ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Sleep plays a critical role in several physiologic processes, and sleep disorders increase the risk of depression, dementia, stroke, cancer, and other diseases. Stress is one of the main causes of sleep disorders. Ginseng Radix et Rhizoma and Polygalae Radix have been reported to have effects of calming the mind and intensifying intelligence in Chinese Pharmacopoeia. Traditional Chinese medicine prescriptions composed of Ginseng Radix et Rhizoma and Polygalae Radix (Shen Yuan, SY) are commonly used to treat insomnia, depression, and other psychiatric disorders in clinical practice. Unfortunately, the underlying mechanisms of the SY extract's effect on sleep are still unknown. AIM OF THE STUDY: This study aimed to investigate the hypnotic effect of the SY extract in normal mice and mice with chronic restraint stress (CRS)-induced sleep disorders and elucidate the underlying mechanisms. MATERIALS AND METHODS: The SY extract (0.5 and 1.0 g/kg) was intragastrically administered to normal mice for 1, 14, and 28 days and to CRS-treated mice for 28 days. The open field test (OFT) and pentobarbital sodium-induced sleep test (PST) were used to evaluate the hypnotic effect of the SY extract. Liquid chromatography-tandem mass spectrometry and enzyme-linked immunosorbent assay were utilized to detect the levels of neurotransmitters and hormones. Molecular changes at the mRNA and protein levels were determined using real-time quantitative polymerase chain reaction and Western blot analysis to identify the mechanisms by which SY improves sleep disorders. RESULTS: The SY extract decreased sleep latency and increased sleep duration in normal mice. Similarly, the sleep duration of mice subjected to CRS was increased by administering SY. The SY extract increased the levels of tryptophan (Trp) and 5-hydroxytryptamine (5-HT) and the expression of tryptophan hydroxylase 2 (TPH2) in the cortex of normal mice. The SY extract increased the Trp level, transcription and expression of estrogen receptor beta and TPH2 in the cortex in mice with sleep disorders by decreasing the serum corticosterone level, which promoted the synthesis of 5-HT. Additionally, the SY extract enhanced the expression of arylalkylamine N-acetyltransferase, which increased the melatonin level and upregulated the expressions of melatonin receptor-2 (MT2) and Cryptochrome 1 (Cry1) in the hypothalamus of mice with sleep disorders. CONCLUSIONS: The SY extract exerted a hypnotic effect via the Trp/5-HT/melatonin pathway, which augmented the synthesis of 5-HT and melatonin and further increased the expressions of MT2 and Cry1.
Subject(s)
Drugs, Chinese Herbal , Melatonin , Sleep Initiation and Maintenance Disorders , Humans , Mice , Animals , Hypnotics and Sedatives/pharmacology , Hypnotics and Sedatives/therapeutic use , Tryptophan , Serotonin/metabolism , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Melatonin/pharmacology , Sleep Initiation and Maintenance Disorders/drug therapyABSTRACT
ETHNOPHARMACOLOGY RELEVANCE: Parishin C (Par), a prominent bioactive compound in Gastrodia elata Blume with little toxicity and shown neuroprotective effects. However, its impact on depression remains largely unexplored. AIM OF THE STUDY: This study aims to investigate the antidepressant effects of Par using a chronic social defeat stress (CSDS) mouse model and elucidate its molecular mechanisms. MATERIALS AND METHODS: The CSDS-induced depression mouse model was used to evaluate the therapeutic efficacy of Par. The social interaction test (SIT) and sucrose preference test (SPT), tail suspension test (TST) and forced swim test (FST) were conducted to assess the effects of Par on depressive-like behaviours. The levels of corticosterone, neurotransmitters (5-HT, DA and NE) and inflammatory cytokines (IL-1ß, TNF-α, and IL-6) were evaluated by enzyme-linked immunosorbent assay (ELISA). Activation of a microglia was assessed by immunofluorescence labeling Iba-1. The protein expressions of NLRP3, ASC, caspase-1, and IL-6 verified by Western blot. RESULT: Oral administration of Par (4 and 8 mg/kg) and fluoxetine (10 mg/kg, administration significantly ameliorate depression-like behaviors induced by CSDS, as shown by the increase social interaction in SIT, increase sucrose preference in SPT and the decrease immobility in TST and FST. Par administration decreased serum corticosterone level and increased the 5-HT, DA and NE concentration in the hippocampus and prefrontal cortex. Furthermore, Par treatment suppressed microglial activation (Iba1) as well as reduced levels of IL-1ß, TNF-α, and IL-6) with decreased protein expressions of NLRP3, ASC, caspase-1, and IL-6. CONCLUSIONS: our study provides the first evidence that Par exerts antidepressant-like effects in mice with CSDS-induced depression. This effect appears to be mediated by the normalization of neurotransmitter and corticosterone levels, inhibition of NLRP3 inflammasome activation. This newfound antidepressant property of Par offers a novel perspective on its pharmacological effects, providing valuable insights into its potential therapeutic and preventive applications in depression treatment.
