echinacoside and Disease-Models--Animal

Echinacoside (ECH) is the dominant phenylethanoid glycoside-structured compound identified from our developed herbal formula Huangci granule, which has been previously reported to inhibit the invasion and metastasis of CRC and prolong patients' disease-free survival duration. Though ECH has inhibitory activity against aggressive colorectal cancer (CRC) cells, its anti-metastasis effect in vivo and the action mechanism is undetermined. Given that ECH has an extremely low bioavailability and gut microbiota drives the CRC progression, we hypothesized that ECH could inhibit metastatic CRC by targeting the gut microbiome.. The purpose of this study was to investigate the impact of ECH on colorectal cancer liver metastasis in vivo and its potential mechanisms.. An intrasplenic injection-induced liver metastatic model was established to examine the efficiency of ECH on tumor metastasis in vivo. Fecal microbiota from the model group and the ECH group were separately transplanted into pseudo-sterile CRLM mice in order to verify the role of gut flora in the ECH anti-metastatic effect. The 16S rRNA gene sequence was applied to analyze the structure and composition of the gut microbiota after ECH intervention, and the effect of ECH on short-chain fatty acid (SCFAs)-producing bacteria growth was proven by anaerobic culturing in vitro. GC-MS was applied to quantitatively analyze the serum SCFAs levels in mice. RNA-seq was performed to detect the gene changes involving tumor-promoting signaling pathway.. ECH inhibited CRC metastasis in a dose-dependent manner in the metastatic colorectal cancer (mCRC) mouse model. Manipulation of gut bacteria in the mCRC mouse model further proved that SCFA-generating gut bacteria played an indispensable role in mediating the antimetastatic action of ECH. Under an anaerobic condition, ECH benefited SCFA-producing microbiota without affecting the total bacterial load, presenting a dose-dependent promotion on the growth of a butyrate producer, Faecalibacterium prausnitzii (F.p). Furthermore, ECH-reshaped or F.p-colonized microbiota with a high butyrate-producing capability inhibited liver metastasis by suppressing PI3K/AKT signaling and reversing the epithelial-mesenchymal transition (EMT) process, whereas this anti-metastatic ability was abrogated by the butyrate synthase inhibitor heptanoyl-CoA.. This study demonstrated that ECH exhibits oral anti-metastatic efficacy by facilitating butyrate-producing gut bacteria, which downregulates PI3K/AKT signaling and EMT. It hints at a novel role for ECH in CRC therapy.

Topics: Animals; Butyrates; Colonic Neoplasms; Colorectal Neoplasms; Disease Models, Animal; Fatty Acids, Volatile; Gastrointestinal Microbiome; Glycosides; Liver Neoplasms; Mice; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; RNA, Ribosomal, 16S; Signal Transduction

Topics: Animals; Bacterial Proteins; Disease Models, Animal; Humans; Methicillin-Resistant Staphylococcus aureus; Mice; Pneumonia; Staphylococcus aureus; Vancomycin

Echinacoside (ECH), a phenylethanoid glycoside, has protective activity in neurodegenerative disease, including anti-inflammation and antioxidation. However, the effects of ECH in Alzheimer's disease (AD) are not very clear. This present study investigates the role and mechanism of ECH in the pathological process of AD. APP/PS1 mice treated with ECH in 50 mg/kg/day for 3 months. Morris water maze, nesting test, and immunofluorescence staining used to observe whether ECH could improve AD pathology. Western blot used to study the mechanism of ECH improving AD pathology. The results showed that ECH alleviated the memory impairment of APP/PS1 mice by reducing the time of escape latency as well as increasing the times of crossing the platform and rescued the impaired ability to construct nests. In addition, ECH significantly reduced the deposition of senile plaques in the brain and decreased the expression of BACE1 in APP/PS1 mice through activating PI3K/AKT/Nrf2/PPARγ pathway. Furthermore, ECH decreased ROS formation, GP91 and 8-OHdG expression, upregulated the expression of SOD1 and SOD2 as well as activating the PI3K/AKT/Nrf2 signaling pathway. Moreover, ECH inhibited glia cells activation, pro-inflammatory cytokine IL-1β and TNF-α release, NLRP3 inflammasome formation through TXNIP/Trx-1 signaling pathway. In conclusion, this paper reported that ECH improved cognitive function, inhibited oxidative stress, and inflammatory response in AD. Therefore, we suggest that ECH may considered as a potential drug for AD treatment.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Amyloid Precursor Protein Secretases; Animals; Aspartic Acid Endopeptidases; Cognitive Dysfunction; Disease Models, Animal; Glycosides; Mice; Mice, Transgenic; Neurodegenerative Diseases; NF-E2-Related Factor 2; Phosphatidylinositol 3-Kinases; PPAR gamma; Presenilin-1; Proto-Oncogene Proteins c-akt; Signal Transduction

