The effects of antioxidant supplementation on short-term mortality in sepsis patients.

Background: The occurrence and development of sepsis are related to the excessive production of oxygen free radicals and the weakened natural clearance mechanism. Further dependable evidence is required to clarify the effectiveness of antioxidant therapy, especially its impact on short-term mortality. Objectives: The purpose of this systematic review and meta-analysis was to evaluate the effect of common antioxidant therapy on short-term mortality in patients with sepsis. Methods: According to PRISMA guidelines, a systematic literature search on antioxidants in adults sepsis patients was performed on PubMed/Medline, Embase, and the Cochrane Library from the establishment of the database to November 2023. Antioxidant supplements can be a single-drug or multi-drug combination: HAT (hydrocortisone, ascorbic acid, and thiamine), ascorbic acid, thiamine, N-acetylcysteine and selenium. The primary outcome was the effect of antioxidant treatment on short-term mortality, which included 28-day mortality, in-hospital mortality, intensive care unit mortality, and 30-day mortality. Subgroup analyses of short-term mortality were used to reduce statistical heterogeneity and publication bias. Results: Sixty studies of 130,986 sepsis patients fulfilled the predefined criteria and were quantified and meta-analyzed. Antioxidant therapy reduces the risk of short-term death in sepsis patients by multivariate meta-analysis of current data, including a reduction of in-hospital mortality (OR = 0.81, 95% CI 0.67 to 0.99; P = 0.040) and 28-day mortality (OR = 0.81, 95% CI 0.69 to 0.95]; P = 0.008). Particularly in subgroup analyses, ascorbic acid treatment can reduce in-hospital mortality (OR = 0.66, 95% CI 0.90 to 0.98; P = 0.006) and 28-day mortality (OR = 0.43, 95% CI 0.24 to 0.75; P = 0.003). However, the meta-analysis of RCTs found that antioxidant therapy drugs, especially ascorbic acid, did substantially reduce short-term mortality(OR = 0.78, 95% CI 0.62 to 0.98; P = 0.030; OR = 0.57, 95% CI 0.36 to 0.91; P = 0.020). Conclusions: According to current data of RCTs, antioxidant therapy, especially ascorbic acid, has a trend of improving short-term mortality in patients with sepsis, but the evidence remains to be further demonstrated.

Traditional Chinese medicine for the treatment of Alzheimer's disease: A focus on the microbiota-gut-brain axis.

Alzheimer's disease (AD), the most frequent cause of dementia, is a neurodegenerative disorder characterised by a progressive decline in cognitive function that is associated with the formation of amyloid beta plaques and neurofibrillary tangles. Gut microbiota comprises of a complex community of microorganisms residing in the gastrointestinal ecosystem. These microorganisms can participate in gut-brain axis activities, thereby affecting cognitive function and associated behaviours. Increasing evidence has indicated that gut dysbiosis can jeopardise host immune responses and promote inflammation, which may be an initiating factor for the onset and evolution of AD. Traditional Chinese medicine (TCM) is a promising resource which encompasses immense chemical diversity and multiple-target characteristics for the treatment of AD. Many TCMs regulate the gut microbiota during treatment of diseases, indicating that gut microbiota may be an important target for TCM efficacy. In this review, we summarised the role of the microbiota-gut-brain axis in the development of AD and the effects of TCM in treating AD by regulating the gut microbiota. We anticipate that this review will provide novel perspectives and strategies for future AD research and treatments.

[Shenfu Injection alleviates sepsis-associated lung injury by regulating HIF-1α].

