RESUMEN
The cardioprotective activity of hesperidin has been well demonstrated in several clinical studies. Also, there is a meta-analysis published on this topic in 2019. However, considering the recently published clinical studies, there is a scope for performing a systematic review and meta-analysis of hesperidin to determine its beneficial effect in alleviating alterations in cardiovascular parameters. In this study, the literature search was performed using online databases such as PubMed and Google Scholar till April 2023 involving randomized controlled studies conducted on hesperidin against various cardiovascular disorders including metabolic disorders in healthy/diseased individuals compared to the placebo/control. Based on the inclusion and exclusion criteria, nine clinical studies involving 2414 subjects were included. The meta-analysis revealed that hesperidin has significantly reduced the low-density lipoprotein (LDL) (IV: -0.55 (-0.94 to -0.16) at 95% CI, p = 0.005, I2 = 70%), total cholesterol (TC) (IV: -61 (-0.82 to -0.41) at 95% CI, p < 0.00001, I2 = 69%), and triglycerides (TG) (IV: -0.21 (-0.40 to -0.02) at 95% CI, p = 0.03, I2 = 12%). However, there were no statistically significant changes in the systolic blood pressure (IV: -0.29 (-2.21 to 1.63) at 95% CI, p = 0.77, I2 = 60%), diastolic blood pressure (IV: 0.79 (-0.74 to 2.31) at 95% CI, p = 0.31, I2 = 49%), and high-density lipoprotein (IV: 0.04 (-0.25 to 0.34) at 95% CI, p = 0.78, I2 = 56%) in the hesperidin treatment compared to the placebo/control. In conclusion, the outcomes of this meta-analysis suggest that hesperidin administration could benefit patients with CVD by reducing LDL, TC, and TG. Further high-quality studies are needed to firmly establish the clinical efficacy of hesperidin for its benefits in treating cardiovascular conditions.
Asunto(s)
Presión Sanguínea , Hesperidina , Ensayos Clínicos Controlados Aleatorios como Asunto , Hesperidina/farmacología , Humanos , Presión Sanguínea/efectos de los fármacos , Lípidos/sangre , Triglicéridos/sangre , Enfermedades Cardiovasculares/prevención & controlRESUMEN
The cardioprotective role of naringin has been scientifically well demonstrated in various experimental models such as diabetic cardiomyopathy, ischemic heart diseases, diet-induced cardiac injury, antihypertensive and anti-platelet activities through various mechanisms. However, there is no meta-analysis performed on the cardioprotective activity of naringin. This systematic review and meta-analysis were focused to summarize and conclude the therapeutic benefits of naringin in various cardiovascular disorders using pre-clinical evidence. The online search was performed using electronic databases such as PubMed/Medline, Scopus, ScienceDirect, and Google scholar. The search was mainly focused on the role of naringin in various cardiovascular disorders in experimental animals. Based on the inclusion and exclusion criteria 34 studies were selected. The meta-analysis revealed that naringin could significantly alleviate various physical and chemical stimuli induced cardiovascular disorders such as diabetic cardiomyopathy, ischemic heart diseases, oxidative stress-induced cardiac injury, diet-induced cardiovascular dysfunctions in experimental models involving multiple mechanisms such as antioxidant (ROS/RNS pathways), anti-inflammatory (COX-2, IL-6, TNF-α, NF-κB pathways), enhancing angiogenic factors (VEGF, VCAM, HIF-1α, iNO), suppressing the apoptotic factors (BCL-2, BAX, caspases) and modulation of PCSK-9, PKCα/ß, PPAR-α, JAK/STAT, MAPKs (p38α, ERK1/2, JNK), and PI3K/AKT/mTOR/p70S6K associated pathways. Further, these changes at the cellular and molecular levels were manifested as improvement in the structural, functional, and physiology of the heart upon the naringin treatment. In conclusion, this systematic review and meta-analysis support the available scientific evidence on the therapeutic benefits of naringin in the management of various cardiovascular conditions.