Amyotrophic lateral sclerosis (ALS), also known as a major type of motor neuron disease, is a disease characterized by the degeneration of both upper and lower motor neurons. Astragaloside IV (AST) is one of the most effective compounds isolated from Astragalus membranaceus. Echinacoside (ECH) is also an active constituent in Cistanche tubulosa. These two herbs had been used in treating disease described like ALS in ancient China under the guidance of traditional Chinese medicine theory and now they are still being used extensively for ALS in current Chinese medicine practice, but whether AST or ECH has effect on ALS disease condition is still unclear. Survivals of primary cultured neuron and astrocyte were determined by the MTS assay. Proteins including GLT1 and GFAP, from SOD1 G93A Tg (transgenic) astrocyte lysate were determined by Western blot. Synaptic markers, PSD95 and VGLUT1, were stained by immunofluorescence and observed by a confocal microscope. Proper dilution of AST and ECH was confirmed to be not harmful to both astrocytes and neurons. AST and ECH enhanced neuronal synaptic markers density or intensity/area in different aspects. Both AST and ECH could significantly rescue SOD1 astrocyte conditional medium-treated neuronal survival and synapse loss. Ten micromolars ECH could significantly rescue the suppressed GLT1 level expressed by SOD1 Tg astrocyte. This present research proved that AST and ECH could benefit neuronal properties and rescue certain dysfunction, such as GLT1 low expression, loss of neuron-supporting function, of astrocytes under SOD1 condition.

Topics: Amyotrophic Lateral Sclerosis; Animals; Astragalus propinquus; Astrocytes; Cistanche; Disease Models, Animal; Excitatory Amino Acid Transporter 2; Glycosides; Mice; Mice, Inbred C57BL; Mice, Transgenic; Motor Neurons; Saponins; Superoxide Dismutase-1; Triterpenes; Up-Regulation

Topics: Animals; beta Catenin; Casein Kinase II; Disease Models, Animal; Gene Expression Regulation; Gene Knockdown Techniques; Glycosides; GTP Phosphohydrolases; Humans; Infarction, Middle Cerebral Artery; Ischemic Stroke; Lymphoid Enhancer-Binding Factor 1; Mice; Mitochondrial Dynamics; Multiprotein Complexes; Neuroprotection; Nuclear Proteins; T Cell Transcription Factor 1; Transcription Factors; Transcription, Genetic

Hypoxic pulmonary hypertension (HPH) is a progressive and irreversible disease that reduces survival. Echinacoside is a phenylethanoid glycoside from Tibetan herbs known for its vasorelaxant effect and for inhibiting the proliferation of rat pulmonary arterial smooth muscle cells. This study aimed to investigate the effect of echinacoside on HPH. Sprague Dawley rats were housed in a hypobaric hypoxia chamber (4500 m) for 28 days to obtain the HPH model. Echinacoside (3.75, 7.5, 15, 30 and 40 mg/kg) was administered by intraperitoneal injection from the 1st to the 28th day. The mean pulmonary artery pressure (mPAP), right ventricular hypertrophy index, hemoglobin, hematocrit, red blood cell concentration and morphological change of pulmonary arteries were evaluated. Vascular perfusion assay was used to assess the pulmonary artery function. Echinacoside reduced mPAP, hemoglobin, hematocrit, right ventricular hypertrophy index and mean wall thickness% of pulmonary arteries in HPH rats. It significantly increased maximum vasoconstriction percentage of pulmonary arteries induced by noradrenaline in a dose-dependent manner. In addition, it improved the responsiveness of pulmonary arteries to acetylcholine and sodium nitroprusside. Therefore, Echinacoside might be an effective treatment against HPH, since it regulated pulmonary artery endothelium and smooth muscle layer function and improved the remodeling of pulmonary artery.