Subject(s)
Glucosides , NLR Family, Pyrin Domain-Containing 3 Protein , Tumor Necrosis Factor-alpha , Mice , Animals , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Tumor Necrosis Factor-alpha/metabolism , Interleukin-6/metabolism , Social Defeat , Corticosterone , Serotonin/metabolism , Behavior, Animal , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Depression/drug therapy , Depression/metabolism , Hippocampus , Sucrose/metabolism , Caspases/metabolism , Stress, Psychological/drug therapy , Stress, Psychological/metabolism , Disease Models, AnimalABSTRACT
Jujube is a plant native to China that could be used in medicine and food. Its dried fruit is a superior herb commonly used in traditional Chinese medicine formulations for its calming effect and for nourishing the blood and strengthening the spleen and stomach. Jujube contains numerous active components including polysaccharides, phenols, and triterpene acids, which show a diverse array of pharmacological activities such as neuroprotection and the prevention and treatment of cardiovascular diseases. In this paper, the research status of jujube over the past two decades has been statistically evaluated. Meanwhile, by tracking the latest research advances, the pharmacological efficacy and molecular mechanisms of jujube are exhaustively expounded to provide specific and systematic references for further research on the pharmacological effects of jujube and its application in the food and pharmaceutical industries.
ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Dendrobium nobile Lindl (DNL), a valued time-honored herb, possesses immune-boosting and age-delaying properties, has been widely used to treat hyperglycemia and neurological diseases, and is probably a potential drug for improving learning and memory. Scopolamine (Scop), an antagonist for muscarinic receptors, potentially impairing intelligence and memory. AIM OF THE STUDY: This investigation aimed to assess the efficacy of DNL in alleviating scopolamine-induced cognitive deficits in mice and its mechanisms. MATERIALS AND METHODS: We utilized the open-field test, novel object recognition test (NOR), and Morris water maze test (MWM) to assess the potential of DNL in ameliorating learning and memory dysfunction caused by scopolamine in mice. Enzyme-linked immunosorbent assay (ELISA) was employed to measure Choline acetyltransferase (ChAT) content and Acetylcholinesterase (AChE) activities in the brain, and oxidative stress-related factors in the serum, including Malondialdehyde (MDA), Superoxide dismutase (SOD), and glutathione (GSH) content. RESULTS: Scopolamine injection significantly reduced the discrimination index of mice in the NOR test and impaired their performance in the MWM test, as demonstrated by longer escape latency, fewer target crossings, and less time spent in the target quadrant in the MWM. After 25 days of administration, DNL increased the discrimination index of the scopolamine-treated mice in the NOR test. DNL reduced the escape latency in the MWM test in the model mice. DNL increased the target crossing number and the percentage of time spent in the target quadrant in the MWM test. ELISA experiments indicated that DNL decreased the AChE activities, increased the ChAT activities, and modulated oxidative stress makers (GSH, SOD, and MDA) in scopolamine-induced mice. CONCLUSIONS: DNL may improve the learning and memory in mice treated with scopolamine, possibly by modulating oxidative stress and impaired cholinergic function.
