Protective effects of Radix Stellariae extract against Alzheimer's disease via autophagy activation in Caenorhabditis elegans and cellular models.

Enhancing the clearance of proteins associated with Alzheimer's disease (AD) emerges as a promising approach for AD therapeutics. This study explores the potential of Radix Stellariae, a traditional Chinese medicine, in treating AD. Utilizing transgenic C. elegans models of AD, we demonstrated that a 75% ethanol extract of Radix Stellariae (RSE) (at 50 µg/mL) effectively diminishes Aß and Tau protein expression, and alleviates their induced impairments including paralysis, behavioral dysfunction, neurotoxicity, and ROS accumulation. Additionally, RSE enhances the stress resistance of C. elegans. Further investigations revealed that RSE promotes autophagy, a critical cellular process for protein degradation, in these models. We found that inhibiting autophagy-related genes negated the neuroprotective effects of RSE, suggesting a central role for autophagy in the actions of RSE. In PC-12 cells, we observed that RSE not only inhibited Aß fibril formation but also promoted the degradation of AD-related proteins and reduced their cytotoxicity. Mechanistically, RSE was found to induce autophagy via modulating PI3K/AKT/mTOR and AMPK/mTOR signaling pathways. Importantly, inhibiting autophagy counteracted the beneficial effects of RSE on the clearance of AD-associated proteins. Moreover, we identified Dichotomine B, a ß-carboline alkaloid, as a key active constituent of RSE in mitigating AD pathology in C. elegans at concentrations ranging from 50 to 1000 µM. Collectively, our study presents novel discoveries that RSE alleviates AD pathology and toxicity primarily by inducing autophagy, both in vivo and in vitro. These findings open up new avenues for exploring the therapeutic potential of RSE and its active component, Dichotomine B, in treating neurodegenerative diseases like AD.

Ameliorative effect of Luffa cylindrica fruits on Caenorhabditis elegans and cellular models of Alzheimer's disease-related pathology via autophagy induction.

BACKGROUND: Alzheimer's disease (AD) is a prevalent neurodegenerative disorder without an effective cure. Natural products, while showing promise as potential therapeutics for AD, remain underexplored. AIMS: This study was conducted with the goal of identifying potential anti-AD candidates from natural sources using Caenorhabditis elegans (C. elegans) AD-like models and exploring their mechanisms of action. MATERIALS & METHODS: Our laboratory's in-house herbal extract library was utilized to screen for potential anti-AD candidates using the C. elegans AD-like model CL4176. The neuroprotective effects of the candidates were evaluated in multiple C. elegans AD-like models, specifically targeting Aß- and Tau-induced pathology. In vitro validation was conducted using PC-12 cells. To investigate the role of autophagy in mediating the anti-AD effects of the candidates, RNAi bacteria and autophagy inhibitors were employed. RESULTS: The ethanol extract of air-dried fruits of Luffa cylindrica (LCE), a medicine-food homology species, was found to inhibit Aß- and Tau-induced pathology (paralysis, ROS production, neurotoxicity, and Aß and pTau deposition) in C. elegans AD-like models. LCE was non-toxic and enhanced C. elegans' health. It was shown that LCE activates autophagy and its anti-AD efficacy is weakened with the RNAi knockdown of autophagy-related genes. Additionally, LCE induced mTOR-mediated autophagy, reduced the expression of AD-associated proteins, and decreased cell death in PC-12 cells, which was reversed by autophagy inhibitors (bafilomycin A1 and 3-methyladenine). DISCUSSION: LCE, identified from our natural product library, emerged as a valuable autophagy enhancer that effectively protects against neurodegeneration in multiple AD-like models. RNAi knockdown of autophagy-related genes and cotreatment with autophagy inhibitors weakened its anti-AD efficacy, implying a critical role of autophagy in mediating the neuroprotective effects of LCE. CONCLUSION: Our findings highlight the potential of LCE as a functional food or drug for targeting AD pathology and promoting human health.

Folium Hibisci Mutabilis extract, a potent autophagy enhancer, exhibits neuroprotective properties in multiple models of neurodegenerative diseases.