Shenfu Injection(SFI) is praised for the high efficacy in the treatment of septic shock. However, the precise role of SFI in the treatment of sepsis-associated lung injury is not fully understood. This study investigated the protective effect of SFI on sepsis-associated lung injury by a clinical trial and an animal experiment focusing on the hypoxia-inducing factor-1α(HIF-1α)-mediated mitochondrial autophagy. For the clinical trial, 70 patients with sepsis-associated lung injury treated in the emergency intensive care unit of the First Affiliated Hospital of Zhengzhou University were included. The levels of interleukin(IL)-6 and tumor necrosis factor(TNF)-α were measured on days 1 and 5 for every patient. Real-time quantitative polymerase chain reaction(RT-qPCR) was performed to determine the mRNA level of hypoxia inducible factor-1α(HIF-1α) in the peripheral blood mononuclear cells(PBMCs). For the animal experiment, 32 SPF-grade male C57BL/6J mice(5-6 weeks old) were randomized into 4 groups: sham group(n=6), SFI+sham group(n=10), SFI+cecal ligation and puncture(CLP) group(n=10), and CLP group(n=6). The body weight, body temperature, wet/dry weight(W/D) ratio of the lung tissue, and the pathological injury score of the lung tissue were recorded for each mouse. RT-qPCR and Western blot were conducted to determine the expression of HIF-1α, mitochondrial DNA(mt-DNA), and autophagy-related proteins in the lung tissue. The results of the clinical trial revealed that the SFI group had lowered levels of inflammatory markers in the blood and alveolar lavage fluid and elevated level of HIF-1α in the PBMCs. The mice in the SFI group showed recovered body temperature and body weight. lowered TNF-α level in the serum, and decreased W/D ratio of the lung tissue. SFI reduced the inflammatory exudation and improved the alveolar integrity in the lung tissue. Moreover, SFI down-regulated the mtDNA expression and up-regulated the protein levels of mitochondrial transcription factor A(mt-TFA), cytochrome c oxidase Ⅳ(COXⅣ), HIF-1α, and autophagy-related proteins in the lung tissue of the model mice. The findings confirmed that SFI could promote mitophagy to improve mitochondrial function by regulating the expression of HIF-1α.

Inhibition of SARS-CoV-2 replication by zinc gluconate in combination with hinokitiol.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic is currently the major challenge to global public health. Two proteases, papain-like protease (PLpro) and the 3-chymotrypsin-like protease (3CLpro or Mpro), are indispensable for SARS-CoV-2 replication, making them attractive targets for antiviral therapy development. Here we screened a panel of essential metal ions using a proteolytic assay and identified that zinc gluconate, a widely-used zinc supplement, strongly inhibited the proteolytic activities of the two proteases in vitro. Biochemical and crystallographic data reveal that zinc gluconate exhibited the inhibitory function via binding to the protease catalytic site residues. We further show that treatment of zinc gluconate in combination with a small molecule ionophore hinokitiol, could lead to elevated intracellular Zn2+ level and thereby significantly impaired the two protease activities in cellulo. Particularly, this approach could also be applied to rescue SARS-CoV-2 infected mammalian cells, indicative of potential application to combat coronavirus infections. Our studies provide the direct experimental evidence that elevated intracellular zinc concentration directly inhibits SARS-CoV-2 replication and suggest the potential benefits to use the zinc supplements for coronavirus disease 2019 (COVID-19) treatment.

The Effect of Guilingji Capsules on Vascular Mild Cognitive Impairment: A Randomized, Double-Blind, Controlled Trial.

Guilingji capsules (GLJC) have been shown to have antiaging effects and improve cognitive function. The aim of this study was to evaluate the clinical efficacy and safety of GLJC for the treatment of vascular mild cognitive impairment (VaMCI). A total of 96 patients with VaMCI (aged 60-85 years) were enrolled in this 24-week, randomized, double-blind, controlled clinical trial. The patients were randomly assigned to a GLJC group (n = 48) or a Ginkgo group (n = 48). Patients in the GLJC group were treated using GLJC, whereas those in the Ginkgo group received Ginkgo extract tablets. We evaluated the participants at baseline and after a 12- and 24-week treatment period using the Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and Chinese Medicine Symptom Scale (CM-SS). The serum acetylcholine (Ach), acetylcholinesterase (AchE), homocysteine (Hcy), and high-sensitivity C-reactive protein (hs-CRP) serum levels of the patients were measured before and after 24-week treatment. Analysis of the results of both groups showed that both interventions significantly increased the MoCA and MMSE scores of the patients and decreased their ADAS-Cog and CM-SS scores (P < 0.05). The GLJC group showed greater improvement in MoCA, MMSE, and CM-SS scores than the Ginkgo group (P < 0.05). However, both groups showed a significant increase in serum Ach and a decrease in serum AchE, Hcy, and hs-CRP levels (P < 0.05). Furthermore, serum Ach increased and Hcy decreased more significantly in the GLJC group than in the Ginkgo group (P < 0.05). These findings indicate that GLJC can improve the cognitive function, cholinergic system, and inflammatory cytokine levels of patients with VaMCI. Furthermore, this treatment can improve symptoms of syndromes diagnosed according to traditional Chinese medicine practice in patients with VaMCI.

A network meta-analysis on the improvement of cognition in patients with vascular dementia by different acupuncture therapies.