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Flavanonas , Fosfatidilinositol 3-Quinasas , Animales , Flavanonas/farmacología , Flavanonas/uso terapéutico , FN-kappa B/metabolismo , Estrés Oxidativo , Fosfatidilinositol 3-Quinasas/metabolismoRESUMEN
AIMS: The objective of this study was to assess the anti-stroke activity of acteoside isolated from methanolic root extract of C. oppositifolia METHODS: Ischemia-reperfusion(I/R) brain injury was induced in Wistar rats to assess the anti-stroke activity of acteoside. Rats were pretreated with acteoside (10, 25 & 50 mg/kg, p.o.) before the induction of I/R injury. Parameters such as neurological, motor-cognitive functions were evaluated along with morphological (brain volume, infarct size), biochemical (SOD, Catalase, GSH, lipid peroxidation, TNF-α, IL-6, IL-10, ICAM-1, HIF-1α, VEGF, and NF-κB), histopathological, and gene expression studies (HIF-1α, VEGF) were performed to study the protective effect of acteoside against I/R induced brain injury. RESULTS: I/R injury caused significant deterioration of neurological (p < 0.01), motor (p < 0.01) and cognitive (p < 0.01) functions, associated with increase in the brain volume (p < 0.01), and infarct size (p < 0.01); increase in the levels of MDA, TNF-α, IL-6, ICAM-1, HIF-1α, VEGF, and NF-κB along with significant decrease in SOD, catalase, GSH, and IL-10 (p < 0.01 for all parameters) compared to Sham control group. Histology of brain tissue of disease control group exhibited significant vascular changes, neutrophil infiltration, cerebral oedema, and necrosis of the neuronal cells. Further, the gene-expression studies showed significant increase in the HIF-1α (p < 0.01) and VEGF (p < 0.01) mRNA levels in the I/R control compared to Sham control. Interestingly, the acteoside (10, 25 & 50 mg/kg) has prevented the neurological, motor and cognitive dysfunctions, along with inhibiting the morphological, biochemical, histological and gene expression changes induced by I/R-injury (p < 0.05 for 10 mg; p < 0.01 for 25 & 50 mg/kg of acteoside for all the parameters). CONCLUSION: These findings suggest that acteoside possess potent anti-stroke activity through modulation of HIF-1α, NF-κB, and VEGF pathway along with its potent antioxidant activity.
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Glucósidos/farmacología , Lamiaceae/química , Fenoles/farmacología , Extractos Vegetales/farmacología , Accidente Cerebrovascular/prevención & control , Animales , Antioxidantes/administración & dosificación , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Glucósidos/administración & dosificación , Glucósidos/aislamiento & purificación , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Masculino , FN-kappa B/metabolismo , Fenoles/administración & dosificación , Fenoles/aislamiento & purificación , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Ratas , Ratas Wistar , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/fisiopatología , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
The present study was aimed to evaluate the anticonvulsant activity of acteoside and explore its mechanism of action. Initially, the acteoside was evaluated in maximal electroshock (MES) and pentylenetetrazole (PTZ)-induced convulsions, and later it was evaluated against N-methyl-D-aspartic acid (NMDA)-induced mortality in Swiss albino mice. Based on the response in these models, further evaluations were performed to explore the mechanism of action. In the results, the acteoside (10, 25, and 50 mg/kg) has shown significant anticonvulsant activity in the PTZ model (p < 0.01 for all doses); however, there was no protection observed in MES and NMDA models. Therefore, further mechanism-based studies were performed on the PTZ model, and the outcomes have revealed that there was a significant reduction in GABA (p < 0.01 for both regions) and elevation of glutamate (p < 0.01 for both regions) in the cortex and hippocampus regions of PTZ-treated animals. Further, the antioxidant levels (SOD, catalase, GPx, GR, GSH, LPO) were altered significantly (p < 0.01 for all parameters), with reduced GABAA mRNA levels (p < 0.01) in the PTZ control compared with the normal control. Interestingly, co-administration of acteoside (25 mg/kg) (p < 0.01 for all parameters) has restored all the PTZ-induced alterations compared to PTZ-control. Moreover, the anti-PTZ action of acteoside was completely blocked in the presence of flumazenil, and thus confirmed the GABAergic mechanism behind the anticonvulsant activity of acteoside. Besides, actophotometer and rotarod tests have confirmed that the acteoside is free from central side effects like motor incoordination and locomotor deficits.