Topics: Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Glycosides; Hypertension, Pulmonary; Hypoxia; In Vitro Techniques; Injections, Intraperitoneal; Male; Phytotherapy; Pulmonary Artery; Rats, Sprague-Dawley; Vascular Remodeling; Vasoconstriction; Vasodilator Agents

Cistanches Herba is a popular Traditional Chinese Medicine and functional food that is used to treat kidney yang deficiency (KYD) in China. In this study, we investigated the effects of different drying methods for Cistanches Herba on kidney invigoration and yang strengthening. We established a mouse model of KYD by intraperitoneal injection of hydrocortisone for 8 days. We dried slices of Cistanches Herba in the sun, in the shade, in a microwave, or in an oven at 40°C, 60°C, 80°C or 100°C, then prepared and administered extracts to the mice by gastric gavage. We measured and evaluated the echinacoside (ECH) and acteoside (ACT) contents of the extracts, as well as the mice's body weight; testicular, epididymal, hepatic, and renal coefficients; and semen quality. All the Cistanches Herba extracts, obtained using different drying techniques, improved symptoms of KYD diagnosis in mice. Among them, treatments with Cistanches Herba dried in a microwave and dried in an oven at 100°C had the best therapeutic effects. Our results suggested that the higher the total content of ECH and ACT in Cistanches Herba extracts, the better the effects of kidney invigoration and yang strengthening. In addition, shorter drying times at higher temperatures lead to the highest recoveries of active components, and Cistanche dried in the sun at a medium-high temperature can improve sperm quality in mice.

Topics: Animals; China; Cistanche; Desiccation; Disease Models, Animal; Drugs, Chinese Herbal; Functional Food; Glycosides; Hydrocortisone; Kidney; Kidney Diseases; Male; Medicine, Chinese Traditional; Mice; Temperature; Yang Deficiency

Parkinson's disease (PD) is a common chronic neurodegenerative disease and greatly affects the quality of PD patients' life. Current symptomatic treatment of PD is limited. There are no effective treatment and drugs that could radically cure PD. Increasing experimental evidence has proven a causal relationship between alpha-synuclein (α-synuclein, α-syn) and the neuropathology of Parkinson's diseases, although the exact pathophysiological role of α-synuclein is not fully clarified. Previous studies showed that monomers and polymers of α-synuclein were secreted from damaged nerve cells via exocytosis and occupied healthy nerve cells via endocytosis, which afford evidence for the prion-like role of α-synuclein. Autophagy is the known mechanism for eukaryotic cells to degrade protein polymers and damaged organelles that proteasome does not cope with. Therefore, promoting the clearance of α-synuclein by enhancing autophagy in neuronal cells could be a promising treatment in the early stage of PD. SIRT1 is a potent regulator of autophagy, because it deacetylates a mass of important transcription factors such as Forkhead Box subgroup O (FoxO) transcription factors family. SIRT1's action relates to FoxO, because FoxO transcription factors are involved in various molecular pathways underlying neuronal protection and autophagy. Moreover, Sirt1 deacetylates proautophagic proteins such as Atg5, Atg7, and Atg8. Echinacoside (ECH) is the main active ingredient of a widely used Chinese herb cistanche, which has been proven to elicit neuroprotective effects in models of neurodegenerative diseases. In this study, we found that ECH could improve PD-like symptoms in MPTP-lesioned mouse model. We further showed that the underlying mechanism of the action of ECH was associated with enhancing autophagy in neurons via bind to Sirt1 directly and affect FoxO expression. Our study demonstrated ECH as a potential therapeutic agent against PD.