Subject(s)
Dendrobium , Scopolamine , Mice , Animals , Acetylcholinesterase/metabolism , Maze Learning , Hippocampus/metabolism , Memory Disorders/chemically induced , Memory Disorders/drug therapy , Oxidative Stress , Glutathione/metabolism , Superoxide Dismutase/metabolismABSTRACT
Background: Uterine fibroids (UFs) are the most common benign tumors in women of reproductive age. The most effective treatment is myomectomy, but there is no long-term or low-invasive treatment option exists. Acupuncture can be used to treat UFs in a variety of ways. However, there is no meta-analytic synthesis including valid data that explored the efficacy of acupuncture for UFs. Objective: To assess the efficacy and safety of acupuncture for treating UFs. Methods: The PRISMA 2020 checklist was used. We identified and extracted the trials through may 2023 from six databases. The quality of the trials was assessed using the risk of bias (2.0). Meta-analysis was performed using RevMan 5.4 software, and it was synthesized using the random-effects model if the included studies were in high heterogeneity. Subgroup and sensitivity analysis were used if necessary. Results: A total of 1,035 trials were identified, of which 11 were included in the review and meta-analysis. In terms of acupuncture scheme design and fibroid-related symptoms, the trials are highly heterogeneous. All 11 trials have reported acupuncture types, with traditional acupuncture and electroacupuncture being the more representative subgroups. A qualitative review of existing evidence shows that acupuncture has no serious adverse reaction on UFs. Meta-analysis shows that acupuncture can effectively reduce the volume of UFs (MD - 3.89, 95% CI - 5.23 to - 2.56, P < 0.00001) or uterine volume (MD - 16.22, 95% CI - 19.89 To - 12.55, p < 0.00001), reduce the score of fibroid symptoms (MD - 3.03, 95% CI - 3.45 to - 2.60, p < 0.00001), improve the treatment efficiency (RR: 0.19, 95% CI: 0.13 to 0.25, p < 0.00001), and likely do not affect the estrogen level.
ABSTRACT
Myelin repair, which is known as remyelination, is critical to the treatment of neurodegenerative diseases, and myelination depends on not only the differentiation of oligodendrocyte precursor cells toward oligodendrocytes but also the renewal of oligodendrocyte precursor cells under pathological conditions. However, simultaneously promoting the differentiation and proliferation of oligodendrocyte precursor cells in lesions remains an unmet challenge and might affect demyelinating diseases. Kidney-tonifying herbs of traditional Chinese medicine (TCM) are effective in improving the symptoms of degenerative patients. However, herbs or compounds with dual functions are unverified. The purpose of this study was to find a kidney-tonifying TCM that synchronously improved the differentiation and proliferation of oligodendrocyte precursor cells under pathological conditions. Compounds with dual functions were screened from highly frequently used kidney-tonifying TCM, and the effects of the obtained compound on remyelination were investigated in an in vitro oligodendrocyte precursor cell differentiation model under pathological conditions and in demyelinating mice in vivo. The compound icaritin, which is an active component of Yin-Yang-Huo (the leaves of Epimedium brevicornu Maxim), demonstrated multiple effects on the remyelination process, including enhancing oligodendrocyte precursor cell proliferation, facilitating the differentiation of neural progenitor cells toward oligodendrocyte precursor cells and further toward oligodendrocytes, and maturation of oligodendrocytes under corticosterone- or glutamate-induced pathological conditions. Importantly, icaritin effectively rescued behavioral functions and increased the formation of myelin in a cuprizone-induced demyelination mouse model. The multiple effects of icaritin make it a promising lead compound for remyelination therapy.