Introduction: The second most prevalent cause of dementia is vascular dementia (VaD). Furthermore, acupuncture is a relatively safe and effective traditional therapy for individuals with VaD. We performed a network meta-analysis to assess the effectiveness and safety of various acupuncture therapies for VaD based on existing research. Methods: We searched six electronic databases to screen for randomized controlled trials (RCTs) comparing different acupuncture treatments in VaD patients. The Cochrne tool (Review Manager 5.3) was used to evaluate the risk of bias of the included RCTs. Based on the Grading of Recommendations Assessment, Development and Evaluation framework, we assessed the confidence in the evidence using the Confidence In the results from Network Meta-Analysis approach. We used the frequency approach to perform the network meta-analysis. Data were analyzed using R 4.1.1. Results: In total, we included 46 eligible studies. The results of the network analysis showed that the combined interventions of moxibustion (MB) with body acupuncture (BA) (MB + BA) and electroacupuncture (EA) with scalp acupuncture (SA) with BA (EA + SA + BA) were more effective in improving cognitive functions and activities of daily living compared with SA or BA alone. However, in the subgroup analysis, EA + SA + BA showed better efficacy in short- and mid-term acupuncture compared with other acupuncture therapies. Conclusion: Combined acupuncture therapy may be a safe and effective intervention for individuals with VaD, and MB + BA and EA + SA + BA appear to be the most effective interventions. However, because the analysis of this study was based on low-to-moderate evidence, there remains no strong supporting evidence. Thus, high-quality, large-scale, and long-term studies should be conducted in the future to assess the effectiveness and safety of acupuncture in VaD. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022354573.

Tribulus terrestris L. protects glomerular endothelial cells via the miR155-H2AC6 interaction network in hypertensive renal injury.

BACKGROUND: Hypertensive renal injury is one of the most lethal complications of hypertension. At present, renin-angiotensin-aldosterone system (RAAS) blockers are considered the best drugs for the treatment of renal injury in hypertension because of their nephroprotective effect of reducing proteinuria, but there are no specific drugs for this purpose, however, clinical trials proved that Chinese medicine has a protective effect on target organs in the treatment of hypertension. Tribulus terrestris L. (TrT), a traditional Chinese medicine (TCM), has potential applications due to its reno-protective and immunomodulatory effects. METHODS: We investigated the underlying reno-protective mechanism of TrT on Angiotensin II (AngII)-induced hypertensive renal injury in glomerular endothelial cells by integrating the differential expression profiles of micro RNA (miRNA) and messenger RNA (mRNA) to construct a miRNA-mRNA interaction network associated with hypertensive kidney injury, followed by quantitative real-time polymerase chain reaction (qRT-PCR) for validation. RESULTS: Seventy-six differentially expressed mRNAs (DEmRNAs) and 1 differentially expressed miRNAs (DEmiRNAs) were identified in the control group and the AngII-induced hypertensive renal injury group, respectively. 110 DEmRNAs and 27 DEmiRNAs were identified in the TrT treatment group and the AngII-induced group, respectively. The core component of the miRNA-mRNA network was miR-155-5p. Our study showed that miR-155-5p expression levels were more decreased in the AngII-induced hypertensive renal injury group than the control group. TrT treatment also significantly upregulated miR-155-5p. Additionally, we found that miR-155-5p expression levels were negatively correlated with H2A clustered histone 6 (H2AC6). CONCLUSIONS: The results of this study indicate that TrT has a reno-protective effect on AngII-induced hypertensive renal injury by miR-155-5p, which negatively regulates the expression of H2AC6. Our findings offer a new therapeutic strategy and have identified an effective candidate target for the treatment of hypertensive renal injury in clinical settings.

Comparative transcriptome analysis to identify candidate genes involved in 2-methoxy-1,4-naphthoquinone (MNQ) biosynthesis in Impatiens balsamina L.

Impatiens balsamina L. is a tropical ornamental and traditional medicinal herb rich in natural compounds, especially 2-methoxy-1,4-naphthoquinone (MNQ) which is a bioactive compound with tested anticancer activities. Characterization of key genes involved in the shikimate and 1,4-dihydroxy-2-naphthoate (DHNA) pathways responsible for MNQ biosynthesis and their expression profiles in I. balsamina will facilitate adoption of genetic/metabolic engineering or synthetic biology approaches to further increase production for pre-commercialization. In this study, HPLC analysis showed that MNQ was present in significantly higher quantities in the capsule pericarps throughout three developmental stages (early-, mature- and postbreaker stages) whilst its immediate precursor, 2-hydroxy-1,4-naphthoquinone (lawsone) was mainly detected in mature leaves. Transcriptomes of I. balsamina derived from leaf, flower, and three capsule developmental stages were generated, totalling 59.643 Gb of raw reads that were assembled into 94,659 unigenes (595,828 transcripts). A total of 73.96% of unigenes were functionally annotated against seven public databases and 50,786 differentially expressed genes (DEGs) were identified. Expression profiles of 20 selected genes from four major secondary metabolism pathways were studied and validated using qRT-PCR method. Majority of the DHNA pathway genes were found to be significantly upregulated in early stage capsule compared to flower and leaf, suggesting tissue-specific synthesis of MNQ. Correlation analysis identified 11 candidate unigenes related to three enzymes (NADH-quinone oxidoreductase, UDP-glycosyltransferases and S-adenosylmethionine-dependent O-methyltransferase) important in the final steps of MNQ biosynthesis based on genes expression profiles consistent with MNQ content. This study provides the first molecular insight into the dynamics of MNQ biosynthesis and accumulation across different tissues of I. balsamina and serves as a valuable resource to facilitate further manipulation to increase production of MNQ.