Topics: Animals; Autophagy; Disease Models, Animal; Glycosides; Male; Mice; MPTP Poisoning; Neurons; Neuroprotective Agents; PC12 Cells; Rats; Signal Transduction; Sirtuin 1

To study the protective effect of Echinacoside for 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced dopaminergic (DA) neurons injury in the subacute mouse model of Parkinson's disease (PD) and to explore its mechanism of action.. We chose 10 weeks of healthy wild type C57BL/6 male mice, hypodermic MPTP 30 mg/kg/day, five days, to prepare PD subacute mouse model. Behavior indexes of open field test and pole test were applied to examine the function of ECH to PD subacute mice model of PD sample action. The effects of ECH on dopaminergic neurons and astrocyte were examined using Immunohistochemistry including tyrosine hydroxylase (TH) and glial fibrillary acidic protein (GFAP) expression. The total numbers of TH-positive neurons and GFAP-positive cells in the substantia nigra pars compacts (SNpc) and ventral tegmental area (VTA) were obtained stereologically using the optical fractionator method. Enzyme-linked immunosorbent assay (ELISA) method was used to detect the inflammatory cytokines in the serum, including TNF-. ECH reversed the reduction of total distance in open field test in MPTP-induced PD model mice (P < 0.01), shortened the return time and total time of PD subacute model mice in pole test (P < 0.01, P < 0.05), significantly reversed the reduction of TH positive neurons induced by MPTP (P < 0.05), and reduced the activation of astrocytes (P < 0.05). Meanwhile, ECH significantly inhibited the expression of IBA-1, Cleaved caspase-3, and TNF-. ECH has protective effects on the MPTP subacute model mice, its mechanism may be through inhibiting activation of microglia and astrocytes, reducing inflammatory reaction and promoting the secretion of neurotrophic factors, and eventually resulting in the reduction of the DA neurons apoptosis.

Topics: Animals; Calcium-Binding Proteins; Caspase 3; Corpus Striatum; Disease Models, Animal; Dopaminergic Neurons; Gene Expression Regulation; Glial Fibrillary Acidic Protein; Glycosides; Humans; Immunohistochemistry; Mice; Microfilament Proteins; Microglia; MPTP Poisoning; Neuroprotective Agents; Parkinson Disease; Substantia Nigra; Tumor Necrosis Factor-alpha; Tyrosine 3-Monooxygenase

Echinacoside is a major compound of Cistanche Herb and has glutamate release-inhibiting activity in the brain. Given the involvement of excitotoxicity caused by massive glutamate in the pathophysiology of epilepsy, we explored the antiepileptic effect of echinacoside on kainic acid-induced seizures in rats. The rats were intraperitoneally administrated echinacoside for 30 min prior to intraperitoneal injection with kainic acid. The results showed that kainic acid induced seizure-like behavioral patterns, increased glutamate concentrations, caused neuronal loss and microglial activation, and stimulated proinflammatory cytokine gene expression in the hippocampus. These kainic acid-induced alternations were found to be attenuated by echinacoside pretreatment. Furthermore, decreased Akt and glycogen synthase kinase 3β (GSK3β) phosphorylation as well as Bcl-2 expression in the hippocampus was reversed by the echinacoside pretreatment. These results demonstrate that echinacoside exert its antiepileptic and neuroprotective actions in a kainic acid rat model through suppressing inflammatory response and activating the Akt/GSK3β signaling. Therefore, the present study suggests that echinacoside is the potentially useful in the prevention of epilepsy.