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Epilepsia/tratamiento farmacológico , Epilepsia/metabolismo , Glucósidos/uso terapéutico , Lamiaceae , Fenoles/uso terapéutico , Extractos Vegetales/uso terapéutico , Ácido gamma-Aminobutírico/metabolismo , Animales , Anticonvulsivantes/aislamiento & purificación , Anticonvulsivantes/farmacología , Anticonvulsivantes/uso terapéutico , Relación Dosis-Respuesta a Droga , Epilepsia/inducido químicamente , Antagonistas del GABA/aislamiento & purificación , Antagonistas del GABA/farmacología , Antagonistas del GABA/uso terapéutico , Glucósidos/aislamiento & purificación , Glucósidos/farmacología , Masculino , Ratones , N-Metilaspartato/toxicidad , Pentilenotetrazol/toxicidad , Fenoles/aislamiento & purificación , Fenoles/farmacología , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Raíces de Plantas , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiologíaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: In the traditional system of Indian medicine, the whole plant and roots of Achyranthes aspera L have been extensively used to treat neurological conditions such as epilepsy and stroke by the various ethnic communities of India. AIM OF THE STUDY: The present study was aimed to evaluate the cerebroprotective potential of methanol extract of A. aspera aerial parts (MeAA). MATERIALS AND METHODS: Initially the MeAA was evaluated for total phenolic content and subjected to detailed liquid chromatography-mass spectrometry analysis. Additionally, it was evaluated for in vitro antioxidant activity in ferric reducing antioxidant power, 2, 2-diphenyl-1-picrylhydrazyl and oxygen radical absorbance capacity assays. Furthermore, in RAW 264.7 cell lines the effect of MeAA was evaluated on lipopolysaccharide-induced generation of reactive oxygen species, nitrite and tumor necrosis factor-α. Finally, the MeAA (400 and 800â¯mg/kg) was evaluated against ischemia-reperfusion (I/R)-induced brain injury in rats. In brief, male Wistar rats were allocated in to five groups (G-I to G-V, nâ¯=â¯10). G-I and G-II assigned as sham control and I/R control, and received only vehicle (carboxy methyl cellulose 0.5% w/v, 10â¯ml/kg, p.o.). G-III received quercetin (20â¯mg/kg, p.o.) and assigned as reference standard. G-IV and G-V group animals received 400 and 800â¯mg/kg oral doses of MeAA, respectively. All the treatments were given orally for a period of seven days and the parameters such as functional (neurological, cognitive and motor), morphological (edema and infarct area), biochemical (superoxide dismutase, catalase, reduced glutathione, lipid peroxidation, cytokines), and histopathological evaluations of the brain tissue was performed. RESULTS: The MeAA exhibited 72.48â¯mg gallic acid equivalents/g of total phenolic content and the LC-MS/MS analysis showed acteoside, apigenin, and pentagalloyl glucose as major ingredients in the MeAA. In in vitro antioxidant assays, the MeAA showed good antioxidant activity with IC50 of 126.50⯵g/ml in DPPH assay; FRAP and ORAC values of 759.65 and 979.4 in FRAP and ORAC assays, respectively. Further, the MeAA significantly suppressed the generation of ROS, nitrite and TNF-α in LPS activated RAW 264.7 cell lines. Besides, sixty mins of global cerebral ischemia followed by 24â¯h of reperfusion produced considerable alterations in neurobehavioral functions in the I/R control group compared to sham control, with a significant reduction in catalase and superoxide dismutase enzyme activities. Moreover, there was a significant reduction in reduced glutathione levels with increased lipid peroxidation. Furthermore, the levels of pro-inflammatory cytokines (TNF-α, IL-6, and ICAM-I) increased significantly and those of anti-inflammatory (IL-10) decreased. I/R insult increased the brain volume and aggravated cerebral infarct formation. Histopathological examination of the brain tissue revealed vascular congestion, cerebral edema, leukocyte infiltration, and brain tissue necrosis. Interestingly, seven days pretreatment with MeAA (800â¯mg/kg, p.o.) has offered significant protection against I/R-induced functional, morphological, biochemical and histopathological alterations in Wistar rats. CONCLUSIONS: These findings suggest that the MeAA possesses potent cerebroprotective action through its antioxidant and anti-inflammatory mechanisms.