Efficacy and safety of Lianhua Qingwen in the treatment of patients with moderate COVID-19 infection: A protocol for systematic review and meta analysis.

BACKGROUND: As of June 2020, more than 7 million cases of coronavirus disease (COVID-2019) have been reported worldwide. At present, there is no vaccine or antiviral for the novel coronavirus pneumonia. Lianhua Qingwen (LQ), a Chinese medicine formula, has been authorized by the Chinese government for treating COVID-2019. This systematic review and meta-analysis will evaluate the efficacy and safety of LQ on patients with COVID-19. METHODS: Two independent reviewers will search the following databases of the China Biology Medicine disc, China National Knowledge Infrastructure, China Science and Technology Periodical Database, Wanfang database, Embase, PubMed, and Cochrane Library from the date of conception to June 1, 2020. We will use the MeSH/Emtree terms, combining free-text words that were properly adjusted for the different databases in all of the search strategies. We will take primary clinical symptoms, total efficacy, and adverse event into consideration for our primary outcomes. As secondary outcomes, we will estimate the chest computed tomography manifestations, the rate of conversion to severe cases, and secondary clinical symptoms. We will evaluate the quality of including studies through the risk of bias assessment tool provided by the Cochrane Collaboration. Fixed-or random-effect model will be utilized to calculate the overall pooled risk estimates. Forest plots will be generated to prove the pooled results. Sensitivity analysis will be carried out to identify sources of heterogeneity. The Begg rank correlation test and Egger linear regression test will be used to explore publication bias. RESULTS: This systematic review and meta-analysis will compare the primary and secondary outcomes at baseline and endpoint in the treatment and control groups to investigate the efficacy and safety of LQ for treatment COVID-2019. DISCUSSION: Data from this study will provide strong evidence for clinical decision if the findings are positive.PROSPERO registration number: CRD42020190757.

Efficacy and Safety of Guilingji Capsules () for Treating Mild-to-Moderate Cognitive Impairment: Study Protocol for A Randomized, Double-Blind, Positive-Controlled, Multicenter and Noninferiority Trial.

BACKGROUND: The incidence of cognitive impairment (CI) is gradually increasing, which has attracted more attention from medical researchers worldwide. Definitive mechanisms of pathogenesis remain elusive, and there are few medications that have been proven effective for CI. The utilization of Chinese herbal medicine has shown positive therapeutic effects for a broad spectrum of diseases, including CI. OBJECTIVE: The purpose of this study is to evaluate the safety and efficacy of Guilingji Capsules (GLJC, ) in treating mild-to-moderate CI with Shen (Kidney) and marrow deficiency syndrome. METHODS: This is a randomized, double-blind, positive-controlled, multicenter clinical trial with a noninferiority design that included 348 participants randomly divided into an experimental arm and an active comparator arm. Individuals in the experimental arm (174 cases) took 0.6 g of GLJC once a day and 19.2 mg of Gingko biloba extract mimetic 3 times a day. Individuals in the active comparator arm (174 cases) took 0.6 g of GLJC mimetic once a day and 19.2 mg of Gingko biloba extract in tablet form 3 times a day. The intervention period included two sessions over 24 weeks. The primary outcome be the effectiveness of GLJC on cognitive improvement after 24 weeks of treatment, which was defined as an increase in the Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) Scale. The secondary outcomes were improvement in independence, daily living ability, and Chinese medicine (CM) syndrome, which were measured with the Alzheimer's disease Rating Scale-Cognitive Project (ADAS-Cog), Clinical Dementia Rating (CDR) Total Score, Activities of Daily Living (ADL) Total Score and the Chinese Medicine Symptom Scale (CM-SS), respectively. Serum acetylcholine, acetylcholinesterase, bax and bcl-2 were monitored to explore the mechanism of GLJC on CI. In addition, safety measures, including vital signs, electrocardiography, laboratory indicators (full blood count, kidney and liver function tests, routine urine test and routine stool test) and adverse events, were also recorded. DISCUSSION: The purpose of this trial is to evaluate the efficacy and safety of GLJC in patients with mild-to-moderate CI with kidney and marrow deficiency syndrome. If successful, the results would provide a viable treatment for patients with mild-to-moderate CI. (Clinical Trials.gov. ID: NCT03647384. Registered on 23 August 2018).

