, known as galphimines, have been identified from the active extract. Galphimine-B (G-B) possesses anxiolytic activity and is able to selectively inhibit discharges of dopaminergic neurons in the ventral tegmental area in rats. Nevertheless, there have been no toxicological investigations carried out with products obtained from this plant. In this work three different extracts (aqueous, ethanolic, and methanolic) of Galphimia glauca, standardized in the content of three galphimines, were evaluated for their behavioral and pharmaco-toxicological effects. After administering the extracts to mice for 28 days (2.5 g/kg, p.o.), no deaths were found and the histopathological analysis of different organs did not show alterations; only the behavioral parameters analyzed showed a diminution of spontaneous activity. The administration of these extracts for 56 days (same doses and route) in mice did not cause any changes in the biochemical parameters that evaluate liver function. On the other hand, no cytotoxic effects were found on KB, UISO, and OVCAR-5 transformed cell lines, but all extracts specifically inhibited colon cancer cell line growth with an ED 50 lower than 2 μg/ml. The extracts were also evaluated in genotoxicity tests in vitro (250, 100 and 50 μg/ml), which demonstrate that none of the three extracts from Galphimia glauca showed a genotoxic effect.

In vitroPropagation ofGalphimia glaucaand Content of the Sedative Compound Galphimine-B in Wild and Micropropagated Plants

An in vitro micropropagation protocol is described for Galphimia glauca Cav. (Malpighighiaceae). Multiple shoots were formed in vitro from axillary bud explants inoculated on MS medium supplemented with indole-3-acetic acid (IAA) and kinetin (KN) combinations. A maximum of 20 shoots was obtained from a single bud in a 60-day culture period. In vitro-grown shoots were successfully rooted and transferred to field conditions (90 % survival). The sedative triterpenoid galphimine-B (1) content of micropropagated plants transferred to field conditions was similar to that of wild plants. Our results suggest that the in vitro propagation protocol described here will have positive effects on conservation of natural resources as well as on adequate techniques for multiplication of an important Mexican medicinal plant.

Effect of Neutralizing Irrigation Water Alkalinity with Acid on Nutritional Status and Growth of Thryallis (Galphimia glauca Cav.)

Sources of irrigation water in South Florida typically contain high levels of dissolved carbonates and bicarbonates. Repeated application of high alkalinity water can cause substrate-solution pH to rise, thereby altering nutrient availability, and possibly leading to the development of nutrient disorders and a reduction in plant growth. The objectives of the current study were to determine the effects of neutralizing alkalinity of irrigation water on the nutritional status and growth of Thryallis (Galphimia glauca Cav.). Plants were grown in 11.4-L containers in a 5 peat: 4 pine bark: 1sand (v:v:v) mix. Treatments were prepared with water collected from a commercial nursery with inherent calcium carbonate levels in excess of 260 mg·L-1 and pH above 7.3. Treatments consisted of 0% (control), 40%, or 80% alkalinity neutralized with sulfuric acid. At harvest, 51 weeks after initiating treatments, foliar levels of Fe were 28% greater, Mn 55% greater, and Zn 27% greater in the 80% than 0% neutralized alkalinity treatment. Growth indices and leaf greenness averaged over the course of the study were significantly greater in the 40% than in the 0% or 80% alkalinity neutralized treatments. Over the course of the study, leachate pH averaged 7.5, 6.8, and 5.3; and electrical conductivity (EC) averaged 1.4, 1.9, and 2.2 dS·m-1 in the 0%, 40%, and 80% alkalinity neutralized treatments, respectively.

Galphimine B modulates synaptic transmission on dopaminergic ventral tegmental area neurons.

Galphimine B (GB) is a bioactive compound isolated from the plant Galphimia glauca Cav. (Malpighiaceae) and has been shown to have central nervous system depressant properties. In an earlier study, it was reported that both systemic and local administration of GB modified the extracellular spontaneous spiking activity in the ventral tegmental area (VTA) neurons. In the present study we analyzed the synaptic effects of this compound on dopaminergic neurons. Recordings were made in brain slices using intracellular and patch-clamp techniques, in dopaminergic (DA) VTA neurons. Spontaneous miniature excitatory postsynaptic currents (mEPSCs), excitatory postsynaptic currents (EPSCs) and inhibitory postsynaptic potentials (IPSPs) were recorded in control situation and after bath infusions of several concentrations of GB (1 microM-5 mM), GABA (1 nM-100 microM) and the GABA A blockers, picrotoxin (100 microM) and bicuculline (10 microM), and GABA B blocker saclofen (200 microM). GB administration reduced the frequency (p < 0.05) but not the amplitude of mESPCs. However, GABA (IC 50 = 645 nM) and GB (IC 50 = 174.5 microM) infusion significantly reduced the amplitude of stimuli induced EPSCs, Bicuculline (10 microM) co-administration only reduced GABA effects and did not modify the GB depressant action. Finally, isolated GABAergic IPSPs were modified by the addition of picrotoxin, but GB had no effect on these evoked synaptic responses. The present results indicate that GB modifies synaptic activity on dopaminergic VTA neurons by a non-GABAergic mechanism.

Galphimine-B modifies electrical activity of ventral tegmental area neurons in rats.

Galphimine-B (G-B) is a bioactive compound isolated from the plant Galphimia glauca Cav. (Malpighiaceae) with central nervous system depressant properties previously described. In the present study, extracellular spiking activity records in either somatosensorial cortex or ventral tegmental area (VTA) neurons, were performed in rats after i.p. or local administration of G-B. None of the cortical neurons displayed significant changes induced by any of the applied doses. In VTA cells, two patterns of electrical discharge were recorded, bursting (57%) and nonbursting (43%) types. Systemic administration of G-B induced excitatory effects in neurons with a bursting firing pattern and mixed responses on nonbursting units. When this compound was applied locally by microiontophoresis, most of the bursting and nonbursting spiking neurons showed a firing depression and only a few of the nonbursting neurons showed an increment of discharge frequency. These results are important since VTA is a major dopaminergic center responsible for the innervation of the prefrontal cortex, nucleus accumbens and entorhinal region. These areas are targets for the action of antipsychotic drugs.

Sedative effect of galphimine B, a nor-seco-triterpenoid from Galphimia glauca.

Galphimia glauca Cav. (Malpighiaceae) is used in Mexican traditional medicine as a sedative in the treatment of mental disorders. Sedative properties of a methanolic extract of the aerial parts of this plant have been established in animal trials and an active compound, named galphimine B, has already been isolated. This compound was submitted to neuropharmacological testing, where it was shown that galphimine B had no significant effect as an anticonvulsant, while it exhibited a strong depressant activity on the nervous system.

Effect of Galphimia glauca methanolic extract on neuropharmacological tests.

Galphimia glauca Cav. (Malpighiaceae) is used in Mexican traditional medicine for the treatment of nervous excitement. A methanolic extract from its aerial parts (MEGA) was tested in several neuropharmacological animal models including among others: hypothermic activity, barbiturate potentiation, protection against strychnine- and leptazol-induced convulsions. The combined data obtained from all biological models demonstrate the sedative property of this plant product.