BACKGROUND: Protein aggregates are considered key pathological features in neurodegenerative diseases (NDs). The induction of autophagy can effectively promote the clearance of ND-related misfolded proteins. OBJECTIVE: In this study, we aimed to screen natural autophagy enhancers from traditional Chinese medicines (TCMs) presenting potent neuroprotective potential in multiple ND models. METHODS: The autophagy enhancers were broadly screened in our established herbal extract library using the transgenic Caenorhabditis elegans (C. elegans) DA2123 strain. The neuroprotective effects of the identified autophagy enhancers were evaluated in multiple C. elegans ND models by measuring Aß-, Tau-, α-synuclein-, and polyQ40-induced pathologies. In addition, PC-12 cells and 3 × Tg-AD mice were employed to further validate the neuroprotective ability of the identified autophagy enhancers, both in vitro and in vivo. Furthermore, RNAi bacteria and autophagy inhibitors were used to evaluate whether the observed effects of the identified autophagy enhancers were mediated by the autophagy-activated pathway. RESULTS: The ethanol extract of Folium Hibisci Mutabilis (FHME) was found to significantly increase GFP::LGG-1-positive puncta in the DA2123 worms. FHME treatment markedly inhibited Aß, α-synuclein, and polyQ40, as well as prolonging the lifespan and improving the behaviors of C. elegans, while siRNA targeting four key autophagy genes partly abrogated the protective roles of FHME in C. elegans. Additionally, FHME decreased the expression of AD-related proteins and restored cell viability in PC-12 cells, which were canceled by cotreatment with 3-methyladenine (3-MA) or bafilomycin A1 (Baf). Moreover, FHME ameliorated AD-like cognitive impairment and pathology, as well as activating autophagy in 3 × Tg-AD mice. CONCLUSION: FHME was successfully screened from our natural product library as a potent autophagy enhancer that exhibits a neuroprotective effect in multiple ND models across species through the induction of autophagy. These findings offer a new and reliable strategy for screening autophagy inducers, as well as providing evidence that FHME may serve as a possible therapeutic agent for NDs.

Chlorogenic acid delays the progression of Parkinson's disease via autophagy induction in Caenorhabditis elegans.

OBJECTIVES: Parkinson's disease (PD) is the second most common neurodegenerative disease. Chlorogenic acid (CGA) is a polyphenolic substance derived from various medicinal plants. Although CGA is reported to have potential anti-PD effect, the beneficial effect and the underlying mechanism remain unclear. In this study, we aimed to further investigate the protective effect and clarify the mechanism of action of CGA in Caenorhabditis elegans (C. elegans) models of PD. METHODS: Measurements of a-synuclein aggregation, movement disorders, and lipid, ROS and malondialdehyde (MDA) contents were observed in NL5901 nematodes. Determinations of dopamine (DA) neuron degeneration, food perception, and ROS content were performed in 6-OHDA-exposed BZ555 nematodes. The autophagy activation of CGA was monitored using DA2123 and BC12921 nematodes. Meanwhile, RNAi technology was employed to knockdown the autophagy-related genes and investigate whether the anti-PD effect of CGA was associated with autophagy induction in C. elegans. RESULTS: CGA significantly reduced α-synuclein aggregation, improved motor disorders, restored lipid content, and decreased ROS and MDA contents in NL5901 nematodes. Meanwhile, CGA inhibited DA neuron-degeneration and improved food-sensing behavior in 6-OHDA-exposed BZ555 nematodes. In addition, CGA increased the number of GFP::LGG-1 foci in DA2123 nematodes and degraded p62 protein in BC12921 nematodes. Meanwhile, CGA up-regulated the expression of autophagy-related genes in NL5901 nematodes. Moreover, the anti-PD effect of CGA was closely related to autophagy induction via increasing the expression of autophagy-related genes, including unc-51, bec-1, vps-34, and lgg-1. CONCLUSIONS: The present study indicates that CGA exerts neuroprotective effect in C. elegans via autophagy induction.

Citri Reticulatae Semen Extract Promotes Healthy Aging and Neuroprotection via Autophagy Induction in Caenorhabditis elegans.