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Achyranthes , Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Isquemia Encefálica/tratamiento farmacológico , Disfunción Cognitiva/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Extractos Vegetales/uso terapéutico , Daño por Reperfusión/tratamiento farmacológico , Animales , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Masculino , Ratones , Fármacos Neuroprotectores/farmacología , Componentes Aéreos de las Plantas , Extractos Vegetales/farmacología , Células RAW 264.7 , Ratas WistarRESUMEN
OBJECTIVES: The present study was aimed to evaluate the effect of methanolic fruit extract of Momordica cymbalaria (MeMC) against high-fat diet-induced obesity and diabetes in C57BL/6 mice. MATERIALS AND METHODS: In the present study, six weeks old male C57BL/6 mice were divided into four groups. G-1 and G-2 served as lean control and HFD control, G-3 and G-4 received MeMC 25 and 50 mg/kg, BW doses; all the treatments were given for a period of 11 weeks. The parameters such as body weight, fasting blood glucose, insulin, cholesterol, free fatty acid, and oral glucose tolerance tests were performed, further, at the end of the study fasting body weight, and weights of organs such as the liver, heart, and adipose tissue were measured and the liver tissue was subjected to histopathology evaluation, and insulin resistance was expressed as HOMA-IR index. RESULTS: The high-fat diet fed C57 mice showed significant elevation of body weight (P<0.01), blood glucose (P<0.01), insulin (P<0.01), cholesterol (P<0.01), free fatty acid (P<0.01), and HOMA-IR index (P<0.01) along with significant elevation of all organ weights and reduction in oral glucose tolerance (P<0.01) and brown adipose weight (P<0.01). The histopathology showed significant fatty infiltration and hypertrophy of hepatocytes. Interestingly, MeMC (50 mg/kg) alleviated all the HFD-induced perturbances significantly. Further, the HPLC analysis of MeMC revealed the presence of gallic acid and rutin as chief ingredients. CONCLUSION: MeMC possesses potent antidiabetic activity and ameliorates insulin resistance in HFD diet fed C57 mice.
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ETHNOPHARMACOLOGICAL RELEVANCE: Colebrookea oppositifolia Smith is one of the extensively used plants to treat neurological conditions such as epilepsy by the various ethnic communities in sub-Himalayan regions of India such as Bhoxa, Tharu and nomadic Gujjars. AIM OF THE STUDY: This study was conducted to evaluate the cerebroprotective effect of C. oppositifolia methanolic root (MeCO) extract in Wistar rats. MATERIALS AND METHODS: The MeCO was characterized for total phenolic content and later subjected for detailed liquid chromatography-mass spectrometry analysis. Further, it was evaluated for in vitro antioxidant activity using 2, 2-diphenyl-1-picrylhydrazyl, ferric reducing antioxidant power and oxygen radical absorbance capacity assays. In addition, the MeCO was investigated on generation of ROS, nitrite, and TNF-α in LPS-stimulated RAW 264.7 cell lines. Finally, the cerebroprotective effect of MeCO was examined against global ischemia and reperfusion (I/R)-induced brain injury in Wistar rats. Male Wistar rats were allocated in to five groups (G-I to G-V, nâ¯=â¯10). G-I and G-II served as sham control and I/R control, respectively, and received only vehicle (0.5% w/v carboxy methyl cellulose, 10â¯ml/kg, p.o.). G-III served as reference standard and received quercetin (20â¯mg/kg, p.o.). G-IV and G-V animals received 200 and 400â¯mg/kg oral doses of MeCO, respectively. All the treatments were given for a period of seven days and the parameters such as neurobehavioral (neurological, and cognitive), and motor functions, biochemical (enzymatic and non-enzymatic antioxidants, TNF-α, IL-6, IL-10, ICAM-I), morphological (cerebral edema and infarct area) and histopathological evaluations were performed. RESULTS: The MeCO showed a total phenolic content of 137.28â¯mg gallic acid equivalents/g, and LC-MS/MS analysis of MeCO showed presence of acteoside, gossypin, quercetin