Subject(s)
Demyelinating Diseases , Oligodendrocyte Precursor Cells , Mice , Animals , Oligodendrocyte Precursor Cells/pathology , Demyelinating Diseases/chemically induced , Demyelinating Diseases/drug therapy , Demyelinating Diseases/pathology , Cell Differentiation , Cell Proliferation , Mice, Inbred C57BLABSTRACT
BACKGROUND: Hyperglycemia is a characteristic feature of diabetes that often results in neuropsychological complications such as depression. Diabetic individuals are more vulnerable to experience depression compared to the normal population. Thus, novel treatment approaches are required to reduce depressive symptoms among diabetic individuals. Traditional Chinese medicines (TCMs) such as Shengmai San (SMS) and Radix puerariae (R) are usually widely used to treat ailments such as neurological complications since ancient time. METHODS: In this study, SMS was combined with R to prepare an R-SMS formulation and screened for their antidepressant activity in diabetic rats. The antidepressant potential of the prepared combination was evaluated behaviorally using open field test, novelty-induced hypophagia, and forced swim test in diabetic rats with biochemical and protein expression (PI3K, BDNF [brain-derived neurotrophic factor], and SYN [presynaptic vesicle protein]) analysis. RESULTS: Diabetic rats (streptozotocin, 45 mg/kg) showed elevated fasting blood glucose (FBG) >12 mM with depressive symptoms throughout the study. Treatment with R-SMS (0.5, 1.5, and 4.5 g/kg) significantly reverted depressive symptoms in diabetic rats as evinced by significantly (p < 0.05) reduced immobility time with an increased tendency to eat food in a novel environment. Treatment with R-SMS also significantly increased the protein expression of PI3K, BDNF, and SYN protein, which play a crucial role in depression. CONCLUSION: This study showed that R-SMS formulation antagonized depressive symptoms in diabetic rats; thus, this formulation might be studied further to develop as an antidepressant.
Subject(s)
Diabetes Mellitus, Experimental , Pueraria , Rats , Animals , Depression/etiology , Depression/chemically induced , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Phosphatidylinositol 3-Kinases , Pueraria/metabolism , Brain-Derived Neurotrophic Factor/metabolism , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic useABSTRACT
In aerospace medicine, the influence of microgravity on cognition has always been a risk factor threatening astronauts' health. The traditional medicinal plant and food material Gastrodia elata Blume has been used as a therapeutic drug for neurological diseases for a long time due to its unique neuroprotective effect. To study the effect of fresh Gastrodia elata Blume (FG) on cognitive impairment caused by microgravity, hindlimb unloading (HU) was used to stimulate weightlessness in mice. The fresh Gastrodia elata Blume (0.5 g/kg or 1.0 g/kg) was intragastrically administered daily to mice exposed to HU and behavioral tests were conducted after four weeks to detect the cognitive status of animals. The behavioral tests results showed that fresh Gastrodia elata Blume therapy significantly improved the performance of mice in the object location recognition test, Step-Down test, and Morris Water Maze test, including short-term and long-term spatial memory. According to the biochemical test results, fresh Gastrodia elata Blume administration not only reduced serum factor levels of oxidative stress but also maintained the balance of pro-inflammatory and anti-inflammatory factors in the hippocampus, reversing the abnormal increase of NLRP3 and NF-κB. The apoptosis-related proteins were downregulated which may be related to the activation of the PI3K/AKT/mTOR pathway by fresh Gastrodia elata Blume therapy, and the abnormal changes of synapse-related protein and glutamate neurotransmitter were corrected. These results identify the improvement effect of fresh Gastrodia elata Blume as a new application form of Gastrodia elata Blume on cognitive impairment caused by simulated weightlessness and advance our understanding of the mechanism of fresh Gastrodia elata Blume on the neuroprotective effect.
ABSTRACT
Polygonum sibiricum polysaccharides (PSP) are one of the main active components of Polygonatum sibiricum, which is a traditional Chinese medicine with food and drug homologies. Recent studies have revealed the antidepressant-like effects of PSP. However, the precise mechanisms have not been clarified. Therefore, the present study was conducted to explore that whether PSP could exert the antidepressant-like effects via microbiota-gut-brain (MGB) axis in chronic unpredictable mild stress (CUMS)-induced depressive mice by transplantation of fecal microbiota (FMT) from PSP administration mice. FMT markedly reversed the depressive-like behaviors of CUMS-induced mice in the open field, the sucrose preference, the tail suspension, the forced swimming, and the novelty-suppressed feeding tests. FMT significantly increased the levels of 5-hydroxytryptamine and norepinephrine, decreased the levels of the pro-inflammatory cytokines in the hippocampus and reduced the levels of corticosterone, an adrenocorticotropic-hormone, in the serum of CUMS-induced mice. In addition, administration of PSP and FMT significantly increased the expressions of ZO-1 and occludin in the colon and decreased the levels of lipopolysaccharide and interferon-γ in the serum of CUMS-induced mice. Moreover, administration of PSP and FMT regulated the signaling pathways of PI3K/AKT/TLR4/NF-κB and ERK/CREB/BDNF. Taken together, these findings indicated that PSP exerted antidepressant-like effects via the MGB axis.
