The water extract of Amydrium sinense (Engl.) H. Li ameliorates Isoproterenol-induced cardiac hypertrophy through inhibiting the NF-κB signaling pathway.

OBJECTIVE: Pathologic cardiac hypertrophy (PCH) is a precursor to heart failure. Amydrium sinense (Engl.) H. Li (AS), a traditional Chinese medicinal plant, has been extensively utilized to treat chronic inflammatory diseases. However, the therapeutic effect of ASWE on PCH and its underlying mechanisms are still not fully understood. METHODS: A cardiac hypertrophy model was established by treating C57BL/6 J mice and neonatal rat cardiomyocytes (NRCMs) in vitro with isoprenaline (ISO) in this study. The antihypertrophic effects of AS water extract (ASWE) on cardiac function, histopathologic manifestations, cell surface area and expression levels of hypertrophic biomarkers were examined. Subsequently, the impact of ASWE on inflammatory factors, p65 nuclear translocation and NF-κB activation was investigated to elucidate the underlying mechanisms. RESULTS: In the present study, we observed that oral administration of ASWE effectively improved ISO-induced cardiac hypertrophy in mice, as evidenced by histopathological manifestations and the expression levels of hypertrophic markers. Furthermore, the in vitro experiments demonstrated that ASWE treatment inhibited cardiac hypertrophy and suppressed inflammation response in ISO-treated NRCMs. Mechanically, our findings provided evidence that ASWE suppressed inflammation response by repressing p65 nuclear translocation and NF-κB activation. ASWE was found to possess the capability of inhibiting inflammation response and cardiac hypertrophy induced by ISO. CONCLUSION: To sum up, ASWE treatment was shown to attenuate ISO-induced cardiac hypertrophy by inhibiting cardiac inflammation via preventing the activation of the NF-kB signaling pathway. These findings provided scientific evidence for the development of ASWE as a novel therapeutic drug for PCH treatment.

Intervention Effect of Traditional Chinese Medicine Hot Pressing Combined with Health Education on the Adolescent's Visual Fatigue.

To explore the intervention effect of traditional Chinese medicine hot pressing combined with health education in adolescents with asthenopia, 92 adolescents with asthenopia admitted to the outpatient department of Guangming Traditional Chinese Medicine Hospital in Pudong New Area from October 2019 to January 2021 were selected and randomly divided into two groups: the control group and the test group, each with 46 cases. Both received health education. The control group was given sodium hyaluronate eye drops, and the test group was given traditional Chinese medicine hot ironing technique intervention. After 2 courses of treatment, the scores of visual fatigue symptoms, clinical curative effect, and eye refractive power of the two groups were observed. The satisfaction of treatment was compared between the two groups. The scores of asthenopia of the two groups were compared at 6 months after intervention. After the intervention, the scores of visual fatigue symptoms in the control group and the test group were reduced after one or two courses of treatment (control group: t = 4.167, 6.318, and P=0.027, 0.010; test group: t = 4.820, 6.834, and P=0.013, <0.001). The scores of asthenopia symptoms of the trial group after the intervention for one and two courses were significantly lower than those of the control group (P < 0.05); the total clinical effective rate of the trial group was 93.48%, which was significantly higher than that of the control group (80.43%). The difference between the groups was statistically significant (P < 0.05); the left and right eyes of the control group did not change significantly before and after the intervention (P > 0.05). After the intervention, the left and right eyes of the paper group were significantly reduced (P < 0.05). After the intervention, the difference of the two groups in the refractive power of the left and right eyes was statistically significant (P < 0.05). After treatment, the satisfaction of the experimental group was significantly higher than that of the control group (P < 0.05). After 6 months, there was no significant change in the visual fatigue score of the experimental group, while the visual fatigue score of the control group increased significantly. The traditional Chinese medicine ironing combined with health education intervention can improve the symptoms of adolescents' asthenopia and improve the treatment efficiency. The method is safe, and the operation is convenient. It is worthy of clinical promotion.

Traditional Chinese Medicine in Depression Treatment: From Molecules to Systems.