Nutrition intervention has emerged as a potential strategy to delay aging and promote healthy longevity. Citri Reticulatae Semen (CRS) has diverse beneficial effects and has been used for thousands of years to treat pain. However, the health benefits of CRS in prolonging health span and improving aging-related diseases and the exact mechanisms remain poorly characterized. In this study, Caenorhabditis elegans (C. elegans) was used as a model organism to study the antiaging and health span promoting activities of 75% ethanol extract of CRS (CRSE). The results showed that treatment with CRSE at 1 000 µg/mL significantly extended the life span of worms by 18.93% without detriment to health span and fitness, as evidenced by the delayed aging-related phenotypes and increased body length and width, and reproductive output. In addition, CRSE treatment enhanced the ability of resistance to heat, oxidative, and pathogenic bacterial stress. Consistently, heat shock proteins and antioxidant enzyme-related and pathogenesis-related genes were up-regulated by CRSE treatment. Furthermore, CRSE supplementation also improved α-synuclein, 6-OHDA, and polyQ40-induced pathologies in transgenic C. elegans models of Parkinson's disease and Huntington's disease. The mechanistic study demonstrated that CRSE induced autophagy in worms, while the RNAi knockdown of 4 key autophagy-related genes, including lgg-1, bec-1, vps-34, and unc-51, remarkably abrogated the beneficial effects of CRSE on the extending of life span and health span and neuroprotection, demonstrating that CRSE exerts beneficial effects via autophagy induction in worms. Together, our current findings provide new insights into the practical application of CRS for the prevention of aging and aging-related diseases.

Shengmai San for Treatment of Cardiotoxicity from Anthracyclines: A Systematic Review and Meta-Analysis.

OBJECTIVE: To systematically evaluate the efficacy of Shengmai San in patients with cardiotoxicity of anthracyclines. METHODS: Randomized controlled trials (RCTs) were identified by searching China National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Biomedical Literature Database (CBM), PubMed, Cochrane Library, and Embase Databases from the inceptions until December 2020. The Cochrane Handbook was used to evaluate the risk of bias in the included studies. Data analysis was conducted using RevMan 5.3 software. RESULTS: Totally 19 RCTs with 2,331 participants were included in this review. Results showed that in improving arrhythmia (13 RCTs, n=1,877, RR=0.37, 95%CI 0.25 to 0.52, P<0.00001), the treatment group was superior to the control group. In terms of reducing left ventricular end-diastolic diameter (LVEDD, 2 RCTs, n=128, MD=-0.79, 95%CI -0.93 to -0.65, P<0.00001) and left ventricular end systolic diameter (LVESD, 2 RCTs, n=128, MD=-0.58, 95%CI -0.82 to -0.35, P<0.00001), the treatment group was also better than the control group. In reducing myocardial enzymes such as creatine kinase (CK) [(3 RCTs, n=256, SMD=-0.80, 95%CI -1.16 to -0.44, P<0.0001), (2 RCTs, n=126, SMD=-0.62, 95%CI -0.98 to -0.26, P=0.0007)], the treatment group was superior to the control group. CONCLUSION: Shengmai San has a positive effect on the treatment of cardiotoxicity from anthracyclines. However, in the future, it is still necessary to conduct high-quality RCTs to verify its efficacy.

A Study of Logistic Regression for Fatigue Classification Based on Data of Tongue and Pulse.

Methods: The Tongue and Face Diagnosis Analysis-1 instrument and Pulse Diagnosis Analysis-1 instrument were used to collect the tongue image and sphygmogram of the subhealth fatigue population (n = 252) and disease fatigue population (n = 1160), and we mainly analyzed the tongue and pulse characteristics and constructed the classification model by using the logistic regression method. Results: The results showed that subhealth fatigue people and disease fatigue people had different characteristics of tongue and pulse, and the logistic regression model based on tongue and pulse data had a good classification effect. The accuracies of models of healthy controls and subhealth fatigue, subhealth fatigue and disease fatigue, and healthy controls and disease fatigue were 68.29%, 81.18%, and 84.73%, and the AUC was 0.698, 0.882, and 0.924, respectively. Conclusion: This study provided a new noninvasive method for the fatigue diagnosis from the perspective of objective tongue and pulse data, and the modern tongue diagnosis and pulse diagnosis have good application prospects.