and ferulic acid as major ingredients (6680.3, 1.55, 3.52 and 431.1â¯ng/mg). In in vitro antioxidant assays, the MeCO exhibited potent activity with IC50 of 49.10⯵g/ml in DPPH assay; FRAP and ORAC values of 1180.5 and 2983.5 respectively. Furthermore, the MeCO significantly inhibited generation of ROS, nitrite and TNF-α in LPS-stimulated RAW 264.7 cell lines. Sixty min of global ischemia with 24â¯h reperfusion produced substantial alterations in neurobehavioral functions in the I/R control group compared to sham control. In addition, a significant reduction in catalase and superoxide dismutase activities was observed. Moreover, lipid peroxidation increased and reduced glutathione levels decreased significantly. Furthermore, the levels of pro-inflammatory cytokines (TNF-α, IL-6, and ICAM-I) increased significantly and those of anti-inflammatory (IL-10) decreased. I/R insult increased the brain volume and aggravated cerebral infarct formation. Histopathological examination of the rat brain revealed vascular congestion, cerebral edema, leukocyte infiltration, and brain tissue necrosis. Interestingly, seven days pretreatment with MeCO (200 and 400â¯mg/kg) alleviated all the I/R-induced perturbances (neurobehavioral, and motor functions, biochemical, morphological and histopathological) compared with the I/R control. CONCLUSIONS: The MeCO exhibit potent cerebroprotective activity through its potent antioxidant and anti-inflammatory mechanisms, and hence may be useful in the management of ischemic stroke and associated complications.
Asunto(s)
Lamiaceae , Fármacos Neuroprotectores/uso terapéutico , Extractos Vegetales/uso terapéutico , Daño por Reperfusión/tratamiento farmacológico , Animales , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología , Catalasa/metabolismo , Supervivencia Celular/efectos de los fármacos , Citocinas/metabolismo , Glutatión/metabolismo , Masculino , Metanol/química , Ratones , Fármacos Neuroprotectores/farmacología , Nitritos/metabolismo , Fenoles/análisis , Fenoles/farmacología , Fenoles/uso terapéutico , Fitoterapia , Extractos Vegetales/análisis , Extractos Vegetales/farmacología , Raíces de Plantas/química , Células RAW 264.7 , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Daño por Reperfusión/fisiopatología , Solventes/química , Superóxido Dismutasa/metabolismoRESUMEN
OBJECTIVES: Naringin is a bioflavonoid, very abundantly found in citrus species. In literature, naringin has been scientifically well documented for its beneficial effects in various neurological disorders. In this systematic review and meta-analysis, we have made an attempt to correlate the protective role of naringin against oxidative stress-induced neurological disorders in rodents. METHODS: The systematic search was performed using electronic databases; the search was mainly focused on the role of naringin in oxidative stress-induced neuropathological conditions in rodents. While, the meta-analysis was performed on the effect of naringin on oxidative stress markers [superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), reduced glutathione (GSH), lipid peroxidation (LPO)], nitrite, mitochondrial complexes (I to IV) and enzymes (acetylcholinesterase, Na+-K+-ATPase, Ca2+-ATPase, and Mg2+-ATPase) in the rodent brain. The data was analyzed using Review Manager Software. THE RESULTS: Based on the inclusion and exclusion criteria, twenty studies were selected. The meta-analysis revealed that, naringin could significantly inhibit various physical and chemical stimuli- induced neurological perturbances in the rodent brain, mediated through oxidative stress. Further, naringin also significantly restored the levels of all the oxidative stress markers (oxidative, nitrosative, enzymes, and mitochondrial complexes) in different parts of the rodent brain. SUMMARY: This systematic review and meta-analysis supports the available scientific evidence on the beneficial role of naringin in the management of various neurological ailments. However, further studies involving human subjects is recommended to establish the safety and therapeutic efficacy in humans.