Depression is a multigenetic or multifactorial syndrome. The central neuron system (CNS)-orientated, single target, and conventional antidepressants are insufficient and far from ideal. Traditional Chinese Medicine (TCM) has historically been used to treat depression up till today, particularly in Asia. Its holistic, multidrug, multitarget nature fits well with the therapeutic idea of systems medicine in depression treatment. Over the past two decades, although efforts have been made to understand TCM herbal antidepressants at the molecular level, many fundamental questions regarding their mechanisms of action remain to be addressed at the systems level in order to better understand the complicated herbal formulations in depression treatment. In this Mini Review, we review and discuss the mechanisms of action of herbal antidepressants and their acting targets in the pathological systems in the brain, such as monoamine neurotransmissions, hypothalamic-pituitary-adrenal (HPA) axis, neurotropic factor brain-derived neurotrophic factor (BDNF) cascade, and glutamate transmission. Some herbal molecules, constituents, and formulas are highlighted as examples to discuss their mechanisms of action and future directions for comprehensive researches at the systems level. Furthermore, we discuss pharmacological approaches to integrate the mechanism of action from the molecular level into the systems level for understanding of systems pharmacology of TCM formulations. Integration of the studies at the molecular level into the systems level not only represents a trend in TCM study but also promotes our understanding of the system-wide mechanism of action of herbal antidepressant formulations.

Excessive Daytime Sleepiness in Parkinson's Disease: Clinical Implications and Management.

OBJECTIVE: Excessive daytime sleepiness (EDS) is one of the most common sleep abnormalities in patients with Parkinson's disease (PD), yet its multifactorial etiology complicates its treatment. This review summarized recent studies on the epidemiology, etiology, clinical implications, associated features, and evaluation of EDS in PD. The efficacy of pharmacologic and non-pharmacologic treatments for EDS in PD was also reviewed. DATA SOURCES: English language articles indexed in PubMed and Cochrane databases and Chinese-language papers indexed in Wanfang and National Knowledge Infrastructure databases that were published between January 1987 and November 2017 were located using the following search terms: "sleepiness", "sleep and Parkinson's disease", and "Parkinson's disease and treatment". STUDY SELECTION: Original research articles and critical reviews related to EDS in PD were selected. RESULTS: EDS is a major health hazard and is associated with many motor and nonmotor symptoms of PD. Its causes are multifactorial. There are few specific guidelines for the treatment of EDS in PD. It is first necessary to identify and treat any possible factors causing EDS. Recent studies showed that some nonpharmacologic (i.e., cognitive behavioral therapy, light therapy, and repetitive transcranial magnetic stimulation) and pharmacologic (i.e., modafinil, methylphenidate, caffeine, istradefylline, sodium oxybate, and atomoxetine) treatments may be effective in treating EDS in PD. CONCLUSIONS: EDS is common in the PD population and can have an immensely negative impact on quality of life. Its causes are multifactorial, which complicates its treatment. Further investigations are required to determine the safety and efficacy of potential therapies and to develop novel treatment approaches for EDS in PD.

Polydatin attenuates AGEs-induced upregulation of fibronectin and ICAM-1 in rat glomerular mesangial cells and db/db diabetic mice kidneys by inhibiting the activation of the SphK1-S1P signaling pathway.

We previously demonstrated that activation of sphingosine kinase 1 (SphK1)- sphingosine 1- phosphate (S1P) signaling pathway by high glucose (HG) plays a pivotal role in increasing the expression of fibronectin (FN), an important fibrotic component, by promoting the DNA-binding activity of transcription factor activator protein 1 (AP-1) in glomerular mesangial cells (GMCs) under diabetic conditions. As a multi-target anti-oxidative drug, polydatin (PD) has been shown to have renoprotective effects on experimental diabetes. However, whether PD could resist diabetic nephropathy (DN) by regulating SphK1-S1P signaling pathway needs further investigation. Here, we found that PD significantly reversed the upregulated FN and ICAM-1 expression in GMCs exposed to AGEs. Simultaneously, PD dose-dependently inhibited SphK1 levels at the protein expression and kinase activity and attenuated S1P production under AGEs treatment conditions. In addition, PD reduced SphK activity in GMCs transfected with wild-type SphK(WT) plasmid and significantly suppressed SphK1-mediated increase of FN and ICAM-1 levels under normal conditions. Furthermore, we found that the AGEs-induced upregulation of phosphorylation of c-Jun at Ser63 and Ser73 and c-Fos at Ser32, DNA-binding activity and transcriptional activity of AP-1 were blocked by PD. In comparison with db/db model group, PD treatment suppressed SphK1 levels (mRNA, protein expression, and activity) and S1P production, reversed the upregulation of FN, ICAM-1, c-Jun, and c-Fos in the kidney tissues of diabetic mice, and finally ameliorated renal injury in db/db mice. These findings suggested that the downregulation of SphK1-S1P signaling pathway is probably a novel mechanism by which PD suppressed AGEs-induced FN and ICAM-1 expression and improved renal dysfunction of diabetic models.