Subject(s)
Depression , Polygonum , Mice , Animals , Depression/drug therapy , Depression/metabolism , Polygonum/metabolism , Brain-Gut Axis , Phosphatidylinositol 3-Kinases/metabolism , Antidepressive Agents/pharmacology , Polysaccharides/pharmacology , Polysaccharides/metabolism , Hippocampus , Stress, Psychological/drug therapy , Stress, Psychological/metabolism , Disease Models, AnimalABSTRACT
Tenuifolin (TEN), a natural neuroprotective compound obtained from the Polygala tenuifolia Willd plant, has improved cognitive symptoms. However, the impact of TEN on memory impairments caused by sleep deprivation (SD) is unclear. Accordingly, the objective of this study was to investigate the mechanisms behind the preventative benefits of TEN on cognitive impairment caused by SD. TEN (10 and 20 mg/kg) and Huperzine A (0.1 mg/kg) were given to mice through oral gavage for 28 days during the SD process. The results indicate that TEN administrations improve short- and long-term memory impairments caused by SD in the Y-maze, object identification, and step-through tests. Moreover, TEN stimulated the generation of anti-inflammatory cytokines (interleukin-10), lowered the production of pro-inflammatory cytokines (interleukin-1ß, interleukin-6, and interleukin-18), and activated microglia, improving antioxidant status in the hippocampus. TEN treatments significantly boosted the expression of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 while considerably decreasing the expression of NOD-like receptor thermal protein domain associated protein 3 and caspase-1 p20. Additionally, TEN restored the downregulation of the brain-derived neurotrophic factor signaling cascade and the impaired hippocampal neurogenesis induced by SD. When considered collectively, our data suggest that TEN is a potentially effective neuroprotective agent for cognition dysfunction.
Subject(s)
Cognitive Dysfunction , Sleep Deprivation , Animals , Mice , Cognition , Cognitive Dysfunction/drug therapy , Cytokines/metabolism , Hippocampus , Maze Learning , Sleep Deprivation/complications , Sleep Deprivation/drug therapyABSTRACT
Nelumbo nucifera Gaertn. is an important aquatic vegetable, and its dried stamen (Nelumbinis stamen, NS) is a valuable nutraceutical usually used as a herbal tea. Here, we used ultrahigh-performance liquid chromatography (UPLC)-quadrupole time-of-flight mass spectrometry and high-performance liquid chromatography (HPLC) to chemically profile NS and quantify their main constituent flavonoids, respectively. In total, 44 components were identified, including organic acids, flavonoids, monoterpene glycosides, and fatty acids. Experimental mice were induced with fatigue by exposure to chronic restraint stress (CRS) for 8 h daily for 15 days and then treated with an aqueous extract of NS (0.5 and 1 g/kg) via gavage. NS significantly mitigated CRS-induced skeletal muscle dysfunction and fatigue in mice possibly by lowering serum corticosterone levels and restoring Sestrin2 expression in the gastrocnemius to regulate metabolism, preserve mitochondrial homeostasis, and promote antioxidant capacity. These results demonstrate that NS can be used as a nutraceutical or supplement for controlling stress-induced muscle dysfunction and fatigue.
Subject(s)
Corticosterone , Flavonoids , Mice , Animals , Flavonoids/chemistry , Plant Extracts/chemistry , Fatigue/drug therapy , Fatigue/etiology , Muscles/chemistryABSTRACT
Pectin is a major component in many agricultural feedstocks. Despite the wide use in industrial production of cellulases and hemicellulases, the fungus Trichoderma reesei lacks a complete enzyme set for pectin degradation. In this study, three representative pectinolytic enzymes were expressed and screened for their abilities to improve the efficiency of T. reesei enzymes on the conversion of different agricultural residues. By replacing 5 % of the T. reesei proteins, endopolygalacturonase and pectin lyase remarkably increased the release of sugars from inferior tobacco leaves. In contrast, pectin methylesterase showed the strongest improving effect (by 31.1 %) on the hydrolysis of beetroot residue. The pectin in beetroot residue was only mildly degraded with the supplementation of pectin methylesterase, which allowed the extraction of pectin keeping the original emulsifying activity with a 51.1 % higher yield. The results provide a basis for precise optimization of lignocellulolytic enzyme systems for targeted valorization of pectin-rich agricultural residues.