Shengmai San for Treatment of Cardiotoxicity from Anthracyclines: A Systematic Review and Meta-Analysis / 中国结合医学杂志

OBJECTIVE@#To systematically evaluate the efficacy of Shengmai San in patients with cardiotoxicity of anthracyclines.@*METHODS@#Randomized controlled trials (RCTs) were identified by searching China National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Biomedical Literature Database (CBM), PubMed, Cochrane Library, and Embase Databases from the inceptions until December 2020. The Cochrane Handbook was used to evaluate the risk of bias in the included studies. Data analysis was conducted using RevMan 5.3 software.@*RESULTS@#Totally 19 RCTs with 2,331 participants were included in this review. Results showed that in improving arrhythmia (13 RCTs, n=1,877, RR=0.37, 95%CI 0.25 to 0.52, P<0.00001), the treatment group was superior to the control group. In terms of reducing left ventricular end-diastolic diameter (LVEDD, 2 RCTs, n=128, MD=-0.79, 95%CI -0.93 to -0.65, P<0.00001) and left ventricular end systolic diameter (LVESD, 2 RCTs, n=128, MD=-0.58, 95%CI -0.82 to -0.35, P<0.00001), the treatment group was also better than the control group. In reducing myocardial enzymes such as creatine kinase (CK) [(3 RCTs, n=256, SMD=-0.80, 95%CI -1.16 to -0.44, P<0.0001), (2 RCTs, n=126, SMD=-0.62, 95%CI -0.98 to -0.26, P=0.0007)], the treatment group was superior to the control group.@*CONCLUSION@#Shengmai San has a positive effect on the treatment of cardiotoxicity from anthracyclines. However, in the future, it is still necessary to conduct high-quality RCTs to verify its efficacy.

The Influence of Stomach Back-Shu and Front-Mu Points on Insular Functional Connectivity in Functional Dyspepsia Rat Models.

Functional Dyspepsia (FD) is a common functional gastrointestinal disease, which can reduce the quality of life in patients. Prior research has indicated that insula is closely related to FD and that acupuncture can regulate the functional connectivity (FC) of FD. Therefore, we hypothesized that acupuncture on FD was effected through the insular pathway. To test our hypothesis, we performed electroacupuncture (EA) on FD rat models and then examined the FC between insula and other brain regions through resting-state functional magnetic resonance imaging (rs-fMRI). Seven-day-old male infant Sprague-Dawley (SD) rats were randomly divided into control group, FD model group, and FD acupuncture group, with twelve rats per group (n = 36). Upon establishing successful models, the FD acupuncture group was subjected to EA intervention using Stomach back-shu (BL-21) and front-mu (RN-12) points for ten consecutive days for durations of 20 minutes each day. After intervention, each group was subject to rs-fMRI. The digital image data obtained were analyzed using FC analysis methods. Subsequently, gastric ligation was performed to measure gastric emptying rates. Before EA intervention, the FD model group exhibited decreased functional connections between the insula and a number of brain regions. After EA intervention, FD acupuncture group exhibited increasing FC between insula and regions when compared to the FD model group, such as the primary somatosensory cortex (S1), hippocampal CA3 (CA3), polymorphic layer of dentate gyrus (PoDG), caudate putamen (CPu), and oral pontine reticular nuclei (PnO) (P < 0.05); decreasing FC was also exhibited between insula and regions such as the bilateral primary and secondary motor cortexes (M1/2), paraventricular hypothalamic nucleus (PVA), and limbic cortex (LC). These findings indicate that the effective treatment of FD using EA may be through regulating the abnormal FC between insula and several brain regions, in particular CA3, PoDG, and PVA.

Cupping Therapy for Diseases: An Overview of Scientific Evidence from 2009 to 2019.

Cupping therapy has been accepted worldwide, and many studies have been conducted to reveal its curative effects and mechanisms. To comprehensively evaluate the effect of cupping therapy, database including China Network Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database VIP, Wan Fang Database, Chinese Biomedicine (CBM), PubMed and Web of Science were searched from 2009-2019. We summarized all the meta-analyses, randomized controlled trials, clinical trials and the mechanisms studies of cupping therapy in the previous 10 years, hoping to provide a reference for the clinical applications and studies.

Discovery of hCES2A inhibitors from Glycyrrhiza inflata via combination of docking-based virtual screening and fluorescence-based inhibition assays.