Topics: Animals; Brain; Cistanche; Cytokines; Disease Models, Animal; Epilepsy; Glutamic Acid; Glycogen Synthase Kinase 3 beta; Glycosides; Inflammation; Kainic Acid; Male; Microglia; Neuroprotective Agents; Neurotoxicity Syndromes; Phosphorylation; Phytotherapy; Plant Extracts; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-bcl-2; Rats, Sprague-Dawley; Seizures; Signal Transduction

To investigate whether echinacoside (ECH) protects the retina against ischemia/reperfusion (I/R) injury and the underlying mechanisms.. Adult male Wistar rats were randomly divided into four groups: sham, sham plus ECH, I/R plus vehicle, and I/R plus ECH. Before the retinal I/R injury produced by high intraocular pressure (HOP), ECH was administered (20 mg/kg daily) for 7 days. The level of retinal cell damage was evaluated using Fluoro-Gold (FG) retrograde labeling and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) analysis 7 days after I/R. Optic nerve histology was analyzed with transmission electron microscopy. Levels of retinal malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were determined. The expression of apoptosis-associated factors (Apaf-1, Parp, and Bad) were analyzed with western blotting and quantitative real-time PCR (qPCR). The production of proinflammatory cytokines (tumor necrosis factor-α [TNFα], interleukin-1 beta [IL-1β], and IL-6) was analyzed with enzyme-linked immunosorbent assay (ELISA) 7 days after the I/R injury as well.. The administration of ECH not only preserved retinal morphology but also attenuated retinal inflammation and apoptosis at 7 days after the I/R injury and decreased I/R-induced oxidative stress in the retina statistically significantly.. ECH protected against I/R-induced retinal injury, via activation of antioxidant enzymes and suppression of inflammation. Therefore, ECH could be a potential therapeutic candidate for the treatment and management of I/R retinal diseases.

Topics: Animals; Antioxidants; Apoptotic Protease-Activating Factor 1; bcl-Associated Death Protein; Catalase; Disease Models, Animal; Drug Administration Schedule; Gene Expression Regulation; Glutathione Peroxidase; Glycosides; Interleukins; Male; Malondialdehyde; Optic Nerve; Oxidative Stress; Poly(ADP-ribose) Polymerases; Rats; Rats, Wistar; Reperfusion Injury; Retina; Signal Transduction; Superoxide Dismutase; Tumor Necrosis Factor-alpha

Kidney fibrosis and renal tubular epithelial-to-mesenchymal transition (EMT) are the main pathological changes of diabetic nephropathy (DN), which eventually leads to end-stage renal disease. Previous studies have suggested that echinacoside (ECH) is antifibrotic in the liver. However, the effect of ECH on kidney fibrosis in DN and its mechanisms are unknown. This study was performed to explore the effect of ECH on kidney fibrosis and also the molecular mechanisms of ECH in a db/db mice model of DN. Our results showed that, relative to db/db mice, the mice in the ECH group had an improved general state and reduced blood glucose and 24-hour urinary protein levels. The deterioration of renal function was delayed due to treatment with ECH. We also observed that ECH can improve histopathological findings in the kidneys of db/db mice, including collagen deposition, mesangial cell and mesangial matrix hyperplasia, basement membrane thickening, and podocyte reduction. Moreover, ECH inhibited the TGF-β1/Smads signaling pathway, downregulated fibronectin (FN), collagen IV, and alpha-smooth muscle actin (α-SMA) levels, and upregulated E-cadherin level in the db/db mice model of DN. Our findings indicate that ECH has a therapeutic effect on DN, including the inhibition of renal tubular EMT and kidney fibrosis. Furthermore, ECH inhibits kidney fibrosis through regulation of the TGF-β1/Smads signaling pathway.

Topics: Animals; Diabetic Nephropathies; Disease Models, Animal; Epithelial-Mesenchymal Transition; Fibrosis; Glycosides; Kidney; Male; Mice; Signal Transduction; Smad Proteins; Transforming Growth Factor beta1