Subject(s)
Cellulase , Cellulases , Trichoderma , Biomass , Cellulase/metabolism , Cellulases/metabolism , Hydrolysis , Pectins/metabolism , Polygalacturonase/metabolism , Sugars/metabolismABSTRACT
Polycystic ovary syndrome (PCOS) is a common multisystem disease with reproductive, metabolic and psychological abnormalities. It is characterized by a high prevalence rate in women of childbearing age and highly heterogeneous clinical manifestations, which seriously harm women's physical and mental health. Quercetin (QUR) is a natural compound of flavonoids found in a variety of foods and medicinal plants. It can intervene with the pathologic process of PCOS from multiple targets and channels and has few adverse reactions. It is mentioned in this review that QUR can improve ovulation disorder, relieve Insulin resistance (IR), reduce androgen, regulate lipid metabolism, regulate gut microbiota and improve vascular endothelial function, which is of great significance in the treatment of PCOS.
Subject(s)
Insulin Resistance , Polycystic Ovary Syndrome , Androgens , Female , Humans , Ovulation , Polycystic Ovary Syndrome/drug therapy , Polycystic Ovary Syndrome/metabolism , Quercetin/pharmacology , Quercetin/therapeutic useABSTRACT
Objective: To analyze the characteristics of the intestinal microbiota of polycystic ovarian syndrome with insulin resistance (PCOS-IR) and explore the possible mechanism of modified Banxia Xiexin Decoction in the treatment of PCOS-IR. Methods: A total of 17 specific pathogen-free (SPF) female Sprague-Dawley (SD) rats, aged 21 days, were selected and randomly divided into the control group (group Z, n = 6), model group (group M, n = 6), and treatment group (group A, n = 5). Letrozole combined with a high-fat diet was used to induce the PCOS-IR model. Rats in group A were treated with modified Banxia Xiexin Decoction for 2 weeks after the end of modeling; then the characteristics of reproductive, metabolic, inflammatory, and intestinal microbiota were compared among three groups. Results: The PCOS-IR model had an imbalance of intestinal microbiota, and the enriched microbiota was mainly class Coriobacteria, order Clostridiales, and genus Clostridium_sensu_stricto_1. Modified Banxia Xiexin Decoction can regulate the disorder of intestinal microbiota diversity, significantly increase the abundance of phyla Verrucomicrobiota Proteobacteria and genera Akkermansia and Blautia, and decrease the abundance of genus Clostridium_sensu_stricto_1. Conclusion: Genus Clostridium_sensu_stricto_1 might be the pivotal pathogenic bacteria of PCOS-IR. Modified Banxia Xiexin Decoction may ameliorate PCOS-IR by regulating intestinal microbiota imbalance and improving metabolic disorders.