Human carboxylesterase 2 (hCES2A) is a key target to ameliorate the intestinal toxicity triggered by irinotecan that causes severe diarrhea in 50%-80% of patients receiving this anticancer agent. Herbal medicines are frequently used for the prevention and treatment of the intestinal toxicity of irinotecan, but it is very hard to find strong hCES2A inhibitors from herbal medicines in an efficient way. Herein, an integrated strategy via combination of chemical profiling, docking-based virtual screening and fluorescence-based high-throughput inhibitor screening assays was utilized. Following the screening of a total of 73 herbal products, licorice (the dried root of Glycyrrhiza species) was found with the most potent hCES2A inhibition activity. Further investigation revealed that the chalcones and several flavonols in licorice displayed strong hCES2A inhibition activities, while isoliquiritigenin, echinatin, naringenin, gancaonin I and glycycoumarin exhibited moderate inhibition of hCES2A. Inhibition kinetic analysis demonstrated that licochalcone A, licochalcone C, licochalcone D and isolicoflavonol potently inhibited hCES2A-mediated fluorescein diacetate hydrolysis in a reversible and mixed inhibition manner, with Ki values less than 1.0 µM. Further investigations demonstrated that licochalcone C, the most potent hCES2A inhibitor identified from licorice, dose-dependently inhibited intracellular hCES2A in living HepG2 cells. In summary, this study proposed an integrated strategy to find hCES2A inhibitors from herbal medicines, and our findings suggested that the chalcones and isolicoflavonol in licorice were the key ingredients responsible for hCES2A inhibition, which would be very helpful to develop new herbal remedies or drugs for ameliorating hCES2A-associated drug toxicity.

Research progress on active components and mechanism of Isatidis Radix for influenza virus / 中国中药杂志

Isatidis Radix is the dried root of the Isatis indigotica, with pharmacological effects such as heat-clearing and detoxification, cooling blood and pharyngeal relief, antibacterial and anti-inflammatory effects. It is often used clinically to prevent and treat influenza and other diseases. In this paper, relevant domestic and foreign literatures in recent years were summarized, and it was found that Isatidis Radix lignans, indole alkaloids, polysaccharides, etc. were the main active components against influenza virus. Then its pharmacological effects and the mechanism of action were reviewed, providing a basis for in-depth research on the antiviral effect of Isatidis Radix.

Cupping Therapy for Diseases: An Overview of Scientific Evidence from 2009 to 2019 / 中国结合医学杂志

Cupping therapy has been accepted worldwide, and many studies have been conducted to reveal its curative effects and mechanisms. To comprehensively evaluate the effect of cupping therapy, database including China Network Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database VIP, Wan Fang Database, Chinese Biomedicine (CBM), PubMed and Web of Science were searched from 2009-2019. We summarized all the meta-analyses, randomized controlled trials, clinical trials and the mechanisms studies of cupping therapy in the previous 10 years, hoping to provide a reference for the clinical applications and studies.

The efficacy and safety of acupoint injection for diabetic gastroparesis: A protocol for systematic review and meta-analysis.

BACKGROUND: Diabetic gastroparesis (DGP) is one of the common complications of diabetes. Accumulated evidences have shown that acupoint injection is beneficial for the clinical treatment of diabetic gastroparesis. However, there is currently no systematic review to assess this therapy. This program aims to evaluate the effectiveness and safety of this therapy for the patients with DGP. METHODS AND ANALYSIS: Literature search will be conducted via following electronic bibliographic databases from inception to Aug 2020: the Cochrane Library, PubMed, MEDLINE, Web of Science, EMBASE, Springer, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), Chinese Scientific Journal Database (VIP), Wan-Fang Database. All randomized controlled trials published in English or Chinese related to acupoint injection for DGP will be included. The primary outcome is the total effective rate. The secondary outcomes are the change of motilin and gastrin levels before and after the treatment. Two researchers will be responsible for the selection of study, extraction of data, and assessment of study quality independently. RevMan V5.3 Software will be used for assessing the risk of bias and synthesizing data. RESULTS: This study will provide a high-quality synthesis of current available evidence for the treatment of DGP with this therapy clinically. CONCLUSION: The conclusions of our study will provide new evidence to judge whether acupoint injection is an effective intervention for patients suffered from DGP. OSF REGISTRATION NUMBER:: osf.io/ms58j.