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Citrus/química , Disfunción Cognitiva/tratamiento farmacológico , Flavanonas/farmacología , Flavonoides/farmacología , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Animales , Humanos , RoedoresRESUMEN
BACKGROUND: Colebrookea oppositifolia Smith is one of the commonly used plants to treat epilepsy by various folk medicine communities like nomadic Gujjars, Tharu and Bhoxa in sub-Himalayan regions of India. PURPOSE: The present study was undertaken to evaluate the anticonvulsant activity of roots of Colebrookea oppositifolia using various experimental models of epilepsy in mice. METHODS: Petroleum ether extract of roots of C. Oppositifolia (PeCO), methanolic eCO (MeCO) and aqueous eCO (AeCO) was initially evaluated in six-hertz-seizure test in mice, the effective extract was further evaluated against maximal electroshock (MES) and pentylenetetrazole (PTZ) models in mice. In addition, the potent extract was evaluated against the PTZ model by co-administering with flumazenil (FMZ), and also evaluated for its effect on brain GABA levels in brain and NMDA-induced lethality in mice. Furthermore, the possible locomotor deficit-inducing property of the extract was evaluated by actophotometer test in mice. RESULTS: In six-hertz-seizure test the MeCO (25, 50, 100 and 200mg/kg) and AeCO (50, 100, 200, 400 and 800mg/kg) showed significant protection compared to control group, and MeCO was more potent than AeCO. Based on these outcomes, only MeCO was evaluated in MES and PTZ models. Notably, the MeCO (25, 50, 100 and 200mg/kg) has offered significant and dose- dependent protection against MES and PTZ-induced seizures in mice. Alongside, the MeCO (100 and 200mg/kg) showed a significant increase in GABA levels in the brain compared to control. In line with these findings, the anti-PTZ effect of MeCO (100mg/kg, p.o.) was blocked when co-administered with flumazenil (3mg/kg, i.p.),and in NMDA-induced mortality test, the MeCO has shown only 50% protection at 200mg/kg dose, thus confirmed the significant role of GABA pathway. Interestingly, the MeCO did not cause significant change in locomotor activity compared to before treatment. CONCLUSION: These findings suggest that MeCO possess significant anticonvulsant activity and the outcomes further confirmed the involvement of GABAergic mechanisms behind the anticonvulsant activity of MeCO.
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Epilepsia/tratamiento farmacológico , Lamiaceae/química , Extractos Vegetales/farmacología , Raíces de Plantas/química , Ácido gamma-Aminobutírico/metabolismo , Animales , Anticonvulsivantes/farmacología , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Electrochoque/métodos , Medicina Tradicional/métodos , Metanol/química , Ratones , Modelos Teóricos , Pentilenotetrazol/farmacología , Fitoterapia/métodos , Convulsiones/tratamiento farmacológico , Convulsiones/metabolismo , Solventes/químicaRESUMEN
The present study was aimed to examine the possible anticonvulsant property of aerial parts of Achyranthes aspera using various experimental models of epilepsy in mice. Petroleum ether extract of aerial parts of A. aspera (PeAA), methanolic eAA (MeAA) and aqueous eAA (AeAA) was initially evaluated against six-hertz seizure model in mice, based on the outcomes the effective extract was further evaluated against maximal electroshock (MES) and pentylenetetrazole (PTZ) models in mice. In addition, the potent extract was evaluated against the PTZ model by co-administering with flumazenil (FMZ), and also evaluated for its effect on GABA levels in brain and NMDA-induced lethality in mice. Furthermore, the probable locomotor deficit-inducing property of the extract was evaluated by actophotometer test in mice. In results, only MeAA showed protection against six-hertz-induced seizures in mice, based on these outcomes only MeAA was evaluated in MES and PTZ models. Notably, the MeAA (200, 400 and 800 mg/kg) has offered mild and dose dependent protection against MES and PTZ-induced seizures in mice. Alongside, the MeAA (400 mg/kg) showed a significant increase in GABA levels in the brain compared to control, and in line with these findings the anti-PTZ effect of MeAA (400 mg/kg, p.o.) was blocked when co-administered with flumazenil (5 mg/kg, i.p.). However, the MeAA has not shown significant protection against NMDA-induced mortality and also did not cause significant change in locomotor activity compared to before treatment. These findings suggest that MeAA possess mild anticonvulsant activity and the outcomes further confirmed the involvement of GABAergic mechanism behind the anticonvulsant activity of MeAA.
