Effect of hesperidin on blood pressure and lipid profile: A systematic review and meta-analysis of randomized controlled trials.

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.

A systematic review and meta-analysis on the cardio-protective activity of naringin based on pre-clinical evidences.

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.

Acteoside isolated from Colebrookea oppositifolia attenuates I/R brain injury in Wistar rats via modulation of HIF-1α, NF-κB, and VEGF pathways.

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.

Acteoside Isolated from Colebrookea oppositifolia Smith Attenuates Epilepsy in Mice Via Modulation of Gamma-Aminobutyric Acid Pathways.

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.

Achyranthes aspera Linn. alleviates cerebral ischemia-reperfusion-induced neurocognitive, biochemical, morphological and histological alterations in Wistar rats.

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 800 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, n = 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, 10 ml/kg, p.o.). G-III received quercetin (20 mg/kg, p.o.) and assigned as reference standard. G-IV and G-V group animals received 400 and 800 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 72.48 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 µg/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 24 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 (800 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.

Amelioration of immobilization stress-induced biochemical and behavioral alterations and mitochondrial dysfunction by naringin in mice: possible mechanism of nitric oxide modulation.

OBJECTIVE: The present study was undertaken to evaluate the effects of naringin on immobilization stress-induced biochemical-behavioral changes and mitochondrial dysfunction in mice. METHODS: Mice were randomized and grouped based on body weights. Respective drug treatments were given for 14 d, and on the 15th day all the animals were subjected to a 6-hour immobilization stress; then all the animals were subjected to various behavioral paradigms and were sacrificed. Various biochemical parameters and mitochondrial functions were analyzed using brain homogenate. RESULTS: The 6-hour acute immobilization stress significantly altered the behavioral (anxiety and memory) and biochemical parameters coupled with mitochondrial dysfunction in mice. Fourteen days pretreatment with naringin (50 and 100 mg/kg, per oral) significantly inhibited the behavioral and biochemical alterations and mitochondrial dysfunction caused by acute immobilization stress (P<0.05). Further, pretreatment with L-arginine (50 mg/kg, intraperitoneally), a nitric oxide precursor, reversed the protective effect of naringin (P<0.05). In addition, pretreatment with NG-nitro-L-arginine methyl ester (5 mg/kg, intraperitoneally) caused potentiation in the protective effect of naringin. CONCLUSION: These results suggest the possible involvement of nitrergic pathway in the protective effect of naringin against immobilization stress-induced behavioral, biochemical and mitochondrial dysfunctions in mice.

Antidiarrheal effect of fractions from stem bark of Thespesia populnea in rodents: Possible antimotility and antisecretory mechanisms

OBJECTIVE@#To evaluate antidiarrheal activity of the fractions of aqueous extract from stem barks of Thespesia populnea (Malvaceae).@*METHODS@#From the aqueous extract three fractions namely ethyl acetate fraction (EAF), methanolic fraction (MF) and residue fraction (RF) were made and studied for antidiarrheal activity. Antidiarrheal activity of the fractions were evaluated in castor oil induced diarrhea, prostaglandin E(2) (PG-E(2)) induced diarrhea and charcoal meal test as in vivo models and the most potent fraction was further evaluated with in vitro models to determine the possible antimotility effect.@*RESULTS@#In castor oil induced diarrhea model, the RF (10, 25, 50 and 100 mg/kg, po.) and MF (100 mg/kg, po.) has significantly reduced the cumulative wet faecal mass, where as the EAF have not shown any significant antidiarrheal activity, RF was found to be more potent than MF. Based on these results and percentage yield, only RF was evaluated in PG-E(2) induced enteropooling and charcoal meal test. RF (10, 25 and 50 mg/kg) had shown significant inhibition of PG-E(2) induced secretions (antisecretory) and decreased the movement of charcoal in charcoal meal test indicating its antimotility activity. Furthermore, RF has showed significant inhibition of acetylcholine, histamine and BaCl(2) induced contractions on rat colon, guinea pig ileum and rabbit jejunum with EC(50) values of 241.7, 303.1 and 286.1 μg/mL, respectively indicating the antimotility effect of RF. The phytochemical analysis of RF showed presence of gums and mucilages and the possible mechanism may be the combination inhibition of elevated prostaglandin biosynthesis and reduced propulsive movement of the intestine.@*CONCLUSIONS@#RF possesses good antidiarrheal activity comparing with other two fractions and the possible mechanism thought to be associated with combination of antisecretory and antimolity.