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).

Regulatory Effect of Modified Erchentang on Levels of Lymphokines Relating to Th1,Th2 and Th9 Cells and Expressions of IL-4R1/IL-13RA1 in Bronchioles of Rats with Chronic Obstructive Pulmonary Disease / 中国实验方剂学杂志

Objective:To study the effect of modified Erchentang on levels of interleukin-12 (IL-12), interferon-γ (IFN-γ), interleukin-9 (IL-9), interleukin-4 (IL-4) and interleukin-13 (IL-13) in plasma and bronchoalveolar lavage fluid (BALF) of all rats, as well as expressions of interleukin-4 (IL-4) receptor (IL-4R1) and interleukin-13 (IL-13) receptor (IL-13RA1) in bronchioles tissue of rats with chronic obstructive pulmonary disease (COPD). Method:Fifty SD rats were randomly divided into 5 groups, namely normal group, model group, and low, middle and high-dose modified Erchentang groups (5, 10, 20 g·kg-1), with 10 rats in each group. COPD in rat was prepared by using cigarette smoke combined with dripping lipopolysaccharide (LPS) in trachea. After the modeling, normal and model groups were given normal saline solution through intragastric (ig) administration, while other groups were given corresponding herbal drugs (5, 10, 20 g·kg-1) intragastrically (ig) for 14 days. The levels of IL-12, IFN-γ, IL-9, IL-4 and IL-13 in plasma and BALF were detected by Enzyme-linked immunosorbent assay (ELISA) method， and immunohistochemistry (IHC) method was used to detect the expressions of IL-4R1 and IL-13RA1 in bronchioles tissue of all of the groups. Result:Compared with the normal group, the levels of IL-12 and IFN-γ were decreased significantly (P<0.01), but the levels of IL-9, IL-4 and IL-13 in plasma and BALF were significantly increased (P<0.01), and the expressions of IL-4R1 and IL-13RA1 in bronchioles tissue were increased significantly (P<0.01) in model group. Compared with the model group, the levels of IL-12 and IFN-γ were increased significantly, while the levels of IL-9, IL-4 and IL-13 in plasma and BALF were decreased significantly (P<0.01), and the expressions of IL-4R1 and IL-13RA1 in bronchioles tissue were decreased significantly (P<0.01) in modified Erchentang groups (10, 20 g·kg-1). Conclusion:Modified Erchentang has effects in resisting inflammatory and protecting tissue structure of bronchioles. Its mechanism may be correlated with increasing the levels of IL-12, IFN-γ and reducing the levels of IL-9, IL-4 and IL-13 in plasma and BALF, and inhibiting the expressions of IL-4R1 and IL-13RA1 in bronchioles tissue.

Mechanism of Modified Erchentang on Expression of CXCL8-CXCR1/2 Axle Genes in Lung Tissue of Rats with Chronic Obstructive Pulmonary Disease / 中国实验方剂学杂志

Objective:To observe the effect of modified Erchentang on the expression of CXC chemokine ligand (CXCL) 8-CXC chemotaxis factor receptor (CXCR) 1/2 genes in the lung tissue of rats with chronic obstructive pulmonary disease (COPD), in order to explore the anti-inflammatory molecular mechanism of Erchentang on COPD. Method:Forty SD rats were randomly divided into normal group, model group, Jizhi syrup group and modified Erchentang group. COPD models in rats were prepared by cigarette smoke and dripping lipopolysaccharide (LPS) in the trachea. After modeling, normal and model groups were intragastrically given normal saline solution, Jizhi syrup group was given Jizhi syrup（10 g·kg-1），and modified Erchentang group was given intragastrically corresponding herbal drugs (10 g·kg-1) for 14 days. The levels of chemokines CXCL1, CXCL8 were detected by enzyme-linked immunosorbent assay in rat bronchoalveolar lavage fluid (BALF). The mRNA expressions of CXCL8, CXCR1 and CXCR2 were detected by quantitative real time PCR (Real-time PCR). Western blot was used to detect the levels of CXCL8, CXCR1 and CXCR2 protein, the pathological changes of lung tissues were observed by hematoxylin-eosin(HE) staining,and immunohistochemistry (IHC) method was used to detect the expressions of CXCL8, CXCR1 and CXCR2 protein in the lung tissue of all the groups. Result:The levels of chemokines CXCL1, CXCL8 in rats BALF were increased significantly (P<0.01), the expressions of CXCL8，CXCR1 and CXCR2 mRNA and protein were increased significantly (P<0.05, P<0.01) in model group compared with normal group. Compared with model group, the expressions of CXCL8, CXCR1 and CXCR2 mRNA and protein were decreased significantly (P<0.05), and the levels of chemokines CXCL1, CXCL8 in rats BALF were decreased significantly (P<0.01) in modified Erchentang. Conclusion:Modified Erchentang has an anti-inflammatory effect on COPD. The mechanism may be related to inhibiting the expressions of CXCL8, CXCR1, CXCR2 mRNA and protein, and reducing the release of chemokines CXCL1, CXCL8.