Echinacoside (ECH) is a major bioactive phenyethanoids in medicinal herba Cistanche and has been reported to have antiinflammatory activity and beneficial effect on wound healing in many experimental studies. This study was to test the efficacy of ECH-enriched extract of Cistanche tubulosa in the treatment of dextran sulphate sodium (DSS)-induced colitis, a preclinical model of ulcerative colitis. Oral administration of ECH extract significantly suppresses the development of acute colitis, indicated by lowering disease activity index (p < 0.0001, n = 8) and preventing colonic damage (p = 0.0336). Histological examinations showed that ECH extract treatment protected intestinal epithelium from inflammatory injury (p = 0.0249) but had less effect on inflammatory cellular infiltration (p = 0.1753). The beneficial effect of ECH extract treatment was associated with upregulation of transforming growth factor (TGF)-β1 as well as with an increase in the number of Ki67(+) proliferating cells in diseased colons (p < 0.0001). In cultured MODE-K cells, the addition of ECH extract enhanced in vitro wound healing that depended on TGF-β1 expression. These data suggest that ECH extract possesses a greater efficacy in preventing DSS-induced colitis in mice, implying the potential of ECH or its derivatives for clinically treating inflammatory bowel disease.

Topics: Animals; Anti-Inflammatory Agents; Cell Line; Cell Proliferation; Cistanche; Colitis; Colitis, Ulcerative; Colon; Dextran Sulfate; Disease Models, Animal; Glycosides; Intestinal Mucosa; Male; Mice; Mice, Inbred C3H; Plant Extracts; Transforming Growth Factor beta1; Wound Healing

This study aimed to investigate the protective effects of echinacoside, one of the phenylethanoids isolated from the stems of Cistanche salsa, a Chinese herbal medicine, on D-galactosamine (GalN) and lipopolysaccharide (LPS)-induced acute liver injury in mice.. We administered GalN (650 mg/kg) together with LPS (30 μg/kg) to mice by intraperitoneal injection to induce acute liver damage. Echinacoside (60 mg/kg) was given intraperitoneally to mice at 1 h prior to GalN/LPS exposure. Mice were sacrificed at different time points following GalN/LPS treatment, and the liver and blood samples were collected for future analysis.. It showed that GalN/LPS treatment produced severe hepatic injury, evidenced by significantly elevated plasma alanine aminotransferase (ALT) levels and abnormal histological changes such as hepatocyte necrosis or apoptosis, hemorrhage, fatty degeneration, and neutrophil infiltration. Notably, pretreatment with echinacoside remarkably improved the survival rate of GalN/LPS-treated mice and attenuated acute hepatotoxicity, as demonstrated by decreased ALT levels and improved histological signs. Echinacoside shows both anti-apoptotic and anti-inflammatory properties, characterized by a substantial inhibition of hepatocyte apoptosis and a significant reduction in the inflammatory markers, including myeloperoxidase, extracellular nucleosomes, high-mobility group box 1, and inflammatory cytokines in the plasma of mice, which may be important mechanisms related to its protective effect.. Our results suggest that echinacoside can provide a pronounced protection against GalN/LPS-induced acute liver injury in mice, which may complement the available strategies for management of acute liver damage in clinical settings.

Topics: Alanine Transaminase; Animals; Anti-Inflammatory Agents; Apoptosis; Biomarkers; Chemical and Drug Induced Liver Injury; Disease Models, Animal; Galactosamine; Glycosides; Hepatocytes; Inflammation; Injections, Intraperitoneal; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; Treatment Outcome

To observe the protective effects of echinacoside on rotenone-induced damages in rats.. Healthy male Sprague-Dawley rats, weighing from 200 to 220 g, were randomly divided into five groups with 20 rats in each group: control group, rotenone group and echinacoside groups of low, medium and high doses (20, 40 and 80 mg/(kg·d)). Rats in the rotenone group were injected intraperitoneally for four weeks with rotenone (2.75 mg/(kg·d)), dissolved into dimethyl sulfoxide; rats in the control group were injected intraperitoneally with dimethyl sulfoxide daily, and rats in the echinacoside groups received daily intraperitoneal injection of rotenone along with echinacoside gastric perfusion for four weeks. Modified neurological severity score was used to evaluate neurobehavior of the animals; dopaminergic neurons in substantia nigra were observed by immunochemical method and dopamine concentration in striatum was determined by a fluorescence spectrophotometer. Biomarkers of liver and kidney damage were also measured.. In the rotenone group, the rats suffered from severe neurological disability (P<0.01), and the number of dopaminergic neurons in substantia nigra and dopamine concentration in striatum were decreased (P<0.05) compared with the normal control group; levels of the biomarkers for evaluating liver and kidney damage were increased (P<0.05). In the echinacoside groups, the neurological disability and the loss of dopaminergic neurons in substantia nigra were suppressed and dopamine concentrations in striatum were increased (P<0.05), but the liver and kidney damage was not improved (P>0.05).. Rotenone causes severe damages to dopaminergic neurons, liver and kidney in rats and echinacoside selectively reverses dopaminergic neuronal injury.