Polydatin ameliorates lipid and glucose metabolism in type 2 diabetes mellitus by downregulating proprotein convertase subtilisin/kexin type 9 (PCSK9).

BACKGROUND: Abnormalities in lipid and glucose metabolism are constantly observed in type 2 diabetes. However, these abnormalities can be ameliorated by polydatin. Considering the important role of proprotein convertase subtilisin/kexin type 9 (PCSK9) in metabolic diseases, we explore the possible mechanism of polydatin on lipid and glucose metabolism through its effects on PCSK9. METHODS: An insulin-resistant HepG2 cell model induced by palmitic acid (PA) and a db/db mice model were used to clarify the role of polydatin on lipid and glucose metabolism. RESULTS: In insulin-resistant HepG2 cells, polydatin upregulated the protein levels of LDLR and GCK but repressed PCSK9 protein expression, besides, polydatin also inhibited the combination between PCSK9 and LDLR. Knockdown and overexpression experiments indicated that polydatin regulated LDLR and GCK expressions through PCSK9. In the db/db mice model, we found that polydatin markedly enhanced GCK and LDLR protein levels, and inhibited PCSK9 expression in the liver. Molecular docking assay was further performed to analyze the possible binding mode between polydatin and the PCSK9 crystal structure (PDB code: 2p4e), which indicated that steady hydrogen bonds formed between polydatin and PCSK9. CONCLUSIONS: Our study indicates that polydatin ameliorates lipid and glucose metabolism in type 2 diabetes mellitus by downregulating PCSK9.

Polydatin improves glucose and lipid metabolism in experimental diabetes through activating the Akt signaling pathway.

Recently, the effect of polydatin on lipid regulation has gained considerable attention. And previous study has demonstrated that polydatin has hypoglycemic effect on experimental diabetic rats. Repressed Akt pathway contributes to glucose and lipid disorders in diabetes. Thus, whether polydatin regulates glucose and lipid metabolism in experimental diabetic models through the Akt pathway arouses interest. The purpose was to explore the regulatory mechanism of polydain on glucose and lipid through Akt pathway. We used a diabetic rat model induced by high-fat and -sugar diet with low-dose of streptozocin and an insulin resistant HepG2 cell model induced by palmitic acid to clarify the role of polydatin on glucose and lipid metabolism. Here, we found that polydatin significantly attenuated fasting blood­glucose, glycosylated hemoglobin, glycosylated serum protein, total cholesterol, triglyceride, and low-density lipoprotein cholesterol in diabetic rats. Furthermore, polydatin significantly increased glucose uptake and consumption and decreased lipid accumulation in insulin resistant HepG2 cells. Polydatin markedly increased serum insulin levels in diabetic rats, and obviously activated the Akt signaling pathway in diabetic rat livers and insulin resistant HepG2 cells. Polydatin markedly increased phosphorylated GSK-3ß, decreased the protein levels of G6Pase and SREBP-1c, and increased protein levels of GCK, LDLR, and phosphorylated IRS in livers and HepG2 cells. Overall, the results indicate that polydatin regulates glucose and lipid metabolism in experimental diabetic models, the underlying mechanism is probably associated with regulating the Akt pathway. The effect of polydatin on increased Akt phosphorylation is independent of prompting insulin secretion, but dependent of increasing IRS phosphorylation.

[Effect of compound Polygonum multiflorum extract on Alzheimer's disease].

OBJECTIVE: To observe the clinical effect of compound Polygonum multiflorum extract on Alzheimer's disease (AD). METHODS: We collected 209 AD patients, among whom 120 were treated with compound Polygonum multiflorum extract as a treatment group, 60 were treated with Polygonum multiflorum extract as a Chinese herb control group, and 29 were treated with Naofukang as a western medicine control group. The scores for the Mini-Mental State Examination (MMSE), Ability of Daily Living Scale (ADL) and the therapeutic effect were assessed and compared before and after the 12 week treatment. RESULTS: After the treatment the scores for MMSE and ADL were improved in all groups. The scores of MMSE and ADL in the compound Polygonum multiflorum extract treatment group were significantly improved compared with the Chinese herb control group and the western medicine control group (P < 0.01). The total effective rate of 93.33% in the compound Polygonum multiflorum extract treatment group was better than 73.33% in the Chinese herb control group and 68.97% in the western medicine control group (P < 0.01). CONCLUSION: Compound Polygonum multiflorum extract has effect on AD, and it is superior to Polygonum multiflorum extractor Naofukang.