Shenmayizhi Formula Combined with Ginkgo Extract Tablets for the Treatment of Vascular Dementia: A Randomized, Double-Blind, Controlled Trial.

Shenmayizhi formula (SMYZF) has been shown to have an effect on vascular dementia (VaD) in previous studies. The aim of this study was to evaluate whether a combination of SMYZF with Ginkgo extract tablets improves mild-to-moderate VaD. In this 12-week, randomized, double-blind, controlled study, we randomly assigned 196 patients with VaD (aged 50-85 years) to either the SMYZF group (n = 98) or the Ginkgo group (n = 98). All patients received Ginkgo extract tablets as a basic treatment, while the SMYZF group also received SMYZF treatment. We evaluated the participants at baseline and after 12 weeks of the intervention for the following: the Mini-Mental State Examination (MMSE), National Institutes of Health Stroke Scale (NIHSS), activities of daily living (ADL), Chinese Medicine Symptom Scale (CM-SS) scores, serum endothelin-1 (ET-1), nitric oxide (NO), vascular endothelial growth factor (VEGF), von Willebrand factor (vWF), neuron-specific enolase (NSE), brain-derived neurotrophic factor (BDNF), and homocysteine (Hcy) serum levels. Both interventions significantly increased MMSE scores and decreased NIHSS, ADL, and CM-SS scores. The SMYZF group showed greater improvement in MMSE, NIHSS, and CM-SS scores. Both groups showed a significant decrease in serum ET-1 and an increase in serum VEGF. Furthermore, serum NO increased, and vWF decreased significantly in the SMYZF group. Changes in serum ET-1 and NO were greater in the SMYZF group. Both groups showed a significant increase in serum BDNF and a decrease in serum NSE and Hcy. Improvement in serum NSE and BDNF was greater in the SMYZF group. SMYZF combined with Ginkgo extract tablets improved vascular endothelial and cognitive functions, as well as the syndromes diagnosed based on the traditional Chinese medicine in patients with VaD.

Traditional Chinese Medicine for Alzheimer's Disease and Other Cognitive Impairment: A Review.

Cognitive impairment (CI) refers to the dysfunction of memory, language, visual space, execution, calculation, understanding, and judgment in one or more aspects. With global aging, CI will become prevalent worldwide. At present, there is no effective cure for CI. However, Nobel laureate Tu Youyou's research on artemisinin has inspired Chinese researchers to focus on traditional Chinese herbs (TCHs) for the treatment of CI. Traditional Chinese Medicine (TCM) has led to a theory for an independent CI system. The pathogenesis of such impairment involves deficiency, phlegm, and stagnation and involves a range of organs, including the brain, kidneys, heart, liver, and spleen. Our current understanding of the etiology and pathogenesis of this condition has led to the realization that TCHs can improve cognitive dysfunction. Clinical research has shown that TCHs can improve the neuropsychological scale score of patients, the TCM symptom score, and the patient's quality of life. Research has also suggested that TCHs can retard Aß deposits and tauopathy, regulate the metabolism of cholinergic neurotransmitters, and so on. However, due to their complexity, little is known of the safety and efficacy of TCHs in patients with CI. It is likely that we will be able to identify the precise mechanisms associated with the action of TCHs in such patients due to the integration of multiple technologies. This paper summarizes the pharmacokinetics, curative effect, and mechanisms of action of traditional Chinese herbs in order to provide a scientific basis for the improvement of cognitive dysfunction by TCHs.

Clinical Experience in Treatment of Alzheimer's Disease with Jiannao Yizhi Formula () and Routine Western Medicine.