Topics: Animals; Disease Models, Animal; Dopaminergic Neurons; Glycosides; Male; Neuroprotective Agents; Parkinson Disease; Random Allocation; Rats; Rats, Sprague-Dawley; Rotenone

In the present study, we investigated the neuroprotective effects of echinacoside, a phenylethanoid glycoside extracted from the medicinal Chinese herb Cistanches salsa, against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic toxicity. We confirmed that exposure to MPTP in mice leads to permanent behavioral deficits and depletion of dopamine and its metabolites. When administered prior to MPTP, echinacoside reduced behavioral deficits, increased striatal dopamine and dopamine metabolite levels, reduced cell death, and led to a marked increase in tyrosine hydroxylase expression relative to mice treated with MPTP alone. In addition, pre-treatment with echinacoside significantly reduced caspase-3 and caspase-8 activation in 1-methyl-4-phenylpyridinium (MPP(+))-induced apoptosis in cerebellar granule neurons. Taken together, these findings suggest that echinacoside improves the behavioral and neurochemical outcomes in MPTP mice model of Parkinson's disease and inhibits caspase-3 and caspase-8 activation in cerebellar granule neurons, making the compound an attractive candidate treatment for various neurodegenerative disorders, including Parkinson's disease.

Topics: Animals; Apoptosis; Behavior, Animal; Caspase 3; Caspase 8; Cell Death; Cerebellum; Cistanche; Disease Models, Animal; Dopamine; Dose-Response Relationship, Drug; Glycosides; Male; Mice; Mice, Inbred C57BL; MPTP Poisoning; Neurons; Neuroprotective Agents; Parkinson Disease, Secondary; Plant Extracts; Tyrosine 3-Monooxygenase

Phytochemical constituents of medicinal plants demonstrate inhibition of tissue and bacterial hyaluronidase. Echinacoside is a caffeoyl conjugate of Echinacea with known anti-hyaluronidase properties. The purpose of this study was to investigate the wound healing effects of Echinacea on vocal fold wound healing and functional voice outcomes. Pig animal model.. Vocal fold injury was induced in 18 pigs by unilateral vocal fold stripping. The uninjured vocal fold served as control. Three groups of six pigs randomly received a topical application of 300, 600, or 1,200 mg of standardized Echinacea on the injured side. Animals were euthanized after 3, 10, and 15 days of wound healing. Phonation threshold pressure and vocal economy measurements were obtained from excised larynges. Treatment outcomes were examined by comparing the animals receiving treatment with a set of 19 untreated and 5 historical controls. Treatment effects on wound healing were evaluated by histologic staining for hyaluronan and collagen. Treated larynges revealed improved vocal economy and phonation threshold pressure compared with untreated larynges. Histologically, treated vocal folds revealed stable hyaluronan content and no significant accumulation of collagen compared with control. Findings provide a favorable outcome of anti-hyaluronidase treatment on acute vocal fold wound healing and functional measures of voice.

Topics: Animals; Collagen; Disease Models, Animal; Echinacea; Glycosides; Humans; Hyaluronic Acid; Hyaluronoglucosaminidase; Image Processing, Computer-Assisted; Laryngoscopy; Phonation; Phytotherapy; Plant Extracts; Pressure; Random Allocation; Swine; Treatment Outcome; Vibration; Vocal Cords; Wound Healing; Wounds and Injuries