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 / 中国结合医学杂志

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).

Protective effects of trans-2,3,5,4'-tetrahydroxystilbene 2-O-ß-d-glucopyranoside on liver fibrosis and renal injury induced by CCl4via down-regulating p-ERK1/2 and p-Smad1/2.

Both as a food and an herbal plant, Polygonum multiflorum (PM) has long been used in food and prescriptions for several centuries in Southeast Asia. trans-2,3,5,4'-tetrahydroxystilbene 2-O-ß-d-glucopyranoside (trans-THSG) is one of the major compounds derived from PM and has been reported to exhibit multiple biological activities such as antioxidation and anti-obesity activities among others. The current study was aimed at investigating the effects of trans-THSG on liver fibrosis and renal injury in a carbon tetrachloride (CCl4) induced rodent model via oral feeding. Research results have demonstrated that administration of trans-THSG (100 and 300 mg kg-1) significantly ameliorated liver fibrosis, manifested by reduced expression of desmin and α-smooth muscle actin (α-SMA) plus collagen deposition. Specifically, treatment with trans-THSG effectively decreased the levels of transforming growth factor-ß (TGF-ß) and reduced the phosphorylation of Smad1/2 (p-Smad1/2) and extracellular signal-regulated kinases 1/2 (p-ERK1/2). Furthermore, we found that trans-THSG significantly down-regulated CCl4-induced excessive collagen secretion and increased the levels of desmin, MMP2 and MMP9 in rat liver tissues, suggesting that trans-THSG prevents liver fibrosis by attenuating the activation of hepatic stellate cells (HSCs) through the inhibition of Smad and ERK signaling pathways. Hence, the present findings demonstrate that trans-THSG is an effective antifibrotic agent in protecting liver from CCl4-induced toxicity.

Supercritical fluid CO2 extraction of three polymethoxyflavones from Citri reticulatae pericarpium and subsequent preparative separation by continuous high-speed counter-current chromatography.

Polymethoxyflavones (PMFs) are widely found in Citri Reticulatae Pericarpium (CRP) and have been investigated with a broad spectrum of biological activities as well as health promoting properties. However, separation of the PMFs from a complex sample, especially preparative separation of these PMFs with high purity, remains challenging. In the present study, an efficient method based on supercritical fluid extraction (SFE) and continuous high-speed counter-current chromatography (HSCCC) has been developed for extracting and preparative purification PMFs from CRP. Various experimental conditions were investigated to optimize the SFE and HSCCC processes. Under these optimized conditions, crude extract of CRP (extract I) was obtained with a maximum contents of nobiletin, 3,5,6,7,8,3',4'-heptamethoxyflavone and tangeretin. Further extraction of crude extract I was carried out to obtain crude extract II, which was further isolated and purified by HSCCC. It was worth mentioned that continuous injection HSCCC process were realized without lost of separation efficiency, which allowed for multiple purification cycles and therefore saved a lot of labor and time. Furthermore, high-performance liquid chromatography (HPLC) was employed to analyze the fractions separated by HSCCC, which revealed that the purities of the three PMFs were all above 98%. The structures of the three PMFs were identified by LC-MS and 1H NMR spectroscopy.