OBJECTIVE: To investigate the long-term therapeutic effects of the Chinese medicine Jiannao Yizhi Formula (, JYF) in the treatment of Alzheimer's disease (AD). METHODS: Sixty mild-to-moderate AD participants were recruited and randomly allocated to the treatment (30 with JYF) and the control groups (30 with donepezil) for 6 months with the random numbers. The primary outcomes were scores of Alzheimer's Disease Rating Scale-Cognitive (ADAS-Cog) and Chinese Medicine Symptom Scale (CM-SS). The secondary outcomes were scores of Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Activities of Daily Living (ADL). Safety assessments were conducted at baseline and the 6th month of treatment. Serum levels of acetylcholine (Ach), amyloid-ß protein 42 (Aß42), and the microtubule-associated protein tau (Tau) were also determined by enzyme-liked immunosorbent assay. RESULTS: Fifty-one participants were included in the final analyses (JYF n=27; donepezil n=24). Compared with baseline, both JYF and donepezil increased the MoCA and MMSE scores and decreased the ADAS-Cog and CM-SS scores (P<0.05 or P<0.01). Both drugs increased the serum levels of Ach and decreased the serum levels of Aß42 and Tau (all P<0.05). There was no significant difference in these variables between the two groups, which showed that JYF was not inferior to donepezil. No obviously significant changes were observed in the ADL. No severe adverse events were observed in both groups. CONCLUSION: The effect and safety of JYF for the treatment of AD were not inferior to those of donepezil.

Rhizoma Coptidis for Alzheimer's Disease and Vascular Dementia: A Literature Review.

BACKGROUND: Alzheimer's disease (AD) and vascular dementia (VaD) are major types of dementia, both of which cause heavy economic burdens for families and society. However, no currently available medicines can control dementia progression. Rhizoma coptidis, a Chinese herbal medicine, has been used for >2000 years and is now gaining attention as a potential treatment for AD and VaD. METHODS: We reviewed the mechanisms of the active ingredients of Rhizoma coptidis and Rhizoma coptidis-containing Chinese herbal compounds in the treatment of AD and VaD. We focused on studies on ameliorating the risk factors and the pathological changes of these diseases. RESULTS: The Rhizoma coptidis active ingredients include berberine, palmatine, coptisine, epiberberine, jatrorrhizine and protopine. The most widely studied ingredient is berberine, which has extensive therapeutic effects on the risk factors and pathogenesis of dementia. It can control blood glucose and lipid levels, regulate blood pressure, ameliorate atherosclerosis, inhibit cholinesterase activity, Aß generation, and tau hyperphosphorylation, decrease neuroinflammation and oxidative stress and alleviate cognitive impairment. Other ingredients (such as jatrorrhizine, coptisine, epiberberine and palmatine) also regulate blood lipids and blood pressure; however, there are relatively few studies on them. Rhizoma coptidis-containing Chinese herbal compounds like Huanglian-Jie-Du-Tang, Huanglian Wendan Decoction, Banxia Xiexin Decoction and Huannao Yicong Formula have anti-inflammatory and antioxidant stress activities, regulate insulin signaling, inhibit γ-secretase activity, neuronal apoptosis, tau hyperphosphorylation, and Aß deposition, and promote neural stem cell differentiation, thereby improving cognitive function. CONCLUSION: The "One-Molecule, One-Target" paradigm has suffered heavy setbacks, but a "multitarget- directed ligands" strategy may be viable. Rhizoma coptidis active ingredients and Rhizoma coptidiscontaining Chinese herbal compounds have multi-aspect therapeutic effects on AD and VaD.

Traditional Chinese Medicine Shenmayizhi Decoction Ameliorates Memory And Cognitive Impairment Induced By Scopolamine Via Preventing Hippocampal Cholinergic Dysfunction In Rats.

PURPOSE: Clinical trials have illustrated that Shenmayizhi decoction (SMYZ) could improve the cognitive functions in patients with dementia. However, the mechanism needs to be explored. METHODS: Fifty adult male rats (Wistar strain) were divided into five groups equally and randomly, including control, model, and SMYZ of low dose, medium dose and high dose. Rats in each group received a daily gavage of respective treatment. Rats in control and model group were administrated by the same volume of distilled water. Memory impairment was induced by intraperitoneal administration of scopolamine (0.7 mg/kg) for 5 continuous days. Four weeks later, Morris water maze (MWM) was performed to evaluate the spatial memory in all rats. Then, rats were sacrificed and the hippocampus was removed for further tests. Furthermore, Western blot analysis was employed to assess the levels of acetylcholine M1 receptor (M1), acetylcholine M2 receptor (M2), acetylcholinesterase (AChE) and cholineacetyltransferase (ChAT). AChE and ChAT activities were determined. RESULTS: The SMYZ decoction significantly improved behavioral performance of rats in high dose. The SMYZ decoction in three doses exhibited anti-acetylcholinesterase activity. In addition, a high dose of SMYZ promoted ChAT activity. Moreover, a high dose of SMYZ increased the level of ChAT and declined the level of AChE assessed by Western blotting. Besides, an increased level of M1 receptor was found after treatment. CONCLUSION: Shenmayizhi decoction could mitigate scopolamine-induced cognitive deficits through the preventative effect on cholinergic system dysfunction.