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Achyranthes , Epilepsia/tratamiento farmacológico , Epilepsia/metabolismo , Neuronas GABAérgicas/metabolismo , Extractos Vegetales/uso terapéutico , Ácido gamma-Aminobutírico/metabolismo , Animales , Relación Dosis-Respuesta a Droga , Femenino , Neuronas GABAérgicas/efectos de los fármacos , Masculino , Ratones , Componentes Aéreos de las Plantas , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacologíaRESUMEN
OBJECTIVES: The present study was undertaken to evaluate the immunomodulatory (IM) activity of IM-133N, a herbal combination in various immunotherapeutic experimental models. METHODS: The IM activity of IM-133N was evaluated against three experimental models namely, effect of IM- 133N against Escherichia coli (E. coli)-induced abdominal sepsis in mice, and carbon clearance test was performed in Wistar albino rats to evaluated the phagocytic potential of IM-133N, in addition IM-133N was evaluated for its immunoglobulin enhancing potential in rats, where the immunoglobulin levels were measured by zinc sulphate turbity (ZST) test. Further, IM-133N was subjected for detailed liquid chromatography-mass spectrometry (LC-MS)/MS analysis to identify the probable active constituents present in it. RESULTS: The findings of the present study has demonstrated very promising IM property of IM-133N in all the experimental models. Briefly, pretreatment with IM-133N at 125, 250, 500 and 1,000 mg/kg, p.o. doses had protected the mice against E. coli-induced abdominal sepsis and mortality, further the effect of IM- 133N was found to be significant and dose-dependent. In support of this, in another study administration of IM-133N showed a significant and dose-dependent increase in serum immunoglobulin levels, estimated by ZST test. In line with the above findings, in the carbon clearance test the low doses (125 and 250 mg/ kg, p.o.) of IM-133N increased the rate of carbon clearance, whereas the higher doses (500 and 1,000 mg/kg, p.o.) did not sustain the response, and saturation effect was considered as one of the possible reason for futility of higher doses for IM-133N. In addition, A detailed LC-MS/MS analysis of IM-133N showed 17 bioactive phytochemical constituents: namely, apigenin, chaulmoogric acid, mesquitol, quercetin, symphoxanthone, salireposide, ß-sitosterol, nonaeicosanol, ß-amyrin, betulic acid, oleanolic acid, symplososide, symponoside, symploveroside, symplocomoside, symconoside A and locoracemoside B. CONCLUSION: These findings suggest that IM-133N possesses significant IM activity and, hence, could be useful for eradicating opportunistic disease-triggering pathogens via immunotherapeutic mechanisms. The findings also suggest IM-133N may also useful in other immunity disorders.