Subject(s)
Gastrointestinal Microbiome , Insulin Resistance , Polycystic Ovary Syndrome , Animals , Drugs, Chinese Herbal , Female , Gastrointestinal Microbiome/physiology , Humans , Insulin Resistance/physiology , Polycystic Ovary Syndrome/drug therapy , Polycystic Ovary Syndrome/metabolism , Rats , Rats, Sprague-DawleyABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Radix Polygalae, a commonly used traditional Chinese herb, has conventionally functioned in tranquilization and sedation, where anti-inflammation may be the underlying mechanism. AIM OF THE STUDY: Chronic restraint stress (CRS), a risk factor for the etiology of intestinal disorders, was used in the present study to examine whether Radix Polygalae extract (RPE) could modulate colonic dysfunction in CRS rats. MATERIALS AND METHODS: Wistar rats were exposed to 28-day CRS (6 h daily), and RPE (135 mg/kg and 270 mg/kg) was intragastrically administered 1 h before CRS. Subsequently, the gut microbiota was determined using metagenomic sequencing. Colonic proinflammatory interleukin-1ß, -6, and -18 were assayed using qRT-PCR and ELISA. Tight junction proteins were quantified by qRT-PCR and western blotting (WB), and tryptophan metabolic enzymes and metabolites were determined using qRT-PCR and UFLC-QTRAP-5500/MS. Moreover, protein expression of colonic tight junction proteins, NF-κB-NLRP3 signaling involved in the underlying mechanism of RPE were detected by WB. RESULTS: RPE significantly decreased proinflammatory cytokines and reshaped the gut microbiota, especially the probiotics, including Lactobacillus and Bacteroides. Moreover, RPE could modulate the metabolite contents and enzyme expression associated with colonic tryptophan-kynurenine (TRP-KYN) metabolism and could increase tight junction protein expression in CRS rats. Furthermore, RPE inhibited the activation of NF-κB-NLRP3 signaling in the colon of CRS rats. CONCLUSION: RPE could modulate colonic inflammation, colonic microbiota, tight junction, TRP-KYN metabolism and NF-κB-NLRP3 signaling to reach a colonic balance of CRS rats. The present study helped us to better understand and appreciate the various beneficial effects of RPE.
Subject(s)
NF-kappa B , Tryptophan , Animals , Colon/metabolism , Drugs, Chinese Herbal , NF-kappa B/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Rats , Rats, Wistar , Tight Junction Proteins/genetics , Tight Junction Proteins/metabolism , Tryptophan/metabolismABSTRACT
Mounting evidence suggests that there is a close association between chronic sleep deprivation (CSD) and cognitive deficits. The animal model of CSD-induced cognitive deficits is commonly used to seek potential treatments. Soy isoflavones (SI) have been reported to possess antioxidant, anti-inflammation, and neuroprotective effects. In the present study, the effects of SI on CSD-induced memory impairment were investigated. The mice were subjected to the sleep interruption apparatus and continuously sleep deprived for 2 weeks, while orally administrated with SI (10, 20, and 40 mg/kg) or Modafinil (MOD,100 mg/kg) during the CSD process. Immediately after the SD protocol, cognitive performance of mice was evaluated by the object location recognition (OLR) test, the novel object recognition (NOR) test, and the Morris water maze (MWM) task, as well as the hippocampus, was extracted for evaluation of oxidative stress parameters and inflammation levels through biochemical parameter assay and western blotting analysis. The results showed that SI administration remarkably improved the cognitive performance of CSD-treated mice in OLR, NOR, and MWM tests. In addition, SI significantly elevated total antioxidant capacity and superoxide dismutase enzyme activities, decreased malondialdehyde level, promoting antioxidant element nuclear erythroid-2-related factor 2, and its downstream targets, including heme oxygenase 1, and quinone oxidoreductase 1 protein expressions. Moreover, SI treatment significantly suppressed nuclear factor kappa B p65, nitric oxide synthase, and cyclooxygenase 2 activation, as well as the pro-inflammatory cytokines (Tumor necrosis factor-α [TNF-α], interleukin-6 [IL-6], and interleukin-1ß [IL-1ß]) release in the hippocampus of CSD-treated mice. In summary, the current study provides an insight into the potential of SI in treatment of cognitive deficits by CSD.
Subject(s)
Cognitive Dysfunction , Isoflavones , Animals , Antioxidants/metabolism , Antioxidants/pharmacology , Cognition , Cognitive Dysfunction/drug therapy , Hippocampus , Isoflavones/metabolism , Isoflavones/pharmacology , Maze Learning , Mice , Neuroinflammatory Diseases , Oxidative Stress , Sleep Deprivation/complications , Sleep Deprivation/drug therapyABSTRACT
Two new ursane-type triterpenoids, named Polyanside A (1) and B (2), along with eleven known compounds (3-13), were isolated and elucidated from Maranthes polyandra (Benth.) Prance. The structures of these compounds were elucidated based on chemical evidence and multiple spectroscopic data. Isolated compounds were evaluated for anti-cancer, anti-inflammatory activities, and cytotoxicity on a normal human cell line (BJ). None of them showed activity and cytotoxicity. The hexane fraction was analyzed by GC-MS, resulting in the identification of forty-one compounds. This is the first comprehensive study on the phytochemistry of M. polyandra.