Efficacy and safety of Shenmayizhi decoction as an adjuvant treatment for vascular dementia: Study protocol for a randomized controlled trial.

BACKGROUND: Vascular dementia (VaD) is the second most common cause of dementia. The treatment of VaD still remains a challenge so far. Traditional Chinese Herbal medicine is a promising therapy due to their multiple components and targets. Shenmayizhi decoction (SMYZD), a Chinese Herbal prescription, has been reported its effective in alleviating cognitive dysfunction in clinical practice. However, strong clinical research of SMYZD in the treatment of VaD was lack. Therefore, we design this study to evaluate the adjuvant role of SMYZD in the treatment of VaD. METHODS: This is a multicenter, randomized, blind, controlled trial. A total of 196 eligible patients will be assigned to receive Ginkgo biloba extracts (GBEs) plus SMYZD granule or GBEs plus SMYZD mimetic granule in a 1:1 ratio. The duration of the trial will be 12 weeks, and a follow-up will be performed at the 24th week. The primary outcomes are the National Institute of Health stroke scale (NIHSS) and the Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-cog). The secondary outcomes include the Mini-Mental State Examination (MMSE), the traditional Chinese Medicine (TCM) syndrome scale, Activities of Daily Living (ADL), concentrations of hypersensitive C-reactive protein (Hs-CRP), neuron-specific enolase (NSE) and homocysteine (HCY) in serum. Researchers will record any adverse events throughout the trial. DISCUSSION: This study will provide evidences to evaluate the efficacy and safety of SMYZD in combination with GBEs in treatment of VaD, as well as the adjuvant role of SMYZD in combination. TRIAL IS REGISTERED AT CHINESE CLINICAL TRIAL REGISTRY: ChiCTR1800017359.

The Chinese herbal formula Fuzheng Quxie Decoction attenuates cognitive impairment and protects cerebrovascular function in SAMP8 mice.

PURPOSE: This study was designed to explore the underlying mechanism of action for a Fuzheng Quxie Decoction (FQD) in Alzheimer's disease (AD), to validate its neuroprotective effects, and to provide experimental support for its predicted mechanism of action. METHODS: An integrative approach to network pharmacology was performed to predict the mechanism of action for treatment of AD with FQD. The predicted mechanism was validated in SAMP8 mice. RESULTS: With predicted putative FQD targets and a collection of AD-related genes, 245 possible regulatory targets of FQD were identified for the treatment of AD. Pathway-enrichment analysis for the possible regulatory targets indicated that vascular endothelial growth factor (VEGF) and VEGF-receptor signaling were pivotal in the treatment of AD with FQD. In vivo experiments confirmed the neuroprotective effect and the predicted mechanism of action for treatment of AD with FQD. CONCLUSION: This study contributes to an understanding of the neuroprotective effect of FQD and its potential mechanism of action for the treatment of AD.

The use of a novel non-steroidal mineralocorticoid receptor antagonist finerenone for the treatment of chronic heart failure: A systematic review and meta-analysis.

BACKGROUND: The non-steroidal mineralocorticoid receptor antagonist finerenone (BAY 94-8862) has been used to treat chronic heart failure (CHF) with reduced ejection fraction (HFrEF). However, conflicting results were reported for its efficacy and safety. The study aimed to compare the efficacy and safety of finerenone versus spironolactone or eplerenone in patients with chronic heart failure. METHODS: Electronic databases including MEDLINE, EMBASE, and CENTRAL were searched from inception to December 2017 for randomized controlled trials assessing finerenone treatment in patients with chronic heart failure. Data concerning the study's design, patients' characteristics, and outcomes were extracted. Risk ratio (RR) and mean differences (MD) were calculated using either fixed or random effects models. RESULTS: Three trials with 1520 CHF patients were included in the systematic review. In terms of anti-ventricular remodeling, we calculated the effective number of cases with a 30% reduction in NT-proBNP. Finerenone was equivalent to the existing steroidal mineralocorticoid antagonist (P < .05). However, the efficacy of finerenone appeared to be dose-dependent. At a dose of 10 mg/d finerenone was found to be marginally better than that of steroidal mineralocorticoid receptor antagonists (MRAs) (RR = 1.18, 95% confidence interval [CI] 0.88, 1.57, P > .05). The incidence of treatment-related adverse events (TEAEs) of finerenone at 10 mg/d was significantly lower than 25 to 50 mg/d of steroidal MRAs (RR = 0.81, 95% CI = 0.66-0.99, P = .04). Moreover, the serum potassium levels in the finerenone 10 mg/d group were lower than those in the 25 to 50 mg/d steroidal MRAs group (MD = -0.14, 95% CI -0.30-0.02, P = .09), whereas the estimated glomerular filtration rate (eGFR) was higher in finerenone versus steroidal MRAs treated patients (MD = 2.07, 95% CI -0.04-4.17, P = .05). CONCLUSIONS: Finerenone reduced NT-proBNP level, urinary albumin/creatinine ratio (UACR), and other biochemical indicators, in a dose-dependent manner. In terms of anti-ventricular remodeling in patient with chronic heart failure, finerenone at 10 mg/d is as effective as 20 to 50 mg/d of steroidal MRAs. However, finerenone is much safer to patients with chronic kidney disease.