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OBJECTIVE: The aim of this study was to evaluate the possible beneficial effects of Mentat against transient global ischemia and reperfusion-induced brain injury in rats. METHODS: The neuroprotective effects of Mentat were evaluated against transient global ischemia and reperfusion (I/R)-induced brain injury in rats. Various neurobehavioral and biochemical parameters were assessed, followed by morphologic and histopathologic evaluation of brain tissue to conclude the protective effect of Mentat. Additionally, in vitro antioxidant assays were performed to explore the antioxidant capacity of Mentat and detailed liquid chromatography-mass spectrometry (LC-MS/MS) profiling was carried out to identify the active phytoconstituents responsible for the protective effects of Mentat. RESULTS: Sixty minutes of transient global ischemia followed by 24 h reperfusion (I/R) caused significant alterations in the cognitive and neurologic functions in the ischemia control group (P < 0.01) compared with the sham control. Furthermore, 2,3,5-triphenyltetrazolium chloride staining of the ischemia control group showed 20.85% ± 0.39% of cerebral infarct area (P < 0.01), increased brain volume (% edema 17.81% ± 1.576%; P < 0.01), and increased lipid peroxidation (P < 0.01) in the brain homogenate. Additionally, the histopathology of the ischemia control group showed severe brain injury compared with the sham control group. Interestingly, pretreatment with Mentat (250 and 500 mg/kg, p.o.) and quercetin (20 mg/kg, p.o.) for 7 d has alleviated all pathological changes observed due to I/R injury. Mentat also showed very good antioxidant activity in in vitro assays (2,2-diphenyl-l-picrylhydrazyl, ferric-reducing antioxidant power, and oxygen radical absorbance capacity assays). Furthermore, the detailed LC-MS/MS analysis of Mentat was performed and enclosed for identifying the actives responsible for its protective effects. CONCLUSIONS: These findings suggest that Mentat is a neuroprotective agent that may be a useful adjunct in the management of ischemic stroke and its rehabilitation especially with respect to associated memory impairment and other related neurologic conditions.
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Infarto Cerebral/prevención & control , Ataque Isquémico Transitorio/tratamiento farmacológico , Peroxidación de Lípido/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Extractos Vegetales/farmacología , Daño por Reperfusión/prevención & control , Animales , Antioxidantes/administración & dosificación , Antioxidantes/farmacología , Edema Encefálico/tratamiento farmacológico , Edema Encefálico/etiología , Infarto Cerebral/etiología , Infarto Cerebral/patología , Cromatografía Liquida/métodos , Modelos Animales de Enfermedad , Ataque Isquémico Transitorio/complicaciones , Ataque Isquémico Transitorio/patología , Masculino , Espectrometría de Masas/métodos , Fármacos Neuroprotectores/administración & dosificación , Extractos Vegetales/administración & dosificación , Quercetina/administración & dosificación , Quercetina/farmacología , Ratas , Ratas Wistar , Daño por Reperfusión/etiología , Daño por Reperfusión/patología , Factores de Tiempo , Resultado del TratamientoRESUMEN
Objective. To improve the existing experimental model of croton oil-induced hemorrhoids in rats by using Evans Blue (EB) dye extravasation technique. Further, an herbal formulation (Pilex) was evaluated for its antihemorrhoidal activity in this model. Methods. Two sets of experiments were carried out: first to improve the experimental model and to validate the same using Pilex and second to evaluate the effect of Pilex on cytoarchitecture of rectoanal tissue in croton oil-induced hemorrhoids. In both sets, hemorrhoids were induced to all the animals, except normal controls, by applying croton oil via rectoanal region and the effect of Pilex ointment (PO), Pilex granules (PG), and combination of PG and PO was evaluated. In the first set, extravasation of EB dye, TNF- α , IL-6, and rectoanal coefficient (RAC) was determined. In the second set, severity of score, RAC, and histopathology were evaluated. Results. The elevated levels of TNF- α , IL-6, and extravasations of EB dye were decreased with the Pilex treatment. The cytoarchitecture of rectoanal portion of the animals treated with Pilex was near to normal. Conclusion. The improved experimental model of hemorrhoid is useful in quantifying the inflammatory exudates and extent of inflammation. In this improved experimental model Pilex showed antihemorrhoidal activity, which further validates its clinical usage.