Subject(s)
Chrysobalanaceae/chemistry , Phytochemicals/analysis , Phytochemicals/chemistry , Chemical Fractionation , Gas Chromatography-Mass Spectrometry , Humans , Molecular Structure , Phytochemicals/isolation & purification , Plant Extracts/analysis , Plant Extracts/chemistry , Plant Extracts/isolation & purificationABSTRACT
The general consensus is that stress affects the central nervous system and can lead to cognitive problems. The root of Polygala tenuifolia (P. tenuifolia) is a well-known traditional Chinese medicine used for improving brain function. Tenuifolin (TEN) is the major constituent of P. tenuifolia and has a promising neuroprotective property. The purpose of this study was to investigate the alleviating effect of TEN on cognitive impairment induced by chronic restraint stress (CRS) and its mechanism. Our results showed that CRS exposure resulted in impaired cognitive performance in C57BL/6J mice, as indicated by decreased responses in Y-maze, novel objects recognition, and step-through passive avoidance tests. TEN treated daily orally (10 and 20 mg/kg) for 30 days reversed these behavior changes. Meanwhile, TEN could significantly regulate interleukin (IL)-6 and IL-10 levels in the hippocampus. TEN inhibited the toll-like receptor 4/nuclear factor-kappa B-mediated inflammation, as well as adrenocorticotropic hormone and corticosterone levels in serum. Most importantly, we found that TEN also upregulated the expressions of brain-derived neurotrophic factor, tropomyosin kinase B, glucocorticoid receptor, glutamate receptor 1, and synapse-associated proteins. Collectively, these data suggest that TEN has a potential improvement effect on memory loss caused by CRS.
Subject(s)
Cognitive Dysfunction , Polygala , Animals , Mice , Brain-Derived Neurotrophic Factor/metabolism , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/etiology , Hippocampus , Mice, Inbred C57BL , Polygala/metabolismABSTRACT
BACKGROUND: Rhizoma coptidis (RC) showed a significant effect on PCOS, but its mechanism in PCOS remains unclear. METHODS: The components of RC were searched by TCMSP. The Smiles number of the active ingredients was queried through PubChem, and the predicted targets were obtained from the SwissTargetPrediction database. The DrugBank, GeneCards, and DisGeNET databases were retrieved to acquire the related targets of PCOS. Then, the network of compound-target was constructed. The core targets were analyzed using protein-protein interaction (PPI) analysis, and the binding activities were verified by molecular docking. The enriched pathways of key targets were examined by GO and KEGG. RESULTS: 13 components and 250 targets of RC on PCOS were screened. The core network was filtered based on topological parameters, and the key components were palmatine, berberine, berberrubine, quercetin, and epiberberine. The key targets included DRD2, SLC6A4, CDK2, DPP4, ESR1, AKT2, PGR, and AKT1. Molecular docking displayed that the active ingredients of RC had good binding activities with potential targets of PCOS. After enrichment analysis, 30 functional pathways were obtained, including neuroactive ligand-receptor interaction, dopaminergic synapse, and cAMP signaling pathway. CONCLUSION: In summary, this study clarified the potential effect of RC on PCOS, which is helpful to provide references for clinical practice. It is also conducive to the secondary development of RC and its monomer components.
ABSTRACT
One new secoiridoid compound swertiamarin B (1), along with a known compound lytanthosalin (2), were isolated from ethanol extract of the aerial parts of Swertia mussotii. Their structures were elucidated by the detailed analysis of comprehensive spectroscopic data. All compounds were first isolated from the Swertia genus. Their antitumor activities were evaluated for four human tumor cell lines (HCT-116, HepG2, MGC-803 and A549). Compounds 1 and 2 showed excellent cytotoxic activities toward the MGC-803 cell lines with IC50 values 3.61 and 12.04 µM, respectively.