Production of oridonin-rich extracts from Rabdosia rubescens using hyphenated ultrasound-assisted supercritical carbon dioxide extraction.

BACKGROUND: Among active components in Rabdosia rubescens, oridonin has been considered a key component and the most valuable compound because it has a wide range of activities beneficial to human health. To produce a high-quality oridonin extract, an alternative hyphenated procedure involving an ultrasound-assisted and supercritical carbon dioxide (HSC-CO2 ) extraction method to extract oridonin from R. rubescens was developed in this study. Fictitious solubilities of oridonin in supercritical CO2 (SC-CO2 ) with ultrasound assistance were measured by using the dynamic method at temperatures ranging from 305.15 K to 342.15 K over a pressure range of 11.5 to 33.5 MPa. RESULTS: Fictitious solubilities of oridonin at different temperatures and pressures were over the range of 2.13 × 10-6 to 10.09 × 10-6 (mole fraction) and correlated well with the density-based models, including the Bartle model, the Chrastil model, the Kumar and Johnston model and the Mendez-Santiago and Teja model, with overall average absolute relative deviations (AARDs) of 6.29%, 4.39%, 3.12% and 5.07%, respectively. CONCLUSION: Oridonin exhibits retrograde solubility behaviour in the supercritical state. Fictitious solubility data were further determined and obtained a good fit with four semi-empirical models. Simultaneously, the values of the total heat of solution, vaporisation and solvation of oridonin were estimated. © 2016 Society of Chemical Industry.

[Impact of Phosphogypsum Wastes on the Wheat Growth and CO2 Emissions and Evaluation of Economic-environmental Benefit].

Phosphogypsum is a phosphorus chemical waste which has not been managed and reused well, resultantly, causing environmental pollution and land-occupation. Phosphogypsum wastes were used as a soil amendment to assess the effect on wheat growth, yield and CO2 emissions from winter wheat fields. Its economic and environmental benefits were analyzed at the same time. The results showed that wheat yield was increased by 37.71% in the treatment of phosphogypsum of 2 100 kg x hm(-2). Compared with the control treatment, throughout the wheat growing season, CO2 emission was accumulatively reduced by 3% in the treatment of phosphogypsum waste of 1050 kg x hm(-2), while reduced by 8% , 10% , and 6% during the jointing stage, heading date and filling period of wheat, respectively; while CO2 emission was accumulatively reduced by 7% in the treatment of phosphogypsum waste of 2 100 kg x hm(-2) throughout the wheat growing season, as reduced by 11% , 4% , and 12% during the reviving wintering stage, heading date and filling period of wheat, respectively. It was better for CO2 emission reduction in the treatment of a larger amount of phosphogypsum waste. In the case of application of phosphogypsum waste residue within a certain range, the emission intensity of CO2 ( CO2 emissions of per unit of fresh weight or CO2 emissions of per unit of yield) , spike length, fresh weight and yield showed a significantly negative correlation--the longer the ear length, the greater fresh weight and yield and the lower the CO2 emissions intensity. As to the carbon trading, phosphogypsum utilization was of high economic and environmental benefits. Compared with the control, the ratio of input to output changed from 1: 8.3 to 1: 10.7, which in the same situation of investment the output could be increased by 28.92% ; phosphogypsum as a greenhouse gas reducing agent in the wheat field, it could decrease the cost and increase the environmental benefit totally about 290 yuan per unit of ton. The results demonstrated phosphogypsum wastes could obviously decrease the CO2 emission from field soil and had a great potential to control agricultural greenhouse gases. Hopefully it has an important application perspective for the low-carbon, ecological and sustainable agricultural development.